cssi/SciSciGPT-SciSciNet huggingface dataset:
Comparison of the effects of a new conjugated oral estrogen, estradiol-3β-glucoside, with oral micronized 17β-estradiol in postmenopausal women

The objective of this article is to evaluate the pharmacokinetics of serum estrone and estradiol levels in women who were taking either 17β-estradiol-3β-glucoside (E 2 -3β-glucoside) or 17β-estradiol (E 2 ) daily and to examine the effects of E 2 -3β-glucoside and E 2 on postmenopausal symptoms, gonadotropins, hepatic metabolism, and coagulation factors. Healthy postmenopausal women on estrogen who had undergone a hysterectomy were recruited. Subjects were randomly assigned to receive equivalent doses of either E 2 -3β-glucoside or micronized E 2 for 28 days. Pharmacokinetic studies of estrone and estradiol were performed on days 1, 2, 28, and 29. Gonadotropin levels and Kupperman Index (KI) scores were determined at baseline and on treatment day 28. Mean serum estradiol and estrone concentrations in those taking E 2 -3β-glucoside were comparable with those taking E 2 . Mean baseline follicle stimulating hormone (FSH) levels were 84 ± 27 mIU/mL and 71 ± 24 mIU/mL in the E 2 -3β-glucoside and E 2 groups, respectively, with significant decreases ( P 2 -3β-glucoside group were 10 ± 6 compared with 5 ± 4 on treatment day 28, which is equivalent to a 50% reduction in menopausal symptoms ( P = 0.003). The change in KI scores in the E 2 group was not statistically significant. Total serum estradiol and estrone levels in women taking E 2 -3β-glucoside are comparable with those in women taking E 2 . E 2 -3β-glucoside reduces serum gonadotropin levels to the premenopausal range and is effective at reducing postmenopausal symptoms. E 2 -3β-glucoside is a novel synthetic estrogen that is well tolerated and has promise as a hormone replacement therapy.
The effect of luteinizing hormone on the ultrastructure of the leydig cell of the chick

Leydig cells from testes of two-day-old chicks show a decrease in the size of the lipid droplets, an increase in rough endoplasmic reticulum, the appearance of bizarre mitochondrial shapes and the striking development of polysomes after stimulation with luteinizing hormone in a dosage known to stimulate testosterone synthesis.
Ozone, nitric acid, and ammonia air pollution is unhealthy for people and ecosystems in southern Sierra Nevada, California.

Abstract Two-week average concentrations of ozone (O 3 ), nitric acid vapor (HNO 3 ) and ammonia (NH 3 ) were measured with passive samplers during the 2002 summer season across the central Sierra Nevada Mountains, California, along the San Joaquin River drainage. Elevated concentrations of the pollutants were determined with seasonal means for individual sites ranging between 62 and 88 ppb for O 3 , 1.0–3.8 μg m −3 for HNO 3 , and 2.6–5.2 μg m −3 for NH 3 . Calculated O 3 exposure indices were very high, reaching SUM00-191 ppm h, SUM60-151 ppm h, and W126-124 ppm h. Calculated nitrogen (N) dry deposition ranged from 1.4 to 15 kg N ha −1 for maximum values, and 0.4–8 kg N ha −1 for minimum values; potentially exceeding Critical Loads (CL) for nutritional N. The U.S., California, and European 8 h O 3 human health standards were exceeded during 104, 108, and 114 days respectively, indicating high risk to humans from ambient O 3 .
Comparison of two alternative forms of polysilole: Another quasidegenerate polymer?

Abstract Two alternative structures of the five-membered ring form of the -[-C4H2SiR2-]n- polymer have been considered. Full geometry optimization indicates, that the structure with the two endocyclic double bonds, 1, is less stable, by about 2 kcal/mol than the other one containing one endo- and one exocyclic double bonds per repeat unit. Polymer 1 has a rather low band gap of 1.44 eV, in contrast to the experimental value of 2 eV, while 3 has a calculated band gap of 1.95 eV. Therefore, this structure is more consistent with the experimental absorption spectrum of the polymer than structure 1. As discussed in our previous report, an alternative structure 2 with 4 membered rings, polydiethynylsilane, although less stable is also consistent with the absorption spectrum.
Age-related changes in pineal "synaptic" ribbon populations in rats exposed to continuous light or darkness.

“Synaptic” ribbon (SR) populations in the rat pineal gland were analyzed morphometrically at various ages from birth to early adulthood. The rats were born and raised in continuous light or continuous darkness. SR numbers were high irrespective of the presence or absence of light during the early neonatal period. However, SR numbers decreased substantially during the second neonatal week of continuous light, remaining low at subsequent ages, including early adulthood. In contrast, SR numbers apparently remained elevated during continuous darkness at various ages from the early neonatal period to early adulthood. Stimulation of pineal adrenergic receptors with L-isoproterenol during continuous light resulted in an acute, reversible increase in SR numbers; blockade of these receptors with L-propranolol during continuous darkness resulted in an acute decrease in SR numbers. These results indicate that light-mediated changes in SR populations were (1) age related and (2) related to some component of the pineal beta-adrenergic receptor mechanism. A hypothesis that SR formation may be related to beta-adrenergic receptor-associated membrane turnover is presented.
CHROMOSOMAL EVOLUTION IN RHOGEESSA (CHIROPTERA: VESPERTILIONIDAE): POSSIBLE SPECIATION BY CENTRIC FUSIONS

