cssi/SciSciGPT-SciSciNet huggingface dataset:
Evaluation of Supplementation Programs for Growing Cattle Grazing Tall Fescue1

Abstract Eighty steers and heifers were used to determine the effects of supplemental energy or undegradable intake protein (UIP) on the performance of growing cattle grazing tall fescue. Treatments included 1) no supplemental feed offered (control), 2) 0.91 kg/d of supplemental corn supplying 26 g UIP/d, 3) low-escape protein—0.91 kg/d of a 22% CP supplement supplying 117g UIP/d, or 4) high-escape protein—0.91 kg/d of a 42% CP supplement supplying 239 g UIP/d. Effective N degradabilities of the supplements were 63.6, 43.8, and 37.5%, respectively. All supplements also supplied 224 mg of lasalocid/ kg. Calf ADG was increased by an average of 0.11 kg by supplementation (control vs supplement, P = 0.02), and supplement type did not affect ADG (linear and quadratic responses of UIP, P > 0.36). The ratio of in-situ ruminallydegraded OM to ruminally-degraded CP (RDOM:RDCP) can be an effective predictor of the balance of ruminally available N and energy for designing supplementation programs for grazing cattle. Thus, the ratio of forage RDOM:RDCP was determined at 0, 8, 16, 24, 36, and 48 h of in situ incubation. The ratio of RDOM:RDCP of the forage samples remained essentially unchanged after 24 h of incubation, indicating that a single point in situ analysis can be used to determine this ratio. In conclusion, calves grazing tall fescue with 24-h in situ RDOM:RDCP ratios of 4.32 or less benefited equally from grain-based energy supplements or supplements supplying 117 and 239 g of UIP daily.
Correlation Between In Vivo and In Vitro Pulmonary Responses to Jet Propulsion Fuel-8 Using Precision-Cut Lung Slices and a Dynamic Organ Culture System

In tissue slice models, interactions between the heterogeneous cell types comprising the lung parenchyma are maintained thus providing a controlle d system for the study of pulmonary toxicology in vitro. However, validation of the model in vitro system must be affirmed. Previous reports, in in vivo systems, have demonstrated that Clara cells and alveolar type II cells are the targets following inhalation of JP-8 jet fuel. We have utilized the lung slice model to determine if cellular targets are similar following in vitro exposure to JP-8. Agar-filled adult rat lung explants were cored and precis ion cut, using the Brendel/Vitron tissue slicer. Slices were cultured on titanium screens located as half-cylinders in cylindrical Teflon cradles that w ere loaded into standard scintillation vials and incubated at 37 ‐ C. Slices were exposed to JP-8 jet fuel (0.5 mg/ml, 1.0 mg/ml, and 1.5 mg/ml in medium) for up to 24 hours. We determined ATP content using a luciferin-luciferase bioluminescent assay. No significant difference was found between the JP-8 jet fuel doses or time points, when compared to controls. Results were correlated with structural alterations following aerosol inhalation of J P-8. As a general observation, ultrastructural evaluation of alveolar type II cells revealed an apparent increase in the number and size of surfactant sec reting lamellar bodies that was JP-8 jet fuel-dose dependent. These results are similar to those observed following aerosol inhalation exposure. Thus, the lung tissue slice model appears to mimic in vivo effects of JP-8 and therefore is a useful model system for studying the mechanisms of lung injury following JP-8 exposure.
Fair and square: the four sides of distributive justice

Recent theoretical progress on inequity has left unresolved the crucial question of what constitutes equity. This paper proposes a positive theory of distributive justice, in a framework of inequity aversion, that depends on three general justice principles and context. The current study challenges the view of many previous inquiries that justice is context-specific and instead advances a theory in which justice is context-dependent: context matters, not because of the lack of general principles of justice, but due to its effect on the interpretation of those principles. Results from telephone interviews and written questionnaires are presented in support of the theory.
Packet output processes of CSMA protocols with common channel acknowledgement

The effect of common channel acknowledgement traffic on the packet departure process is studied for nonslotted CSMA (carrier-sense multiaccess) systems without capture. Both non-persistent and 1-persistent protocols are considered along with two acknowledgement schemes for each protocol. The packet interdeparture time moment generating function is explicitly derived in each case under a Poisson arrival model. >
RF BIST for ADPLL-based polar transmitters with wide-band DCO gain calibration

We propose a BIST scheme to provide online testing for all-digital PLL based polar transmitters. Multiple digital signatures are collected by adding a branch digital filter optimized to increase the sensitivities to non-idealities. The test signatures are processed using simple digital processing to provide an estimate for error vector magnitude (EVM), a key RF performance measure for the transmitter. Additionally a digital self-calibration scheme is proposed to eliminate the EVM degradation due to large wide-band DCO gain mismatch. We show that a proper exploration of digital implementation style is instrumental for facilitating novel low-cost built-in test and calibration solutions for mixed-signal and RF applications.
Pravastatin Alone and in Combination With Low-Dose Cholestyramine in Patients With Primary Hypercholesterolemia and Coronary Artery Disease

