cssi/SciSciGPT-SciSciNet huggingface dataset:
Exploring sequence-structure relationships in the tyrosine kinome space

Motivation: Evolutionary and structural conservation patterns shared by more than 500 of identified protein kinases have led to complex sequence-structure relationships of cross-reactivity for kinase inhibitors. Understanding the molecular basis of binding specificity for protein kinases family, which is the central problem in discovery of cancer therapeutics, remains challenging as the inhibitor selectivity is not readily interpreted from chemical proteomics studies, neither it is easily discernable directly from sequence or structure information. We present an integrated view of sequence-structure-binding relationships in the tyrosine kinome space in which evolutionary analysis of the kinases binding sites is combined with computational proteomics profiling of the inhibitor–protein interactions. This approach provides a functional classification of the binding specificity mechanisms for cancer agents targeting protein tyrosine kinases. Results: The proposed functional classification of the kinase binding specificities explores mechanisms in which structural plasticity of the tyrosine kinases and sequence variation of the binding-site residues are linked with conformational preferences of the inhibitors in achieving effective drug binding. The molecular basis of binding specificity for tyrosine kinases may be largely driven by conformational adaptability of the inhibitors to an ensemble of structurally different conformational states of the enzyme, rather than being determined by their phylogenetic proximity in the kinome space or differences in the interactions with the variable binding-site residues. This approach provides a fruitful functional linkage between structural bioinformatics analysis and disease by unraveling the molecular basis of kinase selectivity for the prominent kinase drugs (Imatinib, Dasatinib and Erlotinib) which is consistent with structural and proteomics experiments. Contact:verk@ku.edu or gverkhiv@ucsd.edu Supplementary information: Supplementary data are available at Bioinformatics online.
Bandwidth, cross-polarization, and feed-point characteristics of matched Hilbert antennas

We have applied a moment-method-based simulation code to perform a detailed parametric study of the bandwidth, cross-polarization level, and the feed location characteristics of the matched Hilbert antenna. It is shown that a properly chosen off-center near-the-end feed point may provide an approximate 50 /spl Omega/ real input impedance at the fundamental resonant frequency. The role of different iteration orders for Hilbert antennas, approximately matched to the 50 /spl Omega/ line, on the bandwidth and cross-polarization level of such antennas is investigated numerically. As was shown by K.J. Vinoy et al., the radiation patterns resemble those of a linear dipole and, for a fixed-area-matched Hilbert antenna, the resonant frequency can be lowered by increasing the iteration order n. However, for such matched antennas, the bandwidth for VSWR<2 is decreased and the cross-polarization level may be different for the higher iteration-order antennas.
An Iterative Method for the Displacement Analysis of Spatial Mechanisms

An algebraic method for the displacement analysis of linkages has been the subject of earlier publications [1, 2]. This method, based on the use of a symbolic notation, allows the application of matrix algebra to the study of displacements in linkages, and permits formulation of all the kinematic relations of a linkage in terms of matrix equations. Based on this earlier work, the present paper develops an iterative method for the solution of the matrix equations required in displacement analysis. A complete solution is given for simple-closed linkages consisting of revolute and prismatic pairs (and their combinations). A brief indication of how higher pairs and multiple-closed chains may be handled is also given. Particularly useful in spatial problems, since it does not depend on visualization, this approach is developed in a manner intended for digital-computer operation.
Development of microlens arrays for high-speed optical communication

In this study, polymeric microlens arrays, well suited for high-volume and low-cost production, were developed for efficiently coupling the light from vertical-cavity surface emitting lasers (VCSELs) to multi-mode fiber ribbon. They were fabricated by microinjection molding with Ni-electroplated mold insert. Modified LIGA processes and the Ni-electroplating are used to make the master and the metallic mold insert, respectively. In this study, microinjection molding with metallocene based cyclic olefin copolymer (mCOC) was chosen to replicate microlenses. Good surface profile and high dimensional accuracy are achieved. Coupling efficiency of 55 +/- 3 % with a working distance of 400 +/- 60 micrometer is obtained. To verify its applications on high-speed interconnections, we also designed the evaluated board and set up an opto-electronic measurement platform. The high-speed measurement shows that the electrical-to-optical conversion 3dB-bandwidth is above 1.8 GHz, and the eye diagram at 2.488 Gbps is acceptable for the SONET OC-48 eye mask.
Stress In Molybdenum Films Used For Fea Display Technology

Flat-panel displays based on cold-cathode field emission are actively being developed in a number of laboratories world-wide. Once fully developed, Field Emitter Displays (FEDs) will compete directly with Liquid Crystal Displays (LCDs). FEDs offer several significant advantages over LCDs including higher screen brightness, wider viewing angle, lower power consumption, and operation over a broader temperature range, making FEDs desirable for applications such as lap-top computers. Presently, several materials are being evaluated for use as coldcathode field emitters including molybdenum 1 , silicon 2 , and DLC 3 . At this time it is unclear which material (or materials) will ultimately be incorporated into commercial or military flatpanel display products. Each potential cathode material has its own set of advantages and disadvantages, and the ultimate choice will depend on the particular display requirements and architecture.
Gefitinib: an adverse effects profile.

