cssi/SciSciGPT-SciSciNet huggingface dataset:
Mouse Models in Preclinical Drug Development: Applications to CNS Models

Primary tumors of the CNS can be divided into several groups; the most common in adults being the gliomas and in children the medulloblastomas (Kleihues et al. J Neuropathol Exp Neurol 61(3):215–225, 2002). Gliomas are thought to arise from cells at some point of differentiation along glial lineage leading to astrocytes and oligodendrocytes. In the normal brain, the primary function of astrocytes is to maintain homeostasis of neuronal extracellular milieu and protect the neurons by establishing the blood–brain barrier during development. Oligodendrocytes provide the CNS axons with myelin sheaths that insulate the neurons and thereby accelerating the action potential transduction. By contrast, medulloblastomas appear to arise from cells of the external granule layer in the developing cerebellum that give rise to the internal granule layer neurons. These tumors are the most common tumor found in children. Gliomas are relatively radiation-resistant and the clinical outcome for patients with the most aggressive and common of the gliomas, Glioblastoma Multiforme or GBM, has been poor and essentially unchanged in the last 50 years with the median survival averaging 12–14 months (CBTRUS. Statistical report: primary brain tumors in the USA). Medulloblastomas on the other hand are much more responsive than GBMs to radiation and chemotherapy with a 70% cure rate. An important step toward improving existing treatments and discovering new ones comes from creating genetically and histologically accurate mouse models that can be used as a representative system of human tumors in order to study the biological and mechanistic causes of brain cancer and the way that these tumor interact with their microenvironment. Furthermore, accurate mouse models of these tumors are helping us to identify novel targets and therapies for clinical testing (Hambardzumyan et al. Expert Opin 2(11):1435–1451, 2007).
Photoacoustic Image-Guided Delivery of Plasmonic-Nanoparticle-Labeled Mesenchymal Stem Cells to the Spinal Cord.

Regenerative therapies using stem cells have great potential for treating neurodegenerative diseases and traumatic injuries in the spinal cord. In spite of significant research efforts, many therapies fail at the clinical phase. As stem cell technologies advance toward clinical use, there is a need for a minimally invasive, safe, affordable, and real-time imaging technique that allows for the accurate and safe monitoring of stem cell delivery in the operating room. In this work, we present a combined ultrasound and photoacoustic imaging tool to provide image-guided needle placement and monitoring of nanoparticle-labeled stem cell delivery into the spinal cord. We successfully tagged stem cells using gold nanospheres and provided image-guided delivery of stem cells into the spinal cord in real-time, detecting as few as 1000 cells. Ultrasound and photoacoustic imaging was used to guide needle placement for direct stem cell injection to minimize the risk of needle shear and accidental injury and to improve t...
MyD88 signalling is critical in the development of pancreatic cancer cachexia.

Background Up to 80% of pancreatic cancer patients suffer from cachexia, a devastating condition that exacerbates underlying disease, reduces quality of life, and increases treatment complications and mortality. Tumour-induced inflammation is linked to this multifactorial wasting syndrome, but mechanisms and effective treatments remain elusive. Myeloid differentiation factor (MyD88), a key component of the innate immune system, plays a pivotal role in directing the inflammatory response to various insults. In this study, we tested whether MyD88 signalling is essential in the development of pancreatic cancer cachexia using a robust mouse tumour model. Methods Sex, age, and body weight-matched wide type (WT) and MyD88 knockout (MyD88 KO) mice were orthotopically or intraperitoneally implanted with a pancreatic tumour cell line from a syngeneic C57BL/6 KRASG12D/+ P53R172H/+ Pdx-Cre (KPC) mouse. We observed the effects of MyD88 signalling during pancreatic ductal adenocarcinoma progression and the cachexia development through behavioural, histological, molecular, and survival aspects. Results Blocking MyD88 signalling greatly ameliorated pancreatic ductal adenocarcinoma-associated anorexia and fatigue, attenuated lean mass loss, reduced muscle catabolism and atrophy, diminished systemic and central nervous system inflammation, and ultimately improved survival. Our data demonstrate that MyD88 signalling plays a critical role in mediating pancreatic cancer-induced inflammation that triggers cachexia development and therefore represents a promising therapeutic target. Conclusions MyD88-dependent inflammation is crucial in the pathophysiology of pancreatic cancer progression and contributes to high mortality. Our findings implicate the importance of innate immune signalling pathways in pancreatic cancer cachexia and a novel therapeutic target.
My Patient’s Aorta Was Repaired. What Complications Arise from AAA Repair? When Should I Be Concerned About Recurrence?

As the number of patients undergoing abdominal aortic aneurysm (AAA) repair increases, it has become increasingly important for acute care providers to understand the complications associated with these procedures. Both open and endovascular aortic repair (EVAR) techniques are widely used. Patients with history of open AAA repair may present with ischemic colitis, aortoenteric fistula, or graft infection. Patients who have undergone EVAR may present with ischemia or endoleak. Rupture is a known complication of EVAR and requires routine imaging surveillance. Computed tomography (CT) angiography or CT with triple-phase contrast helps evaluate for many AAA repair complications. Vascular surgery consultation, often early, is generally indicated when complications are suspected or discovered.
Complement Membrane Attack Complex: New Roles, Mechanisms of Action, and Therapeutic Targets.