This randomized, open-label study compared the cost efficiency of low-dose pravastatin combined with low-dose cholestyramine with high-dose pravastatin monotherapy in 59 patients with moderate hypercholesterolemia and coronary disease. Both regimes were effective in improving lipid profiles in these patients; however, low-dose combination therapy enhanced achievement in therapeutic goals and cost efficiency.
Coalitional mate retention is correlated positively with friendship quality involving women, but negatively with male–male friendship quality

Abstract Friendship solved adaptive problems over human evolutionary history, including cooperative hunting and alloparenting. Pham, Barbaro, and Shackelford (in press) investigated another potential function of friendship: the provision of coalitional mate retention, whereby individuals ask an ally to assist with thwarting their romantic partner’s infidelity. In the current research, 387 participants (176 women) reported how often they requested or received coalitional mate retention from a male friend and from a female friend and reported on the quality of each friendship. The results indicate that the deployment of coalitional mate retention is positively associated with the quality of friendships with women (female–female friendships, male–female friendships, female–male friendships), but negatively associated with the quality of male–male friendships.
Brief announcement: a shorter and stronger proof of an Ω(d log(n/d)) lower bound for broadcast in radio networks

A seminal 1998 paper by Kushilevitz and Mansour [10] proved that for any randomized radio network broadcast algorithm, there exists a network in which the algorithm requires an expected time of Ω(Dlog(n/D)) rounds, for network size n and diameter D. In this study, we apply a new technique to generate a shorter and stronger version of this proof. In more detail, our new version fits in two pages, and it strictly strengthens the existing result by now allowing for active collision detection and an unlimited number of communication channels - assumptions which break the proof argument of [10].
Laparoscopic radical prostatectomy: Conventional and robotic

By 2015, prostate cancer will become the most commonly diagnosed cancer in men. Radical prostatectomy reduces disease-specific mortality in patients with localized prostate cancer; however, the invasiveness of surgery and its resultant side effects cause many men to seek other treatments. In 2000, laparoscopic radical prostatectomy emerged as a minimally invasive alternative to open surgery; it has been refined recently by the addition of robotic technology. To examine the outcomes of robotic radical prostatectomy and compare them with those from open and conventional laparoscopic radical prostatectomy, we prospectively collected baseline demographic data on all patients undergoing surgery for prostate cancer over a 4-year period at our center. Urinary function and sexual function were evaluated using standardized criteria as well as a questionnaire preoperatively and at 1, 3, 6, 12, and 18 months after their procedure. Operative and postoperative outcomes were compared using values for open radical prostatectomy as the reference standard. A total of 100 men underwent open radical prostatectomy with conventional laparoscopic radical prostatectomy (n = 50) and robotic radical prostatectomy (n = 500). The odds ratios for operative times, blood loss, postoperative pain, complications, and median times to urinary continence and resumption of sexual activity all were lower for robotic than for open or laparoscopic radical prostatectomy. It appears safe to conclude that conventional laparoscopic radical prostatectomy is a reasonable alternative to open radical prostatectomy in the surgical treatment of patients with clinically localized prostate cancer. The incorporation of robotics may result in even better surgical outcomes than conventional laparoscopy. However, the surgical robot is expensive; few centers have access to the technology and even fewer have expertise in the technique. For robotic radical prostatectomy to become the standard of care for the treatment of localized prostate cancer will require economies of cost, dissemination of surgical expertise, and data from randomized trials.
Detection of apoptosis induced DNA cleavage in scrapie-infected sheep brain

The pathogenesis and molecular basis of nerve cell death which accompanies scrapie infections in sheep are not well understood. Degeneration of neurons in culture caused by prion fragments has been reported to be consistent with mechanisms of cell death by apoptosis or programmed cell death. Apoptosis activation during prion-related encephalopathies has not yet been established in vivo. We report here the detection of DNA damage consistent with apoptosis in the brain cells of sheep infected with scrapie using laser scanning microscopic analysis of the single cell gel assay. We suggest that this DNA fragmentation is the result of the activation of the mechanisms characteristic of apoptotic cell death.
Identification and Treatment of Borderline Personality Disorder

THE INCLUSION of the borderline personality disorder diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III) is evidence that there is increasing recognition of this syndrome.1 Because social workers often serve as intake workers, they are in the unique position of being able to identify these clients early on. Such early identification and diagno sis facilitates the planning of appropri ate and effective treatment. More and
The Nature of Ultimate Reality & Recipe of Consciousness for Transformation

Understanding the nature of ultimate reality is the basis for a better World. Adding thoughts, intentions, and emotions to this understanding, we will have the complete recipe of consciousness for transformation.
Feature-Based variability meta-modeling for service-oriented product lines

Service Oriented Architecture (SOA) has emerged as a paradigm for distributed computing that promotes flexible deployment and reuse. However, SOA systems currently lack a systematic approach for managing variability in service requirements and design. Our paper addresses this problem by applying software product line (SPL) concepts to model SOA systems as service families. We introduce an approach to model SOA variability with a multiple-view SOA variability model and a corresponding meta-model. The approach integrates SPL concepts of feature modeling and commonality/variability analysis with different service views using UML and SoaML. This paper describes a multiple-view meta-model that maps features to variable service models as well as model consistency checking rules. We describe how to derive family member applications and also present a validation of the approach.
The Political Geography of Kurdistan

