cssi/SciSciGPT-SciSciNet huggingface dataset:
VITAMIN D PROMOTES PROTEIN HOMEOSTASIS AND LONGEVITY VIA STRESS RESPONSE GENES SKN-1, IRE-1, AND XBP-1

Vitamin D has multiple roles including the regulation of bone and calcium homeostasis. Deficiency of 25-hydroxyvitaminD, the major circulating form of vitamin D, is associated with an increased risk of age-related chronic diseases including Alzheimer’s disease, Parkinson’s disease, cognitive impairment, and cancer. In this study, we utilized Caenorhabditis elegans to examine the mechanism by which vitamin D influences aging. We found that Vitamin D3-induced lifespan extension requires the stress response pathway genes SKN-1, IRE-1, and XBP-1. Vitamin D3 (D3) induced expression of SKN-1 target genes, but not canonical targets of IRE-1/XBP-1. D3 suppressed an important molecular pathology of aging, that of widespread protein insolubility, and prevented toxicity caused by human β-amyloid. Our observation that D3 improves protein homeostasis and slows aging highlights the importance of maintaining appropriate vitamin D serum levels, and may explain why such a wide variety of human age-related diseases are associated with vitamin D deficiency.
SAT Based Fitness Scoring for Digital Circuit Evolution

Evolutionary computation uses Darwinian principles to find solutions from a given search space and forms the basis for evolving digital circuits. One of the most computationally expensive steps in evolutionary computation is the comparison of the candidate circuit or chromosome with the target truth table. We propose to use a satisfiability solver, to improve upon the efficiency of this process, which is traditionally done using exhaustive simulation. The paper presents an implementation of the satisfiability solver, which is in turn used to develop a digital circuit evolution methodology based on the principles of cartesian genetic programming. The proposed methodology performs better, in terms of speed of design space exploration, for circuits whose behavior can be expressed compactly in terms of conjunctive normal form clauses. For illustration purposes, the proposed methodology has been used to evolve various commonly used digital circuits and a few benchmarks.
The Evolving Patent Pledge Landscape

Patent pledges – public commitments to limit the enforcement or other exploitation of one’s patent rights – are increasing in popularity in a range of market sectors from telecommunications and software to biopharma and green technology. Following initial work that sought to classify and understand patent pledges as a distinct category of firm behavior, the author and collaborators have identified a range of recent development in the evolution of patent pledges. These include increasing structural complexity and sophistication of patent pledges, a richer set of motivations leading firms to pledge patents, increased attention to the role that patent pledges play in innovation and on the governance of collective pledges, and a trend toward democratization and internationalization of pledge behavior. These trends were discussed at the Evolving Pledges Workshop in Washington DC in September 2017 and are summarized herein.
Surface functionalization of nanoporous PLGA microparticles

Poly lactic-co-glycolic acid (PLGA) microparticles are widely used for drug delivery. In a cancer cell, ion channels have been recognized to play important roles in cancer pathology, as these regulate key events in cell proliferation and cancer initiation and progression. Ion channels are ideal drug targets as the respective small molecules may be effective from the extracellular space and do not need to enter the target cells. The development of cancer treatment using ion channel targeting compounds is still in early stages, although some studies have shown that some voltage-gated ion channel (VGIC) blockers can inhibit cell behaviors associated with metastasis. We developed a simple and effective method to control nanoporous formation, size, density and the surface functionalization of PLGA microparticles. PLGA microparticles were synthesized using water-in-oil-in-water (w/o/w) double emulsion method. The synthesis of nanoporous microparticles with this novel, rapid, inexpensive method and easily controllable properties can be useful for applications in targeting one or multiple VGIC in cancer patients.
The role of Title IV-E education and training in child protection workforce diversification

ABSTRACTEducating, training, and diversifying the workforce are strategies that may help reduce racial/ethnic disparities that plague child protection system (CPS). Title IV-E education and training programs support the development of a specially trained, highly skilled workforce; yet, little research examining their impact on workforce diversification exists. The current study assessed the relationship between Title IV-E education and training and workforce diversity and leadership in a state system that is plagued with racial disparities using data from a statewide child welfare survey (n = 679) and existing population-level sources. Findings revealed that while children of color were disproportionately overrepresented in the CPS, professionals of color were disproportionately underrepresented (as compared to the state’s overall population and the population of children served within CPS). Title IV-E education and training programs were associated with both child protection workforce diversity and CPS l...
The effect of excess trace minerals on pig performance and dietary tocopherols

Two experiments were conducted to evaluate the effect of the addition of high levels of copper, iron or zinc to swine starter and grower diets on pig performance and vitamin E-selenium status. The stability of natural tocopherols in mixed feeds was evaluated during storage. Addition of 1000 ppm iron or 1000 ppm zinc had no affect on performance in either experiment. In Exp. 1, the addition of 250 ppm copper improved gains and feed efficiency (P<.05) during the first three weeks of the experiment. The advantage was lost during week four and no other effect was seen on performance in either experiment as result of the addition of copper. Serum lactic dehydrogenase (LDH) or glutathione peroxidase (GSH-Px) activity was not affected by any of the mineral additions. Serum tocopherols were not affected by the mineral treatments in Exp. 1. In Exp. 2, addition of 250 ppm Cu decreased (P<.05) serum tocopherol levels throughout the entire 8 week experiment. The alpha-tocopherol levels of the starter diet decreased (P<.05) during storage. Addition of 250 ppm Cu (P<.01) or 1000 ppm Fe (P<.05) or 1000 ppm Zn (P<.05) increased the destruction of alpha-tocopherol in the starter diet. Alphaand gamma-tocopherol levels of the starter diet
Improving Corporate Governance: Lessons From the European Community

