cssi/SciSciGPT-SciSciNet huggingface dataset:
PBTI and PBTS testing of 0.25 μm pMOSFET devices for analog circuits

Parametric device shifts occur in a 0.25 μm CMOS sense amp circuit during a High Temperature Operation Life (HTOL) test, due to the positive bias stress on the pMOSFET devices. The positive gate bias from the HTOL stress causes a larger negative shift in the threshold voltage of the 5V pMOSFET devices and a mismatch in the transconductance of the differential pair, resulting in a decrease in the gain of the amplifier. Negative shifts in threshold voltage are also observed for 5V pMOSFET test structures for devices with no protect diodes (antenna ratio = 1000:1) after either Positive Bias Temperature Instability (PBTI) tests or Positive Bias Temperature Stress (PBTS). The PBTI and PBTS are caused by positive charge from interface states and bulk oxide traps.
Finite-time Circle Surrounding Control for Multi-agent Systems

In this paper, a finite-time circle surrounding control problem for multi-agent systems is investigated. The objective is to make all the surrounding agents eventually distribute on a circle uniformly and all the target agents surrounded by this circle in the finite time. Both a distributed estimator and a distributed control protocol are presented to achieve such a goal. Firstly, an estimator of the targets’ geometric center is used to estimate the center of targets. Secondly, a distributed control protocol is proposed for each surrounding agent by using the value of the estimator to guarantee all the surrounding agents uniformly distribute on a circle and all the target agents are surrounded by this circle in the finite time. Then it is proved that the control goal can be achieved in the finite time. Finally, a simulation example is given to show the effectiveness of the proposed method.
How Do You Intentionally Design to Maximize Success in the Academically Diverse Classroom

Addressing academic diversity in today's college classroom is challenging. This chapter explores Universal Design for Learning as a viable framework for removing barriers for all students in higher education.
Integrins in Vascular Development and Pathology

During vascular development, endothelial cells (ECs) and neighboring stromal cells interact and communicate through autocrine and paracrine signaling mechanisms involving extracellular matrix (ECM) proteins and their cell surface integrin adhesion receptors. Integrin-mediated adhesion and signaling pathways are crucial for normal vascular development and physiology, and alterations in integrin expression and/or function drive several vascular-related pathologies including thrombosis, autoimmune disorders, and cancer. The purpose of this chapter is to discuss integrin adhesion and signaling pathways important for EC growth, survival, and migration. Integrin-mediated paracrine links between ECs and surrounding stromal cells in the organ microenvironment will also be discussed. Lastly, we will review roles for integrins in vascular pathologies and discuss possible targets for therapeutic intervention.
Does left atrial appendage ligation during coronary bypass surgery decrease the incidence of postoperative stroke

Abstract Objective The study objective was to evaluate the association between surgical left atrial appendage ligation and in-hospital stroke incidence after coronary artery bypass grafting among patients with atrial fibrillation. Methods A retrospective cohort study was performed by using the Nationwide Inpatient Sample between 2008 and 2014. All atrial fibrillation patients who underwent coronary artery bypass graft were included and categorized as left atrial appendage ligation or control group. Propensity score–weighted regression analyses were performed to assess the impact of left atrial appendage ligation on stroke incidence. Results A total of 234,642 patients were identified, among whom 20,664 (8.81%) received concomitant left atrial appendage ligation. The national postoperative stroke incidence was 0.92%. Results of the propensity-weighted regression analysis showed no significant association between LAA ligation and control with regard to postoperative stroke (odds ratio [OR], 0.83; confidence interval [CI], 0.57-1.22; P = .35), pericardial complications (OR, 1.15; CI, 0.88-1.49; P = .31), hemorrhage and/or hematoma (OR, 1.08; CI, 0.99-1.17; P = .07), mortality (OR, 1.29; CI, 0.99-1.68; P = .06), and length of stay (coefficient −0.21; CI, −0.44-0.02; P = .08). There was no specific CHA2DS2VASC score cutoff above which left atrial appendage ligation was demonstrated to have lower postoperative stroke incidence. Conclusions The postoperative stroke risk after coronary artery bypass grafting was low at approximately 1% among patients with atrial fibrillation in the United States. Concomitant left atrial appendage ligation was not associated with lower postoperative stroke risk.
A team software process approach to database course

In recent years, some programs have created a database track to provide an opportunity for students to further their database skills and expertise. As database management systems are being utilized widely in the real-world and become an integral part of computer science applications, it is critical for students to gain practical experiences in this field.
Disability Saliency and Discrimination in Hiring

Theory suggests that disability discrimination protections may adversely affect the hiring of individuals with disabilities by making them more expensive. Using SIPP data, we explore how the ADA Amendments Act (ADAAA), which expanded disability discrimination protections, affected the relative hiring rate of individuals with disabilities. We employ new categorizations of disability type: salient physical conditions, non-salient physical conditions, mental retardation and developmental disability, and other mental conditions. We find that the ADAAA had no effect other than increasing hiring for those with non-salient physical conditions. These results suggest that condition saliency may mediate the effects of discrimination protections on hiring.
Galileo’s Copernicanism and the Acceptability of Guiding Assumptions