Gefitinib, an epidermal growth factor receptor inhibitor, is currently approved for use in patients with advanced non-small cell lung cancer who have failed previous chemotherapy or who are not suitable for chemotherapy in > 30 countries. The approved dose in patients with non-small cell lung cancer is 250 mg/day. The most common adverse effects are rash, diarrhoea, acne, dry skin, nausea and vomiting. Most of the effects are mild-to-moderate in nature and do not require discontinuation of therapy. The severity of many of these effects is dose-related with grade 3 – 4 effects more likely at a dose > 250 mg/day. The most severe adverse effect is interstitial lung disease (ILD), which occurs in ∼ 1% of patients worldwide except for Japan where the incidence of ILD is 2%. ILD is fatal in approximately one out of three of the cases. The most common adverse effects associated with chemotherapy, myelosuppression and alopecia, are not commonly seen with gefitinib monotherapy.
A Home Monitoring System for Nasal CPAP

A compact portable sensing system (PSS) was developed for home monitoring of patients with obstructive sleep apnea treated with nasal continuous positive-airway pressure (CPAP). The system consisted of a solid-state pressure sensor connected with plastic tubing to the side port of the nasal CPAP mask, a power supply, and a strip chart recorder. The device was validated against standard polysomnography in ten patients with obstructive sleep apnea undergoing overnight nasal CPAP trials. A total of 397 apneas and hypopneas were observed in the ten patients. The PSS device detected 386 events (sensitivity, 97.2 percent). In addition, there were 29 false positive events noted by the device (positive predictive value, 93 percent). The device was then tested at home in 23 patients on nasal CPAP. Eight of these patients had persistent apneas requiring adjustment of their CPAP pressure. The PSS device allowed for accurate reevaluation of nasal CPAP settings in the patient's home without necessitating expensive, time-consuming in-hospital laboratory polysomnographic studies.
Surgical pearl: evacuation of milia with a paper clip.

M ilia can be treated by destruction or evacuation. Destructive techniques, including electrocautery and low current electrodesiccation, effectively remove milia with minimal scarring or postinflammatory pigmentary change. Techniques involving evacuation of the cyst contents are more commonly done for isolated lesions. Evacuation is accomplished by first nicking the papule with a needle, scalpel blade, or stylet, followed by application of tangential pressure to the milium with a comedo extractor, the flat surface of a scalpel blade, a tongue blade, or a curet.
Asset‐based reserve requirements: reasserting domestic monetary control in an era of financial innovation and instability

This paper argues for developing a new system of financial regulation based upon asset‐based reserve requirements (ABRRs). Such a system represents a shift in regulatory focus away from the traditional concern with the liability side of financial intermediaries' balance sheets. ABRRs have both significant macroeconomic and microeconomic advantages. At the macroeconomic level, they can provide policy makers with additional policy instruments. This is particularly useful in light of recent concerns about the dangers of asset price inflation and the potential need to target asset prices. They can also help restore the traction of monetary policy at a time when banks are becoming a smaller part of the financial landscape. At the microeconomic level, they can be used to discourage excessive risk taking by financial intermediaries. Finally, they can also raise considerable seignorage. To be fully effective, a system of ABRRs should be applied to all financial intermediaries.
Opening the Contemplative Mind in the Sociology Classroom

We examined the usefulness of mindfulness practices for developing understandings of the intersection between the individual and social milieu. After incorporating mindfulness practices in a sociol...
IMPROVING SHEAR CAPACITY OF EXISTING RC T-SECTION BEAMS USING CFRP COMPOSITES

This paper presents the shear performance of reinforced concrete (RC) beams with Tsection. Different configurations of externally bonded carbon fiber reinforced polymer (CFRP) sheets were used to strengthen the specimens in shear. The experimental program consisted of six full-scale, simply supported beams. One beam was used as a bench mark and five beams were strengthened using different configurations of CFRP. The parameters investigated in this study included wrapping schemes, CFRP amount, 90 0 /0 0 ply combination, and CFRP end anchorage. The experimental results show that externally bonded CFRP can increase the shear capacity of the beam significantly. In addition, the results indicated that the most effective configuration was the U-wrap with end anchorage. Design algorithms in ACI Code format as well as Eurocode format are proposed to predict the capacity of referred members. Results showed that the proposed design approach is conservative and acceptable.
Characterization of a tomato protein that inhibits a xyloglucan-specific endoglucanase.