Recently, the U.S. has witnessed bold and vigorous activity by the boards of directors of several large publicly held corporations. Within the last year, corporate boards of several major U.S. corporations have either dismissed or requested the resignation of their chief executive officers. Directors have replaced chief executives at such blue chip corporations as Eastman Kodak,2 General Motors,3 Digital Equipment Corporation,4 Tenneco,5 Compaq Computer,6 International Business Machines Corporation,7 American Express Company,8 Westinghouse Electric Corporation,9 Time-Warner,10 Goodyear Tire and Rubber,11 Sunbeam Oster Company,12 and Ames Department Store.13 This mass removal of chief and senior executives from several of the most prestigious corporations
Stochastic Processes (ii): Random Walks

Random walks are special cases of Markov chains, and thus can be analyzed by Markov chain methods. However, the special features of random walks allow specific methods of analysis. Some of these methods are introduced in this chapter.
Feasibility of providing child restraint devices after a motor vehicle crash in a pediatric emergency department

Objective: Motor vehicle crashes (MVCs) cause disproportionate childhood morbidity and mortality. Ensuring that children are placed in appropriate child restraint devices (CRDs) would significantly...
Agency Costs and the Price Effects of Corporate Litigation

The substantial empirical literature on corporate litigation has only recently turned its attention to the interaction between corporate governance and litigation strategy. Haslem (2005) shows that managers at defendant firms with weak governance may be too eager to settle cases in order to avoid embarrassing disclosures. This paper extends this finding by examining the impact of agency costs on plaintiff firms’ litigation decisions. I find that firms with weaker governance show significantly lower abnormal stock returns around the time they file a lawsuit. These abnormal returns likely result from firms pursuing suits with negative value. The findings suggest that managers may derive private benefits from litigating.
Computer-aided dosage form design. I. Methods for defining a long-acting first-order delivery system of maximum formulating flexibility

The method provides an a priori assessment of the maximum allowable flexibility in the rate of release from a prolonged-release formulation. The clinical pharmacokinetic parameters describing the drug candidate are employed to calculate the ranges of rate constants and doses required for the formulation to provide a selected therapeutic duration. For a given patient, there may be an infinite number of combinations of release rate constants and dose sizes which will maintain steady-state plasma drug concentrations within a desired range when the formulation is administered at the selected dosing interval. Computer simulations of steady-state plasma concentrations are employed to establish the ranges for all of the acceptable rate constants and doses for each member of a group. The entire group is then examined to define the range of release rate constants and doses which would provide a useful formulation for every member in the group. Literature values for theophylline clinical pharmacokinetics in children and adults have been employed to illustrate the application of this method. The method is unique in that it provides an entire range of release rates on which to gauge the feasibility for success.
PI3K alpha and delta promote hematopoietic stem cell activation

Many cytokines and chemokines that are important for hematopoiesis activate the PI3K signaling pathway. Because this pathway is frequently mutated and activated in cancer, PI3K inhibitors have been developed for the treatment of several malignancies, and are now being tested in the clinic in combination with chemotherapy. However, the role of PI3K in adult hematopoietic stem cells (HSCs), particularly during hematopoietic stress, is still unclear. We previously showed that the individual PI3K catalytic isoforms P110α or P110β have dispensable roles in HSC function, suggesting redundancy between PI3K isoforms in HSCs. We now demonstrate that simultaneous deletion of P110α and P110δ in double knockout (DKO) HSCs uncovers their redundant requirement in HSC cycling after 5-fluorouracil (5-FU) chemotherapy administration. In contrast, DKO HSCs are still able to exit quiescence in response to other stress stimuli, such as LPS. We found that DKO HSCs and progenitors have impaired sensing of inflammatory signals ex vivo, and that levels of IL1-β and MIG are higher in the bone marrow after LPS than after 5-FU administration. Furthermore, exogenous in vivo administration of IL1-β can induce cell cycle entry of DKO HSCs. Our findings have important clinical implications for the use of PI3K inhibitors in combination with chemotherapy.
Lack of an Association between a Polymorphism in the KRAS 3' Untranslated Region (rs61764370) and Endometriosis in a Large European Case-Control Study.

Background Endometriosis is a common disorder that affects 6-10% of reproductive age women. In a previous study, we demonstrated that a polymorphism in let-7 microRNA-binding site in the 3a untranslated region of the KRAS gene was found in 31% of subjects with endometriosis resistant to medical therapy. This polymorphism was now tested in a large, case-control study. Methods Peripheral blood or peritoneal biopsies from 2,077 European subjects with or without endometriosis and known infertility were tested for the presence of the variant allele using polymerase chain reaction. Results Histologically proven endometriosis was found in 1,140 subjects, while 937 subjects were disease free. Variant allele carrier rates in subjects with and without endometriosis were 15.7 and 15.1%, respectively. No association between the variant KRAS allele and stage of the disease, age at surgery, body mass index, or type of infertility was identified. Conclusion A germ-line single-nucleotide polymorphism in the let-7 microRNA-binding site of the KRAS gene was not associated with sporadic endometriosis in an infertile Caucasian population in this large case-control study. However, it remains possible that this gene variant may be a marker of treatment resistance. Further studies on the role of this polymorphism in endometriosis are needed.
Hippocampal Neurogenesis Is Enhanced in Adult Tau Deficient Mice.