The aim of this paper is to examine the problem of the appraisal of guiding assumptions on the basis of historical evidence about Galileo’s Copernicanism. That is, I plan to determine whether this episode confirms or disconfirms (GA1.1) - (GA1.5). To be more exact, I shall be examining the evolution of Galileo’s attitude toward Copernicanism in order to ascertain whether the acceptability of a set of guiding assumptions is judged largely on the basis of: (GA1.1) empirical accuracy, (GA1.2) the success of its associated theories at solving problems, (GA1.3) the success of its associated theories at making novel predicions, (GA1.4) its ability to solve problems outside the domain of its initial success, and (GA1.5) its ability to make successful predictions using its central assumptions rather than assumptions invented for the purpose at hand. Such testing will be impossible to carry out without a number of clarifications, to which we now turn.
Plasminogen activator inhibitor-1 deficiency protects against atherosclerosis progression in the mouse carotid artery

Dissolution of the fibrin blood clot is regulated in large part by plasminogen activator inhibitor-1 (PAI-1). Elevated levels of plasma PAI-1 may be an important risk factor for atherosclerotic vascular disease and are associated with premature myocardial infarction. The role of the endogenous plasminogen activation system in limiting thrombus formation following atherosclerotic plaque disruption is unknown. This study found that genetic deficiency for PAI-1, the primary physiologic regulator of tissue-type plasminogen activator (tPA), prolonged the time to occlusive thrombosis following photochemical injury to carotid atherosclerotic plaque in apolipoprotein E-deficient (apoE(-/-)) mice. However, anatomic analysis revealed a striking difference in the extent of atherosclerosis at the carotid artery bifurcation between apoE(-/-) mice and mice doubly deficient for apoE and PAI-1 (PAI-1(-/-)/apoE(-/-)). Consistent with a previous report, PAI-1(+/+)/apoE(-/-)and PAI-1(-/-)/apoE(-/-) mice developed similar atherosclerosis in the aortic arch. The marked protection from atherosclerosis progression at the carotid bifurcation conferred by PAI-1 deficiency suggests a critical role for PAI-1 in the pathogenesis of atherosclerosis at sites of turbulent flow, potentially through the inhibition of fibrin clearance. Consistent with this hypothesis, intense fibrinogen/fibrin staining was observed in atherosclerotic lesions at the carotid bifurcation compared to the aortic arch. These observations identify significant differences in the pathogenesis of atherosclerosis at varying sites in the vascular tree and suggest a previously unappreciated role for the plasminogen activation system in atherosclerosis progression at sites of turbulent flow. (Blood. 2000;96:4212-4215)
The Analysis of Immunohistochemical Data

Neuroscientists have been interested for many years in the anatomic distribution and concentration of neurochemicals in the brain. Particular attention has focused on the localization of neurotransmitters. Biochemical techniques are now used routinely to assay for the concentration, uptake, or evoked release of neurotransmitters in brain. Microdissection techniques allow one to make these measurements in relatively small brain regions. However, the spatial resolution of biochemical assays is extremely coarse relative to the anatomic complexity of the brain, and it has rarely been possible to measure concentrations at the level of single cells and fibers.
Quinacrine studies of sex chromatin and nucleoli in human brain.

Quinacrine fluorescent studies of sex chromatin in human neurons indicate that the distal portion of the Y chromosome is constantly seen in association with the nucleolus in the male. The degree of association between the “Y body” and the nucleolus in other cell types is much lower. The degree of association between the X chromatin and the nucleolus in human female neurons was also analyzed by this method, indicating the feasibility of studying both the X and Y chromatin in quinacrine-stained preparations of human neurons.
Self-Reported Versus Digitally Recorded: Measuring Political Activity on Facebook

Facebook has been credited with expanding political activity by simultaneously lowering barriers to participation and creating new ways to engage. However, many of these findings rely on subjects’ ...
Uveitis in spondyloarthritis including psoriatic arthritis, ankylosing spondylitis, and inflammatory bowel disease

Uveitis is a common complication of spondyloarthritis. The “phenotype” of the uveitis characteristic of ankylosing spondylitis (sudden onset, anterior, unilateral, recurrent, more often male) may differ from the phenotype often seen with either psoriatic arthritis or inflammatory bowel disease (insidious onset, anterior and intermediate, bilateral, chronic, and/or more often female). The frequency of uveitis is also much greater in association with ankylosing spondylitis than with either inflammatory bowel disease or psoriasis. Uveitis may affect the choice of therapy and can rarely be a complication of therapy. Uveitis and arthritis also co-exist in several animal models.
Transcatheter Aortic Valve Replacement in Low-Risk Patients: A Meta-Analysis of Randomized Controlled Trials