A basic, 51 kDa protein was purified from suspension-cultured tomato and shown to inhibit the hydrolytic activity of a xyloglucan-specific endoglucanase (XEG) from the fungus Aspergillus aculeatus. The tomato (Lycopersicon esculentum) protein, termed XEG inhibitor protein (XEGIP), inhibits XEG activity by forming a 1 : 1 protein:protein complex with a Ki approximately 0.5 nm. To our knowledge, XEGIP is the first reported proteinaceous inhibitor of any endo-beta-1,4-glucanase, including the cellulases. The cDNA encoding XEGIP was cloned and sequenced. Database analysis revealed homology with carrot extracellular dermal glycoprotein (EDGP), which has a putative role in plant defense. XEGIP also has sequence similarity to ESTs from a broad range of plant species, suggesting that XEGIP-like genes are widely distributed in the plant kingdom. Although Southern analysis detected only a single XEGIP gene in tomato, at least five other XEGIP-like tomato sequences have been identified. Similar small families of XEGIP-like sequences are present in other plants, including Arabidopsis. XEGIP also has some sequence similarity to two previously characterized proteins, basic globulin 7S protein from soybean and conglutin gamma from lupin. Several amino acids in the XEGIP sequence, notably 8 of the 12 cysteines, are generally conserved in all the XEGIP-like proteins we have encountered, suggesting a fundamental structural similarity. Northern analysis revealed that XEGIP is widely expressed in tomato vegetative tissues and is present in expanding and maturing fruit, but is downregulated during ripening.
The Measurement and Improvement of the Transient A/F Characteristics of an Electronic Fuel Injection System

Mesure et amelioration des caracteristiques transitoires (melange air-carburant) d'un systeme d'injection electronique de carburant
Health Equity, Healthy People 2020, and Coercive Legal Mechanisms as Necessary for the Achievement of Both

Principles of health equity require that all people have equal opportunity to develop and maintain their health, yet in the face of widespread and presumptively inequitable health disparities, the law has done little. This paper argues that health equity demands the use of coercive legal mechanisms in certain circumstances given the existence of current disparities and the evidence of effectiveness of direct regulation as compared to its alternatives. Moreover, the paper argues that Healthy People 2020, which is the nation’s “master blueprint for health” and explicitly seeks to achieve health equity, has not fully incorporated the principles of health equity in the formulation of its objectives and indicators because it fails to recognize the varying distributive effects of policies that could achieve population health targets. To truly incorporate the principles of health equity, Healthy People 2020 should advocate for those demonstrably effective coercive legal mechanisms that would both achieve its population health objectives and reduce health disparities.
Petite histoire des réinventions et des récupérations de Montaigne au cours des siècles

Montaigne's work has always been ideologically diverted for the sake of various schools of thought. After his death in 1592, the emphasis was put on a political reading: Montaigne was even published in Geneva, on Protestant ground. Later he was considered not to be Christian enough and his work had to be transformed into that of a moralist. In the 18th century, the Essays were reduced to a compilation of disjointed moral sentences. During the 19th century, publication of Montaigne's work soared: Montaigne gained an unexpected visibility and was paradoxically seen as a moralist. This heavily Christian interpretation of his work was succeeded in the 20th century by a secular reading emphasising the idea of the man Montaigne at home surrounded by his books. Today in the 21st century, Montaigne's attraction lies in his hyper-subjectivity in an increasingly objectified and globalized world.
The FCC's ATSC Tuner Rules Are No Longer Economically Necessary

The Federal Communications Commission, based on a rule adopted in 2002 to facilitate the transition to digital broadcasting, requires by regulation that television sets sold in the United States have an Advanced Television Systems Committee (ATSC) tuner. The ATSC tuner rule is still in effect even though the transition to digital broadcasting was largely completed several years ago and the vast majority of American households do not rely on the tuner. Current ATSC tuners enable television sets to receive over-the-air digital signals, although the vast majority of American households do not view television from such signals. The ATSC tuner rules are no longer economically useful.
A multiyear assessment of hookah use prevalence among Florida high school students.

INTRODUCTION The purpose of this study was to assess the prevalence of hookah use among Florida high school students over time. Alternative tobacco products, including hookah, pose a public health threat to tobacco prevention efforts, especially among adolescents. METHODS Florida Youth Tobacco Survey data, representing all public high school students in the state, were analyzed to assess the prevalence of lifetime and current hookah use and were compared by demographic groups. Multiple years of data (2007-2012) were examined to assess changes over time. RESULTS During the past 6 years, there was an increase in lifetime hookah use among Florida high school students. While males remained at a higher rate overall, female adolescents increased at a faster rate. Hispanic and non-Hispanic White respondents reported increased trends as well. Current use trends did not change over 4 years, remaining at about 8%. CONCLUSIONS Hookah is a new tobacco product in the United States that appears attractive to youth, with dramatic increases among the state population. While cigarette use among youth is declining in Florida, the increasing uptake of alternative tobacco products may lessen the overall public health gains for tobacco use. There is a need for continued monitoring of hookah use among the adolescent population, for both prevention and cessation efforts as well as policy interventions to address this emerging trend.
A Descriptive and Graphical Analysis of the (Lack of) Association Between Age and Homicide Cross-Nationally:

Why is it necessary to control for the percentage of the population between the ages of 15 and 24 in cross-national homicide studies? While it seems like a simple question, the answer is elusive. T...
Ovarian cancer update: management challenges and advances.