Tau dysfunction is common in several neurodegenerative diseases including Alzheimer’s disease (AD) and frontotemporal dementia (FTD). Affective symptoms have often been associated with aberrant tau pathology and are commonly comorbid in patients with tauopathies, indicating a connection between tau functioning and mechanisms of depression. The current study investigated depression-like behavior in Mapt−/− mice, which contain a targeted deletion of the gene coding for tau. We show that 6-month Mapt−/− mice are resistant to depressive behaviors, as evidenced by decreased immobility time in the forced swim and tail suspension tests, as well as increased escape behavior in a learned helplessness task. Since depression has also been linked to deficient adult neurogenesis, we measured neurogenesis in the hippocampal dentate gyrus and subventricular zone using 5-bromo-2-deoxyuridine (BrdU) labeling. We found that neurogenesis is increased in the dentate gyrus of 14-month-old Mapt−/− brains compared to wild type, providing a potential mechanism for their behavioral phenotypes. In addition to the hippocampus, an upregulation of proteins involved in neurogenesis was observed in the frontal cortex and amygdala of the Mapt−/− mice using proteomic mass spectrometry. All together, these findings suggest that tau may have a role in the depressive symptoms observed in many neurodegenerative diseases and identify tau as a potential molecular target for treating depression.
Impact of early direct patient care introductory pharmacy practice experiences on student pharmacists' career exploration.

Abstract Background and purpose The University of Kentucky College of Pharmacy piloted a novel longitudinal introductory experiential program to provide second (P2) and third (P3) year professional students early exposure to pharmacist-provided direct patient care, opportunity to develop professionally expected behaviors, and ability to explore contemporary pharmacy career options. This paper describes the influence of the pilot on pre-advanced pharmacy practice experiences (APPEs) career interests and professional development. Educational activity and setting Forty P2 and P3 students participated in the longitudinal experiential pilot course. Students were assigned to 32 pharmacist preceptors in a variety of direct patient care practices. Students completed 16 onsite hours over the fall semester. Influence of the pilot experience on APPE plans and future career interests was assessed by an end of experience reflective assignment and survey. Findings The pilot course served as the initial exposure for the majority of students to both direct patient care and specialized areas of pharmacy practice. Nearly half of students indicated the experience advanced their knowledge of pharmacists' scope of practice and potential career opportunities. Most students (85%) reported the experience influenced future career plans, with half indicating increased interest in their specific practice specialty. Over 75% planned to pursue an APPE in that practice area. Nearly all students reported making professional contacts through this experience. Summary Early exposure to direct patient care and specialized pharmacy practice areas through this IPPE provided students opportunity to inform career interest and develop professional contacts with preceptors in specialized practice areas.
Early Chemoprophylaxis Against Venous Thromboembolism in Patients With Traumatic Brain Injury.

IntroductionTiming to start of chemoprophylaxis for venous thromboembolism (VTE) in patients with traumatic brain injury (TBI) remains controversial. We hypothesize that early administration is not...
Binding mode of SARS-CoV-2 fusion peptide to human cellular membrane.

Infection of human cells by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) relies on its binding to a specific receptor and subsequent fusion of the viral and host cell membranes. The fusion peptide (FP), a short peptide segment in the spike protein, plays a central role in the initial penetration of the virus into the host cell membrane, followed by the fusion of the two membranes. Here, we use an array of molecular dynamics simulations that take advantage of the highly mobile membrane mimetic model to investigate the interaction of the SARS-CoV2 FP with a lipid bilayer representing mammalian cellular membranes at an atomic level and to characterize the membrane-bound form of the peptide. Six independent systems were generated by changing the initial positioning and orientation of the FP with respect to the membrane, and each system was simulated in five independent replicas, each for 300 ns. In 73% of the simulations, the FP reaches a stable, membrane-bound configuration, in which the peptide deeply penetrated into the membrane. Clustering of the results reveals three major membrane-binding modes (binding modes 1-3), in which binding mode 1 populates over half of the data points. Taking into account the sequence conservation among the viral FPs and the results of mutagenesis studies establishing the role of specific residues in the helical portion of the FP in membrane association, the significant depth of penetration of the whole peptide, and the dense population of the respective cluster, we propose that the most deeply inserted membrane-bound form (binding mode 1) represents more closely the biologically relevant form. Analysis of FP-lipid interactions shows the involvement of specific residues, previously described as the "fusion-active core residues," in membrane binding. Taken together, the results shed light on a key step involved in SARS-CoV2 infection, with potential implications in designing novel inhibitors.
Seminole Food: Patterns of Indigenous Foodways in South Florida, 1855 to 1917