INTRODUCTION Transcatheter aortic valve replacement (TAVR) has become the standard treatment option for patients with symptomatic severe aortic stenosis (AS) with high surgical risk and a reasonable option for intermediate surgical risk as an alternative to surgical aortic valve replacement (SAVR). The role of TAVR in lower risk patients is less established but has been the focus of recent randomized controlled trials (RCTs). We performed a meta-analysis of RCTs to assess TAVR outcomes among low surgical risk patients. METHODS AND RESULTS Systematic search of RCTs was done using PubMed, EMBASE, and Cochrane Library databases. Statistical analysis was performed with RevMan v5.3 software using a random effects model to report risk ratio (RR) with 95% confidence interval (CI). A total of three RCTs including 2698 patients (1375 TAVR and 1323 SAVR) were analyzed. Compared to SAVR, TAVR was not associated with all-cause mortality [RR 0.86 (95% CI 0.61-1.19); P = 0.36; I2 = 8%] or stroke [RR 0.82 (0.48-1.43); P = 0.49; I2 = 42%]. However, TAVR was significantly associated with lower risk of acute kidney injury [RR 0.27 (0.13-0.54); P = 0.0002; I2 = 0%], new-onset atrial fibrillation [RR 0.26 (0.18-0.39); P < 0.00001; I2 = 80%], and life-threatening or disabling bleeding [RR 0.35 (0.22-0.55); P < 0.00001; I2 = 57%], but a higher risk of moderate-severe paravalvular leak [RR 4.40 (1.22-15.86); P = 0.02; I2 = 26%] and permanent pacemaker insertion [RR 2.73 (1.41-5.28); P = 0.003; I2 = 83%]. CONCLUSIONS There is no difference in all-cause mortality or stroke between TAVR and SAVR, but TAVR is associated with lower risk of other perioperative complications except for moderate-severe paravalvular leak and the need for permanent pacemaker implantation.
Inductive quantification of energy absorption of high-density polyethylene foam for repeated blunt impact:

Foams are used in a variety of impact energy absorption applications because of their ability to engage in large deformations under steady load transfer during the cell collapse. Quantification of ...
Semiotics Applied to Human-Robot Interaction in Welding Processes

Teleoperation of robotic systems requires efficient and effective human-robot interactions. The present work presents the development of a semiotic-based human-robot interaction interface through the identification of the signs classes presented in the original interface of the robotic welding equipment BUG-O MDS-1005. Among the hardware equipments necessary to construct the proposed interface there are a Raspberry Pi 3 with a 7 inch touchscreen display, an Odroid XU4 and an Arduino Uno. In order to enable users to make use of an intuitive system that meets industry standards, HumanRobot Interaction (HRI) technologies are used. Furthermore, the proposed human-robot interaction interface provides new functionalities enhancing not only the system usability but also the operator productivity during welding processes
Variability in Language used on Social Media prior to Hospital Visits.

Forecasting healthcare utilization has the potential to anticipate care needs, either accelerating needed care or redirecting patients toward care most appropriate to their needs. While prior research has utilized clinical information to forecast readmissions, analyzing digital footprints from social media can inform our understanding of individuals’ behaviors, thoughts, and motivations preceding a healthcare visit. We evaluate how language patterns on social media change prior to emergency department (ED) visits and inpatient hospital admissions in this case-crossover study of adult patients visiting a large urban academic hospital system who consented to share access to their history of Facebook statuses and electronic medical records. An ensemble machine learning model forecasted ED visits and inpatient admissions with out-of-sample cross-validated AUCs of 0.64 and 0.70 respectively. Prior to an ED visit, there was a significant increase in depressed language (Cohen’s d = 0.238), and a decrease in informal language (d = 0.345). Facebook posts prior to an inpatient admission showed significant increase in expressions of somatic pain (d = 0.267) and decrease in extraverted/social language (d = 0.357). These results are a first step in developing methods to utilize user-generated content to characterize patient care-seeking context which could ultimately enable better allocation of resources and potentially early interventions to reduce unplanned visits.
12 – Dynamic Analysis

Publisher Summary This chapter deals with the derivation of finite element equations for a dynamic problem. In dynamic problems, the displacements, velocities, strains, stresses, and loads are all time dependent. The procedure involved in deriving the finite element equations of a dynamic problem involves six steps. The first step is to idealize the body into E finite elements. The second step is to assume the displacement model of the element. The third step is to derive the characteristic (stiffness and mass) matrices and characteristic (load) vector. The fourth step is to assemble the element matrices and vectors and to derive the overall system equations of motion. Finally, the equations of motion are solved by applying the boundary and initial conditions in last steps. The chapter also discusses the consistent and lumped mass matrices which are used for solving several dynamic problems. In the finite element analysis of large systems, the number of equations to be solved for an accurate solution is quite large. In such cases, the method of substructures is used to reduce the number of equations to manageable size. The system (or structure) is divided into a number of parts or segments, each called a substructure. Each substructure, in turn, is divided into several finite elements. The concept of substructuring has been used for the analysis of static, dynamic, and non-linear analyses.
Developmental stage-dependent relationships between ghrelin levels and hippocampal white matter connections in low-weight anorexia nervosa and atypical anorexia nervosa.

