Results 1 - 16 of 52 Glutathione, The Biochemical Powerhouse - Health Educator Report # Apr 1, | Kindle eBook. by C.N.C. Billie J. Sahley Ph.D.
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A selection of your thoughts: The entire sys- tem of academic publishing is broken. Open Access is an attempt by many to build a new system. It is unfortunate that it has been diverted from its course by those who do not share its values. Determining the degree of similar problems in paper journals would require a similar study. We have all seen stupidity among reviewers and authors at paper journals. What we do not see in subscription journals is the cash incentive to publish utter rubbish.
Operating a sting to discredit an OA publication is not science, not journalism, and not entertainment. The authors and the editors of Science should feel embarrassed…. The program aims to produce creative responses to climate change and to involve local initia- tives, concerns, and knowl- edge in the process. To do so, it has initiated partner- ships with a range of com- munity groups, cultural pro- ducers, research teams, and education sites across Scotland.
Small enclosed areas lodging video instal- lations punctuate the oval. Near the entrance, Sea Change marks the site of the exhibition itself with pressed herbarium speci- mens of bog species col- lected during historical botanical expeditions to the Scottish Hebrides. Her images evoke a sense of the tur- bulence of north Atlantic weather systems and their uncanny power to frustrate various marine and aeronautical feats of engineer- ing that promise some measure of control over the wind-blown landscape. Through 26 January Others seem to take a cancer diagno- sis in stride and overtly show no changes in the activities of their daily lives.
Commonly, when scientists are diagnosed with a particular cancer, their response is to learn everything possible about the disease in an effort to feel some sort of control over the situation. The task is overwhelming. The Cancer Chronicles comprises two distinct narratives. Both his wife and, later, his brother were diagnosed with advanced- stage cancers, which carry grim prognoses.
Johnson takes the reader step by step through diagnosis, treatment, and disease outcomes. The second, interwoven, chronicle tells the story of cancer cells themselves. John- son details the documentation of cancer in dinosaurs, prehistoric humans, Greek and Roman civilizations, and bodies from medieval times. He follows his epide- miologic review of ancient cases with a well- annotated progression through key discover- ies that have shaped our understanding and treatment of cancer.
Johnson discusses com- plex issues in cancer etiology, cancer biology, and even cancer politics. In addition, the studies considered address important questions the author has posed: The book succeeds on many levels. Johnson alter- nates between the two chron- icles from chapter to chap- ter. The device of using his personal experience to select the breakthroughs or top- ics he discusses works well. He tells his personal story with an emotional distance that allows a smooth transi- tion from technically oriented material to the family thread and back again.
In addition, the book is artfully written. Photomicrograph of breast tissue with cancer cells. Knopf, New York, In bringing home the impact of cli- mate change on place, the Sea Change exhi- bition makes a persuasive case for climate change as a complex, ever-present problem that admits of no single, overarching solution but which can, nevertheless, be addressed in the everyday actions of local communities. This is a fragmented, disconnected view; innovation demands to be looked at as a system, from early-stage research through production. In contrast, Germany has a culture of engineer- ing and Japan of artisanship and quality that embrace histories of production innovation and manufacturing success.
Can the United States reinvigorate its manufacturing sector? Production in the U. Innovation System Much innovation occurs in the production stage. Moving from prototype to product can take years. The initial innovation is often thoroughly reworked. These are highly creative elements needed at the outset of production at scale, requiring much science and engineering at nearly every point.
The research-to-prototype stages begin the innovation process, but the pre- and outset-of-production stages are also vital. These stages are critical for incremen- tal technology advance, as well as for break- through and radical technology innovation. Despite manufacturing strength in the 19th and early 20th centuries, U. If an innovation system must also encompass the back end—the prototype, demonstration, test-bed, and initial produc- tion phases—the United States has a gap One part of the U. This system 13 jump- started key innovation waves of the 20th cen- tury: Some have argued that this is due to productivity gains, but recent data do not bear this out.
Output fell in this period in 16 of the 19 manufactur- ing sectors per government data mea- sures, and output appears overstated in the remaining sectors. Because output is a key factor in productivity, manu- facturing productivity appears substan- tially lower than we have been assum- ing; therefore, there are other structural causes of the deep manufacturing job losses.
Recent data suggest that an uptick in U. Yet manufacturing remains crucial: The operating assumption was that the United States would innovate and translate those innovations into products. The United States since has been playing out economic growth theory—that the predominant factor in economic growth is technological and related innovation 22 — and demonstrating that it works, with its model increasingly emulated abroad. But in recent years, with the advent of a global econ- omy, the innovate-here-and-produce-here model is breaking down. Now the innovate-here-and- produce-there model appears to work well for many IT and commodity products.
However, there appear to be many sec- tors where the distributed model does not work and that still require a close connec- tion between research, design, and produc- tion, e. Produce-here-and-innovate-there may be even more disruptive than innovate-here- and-produce-there. This brings the founda- tions of U. Paradigms for Manufacturing Innovation If technological and related innovation is the core factor in economic growth, this points toward an innovation-oriented strategy in production.
Although industry has been dis- cussing macro factors in manufacturing recovery—tax, trade, currency valuation, and regulation—there are structural factors in the manufacturing innovation system that require focus. If production turns out to be important to the health of the overall innovation system because the two are interdependent, we have a systems problem not simply a macro policy problem. What could be undertaken? The United States will not be interested in competing with low-cost, low-wage, increasingly innovative emerging nations by slashing its wage base, so it must improve its productivity and efficiency to be cost-competi- tive.
The willingness of numerous industries to compete for and share the costs of federal investments in AM areas indicates that these are well past the speculative stage. Integrat- ing software development at the outset with design, as well as new systems for hardware and software integration, appears to be key. Evolve new biomaterials from synthetic biology.
Fabricate at the nano scale. Produce one or small lots at the cost of mass production—for example, through three-dimensional printing and additive manufacturing, where products can be fabricated in highly complex forms through printing from powders as opposed to traditional machine-tool processes. One institute, an industry- university consortium around additive man- ufacturing 29 , has now started.
Other insti- tutes, with costs shared between federal agencies, states, and industry, are proposed for digital manufacturing, lightweight mate- rials, and power electronics. The majority of the U. Therefore, they are less able to assist suppliers and have their own competitive problems adapting. A fourth gap is talent. How will tech- nical workers and engineers be trained to work with advanced technologies and develop processes and routines so as to introduce them into produc- tion systems?
A new credentialing system between com- munity colleges and industry organi- zations for manufacturing skills and development of an AM engineering curriculum could help. Economy-wide macro policies in trade, tax, and currency valuation will be needed, too. But a focus on the structural problems in the gap-ridden manufacturing innovation system is critical. The AMP report proposes addressing a number of these gaps 17, Production is the central way an economy scales growth.
Services are largely face-to- face and tend to scale gradually, but produc- tion can scale rapidly and enable geometric economic expansion. Firms will also increas- ingly offer high-value goods tied to services to provide customers with solutions; the trad- able good can scale, making the accompany- ing service tradeable and scaleable as well [pp.
This means the suc- cess of services-dominant economies like the United States increasingly will be linked to success in manufacturing Unless the United States treats produc- tion as a critical element that must be better connected into its innovation system, it risks erosion of that system. References and Notes 1. Bureau of Economic Analysis, U. International Trade in Goods and Services — ; www. About the Advanced Manufacturing Partnership 2. Recommendations for implementing the strategic initiative Industry 4. Press, New Haven, CT, Press, New York, Online Winter ; www.
Sources for data in this paragraph are 17 , 18 ; pp. Bonvillian, Innovations 7, 97 Wial, Why Does Manufacturing Matter? Bureau of Labor Statistics, Databases, tables and calcula- tions, manufacturing-all employees ; http: Tassey, Rationales and mechanisms for revitalizing U. Press, New York, ed. Berger, How We Compete: Morris, The Dawn of Innovation: National Additive Manufacturing Innovation Institute, http: This is important because genetic changes could result in long-term reductions in catches. To tease apart ecological and genetic contributions, Wijk et al.
Only adult male body size was selected for, because females continue to grow after maturation. The authors provide evidence of changes at individual genetic loci in the male guppies; some of these loci have previously been associated with body size. The authors compared two models. In the second, no evolutionary changes could occur.
Fisheries-induced evolution may also affect macroecological patterns of functional traits. Such patterns include relationships between body size, abundance, and latitu- dinal distribution of different species 6, 7. The effects of commercial fishing are not the only example of human-induced trait changes among wild populations; such changes have also been seen in terrestrial and freshwater systems 3.
The resulting changes are often detrimental to the health of the ecosystems; recovery involves evolutionary time scales, and there may be enduring loss of ecosystem services. Body size is a useful trait to help guide management and conservation because it is involved in many macroecological patterns that account for the numerous interactions among species within complex food webs 3, 4 and within webs of ecoevolutionary inter- actions 3. Shaw 1, 2 The T cell immunological synapse may function as a surrogate cilium. There is an urgent need to define what is sustainable in terms of selectivity, both within and among species 2 , across the full range of body size to address the evolution- ary effects of commercial harvesting 9, Environ 11, I t is claimed that all mammalian cells express a single cilia.