A U.S. geographer specializing in Kurdistan surveys that stateless region's complex historical, ethnographic, and cultural elements. Of particular interest is an analysis of the situation of the Kurds in each of the four major countries in which their homeland is found—Turkey, Iran, Iraq, and Syria—and where they comprise roughly 8-20 percent of each country's total population. The study is based on recent field work, interviews with numerous Kurds in government and political organizations as well as Kurdish refugees, and a literature survey, including regional sources. The paper concludes by assessing the implications of the changed, post-September 11 political situation in the region for Kurdish political influence and territorial sovereignty. Journal of Economic Literature, Classification Numbers: H10, I00, I31. 2 maps, 2 tables, 66 references.
Muc1 mucins on the cell surface are adhesion sites for Pseudomonas aeruginosa.

Recently, we cloned and characterized a full-length cDNA of the hamster Muc1 gene, the expression of which appears to be associated with secretory cell differentiation (Park HR, Hyun SW, and Kim KC...
The myomatous uterus complicated by pregnancy.

THE purpose of this presentation is to report a series of unusual c·linical problems in which uterine myomas were complicated by pregnancy. Examples shown here represent some of the more unusual eomplieations oceurring in different periods of preg·nanc·y. The myomas in this series were selected from a study of 8,968 patients delivered at the George Washington Universit.'" Hospital and 41,052 patients delivered at the <iallinger Muniripal Hospital. In this survey of 50,020 deliveries, no attempt has heen made to arrive at a statistical analysis. Previous reports have indicated that the in<'idener of uterine myomas in pregnancy varies from 0.3 to 7.2 per cent.'· 2 During pregnancy many small myomas may be discovered. hnt usually only those 8 em. or more in diameter become clinically signifieant. Serious complications of the pregnant myomatous uterus occur more rommonly in Negro than ir1 white patients, and more often in elderly primigravidas than in any other age or state .of pal'ity. In practically all instances, large or multiple myomas wrre incorporated in the uterus prior to eonception. • 4
Quo Vadis Strangeness? Strangeness - Open Questions

The study of strange and also charmed hadronic particle production in nuclear relativistic collisions offers an opportunity to explore the physical properties of the deconfined quark-gluon phase. We survey the recent accomplishments and the future directions of this research program.
Receptors Mediating Host-Seeking Behaviour in Mosquitoes and their Regulation by Endogenous Hormones

The behavioural process by which a mosquito finds a potential host organism is mediated by olfactory receptors on the insect’s antennae. Lactic acid (LA) is a host-related odour common to all potential hosts. On the antennae of the female are two LA-sensitive neurons; one of these is excited by LA but the other is inhibited by LA. Furthermore, the sensitivity of the LA-excited neuron is correlated 1:1 with the presence of host-seeking behaviour such that when host-seeking behaviour is inhibited following a blood meal, the sensitivity of the LA-excited neuron is markedly decreased. The inhibition of host-seeking behaviour and the decrease in LA-sensitivity are induced by a hemolymph-borne factor released during oocyte maturation. The source of this factor is the fat body of blood-fed females, which requires a vitellogenic ovary for its production and/or release. The combined activity of the two types of LA-sensitive neurons together with the shift in sensitivity of the LA-excited neuron from a range where host levels of LA are present to a range exceeding LA levels expected from a host are sufficient to account for the inhibition of host-seeking behaviour following a blood meal.
Nanopore Subangstrom-Resolution Single-Molecule Tool

We have developed a high-resolution nanopore sensor to observe enzyme activity with high positional sensitivity. In this method, single stranded DNA coupled to an enzyme is drawn through the engineered protein pore MspA. Nucleotides along DNA pass through the pore and modulate an ion current that flows through the pore. Analysis of this ion current indicates the precise position of the DNA and thereby provides a real-time record of the enzyme's activity. The position of DNA within MspA can be measured on millisecond time scales with a position resolution as small as ∼40 picometers. We demonstrate this sensitivity on a Hel308 helicase, where we observe two distinct sub-states for each nucleotide processed. One of these about half-nucleotide long steps is ATP-dependent and the other is ATP-independent. The spatial and temporal resolution of this low-cost single molecule technique allows exploration of hitherto unseen enzyme dynamics in real-time.
Lipid management after acute coronary syndrome.

PURPOSE OF REVIEW Despite advances in medical therapy and percutaneous revascularization, patients with acute coronary syndrome face a high risk of early, recurrent cardiovascular events. Interventions targeting atherogenic lipoproteins may favorably modify this risk. RECENT FINDINGS Two randomized clinical trials, MIRACL and PROVE-IT, demonstrated efficacy of early, intensive statin therapy after acute coronary syndrome. Recent observational and meta-analyses corroborate the findings of these trials. The benefit of intensive statin treatment appears to apply broadly to elderly as well as younger patients, and to patients with or without diabetes or metabolic syndrome. Randomized trials demonstrating the efficacy of early, intensive statin treatment after acute coronary syndrome employed fixed statin dosages, and there does not appear to be an initial or achieved LDL-cholesterol level below which benefit is absent. As such, broad application of intensive statin therapy after acute coronary syndrome may be preferable to titration of statin dose to achieve specific LDL goals. Low HDL-cholesterol predicts risk after acute coronary syndrome; therefore, pharmacologic interventions to raise HDL concentration or mimic its function may help reduce that risk. SUMMARY Early, intensive statin therapy is safe and effective after acute coronary syndrome. Future research will determine whether drugs that raise or mimic HDL-cholesterol are effective adjuncts to statin therapy.
Electric bugle: nifty assignment