Abstract Introduction Disruptions in homeostatic and hedonic food motivation are proposed to underlie anorexia nervosa (AN) and atypical AN, restrictive eating disorders which commonly onset in puberty. Ghrelin, a neuroprotective hormone that drives hedonic eating is increased in AN and is expressed in the hippocampus. White matter (WM) undergoes significant change during puberty in regions involved in food motivation, particularly WM tracts connected with the hippocampus. The association between ghrelin and WM region of interest (ROI) with hippocampal connections in restrictive eating disorders, particularly in adolescence during key neurodevelopmental growth, is unknown. Methods We evaluated fasting plasma ghrelin and WM microstructure (measured by free-water corrected fractional anisotropy (FA-t)) in WM ROIs with hippocampal connections - the fornix and the hippocampal portion of the cingulum - in 56 adolescent females (age range: 11.9 - 22.1 y; mean: 19.0 y) with low-weight eating disorders including AN and atypical AN (N = 36) and healthy controls (N = 20). Results FA-t in the fornix or hippocampal portion of the fornix did not differ between groups. Ghrelin was higher in AN/atypical AN vs. HC and was positively correlated with puberty stage in the AN/atypical AN group, but not the HC group. The correlation between ghrelin and FA-t in the fornix was significantly different in females with AN/atypical AN compared to controls. In AN/atypical AN, pubertal stage moderated the relation between fasting plasma ghrelin and FA-t in the fornix: higher fasting ghrelin was associated with lower FA-t in the fornix in late-post-puberty, but was not associated with FA-t in the early to mid stages of puberty. Conclusions In post-pubertal females with low-weight AN/atypical AN, higher levels of ghrelin are associated with lower FA-t in the fornix. This relationship is not evident in the early to mid stages of puberty in AN/atypical AN or in HC, and may reflect a lack of possible neuroprotective effects of ghrelin in late-post puberty only. Understanding the effects of ghrelin on WM microstructure longitudinally and following recovery from AN/Atypical AN and how this differs across pubertal stages will be an important next step. These findings could ultimately inform treatment staging and aid in diagnosis and detection of AN/atypical AN.
Line-shape analysis of double-quantum multidimensional coherent spectra

Double-quantum two-dimensional (2D) coherent spectroscopy (MDCS) is a powerful optical method that is used to study the optical properties of atomic and complex molecular systems and semiconductor materials. Double-quantum 2D spectra and particularly the peak line shapes on the spectra can also provide information about many-body interactions. We model 2D spectra by solving the optical Bloch equations and show the effects of correlation between coupled resonances, which also explains the discrepancies between the experimental results reported by multiple groups.
Nucleobase-Functionalized Poly(alkylthiophene)s: One-Pot, Sequential Direct Arylation Polymerization and Deprotection, and Surface Modification for Oil–Water Separations

Direct arylation polymerization (DArP) has emerged as an environmentally friendly, atom efficient method of synthesizing a variety of conjugated polymers. Here, we report a one-pot approach consist...
Resistance, Indifference or Ignorance? Explaining Russians' Nonuse of Mediation

Russia is a late developer as to mediation. In contrast to the United States, Western Europe, and the Far East, where mediation has been available for decades, legislation authorizing mediation in Russia went into effect only at the beginning of 2011. Although Russian law scholars greeted this institutional innovation with enthusiasm, ordinary Russians paid little attention. Few have taken advantage of it. The leaders of the Moscow-based Center for Mediation and Law argue that "[a]bsolutely all experts agree that the development of mediation in Russia has been very weak." The Russian scholarly literature is replete with explanations for the nonuse of mediation. Most focus on the shortcomings of the legislation, with an occasional nod to the potential role of legal culture. Given the historical preference for doctrinally-driven research, the failure to ground theory in empirical data is not surprising. This article, which analyzes Russians' views of mediation gleaned through a series of 2014 focus groups, begins to fill that gap.
Epidemiology of Ophidiomycosis In Lake Erie Watersnakes (Nerodia sipedon insularum).

Ophidiomycosis, caused by the fungus Ophidiomyces ophidiicola, is an infectious disease of wild and managed snakes worldwide. Lake Erie watersnakes (LEWS; Nerodia sipedon insularum) were listed as threatened under the US Endangered Species Act from 1999 to 2011 and were first diagnosed with ophidiomycosis in 2009. Our objective was to characterize the epidemiology of ophidiomycosis in LEWS. We hypothesized that the prevalence of skin lesions, O. ophidiicola DNA, and ophidiomycosis disease categories would show spatial and temporal variation and clustering, with higher prevalence at sites with greater human disturbance and prevalence increasing over time. Snakes were captured via visual encounter surveys at five sites across four islands and visually inspected for skin lesions suggestive of ophidiomycosis, and then body swabs were collected to detect O. ophidiicola DNA using the quantitative PCR assay. Each snake was assigned an ophidiomycosis category based on the presence of skin lesions and O. ophidiicola. We evaluated 837 LEWS between 2017 and 2020 and detected ophidiomycosis at all five sites. Logistic regression analysis showed temporal and spatial variation in disease, with higher risk of apparent ophidiomycosis (lesions present and O. ophidiicola detected) at Kelleys Island State Park, compared to all other sites; in May, compared to July; and in 2019, compared to 2018. The presence of emerging herbaceous wetlands, urban land change, and certain soil types increased the odds of both lesion presence and quantitative PCR detection of O. ophidiicola. Overall, ophidiomycosis epidemiology varied among sites: the disease appeared to be endemic at most sites and emerging at one site. Ongoing efforts to monitor population health and mortality associated with disease prevalence are needed to inform mitigation aimed at reducing the impact of ophidiomycosis in LEWS.
Enhanced photo-response in p-Si/MoS2 heterojunction-based solar cells