But is this a fruitless search? On page of this issue, de la Roche et al. At the base of a cilium is the basal body, composed of the two centrioles. When not attached to the plasma membrane, the two centrioles constitute the microtubule- organizing center MTOC or centrosome, a structure that nucleates microtubules. Cilia have not previously been observed in lymphocytes, so evidence for their pres- ence in these cells is indirect and function- ally based. During cytolytic cell killing, the MTOC in T cells becomes juxtaposed with the plasma membrane 3 , similar to the posi- tioning of centrioles during mitosis and like the basal body at the base of a cilium 2.
With the MTOC apposed to the membrane, motors that are directed toward the MTOC dyneins are suff icient to transport secre- tory vesicles to the membrane. Primary cilia function mainly as a sensory organ. Important signal transduction receptors are transported to the tip of the cilium where they initiate signaling pathways. An impor- tant ciliary signaling pathway is controlled by the secreted protein Hedgehog Hh.
Hh plays critical roles during embryogenesis and adult tissue homeostasis. Disruptions of Hh signal transduction lead to congenital abnormalities such as polydactyly, skeletal abnormalities, and holoprosencephaly, whereas persistent Hh signaling is associated with various can- cers 5. Because Hh signaling in mammalian cells requires primary cilia, de la Roche et al. A Conventional Hh signaling pathway is initiated by extracellular Hh binding to Ptch. This releases Smo, which migrates to the cilium where it induces Gli activation GliA.
This leads to the trans- location of vesicles containing Smo to the plasma membrane, activation of Gli, and MTOC recruitment to the immune synapse. Hh signaling involves the ligand, Hh; its cell surface receptor, Patched Ptch ; and another transmembrane protein, Smooth- ened Smo. In the absence of Hh, Ptch func- tions as an inhibitor of Smo. Hh binding to Ptch releases Smo, allowing it to be trans- ported to the tip of the cilium. This activates the Gli family of transcription factors to con- trol genes involved in proliferation, devel- opment, and pattern formation 5 ; activates the RAC guanosine triphosphatase to modify actin important for cell migration and den- dritic spine formation 6, 7 ; and induces a metabolic switch to glycolysis 8.
Gli1 induces its own expression 2 , so an increase in Gli1 is indicative of Hh signal- ing. Hh appears to stimulate Ptch in the same cell, as both ligand and receptor are found together in secretory vesicles. Ptch signal- ing only occurs in the vesicle as cells did not respond to exogenous Hh. Imaging showed that these vesicles are distinct from the late endosomes that contained internalized Smo. This indicates that Hh binds to its cognate receptor within the same T cell. Moreover, activation of the T cell receptor and presum- ably Hh signaling increased Hh production and induced the translocation of Smo to the immunological synapse.
The absence of Smo or treatment of T cells with inhibitors of the Hh signaling pathway attenuated the ability of cytotoxic T cells to kill target cells in vitro. The immunological synapse is a specialized organization of proteins at the contact surface between a T cell and an antigen-presenting cell. It is composed of an outer ring that is rich in actin and adhesion proteins integrins , and a central region that is free of actin, where secretion occurs. Because the MTOC makes contacts with the membrane in this central area, the authors suggest that the center of the synapse func- tions as the lymphocyte equivalent of a cil- ium.
Rac-medi- ated actin remodeling is also controlled by Hh 6, 7 , and de la Roche et al. The observation that Smo relo- cates to the immunological synapse follow- ing T cell receptor activation with antigen- presenting cells is consistent with the role of the synapse as a cilium surrogate. Several aspects of the pathway described by de la Roche et al.
Hh is usually secreted and functions in a concentration gradient, but the pathway described by the authors occurs within a single cell and is therefore not dependent on a gradi- ent. Because Smo and Ptch are localized in distinct vesicles, how Ptch regulates Smo and whether translocation of Smo to the membrane requires intraflagellar transport proteins is unclear. T cell receptor signaling increased their expression but did not enhance colocal- ization of Ptch and Hh in secretory vesicles, so why activation of the Hh pathway is not constitutive is not clear.
How Smo relocation leads to Gli activation, and if it is important for MTOC polarization toward the immunologi- cal synapse, remains to be determined. Do these data support the idea that the immunological synapse is a frustrated cil- ium? Hh signaling functions in Drosophila melanogaster without cilia, so Hh signal- ing does not necessarily require cilia 5. And while the ability of the MTOC to inter- act with the plasma membrane during secre- tion is reminiscent of the basal body below the cilia, basal bodies are anchored to the plasma membrane by a specialized complex of proteins.
The MTOC of the cytotoxic T cell appears to have a much more dynamic inter- action with the plasma membrane, interact- ing only transiently with it 3. W hy did the plate boundary fault at the Japan Trench slip tens of meters to generate a devastating tsunami in the Tohoku—Oki earthquake on 11 March ? Based on differ- ent types of observations, Chester et al. According to various observations, the maxi- mum slip exceeded 50 m near or at the trench. Faults slip at a wide variety of rates. Earthquake rupture, or seismic slip, is fault slip at the highest rate.
This model is supported by observations in some subduction zones, such as Sumatra 5 , and is similar to what is seen for many continental earthquakes, in which surface rupture is often smaller than slip at depth. The large shallow slip in the Tohoku- Oki earthquake thus came as a surprise. There are different hypotheses regarding the shallow megathrust at the Japan Trench. In one view, the rate-weakening seismo- genic zone extends all the way to the trench.
In another, the shallow megathrust is rate- strengthening but unable to resist a large slip propagating from the deeper part of the fault 4, 6. Such high-rate weakening has been observed in recent laboratory rock fric- tion experiments regardless of rock type, and various mechanisms have been proposed to explain it 8. Somewhat similar to the third view but without involving high-rate slip is the idea of conditional stability, accord- ing to which some rate-strengthening faults can become rate-weakening in response to a small sudden increase in slip rate.
By analyzing core samples and in situ geophysical measurements made in the bore- holes, Chester et al. The extraordinary localiza- tion of shear is caused by a layer of weak clay along which the fault develops. However, by exposing the available samples to friction experiments, Ujiie et al. With temperature monitoring in a nearby hole, Ful- ton et al. The weakness of plate boundary faults has long been recognized.
An earlier sugges- tion of extremely low strength of the Japan Trench megathrust 12 has been dramati- cally verified by a reversal of upper-plate stress from compression to tension as a result of the Tohoku-Oki earthquake 13, The JFAST results not only identify the geo- logical reason why the shallow megathrust is so weak, but also show that it may have become even weaker during the magnitude 9 earthquake. Seismic rupture occurs along extremely thin slip zones The weak clay layer that makes the fault zone very thin provides a structural condition to host seismic rupture.
The third view about the Japan Trench shallow megathrust discussed above—low-rate strengthening but high-rate weakening—can explain why the huge shal- low slip did not happen everywhere along the trench during the Tohoku-Oki earthquake and not every time the seismogenic zone rup- tured in the past. Although very large slip occurred at the trench in the Tohoku-Oki earthquake, it is unclear whether the peak value of the slip was at the trench or some distance landward of it, and why there were no aftershocks in the most seaward 45 km of the upper plate Further research is required to deter- mine how fault behavior varies with depth as well as laterally along the trench.
These results suggest that the trench-breaching large slip was facilitated by a thin and weak fault zone at shallow depths. The results of Chester et al. The JFAST data show how direct borehole sampling and monitoring can help to eluci- date the slip behavior of the shallow megath- rust. Results from other ongoing and future megathrust drilling projects, such as those at Nankai and off Costa Rica, will enable com- parisons between different subduction zones.
However, while studying the shallow part of the fault, scientists must keep in mind that subduction earthquakes may generate dev- astating tsunamis even without huge shallow slip as in Tohoku, such as in Sumatra in and Chile in Lapusta, Nature , Di Toro et al. Geology 41, Brod- sky, in Earthquakes: Unlike fault strength, stress drop along the megathrust during an earthquake can be estimated from seismic and geodetic measurements. The stress drop during the Tohoku-Oki earthquake is measured at only a few megapascals.
A stress reversal in the upper plate would not happen if this value were only a small fraction of megathrust strength. Nowhere is this more true than in the plant kingdom. Here, microtubule organization patterns the deposition of cellulose, the prime constituent of cell walls, thus controlling the ability of plants to grow in the direction of light, or pho- totropism.
The research article by Lindeboom et al. In an imaging tour de force, Lindeboom et al. Microtubule crossovers were previously shown to be hotspots for sev- ering in cortical arrays 4. The key player in this process is the micro- tubule-severing enzyme katanin, an AAA adenosine triphosphatase ATPase that is thought, by analogy with its family mem- ber spastin, to sever the microtubule through extraction of tubulin subunits from the microtubule lattice 5, 6.
A katanin null mutant shows no creation of new micro- tubule plus ends, as well as impaired reori- entation of the array upon exposure to light. Because some of the new ends created by sev- ering the microtubules do not depolymerize but are stable and able to regrow, severing has an overall constructive rather than destructive role and contributes to the net growth of the microtubule array. One implication of this crossover-activated severing mechanism is that as the array gradu- ally reorients and the population of longitudi- nal microtubules increases, the frequency of severing decreases because there are fewer crossovers , thus dampening new microtubule generation and stabilizing the array in its new orientation.