The complement membrane attack complex (MAC) is classically known as a cytolytic effector of innate and adaptive immunity that forms pores in the plasma membrane of pathogens or targeted cells, leading to osmolysis. Nucleated cells resist MAC-mediated cytolysis by expression of inhibitors that block MAC assembly or by rapid removal of MAC through endocytosis or shedding. In the absence of lysis, MAC may induce intracellular signaling and cell activation, responses implicated in a variety of autoimmune, inflammatory, and transplant disease settings. New discoveries into the structure and biophysical properties of MAC revealed heterogeneous MAC precursors and conformations that provide insights into MAC function. In addition, new mechanisms of MAC-mediated signaling and its contribution to disease pathogenesis have recently come to light. MAC-activated cells have been found to express proinflammatory proteins—often through NF-κB–dependent transcription, assemble inflammasomes, enabling processing, and facilitate secretion of IL-1β and IL-18, as well as other signaling pathways. These recent insights into the mechanisms of action of MAC provide an updated framework to therapeutic approaches that can target MAC assembly, signaling, and proinflammatory effects in various complement-mediated diseases.
Acute Start Peritoneal Dialysis during the COVID-19 Pandemic: Outcomes and Experiences.

No abstract available Keywords: COVID-19; acute renal failure; dialysis; peritoneal dialysis.
Uniformity and Yield Optimization for a highly diverse Product Mix : Topic: YE

Recent developments in the Semiconductor industry are moving away from the trend of transition to the next technology node, instead diversifying to address different markets. We discuss some implications of a change, which in our case involves a transition in chip size. Even when the node remains the same, changing the chip size affects process as well as process control and productivity. We discuss the effects of the introduction of products with a small chip size in a production line optimized for large Logic chips. We also describe specific changes made to optimize our Lithography, Reactive Ion Etching (RIE) and Chemical-Mechanical Polishing (CMP) process for small chips.
Standardizing a volume benchmark for cerebrospinal fluids for optimal diagnostic accuracy.

INTRODUCTION Cerebral spinal fluid (CSF) cytomorphologic analysis remains the gold standard in the evaluation of malignant leptomeningeal involvement. However, collection of optimal volumes for adequate cytomorphologic evaluation is not standardized. Our study investigated optimal CSF volumes that result in a significant diagnostic result. METHODS A total of 4114 samples were retrospectively identified from 2014 to 2018, and 2557 samples had concurrent flow cytometry (FC) study. Each specimen was grouped as unsatisfactory, negative, atypical, or positive. Positive samples were grouped as either solid tumors, leukemia, or lymphoma by the type of malignancy detected. Demographic data as well as CSF source was recorded. Specimens with FC were separated by detection on cytology and/or FC. A t-test and ANOVA test were used to compare the average volumes for each group. RESULTS Average volumes for negative, atypical, and positive samples are 7.48 mL (95% CI: 7.33, 7.63), 7.97 mL (95% CI: 7.37, 8.57), and 8.44 mL (95% CI: 7.46, 9.43), respectively. Average volumes for solid tumors, leukemia, and lymphoma positive samples are 12.0 mL (95% CI: 9.11, 14.89), 6.73 mL (95% CI: 5.94, 7.53), and 8.44 mL (95% CI: 6.78, 10.09). For cases with FC, the volumes are 10.11 mL (95% CI: 9.28, 10.96), 7.28 mL (95% CI: 6.87, 7.70), and 6.86 mL (95% CI: 6.25, 7.49) for positive cytology only, positive cytology/FC, and negative for both, respectively. CONCLUSIONS Our results suggest that higher volumes produce better results for analysis. We recommend an optimal volume of 8.44 mL for cytologic work-up of malignancies. However, optimal volumes may differ based upon malignancy type and utilization of flow cytometry.
Autism and Neurodiversity: Addressing Concerns and Offering Implications for the School-Based Speech-Language Pathologist

Purpose The purpose of this article is to address some common concerns associated with the neurodiversity paradigm and to offer related implications for service provision to school-age autistic stu...
The History of Hemorrhagic Shock and Damage Control Resuscitation.

The understanding and management of hemorrhagic shock have evolved significantly over the last 400 years. Injured patients in shock mandate immediate surgeon involvement. Every graduating surgical ...
Congenital Chagas disease: progress toward implementation of pregnancy-based screening.