Abstract High quality ultrathin transition-metal dichalcogenide films and their Vander Waals heterostructures are very promising for fabrication of optoelectronic devices for their superior photovoltaic performance, extreme flexibility and long lifetime due to suitable band gap and excellent light absorption capability. Designing the appropriate and suitable band structures of these materials is crucial for its promising applications. Especially, thin molybdenum disulfide (MoS 2 ) film is further attractive as compare to its monolayer counterpart for broad-spectral photo-detectors and photovoltaic application. However, very little understanding regarding the underlying physics behind the photo-response behavior of thin MoS 2 films is known. Here, we demonstrate a large photovoltaic response in thin MoS 2 films which produces an enormous photo-generated carrier and enhance the photocurrent by forming a heterojunction with p-type Si substrate. MoS 2 based photovoltaic devices efficiently produce high short-circuit photocurrent values of 18 mA/cm 2 and reasonably high power-conversion efficiency up to 4.5%. The present work will provide valuable scientific input of layered MoS 2 films for other emerging optoelectronic applications.
Data Clustering in Tolerance Space

This paper studies an abstract data clustering model, in which the similarity is explicitly represented by a tolerance relation. Three basic types of clusters are defined from each tolerance relation: maximal complete similarity clusters, representative clusters, and closure clusters. Heuristic methods of computing corresponding clusterings are introduced and an experiment on two real-world datasets are discussed. This paper provides a different view in the study of data clustering, where clusters are derived from a given similarity and different clusters may have non-empty intersection.
Urea Nitrogen Excretion in Critically Ill Children

Urinary urea nitrogen (UUN) excretion as an index of both total nitrogen excretion and protein catabolism was assayed in 32 children (aged 2 months to 15 years, median 6 years) (50% mechanically ventilated) during an intensive care unit course of one to ten days (median three days). The daily UUN excretion was 4.38 +/- 2.22 gm/sq m (171 +/- 89 mg/kg) (N = 121 patient days). The average daily UUN excretion (N = 32 children) was well described by a linear regression equation for square meters of body surface area (BSA) (milligrams of UUN = 4,421.5 x BSA; r2 = .903). This linear relationship permitted the valid comparison of both individuals and subgroups despite wide age differences. Excretion data in the mechanically ventilated vs the spontaneously breathing children, and in four diagnostic subgroups (Reye syndrome, seven; sepsis, six; elective surgery, seven; and miscellaneous, 12) were evenly distributed about the regression line for body surface area. Variability in average daily UUN excretion was on individual basis, and was independent of diagnostic or therapeutic subgroup.
The competitive analysis of risk taking with applications to online trading

Competitive analysis is concerned with minimizing a relative measure of performance. When applied to financial trading strategies, competitive analysis leads to the development of strategies with minimum relative performance risk. This approach is too inflexible. Many investors are interested in managing their risk: they may be willing to increase their risk for some form of reward. They may also have some forecast of the future. We extend competitive analysis to provide a framework in which investors can develop optimal trading strategies based on their risk tolerance and forecast. We first define notions of risk and reward that are smooth extensions of classical competitive analysis. We then illustrate our ideas using the ski-rental problem. Finally, we analyze a financial game, the unidirectional conversion problem. In particular, we present an optimal risk-tolerant algorithm for the forecast that prices will reach a certain level at some point during the game, and give numerical results of the investor's reward for making such a forecast.
POSC—a partitioning and optimizing SISAL compiler

Single-assignment languages like SISAL offer parallelism at all levels—among arbitrary operations, conditionals, loop iterations, and function calls. All control and data dependencies are local, and can be easily determined from the program. Various studies of SISAL programs have shown that they contain massive amounts of potential parallelism. There are two major challenges in converting this potential parallelism into real speedup on multiprocessor systems. First, it is important to carefully select the useful parallelism in a SISAL program, so as to obtain good speedup by trading off parallelism with overhead. Second, it is important to do sequential optimizations, so that the sequential components (tasks) of the SISAL program have comparable execution times with sequential languages such as Fortran, Pascal and C. The POSC compiler system described in this paper addresses both issues by integrating previous work on efficient sequential implementation of SISAL programs with previous work on selecting the useful parallelism in a SISAL program. The combined approach is validated by real speedup measurements on a Sequent Balance multiprocessor.
Role of a Guanidinium Cation-Phosphodianion Pair in Stabilizing the Vinyl Carbanion Intermediate of Orotidine 5'-Phosphate Decarboxylase-Catalyzed Reactions.