BACKGROUND Although less common than cervical or uterine cancer, ovarian cancer accounts for more deaths than the other two gynecologic malignancies combined. SUMMARY Ovarian cancer produces few symptoms while confined to the ovary. A palpable ovary in a postmenopausal woman should arouse the clinician’s suspicion. Most tumors have already spread at the time of the initial laparotomy and require chemotherapy. The standard regimen contains cisplatin or carboplatin plus cyclophosphamide; paclitaxel (Taxol) shows promise and will probably be incorporated into the standard regimen, as well. Estrogen replacement therapy is not contraindicated. The rate of relapse is high, even in women who have achieved a complete clinical response. If persistent disease is found at a second laparotomy, intraperitoneal chemotherapy may be appropriate in some patients. CONCLUSIONS Because the patient’s chance of survival is much better if the disease is discovered when it is still confined to the ovary, physicians should be alert to the possibility of ovarian cancer, particularly in postmenopausal women with vague abdominal complaints or with a palpable ovary.
Essential Cytopathology Concepts for the Endosonographer

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become the primary diagnostic modality for sampling mucosal and subepithelial gastrointestinal lesions as well as peri-intestinal organs including but not limited to the pancreas, liver, lymph nodes, and adrenal gland. Cooperative efforts between the endoscopist and cytopathologist are necessary to maximize the diagnostic yield of EUS-FNAs, and thus, a basic understanding of cytopathology is a requisite for the successful endoscopist. This chapter discusses the role of rapid on-site evaluation, provides strategies to appropriately triage material obtained by EUS-FNA, and gives the reader a concise overview of the cytopathologic features of the most commonly sampled lesions.
67 THE ROLE OF AGE ADJUSTMENT IN SELF-RATINGS OF HEALTH AMONG OLDER ADULTS.

Background The extent to which older adults take their age into consideration when rating their health is not well understood. Objective The aim of this study is to determine if older adults change their self-rated health (SRH) when instructed to compare with others their own age and, if so, what factors are associated with older adults changing their SRH. Methods We used data from the first wave of the 2nd Longitudinal Study on Aging ( n = 9,447), a population-based face-to-face interview of non-institutionalized US residents over age 70 in 1995. The subjects were asked (1) to rate their health and (2) to rate their health compared to others their own age. Response choices were “excellent,” “very good,” “good,” “fair,” or “poor.” We used ANOVA and chi-squared analyses to examine potential correlates of changing SRH, including sociodemographic and health characteristics. We constructed a logistic regression model to identify characteristics independently correlated with changing SRH. Results 43% of older persons did not change their SRH when asked to compare with others their own age. Increasing one's SRH was associated with older age, being a high school graduate, and having fewer medical conditions, fewer difficulties with activities of daily living (ADLs), and fewer days spent in bed ( p < .01 for all). In multivariate analysis, increasing SRH when comparing with others was positively associated with older age (OR, 1.02; 95% CI, 1.01 to 1.03), higher education (OR, 1.01; 95% CI, 1.01 to 1.06), poor health ratings (OR, 5.2; 95% CI, 4.6. to 5.90) were all independently associated with and inversely associated with greater number of bed days (OR, 0.99; 95% CI, 0.98 to 0.99), medical conditions (OR, 0.80; 95% CI, 0.78 to 0.83), and ADL difficulties (OR, 0.96; 95% CI, 0.93 to 0.99). Conclusions Almost half of older adults do not change their self-rating of health when comparing with others, demonstrating that implicit age adjustment is common among seniors.
Moral hazard and ration of economic agent in the economy

The aim to benefit is both the start and the end of economic agent's behavior. However, if there are no quite perfect law system and moral control mechanism, ethical principles that must be obeyed in the economy and the means to legally realize benefit will not be common in society, but instead, illegal behavior will be dominant. Therefore, we have to continuously deepen the reform to market system, establish perfect law system, make the economic agents under the control of institutional arrangements so that the behavior can be consistent with social values, then economic benefits can be realized.
Risk Management of Project Process Based on Cost-Time-Quality

Because of the binding interaction of cost,time and quality,we need to weigh the relative interaction of the three factors in the different stage of the project life cycle.The AHP along with the knowledge of fuzzy math is introduced to balance the different weight vectors of cost,time and quality and to analyze the probability of different risks and their disparate effects on the three factors.By calculating the synthetic effects of each risk,the ranking of them is made and the level is clear by using ABC analysis method.Thus we can get the theme of risk management of different stage,and carry on dynamic supervision and control the risk of the project.
Center Pivot Irrigation Systems