When teaching about logic circuits in a sophomore-level course on computer organization, we assign students to use breadboards with TTL integrated-circuit chips. It is true that some students find the intricacies of wiring quite bothersome, and we could use logic circuit simulation software such as Logisim. But many other students find that working with physical circuits is a nice change of pace from doing assignments entirely on a computer. It also ensures that students realize that the logic-circuit concepts they are studying are real in the sense that one can actually build working circuits with them.
Evaluation of Impedance Cardiography for Measurement of Stroke Volume in Congenital Heart Disease

Noninvasive measurement of cardiac output (CO) and particularly stroke volume (SV) remain difficult but potentially valuable. These variables can be particularly challenging to measure in children with congenital heart disease (CHD). Impedance cardiography (IC) is a technique shown to be accurate in measuring SV in adults and in children with structurally normal hearts. The ease of use and rapidity of SV measurement using IC makes it potentially attractive for young patients with CHD. Advances in IC technology have led to more sophisticated signal-morphology IC (SMIC) devices that may further improve accuracy. We tested the accuracy of SMIC to measure SV in 21 subjects with CHD by comparing measurements with those from cardiac magnetic resonance (CMR) imaging. There was good agreement between SMIC and CMR in measurement of SV: mean difference = 1.7 ml (p = 0.47); r = 0.89. The agreement and correlation persisted when controlling for the differences in blood pressure and heart rate during the two testing methods. We conclude that SMIC is accurate at measuring SV and thus CO when compared to CMR in a variety of forms of CHD.
Physical Health of Custodial and Caregiving Grandfathers in North America

Across North America, the number of grandchildren living with and being raised by grandparents has doubled in the past few decades. Among custodial grandparents, approximately 25 % have at least one disability and more than half are employed full-time. Like grandmothers, custodial grandfathers experience a variety of positive, neutral, and negative effects related to their caregiving role. Drawing on current national surveys and other empirical studies, we illustrate the broad effects of raising grandchildren on the physical well-being of custodial and caregiving grandfathers in the USA and Canada. Specifically, we examine grandfathers’ self-assessed health and self-reported injuries related to caregiving. We also discuss several factors that may negatively influence the health of grandfathers, including household composition, employment, and social stereotypes.
Preliminary Study of the Carbon Sequestration and Enhanced Coal Bed Methane Production Potential of Subbituminous to High-Volatile Bituminous Coals of the Healy Creek Formation, Nenana Basin, Interior Alaska

Naturally fractured, unmineable coal seam reservoirs are attractive targets for geological sequestration of carbon dioxide (CO2) because of their high CO2 adsorption capacity and possible cost offsets from enhanced coal bed methane production. In this study, we have investigated the CO2 sequestration and coal bed methane (CH4) production potential of the subbituminous to high-volatile C bituminous Healy Creek Formation coals through preliminary sensitivity analyses, experimental design methods, and fluid flow simulations. The sensitivity analyses indicate that the total volumes of CO2 sequestered and CH4 produced from the Healy Creek coals are mostly sensitive to bottom-hole injection pressure, coal matrix porosity, fracture porosity, fracture permeability, coal compressibility, and coal volumetric strain. The results of the Plackett–Burman experimental design were used to further generate proxy models for probabilistic reservoir forecasts. The probabilistic estimates for the mature, subbituminous to high-volatile C bituminous Healy Creek coals in the entire Nenana Basin indicate that it is possible to sequester between 0.41 trillion cubic feet (TCF) (P10) and 0.05 TCF (P90) of CO2 while producing between 0.36 TCF (P10) and 0.05 TCF (P90) of CH4 at the end of 44-year forecast. Fluid flow scenarios show that CO2 sequestration through a primary reservoir depletion method is the most effective way to inject CO2 in the coals of the Nenana Basin. Including a horizontal well instead of the vertical well resulted in relatively high average gas production rates and subsequent total cumulative gas production. The CO2 buoyancy scenario suggests that the effect of CO2 buoyancy and the nature of caprock should be considered in identifying potential geologic sites for CO2 sequestration.
Use of clinical alerting to improve the collection of clinical research data.