Purpose of review Lack of recognition of congenital Chagas disease in infants of mothers from endemic regions who are living in countries nonendemic for Trypanosoma cruzi infection suggests a high rate of underdiagnosis. Pregnancy is the optimal access point for identifying Chagas disease in at-risk mothers and their infants. In this review, we update progress toward implementation of pregnancy-based screening for congenital Chagas disease in nonendemic settings. Recent findings International organizations have updated recommendations for diagnosis, treatment and prevention of congenital Chagas disease. Reports of successful implementation of pregnancy-based screening at some centers provide a model for optimizing diagnosis of congenital Chagas disease. Screening family members of index patients may identify additional T. cruzi-infected persons. Promising tests to augment current diagnostic modalities for maternal and congenital Chagas disease are in development. Universal or risk-based screening would be cost-effective. More healthcare providers are now aware that treatment of congenital Chagas disease is curative and are promoting efforts to make pregnancy-based screening for congenital Chagas disease a standard of care. Summary Ongoing efforts to implement routine pregnancy-based screening for congenital Chagas disease in nonendemic regions will mutually benefit infants, their mothers and family members and can prevent potentially fatal Chagas cardiomyopathy.
Two Decades of TRIPS in China

China became the 143rd member of the World Trade Organization on December 11, 2001. Written as contribution to a volume commemorating the 20th anniversary of China's accession to the international trading body, this chapter reviews the intellectual property developments in China since the country joined the WTO. This chapter begins by highlighting the developments related to the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS Agreement) in the first decade of China's WTO membership. It then discusses the country's "innovative turn" in the late 2000s and its ramifications. The chapter continues to examine the US-China trade war, in particular the second TRIPS complaint that the United States filed against China in March 2018. It concludes with observations about the impact of the TRIPS Agreement on China, China's impact on the Agreement and how the changing Chinese intellectual property landscape has altered the developing countries' coalition dynamics within the WTO.
The (Boundedly) Rational Basis of Trademark Liability

The confusion that has accompanied the effort to graft a dilution remedy onto federal trademark law has sown deep uncertainty about the remedy's proper scope and purpose. This confusion is an outgrowth of the peculiar history of dilution theory in the development of trademark law, and the resulting tension between uniqueness-based theories of dilution and theories based on free-riding concerns. This article takes the position that the current conceptual framework for trademark liability is misguided. By focusing its analysis on consumer beliefs about the relationship between a mark and a manufacturer, current trademark doctrine is ignoring a far more persuasive justification for the imposition of liability: debiasing. This article argues that trademark liability is best understood as a legal regime designed to harness the efficiencies of boundedly rational consumer decision-making, while minimizing the effects of resulting biases and errors. An overview of trademark cases reveals that while courts purport to analyze consumer beliefs about the mark/maker nexus, they in fact rely on a limited set of proxy measurements that have little to do with those beliefs. Instead, the proxy factors appear to represent features of the marketplace with strong potential to trigger cognitive phenomena that can generate bias and error. Understanding these phenomena and using them as a guide to set the boundaries of liability provides a more coherent and persuasive justification for the trademark regime than current competing rationales, and offers a potential solution to the long-standing debate between free-riding and uniqueness theories of dilution that would harmonize those theories with infringement policy.
The past, present, and future of photonic integrated circuits in optical communications

Modern electronics began with the invention of the transistor and the discovery of minority carrier injection [1]. These advances have fundamentally improved and changed our modern world. Essential to this progress is the scalable nature of semiconductor technology and the invention of the integrated circuit (IC) [2, 3]. The IC has become ubiquitous and has had unparalleled impact on our modern world as a result of the ability of semiconductor and transistor technology to continually increase the functionality, performance, and reliability of solid-state circuits, while reducing their size, power, and costs. This scaling has been exponential, resulting in ICs today that contain over a billion transistors per chip with a cost per transistor of <0.1 microcents. A key value of the IC is the ability to realize many of the aforementioned improvements by eliminating the need to discretely package and assemble individual devices or smaller circuits by providing the device and circuit connections via semiconductor batch and wafer scale processing.
A psychophysical evaluation of the accuracy of shape discrimination as an aircraft landing aid

Pilots flying into unfamiliar airports may find it difficult to judge correctly the proper glide angle when landing. Several types of landing aids are now in use to eliminate this problem; however, they are typically expensive to install and maintain. A possible solution to this problem is the replacement of runway centerline striping with painted diamonds. Changes in the projected shape of the diamonds could provide glide angle information. It was the purpose of this study to evaluate the accuracy possible in detecting glide angle using this method. The just-noticeable difference between a square and a diamond shape was determined. This ratio was found to be 1.049/1.00 for the upper just noticeable difference and .945/1.00 for the lower just noticeable difference. This finding indicates that, if discrimination in the real world approaches this accuracy, deviations of approximately .17° above or below glide slope are detectable.
Fuel Economy of the 1975 Models

The fuel economy data obtained from the emission tests run by the U.S. Environmental Protection Agency (EPA) have been used to show passenger car fuel economy trends from model year 1957 to present. This paper adds the 1975 model year to the historical trend and concentrates on comparisons between the 1975 to 1974 models. The net change in fuel economy for the fleet has been estimated at plus 13.8% comparing the 1975 models to the 1974 models assuming no model mix change occurs. General Motors is responsible for the majority of the fleet average improvement.
Income Distribution and Health: A Worldwide Analysis

