cssi/SciSciGPT-SciSciNet huggingface dataset:
Particle entry through reconnection grooves in the magnetopause with a dawnward IMF as simulated by a 3-D EM particle code

We report progress in the long-term eort to represent the interaction of the solar wind with the Earth's magnetosphere using a three-dimensional electromagnetic particle code. After a quasi-steady state is established with an unmagnetized solar wind we gradually switch on a north- ward interplanetary magnetic eld (IMF), which causes a magnetic reconnection on the magnetopause tailward of the dayside cusps and makes the magnetosphere dipolarized. In the case that the northward IMF is switched gradually to dawnward, there is no signature of reconnection in the near- Earth magnetotail in contrast to the case with the south- ward turning. On the contrary analysis of magnetic elds in the magnetopause conrms a signature of magnetic re- connection at both the dawnside and duskside. The plasma sheet in the near-Earth magnetotail clearly thins as in the case of southward turning. Arrival of dawnward IMF to the magnetopause creates a reconnection groove which causes particle entry into the deep region of the magnetosphere via eld lines that go near the magnetopause. This deep connection is more fully recognized tailward of Earth. The flank weak-eld region joins onto the plasma sheet and the current sheet to form a geometrical feature called the cross- tail S that structurally integrates the magnetopause and the tail interior. This structure might contribute to direct en- try between the magnetosheath plasma to plasma sheet, in which the entry process heats the magnetosheath plasma to plasma sheet temperatures. In spite of strong plasma entry into the inner magnetosphere, the dawnward IMF prevents the reconnection in the near-Earth magnetotail due to the penetrated IMF By component. Therefore, the onset of sub- storms may not take place. However, it is still possible that this particle entry causes pseudo-substorm onsets.
Modulation of Sarcolemmal ATP-Sensitive Potassium Channels by Atrial Natriuretic Peptide in Ventricular Cardiomyocytes

ATP-sensitive potassium (KATP) channels couple cell metabolic status to membrane excitability and are crucial for stress adaptation in the heart. Natriuretic peptides (NPs) produced by the heart, the vasculature and the kidney exert physiologically important actions such as natriuresis and inhibition of sympathetic tone and cardiomyocyte hypertrophy. Our recent study reveals that the gaseous messenger nitric oxide evokes cardiac KATP channel stimulation via activation of soluble guanylyl cyclase and subsequently a cGMP-dependent signaling pathway. Binding of NPs like atrial natriuretic peptide (ANP) to the type 1 NP receptor (NPR-A) also increases intracellular cGMP level, through activating guanylyl cyclase intrinsic to the receptor; however, how ANP modulates the function of cardiac KATP channels remains to be established. By performing cell-attached patch recordings in ventricular cardiomyocytes acutely isolated from adult rabbits, we found that the single-channel activity of sarcolemmal KATP (sarcKATP) channels induced by sodium azide through metabolic inhibition was potentiated by addition of ANP (100 nM) (n=16), whereas the potentiation by ANP was abolished when the NPR-A antagonist anantin (1 μM) was coapplied (n=5); these findings suggest that the stimulatory action of ANP is mediated by NPR-A activation, which may depend on generation of diffusible cGMP. Indeed, sarcKATP channel stimulation by ANP in intact ventricular myocytes was significantly abated by inhibition of cGMP-dependent protein kinase (PKG) with KT5823 (1 μM) (n=5). Moreover, the ANP effect was prevented by selective suppression of extracellular signal-regulated protein kinase (ERK)1/2 (n=6) and Ca2+/calmodulin-dependent protein kinase II (CaMKII) (n=6). Collectively, here we demonstrate that the polypeptide hormone ANP positively modulates ventricular KATP channel function via activation of NPR-A, PKG, ERK1/2 and CaMKII. By opening myocardial KATP channels, this signaling pathway may regulate cardiac excitability and contribute to cytoprotection against ischemia-reperfusion injury.
Acute systemic immune activation following vaginal exposure to staphylococcal enterotoxin B-Implications for menstrual shock