Interestingly, a complementary study by Zhang et al. Future studies will likely address the relative contributions of these two outcomes to overall array reorientation. How does katanin distinguish crossover sites from bundled or single microtubules? In vitro, katanin severs microtubules at any point along their length 7 ; however, experiments with dynamic microtubules or complex micro- tubule geometries more closely resembling those in cells have not been performed, and the fate of the new microtubule end gener- ated by a microtubule-severing enzyme in vitro is still not known does it catastrophi- cally depolymerize, or is it able to regrow?
Katanin assembles into a hexamer with multiple microtubule-binding domains that could be maximally engaged only when two microtubules cross each other 5, 6. It is also possible that the regulatory subunit, of which Arabidopsis encodes four, senses microtubule crossovers. Future studies will address whether p60 targeting to crossovers is impaired in p80 mutants.
Additional factors could also sense the microtubule crossover and regulate katanin function. A recent study in Arabidopsis pave- ment and petiole cells revealed that severing frequency at microtubule crossovers inversely correlates with the presence of the micro- tubule-associated protein SPIRAL2, which itself induces microtubule crossovers 3.
The phenotypes of katanin and spriral2 mutants are diametrically opposed. The katanin mutant displays complex crossovers formed by mul- tiple microtubules, whereas the spiral2 mutant has very few. How SPIRAL2 itself senses crossovers is not clear, but it might be trans- ported along the microtubule to crossover sites 3. Future in vitro studies with microtubule arrays of diverse geometries and in the presence of various microtubule- associated proteins will be essential in under- standing the feedback between array architec- ture and katanin function.
Centrosomes act as microtubule-organizing centers in animals; however, they pattern microtubules in an iso- tropic or radial array. Most cells in our body do not have radial microtubule arrays; many cells lack centrosomes altogether Thus, the mechanis- tic insights from the studies by Lindeboom et al.
Vale, Nature , Vale, Cell 75, Roll-Mecak, Cytoskeleton 69, A Severing dependent microtubule growth is analogous to a railroad turntable that splits two tracks. C Microtubules are arranged in diverse patterns best adapted to cell type and organism: One of the simplest exam- ples of a nonlinear effect is doubling the input fre- quency of light with a nonlinear crystal.
The out- put intensity of the fre- quency-doubled light then grows nonlinearly with the intensity of the laser beam. To maximize mac- roscopic nonlinear sig- nals, the wavelets emitted by the elementary nonlin- ear sources need to add up in phase. On page of this issue, Suchowski et al. The authors avoided the phase-matching problem by relying on a metamaterial that has a refrac- tive index for the interacting wavelengths near zero keeping in mind that the refractive index of the vacuum is not zero but unity. Furthermore, they achieve equal nonlinear emission in two opposite directions simulta- neously, whereas conventional phase-match- ing techniques maximize the nonlinear signal in only one direction.
Phase matching is challenging because the wave oscillations in propagation are deter- mined by the refractive index of the material, and the refractive index depends on wave- length. To better understand the phase-match- ing problem, a closer look at frequency dou- bling, or second harmonic SH generation, is helpful. For thicker samples see the figure, panel C , the wave oscillations in propaga- tion become important, and their rate is pro- portional to the refractive index.
In general, however, the refractive index for the SH wavelets is dif- ferent because of the higher frequency. The wavelets from different locations then lose their phase relation after a distance known as coherence length. Perfect phase matching in the forward direction occurs when the refractive indices for the two wavelengths are equal. This con- dition can be achieved in birefringent crystals for different polarizations of the interacting waves. Quasi—phase matching 3 relies on micro- or nanostructuring the material so that it reverses the sign of its nonlinearity after every coherence length, thereby restoring the phase relation between the wavelets.
This approach is possible for either the forward or the backward process, but not for both at the same time. This case is the one demonstrated by Suchowski et al. Metamaterials first received attention because they can possess a negative refrac- tive index 4 , which allows imaging with res- olution below the diffraction limit 5. Meta- materials usually consist of metal-dielectric composites, whose plasmonic resonances collective oscillations of electrons can enhance optical effects, including nonlinear ones 6. Nonlinear experiments on metama- terials in the optical regime have mainly been limited to thin, surface-type samples 7— 9 , where phase matching is not a constraint.
However, negative-index bulk materials and their phase-matching properties have been studied in the microwave regime The spatial oscillations of the fundamental wave and SH source polariza- tion are shown by red and blue lines, respectively; green lines indicate SH wavelets.
A An elementary SH source emits in all direc- tions. C For thick samples, the phase relation between the SH wavelets is lost after a coherence length, because the source and wavelets oscillate at different rates. D In a material with refractive index n of zero for both wavelengths, the oscillations do not occur and all SH wavelets add up in phase in the forward and backward directions. Box , FI Tampere, Finland. Jones Epidermal stem cells produce the signals that control tissue homeostasis.
M aintaining proliferating adult tis- sues involves a critical balance. Exactly the right number of cells must be produced to replace those lost from the tissue; otherwise, tissue failure or tumor formation will ensue. On average, each cell division generates one daughter that goes on to divide and pro- duce more such cells, while the other cell differentiates and migrates to the surface of the epidermis 2.
Cell production must be adjusted in response to surface abrasion or injury, implying that proliferation is regu- lated by signals from nearby cells. One can- didate for this role is the secreted protein Wnt, as mutations that disrupt its down- stream cellular signaling pathway result in hairless, thin epidermis 3, 4. Two studies— by Lim et al.
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They show that Wnt and Wnt inhibitors balance the renewal and differentiation of epidermal stem cells and are both secreted by the stem cells them- selves. Both studies found Axin2-expressing cells in the proliferative basal layer of the epidermis. The label is transmitted to daughter cells, producing clones 8. Using statistical analysis of the clone size distribu- tion, Lim et al.
Each cell in the basal layer divides to generate two divid- ing daughters, two differentiating daughters, or one cell of each type. Although the out- come of individual divisions is unpredict- able, the odds are balanced, so homeostasis is achieved across the Axin2-expressing popu- lation. A question that arises from these obser- vations is how an injury to the paw can be healed. To achieve this, an excess of prolif- erating cells must be produced. The main reason for this is that the structure has a near-zero index only over a narrow wavelength range around nm.
Whereas SH generation involves two very different input and output wavelengths, FWM occurs between nearby wavelengths. The sig- nal can be detected at a nearby frequency, and all the interacting frequencies are now in the range where the metamaterial has a near-zero index. The forward and backward FWM sig- nals are indeed equally strong, even though the sample cannot be considered thin. In the pres- ent experiment, the sample has near-zero index only for light propagating along the sample normal, whereas light propagating in the sample plane experiences a very dif- ferent index In contrast, an isotropic metamaterial with zero index would emit in all directions, which is undesirable for signal collection.
The present metamaterial has a period of 80 nm in the direction of propagation.
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The results could potentially arise from a type of quasi—phase matching, but the authors exclude this possibility by estimating that the coherence length for backward FWM is about nm, much longer than the period. They also show in supplementary material that essentially identical results are obtained from treating the structure as an effective metamaterial and from accounting for each layer of the structure separately.
It is relatively easy to phase-match FWM between nearby wavelengths in almost any material, albeit only in one direction. Never- theless, their work demonstrates a completely new principle for overcoming the phase- matching problem. From a more general viewpoint, the report shows that metamaterials can control nonlinear pro- cesses in unprecedented ways, opening the path toward nonlinear structures with uncon- ventional emission properties.
Photonics 5, Photonics 6, Linden, Science , B 78, Photonics 1, How- ever, Lim et al. This suggests that cells expressing Axin2 in the vicinity of a wound may transiently switch from balanced cell production to generat- ing an excess of proliferating cells, enabling them to heal a wound themselves, behavior also evident in esophageal epithelium These observations add to a growing body of evidence for behav- ioral plasticity in injured epithelia, with pro- liferating cells changing fate and differenti- ated cells reentering the cell division cycle to repair injured tissues 12— This demonstrates that Wnt signaling is active in epidermal stem cells, but does it regulate their behavior?
They also show that Dkk protein accumulates in the supra- basal layers, suggesting that differential dif- fusion of both molecules restricts Wnt activa- tion to the basal layer of the epidermis. Wnt signaling is needed for stem cell self-renewal and the relative amounts of stem cell—derived Wnt and Dkk may regulate stem cell fate. What about the hair follicles? These are sustained by multiple populations of stem cells, both in the upper follicle, which is con- tinuous with the epidermis, and in the bulge and lower follicle, which undergoes cycles of expansion anagen , regression catagen , and quiescence telogen 1.
This indi- cates that Wnt signaling is essential to initiate and sustain follicle expansion. The authors also observed that long-term induction of Dkk1expression pro- duced bald mice, in which the follicle and bulge stem cells persisted. The results of Lim et al. How cells might escape the autocrine loop of Wnt signaling and commence the differentia- tion process remains unclear. Whether Wnt contributes to the injury response of stem cells also remains to be elucidated.
Nusse, Cell , Cancer 13, Cell 18, Jones, Bioessays 35, The daughter cells produce both Wnt blue arrow and Dkk red arrow. Dkk accumulates in the suprabasal layer red , blocks Wnt signaling, and pro- motes differentiation. B In the growth phase of the hair cycle, the lower part of the follicle expands ana- gen. Axin2 expression and Wnt signaling is observed in proliferating cells in the dermal papilla, secondary hair germ, matrix, and hair shaft progenitors, but is absent from the bulge stem cells.