Despite having had nearly a decade of economic growth, the United States is among many developed countries that lag behind under developed countries on various health indicators such as life expectancy. Although access to universal health care is also a major contributor to the level of health of a nation, growing evidence suggests that broader economic forces may be playing a larger role in determining a nation’s health status. This article is available in The Park Place Economist: http://digitalcommons.iwu.edu/parkplace/vol9/iss1/14
Practices of Depression Care in Home Health Care: Home Health Clinician Perspectives

Objective:The study assessed gaps between published best practices and real-world practices of treating depression in home health care (HHC) and barriers to closing gaps.Methods:The qualitative study used semistructured interviews with nurses and administrators (N=20) from five HHC agencies in five states. Audio-recorded interviews were transcribed and analyzed by a multidisciplinary team using grounded theory method to identify themes.Results:Routine HHC nursing overlapped with all functional areas of depression care. However, gaps were noted between best and real-world practices. Gaps were associated with perceived scope of practice by HHC nurses, knowledge gaps and low self-efficacy in depression treatment, stigma attached to depression, poor quality of antidepressant management in primary care, and poor communication between HHC and primary care clinicians.Conclusions:Strategies to close gaps between typical and best practices include enhancing HHC clinicians’ knowledge and self-efficacy with depressi...
SRS text-to-phoneme rules: A three-level rule strategy

SRS (Speech Research System), the interactive speech synthesis system at Cornell University, now allows users to work with three kinds of text-tophoneme rules: text-modification rules, conversion rules, and feature-modification rules. These rules apply in succession to convert a text utterance into a string of phonemes. The SRS strategy is being used to develop a practical set of text-tophoneme rules for English. Performance tests show very promising results.
Brief quiet ego contemplation reduces oxidative stress and mind-wandering

Excessive self-concern increases perceptions of threat and defensiveness. In contrast, fostering a more inclusive and expanded sense of self can reduce stress and improve well-being. We developed and tested a novel brief intervention designed to strengthen a student's compassionate self-identity, an identity that values balance and growth by reminding them of four quiet ego characteristics: detached awareness, inclusive identity, perspective taking, and growth. Students (N = 32) in their first semester of college who reported greater self-protective (e.g., defensive) goals in the first 2 weeks of the semester were invited to participate in the study. Volunteers were randomly assigned to one of three conditions: quiet ego contemplation (QEC), QEC with virtual reality (VR) headset (QEC-VR), and control. Participants came to the lab three times to engage in a 15-min exercise in a 30-days period. The 15-min QEC briefly described each quiet ego characteristic followed by a few minutes time to reflect on what that characteristic meant to them. Those in the QEC condition reported improved quiet ego characteristics and pluralistic thinking, decreases in a urinary marker of oxidative stress, and reduced mind-wandering on a cognitive task. Contrary to expectation, participants who wore the VR headsets while listening to the QEC demonstrated the least improvement. Results suggest that a brief intervention that reduces self-focus and strengthens a more compassionate self-view may offer an additional resource that individuals can use in their everyday lives.
Playing With Fire: The Science of Confronting Adverse Material in Legal Advocacy

For a long time, practitioners and scholars have debated whether volunteering negative information in legal advocacy is strategically advisable. Many advocates consider disclosure of information that is unfavorable to the client's case to be inconsistent with the duty of zealous advocacy, while others consider disclosure to be the surer path to victory. The advocates on both sides of this debate rely largely on legal lore to justify their beliefs about what persuades jurors and judges. Even within this vigorous debate, the growing body of scientific research on the subject of persuasion has not played a pivotal role, and in the few instances when the science is mentioned, the nuances and details of it are glossed over. Playing with Fire changes the nature of the debate by examining in depth the social science studies about disclosure of negative information in a persuasive situation, including all their nuances and complexities. In particular, Playing with Fire is the first law journal article to look at all the major scientific studies in the contexts of law, advertising and politics that examine how an audience reacts to an advocate's voluntary disclosure of negative information. The article applies the results and underlying theories of these studies to the question of disclosure of adverse information in legal advocacy. The result is a deeper, more nuanced picture of how to deal with adverse information than has previously characterized the debate in the legal context.
Neutral and Selective Processes Drive Population Differentiation for Iris hexagona

Gene flow among widespread populations can be reduced by geographical distance or by divergent selection resulting from local adaptation. In this study, we tested for the divergence of phenotypes and genotypes among 8 populations of Iris hexagona. Using a genotyping-by-sequencing approach, we generated a panel of 750 single nucleotide polymorphisms (SNPs) and used population genetic analyses to determine what may affect patterns of divergence across I. hexagona populations. Specifically, genetic differentiation was compared between populations at neutral and nonneutral SNPs and detected significant differences between the 2 types of markers. We then asked whether loci with the strongest degree of population genetic differentiation were also the loci with the strongest association to morphology or climate differences, allowing us to test if pollinators or climate drive population differentiation or some combination of both. We found 2 markers that were associated with morphology and 1 marker associated with 2 of the environmental variables, which were also identified in the outlier analysis. We then show that the SNPs putatively under selection were positively correlated with both geographic distance and phenotypic distance, albeit weakly to phenotypic distance. Moreover, neutral SNPs were only correlated with geographic distance and thus isolation-by-distance was observed for neutral SNPs. Our data suggest that both deterministic and neutral processes have contributed to the evolutionary trajectory of I. hexagona populations.
Characterization of lipids and antioxidant capacity of novel nutraceutical egg products developed with omega‐3‐rich oils