Menstrual toxic shock syndrome (mTSS) is an acute systemic inflammatory disease associated with the superantigenic exotoxin, toxic shock syndrome toxin (TSST)-1, produced by Staphylococcus aureus and the use of high absorbency tampons. Even though S. aureus is capable of elaborating several other superantigenic exotoxins, only TSST-1 has been implicated in the pathogenesis of mTSS possibly because most other superantigenic exotoxins are known enterotoxins. Nonetheless, we have shown recently that one of the enterotoxigenic staphylococcal superantigens, staphylococcal enterotoxin B (SEB), can cause robust systemic immune activation following exposure through non-enteric mucosa, including nasal or conjunctival routes. In a similar manner, we show here that vaginal administration of SEB in HLA class II transgenic mice can cause robust systemic immune activation characterized by profound elevation of proinflammatory cytokines in the serum, activation and expansion of SEB-reactive CD4(+) and CD8(+) T cells in peripheral lymphoid organs and SEB-induced deletion of immature thymocytes. Vaginal administration of SEB also caused leukocytic infiltration in major organs, such as liver and lung, reminiscent of human toxic shock syndrome. Systemic immune activation following vaginal superantigen delivery was independent of the stage of the estrus cycle in the mouse. Using HLA class II transgenic mice, we have shown that exposure to SEB through the vaginal canal can cause robust systemic immune activation. SEB could thus play a role in the pathogenesis of mTSS.
Lotka's Law: A Testing Procedure.

Abstract Instead of the commonly accepted inverse square law, Lotka's original formulation was based on a more general inverse power law: x n · y = c . The exponent and the constant must be estimated from the given set of author productivity data. A step-by-step outline is presented for testing the applicability of Lotka's law. Steps include the computation of the values of the exponent and the constant based on Lotka's method, and the test for significance of the observed frequency distribution against the estimated theoretical distribution derived from Lotka's formula.
Linear programming and the reliability of multicomponent systems

Several problems in the assignment of parallel redundant components to systems composed of elements subject to failure are considered. In each case the problem is to make an assignment which maximizes the system reliability subject to system constraints. Three distinct problems; are treated. The first is the classical problem of maximizing system reliability under total cost or weight constraints when components are subject to a single type of failure. The second problem deals with components which are subject to two types of failure and minimizes the probability of one mode of system failure subject to a constraint on the probability of the other mode of system failure. The third problem deals with components which may either fail to operate or may operate prematurely. System reliability is maximized subject to a constraint ori system safety. In each case the problem is formulated as an integer linear program. This has an advantage over alternative dynamic programming formulations in that standard algorithms may be employed to obtain numerical results.
A concise, asymmetric synthesis of (2R,3R)-3-hydroxyaspartic acid

3-Hydroxyaspartic acid and its derivatives are found both in the free form and as peptide constituents in various microorganisms and fungi. Considering the biological importance of this amino acid and its potential utility as a multifunctional building block in organic syntheses, we have developed a short-step, asymmetric synthetic route to a strategically protected 3-hydroxyaspartic acid derivative in enantiopure form. The key steps in the synthesis involve, Sharpless asymmetric aminohydroxylation of commercially available trans-ethyl cinnamate, and, utilization of the phenyl group as a masked carboxylic acid synthon towards construction of the complete structural framework of the title compound.
Deuteration of verapamil by acid catalyzed exchange

Deuteration of verapamil, 5-[(3,4-dimethoxyphenylethyl)methyl-amino]-2-(3,4-dimethoxyphenyl)-2-isopropyvaleronitrile, an important calcium channel antagonist was accomplished by direct exchange in 25% 2H2SO4 in 2H2O. Refluxing for 140 hr incorporated 4–6 atoms of deuterium, which were distributed into both aromatic rings, but primarily in the ring attached through position 5 of the valeronitrile moiety.
A hybrid Bayesian Network approach to detect driver cognitive distraction

Driver cognitive distraction (e.g., hand-free cell phone conversation) can lead to unapparent, but detrimental, impairment to driving safety. Detecting cognitive distraction represents an important function for driver distraction mitigation systems. We developed a layered algorithm that integrated two data mining methods--Dynamic Bayesian Network (DBN) and supervised clustering--to detect cognitive distraction using eye movement and driving performance measures. In this study, the algorithm was trained and tested with the data collected in a simulator-based study, where drivers drove either with or without an auditory secondary task. We calculated 19 distraction indicators and defined cognitive distraction using the experimental condition (i.e., "distraction" as in the drives with the secondary task, and "no distraction" as in the drives without the secondary task). We compared the layered algorithm with previously developed DBN and Support Vector Machine (SVM) algorithms. The results showed that the layered algorithm achieved comparable prediction performance as the two alternatives. Nonetheless, the layered algorithm shortened training and prediction time compared to the original DBN because supervised clustering improved computational efficiency by reducing the number of inputs for DBNs. Moreover, the supervised clustering of the layered algorithm revealed rich information on the relationship between driver cognitive state and performance. This study demonstrates that the layered algorithm can capitalize on the best attributes of component data mining methods and can identify human cognitive state efficiently. The study also shows the value in considering the supervised clustering method as an approach to feature reduction in data mining applications. Keywords: Driver distraction;
Determination of molecular quadrupole moments from ion-molecule scattering experiments