Streicker Interdisciplinary research on zoonotic pathogens illuminates ecology and evolution, while guiding disease prevention and control. E merging infectious diseases threaten all forms of life on Earth. Many patho- gens of great historical and contem- porary significance have originated from other species, triggering pandemics, disrupting agricul- ture, and challenging efforts to conserve endangered wildlife. Despite decades of research on species-jumping pathogens, the most central questions in the field remain major stumbling blocks for societies that seek to mitigate their impacts.
These questions include which patho- gens are most likely to emerge, which hosts are most likely to share pathogens, and what will be the long-term fate of newly emerged pathogens? Solutions therefore demand innovative pairing of theory and fun- damental science with applied research and evidence-based policy-making. My doctoral research used viral infections of bats to answer fundamental questions about pathogen emergence and to help guide control of a major zoonosis in the developing world. Working on bats was partly pragmatic—natu- ral populations can easily be sampled in large numbers, and existing surveillance systems for reportable diseases, such as rabies, provide rich data sets.
This choice was also driven by the fact that bats are a major source of highly pathogenic viruses, including severe acute respiratory syndrome SARS , Nipah, Hen- dra, and Ebola viruses, which often emerge in the context of anthropogenic change with devastating outcomes for humans and ani- mals 1. From an ecological and evolutionary perspective, the high species diversity of bats also presents a unique and fascinating system to test hypotheses on cross-species emergence in complex host communities. Using ecological and molecular sequence data from both bats and viruses, I developed a novel population genetic framework to quantify transmission rates between spe- cies.
This analysis 2 showed that, counter to the popular notion that rapid evolution in RNA viruses should make eco- logical overlap the best predic- tor of which host species share viruses, the genetic similarity of hosts constituted the strongest barrier to both initial infection and viral establishment in new species.
The strong phylogenetic con- straints on cross-species transmission move us closer to predicting the species origins of viral emergence. Despite recurrent cross-species transmis- sion in many natural systems, sustained patho- gen transmission in newly infected species is rare.
This outcome, although fortu- nate for agricultural, veterinary, and public health interests, represents an obstacle to identifying the mechanistic underpinnings of emergence, because many independent introduction events must be tracked to deduce the predic- tors of successful emergence. Dozens of historical host shifts among Amer- ican bat species make rabies an ideal system to explore the epidemiologi- cal and evolutionary repeatability of viral emergence.
Genomic and demo- graphic inference showed that rabies followed distinct evolutionary path- ways to become established in dif- ferent host species. Further, viruses for which greater adaptive evolution- ary changes occurred took longer to establish endemic transmission in new hosts.
Science - December 6 2013
This work 3 , addressed the outstanding question of how much evolution happens during host shifts, which may help anticipate the speed and likelihood of viral establishment in new host species. A related study explored the interactions between host ecology and viral evolution by quantifying the rate of molecular evolution across 21 bat- associated rabies viruses. The tempo of viral evolution was surprisingly variable and pro- foundly dependent on host ecology. Viruses in temperate bats evolved more slowly by a factor of up to 22 than those in tropical and subtropical species, a likely consequence of seasonal interruption of transmission during hibernation.
These results 4 imply that bat rabies risk for humans and domestic animals in the tropics will be less predictable than in the temperate zone and demonstrated how host biology can shape the speed of viral evo- lution. These studies highlight the power of inte- grated ecological and evolutionary analyses to reveal general patterns in the frequency, ori- gins, and dynamical outcomes of cross-spe- cies transmission. However, they offer no easy solutions for policy-makers seeking to prevent disease. Cross- cutting research across ecology, phylogenetics, mathematical modeling, and public health on species such as the common vampire bat can illuminate basic principles of disease biology and provide crucial tools to mitigate the impacts of emerging viruses on health, agriculture, and conservation.
Yet, interven- tions in reservoirs are notoriously challenging and controversial because of limited under- standing of pathogen persistence in complex wildlife systems 5, 6. The only bat that is culled to manage zoonotic disease is the com- mon vampire bat Desmodus rotundus, found throughout the neotropics see the photo.
Despite control campaigns since the s, lethal human rabies outbreaks transmitted by this species are common, and annual live- stock deaths number in the thousands 7. In , I launched a collaborative research pro- gram aimed at reducing this burden through enhanced understanding of rabies ecology in vampire bats.
Findings from this project ques- tion the core assumptions underlying culling bats for disease control. By monitoring more than bats across a network of colonies in Peru for nearly 4 years, I showed that rabies exposure in vampire bats was unrelated to colony size. This work 8 further showed that culled colonies had either equivalent or higher rates of viral exposure compared with those that were not. These results challenge the con- ventional wisdom that fewer bats equals less disease and provide a view toward more effec- tive rabies control in Latin America through spatially synchronized interventions.
My thesis work at the interface between ecology, evolution, and anthopogenic change underscores emerging diseases as one of the most fascinating, challenging, and impor- tant topics in the environmental life sciences. Together, these studies provide salient exam- ples of how transdisciplinary collaboration can illuminate fundamental concepts in dis- ease biology, while advocating a science- guided path to anticipate and prevent future disease emergence.
He received his Ph. Centers for Disease Control and Prevention. He received the Robert C. Hong received a B. Schmidt is a Strategy Consultant at L. Consulting in London where he works as a strategic adviser to the biopharma and life sciences industry. Before getting his Ph.
Zenobi See also more cell biology in this issue: Such single-cell measurements are providing a wealth of information—sometimes unanticipated and often previously obscured—about how cells respond to perturbations or signals. In this special issue, three Reviews provide examples of fundamental insights into cellular regulation that are revealed when it is possible to measure enzymatic activity, transcriptional responses, or the metabolic state in individ- ual cells. In many instances, it is possible to monitor the time course of cellular responses.
Gene transcription can be particularly noisy, with bursts of RNA synthesis occurring in some cells but not others of the same popu- lation. Thus, fundamental questions arise about the nature of these systems. Perhaps variation in response is advantageous in conserving resources or in assuring that some cells survive in a changing environment. Or it may be that biophysical constraints of small numbers of molecules and the characteristics of the enzymes at work dictate such variability as unavoidable. Sanchez and Golding review recent work in model systems, from bacteria to animal cells, that attempts to resolve whether the kinetics of transcription are encoded in the architecture of promoter sequences in DNA—and might therefore vary through- out the genome—or are determined by physical or biophysical properties that would impose more global constraints throughout the cell.
Continuous measurements of protein activation show that many undergo asynchronous pul- satile responses, which are obscured in average measurements from a popu- lation of cells. They discuss how cellular circuits are wired to produce such responses and what the advantages of such control systems might be.
Zenobi highlights methodological advances, particularly in mass spectrome- try, that are enabling quantitation of the abundance of molecular components of single cells. Challenges abound for the goal of making simultaneous measure- ments to characterize the rapid ly changing metabolic state of individual cells. Often, it occurs in a bursty, intermittent manner. It is still unclear to what degree transcriptional kinetics are specific to each gene and determined by its promoter sequence. Alternative scenarios have been proposed, in which the kinetics of transcription are governed by cellular constraints and follow universal rules across the genome.
Evidence from genome-wide noise studies and from systematic perturbations of promoter sequences suggest that both scenarios—namely gene-specific versus genome-wide regulation of transcription kinetics—may be present to different degrees in bacteria, yeast, and animal cells. The advent of rapid, inexpensive DNA se-quencing methods allows scientists to mapnot only the protein-coding genes in the genomes of many organisms, but also the reg- ulatory sequences present in those genomes.
A key challenge for biologists in the next few decades is understanding how these regulatory sequences control the expression of every gene in the cell and how they collectively determine the topology and dynamics of gene regulatory networks. The regulation of gene expression tradition- ally has been studied in experiments thatmeasured the average gene expression level in populations containing millions of cells. These studies relate the average rate of gene expression for a gene to its regulatory DNA sequence the promoter architecture 1.
This approach has a major short- coming, however, because averaging over pop- ulations masks differences in gene expression that may occur between individual cells 2. These differences may in turn have consequences for the whole multicellular community or organism, which makes it important to understand gene ex- pression in single cells. Within a single cell, gene expression is in- herently stochastic, or random 2. Protein-coding genes are typically present in only one or two copies per cell. Whether a gene is transcribed at any given moment depends on the arrival, by diffusion, of multiple regulatory proteins to their designated binding sites, as well as the occur- rence of multiple biochemical steps required for initiation of transcription 3.
These biochemical reactions are all essentially single-molecule events and thus stochastic, resulting in substantial ran- domness in the production of mRNA. Broadly, two stochastic kinetic modes of transcription have been observed in individual cells: The kinetic fea- tures of mRNA production are in turn propagated to the proteins translated from them. The end re- sult is temporal fluctuations, and corresponding cell-to-cell variability, in mRNA and protein num- bers. This cell-to-cell variability is referred to as gene expression noise Box 2 2.
Bursty transcription typically leads to higher noise than does Poissonian transcription. In par- ticular, the burst size controls the magnitude of the noise, and it is approximately proportional to the Fano factor the ratio between the variance and the mean of the distribution of mRNA or protein numbers per cell.