Data errors in electronic health records have been shown to have the potential to adversely impact the conclusions drawn from clinical research. We prospectively studied the efficacy of a new alert to infer errors in previously stored data and to decrease the frequency of data entry errors, in an attempt to improve the quality of data for clinical trials. For the purpose of this study, we monitored data entry errors in height or weight measurements. We predetermined the criteria for probable error as a ten percent variance from a patient’s reference value. The care provider entering a value satisfying our error criteria received a disruptive pop-up alert message. The study revealed a significant decrease in the frequency of data errors stored in the EHR, from 2.4% before the alert to 0.9% after the alert. These findings have implications for the development of clinical research trial data collection support tools.
A new sub‐pathway of long‐patch base excision repair involving 5′ gap formation

Base excision repair (BER) is one of the most frequently used cellular DNA repair mechanisms and modulates many human pathophysiological conditions related to DNA damage. Through live cell and in vitro reconstitution experiments, we have discovered a major sub‐pathway of conventional long‐patch BER that involves formation of a 9‐nucleotide gap 5′ to the lesion. This new sub‐pathway is mediated by RECQ1 DNA helicase and ERCC1‐XPF endonuclease in cooperation with PARP1 poly(ADP‐ribose) polymerase and RPA. The novel gap formation step is employed during repair of a variety of DNA lesions, including oxidative and alkylation damage. Moreover, RECQ1 regulates PARP1 auto‐(ADP‐ribosyl)ation and the choice between long‐patch and single‐nucleotide BER, thereby modulating cellular sensitivity to DNA damage. Based on these results, we propose a revised model of long‐patch BER and a new key regulation point for pathway choice in BER. ![][1] DNA base excision repair (BER) is essential for coping with highly frequent oxidative and alkylation base damage. Identification of a novel sub‐pathway argues for a revision of mammalian long‐patch BER models and suggests a new key regulation point in BER pathway choice. [1]: /embed/graphic-1.gif
Forest cover, development, and sustainability in Costa Rica: Can one policy fit all?

Abstract Forest Transition Theory offers the hope that global economic development can continue in tandem with forest recovery. Costa Rica has been lauded for its successful forest transition—once the fastest deforesting country in Central America, forests began to regrow in the 1980s and have had a steady trajectory of recovery since. This forest regrowth can be linked temporally to Costa Rican policies that have promoted tourism and discouraged small-scale agriculture. We use a case study from the Bellbird Biological Corridor (Corredor Biologico Pajaro Campana; CBPC), Costa Rica, combining remote sensing analysis with interviews and ethnography, to unravel the relationship between national policy, forest regrowth, and social-ecological sustainability. The forest cover change analysis between 1986 and 2014 indicates that, at the parcel-level, national policy has served to promote farm abandonment in favor of tourism and that this change has been critical to forest regrowth. However, these changes have occurred within a development framework that has created new social-ecological challenges that threaten future forest and economic sustainability. Examining the parcel-level impacts of the driving forces of landscape change highlights that forest cover is an insufficient proxy for conservation success, and conservation policy focused primarily on forest recovery may create new sustainability challenges.
IL2RG, identified as overexpressed by RNA-seq profiling of pancreatic intraepithelial neoplasia, mediates pancreatic cancer growth.

// Michael Ayars 1 , Eileen O’Sullivan 1 , Anne Macgregor-Das 1 , Koji Shindo 1 , Haeryoung Kim 1 , Michael Borges 1 , Jun Yu 1 , Ralph H. Hruban 1,2 and Michael Goggins 1,2,3 1 Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 2 Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 3 Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Correspondence to: Michael Goggins, email: // Keywords : pancreatic cancer, PanIN, RNA-seq, IL2RG, JAK3 Abbreviations : PanIN, pancreatic intraepithelial neoplasia; Il2Rγ, IL2 gamma receptor; IL, interleukin; GMCSF, granulocyte/macrophage colony stimulating factor Received : May 19, 2017 Accepted : July 06, 2017 Published : August 03, 2017 Abstract Pancreatic ductal adenocarcinoma evolves from precursor lesions, the most common of which is pancreatic intraepithelial neoplasia (PanIN). We performed RNA-sequencing analysis of laser capture microdissected PanINs and normal pancreatic duct cells to identify differentially expressed genes between PanINs and normal pancreatic duct, and between low-grade and high-grade PanINs. One of the most highly overexpressed transcripts identified in PanIN is interleukin-2 receptor subunit gamma ( IL2RG ) encoding the common gamma chain, IL2Rγ. CRISPR-mediated knockout of IL2RG in orthotopically implanted pancreatic cancer cells resulted in attenuated tumor growth in mice and reduced JAK3 expression in orthotopic tumors. These results indicate that IL2Rγ/JAK3 signaling contributes to pancreatic cancer cell growth in vivo .
A convergent, scalable and stereoselective synthesis of azole CYP51 inhibitors.

Abstract The study and development of azole-based CYP51 inhibitors is an active area of research across disciplines of biochemistry, pharmacology and infectious disease. Support of in vitro and in vivo studies require the development of robust asymmetric routes to single enantiomer products of this class of compounds. Herein, we describe a scalable and enantioselective synthesis to VNI and VFV, the two potent inhibitors of protozoan sterol 14α-demethylase (CYP51) that are currently under consideration for clinical trials for Chagas disease. A key transformation is the Jacobsen Hydrolytic Kinetic Resolution (HKR) reaction. The utility of the synthetic route is illustrated by the preparation of >25 g quantities of single enantiomers of VNI and VFV.
Evaluation of a complementary and alternative medicine rotation in medical school.