A center pivot irrigation system is a movable pipe structure that rotates around a central pivot point connected to a water supply. Center pivot irrigation systems are the most popular sprinkler irrigation systems in the world because of their high efficiency, high uniformity, ability to irrigate uneven terrain, and low capital, maintenance, and management costs. The history of center pivot irrigation systems began in Nebraska in the 1950s, and there are now hundreds of thousands of center pivot irrigation systems in the world. Center pivots are “perhaps the most significant mechanical innovation in agriculture since the replacement of draft animals by the tractor” (Splitter, Scientific American). The systems move through the field by electrically powered tractor wheels. Sprinkler flow rates increase toward the outer end of the pivot because the end of the pivot travels faster. The primary design constraint is the prevention of runoff at the end of the pivot, where application rates are highest. This chapter covers center pivot pipeline and mainline design, selection of sprinklers, and optimization of the design with respect to yield, energy requirement, components, and economics.
Regulation of phosphatidylinositol 3-kinase by insulin in rat skeletal muscle

The presence of phosphatidylinositol 3-kinase (PI 3-kinase) in mammalian skeletal muscle and its response to insulin stimulation were investigated. PI kinase, immunoprecipitated from rat soleus mus...
Helical Poly(5-alkyl-2,3-thiophene)s: Controlled Synthesis and Structure Characterization

Whereas poly(3-alkyl-2,5-thiophene)s (P3AT), with many potential applications, have been extensively investigated, their ortho-connected isomers, poly(5-alkyl-2,3-thiophene)s (P5AT), have never been reported because of the difficulty in their syntheses. We herein present the first synthesis of regioregular P5AT via controlled Suzuki cross-coupling polymerization with PEPPSI-IPr as catalyst, affording the polymers with tunable molecular weight, narrow polydispersity (PDI), and well-defined functional end groups at the gram scale. The helical geometry of P5AT was studied by a combination of NMR, small-angle X-ray scattering (SAXS), and scanning tunneling microscopy (STM). Particularly, the single polymer chain of poly(5-butyl-2,3-thiophene) (P5BT) on highly oriented pyrolytic graphite (HOPG) substrates with either M or P helical conformation was directly observed by STM. The comparison of UV–vis absorption between poly(5-hexyl-2,3-thiophene) (P5HT) (λ = 345 nm) and poly(3-hexyl-2,5-thiophene) (P3HT) (λ = 45...
Arteriovenous Malformations in the Pediatric Population: Review of the Existing Literature

Arteriovenous malformations (AVMs) in the pediatric population are relatively rare but reportedly carry a higher rate of rupture than in adults. This could be due to the fact that most pediatric AVMs are only detected after rupture. We aimed to review the current literature regarding the natural history and the clinical outcome after multimodality AVM treatment in the pediatric population, as optimal management for pediatric AVMs remains controversial. A multidisciplinary approach using multimodality therapy if needed has been proved to be beneficial in approaching these lesions in all age groups. Microsurgical resection remains the gold standard for the treatment of all accessible pediatric AVMs. Embolization and radiosurgery should be considered as an adjunctive therapy. Embolization provides a useful adjunct therapy to microsurgery by preventing significant blood loss and to radiosurgery by decreasing the volume of the AVM. Radiosurgery has been described to provide an alternative treatment approach in certain circumstances either as a primary or adjuvant therapy.
Effective Electrostatic Discharge detection in equipment via EMI

Electrostatic Discharge (ESD) is a common quality issue in the semiconductor industry. ESD can be caused by improper human handling, poor equipment grounding, triboelectric charging, frictional movement, use of insulator material and many others. It is important to have the right method to detect the ESD event effectively. This paper will illustrate an actual case study on how Electromagnetic Interference (EMI) measurement techniques can be used to effectively detect the high speed ESD events versus the conventional ESD standard practices.
Design of a Plugin Split-Parallel Chevrolet Malibu: Control Strategy Development

As a selected participant in the EcoCAR2: Plugging In to the Future competition, headline sponsored by General Motors and the US Department of Energy, the Rose-Hulman team has completed the second year of a three year design cycle. This paper focuses on the supervisory control system design completed during year one of the competition including plant model development, control system hardware architecture, control system software architecture, vehicle operational modes, automated testing, and fault detection and mitigation.
Device-to-device communications for wireless video delivery

The increasing demand for wireless video transmission requires new transmission paradigms. This paper reviews our recent work on such a new paradigm, namely the combination of caching of popular video files on wireless devices, with device-to-device (D2D) communication, so that users can obtain files from other wireless devices in their vicinity. The D2D communication is controlled by the base station (BS), and occurs only between devices that are within a small area (cluster) in order to allow high frequency reuse. The cluster size can be optimized for maximum overall system throughput. The caching strategy of the devices can be deterministic or random. Besides numerical optimization of the clustering and caching parameters, we also determine analytical upper and lower bound for how the throughput scales with the number of devices in a cell. For highly concentrated video request distributions, the throughput scales linearly, while in other cases only a slower increase is possible.
Low-Input and Intensified Crop Production Systems Effects on Soil Health and Environment