The side chain cation of Arg235 provides a 5.6 and 2.6 kcal/mol stabilization of the transition states for orotidine 5′-monophosphate (OMP) decarboxylase (OMPDC) from Saccharomyces cerevisiae catalyzed reactions of OMP and 5-fluoroorotidine 5′-monophosphate (FOMP), respectively, a 7.2 kcal/mol stabilization of the vinyl carbanion-like transition state for enzyme-catalyzed exchange of the C-6 proton of 5-fluorouridine 5′-monophosphate (FUMP), but no stabilization of the transition states for enzyme-catalyzed decarboxylation of truncated substrates 1-(β-d-erythrofuranosyl)orotic acid and 1-(β-d-erythrofuranosyl) 5-fluorouracil. These observations show that the transition state stabilization results from formation of a protein cation–phosphodianion pair, and that there is no detectable stabilization from an interaction between the side chain and the pyrimidine ring of substrate. The 5.6 kcal/mol side chain interaction with the transition state for the decarboxylation reaction is 50% of the total 11.2 kcal/mo...
A Phase 1 trial of the poly(ADP-ribose) polymerase inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer.

Abstract Background Poly(ADP-ribose) polymerase (PARP)-inhibitors and anti-angiogenics have activity in recurrent ovarian and breast cancer; however, the effect of combined therapy against PARP and angiogenesis in this population has not been reported. We investigated the toxicities and recommended phase 2 dosing (RP2D) of the combination of cediranib, a multitargeted inhibitor of vascular endothelial growth factor receptor (VEGFR)-1/2/3 and olaparib, a PARP-inhibitor (NCT01116648). Methods Cediranib tablets once daily and olaparib capsules twice daily were administered orally in a standard 3+3 dose escalation design. Patients with recurrent ovarian or metastatic triple-negative breast cancer were eligible. Patients had measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or met Gynecologic Cancer InterGroup (GCIG) CA125 criteria. No prior PARP-inhibitors or anti-angiogenics in the recurrent setting were allowed. Results 28 patients (20 ovarian, 8 breast) enrolled to 4 dose levels. 2 dose limiting toxicities (DLTs) (1 grade 4 neutropenia ⩾4 days; 1 grade 4 thrombocytopenia) occurred at the highest dose level (cediranib 30 mg daily; olaparib 400 mg twice daily [BID]). The RP2D was cediranib 30 mg daily and olaparib 200 mg BID. Grade 3 or higher toxicities occurred in 75% of patients, and included grade 3 hypertension (25%) and grade 3 fatigue (18%). One grade 3 bowel obstruction occurred. The overall response rate (ORR) in the 18 RECIST-evaluable ovarian cancer patients was 44%, with a clinical benefit rate (ORR plus stable disease (SD) >24 weeks) of 61%. None of the seven evaluable breast cancer patients achieved clinical response; two patients had stable disease for >24 weeks. Interpretation The combination of cediranib and olaparib has haematologic DLTs and anticipated class toxicities, with promising evidence of activity in ovarian cancer patients.
Mitochondrial dysfunction in autism.

Using data of the current prevalence of autism as 200:10,000 and a 1:2000 incidence of definite mitochondrial (mt) disease, if there was no linkage of autism spectrum disorder (ASD) and mt disease, it would be expected that 1 in 110 subjects with mt disease would have ASD and 1 in 2000 individuals with ASD would have mt disease. The co-occurrence of autism and mt disease is much higher than these figures, suggesting a possible pathogenetic relationship. Such hypothesis was initially suggested by the presence of biochemical markers of abnormal mt metabolic function in patients with ASD, including elevation of lactate, pyruvate, or alanine levels in blood, cerebrospinal fluid, or brain; carnitine level in plasma; and level of organic acids in urine, and by demonstrating impaired mt fatty acid β-oxidation. More recently, mtDNA genetic mutations or deletions or mutations of nuclear genes regulating mt function have been associated with ASD in patients or in neuropathologic studies on the brains of patients with autism. In addition, the presence of dysfunction of the complexes of the mt respiratory chain or electron transport chain, indicating abnormal oxidative phosphorylation, has been reported in patients with ASD and in the autopsy samples of brains. Possible pathogenetic mechanisms linking mt dysfunction and ASD include mt activation of the immune system, abnormal mt Ca 2+ handling, and mt-induced oxidative stress. Genetic and epigenetic regulation of brain development may also be disrupted by mt dysfunction, including mt-induced oxidative stress. The role of the purinergic system linking mt dysfunction and ASD is currently under investigation. In summary, there is genetic and biochemical evidence for a mitochondria (mt) role in the pathogenesis of ASD in a subset of children. To determine the prevalence and type of genetic and biochemical mt defects in ASD, there is a need for further research using the latest genetic technology such as next-generation sequencing, microarrays, bioinformatics, and biochemical assays. Because of the availability of potential therapeutic options for mt disease, successful research results could translate into better treatment and outcome for patients with mt-associated ASD. This requires a high index of suspicion of mt disease in children with autism who are diagnosed early.
Fifty Years of D.H.I.A. Work