Within the Rhogeessa tumida-parvula complex, there are seven cytotypes involving diploid numbers of 30, 32, 34, 42, 44, and 52. Based on G-band analysis, the 30, 32, 34, and 44 forms differ from each other by centric fusions (13 different fusions were identified). Two 2n = 32 samples (one from Belize and one from Nicaragua) having essentially identical standard karyotypes differed from each other by eight fusion events. Cytotypes are allozymically distinct; however, other studies indicate that the cytotypes are morphologically very similar if not indistinguishable (LaVal, 1973; Baker, 1984). G-band chromosomal data are best interpreted as indicating that, within this complex, several species exist which should be maintained by a post-mating isolating mechanism resulting from meiotic problems in F1 individuals. Mus musculus (Capanna et al., 1977; Capanna, 1982; White, 1978) and the Rhogeessa tumida-parvula complex are unusual among mammalian species thus far studied in their pattern of chromosomal variation and presumptive mode of speciation. Strong evidence exists suggesting that in both groups populations differing by multiple centric fusions are biological species. It appears that the population and reproductive biology of Mus and Rhogeessa are quite different and any model that attempts to explain the mode of speciation in these two diverse taxa, must be compatible with their different biological characteristics.
Acquisition and extinction phenomena in human trial-and-error learning under different schedules of reinforcing feedback.

The present program of research on non-verbal selective learning (Noble, 1957a) considers reinforcement ( G ) factors as a major class of experimental variables in human learning and performance. This paper describes an investigation designed to obtain quantitative information about the role of reinforcing feedback schedules in four-choice serial trial-and-error learning by human Ss who performed on the Selective Mathometer. Two widely-accepted generalizations about the effects of partial reinforcement in simple learning situations are ( 1 ) that acquisition rates are faster the higher [he relative frequency of reinforcement and ( 2 ) that resistance to extinction is greater the lower the relative frequency of reinforcement during original learning (Jenkins & Stanley, 1950; Lewis, 1960). Since these two principles are complicated by interactions with task factors, amount of practice, and species differences (Spence, 1960, pp. 91-112), it is necessary to test them under the specific boundary conditions of this research program where human Ss are engaged in complex learning problems for incentives which are not primary. The most comprehensive review of motor-skills learning to date (E. A. Bilodeau & I. McD. Bilodeau, 1961) emphasizes the paucity of our knowledge about frequency schedules in this area.
Perceptions of Longevity and Successful Aging in Very Old Adults

We examined perceptions of longevity and successful aging in young-old (60 to 74 years), old-old (75 to 89 years), and oldest-old (90+ years) adults drawn from the Louisiana Healthy Aging Study. Pa...
Interleukin 2 immediately after autologous bone marrow transplantation for acute lymphoblastic leukemia--a phase I study.

Despite intensive conditioning and marrow purging, leukemia relapse frequently follows autologous BMT for acute lymphoblastic leukemia. To generate antileukemic immunologic activity, we performed a phase I study using recombinant human interleukin 2 given immediately posttransplantation. This early
A troubleshooting guide to the subcutaneous epidural implantable reservoir

Abstract The use of intraspinal narcotics to relieve pain of malignant origin represents a great advance in cancer pain management. Implantation of subcutaneous intraspinal narcotic delivery systems for pain relief has been used with minimal complications. Occasionally problems arise. The purpose of this article is to review the various causes of reservior failure, their diagnosis, and the methods to correct them.
BOOLEAN NETWORK AND SIMMELIAN TIE IN THE CO-AUTHOR MODEL: A STUDY OF DYNAMICS AND STRUCTURE OF A STRATEGIC ALLIANCE MODEL

This article explains a simulation of the Co-Author Model (CAM) applied in strategic alliance setting where firms use and optimize their network resources. To understand its process casualty better, I explain the model's mechanisms in terms of its interactive dynamics and resulting equilibrium structure. Classified as a Boolean network with two inputs, CAM's dynamics cause a biased equilibrium structure that could then be explained by the Simmelian tie and the completion of structure through structural balance. These explanations not only could answer the criticism that a simulation model is merely a toy model without much realism but could also explain and give insights to both substantive theory and methodology development in strategic alliance research. The results include the effect of a third party, the embeddedness of firms in their alliances, and the real-world implications of the "frozen web": a phenomenon drawn parallel to the financial crisis beginning in 2007.
STRUCTURE-BASED METHODS FOR COMPUTATIONAL PROTEIN FUNCTIONAL SITE PREDICTION

Due to the advent of high throughput sequencing techniques and structural genomic projects, the number of gene and protein sequences has been ever increasing. Computational methods to annotate these genes and proteins are even more indispensable. Proteins are important macromolecules and study of the function of proteins is an important problem in structural bioinformatics. This paper discusses a number of methods to predict protein functional site especially focusing on protein ligand binding site prediction. Initially, a short overview is presented on recent advances in methods for selection of homologous sequences. Furthermore, a few recent structural based approaches and sequence-and-structure based approaches for protein functional sites are discussed in details.
The Activation of MAPK in Melanoma Cells Resistant to BRAF Inhibition Promotes PD-L1 Expression That Is Reversible by MEK and PI3K Inhibition