BACKGROUND Despite widespread public use of complementary and alternative medicine (CAM) therapies, no standardized CAM curriculum is available to medical educators, and evaluation of such curricula is limited. OBJECTIVES (1) To evaluate the impact of a 3-week elective CAM rotation--integrating site-visits, small groups lectures and discussion, reference materials, a research paper--on medical students' confidence in their knowledge about CAM, attitudes toward CAM, and perceived effectiveness of CAM therapies. (2) To generate greater interest in evaluation of CAM curricula in medical school. METHODS Students (N=24) completed a pre- and post-course self-assessment tool designed to assess respondents' confidence in their knowledge about CAM (e.g., CAM principles and philosophy, indications for referral), attitudes toward CAM (e.g., its importance to heath professionals), and perceptions of the effectiveness of 10 CAM therapies. RESULTS Students' confidence increased substantially in the 4 domains of knowledge assessed. Students' positive pre-course attitudes toward CAM were sustained or improved, and their views on the effectiveness of CAM modalities increased. CONCLUSION A course that provides students with the opportunity to delve into the vast area of CAM though site visits, small group discussions, lectures, and independent research projects may be an effective means of providing a CAM curriculum.
The Rate of Evolution and the Importance of Isolation

It is a curious fact that when discussing evolution on a large scale even well-disciplined Mendelian geneticists often succumb to a Lamarckian illusion. Thus, to the question of why man does not have body hair, the answer is given that when our brachiating ape ancestors of the forest came out to open ground they were forced to travel long distances carrying heavy burdens on their backs. This tended to overheat their bodies which were covered with hair; hence, the loss of the body hair. This version vividly paints in our mind the picture of a group of traveling man-apes, panting and perspiring, suddenly making a community decision to comply with the dictate of natural selection. The illusory implication is that every member of the group of hairy apes transformed to a hairless ape. Such an unwittingly cultivated illusion tempts one to see the process of evolution as members of a successful species advancing shoulder-to-shoulder to a higher and higher state of being and eventually transforming to a new species. Thus, the process of speciation is viewed as a mere extension of the accumulation of genetic changes which occurred in the previous species, and the mutation rate is freely translated to the rate of evolution.
Industrial tools for the feature location problem: an exploratory study: Practice Articles

Software engineers who maintain and enhance large systems often encounter the feature location problem: where in the many thousands of lines of code is a particular user feature implementedq Several methods of addressing the problem have been proposed, most of which involve tracing the execution of the system and analyzing the traces. Some supporting academic tools are available. However, companies that depend on the successful evolution of large systems are more likely to use new methods if they are supported by industrial-strength tools of known reliability. This article describes a study performed with Motorola, Inc. to see whether there were any pitfalls in using Metrowerks CodeTEST and Klocwork inSight for feature location on message-passing software similar to systems that Motorola maintains. These two tools were combined with TraceGraph, an academic trace comparison tool. The study identified two main problems. First, some ‘glue’ code and workarounds were needed to get CodeTEST to generate a trace for an interval of time in which the feature was operating. Second, getting information out of TraceGraph and into inSight was needlessly complicated for a user. However, with a moderate amount of work, the tool combination was effective in locating, understanding and documenting features. Study participants completed these steps in typically 3–4 hours per feature, studying only a few hundred lines out of a 200 000 line system. An ongoing project with Motorola is focused on improving tool integration with the hope of making feature location common practice at Motorola. Copyright © 2006 John Wiley & Sons, Ltd.
Proton Pump Inhibitor Use Is Associated with an Increased Frequency of New or Worsening Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt Creation.

PURPOSE To determine whether proton pump inhibitor (PPI) use increases the rate of new or worsening hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS In this retrospective study, 284 of 365 patients who underwent TIPS creation from January 1, 2005, to December 31, 2016, were analyzed (186 male, mean age 56 y, range 19-84 y). Dates of PPI use and dates of new or worsening HE, defined as hospitalization or escalation in outpatient medical management, were extracted from medical records. Mixed-effects negative binomial regression was used to test for an association between PPI usage and HE. RESULTS After TIPS creation, among 168 patients on PPIs chronically, there were 235 episodes of new or worsening HE in 106,101 person-days (0.81/person-year). Among 55 patients never on PPIs, there were 37 episodes in 31,066 person-days (0.43/person-year). Among 61 patients intermittently taking PPIs, there were 78 episodes in 37,710 person-days while on PPIs (0.75/person-year) and 25 episodes in 35,678 person-days while off PPIs (0.26/person-year). In univariate regression, PPI usage was associated with a 3.34-fold increased rate of new or worsening HE (incidence rate ratio [IRR] 3.34; P < .001). In multivariate regression, older age (IRR 1.05; P < .001), male sex (IRR 1.58; P = .023), higher Model for End-Stage Liver Disease score (IRR 1.06; P = .015), previous HE or HE-preventive medication use (IRR 1.51; P = .029), and PPI use (IRR 3.19; P < .001) were significant risk factors. Higher PPI doses were associated with higher rates of HE (IRR 1.16 per 10 mg omeprazole equivalent; P = .046). CONCLUSIONS PPI usage is associated with increased rates of new or worsening HE after TIPS creation.
The burden of health conditions for middle-aged and older adults in the United States: disability-adjusted life years