Dairy Herd Improvement Associations, formerly called Cow Testing Associations, have operated in the United States since 1906 ; hence a report of the developments over the last 50 years constitutes a complete history of the work. Credit for organizing the first Dairy Herd Improvement Association in the U n i t e d States goes to a Danish immigrant, Helmer Rabild, and a small group of dairy farmers in Newaygo County, Michigan. Mr. Rabild knew what cow testing associations had meant to the dairy farmers in his native land, and he was convinced that a similar program would be of inestimable value to dairy F. J. Arnold farmers of his adopted country. As a consequence, he was instrumental in getting the first association organized. At the time, Mr. Rabild was employed by the Dairy and Food Division of the Michigan Department of Agriculture. The meeting that resulted in the organization of the first Dairy Herd Improvement Association in the United States was held on Sept. 26, 1905, and was attended by six or eight dairymen. After hearing Mr. Rabild explain the advantages of a production testing program, the group appointed a committee to set up the organization. The Association began operating in January, 1906. Thirty-one herds consisting of 239 cows were tested the first year. News of this new development soon spread. In Michigan the number of associations increased to four in 1907 and continued to grow until 1926, when a peak of 108 associations was reached. The first two states to follow Michigan's lead were Maine and New York. Each organized its first association in 1908. Five states got started in 1909, four in 1910, eight in 1911, three in 1913, seven in 1914, one in 1915, two in 1917, three in 1918, three in 1919, and one in 1920. The last state was Florida, in 1929. Except during the war years when supervisors were not available and during the depression of the 30's, the program grew steadily. On Jan. 1, 1956, 2,266 associations were operating (one or more in each state, Hawaii, and Puerto Rico). These associations were testing 40,984 herds consisting of more than 1,406,306 cows. Through the early years, the moving force behind D.H.I.A. work was the Dairy Division of the U. S. Department of Agriculture. The attention of the department was attracted to the organization in Michigan, and in 1909 promotion of the program became a federal project. Mr. Rabild was employed to head the work, and under his leadership the program was carried to all the states. In the states the organization and supervision of the program was under the direction or sponsorship of the state departments of agriculture or the state agricultural colleges, but by the time the Cooperative Agricultural Extension act was passed in 1914 the associations had become such a promising source of practical information that they were drawn into the state and federal extension programs.
Fine structure of the eyes of jumping spiders.

The four pairs of eyes in two species of jumping spiders (Metaphidippus harfordi and Phidippus johnsoni) were studied by light and electron microscopy. Unique features of the anteromedial eyes, used in acute vision, are: stratification of receptors (basis of color vision?); rhabdomeres in anterior row of receptors in two planes perpendicular to each other (basis of perception of polarized light?); receptors surrounded by extensions of supportive cells containing a labyrinth of cisternae (anatomical and physiological support?); receptors not individually shielded by pigment (implementation of high resolution?); lamination of cornea (basis of green color?). Special features of lateral eyes, used as wide-angle detectors of movement, are: individual shielding of each receptor by six arms of pigmented supportive cells (facilitating detection of motion?); rhabdomeres on axonlike fibers from sensory cell bodies situated outside the eyecup; nonpigmented supportive cells, filled with microtubules, enclose receptors (anatomical and physiological support?).
Severe exercise-induced ischemia does not identify high risk patients with normal left ventricular function and one- or two-vessel coronary artery disease

Abstract Objectives. This study was conducted to determine whether severe exercise-induced ischemia identifies high risk patients with a normal left ventricular ejection fraction and one- or two-vessel coronary artery disease. Background. Severe ischemia during exercise radionuclide angiography has been shown to identify high risk patients among certain other patient subsets. Methods. Four hundred twenty patients with left ventricular ejection fraction ≥50% and one- or two-vessel disease underwent exercise radionuclide angiography within 3 months of coronary angiography. Patients were treated initially with revascularization (n = 140) or medical therapy (n = 280) at the discretion of their physicians. Patients treated with revascularization were more likely to have angina by history, a positive exercise electrocardiogram, a lower exercise ejection fraction, two-vessel disease and proximal left anterior descending coronary artery disease. Two hundred sixty-four of the 280 patients given medical therapy who had complete follow-up data formed the study group. Outcome was compared between patients with (n = 56) and without (n = 208) severe exercise-induced ischemia, defined by previously published criteria (work load ≤600 kg-m/min, ST segment depression ≥1 mm and decrease in ejection fraction with exercise). Results. During follow-up, there were 30 initial cardiac events (12 cardiac deaths and 18 nonfatal myocardial infarctions). There was no difference in the 5-year event-free survival rate: 91% in patients with and 87% in patients without severe ischemia (p = 0.89). There was no association between event-free survival and severe ischemia (χ2= 1.41, p = 0.24). The study had approximately 80% power at α = 0.05 to detect a 25% decrease in event-free survival in the group with severe ischemia. In addition, there was no association between severe ischemia and outcome if late revascularization was included as an event or if the total mortality rate (overall survival) was analyzed. Conclusions. Severe exercise-induced ischemia fails to identify a high risk subgroup among patients with normal left ventricular function and one- or two-vessel disease who are treated initially with medical therapy.
Building Global Capacity with Global Task Teams

General Motors uses action learning to develop global capacity in its potential executives. Called Global Task Teams, they bring together 8–10 high-potential employees from sites around the globe to form an international action learning team. The team is assigned a significant operating challenge to work on, full-time, for three months. The teams are facilitated by two GM facilitators on a part-time basis. After five such teams had operated over the last five years, the Global Task Teams have earned a growing reputation within General Motors for the quality of their work.
Scholarly communication in educational psychology: a journal citation analysis