Purpose: Selective BRAF inhibition (BRAFi) provides a paradigm shift for melanoma treatment. The duration of benefit is typically limited before resistance develops. Interest remains in combining targeted and immune therapies to overcome resistance and improve durability of clinical benefit. One mechanism of evading immune destruction is programmed death-1-ligand 1 (PD-L1) expression by tumors that results in potent antitumor immune suppression. Experimental Design: BRAFi-resistant melanoma cells were examined for changes in PD-L1 expression by immunoblot and flow cytometry. Signaling pathways involved in altering PD-L1 expression were examined. Strategies to maximize the effect of the BRAFi therapy were studied including MEKi, MEKi combinations, and additional pathways including phosphoinositide-3 kinase (PI3K). Results: Melanoma cells resistant to BRAFi exhibit increased MAPK signaling and promotion of PD-L1 expression. PD-L1 expression is transcriptionally modulated by c-Jun and augmented by STAT3. MEK inhibition (MEKi) regains downregulation of MAPK signaling and suppresses the production of PD-L1. MEKi in melanoma cells shows dual therapeutic effects with simultaneous suppression of PD-L1 expression and induction of apoptosis. By combining MEKi with BRAFi, an additive effect on the inhibition of PD-L1 expression results. Conclusions: We report a novel mechanism that suppresses preexisting immune responses in patients with melanoma receiving BRAFi therapy. BRAFi resistance leads to increased expression of PD-L1 in melanoma cells, mediated by c-Jun and STAT3. MEKi may be feasible to counteract BRAFi resistance of MAPK reactivation and also for the additive effect of PD-L1 suppression. Potential therapeutic benefits of combining targeted inhibitors and immune modulation to improve patient outcomes should be investigated. Clin Cancer Res; 19(3); 598–609. ©2012 AACR .
Comparison of slurry and dry erosion behaviour of some HVOF thermal sprayed coatings

The performance of 10 high velocity oxy-fuel (HVOF) sprayed coatings has been evaluated under both dry particle and slurry erosion conditions at 90° and 20° impingement angles. The coatings were six WC cermets with Co- or Ni-based matrices, a Cr3C2–NiCr composite and three metallic alloys. Slurry jet erosion experiments were carried out using a 9 wt.% alumina/water slurry with 35 and 200 μm angular alumina particles, at an impingement velocity of 15 m/s and flow rate of 18 l/min in a re-circulating loop apparatus. Dry erosion was effected in a once-through mode with 50 μm diameter alumina particles at a velocity of 84 m/s and feed rate of 2 g/min. Dry erosion rates three orders of magnitude greater than slurry erosion rates were due mainly to the differences in actual particle-target impact velocities. Coating composition, microstructural integrity and hardness were the major determinants of relative erosion resistance in all tests, with matrix corrosion resistance influencing the surface damage resistance of cermets in longer duration aqueous slurry tests.
Collisional relaxation of the three vibrationally excited difluorobenzene isomers by collisions with CO2: effect of donor vibrational mode.

Relaxation of highly vibrationally excited 1,2-, 1,3-, and 1,4-difluorobenzne (DFB) by collisions with carbon dioxide has been investigated using diode laser transient absorption spectroscopy. Vibr...
Alteration of baroreceptor and chemoreceptor reflexes in spontaneously hypertensive rats.

Summary 1. Electrical stimulation of the aortic depressor nerve elicited depressor and bradycardiac responses in both spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats, but in spontaneously breathing animals responses were weaker in SHR than in WKY. 2. Responses did not significantly differ in artificially ventilated animals except that high stimulation intensity elicited significantly greater bradycardiac responses in WKY. A decrease in ventilatory rate occurred in both strains. 3. Electrical stimulation of the carotid sinus nerve (CSN) elicited an initial pressor response followed by a depressor response with a minimal change in heart rate in either strain. The pressor response in SHR was greater than in WKY. Depressor responses in SHR were weaker than those in WKY with or without artificial ventilation. CSN stimulation increased ventilatory rate in both strains but the frequency-related responses differed at higher stimulation intensity. 4. These results suggest that there are alterations in the function of central or afferent components of chemoreceptor and baroreceptor reflexes in SHR in addition to previously described structural changes at the level of peripheral sensory receptors.
Minimally important difference in diffuse systemic sclerosis : results from the D-penicillamine study