BACKGROUND: Cardiovascular disease has had an unquestioned status of the number one cause of death in the US since 1921. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have cardio-protective benefits. However, egg is typically a poor source of ω-3 PUFAs and, in general, the American diet is low in these cardio-protective fatty acids. Novel, nutritionally enhanced egg products were developed by substituting yolk with ω-3 PUFA-rich flaxseed, menhaden, algae, or krill oil. Experimental egg products matched composition of hen egg (whole egg). The experimental egg products, mixed whole egg, and a liquid egg product (Egg Beaters™) were microwave-cooked and compared. RESULTS: Although fat, protein, and moisture contents of experimental egg products matched (P > 0.05) mixed whole egg, experimental egg products had more (P 0.05) to mixed whole egg, except for experimental egg products with krill oil. However, peroxide value showed that all egg samples had minimal oxidation. Experimental egg products developed with menhaden or flaxseed oil had the highest (P < 0.05) concentration of the antioxidant, ethyoxquin compared to all other egg samples. However, experimental egg products with krill oil likely contained a natural antioxidant, astaxanthin. CONCLUSION: This study demonstrated an alternative approach to developing novel, nutraceutical egg products. Instead of dietary modification of chicken feed, yolk substitution with ω-3 PUFAs oils resulted in enhancement of ω-3 PUFAs beyond levels possible to achieve by modifying chicken feed. Copyright © 2011 Society of Chemical Industry
Delayed biological recovery from extinctions throughout the fossil record

How quickly does biodiversity rebound after extinctions? Palaeobiologists have examined the temporal, taxonomic and geographic patterns of recovery following individual mass extinctions in detail1,2,3,4,5, but have not analysed recoveries from extinctions throughout the fossil record as a whole. Here, we measure how fast biodiversity rebounds after extinctions in general, rather than after individual mass extinctions, by calculating the cross-correlation between extinction and origination rates across the entire Phanerozoic marine fossil record. Our results show that extinction rates are not significantly correlated with contemporaneous origination rates, but instead are correlated with origination rates roughly 10 million years later. This lagged correlation persists when we remove the ‘Big Five’ major mass extinctions, indicating that recovery times following mass extinctions and background extinctions are similar. Our results suggest that there are intrinsic limits to how quickly global biodiversity can recover after extinction events, regardless of their magnitude. They also imply that today's anthropogenic extinctions will diminish biodiversity for millions of years to come.
Tacrolimus toxicity associated with concomitant metoclopramide therapy

Subtherapeutic tacrolimus trough concentrations were noted in a 52-year-old woman who had undergone liver transplantation. Her tacrolimus dosage was increased from 7 to 28 mg twice/day, and ketoconazole therapy was added; however, her tacrolimus concentration remained undetectable. Metoclopramide 10 mg 4 times/day was begun to control the patient's new-onset nausea and vomiting. Within 48 hours of increasing the dosage to 20 mg 4 times/day, her tacrolimus trough concentration exceeded 30 ng/ml. Signs and symptoms were suggestive of tacrolimus nephrotoxicity and neurotoxicity. According to the Naranjo scale, this adverse drug event was probably the result of improved absorption of tacrolimus secondary to metoclopramide therapy. The patient's subtherapeutic tacrolimus concentration at baseline was probably secondary to poor absorption due to impaired gastric emptying. Coadministration of metoclopramide significantly improved gastric motility and delivery of tacrolimus to the small intestine, increasing tacrolimus bioavailability, thus resulting in acute-onset tacrolimus toxicity. When tacrolimus is administered with metoclopramide in patients with gastric dysmotility, tacrolimus concentrations should be monitored closely to minimize the risk of toxicity.
Compact capacitance and capacitive coupling-noise modeling of Through-Oxide Vias in FDSOI based ultra-high density 3-D ICs

Fully-Depleted SOI (FDSOI) technology boosts the opportunity to make 3-D ICs with ultra-high integration density, due to the short and tiny Through-Oxide Vias (TOVs), which are made after removing the entire silicon under the buried-oxide layer. This work, for the first time, develops compact physical models for the capacitance of the TOV and the coupling capacitance between TOV and active regions in presence of periodical power lines, from fundamental electrostatic considerations. Calculation results from the models show good agreement with the simulation results from a full-3D capacitance solver. The models are further used to analyze the threshold voltage (V th ) variation in the FDSOI MOSFETs. The TOV in FDSOI and the Through-Silicon Via (TSV) in bulk CMOS based 3-D ICs are finally compared in terms of the self impedance as well as their impact on MOSFET V th variation through capacitive-noise coupling. These results provide important insights to TOV/TSV design and optimization in emerging 3-D ICs.
Interaction of a new gamma-glutamyl-phosphate analog, 4-(phosphonoacetyl)-L-alpha-aminobutyrate, with glutamine synthetase enzymes from Escherichia coli, plant, and mammalian sources.