Thus, genes with large burst sizes are characterized by broader distri- butions of protein andmRNA, larger Fano factor, and higher noise as comparedwith those of genes with small burst sizes. The inherent randomness associated with gene expression raises an important question: Are the stochastic kinetics of transcription—and therefore the resulting variability in mRNA and protein levels—encoded by the promoter regu- latory sequence, just as the mean expression level of a gene appears to be? Two alternative answers have been put forward. One view is that the sto- chastic kinetics of gene activity are genetically determined by the promoter architecture and gov- erned by the binding and unbinding of various regulatory elements such as histones and tran- scription factors to their corresponding binding sites 9— In this view, it is the process of gene regulation, as it acts on each promoter individu- ally, that causes bursting in some genes but not in others.
An alternative view is that transcription kinetics are dominated by genome-wide constraints that lead to general—as opposed to gene-specific— modulation of transcriptional kinetics 16— These constraints may reflect any number of phys- iological or biophysical mechanisms. Proposed mechanisms include cell-cycle—dependent regula- tion of promoter activity 20 as well as inherent features of the transcription process, such as the cooperative recruitment of RNA polymerases Notwithstanding the specific details, this view im- plies that gene-specific transcriptional regulation acts on top of these gene-nonspecific constraints and has only a secondary effect on the observed kinetic features, such as transcription bursts.
In the first view described above, transcrip- tional kinetics in particular, bursting are gene- specific and free from global constraints. One consequence of this is that at both very low and very high rates of transcription promoter activity is expected to be regular in time andwell-described by Poisson statistics Fig. At intermediate rates of transcription, when genes are neither ex- pressed at full capacity nor very infrequently, dif- ferent genes may vary greatly in their temporal kinetics and exhibit either regular Poissonian or bursty behavior, depending on the particular mechanisms of transcriptional regulation for each gene Fig.
In contrast, global constraints on transcrip- tional kinetics that affect all genes Fig. For instance, one such constraint that has been recently reported 16—18 is the presence of inherent and global bursting kinetics even in fully active gene loci. Thus, highly expressed genes are not Poissonian but instead characterized by large burst sizes Fig. Because this constraint operates globally, all genes in the cell follow a characteristic trend between the burst size and the mean amount of expression Fig. The two views described above represent two limiting cases; it is possible that single-cell tran- scriptional kinetics are affected, to varying de- grees, by both gene-specific promoter architecture and genome-wide processes.
This Review crit- ically examines both views and the evidence sup- porting each of them. An organism forwhich there is strong evidence for a genetic origin of transcrip- tional noise is the yeast Saccharomyces cerevisiae. In the prokaryote Escherichia coli, as well as other eukaryotic systems, the picture is less definitive than in yeast, but some evidence exists pointing to the presence of global constraints. As noted above, it is possible to estimate the burst size from the degree of cell-to-cell variability in pro- tein concentration supplementary materials. The results of all of these experiments are consistent in that they find no obvious trend between the mean expression level from a promoter and the estimated burst size Fig.
The only global constraint observed in the noise measurements is the one corresponding to the limiting case of Poissonian transcription, followed by Poissonian translation of mRNA into protein 2. These global noise experiments also reveal relationships between noise measured for a given promoter and the known properties of that pro- moter.
The majority of low-noise promoters have a characteristic architecture [depleted proximal nucleosome DPN ] that is defined by a nucleosome- free region immediately downstream of the ini- tiation site. In contrast, the majority of high-noise promoters have a second type of architecture [oc- cupied proximal nucleosome OPN ], character- ized by the lack of a nucleosome-free region. They are also enriched for strong TATA boxes 25, The model emerging from these findings is that promoter switching between inactive promoter occluded by nucleosome and active nucleosome free, preinitiation complex formed states may re- sult in bursty transcription, in turn leading to the higher noise observed in nucleosome-covered pro- moters.
Within this picture, the strong TATA box would ensure that the promoter is expressed strong- ly when active, increasing the burst size This model is further supported by single- mRNAcounting experiments in fixed cells Fig. All of these promoters exhibited close-to-Poissonian mRNA copy-number distri- butions and sub-Poissonian with lower variance than a Poissonian distribution of the same mean nascent RNAcopy number distributions, which is consistent with the absence of bursts.
In contrast, promoters that are not constitutive, but regulated by nucleosomes and transcription factors, exhib- ited broader mRNA distributions consistent with bursty transcription Fig. These single-cell mRNA counting experiments substantiated the notion that the observed differences in protein noise between promoters [as in the studies above 22—24 ] reflect the fluctuations of the mRNA species which in turn are driven by transcriptional kinetics. The mRNA-counting studies specifical- ly predicted that in the low-noise, nucleosome- depleted promoters, transcription events should occur regularly in time, in a simple Poissonian manner.
This prediction was confirmed in experi- ments in which the kinetics of transcription were followed in real-time by using temporal correla- tion analysis of fluorescently labeled mRNA molecules in live yeast cells 4. Both the consti- tutive promoterMDN1 and the cell-cycle—activated promoter POL1were transcribed in random, un- correlated events with a single rate of initiation that varied during the cell cycle 4 The evidence above indicates that the kinetic mechanism of transcription for a yeast promoter is mainly encoded by the DNA sequence of the promoter.
To substantiate this picture, investigators deliberately altered yeast promoter architecture and examined the resulting change in gene expression noise. The systematic alterations included the pres- ence or absence of a TATA box and its strength 12, 24 ; the number 15, 29 , location 15 , and nu- cleosomal coverage 30 of transcription-factor bind- ing sites; the presence of nucleosome-disfavoring sequences 13 ; and the mode of action of a tran- scription factor [whether it was acting as an acti- vator or as a repressor 14 ].
All of these architectural elements were found to strongly affect the rela- tionship between the mean amount of expression and the burst size, in a way that is consistent with the expectation from simple models of transcrip- tional kinetics Fig. The evidence indicates that the stochastic transcriptional kinetics for a given gene in yeast is mainly determined by its promoter architecture, and no strong global constraints have been observed.
Promoter switching introduced by transcription factors and nucleosomes stochastically associating and dissociating leads to a bursty transcription and correspondingly higher degree of noise than that observed in constitutive promoters Additional promoter features such as the strength 12, 13 and copy number 15, 29 of transcription-factor bind- ing sites, their location within the promoter 15 , and the specific mechanism of gene regulation by the transcription factors bound to them 14 all affect noise in gene expression.
Evidence for Global Noise Constraints in E. Analysis of how adding an inducer of gene expression affected the bursting parame- ters revealed that the burst frequency was mod- ulated at low concentration of inducer, whereas Fig. Gene-specific versus global determi- nants of transcription kinetics.
Two alternative scenarios are presented, representing different ways in which stochastic promoter activity may be governed. Top In the first scenario, the rates of promoter activation and inactivation are controlled exclusivelybygene-specific mechanisms. A Abstract Index by Name The conference is aimed at college and university undergraduate and graduate students who participate in programs funded by the NSF HRD Unit, including underrepresented minorities and persons with disabilities. Other conference activities include workshops focused on: Exhibitors include representatives from academic, government, business, and the non-profit sector with information about graduate school admissions, fellowships, summer research opportunities, professional development activities, and employment opportunities.
For more information, visit the Web site at http: The creation of new knowledge, innovations, and models for broadening participation in the STEM enterprise. The Division of Human Resource Development HRD serves as a focal point for NSF's agency-wide commitment to enhancing the quality and excellence of STEM education and research through broadening participation by historically underrepresented groups - minorities, women, and persons with disabilities.
Priority is placed on investments that promise innovation and transformative strategies and that focus on creating and testing models that ensure the full participation of and provide opportunities for the educators, researchers, and institutions dedicated to serving these populations. Programs within HRD have a strong focus on partnerships and collaborations in order to maximize the preparation of a well-trained scientific and instructional workforce for the new millennium.
HRD envisions a well-prepared and competitive U. HRD's mission is to grow the innovative and competitive U. The translation of knowledge, innovations, and models for broadening participation in STEM for use by stakeholders. The expansion of stakeholder capacity to support and engage diverse populations in high quality STEM education and research programs. A basic premise of all HRD programs is that increasing the successful participation of individuals from historically underrepresented groups in STEM will result in a diverse, highly capable STEM workforce that can lead innovation and sustain U.
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From this comprehensive input, ENG identifies, evaluates, and prioritizes those frontier topics that best match the EFRI criteria transformative, addressing a national need or grand challenge, multi- or inter-disciplinary, an area where the community is poised to respond, and clearly demonstrating ENG's leadership role. Motivated by the vision of ENG to be the global leader in advancing the frontiers of fundamental engineering research, EFRI serves a critical role in helping ENG focus on important emerging areas in a timely manner.
Each year, EFRI will recommend, prioritize, and fund interdisciplinary initiatives at the emerging frontier of engineering research and education. These investments represent transformative opportunities, potentially leading to: The EFRI process of selecting, announcing, and funding new frontier areas will function throughout the year, ensuring continual input and feedback from the engineering community on promising future research opportunities.
Four primary program areas fulfill the AAAS mission: Science has the largest paid circulation of any peerreviewed general science journal in the world, with an estimated total readership of one million. The non-profit AAAS is open to all and fulfills its mission to "advance science and serve society" through initiatives in science policy; international programs; science education; and more.