Objective: To estimate minimally important differences (MIDs) in scores for the modified Rodnan Skin Score (mRSS) and Health Assessment Questionnaire—Disability Index (HAQ-DI) in a clinical trial on diffuse systemic sclerosis (SSc). Participants and methods: 134 people participated in a 2-year, double-blind, randomised clinical trial comparing efficacy of low-dose and high-dose d-penicillamine in diffuse SSc. At 6, 12, 18 and 24 months, the investigator was asked to rate the change in the patient’s health since entering the study: markedly worsened, moderately worsened, slightly worsened, unchanged, slightly improved, moderately improved or markedly improved. Patients who were rated as slightly improved were defined as the minimally changed subgroup and compared with patients rated as moderately or markedly improved. Results: The MID estimates for the mRSS improvement ranged from 3.2 to 5.3 (0.40–0.66 effect size) and for the HAQ-DI from 0.10 to 0.14 (0.15–0.21 effect size). Patients who were rated to improve more than slightly were found to improve by 6.9–14.2 (0.86–1.77 effect size) on the mRSS and 0.21–0.55 (0.32–0.83 effect size) on the HAQ-DI score. Conclusion: MID estimates are provided for improvement in the mRSS and HAQ-DI scores, which can help in interpreting clinical trials on patients with SSc and be used for sample size calculation for future clinical trials on diffuse SSc.
Activation of diverse signaling pathways by ex-vivo delivery of multiple cytokines for myocardial repair.

We tested the hypothesis that simultaneous transgenic overexpression of a select quartet of growth factors activates diverse signaling pathways for mobilization and participation of various stem/progenitor cells for cardiogenesis in the infarcted heart. Human insulin growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), stromal cell–derived factor-1 (SDF-1a), and hepatocyte growth factor (HGF) plasmids were synthesized and transfected into skeletal myoblasts (SM) from young male wild-type or transgenic rats expressing green fluorescent protein (GFP). Overexpression of growth factors in transfected SM (TransSM) was confirmed by reverse transcription polymerase chain reaction, western blotting, and fluorescence immunostaining. Using our custom-made growth factor array and western blotting, multiple angiogenic and prosurvival factors were detected in TransSM, including secreted frizzled related protein-1,2,4,5, matrix metalloproteinases-3 and 9, connexin-43, netrin-1, Nos-2, Wnt-3, Akt, MAPK42/...
Black–White Achievement Gap and Family Wealth

This article examines the extent to which family wealth affects the Black–White test score gap for young children based on data from the Panel Study of Income Dynamics (aged 3–12). This study found little evidence that wealth mediated the Black–White test scores gaps, which were eliminated when child and family demographic covariates were held constant. However, family wealth had a stronger association with cognitive achievement of school-aged children than that of preschoolers and a stronger association with school-aged children’s math than on their reading scores. Liquid assets, particularly holdings in stocks or mutual funds, were positively associated with school-aged children’s test scores. Family wealth was associated with a higher quality home environment, better parenting behavior, and children’s private school attendance.
The Deployment Page: Integrated real time views of tools, operations, and lots: ASMC 2011 data management

Running a semiconductor manufacturing facility with a large product portfolio creates unique challenges for knowledge management. Complex process controls, tool configurations, and wide ranges of roles and responsibility can quickly lead to increasing information technology (IT) support requirements with decreasing effectiveness. The IBM Burlington 200mm manufacturing facility has successfully met some of these challenges with an effective and efficient knowledge management system known simply as “The Deployment Page” (TDP). Through integration of key pieces of information, this system has successfully built a foundation to enable standardized work for deploying resources, both people and equipment, across a wide range of roles and responsibilities. At the heart of this system is the integrated view of tools, operations and lots. This paper will cover some of the basics of TDP, its evolution in use, planned future enhancements and some examples of how it is used.
Optimizing electrotransfection of Mammalian cells in vitro.

Abstract INTRODUCTION This protocol describes transfection of plasmid DNA into mammalian cell lines using electroporation, a process whereby external application of electric pulses induce cell membrane permeability. A number of factors can affect electrotransfection efficiency. In general, cells in suspension and small volume cells are difficult to transfect, whereas adherent cells and large volume cells are relatively easy. Regardless of cell size or phenotype, transfection efficiency increases with a high concentration of cells in a small volume. The use of plasmid DNA larger than 13 kb reduces transfection efficiency. One important variable is the choice of electroporation buffer--the appropriate buffer can increase cell transfection efficiency 50-98%. Generally, buffers with low ionic constants enhance transfection efficiency.
Physical and biochemical characterization of cloned sbcB and xonA mutations from Escherichia coli K-12.

Abstract In Escherichia coli K-12, sbcB/xonA is the structural gene for exonuclease I, an enzyme that hydrolyzes single-stranded DNA to mononucleotides in the 3'-to-5' direction. This enzyme has been implicated in the DNA repair and recombination pathways mediated by the recB and recC gene products (exonuclease V). We have cloned several sbcB/xonA mutant alleles in bacterial plasmids and have partially characterized the cloned genes and their protein products. Two of the mutations (xonA2 and xonA6) retain no detectable exonucleolytic activity on single-stranded DNA. The xonA6 allele was shown to harbor an insertion of an IS30-related genetic element near the 3' end of the gene. Two other mutations, sbcB15 and xonA8, exhibited significantly reduced levels of exonuclease I activity as compared to the cloned wild-type gene. A correlation was observed between levels of exonuclease I activity and the ability of the sbcB/xonA mutations to suppress UV sensitivity in recB and recC strains. Also, recombinant plasmids bearing either the sbcB15 or xonA6 allele exhibited a high degree of instability during growth of their bacterial hosts. The results suggest that the sbcB/xonA gene product is a bi- or multifunctional protein that interacts with single-stranded DNA and possibly with other proteins in the suppression of genetic recombination and DNA-repair deficiencies in recB and recC mutants.
Progenitor cells confer plasticity to cardiac valve endothelium.