Abstract The interactions of a newly synthesized nonreactive analog of γ-glutamyl-phosphate, 4-(phosphonoacetyl)- l -α-aminobutyrate, PALAB, have been studied with glutamine synthetases from bacterial, plant, and mammalian sources. The Escherichia coli enzyme fails to bind PALAB any more tightly than it does l -glutamate. In contrast, the pea seed enzyme is potently inhibited by PALAB, due to a two-step tight sequestering of PALAB into the active site and very slow release. The relative affinities of these two enzymes for transition state analogs with tetrahedral symmetry at position 5 (e.g., l -methionine-sulfoximine) were found previously to be the reverse of those for PALAB (F. C. Wedler and B. R. Horn, 1976, J. Biol. Chem. 251 , 7530–7538). Interestingly, the mammalian (ovine brain) enzyme exhibits no marked preference for PALAB vs l -methionine-sulfoximine, binding both reversibly about 10-fold tighter than l -glutamate. Noncompetitive kinetics for PALAB vs l -Glu with the ovine brain enzyme appear to arise from several effects: dissociation of PALAB that is much slower ( t 1 2 − 20 s ) than turnover, and preferential binding of PALAB to free E rather than E·ATP, whereas l -Glu prefers E·ATP over free E. The data strongly suggest that γ-Glu-phosphate, a likely intermediate in the reaction pathway, is stabilized in the active sites of these three enzymes to very different extents, implying that the chemical reaction profiles for each enzyme also differ considerably. Other known differences consistent with this hypothesis are: relative rates of PALAB association and dissociation, substrate binding order, the occurrence of isotopic exchanges with partial reaction systems or of analog-induced conformational changes, and different mechanistic roles for divalent metal ions in catalysis.
Gene–environment interactions in genome‐wide association studies: current approaches and new directions

Background Complex psychiatric traits have long been thought to be the result of a combination of genetic and environmental factors, and gene–environment interactions are thought to play a crucial role in behavioral phenotypes and the susceptibility and progression of psychiatric disorders. Candidate gene studies to investigate hypothesized gene–environment interactions are now fairly common in human genetic research, and with the shift toward genome-wide association studies, genome-wide gene–environment interaction studies are beginning to emerge. Methods We summarize the basic ideas behind gene–environment interaction, and provide an overview of possible study designs and traditional analysis methods in the context of genome-wide analysis. We then discuss novel approaches beyond the traditional strategy of analyzing the interaction between the environmental factor and each polymorphism individually. Results Two-step filtering approaches that reduce the number of polymorphisms tested for interactions can substantially increase the power of genome-wide gene–environment studies. New analytical methods including data-mining approaches, and gene-level and pathway-level analyses, also have the capacity to improve our understanding of how complex genetic and environmental factors interact to influence psychologic and psychiatric traits. Such methods, however, have not yet been utilized much in behavioral and mental health research. Conclusions Although methods to investigate gene–environment interactions are available, there is a need for further development and extension of these methods to identify gene–environment interactions in the context of genome-wide association studies. These novel approaches need to be applied in studies of psychology and psychiatry.
Experimental Investigation of Droplet Dynamics on Solid Surfaces: Spreading and Recoil Effects

A study of the normal impact of liquid droplets on a dry horizontal substrate is presented in this paper. The impact dynamics, spreading and recoil behavior are captured using a high-speed digital video camera at 2000 frames per second. A digital image processing software was used to determine the drop spread and height of the liquid on the surface from each frame. To ascertain the effects of liquid viscosity and surface tension, experiments were conducted with four liquids (water, ethanol, propylene glycol and glycerin) that have vastly different fluid properties. Three different Weber numbers (20, 40, and 80) were considered by altering the height from which the drop is released. The high-speed photographs of impact, spreading and recoil are shown and the temporal variations of dimensionless drop spread and height are provided in the paper. The results show that changes in liquid viscosity and surface tension significantly affect the spreading and recoil behavior. For a fixed Weber number, lower surface tension promotes greater spreading and higher viscosity dampens spreading and recoil. Using a simple scale analysis of energy balance, it was found that the maximum spread factor varies as Re1/5 when liquid viscosity is high and viscous effects govern the spreading behavior.Copyright © 2006 by ASME
Trust-based data fusion mechanism design in cognitive radio networks