Abstract Incomplete total cross sections have been measured for K + ions scattered by several molecules. By comparing the cross sections at low energy with those measured for the heavier rare gases, it is possible to determine accurate quadrupole moments for the molecules. A novel method for analyzing the experimental cross sections is described.
Nonclassical effects on divergence and flutter of anisotropic swept aircraft wings

A refined structural model of swept aircraft wings is presented and used to study the associated flutter and divergence instability in an incompressible gas flow. The structural model incorporates nonclassical effects such as anisotropy, heterogeneity, transverse shear, and warping inhibition. An exact solution methodology appropriate for parametric studies is used to specifically determine the effects of transverse shear and warping restraint on aeroelastic instabilities. The results reveal strong quantitative and qualitative implications for instability predictions. The solution methodology yields results that are in excellent agreement with an exact approach devised for a special case and provides a high-efficiency mathematical tool for dealing with flutter and divergence instability problems.
Feedback-driven dynamic invariant discovery

Program invariants can help software developers identify program properties that must be preserved as the software evolves, however, formulating correct invariants can be challenging. In this work, we introduce iDiscovery, a technique which leverages symbolic execution to improve the quality of dynamically discovered invariants computed by Daikon. Candidate invariants generated by Daikon are synthesized into assertions and instrumented onto the program. The instrumented code is executed symbolically to generate new test cases that are fed back to Daikon to help further refine the set of candidate invariants. This feedback loop is executed until a fix-point is reached. To mitigate the cost of symbolic execution, we present optimizations to prune the symbolic state space and to reduce the complexity of the generated path conditions. We also leverage recent advances in constraint solution reuse techniques to avoid computing results for the same constraints across iterations. Experimental results show that iDiscovery converges to a set of higher quality invariants compared to the initial set of candidate invariants in a small number of iterations.
Portfolio maintenance strategies revisited

The results indicate that there appears to be no substantial differences between the buy-and-hold and the fixed proportion strategies regardless of whether an equal allocation scheme or a quadratic programming allocation scheme is employed. Also, when comparing the equal allocation scheme with the quadratic programming allocation scheme on either a buy-and-hold or fixed proportion maintenance strategy, no obvious differences persist. However, the primary focus of this paper was to gain insight into theex post performance of the quadratic programming variable proportions strategy. This latter strategy appears to be far superior to the others — providing greater returns with somewhat less variability. Thus this strategy may provide portfolio managers the where-withal to improve portfolio performance. Future research using other time periods and other samples of securities is necessary to adequately generalize these preliminary results.
Nonlinear characteristics in the Frog's visual system

The receptive fields of retinal fibers in the visual tectum of the frog are mapped with different techniques and the spatial summation characteristics are examined, by presenting stimuli of various shapes and sizes in the center of the receptive field. When the size is increased gradually from the center of the stimulus, for constant stimulus intensity, the maximum response is obtained for stimuli of approximately the size of the most responsive part of the RF. Using a clustering technique to obtain stimuli that are part of the RF and combinations of these parts, it is evident that the spatial summation characteristics are not linear. A model is developed that describes the nonlinear form of these results, based on a power law.
An Experimental Template for Case Study Research

Methods are usually classified as either “experimental” or “observational,” a dichotomy that has governed social science research for centuries. By implication, this dichotomization precludes a consideration of experimental strategies in case study work. Yet, we argue that one gains purchase on the tasks of research design by integrating the criteria traditionally applied to experimental work to all research in the social sciences—including case study work, the focus of this article. Experimental research designs aim to achieve variation through time and across space while maintaining ceteris paribus assumptions, thus maximizing leverage into the fundamental problem of causal inference. We propose to capture these multiple criteria in a four-fold typology: (1) A Dynamic comparison mirrors laboratory experimentation through the use of both temporal and spatial variation; (2) A Longitudinal comparison employs temporal variation; (3) A Spatial comparison exploits variation through space; and (4) A Counterfactual comparison relies on imagined comparison. All comparison case study research designs can be slotted into one of these four categories. Moreover, the typology illustrates in a concise fashion the ways in which case study research designs attempt to mimic the virtues of experimental design and the degree to which they succeed. The classic experiment, with manipulated treatment and randomized control, thus provides a useful template for discussion about methodological issues in experimental and observational contexts.
An autoradiographic investigation of the subcortical visual system in chimpanzee.