The endothelium covering the aortic, pulmonary, mitral, and tricuspid valves looks much like the endothelium throughout the vasculature, in terms of general morphology and expression of many endothelial markers. Closer examination, however, reveals important differences and hints of a unique phenotype that reflects the valvular endothelium's embryonic history, and potentially, its ability to maintain integrity and function over a life span of dynamic mechanical stress. A well-studied property that sets the cardiac valvular endothelium apart is the ability to transition from an endothelial to a mesenchymal phenotype—an event known as epithelial to mesenchymal transition (EMT). EMT is a critical step during embryonic valvulogenesis, it can occur in post-natal valves and has recently been implicated in the adaptive response of mitral valve leaflets exposed to a controlled in vivo setting designed to mimic the leaflet tethering that occurs in ischemic mitral regurgitation. In this review, we will discuss what is known about valvular endothelial cells, with a particular focus on post-natal, adult valves. We will put forth the idea that at subset of valvular endothelial cells are progenitor cells, which may serve to replenish valvular cells during normal cellular turnover and in response to injury and disease.
Modeling in Engineering: The Role of Representational Fluency in Students' Conceptual Understanding

Background Modeling abilities play an important role in engineering. The creation and use of representations is a central aspect of modeling, and students who are learning to model often use a variety of representations to express, test, revise, and communicate their own thinking. Consequently, model development often depends on representational fluency and the ability to translate between and within different representational forms. Purpose This study investigates the role that representations and representational fluency play in conceptual understanding during a complex modeling task related to heat transfer. Design/Method This study involved 16 teams of 3 or 4 college students in a first-semester heat transfer course participating in a complex modeling task. The task of the student teams was to develop a model to predict the interface temperature and the sensation felt by human skin when touching a utensil made of a given material at a given temperature. Data sources included audio recordings of student teams, as well as student-generated artifacts. Results The results show teams thinking about their model through multiple representations and through translations within and among representations. Students' early ways of thinking used a variety of interacting representations but were often unstable and involved incomplete notions of the system to be modeled. Model development involved increasing representational fluency as well as parallel and interacting progress along a variety of dimensions. Conclusions This study furthers the understanding of representational fluency in undergraduate engineering students in a heat transfer setting and how representational fluency contributes to conceptual and application understanding.
Student Walkout: A Fortuitous Examination of Elementary Collective Behavior

The traditional separation of explanations of collective behavior and routine social behavior is noted. Blumer's work is examined as representative of and influential in maintaining this separation. Participants' reports of the initiation and development of an elementary form of collective behavior are presented. This case study records repeated examples of the processes Blumer and others have restricted to routine social behavior and thus challenges the separation they have maintained. These data are used to illustrate some rudimentary principles which are applicable to the production, maintenance, and alteration of lines of social behavior in routine and collective behavior settings.
A Genetic Approach to Mammalian Glycan Function

▪ Abstract The four essential building blocks of cells are proteins, nucleic acids, lipids, and glycans. Also referred to as carbohydrates, glycans are composed of saccharides that are typically linked to lipids and proteins in the secretory pathway. Glycans are highly abundant and diverse biopolymers, yet their functions have remained relatively obscure. This is changing with the advent of genetic reagents and techniques that in the past decade have uncovered many essential roles of specific glycan linkages in living organisms. Glycans appear to modulate biological processes in the development and function of multiple physiologic systems, in part by regulating protein-protein and cell-cell interactions. Moreover, dysregulation of glycan synthesis represents the etiology for a growing number of human genetic diseases. The study of glycans, known as glycobiology, has entered an era of renaissance that coincides with the acquisition of complete genome sequences for multiple organisms and an increased focus ...
Automated validation test generation

This paper describes our experience with requirements-based validation test generation of Electronic Flight Instrumentation System (EFIS) software for small commercial jets. In 1992, Honeywell Technology Center (HTC) began a long-term project to develop a fine-grained EFIS requirements domain model using object-oriented techniques. Our long-range objectives were to automate the generation of software life-cycle artifacts such as system requirements documentation, test matrix, test software, and graphical prototypes based on the EFIS requirements model and demonstrate their reusability across various products. In 1993, to help justify the continuation of the work, we established a short-term objective of automatically generating requirements-based tests used in the V&V of the aircraft display software. We developed rule-based requirements models that described both the static and dynamic characteristics of the aircraft display system. The test generator algorithms used these rule-based requirements models along with information about the testing apparatus and policy-rich testing methodology to automatically generate test plans, automated test equipment (ATE) code, and expected test results. This paper focuses on our process of automating V&V test artifacts, the challenges we faced, the algorithms we developed, and the benefits we realized. We'll also briefly discuss our ongoing efforts in automating additional display software life-cycle artifacts. >
Glial Cell-Line Derived Neurotrophic Factor-Mediated RET Signaling Regulates Spermatogonial Stem Cell Fate