Many adults are living longer with health conditions in the United States. Understanding the disability-adjusted life years (DALYs) for such health conditions may help to inform healthcare providers and their patients, guide health interventions, reduce healthcare costs, improve quality of life, and increase longevity for aging Americans. The purpose of this study was to determine the burden of 10 health conditions for a nationally-representative sample of adults aged 50 years and older in the United States. Data from the 1998–2014 waves of the Health and Retirement Study were analyzed. At each wave, participants indicated if they were diagnosed with the following 10 conditions: cancer, chronic obstructive pulmonary disease (COPD), congestive heart failure, diabetes, back pain, hypertension, a fractured hip, myocardial infarction, rheumatism or arthritis, and a stroke. Years lived with a disability and years of life lost to premature mortality were summed for calculating DALYs. Sample weights were utilized in the analyses to make the DALY estimates nationally-representative. Results for the DALYs were presented in thousands. There were 30,101 participants included. Sex stratified DALY estimates ranged from 4092 (fractured hip)-to-178,055 (hypertension) for men and 13,621 (fractured hip)-to-200,794 (hypertension) for women. The weighted overall DALYs were: 17,660 for hip fractures, 62,630 for congestive heart failure, 64,710 for myocardial infarction, 90,337 for COPD, 93,996 for stroke, 142,012 for cancer, 117,534 for diabetes, 186,586 for back pain, 333,420 for arthritis, and 378,849 for hypertension. In total, there were an estimated 1,487,734 years of healthy life lost from the 10 health conditions examined over the study period. The burden of these health conditions accounted for over a million years of healthy life lost for middle-aged and older Americans over the 16 year study period. Our results should be used to inform healthcare providers and guide health interventions aiming to improve the health of middle-aged and older adults. Moreover, shifting health policy and resources to match DALY trends may help to improve quality of life during aging and longevity.
Maternal Vitamin D Status and Adverse Pregnancy and Neonatal Outcomes in India

ObjectiveTo examine the prevalence of vitamin D deficiency and its association with risk of adverse pregnancy and neonatal outcomes in Southern India. MethodsA total of 366 women participating in a...
Stabilized Carbenium Ions as Latent, Z‐type Ligands

Controlling the reactivity of transition metals using secondary, σ-accepting ligands is an active area of investigation that is impacting molecular catalysis. Herein we describe the phosphine gold complexes [(o-Ph2 P(C6 H4 )Acr)AuCl]+ ([3]+ ; Acr=9-N-methylacridinium) and [(o-Ph2 P(C6 H4 )Xan)AuCl]+ ([4]+ ; Xan=9-xanthylium) where the electrophilic carbenium moiety is juxtaposed with the metal atom. While only weak interactions occur between the gold atom and the carbenium moiety of these complexes, the more Lewis acidic complex [4]+ readily reacts with chloride to afford a trivalent phosphine gold dichloride derivative (7) in which the metal atom is covalently bound to the former carbocationic center. This anion-induced AuI /AuIII oxidation is accompanied by a conversion of the Lewis acidic carbocationic center in [4]+ into an X-type ligand in 7. We conclude that the carbenium moiety of this complex acts as a latent Z-type ligand poised to increase the Lewis acidity of the gold center, a notion supported by the carbophilic reactivity of these complexes.
Gilded Age Literature and Inequality

We are an intensely social species, and often a rivalrous one, prone to measuring ourselves in terms of others, and often directly against others. Accordingly, relative position matters to our sense of wellbeing, although excluded from standard economic models that look only at the utility derived from own consumption of commodities plus leisure. For example, people can have deep-seated psychological responses to inequality and social hierarchy, creating the potential for extreme wealth differences to invoked feelings of superiority and inferiority, or dominance and subordination, that may powerfully affect how we relate to each other. The tools that one needs to understand how and why this matters include the sociological and the qualitative. In my book-in-progress, Dangerous Grandiosity: Literary Perspectives on High-End Inequality Through the First Gilded Age, I use the particular tool of in-depth studies of particular classic works of literature (from Jane Austen’s Pride and Prejudice through Theodore Dreiser’s The Financier and The Titan) that offer suggestive insights regarding the felt experiences around high-end inequality at different times and from different perspectives. A successor volume will carry this account through the twentieth century and up to the present. On May 17, 2018, at Stanford Law School, I gave a talk on the book project in general, and a chapter on E.M. Forster’s Howards End in particular. This paper offers the approximate text of that talk.
Macroeconomics, History of From 1933 to Present

This article is a revision of the previous edition article by M. Schabas, volume 6, pp. 4152–4158, © 2001, Elsevier Ltd.
BEON: A Functional Fluorescence Reporter for Quantification and Enrichment of Adenine Base-Editing Activity.