Based on one adult chimpanze monocularly injected with radioactive proline, retinofugal fibers were found to terminate bilaterally in the suprachiasmatic, prgeniculate, lateral geniculate, olivary, pretectal and lateral terminal nuclei, and the superior colliculi; the existence of a dorsal terminal nucleus of the accessory optic system is in doubt. In the ipsilateral geniculat nucleus, the fibers terminat in layers 2, 3 and 5; in the contralateral nucleus, they end in layers 1, 4, and 6. Miday throuh the geniculate nucleus, 3 and 4 split medially into two daughter layers 3 and 4 split medially into two daughter layers each. In the superior colliculi, most of the retinal terminals are aggregated superficially in a band located in the stratum griseum superficiale. The contralateral band is interrupted by gaps; the ipsilateral band has fewer gaps, is slightly thicker and located more deeply. There is a limited second tier of terminals in the contralateral superficial gray.
Repertoires of registers: dialect in Japanese discourse

Abstract This paper presents discourse data to argue for the treatment of dialect as a variety in a repertoire whose primary function is microcontextually socioindexical. Dialect forms used by bilectal participants minimally encode stances of alterity between interactants. The association of dialect features with regional provenance and judgments of regional identity made for dialect forms are treated as linguistic ideological processes. The interpretation of dialect forms in use as interactional altering devices is explained through a specific Japanese linguistic ideology involving uchi `in group' and soto `out group' boundaries.
Endothelial cell monolayer dysfunction caused by oxidized low density lipoprotein: attenuation by oleic acid

Abstract Oleic acid (18:1) may exert beneficial effects on the pathogenesis of vascular disease by a variety of mechanisms. To determine if 18:1 exerts direct protective effects on vascular endothelial cells, porcine pulmonary artery endothelial cells (PAEC) were supplemented with 0.1 mM 18:1, γ-linolenic acid (18:3), or ethanol vehicle (ETOH) prior to treatment with low density lipoprotein (LDL), or Cu2+-oxidized LDL (OXLDL). Treatment with neither LDL nor OXLDL (100 μg protein/ml) for 24–48 h caused PAEC cytotoxicity, whereas OXLDL, but not LDL, caused derangements in PAEC actin microfilament architecture and monolayer barrier dysfunction. Supplementation with 18:1, but not 18:3, attenuated derangements caused by OXLDL and lysophosphatidylcholine, a component of OXLDL. These results demonstrate that monounsaturated fatty acids directly alter the response of vascular endothelial cells to OXLDL and may retard the atherosclerotic process by decreasing the efflux of macromolecules (e.g. LDL) into the vessel wall.
Speech-Centric Information Processing: An Optimization-Oriented Approach

Automatic speech recognition (ASR) is a central and common component of voice-driven information processing systems in human language technology, including spoken language translation (SLT), spoken language understanding (SLU), voice search, spoken document retrieval, and so on. Interfacing ASR with its downstream text-based processing tasks of translation, understanding, and information retrieval (IR) creates both challenges and opportunities in optimal design of the combined, speech-enabled systems. We present an optimization-oriented statistical framework for the overall system design where the interactions between the subsystems in tandem are fully incorporated and where design consistency is established between the optimization objectives and the end-to-end system performance metrics. Techniques for optimizing such objectives in both the decoding and learning phases of the speech-centric information processing (SCIP) system design are described, in which the uncertainty in speech recognition subsystem's outputs is fully considered and marginalized. This paper provides an overview of the past and current work in this area. Future challenges and new opportunities are also discussed and analyzed.
Relaxant effect of thiphenamil HCl on upper urinary tract frequency of contraction of healthy asymptomatic volunteers

The pharmacologic effect of thiphenamil HCl on the upper urinary tract as a relaxant of renal pelvic contractions was studied. A total of 17 subjects with no known upper urinary tract abnormalities were scanned. A Diasonics ultrasound scanner at 3.5 MHz was used to visualize the kidney and renal pelvis with the subject in the supine position. Control recordings of renal pelvic and calyceal contractility were made on videotape for approximately 30 min. The subject was then given a single dose of 400 mg thiphenamil HCl and visualization of contractility continued for approximately 60-90 min. Criteria for the evaluation of the data were the mean frequency of pelvic contraction cross-section of the pelvis, and velocity and direction contraction. Ultrasonic images were filtered by a video filtering process and averaged using the digital conversion and summation in real time. The results show that under control conditions renal pelvic contractions are at a frequency of 2 +/- 1.8 min-1. Contractions are initiated with the intrarenal pelvis and continue towards the ureter at a rate of 1.3 +/- 0.8 cm/s. Following thiphenamil HCl, there is a significant reduction in pelvic contraction frequency, 0.6 +/- 0.6 min-1, and the opposing walls of the renal pelvis do not completely close in the formation of a bolus. The results obtained from this study demonstrate that thiphenamil suppresses upper urinary tract contractility. As a consequence of this observation, it is postulated that this agent may be of use in the acute relaxation of the upper urinary tract for renal colic and stone management.
Exploring the role of personality in the relationship between maximization and well-being