Normal spermatogenesis is essential for reproduction and depends on proper spermatogonial stem cell (SSC) function. Genes and signaling pathways that regulate SSC function have not been well defined. We report that glial cell-line-derived neurotrophic factor (GDNF) signaling through the RET tyrosine kinase/GFRA1 receptor complex is required for spermatogonial self-renewal in mice. GFRA1 and RET expression was identified in a subset of gonocytes at birth, was restricted to SSCs during normal spermatogenesis, and RET expressing cells were abundant in a cryptorchid model of SSC self-renewal. We used the whole-testis transplantation technique to overcome the limitation of neonatal lethality of Gdnf-, Gfra1-, and Ret-deficient mice and found that each of these genes is required for postnatal spermatogenesis and not for embryological testes development. Each mutant testis shows severe SSC depletion by Postnatal Day 7 during the first wave of spermatogenesis. These defects were due to lack of SSC proliferation and an inability of SSCs to maintain an undifferentiated state. Our results demonstrate that GDNF-mediated RET signaling is critical for the fate of undifferentiated spermatogonia and that abnormalities in this pathway may contribute to male infertility and testicular germ cell tumors.
The dilemma of negative analysis of variance estimators of intraclass correlation

At least two common practices exist when a negative variance component estimate is obtained, either setting it to zero or not reporting the estimate. The consequences of these practices are investigated in the context of the intraclass correlation estimation in terms of bias, variance and mean squared error (MSE). For the one-way analysis of variance random effects model and its extension to the common correlation model, we compare five estimators: analysis of variance (ANOVA), concentrated ANOVA, truncated ANOVA and two maximum likelihood-like (ML) estimators. For the balanced case, the exact bias and MSE are calculated via numerical integration of the exact sample distributions, while a Monte Carlo simulation study is conducted for the unbalanced case. The results indicate that the ANOVA estimator performs well except for designs with family size n = 2. The two ML estimators are generally poor, and the concentrated and truncated ANOVA estimators have some advantages over the ANOVA in terms of MSE. However, the large biases may make the concentrated and truncated ANOVA estimators objectionable when intraclass correlation (ϱ) is small. Bias should be a concern when a pooled estimate is obtained from the literature since ϱ<0.05 in many genetic studies.
The High Mobility Group Protein 1 Is a Coactivator of Herpes Simplex Virus ICP4 In Vitro

ICP4 is an activator of herpes simplex virus early and late gene transcription during infection and in vitro can efficiently activate the transcription of a core promoter template containing only a TATA box and an initiator element. In this study, we noted that the extent of activation by ICP4 in vitro was highly dependent on the purity of TFIID when recombinant TFIIB, TFIIE, and TFIIF were used as sources of these factors. ICP4 efficiently activated transcription with a crude TFIID fraction. However, when immunoaffinity-purified TFIID was used in place of the less pure TFIID, ICP4 activated transcription to a significantly lesser extent. This finding indicated that the crude TFIID fraction may contain additional factors that serve as coactivators of ICP4. To test this hypothesis, the crude TFIID preparation was further fractionated by gel filtration chromatography. The TFIID that eluted from the column lacked the hypothesized coactivator activity. A fraction well separated from TFIID contained an activity that when added with the TFIID fraction resulted in higher levels of transcription in the presence ICP4. Further purification of the coactivator-containing fraction resulted in the isolation of a single 30-kDa polypeptide (p30). p30 was also shown to serve as a coactivator of ICP4 with immunoaffinity-purified TFIID; however, p30 had no effect on basal transcription. Amino acid sequence analysis revealed that p30 was the high mobility group protein 1, which has been shown to facilitate the formation of higher-order DNA-protein complexes.
Expression and distribution of thiol-regulating enzyme glutaredoxin 2 (GRX2) in porcine ocular tissues.

Glutaredoxin2 (Grx2) is a mitochondrial isozyme of the cytosolic glutaredoxin1 (thioltransferase or TTase). Both belong to the large oxidoreductase family and play an important role in maintaining thiol/disulfide redox homeostasis in the cells. Grx2 is recently found in the lens where its activities of disulfide reductase and peroxidase, similar to TTase, can protect the lens against oxidative stress. Since other eye tissues are also highly sensitive to oxidative stress, and TTase's distribution in the eye is known, we focused on this study by investigating the Grx2 distribution in the ocular tissues in comparison to the lens. Fresh porcine eyes were dissected into cornea, iris, ciliary body, the lens, vitreous humor, retina, and optic nerve. Each tissue (pooled from three eyes) was homogenized and processed for mitochondrial isolation. The mitochondrial fraction was analyzed for Grx2 protein using Western blotting with anti-Grx2 antibody, and Grx2 activity using the published procedure. The eye tissues were also measured for Grx2 mRNA expression by RT-PCR with GAPDH as the control. Grx2-rich mouse liver and purified recombinant mouse Grx2 were used as positive controls for the above analyses. It was found that Grx2 was present in all the tested ocular tissues, except vitreous humor. In comparison with the mouse liver, the protein levels of Grx2 in porcine ciliary body and the lens were 27-fold and 0.75-fold, respectively. Comparing to the lens, Grx2 protein was highest in the ciliary body (13.5-fold), followed by retina (9.2-fold), iris and optic nerve (2-fold), and cornea (1.2-fold). Enzyme activity assays showed that the retina had the highest Grx2 specific activity (3.9 mU/mg protein), followed by ciliary body (3.1 mU/mg), the lens (0.58 mU/mg), and optic nerve (0.32 mU/mg). Grx2 gene expression in these ocular tissues was further confirmed by RT-PCR analysis. Grx2 mRNA expression showed the highest in ciliary body, followed by retina, optic nerve, cornea, iris, and the lens. No Grx2 mRNA, protein or enzyme activity could be found in the vitreous humor. The results indicate that Grx2 level was higher in eye tissues rich in vasculature and mitochondria (i.e. ciliary body and retina), corroborating with the levels of mRNA expression and Grx2 activity. The rich presence of Grx2 in these tissues is also consistent with their known sensitivity to oxidative stress.
Latest results from FROST at Jefferson Lab