For the latest research news, log onto EurekAlert! Visit the AAAS website at http: Malcom, Director Yolanda S. Scientific Computation and Visualization: Department of State D. In this role, he is responsible for identifying new enabling technologies to support the development of advanced, Internet-based products and services from Google. Widely known as one of the "Fathers of the Internet," Cerf is the co-inventor of the architecture and basic protocols of the Internet. He has received twenty honorary degrees.
In December , President Clinton presented the U. Kahn, for founding and developing the Internet. Turing award in for their work on the Internet protocols. Cerf served as chairman of the board of Internet Corporation for Assigned Names and Numbers CANN from , founding president of the Internet Society from , and served a term as chairman of the Board in Cerf is honorary chairman of the IPv6 Forum, dedicated to raising awareness and speeding introduction of the new Internet protocol.
He served as a member of the U. Presidential Information Technology Advisory Committee PITAC from to and serves on several national, state and industry boards and committees focused on cyber-security and other topics. He sits on the Board of Associates of Gallaudet University. Crumpton-Young is the recipient of the U. Her research interests include human performance modeling and analysis, human reliability analysis, human fatigue assessment and modeling, use of virtual reality and computer simulation in ergonomics design and analysis, design of displays and controls, workplace design; carpal tunnel syndrome prevention and control; and workplace redesign for disabled persons.
She has served as Principal Investigator on numerous research projects and published hundreds of scholarly publications. She is a fellow in the African Scientific Institute and holds the distinction of being one of the first African-American females to hold the rank of Full Professor in Engineering in the country. She taught mathematics and co-founded the SummerMath for Teachers program at Mount Holyoke College, and served on the mathematics faculty at the University of New Hampshire from through Joan was a faculty member in the MSU departments of mathematics and teacher education, and was named a University Distinguished Professor of Mathematics Education.
Ferrini-Mundy has had a number of public policy-related positions, including as Director of the Mathematical Sciences Education Board at the National Research Council , and in various positions at the National Science Foundation program officer in Teacher Preparation and Enhancement, ; and inaugural director, Division of Research on Learning in Formal and Informal Settings, — Government Senior Executive Service.
She was president of the organization Women and Mathematics Education. Her research interests include calculus teaching and learning, mathematics teacher learning, and STEM education policy. George conducts evaluations, workshops and reviews for the National Institutes of Health and National Science Foundation, as well as for private foundation and public agencies, including the European Commission.
She develops and coordinates conferences and workshops related to STEM undergraduate reform and recruitment and retention of minorities, women, and persons with disabilities in STEM. George serves on a number of boards or committees, including: She has authored or coauthored over 50 papers, pamphlets, and hands-on science manuals. He has also held faculty positions at Clemson University and Auburn University. His research projects include voting technology and accessibility including access for the blind , college admissions software for achieving diversity, automotive user interfaces, internet use among the elderly, investigating player behavior and experience in speech-enabled multimodal video games.
Previously, Holt represented the 12th congressional district of New Jersey for eight terms in the United States House of Representatives. He has held positions as a faculty member at Swarthmore College from , where he taught courses in physics, public policy, and religion. As an arms control expert at the U.
As a result of his alternative energy research, Holt in was issued a patent on an improved solar-pond technology for harnessing energy from sunlight. Holt's science- and education-related roles in Congress have included service on the Committee on Education and the Workforce; the Committee on Natural Resources; and the National Commission on Mathematics and Science Teaching for the 21st Century.
He served as co-chair of the Research and Development Caucus, and sat on other caucuses related to children's environmental health, renewable energy, sustainable development, Alzheimer's and diabetes disease research, biomedical research more broadly, the Internet, community colleges, and more. He is a recipient of the Champion of Science Award from the nonprofit Science Coalition, a group of more than 50 leading public and private research universities. In addition, she holds 16 honorary degrees. As senior program officer and visiting scholar in the Policy and Global Affairs Division, National Academies, she served as study director for the Academies report entitled Partnerships for Emerging Research Institutions and co-study director of Expanding Underrepresented Minority Participation: America's Science and Technology Talent at the Crossroads , a congressionally mandated study focused on the underrepresentation of minorities in science and engineering.
She has made numerous presentations, and is the co-author of copyrights to two software systems. She was honored by the Republic of Senegal through acceptance into the Order of the Lion. Ramirez is a science evangelist who is passionate about getting the general public excited about science. She coauthored with Allen St. Prior to being on the faculty at Yale, she was a research scientist at Bell Laboratories, Lucent Technologies, in Murray Hill, New Jersey were she did award-winning research. She has authored more than 50 technical papers, holds six patents, and has presented her work worldwide.
She now focuses her energies on making science fun, and gave an impassioned called to action at TED on the importance of science, technology, engineering, and math STEM education, which generated widespread enthusiasm. Rastegar has over scientific publications and presentations and has trained 8 PhD and 14 MS students. He is a co-founder of BioTex, Inc. A physics education researcher, his primary interests are in program evaluation, and teacher preparation and enhancement. Additionally, he serves on a number of national and international advisory boards and has been awarded a Doctor of Humane Letters by his alma mater, Virginia State University.
He is married and has three adult daughters and two grandchildren. Department of Agriculture from October to August Before moving to NSF, Tupas was a faculty member at the University of Hawaii at Manoa UHM , where she taught graduate courses and carried out her research in hormone signaling and transcription regulation, while managing two undergraduate student research training and student development programs focused on increasing diversity in biomedical sciences. Her work has provided insight into aging, the cell cycle, and other significant areas of cell biology. Werner-Washburne has been at UNM for more than 20 years, where she has mentored students from many backgrounds, her papers have been cited more than times.
After graduation, she lived in Mexico, Central, and South America, Alaska, and Minnesota—a walkabout that led to her becoming a scientist. During this time, she became interested in ethnobotany the traditional use of plants for food, clothing, and medicine. Athreya University of Iowa Krishna B. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients, and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations.
As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration, and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.
For more information about the AACR, visit www. Graduate students work with faculty at the cutting-edge of disease-relevant research in areas such as: AACR membership includes more than 35, laboratory, translational, and clinical researchers, population scientists, other health care professionals, and cancer advocates residing in 97 countries. The American Society for Microbiology is the oldest and largest single life science membership organization in the world.
Membership has grown from 59 scientists in to more than 39, members today, with more than one third located outside the United States. The members represent 26 disciplines of microbiological specialization plus a division for microbiology educators. ABRCMS is one of the largest, professional conferences for underrepresented minority students and students with disabilities to pursue advanced training in science, technology, engineering and mathematics STEM , attracting approximately 3, individuals, including 1, undergraduate students, graduate students and postdoctoral scientists and faculty, program directors and administrators.
Students come from over U. All are pursuing advanced training in science, technology, engineering and mathematics STEM , and many have conducted independent research. More than representatives from graduate programs at US colleges and universities as well as scientists from government agencies, foundations, and professional scientific societies join ABRCMS in the exhibitors program to share information about graduate school and summer internship opportunities. These representatives present research opportunities, funding sources, and professional networks.
All undergraduate student presentations are judged and those receiving the highest scores in each scientific discipline and in each educational level will be given an award during the final banquet.
- The Auditory System in Sleep;
- Japanese Hot Pots: Comforting One-Pot Meals?
- In Search of Drawing Pins.
- Herland, The Yellow Wall-Paper, and Selected Writings.
The first is the Program in Biomedical Sciences is an interdisciplinary PhD program which integrates the foundations of biomedical research with focused investigation and preparation for career advancement. The third is a university-wide Neuroscience program. Finally, the MD-PhD program balances both clinical and scientific training to develop exceptional physician scientists. Professionalism, Career Development and Mentorship: All PhD students will have the unique opportunity to participate in a dynamic professionalism and mentoring program. Students build professional networks with faculty members who have significant research and publication experience, and who can assist with career development.
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Table 62 Johns Hopkins University N. All of our graduate students, whether involved in research in cell biology, molecular biology, which includes genetics, developmental biology, and biophysics, which includes biochemistry, participate in a core curriculum involving molecular, cellular, developmental biology, and biophysics. Students continue to broaden their knowledge in these areas throughout their graduate training, while they specialize in their own research areas.
Through this cross-training, PhDs emerge from the CMDB with preparation to tackle complex problems in 21st century biosciences. Edwards School of Medicine is a state-supported, community-based medical school established in We specialize in rural health issues as expressed in special efforts to recruit students from rural West Virginia and place graduates in clinical practice in rural areas. We believe that a diverse population offers a rich environment that leads to greater knowledge, understanding, acceptance and mutual respect and we promote an inclusive environment by attracting, recruiting and retaining individuals who represent varying backgrounds and perspectives.
Located in scenic Charleston, South Carolina, we offer competitive stipends, paid health insurance and paid tuition for PhD students. We also have a robust Summer Undergraduate Research Program that provides funding for undergraduates to obtain research experience for 10 weeks in the summer. PhD students participate in an interdisciplinary first year curriculum composed of comprehensive didactic units, selfselected laboratory rotations, and seminars to teach skills important for successful scientific careers.