Few systematic historical studies of Seminole Indian foodways in Florida exist, fewer even for the critical period between Removal and World War I. This paper aims to fill the gap in related foodways and historical literature, while establishing a starting point for zooarchaeological and archaeobotanical studies on the topic. It addresses the issue from the ground up, developing an inventory of Seminole selective preferences in terms of food and tracking changes in those preferences over time. The study borrows the use of presence/absence matrices from archaeology to facilitate that analysis, treating an extensive set of related documents as a stratified matrix in which historical observations of Seminole food consumption are recorded by food type. It relies on Seminole oral histories to supplement the document index by providing additional information as to food preferences and taboos. Results of data analysis lead me to the conclusion that two complimentary channels of foodways existed among Seminole Indians in South Florida at the time: (1) a conservative channel that maintained symbolically and nutritionally important foods and, (2) a more flexible channel that allowed for the incorporation of supplementary foods of various origins.
Using Disciplinary Literacy to Teach Children to Write Science Informational Text

The purpose of the study was to examine how disciplinary literacy instruction influenced the quality of science informational text produced by second-grade students (N = 45) using the compare/contr...
RAD51AP1 mediates RAD51 activity through nucleosome interaction.

Abstract RAD51-associated protein 1 (RAD51AP1) is a key protein in the homologous recombination (HR) DNA repair pathway. Loss of RAD51AP1 leads to defective HR, genome instability, and telomere erosion. RAD51AP1 physically interacts with the RAD51 recombinase and promotes RAD51-mediated capture of donor DNA, synaptic complex assembly, and displacement-loop formation when tested with nucleosome-free DNA substrates. In cells, however, DNA is packaged into chromatin, posing an additional barrier to the complexities of the HR reaction. In this study, we show that RAD51AP1 binds to nucleosome core particles (NCPs), the minimum basic unit of chromatin in which approximately two superhelical turns of 147 bp double-stranded DNA are wrapped around one histone octamer with no free DNA ends remaining. We identified a C-terminal region in RAD51AP1, including its previously mapped DNA-binding domain, as critical for mediating the association between RAD51AP1 and both the NCP and the histone octamer. Using in vitro surrogate assays of HR activity, we show that RAD51AP1 is capable of promoting duplex DNA capture and initiating joint-molecule formation with the NCP and chromatinized template DNA, respectively. Together, our results suggest that RAD51AP1 directly assists in the RAD51-mediated search for donor DNA in chromatin. We present a model, in which RAD51AP1 anchors the DNA template through affinity for its nucleosomes to the RAD51-ssDNA nucleoprotein filament.
Making the case for a pedagogy of civic engagement, antiextremism, and antiracism: a response to forum essays

On January 6, 2021, then-President Trump urged supporters to march to the U.S. Capitol (Dozier & Bergengruen, 2021; Holland et al., 2021; Snyder, 2021). The insurrection that followed was an unprec...
Collagenous Enteritis – An Alternative Cause of Malabsorptive Enteropathy

IntroductionCollagenous Enteritis (CE) is a less common cause of enteropathy presenting with malabsorption as its cardinal symptom. While historically considered a resistant form of celiac disease, newer evidence supports the interaction between genetic predispositions and environmental triggers as the pathophysiologic basis of CE.Case PresentationHerein we present the case of a 40-year-old woman with two-year history of diarrhea and 32 kg weight loss who was incorrectly diagnosed with celiac disease with refractory symptoms despite adherence to a gluten-free diet. Extensive infectious, inflammatory, secretory, autoimmune workup did not reveal an underlying etiology. Endoscopic evidence of severe villous blunting and biopsy with characteristic patchy enlarged subepithelial collagen layer solidified a diagnosis of CE. Treatment with steroids resulted in resolution of malabsorptive symptoms and gradual weight gain.ConclusionThis case highlights the importance of considering CE in patients presenting with malabsorption especially given significant clinical overlap with other malasbsorptive conditions as well as its therapeutic implications.
Shopping Orientation, Demographic and Media Preference Correlates of Electronic Shopping

The purpose of the study is to document the correlates of consumers’ desirability of videotex shopping. Many retailing experts suggest that electronic shopping will become the next revolution in retailing. Several past studies in retailing have demonstrated that much can be learned about retail patronage from the study of consumers’ shopping orientation, demographics, and media preferences. The results suggest that electronic shopping is desirable to white females who are older, educated, working in supervisory or higher level occupations and who also are price conscious shoppers.
Percutaneous Coronary Intervention and the Various Coronary Artery Disease Syndromes

Percutaneous techniques have become the dominant revascularization strategy for the treatment of patients with both acute and chronic coronary artery disease. They have been studied in multiple registries and randomized clinical trials using as comparators medical therapy and coronary bypass graft surgery.
Modeling a dynamic and uncertain world I: symbolic and probabilistic reasoning about change

Abstract Intelligent agency requires some ability to predict the future. An agent must ask itself what is presently its best course of action given what it now knows about what the world will be like when it intends to act. This paper presents a system that uses a probabilistic model to reason about the effects of an agent's proposed actions on a dynamic and uncertain world, computing the probability that relevant propositions will hold at a specified point in time. The model allows for incomplete information about the world, the occurrence of exogenous (unplanned) events, unreliable sensors, and the possibility of an imperfect causal theory. The system provides an application program with answers to questions of the form “is the probability that ϕ will hold in the world at time t greater than τ?” It is unique among algorithms for probabilistic temporal reasoning in that it tries to limit its inference according to the proposition, time, and probability threshold provided by the application. The system will also notify the application if subsequent evidence invalidates its answer to a query.
Mapping the GPS multipath environment using the signal-to-noise ratio (SNR)