The spectrum of broad and overlapping nucleon excitations can be greatly clarified by use of a polarized photon beam incident on a polarized target in meson photoproduction experiments. At Jefferson Lab, a program of such measurements has made use of the Jefferson Lab FROzen Spin Target (FROST). An overview of preliminary results are presented.
Modes and their stability of a symmetric two-element coupled negative conductance oscillator driven spatial power combining array

The modes and their stability of a symmetric two-element coupled negative conductance oscillator driven spatial power combining array were addressed theoretically. It was shown that the symmetric two-element spatial power combining array can produce two stable operation modes, one in-phase, the other 180/spl deg/-out-of-phase. The theory explains all previously published experimental phenomena. Experiments done at C-band with a symmetric two element coupled Gunn oscillator driven spatial power combining array demonstrated the validity of the theory to a certain extent. The theory can be generalized to study the modes and their stability of any coupled oscillator driven spatial power combining arrays.
Structural Seismic Analysis of a Nuclear Fuel Handling Machine

All nuclear plants in the United States use Fuel Handling Machines (FHM). These complex machines are rail mounted, motorized, and computer controlled for precise positioning of the fuel that must be transferred around, over, into, and through the spent fuel pool. These machines are very top heavy and difficult to seismically qualify. Special analysis techniques are required to consider sliding along the rails or back driving of the drive motor/gearing mechanism in order to minimize the seismic response. This paper documents the seismic qualification of a FHM, using the machine’s back drive force for limiting the seismic effect in the direction of the rail. Qualification consideration is given to the member stresses and joint connections using the AISC Steel Manual 9th Edition (Allowable Stress Design) and CMAA-70-2000, “Specifications for Top Running Bridge & Gantry Type Multiple Girder Electric Overhead Traveling Cranes” by the Crane Manufacturers Association of America.Copyright © 2012 by ASME
Village Republics and Venture Capitalists

(2003). Village Republics and Venture Capitalists. Journal of Sustainable Forestry: Vol. 17, No. 1-2, pp. 231-232.
A human in vivo model for the luteoplacental shift.

Objective To study the onset of early placental steroidogenesis in humans. Design Ovarian failure patients who were administered a constant dosage of exogenous estradiol (E 2 ) and progesterone (P) during the luteal phase and early gestation and who conceived after transfer of donated oocytes were used to assess serum hormonal changes throughout early pregnancy. Setting Hormonally replaced ovarian failure patients undergoing an egg donation program in an academic research environment. Patients, Participants Nine human volunteers desiring egg donation. Interventions Replacement of E 2 and P. Main Outcome Measure Serum E 2 and P concentrations were measured weekly throughout the patients' gestations. Results Serum E 2 and P levels of these patients remained low in early gestation but significantly increased 25±1.6 and 34±1.6days post embryo transfer, respectively. Regression lines of E 2 ( r =0.99; P r =0.95; P Conclusion This estimate of the onset of placental steroidogenesis is equal to the 5th gestational week as calculated by the patients' last menses, approximately 3weeks earlier than previously reported.
Mining User Interests to Predict Perceived Psycho-Demographic Traits on Twitter

We analyze the relation between user interests and their perceived psychodemographic attributes using Twitter data, training models for predicting various personal traits of users. In contrast to existing work, which bases predictions on the textual tweets produced by users, we leverage the fact that users are embedded in the Twitter social network. We examine the accounts that our users follow, and use them to determine the high-level interests of these users, then use these areas of interest as features for predicting perceived personal traits. We cover target attributes such as gender, age, educational background, political stand and personality. We evaluate our technique on a dataset of over 4,000 Twitter user profiles. We use crowdsourcing to annotate these user profiles with perceptions regarding their personal traits, and correlate these with user interests, as captured by the accounts they follow and their classification in the Twitter "Who To Follow" hierarchy. We compare the accuracy of our personal trait prediction methods with the state-of-the-art approaches that solely rely on user tweets, and discuss the correlations between perceived user demographics and interests.
Aortic stenosis catheterization revisited: a long sheath single-puncture technique.