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With a combined budget of over two million per year, the CIE provides direct services for close to students in 38 graduate and professional programs across all disciplines. For information please visit our booth. Please visit our website for more information: Diversity is central to our mission of discovery as it drives ideas, builds careers, and enriches communities. Having the greatest number of representatives from the most diverse pool of thinkers poses the most likely opportunity to address a problem from all its perspectives.
The Biological Sciences Division is committed to attracting, mentoring, and promoting a diverse community of scholars in an environment conducive to excellence for students from all backgrounds. The Graduate College encompasses all graduate programs of the university. As the graduate degree-granting college for the University of Idaho, the College of Graduate Studies combines nationally competitive academic and research opportunities - the kind you would expect at a large metro institution - with the small town, hands-on approach that will jump start your research and your career.
Academic opportunities, application fee waivers, and funding packages are extended to prospective and current graduate students intended to support their pursuit of an advanced degree. Illinois offers graduate degrees in over graduate programs, including those in the social sciences, arts and humanities, biological sciences, natural sciences, physical sciences, behavioral sciences, and engineering. Assistantships, traineeships, and fellowships, supplemented with a tuition waiver and stipend are offered to students in all disciplines.
Please visit our website at: Iowa is known around the world for its balanced commitment to the arts, sciences, and humanities. It's home to one of the nation's largest academic medical centers, the pioneering Iowa Writers' Workshop, and hundreds of options for affordable, accessible education. The University of Iowa is located in the casual yet cosmopolitan environment of Iowa City, widely recognized as one of the country's most livable communities.
The campus has built a strong reputation for innovation in nanoscale research, with breadth across many departments, including Chemical Engineering, Electrical and Computer Engineering, Mechanical and Industrial Engineering, Polymer Science and Engineering, Physics, and Chemistry.
We offer a tenweek Research Experience for Undergraduates REU every summer with free travel, housing and competitive stipend. We also offer numerous graduate-level scholarships, funding options, and fee waivers. Stop by our exhibit for more details. Table 10 University of Michigan S. Over 1, faculty in the College of Literature, Science, and the Arts--experts in anthropology through zoology-teach courses that explore the world's cultural, social, and scientific big questions.
Our faculty members produce some of the most notable research in their respective fields. Admitted gradu- Conference Program 39 ate students are offered funding packages that cover at least 5 years of study, including tuition, stipend, and health insurance for students and their dependents. In addition, our facilities include one of the most extensive library systems in the world, seven museums, and research labs for the natural and physical sciences. A vibrant literary and performing arts tradition in the College enriches the minds and hearts of the campus community. All that a college experience should be--the intellectual challenges, the exposure to the new, the growth of knowledge and of individuals--can be found here, in the College of Literature, Science, and the Arts at the University of Michigan.
Talk to us about additional program at UM as well.
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PIBS offers you the flexibility and convenience of applying to any of our programs through one application. Learn more at medicine. Graduate students in Medicinal Chemistry are trained in research pertaining to drug discovery and drug design while those in Pharmaceutical Sciences are focused on the study of drug transport and drug delivery systems. Students with interests in obtaining clinical training with regard to the practice of pharmacy are encouraged to consider the Pharm. The University of Michigan - Pharm.
The educational training and exposure provided through the program prepares students for a broad range of career opportunities upon graduation. For further information, regarding these programs please visit: Experience the Joy of Discovery and Innovation - Graduate Study in the Life Sciences at the University of Missouri The joy of discovery has propelled the University of Missouri to one of the top-ranked Life Sciences research institutions in the 21st Century, offering doctoral degrees in over 25 life sciences departments and programs.
Our PhD programs emphasize interdisciplinary collaboration and innovation. Our PhD students use cutting-edge technologies to solve problems. Our research core facilities include state-of-the-art DNA sequencing, proteomics, nanotechnology, microscopy and whole-animal imaging technologies. We are committed to the success of our graduate students, with strong mentorship programs and career-directed resources. We offer a comprehensive support package including stipend, paid tuition, health insurance and travel funding.
Louis or Kansas City. To learn more please visit http: As a graduate student at Notre Dame, you will benefit from generous financial support that allows you to focus on your degree objectives and from exposure to and participation in innovative, collaborative, and interdisciplinary pursuits. We believe that our voice is best heard through the success of those we train at the highest level to become the academic and professional leaders of tomorrow. To that end, we work in concert with a world-class faculty across a variety of disciplines to mentor and develop our students by engaging them in meaningful research and other professional activities.
All of these pursuits take place in a setting that is small enough to provide you with individual attention and large enough to provide you with all the tools necessary for your transformation from a student of a chosen discipline to a steward of that discipline. Notre Dame is committed to fully funding all doctoraldegree seeking students and many masters-degree seeking students. If you would like more information, please feel free to contact the director of graduate studies in your prospective department of interest.
If you would like to browse our Web site or apply on-line, visit us at http: Visit our Facebook page: In addition to our graduate programs, BGS is pleased to offer research training for individuals at the undergraduate and postbaccalaureate levels. USF is classified by the Carnegie Foundation for the Advancement of Teaching in the top tier of research universities.
Signature STEM research areas include: Sloan University Center of Exemplary Mentoring to provide graduate scholarships for underrepresented doctoral students. PEER provides professional and skills development that goes beyond traditional classroom and research skills. We offer a comprehensive financial package including a salary, paid tuition and health insurance and travel funding. PEER is currently accepting applications. Application deadline is March 15, Applications will be reviewed on a rolling basis for positions in the following departments: Additionally, students explore how to utilize research to manage natural resources, with a particular focus on the issues and challenges related to natural resource management in the Caribbean region.
Further, it is a bridge between academia and natural resource management sectors within the US Virgin Islands, the greater Caribbean, and beyond. The program structure allows students to become conversant in the language of both research and resource management, and then to focus on their area of particular interest. Graduates of the program are prepared for a wide array of careers in academic, government, non-profit, and private sectors. Scholarships as well as Research and Teaching Assistantships are available. Joined by the Institute for Systems Biology and Seattle Biomed, MCB offers a broad range of opportunities for research in all areas of biomedical science.
While completing their degrees, the students in GERS create a community of scholars who meet twice a month for personal and professional development opportunities. Since its inception, the program has graduated 56 PhDs and 61 MS. Already, 14 of the 56 graduates are in faculty positions and an additional 5 are in post-doctoral positions. Over faculty offer training in genomics, cancer biology, computational biology, developmental biology, biomedical engineering, molecular genetics, structural biology, cell biology, chemical biology, systems biology, pharmacology, microbiology, neurosciences and immunology.
The essence of education at UT Southwestern is an exciting research experience in an active, productive and critical scientific environment. We also have two undergraduate research programs focused on providing world-class research experiences during the summer. Information about these programs is available at www. Vanderbilt's PhD alumni can be found pursuing careers in every direction imaginable, including in the commercial sector, in government service and on the faculties of both small colleges and major research universities.
Table 3 Washington University in St. Louis is a world-renowned research university, which fosters a commitment to research, teaching, scholarship and service. To fulfill this commitment we strive to create an inclusive and diverse community of scholars with various programs. Louis provides a collaborative and interdisciplinary research environment with top ranked and award winning faculty. We also offer summer research opportunities as well as a postbaccalaureate program for students interested in pursuing the PhD.
Table 57 Washington University in St. Louis Biology and Biomedical Sciences S. Euclid Box St. Louis, MO Contact s: Division programs provide a broad interdisciplinary approach to graduate education. Students may choose from more than faculty members for laboratory rotation and dissertation research mentors.
More information may be found at http: You will work alongside experts in your field, conducting groundbreaking research with a global reach. And on our Midtown campus, you are just steps away from industry leaders in technology, health care, engineering and more. We are driving the future of a great American city, and we want you to join us.
Come be part of a university that is reshaping our social and economic culture. It is a single virtual system that scientists can use to interactively share computing resources, data, and expertise. Our missions is to enhance the productivity of researchers, engineers, and scholars through access to advanced digital services supporting open research; and to coordinate and support leading cyberinfrastructure resources funded by the NSF XSEDE offers: An advanced hardware and software architecture rooted in user requirements and hardened by systems engineering that allows for individualized user experiences, consistent and enduring software interfaces, improved data management, and ways for campus resources to be transparently integrated into the overall XSEDE infrastructure.
Specialized community-provided services that serve a particular function and allow for rapid innovation and experimentation. Training, Education, and Outreach that expand participation in XSEDE-based projects, curriculum development, and more traditional training opportunities. Advanced support for novel and innovative projects.
Through their collaborative work and creative approaches to problem-solving, faculty and students at WPI will continue to make breakthroughs that improve the quality of our lives. A2 Chemistry and Chemical Sciences A11 Computer Sciences and Information Management A22 Ecology, Environmental, and Earth Sciences A26 Mathematics and Statistics A41 Science and Mathematics Education A43 Social, Behavioral, and Economic Sciences A44 Technology and Engineering A58 Chemistry and Chemical Sciences A77 Computer Sciences and Information Management A80 Ecology, Environmental, and Earth Sciences A85 Mathematics and Statistics A Science and Mathematics Education A Social, Behavioral, and Economic Sciences A Technology and Engineering A Chemistry and Chemical Sciences A Computer Sciences and Information Management A Ecology, Environmental, and Earth Sciences A Mathematics and Statistics Patrice Cagle and Patrick M.