Abstract The present study investigates how the Big Five personality traits may play a role in explaining the negative association between maximization and well-being. Contrary to expectation that conscientiousness drives one’s tendency to maximize, neuroticism emerged as the strongest predictor. Further, when controlling for personality traits, the negative relations between maximization (and its facets) and various well-being variables were appreciably attenuated. However, the tendency to experience regret was found to fully mediate the negative relationship between maximization and satisfaction with life even after controlling for personality traits. Our findings suggest that the measurement of maximization may over-represent an affective component of maximizing that leads to decision-related distress while neglecting a more cognitive component, which might reflect a preference for planned, yet painstaking, searches for the “best.”
A review of phase II trial designs for initial marker validation

Phase II clinical trials aim to identify promising experimental regimens for further testing in phase III trials. In this review article, we focus on phase II designs for initial predictive biomarker validation to determine if a drug should be developed for an unselected patient population or for a biomarker-defined patient subset only. Several prospective designs for biomarker-directed therapy have been proposed, differing primarily in the study population, or randomization scheme, or both. The design choice is driven by scientific rationale, marker prevalence, strength of preliminary evidence, assay performance, and turn-around times for marker assessment. The enrichment design is most appropriate when compelling preliminary evidence suggests treatment benefit in only certain marker-defined subgroups, the all-comers design is useful when preliminary evidence regarding treatment effects in marker subgroups is unclear, and adaptive designs have the most potential in the setting of multiple treatment options and multiple marker-defined subgroups. We recently proposed a 2-stage phase II design that has the option for direct assignment (i.e., stop randomization and assign all patients to the experimental arm in stage 2) based on interim analysis (IA) results. This design not only recognizes the need for randomization but also acknowledges the possibility of promising but inconclusive results after pre-planned IA. Simulation studies demonstrated that the direct assignment-option design has minimal power loss, marginal increase in type I error rates, and reasonable robustness to population shift effects. Systematic evaluation and implementation of these design strategies in the phase II setting are essential for accelerating the clinical validation of biomarker guided-therapy.
Estrogenic compounds decrease growth hormone receptor abundance and alter osmoregulation in Atlantic salmon.

Exposure of Atlantic salmon smolts to estrogenic compounds is shown to compromise several aspects of smolt development. We sought to determine the underlying endocrine mechanisms of estrogen impacts on the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis. Smolts in freshwater (FW) were either injected 3 times over 10 days with 2 l gg 1 17b-estradiol (E2) or 150 l gg 1 4-nonylphenol (NP). Seawater (SW)-acclimated fish received intraperitoneal implants of 30 l gg 1 E2 over two weeks. Treatment with these estrogenic compounds increased hepatosomatic index and total plasma calcium. E2 and NP reduced maximum growth hormone binding by 30–60% in hepatic and branchial membranes in FW and SW, but did not alter the dissociation constant. E2 and NP treatment decreased plasma levels of IGF-I levels in both FW and SW. In FW E2 and NP decreased plasma GH whereas in SW plasma GH increased after E2 treatment. Compared to controls, plasma chloride concentrations of E2-treated fish were decreased 5.5 mM in FW and increased 10.5 mM in SW. There was no effect of NP or E2 on gill sodium–potassium adenosine triphosphatase (Na + /K + -ATPase) activity in FW smolts, whereas E2 treatment in SW reduced gill Na + /K + -ATPase activity and altered the number and size of ionocytes. Our data indicate that E2 downregulates the GH/IGF-I-axis and SW tolerance which may be part of its normal function for reproduction and movement into FW. We conclude that the mechanism of endocrine disruption of smolt development by NP is in part through alteration of the GH/IGF-I axis via reduced GH receptor abundance.
Hepatotoxicity potential of Saw Palmetto (Serenoa repens) in rats

Saw palmetto (Serenoa repens L.) is an herbal drug used to treat symptoms of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). There has been a report that a preparation containing this herb has caused cholestatic hepatitis in one person and some indications exist that it may have the potential to produce liver toxicity. The purpose of this study was to evaluate the effect of saw palmetto on rat liver function by measuring its effects on several enzymes and formation of malondialdehyde (MDA), a byproduct of lipid peroxidation. A significant increase in these parameters is considered an indication of liver toxicity. Thirty-six rats were divided into 6 groups of 6 animals each. They were treated for 2 or 4 weeks with a placebo or saw palmetto at doses of 9.14 or 22.86 mg/kg/body wt./day; that is, 2 x and 5 x the maximum recommended daily human dosages. After 2 or 4 weeks, the animals were sacrificed and blood was collected to prepare serum for enzyme assays, which were performed using commercially available kits. A portion of the liver was removed, and a homogenate prepared for the lipid peroxidation assay. Results showed no significant difference in animal body weight, enzyme activity, or MDA formation at either time or dosage level, as compared to controls. The data indicate that at the doses and time periods tested, saw palmetto did not produce any significant effect on the normal biological markers of liver toxicity.
Mechanism of Mechanical Strength Increase of Soda–Lime Glass by Aging