The material in this chapter covers the concepts of “low-input” and “intensified” production systems in the context of input intensity and sustainability. Research-based case studies are presented that draw out the practicalities of implementing production practices on an input intensity gradient from external inputs to captured inputs. Captured inputs are those generated from natural capital such as N fixation, and biological control. The discussion focuses on how management strategies along this gradient support soil health and crop productivity. Farm-based case studies are used to explore how individual producers have employed or adapted low-input and agroecosystem approaches to build viable environmentally sound farming systems. A national case study, focused on Cuba, furthers understanding of generating a national food system under a constrained input environment that is capable of meeting food security needs. Conclusions are drawn on the practicality of adopting low-input or agroecosystem practices to generate a sustainable intensified agricultural production system needed to supply food, feed, fiber, and fuel to support a growing world population.
Abstract 121: Gstm1 Deletion Exaggerates Hypertension, Oxidative Stress, and Kidney Pathology in Angiotensin II Hypertension Independent of Nox2 and Nox4

Gstm1 gene encodes an enzyme that belongs to a superfamily of Glutathione-S-transferases that metabolize a broad range of reactive oxygen species. In the African American Study of Kidney Disease Trial (AASK), we reported that participants with decreased expression of GSTM1 as carriers of the GSTM1 null allele have accelerated kidney disease progression. To establish cause and effect, we generated Gstm1-/- (KO) mice and determined their response in angiotensin II (AngII)-induced hypertension (at 1000 ng/kg/min for 4 weeks). By radiotelemetry, Gstm1 KO mice (n=6) displayed a modest but significantly higher baseline systolic blood pressure (SBP, mmHg) compared to their wild type (WT) littermates (n=6): KO 135.8 ± 1.4; WT: 129.9 ± 1.2; P = 0.01. AngII augmented the difference in SBP between WT and KO mice (KO 175.4 ± 6.2; WT 158.0 ± 2.6, p = 0.04). There were no differences in albumin/creatinine ratio (μg/mg) either at baseline (KO 29.1± 4.1; WT 27.3 ± 2.9) or after 4 weeks of Ang II (KO 4657 ± 631.6; WT 4697.7 ± 533.8). By quantitative real-time PCR, the renal expressions of Nox2 and Nox4 genes were almost identical and not statistically different between WT and KO mice. However, by luminescence, Gstm1 KO mice had significantly increased levels of superoxide radicals: [counts/min/1 mg of dry tissue] KO 128 ± 12 vs. WT 42 ± 8.5; P < 0.0001. Furthermore, there was significantly worse kidney pathology in Gstm1 KO mice (Figure 1), including focal segmental glomerulosclerosis (FSGS), fibrosis, chronic inflammation and epithelial cell reactivity. In conclusion, loss of GSTM1 enzyme increases Ang II induced hypertension, oxidative stress and kidney injury independent of Nox2 or Nox4. ![][1] [1]: /embed/graphic-1.gif
Despite warnings, fatal overdoses continue with misuse of fentanyl patch

The Food and Drug Administration (FDA) recently updated a public health advisory on the safe use of the fentanyl transdermal system patch after continuing to receive reports of deaths and life-threatening adverse events ([www.fda.gov/cder/drug/advisory/fentanyl_2007.htm][1]). ![Figure][2]
Taste bud-derived BDNF maintains innervation of a subset of TrkB-expressing gustatory nerve fibers

Abstract Taste receptor cells transduce different types of taste stimuli and transmit this information to gustatory neurons that carry it to the brain. Taste receptor cells turn over continuously in adulthood, requiring constant new innervation from nerve fibers. Therefore, the maintenance of innervation to taste buds is an active process mediated by many factors, including brain-derived neurotrophic factor (BDNF). Specifically, 40% of taste bud innervation is lost when Bdnf is removed during adulthood. Here we speculated that not all gustatory nerve fibers express the BDNF receptor, TrkB, resulting in subsets of neurons that vary in their response to BDNF. However, it is also possible that the partial loss of innervation occurred because the Bdnf gene was not effectively removed. To test these possibilities, we first determined that not all gustatory nerve fibers express the TrkB receptor in adult mice. We then verified the efficiency of Bdnf removal specifically in taste buds of K14-CreER:Bdnf mice and found that Bdnf expression was reduced to 1%, indicating efficient Bdnf gene recombination. BDNF removal resulted in a 55% loss of TrkB-expressing nerve fibers, which was greater than the loss of P2X3-positive fibers (39%), likely because taste buds were innervated by P2X3 +/TrkB − fibers that were unaffected by BDNF removal. We conclude that gustatory innervation consists of both TrkB-positive and TrkB-negative taste fibers and that BDNF is specifically important for maintaining TrkB-positive innervation to taste buds. In addition, although taste bud size was not affected by inducible Bdnf removal, the expression of the γ subunit of the ENaC channel was reduced. So, BDNF may regulate expression of some molecular components of taste transduction pathways.
New Laboratory Course for Senior-Level Chemical Engineering Students

A new laboratory course has been developed at the University of Virginia for senior- level chemical engineering students. The new course is based on three 4-week long experiments in bioprocess engineering, energy conversion and catalysis, and polymer synthesis and characterization. The emphasis is on the integration of process steps and the demonstration of how chemical engineering is relevant to different areas of technology. The overall concept of the course and an overview of each experiment are discussed and student feedback is described.
REL proto-oncogene is frequently amplified in extranodal diffuse large cell lymphoma