Objectives To evaluate the accuracy of a new long sheath single-puncture technique in obtaining accurate transvalvular gradients in aortic stenosis. Background Despite advances in echo Doppler, the evaluation of aortic stenosis continues to be a common procedure in the cardiac catheterization laboratory. Experts agree that simultaneous evaluation of the proximal aortic and left ventricular pressures yields the most accurate data; however, this is difficult to achieve unless two arterial punctures are performed. Methods We postulated that using a 4 Fr pigtail catheter inside a 55-cm long 6 Fr sheath would provide accurate simultaneous pressure data, yet avoid the complications of two arterial punctures. We performed this technique in 13 male patients, and placed a second arterial catheter in the aortic root as a control aortic pressure. We then performed this technique in 55 other male patients without placing an additional control arterial catheter. Results In the test population, correlation of aortic valve areas and transvalvular gradients was excellent. In the larger population, adequate hemodynamic data was obtained in 52 patients, with no difficulty engaging coronary arteries or grafts via the long sheath, and with an acceptable major complication rate of 1.5%. Conclusions Using a 4 Fr pigtail catheter with a 55-cm long 6 Fr sheath is a safe, efficient way to obtain excellent hemodynamic data in an aortic stenosis catheterization procedure.
Electrochemical techniques in bioanalysis

Electroanalytical techniques are currently gaining popularity in the area of biochemical analysis. There are several reasons for this growth. Electrochemical techniques provide both excellent detection limits with wide dynamic range. These methods are typically readily amenable to miniaturization. This leads to being able to use very small sample volumes. In vivo analysis is also possible. Finally, electrochemical techniques are generally very selective and when not selective enough can easily be coupled to even more selective techniques such as liquid chromatography or immunoassay. In this chapter, the basic concepts underlying electroanalytical methods of bioanalysis will be described. How these techniques can be used in bioanalytical chemistry will be illustrated. In addition, the interrelationship of the various electroanalytical techniques will be discussed.
Comparison of tibiofemoral joint space width measurements from standing CT and fixed flexion radiography.

The objective of this project was to determine the relationship between medial tibiofemoral joint space width measured on fixed-flexion radiographs and the three-dimensional joint space width distribution on low-dose, standing CT (SCT) imaging. At the 84-month visit of the Multicenter Osteoarthritis Study, 20 participants were recruited. A commercial SCT scanner for the foot and ankle was modified to image knees while standing. Medial tibiofemoral joint space width was assessed on radiographs at fixed locations from 15% to 30% of compartment width using validated software and on SCT by mapping the distances between three-dimensional subchondral bone surfaces. Individual joint space width values from radiographs were compared with three-dimensional joint space width values from corresponding sagittal plane locations using paired t-tests and correlation coefficients. For the four medial-most tibiofemoral locations, radiographic joint space width values exceeded the minimal joint space width on SCT by a mean of 2.0 mm and were approximately equal to the 61st percentile value of the joint space width distribution at each respective sagittal-plane location. Correlation coefficients at these locations were 0.91-0.97 and the offsets between joint space width values from radiographs and SCT measurements were consistent. There were greater offsets and variability in the offsets between modalities closer to the tibial spine. Joint space width measurements on fixed-flexion radiographs are highly correlated with three-dimensional joint space width from SCT. In addition to avoiding bony overlap obscuring the joint, a limitation of radiographs, the current study supports a role for SCT in the evaluation of tibiofemoral OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1388-1395, 2017.
Elastic–Plastic Sinusoidal Waviness Contact Under Combined Normal and Tangential Loading

The behavior of an elastic plastic contact between a deformable three-dimensional sinusoidal asperity and a rigid flat under combined normal and tangential loading is investigated using the finite element method. The sliding inception is determined by the maximum shear stress criterion. The resulting junction growth and static friction coefficient are investigated. It is found that for a general case, at the low dimensionless contact pressures, the static friction coefficient decreases sharply with increasing contact pressure. However, at the medium contact pressures, the static friction coefficient nearly approaches a constant value (around 0.23). Nevertheless, as the contact pressure further increases, the static friction coefficient keeps on reducing at a linear rate. The effects of material properties, geometric properties and critical shear strength on the static friction coefficient are also studied. An empirical expression for the static friction coefficient is provided.
Texting while driving, executive function, and impulsivity in college students

The purpose of the present study was to investigate the cognitive processes underlying texting while driving. A sample of 120 college students completed a survey to assess how frequently they send and read a text message while driving. Based on this information, students were assigned to one of two groups: 20 students who frequently text while driving and 20 matched-control students who infrequently text while driving but were similar in gender, age, years of education, and years driving. The groups were compared on the extent to which they differed in self-reported measures of executive function and impulsivity. The groups were also compared on a behavioral measure of impulsivity: the extent to which they discounted hypothetical monetary rewards as a function of the delay. For this measure, the students made repeated choices between smaller monetary rewards available immediately and larger rewards available after delays ranging from 1 week to 6 months. The results show that the group of students who frequently text while driving showed (a) significantly lower levels of executive function and (b) higher levels of self-reported impulsivity, although the groups did not differ significantly on the behavioral measure of impulsivity. These results support a general conclusion that drivers with lower levels of executive function and higher levels of impulsivity are more likely to text while driving.