Two models have been proposed to explain the mechanical strength increase of abraded or indented soda–lime glasses upon aging, namely, crack tip blunting and the release of residual tensile stress near the crack tip. To clarify the mechanism, the time dependence of the strengthening of an abraded soda–lime glass was investigated. Effects of aging media, such as moist air, distilled water, 1N HCI and 1N NaOH solutions, as well as the abrasion flaw depth, were determined. The strength increase rate in water of abraded soda–lime glass was compared with those of borosilicate and high-silica glasses. The effect of stressing during aging was also investigated. It was found that the rate of strength increase was faster with decreasing abrasion flaw depth and with decreasing chemical durability. For a given flaw depth, an acidic solution produced the fastest strengthening. The strengthening rate was found to accelerate because of the “coaxing’effect of stressing during aging. From these observations, it was concluded that the strengthening rates relate to the diffusion process and chemical reactions, especially the alkali–hydrogen (or hydronium) ion-exchange reaction, near the crack tip. The role of the residual tensile stress appears to be similar to that of the applied tensile stress, helping the diffusion process near the crack tip. The observed strength increase of soda–lime glass by aging was thus attributed to the effective blunting of the crack tip geometry by the glass–water reaction.
Attenuation and efficacy of human parainfluenza virus type 1 (HPIV1) vaccine candidates containing stabilized mutations in the P/C and L genes

Two recombinant, live attenuated human parainfluenza virus type 1 (rHPIV1) mutant viruses have been developed, using a reverse genetics system, for evaluation as potential intranasal vaccine candidates. These rHPIV1 vaccine candidates have two non-temperature sensitive (non-ts) attenuating (att) mutations primarily in the P/C gene, namely CR84GHNT553A (two point mutations used together as a set) and CΔ170 (a short deletion mutation), and two ts att mutations in the L gene, namely LY942A (a point mutation), and LΔ1710–11 (a short deletion), the last of which has not been previously described. The latter three mutations were specifically designed for increased genetic and phenotypic stability. These mutations were evaluated on the HPIV1 backbone, both individually and in combination, for attenuation, immunogenicity, and protective efficacy in African green monkeys (AGMs). The rHPIV1 mutant bearing the novel LΔ1710–11 mutation was highly ts and attenuated in AGMs and was immunogenic and efficacious against HPIV1 wt challenge. The rHPIV1-CR84G/Δ170HNT553ALY942A and rHPIV1-CR84G/Δ170HNT553ALΔ1710–11 vaccine candidates were highly ts, with shut-off temperatures of 38°C and 35°C, respectively, and were highly attenuated in AGMs. Immunization with rHPIV1-CR84G/Δ170HNT553ALY942A protected against HPIV1 wt challenge in both the upper and lower respiratory tracts. In contrast, rHPIV1-CR84G/Δ170HNT553ALΔ1710–11 was not protective in AGMs due to over-attenuation, but it is expected to replicate more efficiently and be more immunogenic in the natural human host. The rHPIV1-CR84G/Δ170HNT553ALY942A and rHPIV1-CR84G/Δ170HNT553ALΔ1710–11 vaccine candidates are clearly highly attenuated in AGMs and clinical trials are planned to address safety and immunogenicity in humans.
Direct Regulation of β3-Integrin Subunit Gene Expression by HOXA10 in Endometrial Cells

Estrogen and progesterone regulate HOXA10 expression in the endometrium, where HOXA10 is necessary for implantation. The integrins are also involved in early embryo-endometrial interactions. Here we show that HOXA10 directly regulates 3integrin subunit expression in the endometrium, likely mediating the effect of sex steroids on 3integrin expression. 3-Integrin expression was decreased in endometrium shown to have low HOXA10 expression. 3-Integrin mRNA levels were increased in endometrial adenocarcinoma cells (Ishikawa) transfected with pcDNA3.1/HOXA10, and decreased in cells treated with HOXA10 antisense. Seven consensus HOXA10 binding sites were identified 5 of the 3-integrin gene. Direct binding of HOXA10 protein to four sites was demonstrated by EMSA. Reporter gene expression increased in BT-20 cells cotransfected with pcDNA3.1/ HOXA10 and pGL3-promoter vector containing region F (encompassing all seven HOXA10 consensus sites). A 41-bp segment (Region A) showed highest affinity binding to HOXA10 protein. Increased reporter expression, equal in magnitude to that obtained with Region F, was obtained with Region A. HOXA10 protein binding within Region A was localized by deoxyribonuclease I footprinting. 3-Integrin expression was directly up-regulated by HOXA10 through a 41-bp 5-regulatory element. Sex steroids regulate the expression of endometrial 3-integrin through a pathway involving HOXA10. (Molecular Endocrinology 16: 571–579, 2002)
Nonlinear Gravity-Capillary Standing Waves in Water of Arbitrary Uniform Depth.