Comparative genomic hybridization (CGH) analysis of DNA extracted from a diffuse lymphoma with a large cell component (DLLC) that displayed double minute chromosomes upon conventional karyotypic analysis indicated overt amplification of DNA sequences derived from the 2p13-15 region. Southern blot analysis of this tumor DNA with a cDNA probe for the proto-oncogene REL, previously mapped to 2p14-15, indicated a greater than 35-fold amplification of REL. To determine the incidence of REL amplification and possible clinical or histologic association with DLLC, a panel of 111 tumor DNAs from DLLC specimens was screened for REL amplification by Southern blot analysis. A copy number of ≥4 was noted in 26 cases (23%). Southern blot analysis of these 26 tumor DNAs with a cDNA probe for TGFA, mapped to 2p13, indicated lack of coamplification except in one case. Another member of the Rel/NF-κB family of transcriptional activators, RELA/p65 mapped to 11q13, was amplified in five cases as determined by Southern blot analysis using a cDNA probe. Nineteen of the 26 DLLC (73%) with REL amplification were primary extranodal lymphomas. As a group, the tumors with REL amplification demonstrated an increased frequency of chromosomal aberrations previously associated with tumor progression, suggesting an oncogenic effect of amplified REL in B-lymphoid cells that already contained a transforming genetic lesion. Thus, REL amplification is a frequent event in DLLC, and probably constitutes a progression-associated marker of primary extranodal lymphomas. This study shows the usefulness of the CGH technique in identifying chromosomal regions overrepresented in tumors that can point to amplified genes and may be correlated with clinical features of the disease.
Combined Molecular Dynamics Simulation–Molecular-Thermodynamic Theory Framework for Predicting Surface Tensions

A molecular modeling approach is presented with a focus on quantitative predictions of the surface tension of aqueous surfactant solutions. The approach combines classical Molecular Dynamics (MD) simulations with a molecular-thermodynamic theory (MTT) [Y. J. Nikas, S. Puvvada, D. Blankschtein, Langmuir 1992, 8, 2680]. The MD component is used to calculate thermodynamic and molecular parameters that are needed in the MTT model to determine the surface tension isotherm. The MD/MTT approach provides the important link between the surfactant bulk concentration, the experimental control parameter, and the surfactant surface concentration, the MD control parameter. We demonstrate the capability of the MD/MTT modeling approach on nonionic alkyl polyethylene glycol surfactants at the air–water interface and observe reasonable agreement of the predicted surface tensions and the experimental surface tension data over a wide range of surfactant concentrations below the critical micelle concentration. Our modeling ap...
Utility of Imaging in Risk Stratification of Chest Pain in Women

Recent decades have seen a growing recognition that the understanding of sex differences in cardiovascular disease (CVD) is vital to optimal diagnosis and management, particularly of women (Mosca et al. Circulation 124:2145-54, 2011). There is simultaneously an increasing appreciation of the multifactorial nature of ischemic heart disease (IHD) in many patients, in whom disease may extend beyond the epicardial coronaries. While obstructive coronary artery disease (CAD) remains underdiagnosed in women and still represents a major burden of disease, women also present with nonobstructive CAD more commonly than men (Patel et al. N Engl J Med 362:886-95, 2010). Indeed, microvascular dysfunction, coronary artery vasospasm, and coronary dissections contribute to a larger proportion of IHD in women than men (Bairey Merz et al. J Am Coll Cardiol 47:S21-9, 2006). Here, we review the symptom presentation of women with IHD and the noninvasive modalities used to risk stratify women with suspected IHD.
Why Archaea Are Limited in Their Exploitation of Other, Living Organisms

Only a handful of Archaea have been suggested to be connected with pathologies or to serve as parasites, and none conclusively. Here I consider what might limit the potential for Archaea to serve as exploiters of other, living organisms. I suggest that this dearth may be a consequence of multiple factors which have a combined impact rather than any one factor serving as a ‘smoking gun’. These factors should be viewed as hypotheses, further exploration of which may be helpful towards refinement of considerations of just what may serve to limit the occurrence of Archaea serving as pathogens. I suggest as well that a spectrum likely exists in which eukaryotes—among the three cellular domains—are most frequently exploitive of other species while Archaea are the least. Bacteria, when serving especially as pathogens but also as predators, in turn display an intermediate propensity to exploit other organisms.
Voices from the harvest: The role of language, identity, and life experience in the education of young children of migrant farmworkers

ABSTRACTThis study is an ethnographic case study that focuses on three family members from Mexican migrant farmworker households (a father, a grandmother, and mother), their discussions around the topic of educating their children, and their engagement in the seasonal early childcare programs that serve farmworker children. This study takes a sociocultural perspective to examine parental lessons in the home, views of institutionalized education, and the role of beliefs, identity, and life experience that contribute to the early years of a child’s education. This study address gaps in the research related to migrant farmworker families with young children in early childhood education programs.
NRF2 regulates core and stabilizing circadian clock loops, coupling redox and timekeeping in Mus musculus