Purpose – This paper aims to study the scholarly communication of educational psychology by exploring its intellectual structure and general journal citation patterns.Design/methodology/approach – Journal citation data were collected from Journal Citation Reports for 2004‐2005. The structure of the subject relatedness of the journals was created through a cluster analysis using the cosine as its measure. The general citation patterns were discussed in terms of cited and citing frequencies and related ratios.Findings – Six clusters of journals were identified, including general educational psychology/learning/literacy, school psychology, measurement and counseling, Germany‐based educational psychology, creativity, and the other. The following general citation patterns emerged in the study: a small number of journals accounted for a relatively high percentage of the intra‐disciplinary citations; the majority of the selected journals cited more than being cited in the field; the major general educational psy...
A Generalized Estimator of the Attributable Benefit of an Optimal Treatment Regime

For many diseases where there are several treatment options often there is no consensus on the best treatment to give individual patients. In such cases, it may be necessary to define a strategy for treatment assignment; that is, an algorithm that dictates the treatment an individual should receive based on their measured characteristics. Such a strategy or algorithm is also referred to as a treatment regime. The optimal treatment regime is the strategy that would provide the most public health benefit by minimizing as many poor outcomes as possible. Using a measure that is a generalization of attributable risk (AR) and notions of potential outcomes, we derive an estimator for the proportion of events that could have been prevented had the optimal treatment regime been implemented. Traditional AR studies look at the added risk that can be attributed to exposure of some contaminant; here we will instead study the benefit that can be attributed to using the optimal treatment strategy. We will show how regression models can be used to estimate the optimal treatment strategy and the attributable benefit of that strategy. We also derive the large sample properties of this estimator. As a motivating example, we will apply our methods to an observational study of 3856 patients treated at the Duke University Medical Center with prior coronary artery bypass graft surgery and further heart-related problems requiring a catheterization. The patients may be treated with either medical therapy alone or a combination of medical therapy and percutaneous coronary intervention without a general consensus on which is the best treatment for individual patients.
Tribasic Copper Chloride Toxicosis in Commercial Broiler Chicks

Two broiler chicken houses containing 17,500 chicks each experienced an extreme elevation in chick mortality beginning on day 3 after placement. Clinical signs observed upon farm visit included numerous small chicks for their age; depressed, lethargic, and comatose chicks; and chicks huddling near feed pans and under heaters. Necropsied chicks were markedly pale and had atrophy of the thymus and bursa, swollen and edematous proventriculus, erosions in the koilin and in the proventricular-ventricular junction, pale kidneys, and yellowish to brownish-orange liver often with linear pale areas. The chicks had watery blood and hematocrits measured from 9.5% to 18%. Chicken infectious anemia was initially suspected based on the clinical signs and gross lesions. Histopathology revealed multifocal acute hepatic degeneration and necrosis with golden-brown pigment in the cytoplasm of hepatocytes and Kupffer cells, moderate to severe koilin degeneration and fragmentation, multifocal mild to moderate proventricular necrosis, mild to moderate necrosis and loss of enterocytes, blunting of small intestinal villi, lymphoid depletion in the thymus and bursa, erythrophagocytosis in the liver and spleen, and acute renal tubular degeneration and necrosis. Special stains revealed mild to abundant accumulation of copper pigment in the cytoplasm of hepatocytes and iron pigment in the cytoplasm of Kupffer cells. Feed analysis revealed 2140 to 2393 parts per million of copper in the starter ration, and heavy metal analysis detected markedly elevated copper levels in formalin-fixed samples of the liver. Excessive amounts of tribasic copper chloride in the starter ration caused copper toxicosis in these chicks. Similar clinical signs and lesions were reproduced when the suspect feed was used in an experimental pen trial.
Pyrolusite surface transformations measured in real-time during the reactive transport of Co(II)EDTA2−

Oxidation of Co(II)EDTA2− to Co(III)EDTA− by manganese and iron hydrous oxide minerals enhances the transport of 60Co in subsurface environments. Until now, reduction of the oxidant MnO2 has not been identified in hydrodynamic systems, leaving the fate and transport mechanisms involving 60Co in natural environments unresolved. We investigated the transport of Co(II)EDTA2− through packed beds of β-MnO2 and identified the reaction mechanism using a novel hydrodynamic flow cell coupled with X-ray absorption near edge structure (XANES) spectroscopy. Using this technique we are able to determine both solution and solid-phase species of cobalt and manganese in real-time. Co(II)EDTA2− is produced while Mn(IV) is reduced to Mn(III) which forms an α-Mn2O3layer on pyrolusite. This layer passivates the surface after an initial reaction period and ultimately limits the production of Co(III)EDTA−. As a consequence, the enhanced transport of 60Co by oxidative processes may be diminished by continual exposure to pyrolusite—an advantage from an environmental quality perspective. It has also been clarified that Mn(III) is formed rather than Mn(II) resulting in formation of a stable trivalent manganese solid (α-Mn2O3).