Adenine base editor (ABE) is a new generation of genome-editing technology through fusion of Cas9 nickase with an evolved E. coli TadA (TadA∗) and holds great promise as novel genome-editing therapeutics for treating genetic disorders. ABEs can directly convert A-T to G-C in specific genomic DNA targets without introducing double-strand breaks (DSBs). We recently showed that computer program-assisted analysis of Sanger sequencing traces can be used as a low-cost and rapid alternative of deep sequencing to assess base-editing outcomes. Here we developed a rapid fluorescence-based reporter assay (Base Editing ON [BEON]) to quantify ABE efficiency. The assay relies on the restoration of the downstream green fluorescent protein (GFP) in ABE-mediated editing of a stop codon located within the guide RNA (gRNA). We showed that this assay can be used to screen for effective ABE variants, characterize the protospacer adjacent motif (PAM) requirement of a novel NNG-targeting ABE based on ScCas9, and enrich for edited cells. Finally, we demonstrated that the reporter assay allowed us to assess the feasibility of ABE editing to correct point mutations associated with dysferlinopathy. Taken together, the BEON assay would facilitate and simplify the studies with ABEs.
Effects of the Culture and Climate of Doctoral-Granting Institutions on the Career Aspirations of Women Midlevel Student Affairs Professionals

Women fill the majority of the entry and midlevel student affairs positions across institution types yet are underrepresented in senior-level roles such as the chief student affairs officer role at...
RSK2 Maintains Adult Estrogen Homeostasis by Inhibiting ERK1/2-Mediated Degradation of Estrogen Receptor Alpha

In response to estrogens, estrogen receptor alpha (ERα), a critical regulator of homeostasis, is degraded through the 26S proteasome. However, despite the continued presence of estrogen before menopause, ERα protein levels are maintained. We discovered that ERK1/2-RSK2 activity oscillates during the estrous cycle. In response to high estrogen levels, ERK1/2 is activated and phosphorylates ERα to drive ERα degradation and estrogen-responsive gene expression. Reduction of estrogen levels results in ERK1/2 deactivation. RSK2 maintains redox homeostasis, which prevents sustained ERK1/2 activation. In juveniles, ERK1/2-RSK2 activity is not required. Mammary gland regeneration demonstrates that ERK1/2-RSK2 regulation of ERα is intrinsic to the epithelium. Reduced RSK2 and enrichment in an estrogen-regulated gene signature occur in individuals taking oral contraceptives. RSK2 loss enhances DNA damage, which may account for the elevated breast cancer risk with the use of exogenous estrogens. These findings implicate RSK2 as a critical component for the preservation of estrogen homeostasis.
Racial disparities in clinical presentation, type of intervention, and in-hospital outcomes of patients with metastatic spine disease: An analysis of 145,809 admissions in the United States

Abstract Background Race is an important determinant of cancer outcome. The purpose of this study was to identify disparities in clinical presentation, treatment use, and in-hospital outcomes of patients with spinal metastases. Methods The United States National Inpatient Sample database (2004–2014) was queried to identify patients with metastatic disease and cord compression (MSCC) or spinal pathological fracture. Clinical presentation, type of intervention, and in-hospital outcomes were compared between races/ethnicities. Multivariate logistic regression analyses were performed and adjusted for differences in patient age, sex, insurance status, income quartile, hospital teaching status and size, Charlson comorbidity index, smoking status, tumor type, and neurological status. Results A total of 145,809 patients were identified – 74.8 % Caucasian, 14.1 % African-American, 7.9 % Hispanic, and 3.2 % Asian. Over one-third of patients (38.1 %) presented with MSCC; 35.7 % of Caucasians, 50.3 % of AAs, 41.1 % of Hispanics, and 39.8 % of Asians (p Conclusion Minority groups with spinal metastatic disease may be at a disadvantage compared to Caucasians, with significant disparities found in presenting characteristics, type of intervention, and in-hospital outcomes. Continued efforts to overcome these differences are needed.
Canonical Rings of \({\mathbb{Q}}\)-Divisors on \({\mathbb{P}^1}\)

The canonical ring \({S_{D} = \oplus_{d\geq0}H^{0}(X, \lfloor dD\rfloor)}\) of a divisor D on a curve X is a natural object of study; when D is a \({\mathbb{Q}}\)-divisor, it has connections to projective embeddings of stacky curves and rings of modular forms. We study the generators and relations of \({S_D}\) for the simplest curve \({X = \mathbb{P}^1}\). When D contains at most two points, we give a complete description of \({S_D}\); for general D, we give bounds on the generators and relations. We also show that the generators (for at most five points) and a Grobner basis of relations between them (for at most four points) depend only on the coefficients in the divisor D, not its points or the characteristic of the ground field; we conjecture that the minimal system of relations varies in a similar way. Although stated in terms of algebraic geometry, our results are proved by translating to the combinatorics of lattice points in simplices and cones.
Risk for cardiovascular events following 'microsize' versus usual myocardial infarctions

Background Microsize myocardial infarction (MI) is a recently described phenomenon that meets rigorous criteria for MI with very low peak troponin elevations. We aim to compare the risk for cardiovascular events and mortality following microsize versus usual MIs. Methods and results Prospective cohort analysis of REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants without a history of coronary heart disease (CHD) who had an incident MI between 2003 and 2015. Incident MIs were classified as microsize MI (peak troponin Conclusion Microsize MIs have a prognostic value for future cardiovascular events and mortality comparable to usual MIs. These findings should encourage clinicians to initiate secondary prevention strategies in patients with microsize MI until this emerging clinical entity is better understood.