Like many other animals, our behavior often follows a familiar pattern each day. We tend to wake up with the morning sunlight and start by eating breakfast to satisfy our hunger. Then, at night, most of us sleep, and our bodies use chemical building blocks from the day's meals to replenish and repair our tissues. As such, its not just our behavior that shows a daily cycle. The countless chemical reactions that keep us alive, collectively referred to as our metabolism, also change over the course of each day. Daily patterns of activity, known as circadian rhythms, can be seen even at the level of individual cells. Each cell in the body has its own molecular clock that works by rhythmically cycling the levels of different molecules. Proteins called CLOCK and BMAL1 trigger the production of proteins PER and CRY. As levels of PER and CRY rise, they interfere with CLOCK and BMAL1, essentially switching off their own production. Then, levels of PER and CRY fall and the cycle starts again. Thus, these molecules rise and fall throughout the day to drive circadian rhythms, similar to how a pendulum swings back and forth to keep a clock ticking. Metabolism and circadian rhythms are clearly linked, but it is not well understood how this works. Now, Wible, Ramanathan et al. identify a protein called NRF2 as an important bridge between the molecular clock and metabolism. NRF2 is a activated by hydrogen peroxide, a byproduct of cell metabolism, and when activated this protein grabs hold of DNA to increase the activity of specific genes. A combination of experiments revealed that mouse liver cells need NRF2 to maintain a normal circadian rhythm, and a closer inspection of the liver cells revealed that NRF2 specifically attaches to part of the gene for a clock protein called CRY2. This enhances the production of this protein, which in turn, switches CLOCK and BMAL1 off. In this way, NRF2 links metabolism signals to the ticking of the circadian clock. Previous research has shown a link between shift work, which disrupt these rhythms, and metabolic diseases like obesity and diabetes. Understanding more about the underlying molecular biology that links metabolism to circadian rhythms could help scientists to find new ways to improve public health.
Application of a Finite Element Hydrodynamic Model to the Great bay Estuary System, New Hampshire, U.S.A.

Abstract A vertically integrated, one layer, hydrodynamic model developed by Connor and Wang for Massachusetts Bay has been adapted to the Great Bay Estuary, New Hampshire. This finite element model was found to be well suited to the complexities of the estuary. Initial model development and testing was carried out. The bottom friction coefficient was the dominant parameter in the calibration process. A method for selection of the bottom friction coefficient in the calibration process was developed. Eddy viscosity terms, which primarily act as numerical damping, were included. The model was calibrated using an extensive set of tidal sea level and current data recently collected by the University of New Hampshire and the National Ocean Survey (NOS). The data sets used in the calibration and validation process include sea level data used to specify open boundary conditions in the model. Validation results show good agreement between tidal elevation measurements and model predictions. Predicted currents have a different scale of resolution than the current measurements, making direct comparisons difficult to interpret. A program for processing current data to make more meaningful comparisons is presented briefly.
Cardiac resynchronization therapy reverses severe dyspnea associated with acceleration‐dependent left bundle branch block in a patient with structurally normal heart

A 55-year-old woman presented with severe dyspnea during acceleration-dependent left bundle branch block (LBBB). Metoprolol initially ameliorated symptoms by preventing the heart rate at which LBBB occurred. Over time LBBB presented at slower heart rates and the patient developed recurrent dyspnea during an activity that correlated with the development of LBBB on event monitors and exercise stress testing. A biventricular pacemaker was implanted, and the patient's symptoms remain resolved after a follow-up of over 4 years. More research is needed to define the use of cardiac resynchronization therapy in patients with normal heart function.
Alpha Blocker and 5-Alpha Reductase Inhibitor Prescribing Habits among Urologists and Primary Care Physicians

AbstractIntroduction:While primary care physicians often prescribe medical therapy for voiding symptoms attributed to benign prostate enlargement, it is not clear to what extent they use novel or v...
An example of enhanced emission of a pyridine containing schiff base zinc2+ complex

Abstract A pentadentate Schiff-based ligand incorporating a pyridine binding moiety has been synthesized and characterized. This ligand is of potential interest in the development of a fluorescent chemosensor for the biologically relevant Zn2+. This mixed oxo and aza donor ligand shows highly selective fluorescent response to Zn2+ compared to alkali, alkaline, transition metal, and lanthanide ions, exhibiting a quantum yield of 1.60% when bound to Zn2+. The system exhibits a limit of detection of 7.2 µM. Examination of twelve other metal ions in competition with the ZnL complex found a unique augmentation in fluorescence upon addition of K, Ca, Mg, and Cd ions, an effect not previously observed in similar chemosensor systems. Cooperative binding of ligand, Zn, and K resulted in the largest increase in quantum yield to 2.71%.
Musician and Nonmusician Hearing Aid Setting Preferences for Music and Speech Stimuli.

Purpose The purpose of this study was to evaluate potential group differences between musicians and nonmusicians in their self-adjusted (SA) gain and compression settings for both music and speech ...