Cognitive radio is a promising solution for spectrum scarcities in the future. Secondary users (SUs) adopt cooperative sensing to learn the primary user’s (PU’s) occupancy activity. This paper develops a trust-based data aggregation scheme to cope with malicious SU attack in cooperative spectrum sensing in cognitive radio networks. The proposed scheme combines the first-hand and second-hand sensing evidence to guarantee the overall performance and adopts a static game model to discourage malicious SUs from reporting fake detection parameters. Both theoretical and simulation results show that the proposed scheme outperforms the traditional majority aggregation scheme despite a high percentage of malicious node population and can effectively distinguish malicious nodes from normal nodes by their reputation scores.
The Monoclonal Antibody SH-2, Raised against Human Mesenchymal Stem Cells, Recognizes an Epitope on Endoglin (CD105)☆

Mesenchymal stem cells are multipotent cells resident in the bone marrow throughout adulthood which have the capacity to differentiate into cartilage, bone, fat, muscle, and tendon. A number of monoclonal antibodies raised against human MSCs have been shown to react with surface antigens on these cells in vitro. A protein of molecular mass 92 kDa was immunoprecipitated using the SH-2 monoclonal antibody. This was purified and identified by peptide sequencing analysis and mass spectrometry as endoglin (CD105), the TGF-β receptor III present on endothelial cells, syncytiotrophoblasts, macrophages, and connective tissue stromal cells. Endoglin on MSCs potentially plays a role in TGF-β signalling in the control of chondrogenic differentiation of MSCs and also in mediating interactions between MSCs and haematopoietic cells in the bone marrow microenvironment.
Epigenetic Regulation of Stem Cell Differentiation

Stem cells undergo extensive self-renewal and have the capacity to differentiate along multiple cell lineages. Progression from stem cells into differentiated progeny requires long-lasting changes in gene expression. Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNA-mediated regulatory events, are essential to controlling the heritable cellular memory of gene expression during development. Recent studies on cell fate specification of embryonic and adult stem cells/progenitors have highlighted a general and critical role for dynamic epigenetic regulation in stem cell self-renewal and differentiation.
Plugging the holes in the sieve of eratosthenes

Several subtle errors in an Ada tasking realization of the well-known Sieve of Eratosthenes algorithm are revealed and corrected. By discussing them here, we hope to increase the tutorial value of the original publication (G. E. Anderson in Ada Letters, September/October 1988).
Probabilistic approach to the Lamé equations of linear elastostatics

Abstract A probabilistic approach to systems of partial differential equations is developed on the basis of the well-known Feynman–Kac and Bismut formulas providing explicit probabilistic representations of the solutions and of their derivatives of scalar differential equations. Some numerical examples are also included. In particular the Lame equations of elastostatics are solved and the results are compared with some known exact analytic solutions to demonstrate the efficiency of the approach.
Habit learning in Tourette syndrome: a translational neuroscience approach to a developmental psychopathology.

Background: The etiology of Tourette syndrome (TS) involves disturbances in the structure and function of the basal ganglia. The basal ganglia mediate habit learning. Objective: To study habit learning in persons with TS. Design: Patients with TS were compared with normal controls in performance on a probabilistic classification, or habit-learning task (weather prediction). Setting: University research institute. Participants: One hundred twenty-three children and adults, 56 with a diagnosis of TS and 67 healthy control subjects.
Notes on a Working Hypothesis: the Retardate Problem Drinker

Numerous writers on the philosophy of science have pointed out that science develops in a more or less orderly fashion by creating levels of explanation. The lowest level would be descriptive, with phenomena collected and classified according to shared characteristics. An attempt is then made to establish a higher level by discovering lawful causal relationships among the classified phenomena. A still higher level of explanation is attempted—the level of theory—by finding laws which in themselves interrelate the relationships found at the intermediate level. Even casual study of the kinds of research data being produced on all aspects of alcoholism shows that the scientific endeavor is proceeding on all three levels simultaneously with attempts at careful description occurring here, some lawful relationships being found there, and efforts at theory-making on elsewhere.
Space-Time Correlations in Anisotropic Heisenberg Paramagnets at Elevated Temperatures

The structure of the space-time-dependent spin-correlation functions for an anisotropic Heisenberg paramagnet with cylindrical symmetry at elevated temperature is analyzed in terms of a two-parameter Gaussian representation representation of the generalized diffusivity. The parameters are chosen so as to exactly preserve the frequency moments, i.e., ${{〈{\ensuremath{\omega}}^{2n}〉}_{\mathrm{K}}}^{\ensuremath{\alpha}\ensuremath{\alpha}}$ ($\ensuremath{\alpha}=z, x, or y$; $n=0, 1, 2$) of the longitudinal and the transverse spectral functions. These moments are calculated for arbitrary spin $S$, arbitrary range of the exchange interactions, and arbitrary dimensionality. The results for the correlation functions are worked out for one, two, and three dimensions. In the extreme transverse limit, the results are compared with the exactly soluble $\mathrm{XY}$ model for a one-dimensional spin-\textonehalf{} system with only nearest-neighbor (transverse) exchange. The agreement of the results is found to be satisfactory.
Real Time Imaging of Human Progenitor Neurogenesis