[1] GPS multipath, where a signal arrives by more than one path, is a source of positioning error which cannot be easily neutralized. Better understanding of the multipath environment, i.e., the direction of and distance to reflecting objects, is important for multipath mitigation during the site construction phase as well as discerning the impact of multipath on positioning estimates for existing sites. This paper presents a tool called power spectral mapping that visually represents the multipath environment of a GPS site. This technique uses the spectral content (frequency and magnitude) of signal-to-noise ratio (SNR) time series to determine which satellites, and therefore which portions of the antenna environment, contribute significant multipath error and at what frequencies. Wavelet analysis is used to extract the time-varying frequency and magnitude content of various multipath constituents, and these data are projected onto a map representing the GPS antenna surroundings. Power spectral map examples from stations with very different multipath environments are presented. The maps are interpreted in terms of potential sources of multipath reflections, and how these multipath signals contribute to positioning error at each station is also assessed.
A GTP-binding protein regulates the activity of (1-->3)-beta-glucan synthase, an enzyme directly involved in yeast cell wall morphogenesis.

Abstract Synthesis of (1-->3)-beta-D-glucan, the major structural component of the yeast cell wall, is synchronized with the budding cycle. Membrane-bound, GTP-stimulated (1-->3)-beta-glucan synthase was dissociated by stepwise treatment with salt and detergents into two soluble fractions, A and B, both required for activity. Fraction A was purified about 800-fold by chromatography on Mono Q and Sephacryl S-300 columns. During purification, GTP binding to protein correlated with synthase complementing activity. A 20-kDa GTP-binding protein was identified by photolabeling in the purified preparation. This preparation no longer required GTP for activity, but incubation with another fraction from the Mono Q column (A1) led to hydrolysis of bound GTP to GDP with a concomitant return of the GTP requirement. Thus, fraction A1 appears to contain a GTPase-activating protein. These results show that the GTP-binding protein not only regulates glucan synthase activity but can be regulated in turn, constituting a potential link between cell cycle controls and wall morphogenesis.
Oligopeptides with the sequences ala-pro-gly and gly-pro-gly as substrates or inhibitors for protocollagen proline hydroxylase.

Sequential oligopeptides prepared by condensation of peptides with the sequence Ala-Pro-Gly or Gly-Pro-Gly were examined as possible substrates or inhibitors for the synthesis of hydroxyproline by protocollagen proline hydroxylase. The tripeptide BOC-Ala-Pro-Gly-OMe (where BOC-represents t-butoxycarboxyl- and Me represents methyl) was not hydroxylated, but oligopeptides ranging in size from BOC(Ala-Pro-Gly)2OMe to BOC(Ala-Pro-Gly)6OMe served as substrates for the synthesis of hydroxyproline. The results indicated that a peptide must contain a minimum of 4 to 6 amino acid residues in order to serve as a substrate, and they supported previous indications that a peptide of more than about 20 residues is required for optimal interaction with the enzyme. The oligopeptides H(Gly-Pro-Gly)2OH and H(Gly-Pro-Gly)4OH were not substrates for the enzyme, but H(Gly-Pro-Gly)4OH was a competitive inhibitor for the hydroxylation of proline in the polymer (Gly-Pro-Pro)n (synthesized as (Pro-Gly-Pro)n). Comparison of H(Gly-Pro-Gly)4OH with H(Pro)12OH indicated that H(Gly-Pro-Gly)4OH was a more effective inhibitor than the proline homopeptide with the same number of amino acid residues. A polymer with the permuted sequence Gly-Pro-Ala had a small inhibitory effect, and it also served as a substrate for the synthesis of hydroxyproline at a small but significant rate.
Phenylglycines, D‐Phenylglycines

Introduction Structure and Nomenclature Derivatives and Usage Production Methods Dynamic Resolution Process Hydantoinase Process Bibliography Keywords: asymmetric hydrolysis; decarbamoylation; dynamic resolution; hydantoin; hydantoinase; d-p-hydroxyphenylglycine; d-phenylglycine; racemization
Taurine attenuates renal disease in chronic puromycin aminonucleoside nephropathy.

Repeated administration of low doses of puromycin aminonucleoside (PAMN) to rats induces a proteinuric renal disease that resembles focal segmental glomerulosclerosis (FSGS). Reactive oxygen molecules may be involved in the progressive course of this nephropathy. Therefore we evaluated whether taurine, an endogenous antioxidant, could limit the extent of renal injury. Sprague-Dawley rats received low-dose injections of PAMN, 2 mg/100 g body wt, over a 12-wk period. Two groups were studied: 1) controls given tap water (n = 23), and 2) an experimental group that drank 1% taurine-supplemented water (n = 22). Taurine-treated nephrotic rats had a reduction in albuminuria, as assessed by the urinary albumin-to-creatinine ratio (26 +/- 4 vs. 44 +/- 4, P less than 0.0001). After 12 wk, creatinine clearance was 0.33 +/- 0.03 (experimental) vs. 0.17 +/- 0.03 ml.min-1.100 g body wt-1 (control) (P less than 0.001), and inulin clearance (n = 6 pairs) was 0.26 +/- 0.04 (experimental) vs. 0.13 +/- 0.02 ml.min-1.100 g body wt-1 (control) (P less than 0.025). Administration of taurine reduced the percentage of segmentally sclerosed glomeruli (9.8 +/- 1.7 vs. 16.2 +/- 1.8%, P less than 0.02) and the tubulointerstitial injury score (1.36 +/- 0.19 vs. 2.61 +/- 0.25, P less than 0.0025) in experimental vs. control rats. Taurine treatment normalized the elevated renal cortical malondialdehyde level in rats with PAMN nephropathy (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Both Memory and CD45RA+/CD62L+ Naive CD4+ T Cells Are Infected in Human Immunodeficiency Virus Type 1-Infected Individuals