Rosehip extracts are derived from the wild rose Rosa canina and have previously shown to reduce proliferation of cancer cells. This study investigates the efficacy of rosehip extracts to inhibit proliferation of human glioblastoma cell lines A, U MG, and U MG. Results demonstrate that rosehip extracts significantly reduced cell proliferation without promoting apoptosis. Furthermore, rosehip extracts increase efficacy of Temozolomide, a chemotherapeutic drug used to treat patients with glioblastomas.
Rosehip also increases the efficacy of Temozlomide in preventing brain tumor cell migration. This study shows the capacity of rosehip extracts to prevent cell proliferation and migration in human brain tumor cells. More importantly, this study also demonstrates that rosehip extracts aid in making Temozolomide more effective as an antitumorigenic compound.
Martin for guidance on this project. The Wnt signaling pathway is essential in normal cell development and has been implicated in breast cancer where it plays a role in cell invasion and cancer stem cell maintenance. Rhodiola crenulata RC is a Tibetan mountainous plant, commonly used in eastern alternative medicine, and is classified as an adaptogen. Previously we have shown that RC inhibits migration and invasion behaviors and increases sensitivity to cell death in TNBC cell lines2.
In this study, we sought to identify the mechanism by which RC could impart these effects. Joseph and Anthony L. Parmar, University of Delhi, New Delhi, India Breast cancer development and progression rely on complex interactions between breast epithelial cells and the microenvironment composition and density. Those interactions may be suitably investigated in 3D in vitro culture systems.
However, current 3D breast tissue systems do not account for the heterogeneous density and composition of the extracellular matrix ECM observed within breast tissue. Here we hypothesized that embedding polylactide beads into our 3D matrix would more closely mimic the heterogeneous microenvironment of breast tissue, leading to the formation of 3D structures.
Treatment groups included polylactide beads coated with saline PBS: The development of complex structures i. The MCF10A cells formed complex structures surrounding cluster of beads with cell strands migrating outward. The cell strands included both acinus- and duct-like structures. The length and the complexity of the cell strands formed in 3D matrix embedded with polylactide beads coated with either PBS, media or collagen I tended to differ.
The data modulating the MCF10A 3D in vitro breast tissue system presented here are an essential step to the definition of reliable tools for the evaluation of early breast cancer progression and the testing of specific treatments. Whether in vitro 3D test system with defined heterogeneity may fully model the effects of heterogeneous density on normal human mammary gland development and cancer progression will be assessed in future studies.
Plant polyphenols have a number of beneficial health effects, and are well noted for their anti-cancer properties. To develop more effective treatments for melanoma, we assessed the chemotherapeutic potential of various plant polyphenol derivatives on the migration ability of A human melanoma cells as an in vitro model. Together, these results show that the polyphenols have the ability to inhibit cell migration, a crucial step of metastasis. Enery Lorenzo, Michael Ortiz, and Mauricio Cabrera -Rios, University of Puerto Rico at Mayaguez Clara Isaza, Ponce School of Medicine and Health Sciences Establishing the role of different genes in the development of cancer can be a daunting task starting with the detection of genes that are important in the illness from high throughput biological experiments.
These experiments belong to the —omics denomination, as in genomics, proteomics, metabolomics and the like. Furthermore, it is safe to say that even with a list of Conference Program A3 potentially important genes; it is highly unlikely that these show changes in expression in isolation. A biological signaling path is a more plausible underlying mechanism.
This work attempts the analysis of a microarray experiment to build a mathematical network problem through methods such as the Traveling Salesman Problem and Minimum Spanning Tree. A pre-selection of genes is carried out with a multiple criteria optimization framework previously published by our research group. Preliminary results are presented in lung cancer. If validation succeeds, uncovering signaling pathways of potential biomarkers could possible further the understanding of the origins and evolution of cancer.
Pondugula, Piyush Trivedi, and Amit K. The multidrug resistance MDR phenotype caused by the overexpression of ABC transporters by tumor cells promotes the cellular efflux of a variety of anticancer drugs and may lead to cancer treatment failures Tiwari et al. Based on our in silico screening and structure-activity relationship studies, we synthesized novel molecules to inhibit ABCG2 transporters. In our experiments, we found several of these molecules to be excellent reversal agents against ABCG2 transporters using cell-based MTT assays.
Additionally, these molecules have limited PXR stimulatory effects. Further in vivo A4 Conference Program studies are required to implement these molecules for in clinic application against difficult-to-treat tumors. Conversations of Native Navigators and Western Medicine have continued for two years. These new findings will be presented in relation to using a hybrid of Traditional Native Medicine and Western Medicine in addressing cancer care Hypothesis American Indians and Alaska Natives face poor survival rates due to medical illness that are contrary to the progress and improvements typical of modern medicine.
Western medicine has increased the lifespan and decreased the burden of disease for many populations in North America. Harold Freeman the founder of Patient Navigation describes navigation as engaging specifically trained individuals to help others i. Navigation processes can be described as education and outreach, aiding with access to screening. This study was conducted to examine the lived experiences of Native American Cancer Patient Navigators Native Navigators with cancer screening and cancer health. The term Native Navigator was used to describe a Native American who helps an individual in a Native American community in navigating the complex system of healthcare along the cancer continuum Eschiti, Burhansstipanov and Watanabe-Galloway, The research design for this study was developed using qualitative methods in alignment with a phenomenological approach.
For data analysis, a phenomenology framework was used. This preliminary study sample then expanded using a snowball recruitment approach. Native Navigators were recruited from across the United States. Native Navigators representing American Indian and Alaskan Native tribes were interviewed from both urban and rural settings.
Collected data consisted of field notes, supporting documents and in-depth ethnographic Native Navigator interviews. Conclusion and Future Research: In spite of the remarkable progress in recent years in Western Medicine, with respect to the health status of Americans Indians and Alaska Natives, in virtually all health measures, the status of Indian health remains below that of other U.
We hypothesize that PGE exerts its effects by activating the pro-inflammatory signaling pathways in cells. Shishir Shishodia Funder Acknowledgement s: Cell and Molecular Biology Grad. Significant concentrations of rhodium, palladium, and platinum have been reported in tunnel dusts and surface road dusts in the Houston area. Humans can be exposed to these metals through inhalation of airborne particulate matter PM that may provoke respiratory diseases and other adverse effects.
Exposure to atmospheric PM is known to induce many respiratory diseases especially in susceptible populations such as children. But it is not clear which constituents of atmospheric PM are responsible for the observed health effects. Although chemically inert, platinum, like other transition metals exist in several different forms having different oxidation states.
It is well known that bioavailability and toxicity of metals are linked to their chemical species. Recent studies on PGE toxicity and environmental bioavailability indicated that once entering environment, anthropogenic PGE might easily be mobilized and transformed into more toxic forms under the actions of various biogeochemical processes, and thereby, enhanced their bioavailability and posed potential health risks to human beings through food chain. Caplan, University of Delaware M. Wisser, Cornell University T. Genetic resistance to this disease is the only realistic way to control it.
To test the hypothesis that different loci act through different mechanisms of action and to characterize their effects on pathogenesis, we are integrating genetics and bio-imaging. Pairs of genetic stocks with distinct alleles at each genomic locus in an otherwise identical genetic background near-isogenic lines [NIL] are spray inoculated with either of the fungal spores. At variable time points during pathogenesis, leaf punches are collected, and conserved using a glutaraldehyde fixative.
Images of the fixed samples are captured with a digital camera in other to record the macroscopic features on the leaf surface. Samples are stained with Wheat germ agglutinin WGA conjugated to AlexaFluor that specifically stains fungi and Calcofluor that stains plant cell walls. In order to image all the way through the sample we modified a technique known as Scale, which is a chemical treatment that clears tissues while maintaining the Conference Program A5 structural integrity of the sample.
A final treatment with glycine enhances the image quality by removing nonspecific auto fluorescence caused by excess aldehyde groups and thereby increasing the ratio of signal-to-noise. After the sample treatments are completed, preliminary images are taken at low magnification using a Zeiss LSM5 DUO High-speed Confocal Microscope to compile a microscopic overview of the leaf punch. Images are processed using Fiji Image software and then visually analyzed for regions with fungal infection. Together, these images reveal previously unknown information about these fungi including the path of infection, type of invasion vascular vs nonvascular , morphological changes, and other events during the disease incubation period.
Comparing image data from NIL pairs enables us to understand what mechanisms are employed by the host to achieve genetic resistance. The data collected from this imaging is crucial in the development of durably resistant crop germplasm. Western blotting of Dictyostelium homogenates also revealed the presence of 24 kDa species that were consistent with GST isozymes expressed in mouse liver.
These results provide strong evidence of role of GST metabolism in vegetative amoebae of Dictyostelium. Future studies will characterize: Biochemistry and Molecular Biology Faculty Advisor: In addition to their role in detoxification, GSTs are implicated to play important functions in signal transduction, development, and differentiation in eukaryotic cells. Recent studies show that the eukaryotic model, Dictyostelium discoideum, undergoes altered development and sensitivity with changes in GSH levels.
The function of many GSH -mediated enzymes in D. The unique exclusivity of alpha class isozyme expression raises interesting questions regarding their importance in D. This study characterized the identity, expression, and activity of GST enzymes in D. Our studies reveal the expression of functional GSTs in D. Sterol synthesis generally increases as cells age.