Gravity–capillary standing waves in water of arbitrary uniform depth are considered. The classical perturbation calculation yields unbounded coefficients for some critical values of the depth. In the present paper solutions valid near the first critical value of the depth are derived. A problem of non-uniqueness is discovered and discussed. It is shown that two solutions exist, one with higher frequency and one with lower frequency than the zeroth-order solution. They are found analytically at the critical value of the depth and numerically in an interval around it. Graphs of the results are included.
Multiple wavelength demultiplexing using an ultrafast nonlinear interferometer

Summary form only given. Optical rate conversion at user access nodes is a necessity in slotted optical time-division multiplexed (OTDM) networks. Various methods of rate conversion have been previously proposed. For instance, a receiver can optically buffer incoming slots and perform an all-optical rate-conversion down to electronic rates. A more practical approach to rate conversion is to consider the incoming slot as N bit-interleaved OTDM channels which can each be optically demultiplexed, detected, and buffered electronically. Multiple channel demultiplexing has been previously demonstrated in a nonlinear optical loop mirror and using four-wave mixing in fiber and a semiconductor optical amplifier. Here, we use the ultrafast nonlinear interferometer (UNI) (Patel et al, Opt. Lett, vol. 21, no. 18, p. 1466, 1996) to demonstrate multiple wavelength all-optical demultiplexing.
Interference in ragweed pollen and honeybee venom radioallergosorbent tests

We studied sera from patients sensitive to short ragweed (SRW) and honeybee venom (HBV) to investigate serum factors able to interfere with the measurement of IgE antibody levels by the radioallergosorbent test (RAST). We heated sera to destroy IgE antibodies and tested them for interference in the RAST. Heating sera for 4 hr at 56 degrees C destroyed up to 98% of the IgE antibody activity. After immunotherapy sera from patients sensitive to SRW and HBV produced striking interference in the RAST. The interference was most marked in the RAST employing 50-microgram quantities of microcrystalline cellulose-linked allergens, but it was also evident in the RAST employing 500-microgram quantities of such allergens and in the commercial RAST in which allergen is linked to paper disks. The interfering substance eluted from diethylaminoethyl (DEAE) cellulose in the IgG fraction. The interference could be eliminated by increasing the relative quantity of solid-phase allergen; RAST interference was not detected when SRW extract was linked to Sepharose 4B. The results indicate that serum factors, presumably IgG antibodies, produce interference in the RAST. Thus immunotherapy studies that measure IgE antibody levels by the RAST must consider the possibility that IgG antibodies can appear to depress IgE antibody levels. Furthermore, because commercially available RAST disks are susceptible to RAST interference, they must be used with caution for the diagnosis of allergy in patients whose sera may contain significant quantities of IgG antibodies.
Inference techniques for fault tolerant distributed database systems

A data inference approach to increase data availability in distributed database systems is proposed. When the requested data are not accessible owing to network and/or site failures, the database system can infer or approximate them from other accessible database fragments. Two different levels of correlated knowledge are used for inference. In the schema level, correlated knowledge between objects is represented as inference paths. Further, in the instance level, correlated rules are used to represent their detail correlations. In general, inference paths suggest proper objects and directions for data inference. By the selection of proper inference paths, correlated rules can be used to derive the inaccessible information. It is noted that a data inference system can be implemented as a front-end system to an existing distributed database system. It consists of a database fragment availability table which provides the data accessibility information for each site, the inference engine that selects inference paths and rules for inferring unavailable data, and the query modification system which transforms the given query to an alternate one such that all the required database fragments are accessible. >
Peroneal Arteriovenous Fistula and Pseudoaneurysm: An Unusual Presentation

Peroneal artery arteriovenous fistulas and pseudoaneurysms are extremely rare with the majority of reported cases due to penetrating, orthopedic, or iatrogenic trauma. Failure to diagnose this unusual vascular pathology may lead to massive hemorrhage or limb threatening ischemia. We report an interesting case of a 14-year-old male who presented with acute musculoskeletal pain of his lower extremity. Initial radiographs were negative. Further imaging workup revealed a peroneal arteriovenous fistula with a large pseudoaneurysm. After initial endovascular intervention was unsuccessful, the vessels were surgically ligated in the operating room. Pathology revealed papillary endothelial hyperplasia consistent with an aneurysm and later genetic testing was consistent with Ehlers-Danlos syndrome Type IV. This case illustrates an unusual cause of acute atraumatic musculoskeletal pain and uncommon presentation of Ehlers-Danlos syndrome.
Aboveground production and species richness of annuals in Chihuahuan Desert grassland and shrubland plant communities