Cellular activation is critical for the propagation of human immunodeficiency virus type 1 (HIV-1) infection. It has been suggested that truly naive CD4(+) T cells are resistant to productive HIV-1 infection because of their constitutive resting state. Memory and naive CD4(+) T-cell subsets from 11 HIV-1-infected individuals were isolated ex vivo by a combination of magnetic bead depletion and fluorescence-activated cell sorting techniques with stringent criteria of combined expression of CD45RA and CD62L to identify naive CD4(+) T-cell subsets. In all patients HIV-1 provirus could be detected within naive CD45RA+/CD62L+ CD4(+) T cells; in addition, replication-competent HIV-1 was isolated from these cells upon CD4(+) T-cell stimulation in tissue cultures. Memory CD4(+) T cells had a median of fourfold more replication-competent virus and a median of sixfold more provirus than naive CD4(+) T cells. Overall, there was a median of 16-fold more integrated provirus identified in memory CD4(+) T cells than in naive CD4(+) T cells within a given patient. Interestingly, there was a trend toward equalization of viral loads in memory and naive CD4(+) T-cell subsets in those patients who harbored CXCR4-using (syncytium-inducing) viruses. Within any given patient, there was no selective usage of a particular coreceptor by virus isolated from memory versus naive CD4(+) T cells. Our findings suggest that naive CD4(+) T cells may be a significant viral reservoir for HIV, particularly in those patients harboring CXCR4-using viruses.
Clear-cell adenocarcinoma of the genital tract in young females. Registry report.

Abstract Among 91 Registry cases of vaginal and cervical adenocarcinoma predominantly of the clear-cell type, the patients, eight to 25 years of age, were born throughout the United States and in three foreign countries. Pregnancy histories of 66 of the patients' mothers have been obtained; 49 received stilbestrol or related drugs, nine received unidentified drugs administered because of bleeding or prior pregnancy loss, and eight had a negative history. The dosage and duration of therapy varied widely. The frequent coexistence of vaginal adenosis and occasional presence of transverse vaginal or cervical ridges suggested abnormal development of mullerian epithelium in utero. Seventeen of 65 patients have died or had recurrences despite brief follow-up periods in many cases. Although these cancers are rare, the frequency of asymptomatic cases and the unreliability of vaginal cytology for detection support the value of screening postmenarchal females who have been exposed prenatally to stilbestrol or relate...
Quantum statistical mechanics of dense partially ionized hydrogen

The theory of dense hydrogenic plasmas beginning with the two component quantum grand partition function is reviewed. It is shown that ionization equilibrium and molecular dissociation equilibrium can be treated in the same manner with proper consideration of all two-body states. A quantum perturbation expansion is used to give an accurate calculation of the equation of state of the gas for any degree of dissociation and ionization. In this theory, the effective interaction between any two charges is the dynamic screened potential obtained from the plasma dielectric function. We make the static approximation; and we carry out detailed numerical calculations with the bound and scattering states of the Debye potential, using the Beth-Uhlenbeck form of the quantum second virial coefficient. We compare our results with calculations from the Saha equation.
Excretion of Sulfathiazole in Tears

SummaryThe tears of 14 patients receiving sulfathiazole were quantitatively analyzed. Sulfathiazole was found in all the cases. The concentrations varied from 0.1 mg % to 0.98 mg %.Four patients suffering from sulfathiazole conjunctivitis showed a tear concentration of 0.6 mg %, or more. On the other hand, 6 of 10 patients without conjunctivitis had a tear concentration of 0.56 mg %.A single case of conjunctivitis was observed in which the eye inflammation disappeared without sequelae despite the uninterrupted administration of sulfathiazole.Among 31 consecutive patients receiving sulfathiazole, 5 developed conjunctivitis. In 4 of these the conjunctivitis appeared during a second or a subsequent course of therapy.Conclusions. 1. The amount of sulfathiazole secreted in the tears is not proportional to the blood sulfathiazole concentration.2. The concentration of sulfathiazole in the tears does not of itself appear to be the cause of the conjunctivitis.
Factors affecting acoustic detection and site occupancy of Indiana bats near a known maternity colony

Indiana bats (Myotis sodalis) are capable of exploiting ephemeral resources in structurally complex, interior forests. Consequently, surveying for this species is difficult, and even in areas harboring known populations, documenting presence remains a challenge. We aimed to determine what factors affected probability of detection (p) and site occupancy (Ψ) for Indiana bats when sampling with acoustic bat detectors near an active maternity colony. From May to August 2012 and 2013, we passively sampled 71 random points near Indianapolis, Indiana, with Wildlife Acoustic SM2BAT+ detectors. On average, sampling occurred ∼2.2 km from maternity colony roosts, which contained ≥ 150 bats by mid-July. Habitat and landscape covariates were measured in the field or via ArcGIS. We reduced model covariates with Pearson's correlation and principal component analysis. Indiana bat calls were identified using Bat Call ID software. We used Presence 6.1 software and Akaike's Information Criteria to assess models for detectab...
The N-terminal SH4 Region of the Src Family Kinase Fyn Is Modified by Methylation and Heterogeneous Fatty Acylation ROLE IN MEMBRANE TARGETING, CELL ADHESION, AND SPREADING