Human neural progenitors are increasingly being employed in drug screens and emerging cell therapies targeted towards neurological disorders where neurogenesis is thought to play a key role including developmental disorders, Alzheimer’s disease, and depression. Key to the success of these applications is understanding the mechanisms by which neurons arise. Our understanding of development can provide some guidance but since little is known about the specifics of human neural development and the requirement that cultures be expanded in vitro prior to use, it is unclear whether neural progenitors obey the same developmental mechanisms that exist in vivo. In previous studies we have shown that progenitors derived from fetal cortex can be cultured for many weeks in vitro as undifferentiated neurospheres and then induced to undergo neurogenesis by removing mitogens and exposing them to supportive substrates. Here we use live time lapse imaging and immunocytochemical analysis to show that neural progenitors use developmental mechanisms to generate neurons. Cells with morphologies and marker profiles consistent with radial glia and recently described outer radial glia divide asymmetrically and symmetrically to generate multipolar intermediate progenitors, a portion of which express ASCL1. These multipolar intermediate progenitors subsequently divide symmetrically to produce CTIP2+ neurons. This 3-cell neurogenic scheme echoes observations in rodents in vivo and in human fetal slice cultures in vitro, providing evidence that hNPCs represent a renewable and robust in vitro assay system to explore mechanisms of human neurogenesis without the continual need for fresh primary human fetal tissue. Knowledge provided by this and future explorations of human neural progenitor neurogenesis will help maximize the safety and efficacy of new stem cell therapies by providing an understanding of how to generate physiologically-relevant cell types that maintain their identities when placed in diagnostic or transplantation environments.
THE DEAL AS A UNIT OF ANALYSIS IN ENTREPRENEURSHIP RESEARCH

ABSTRACT Factor analysis was used to determine the underlying dimensions of the concept of deals versus normal business transactions, based on a survey of the perceptions of both entrepreneurs and business executives. Three factors were found to characterize the deal/normal business transaction contrast: legitimacy, fulfillment and dynamism. Between-group differences were found to be significant relative to the legitimacy and fulfillment factors. The entrepreneurs perceived deals as being lower on the dimension of legitimacy, but higher on the dimension of fulfillment, than did their executive counterparts.
Deformations and Stress Intensities Due to a Craze in an Extended Elastic Material

Analyse mathematique du deplacement et des champs de contrainte dans un milieu elastique etendu du a une fissure mince de longueur finie. Cas des craquelures centrales a l'interieur d'une fissure
Anesthesia information-management systems: their role in risk-versus cost assessment and outcomes research.

Computerized clinical information systems clearly have a role in this era of managed care when outcomes research and cost/benefit analyses are becoming crucial. Despite anesthesiologists' leadership in developing physician-entry systems, automated recordkeeping systems have been underused. This report reviews the problems and possible solutions associated with establishing more effective and user-friendly systems in the anesthesia specialty. A key feature of any cost/benefit analysis or outcome study is the precise definition of data to be collected. Redesign of anesthesia information systems will be required to assist users to enter events according to standardized definitions. To filter the vast amount of data collected by electronic medical-records systems in the ordinary course of care that are not applicable to a specific study, some form of filtering or data reduction on transfer to research or administrative databases will be needed. To allow careful analysis of possible correlations of outcome to care choices requires both the capture of the clinical context—a detailed description of all relevant conditions extending well beyond merely the objective vital signs—throughout a specific medical episode and the establishment of postoperative evaluation systems to allow outcomes capture. Connections to new as well as existing outcome data will provide vast new opportunities for outcomes research.
The Social Foundation of Religious Meaning in Life

The purpose of this study was to see whether informal social support from fellow church members sustains an older person's sense of religious meaning in life over time. Two types of church-based so...
Monochloramine Inhibits Phorbol Ester-inducible Neutrophil Respiratory Burst Activation and T Cell Interleukin-2 Receptor Expression by Inhibiting Inducible Protein Kinase C Activity

Abstract Monochloramine derivatives are long lived physiological oxidants produced by neutrophils during the respiratory burst. The effects of chemically prepared monochloramine (NH2Cl) on protein kinase C (PKC) and PKC-mediated cellular responses were studied in elicited rat peritoneal neutrophils and human Jurkat T cells. Neutrophils pretreated with NH2Cl (30–50 μm) showed a marked decrease in the respiratory burst activity induced by phorbol 12-myristate 13-acetate (PMA), which is a potent PKC activator. These cells, however, were viable and showed a complete respiratory burst upon arachidonic acid stimulation, which induces the respiratory burst by a PKC-independent mechanism. The NH2Cl-treated neutrophils showed a decrease in both PKC activity and PMA-induced phosphorylation of a 47-kDa protein, which corresponds to the cytosolic factor of NADPH oxidase, p47phox. Jurkat T cells pretreated with NH2Cl (20–70 μm) showed a decrease in the expression of the interleukin-2 receptor α chain following PMA stimulation. This was also accompanied by a decrease in both PKC activity and nuclear transcription factor-κB activation, also without loss of cell viability. These results show that NH2Cl inhibits PKC-mediated cellular responses through inhibition of the inducible PKC activity.