The N-terminal SH4 domain of Src family kinases is responsible for promoting membrane binding and plasma membrane targeting. Most Src family kinases contain an N-terminal Met-Gly-Cys consensus sequence that undergoes dual acylation with myristate and palmitate after removal of methionine. Previous studies of Src family kinase fatty acylation have relied on radiolabeling of cells with radioactive fatty acids. Although this method is useful for verifying that a given fatty acid is attached to a protein, it does not reveal whether other fatty acids or other modifying groups are attached to the protein. Here we use matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry to identify fatty acylated species of the Src family kinase Fyn. Our results reveal that Fyn is efficiently myristoylated and that some of the myristoylated proteins are also heterogeneously S-acylated with palmitate, palmitoleate, stearate, or oleate. Furthermore, we show for the first time that Fyn is trimethylated at lysine residues 7 and/or 9 within its N-terminal region. Both myristoylation and palmitoylation were required for methylation of Fyn. However, a general methylation inhibitor had no inhibitory effect on myristoylation and palmitoylation of Fyn, suggesting that methylation occurs after myristoylation and palmitoylation. Lysine mutants of Fyn that could not be methylated failed to promote cell adhesion and spreading, suggesting that methylation is important for Fyn function.
Nonpeptidal P2 Ligands for HIV Protease Inhibitors: Structure-Based Design, Synthesis, and Biological Evaluation

Design and synthesis of nonpeptidal bis-tetrahydrofuran ligands based upon the X-ray crystal structure of the HIV-1 protease-inhibitor complex 1 led to replacement of two amide bonds and a 10 pi-aromatic system of Ro 31-8959 class of HIV protease inhibitors. Detailed structure-activity studies have now established that the position of ring oxygens, ring size, and stereochemistry are all crucial to potency. Of particular interest, compound 49 with (3S,3aS,6aS)-bis-Thf is the most potent inhibitor (IC50 value 1.8 +/- 0.2 nM; CIC95 value 46 +/- 4 nM) in this series. The X-ray structure of protein-inhibitor complex 49 has provided insight into the ligand-binding site interactions. As it turned out, both oxygens in the bis-Thf ligands are involved in hydrogen-bonding interactions with Asp 29 and Asp 30 NH present in the S2 subsite of HIV-1 protease. Stereoselective routes have been developed to obtain these novel ligands in optically pure form.
Nuclear magnetic resonance and 13CH satellite spectra of selenophene and several haloselenophenes

Abstract Proton magnetic resonance spectra and their corresponding 13 CH satellite spectra have been observed at 60 Mc/sec and analyzed for selenophene and a number of its mono- and disubstituted halogen derivatives. Estimates of anisotropy effects produced by the substituents have also been applied to the chemical shift values. All of the parameters obtained have been compared with the corresponding values in the analogous thiophenes and in furan.
PKCδ regulates endothelial basal barrier function through modulation of RhoA GTPase activity

Abstract We have shown that PKCδ enhanced microvascular endothelial basal barrier function, correlating with elevated RhoA GTPase activity and increased focal contact formation. In the current study, we investigated signaling pathways important in PKCδ modulation of barrier function in unstimulated endothelial cell monolayers by assessing the effects of PKCδ inhibition in endothelial cells (EC) derived from rat pulmonary artery (PAEC) and epididymus (FPEC). Rottlerin exposure or Ad PKCδdn infection significantly enhanced monolayer permeability in both EC. Immunofluorescence analyses demonstrated fewer stress fibers and focal contacts in rottlerin-treated or Ad PKCδdn-infected EC; yet, PKCδ inhibition caused no significant changes in microtubule structures. These changes correlated with a reduction in both focal adhesion kinase (FAK) and RhoA GTPase activities. Microfilament stabilization significantly attenuated the focal contact and barrier disruptive effects of rottlerin. FAK overexpression did not blunt the effects of rottlerin-induced barrier dysfunction or stress fiber and focal contact disruption. Conversely, GFP-linked dominant active RhoA overexpression protected EC from stress fiber and focal contact disruption induced by both rottlerin exposure and overexpression of PKCδ dominant negative protein. Additionally, PKCδ immunoprecipitated with p190RhoGAP and p120RasGAP, modulators of RhoA activity. Thus, PKCδ may regulate basal endothelial barrier function by stabilizing microfilaments and focal contacts by regulating RhoA GTPase activity through upstream modulators, p190RhoGAP and p120RasGAP.
The S phase: Beginning, middle, and end: A perspective

Events in the S phase of the cell cycle have been investigated to a relatively limited extent in comparison with those in G1 and M phases. Four aspects of S are briefly discussed in this report: (1) the final biochemical step permitting initiation of DNA synthesis, (2) determination of replication timing of individual genes and its mechanism, (3) S phase processes that lead to the onset of M phase, and (4) resetting the S-phase machinery. J. Cell. Biochem. Suppls. 30/31:1-7, 1998. © 1999 Wiley-Liss, Inc.
Non cystic fibrosis bronchiectasis.

Bronchiectasis (Bx), an old disease, was a popular topic of study mid last century producing a series of articles in 1956– 1963describing thecharacteristicsof affectedchildrenbefore falling into relative obscurity. However a resurgence in the literature since the late 1990s has resulted in similar descriptions demonstrating clear concern about the incidence of children affected, particularly in certain communities – Alaskan native, Aboriginal, Maori & Pacific Islanders, Turkish with rates (likely underestimated) at between 0.2–14.7/ 1,000. There have only been 2 national studies of incidence in children to date – Finland at 0.5/100,000 and New Zealand at 3.7/100,000. Diagnosis has moved from autopsy tobronchography toHRCTscanwith criteria defined as lack of normal tapering, bronchi with an internal diameter greater than the external diameter of the accompanying artery, or visualization of bronchi within 1 cm of the pleura. Concern also surrounds the severity of the disease in those diagnosed. The paediatric studies that describe the degree of lung involvement give this as 39–82% with 4 or more lobes involved, 61–93% with bilateral disease and only 9%, 29% and 43% with single lobe involvement. TB, pertussis, measles and certain types of adenovirus are traditionally implicated. In the more recent series, aetiology has been ascribed to infection 25–95%, unknown 0–50% (noting that those less willing to ascribe to infectious disease without definitive proof had higher numbers in the unknown category), aspiration including foreign body 4–10%, immunodeficiency 0–17%, cilia abnormalities 0–13%. However, recognise with these figures that not all investigations were done in all the populations. The infections above are still apparent, but more now are secondary to pneumonia with organisms unknown. A history of hospitalized pneumonia gave a relative risk of 15.2 for developing Bx, and associations were also strong with recurrent hospitalised pneumonia,
PCR‐Based Detection of Artificial Latent Infections of Geranium by Xanthomonas campestris pv. pelargonii

A procedure entailing biological enrichment and PCR amplification was developed to detect small populations of Xanthomonas campestris pv. pelargonii (X.c, pv. pelargonii) in tissues of geranium. Known numbers of colony forming units (CFU) of X.c. pv. pelargonii were introduced into ‘Red Elite’ geraniums through wounding of petioles and stems. Immediately after inoculation, sections of the petioles and stems were harvested and incubated for 24 or 48 h in nutrient broth (biological enrichment). After enrichment, bacterial cells were collected by centrifugation, followed by rapid extraction of total nucleic acid from the cells with GeneReleaser™, PCR amplification of DNA with pathovar-specific primers, and ethidium bromide-stained agarose gel electrophoretic analysis of the PCR products. After 48 h biological enrichment, it was possible to detect as few as 1 CFU of Xc. pv. pelargonii in stems and petioles collected immediately after inoculation, with the detection limit ranging between 1 and 120 CFU during multiple experiments. It also was possible to detect systemic movement of the bacterium in intact plants sampled 24 h after inoculation with a minimal inoculum (4 CFU). This procedure may have application in geranium certification programs concerned with the detection of latent infections associated with low levels of X.c.pv. pelargonii. Zusammenfassung Erarbeitet wurde eine Methode, die durch biologische Anreicherung und PCR-Amplifikation den Nachweis von kleinen Populationen von Xanthomonas campestris pv pelargonii (X.c.pv. pelargonii) im Geraniengewebe ermoglicht. Eine bekannte Anzahl von kolonienbildenden Einheiten (CFU) von X.c, pv. pelargonii wurden durch Verletzungen in Blattstielen bzw. Stengeln der Geraniensorte Red Elite inokuliert. Unmittelbar nach der Inokulation wurden Teile der Blattstiele und Stengel genommen und in Nutrientbroth (eine biologische Anreicherung) fur 24 oder 48 Std. inkubiert. Die Bakterienzelien wurden durch Zentrifugieren nach der Anreicherung gewonnen. Danach folgte eine rasche Extraktion der gesamten Nukiearsaure aus den Zelien mit GeneReieaser™, eine PCR-Amplifikation der DAN mit pathovar-spezifischen Primern und anschlieβend eine Ethidiumbro-midfarbung der Agarosegelelektrophoreseanalyse der PCR-Produkte. Nach einer biologischen Anreicherung von 48 Std. war es moglich 1 CFU von X.c. pv. pelargonii in Blattstiel-und Stengelteilen nachzuweisen, die sofort nach der Inokulation gesammelt worden waren. Die Nachweisgrenze lag nach mehreren Versuchen zwischen 1 und 120 CFU. Auβerdem war eine systemische Verlage-rung des Bakteriums in intakten Pflanzen, die 24 Std. nach der Inokulation beprobt wurden, mit einem minimalen Inokulum (4 CFU) nachzuweisen. Die hier beschriebene Methode konnte Anwendung bei Zertifikationsprogrammen finden, die sich mit der Nach-weisbarkeit von latenten Infektionen von niedrigeren X.c. pv. pelargonii-Leveh befassen.
Tricritical Universality in Two Dimensions

A powerful, new extension of the Monte Carlo renormalization-group (MCRG) method is used to accurately determine the tricritical point and exponents in two very different two-dimensional models: an Ising antiferromagnet and a Blume-Capel model. We find four relevant tricritical eigenvalues which are essentially identical for both models. We also demonstrate that subtle warning signals appear in a standard Monte Carlo calculation when a second-order transition is being misinterpreted as first order.