Precipitation variability and shrub encroachment in response to global environmental change are likely to affect both richness and aboveground net primary production (ANPP) of annual plants in arid and semi-arid ecosystems in the northern Chihuahuan Desert, especially given the grazing history and desertification potential of this aridland region. Using a nine-year dataset (1999–2007), we examined the spatial and temporal variation in annual plant communities in grass- and shrub-dominated vegetation, and evaluated the relationships between species richness and ANPP with seasonal and annual precipitation and soil moisture. We found that species richness and ANPP varied among seasons and between years in both grass- and shrub-dominated areas. Cryptantha crassisepala, Plantago patagonica, and Phacelia integrifolia were the most common species found in both communities in both seasons, and Chamaesyce serrula, C. serpyllifolia ,a ndKallstroemia parviflora were more common in summer only. We found that species richness in summer was significantly correlated with summer precipitation and summer soil moisture in both communities, but summer ANPP was significantly correlated with summer precipitation and soil moisture only in shrubland. However, richness and ANPP of winter annuals were significantly correlated with winter precipitation and winter soil moisture in shrubland and grassland. Our results demonstrate that temporal variation in rainfall can be as important as annual total amounts for plant performance, and that response to temporal dynamics varies among species but not between grass- and shrub-dominated communities. We conclude that desert annuals provide a highly dynamic system for understanding the processes that influence plant species composition and abundance, and that desert annual systems will likely be highly impacted by shrub encroachment along with increases in precipitation variability as a consequence of anthropogenic climate change. Published by Elsevier Ltd.
Interactive party effects on electoral performance How ethnic minority parties aid the populist right in Central and Eastern Europe

While the rise of right-wing populism in West European politics has received considerable attention in academic circles, the equivalent phenomenon in Central and Eastern Europe (CEE) remains unders...
Applications of the human p53 knock-in (Hupki) mouse model for human carcinogen testing

Tumor-driving mutations in the TP53 gene occur frequently in human cancers. These inactivating mutations arise predominantly from a single-point mutation in the DNA-binding domain of this tumor suppressor gene (i.e., exons 4–9). The human p53 knock-in (Hupki) mouse model was constructed using gene-targeting technology to create a mouse strain that harbors human wild-type TP53 DNA sequences in both copies of the mouse TP53 gene. Replacement of exons 4–9 of the endogenous mouse TP53 alleles in the Hupki mouse with the homologous normal human TP53 gene sequences has offered a humanized replica of the TP53 gene in a murine genetic environment. The Hupki mouse model system has proven to be an invaluable research tool for studying the underlying mechanisms of human TP53 mutagenesis. The utility of the Hupki mouse model system for exploring carcinogen-induced TP53 mutagenesis has been demonstrated in both in vivo animal experiments and in vitro cell culture experiments. Here, we highlight applications of the Hupki mouse model system for investigating mutagenesis induced by a variety of environmental carcinogens, including sunlight ultraviolet radiation, benzo[a]pyrene (a tobacco smoke-derived carcinogen), 3-nitrobenzanthrone (an urban air pollutant), aristolochic acid (a component of Chinese herbal medicine), and aflatoxin B1 (a food contaminant). We summarize the salient findings of the respective studies and discuss their relevance to human cancer etiology.—Besaratinia, A., Pfeifer, G. P. Applications of the human p53 knock-in (Hupki) mouse model for human carcinogen testing.
Common Prefrontal Regions Activate During Self-Control of Craving, Emotion, and Motor Impulses in Smokers

It has been posited that self-regulation of behaviors, emotions, and temptations may all rely on a common resource. Recent reviews suggest this common resource may include the inferior frontal cortex (IFC). However, to our knowledge no single functional neuroimaging study has tested this hypothesis. We obtained fMRI scans as 25 abstinent treatment-seeking cigarette smokers completed motor, affective, and craving self-control tasks before smoking cessation treatment. We identified two regions in left IFC and a region in pre-supplementary motor area (preSMA) that were commonly activated in all three tasks. Further, PPI analyses suggest that IFC may involve dissociable pathways in each self-control domain. Specifically, the IFC showed negative functional connectivity with large portions of the thalamus and precentral gyrus during motor stopping, with the insula and other portions of the thalamus during craving regulation, and potentially with a small limbic region during emotion regulation. We discuss implications for understanding self-control mechanisms.
Genetic and epigenetic regulation and expression signatures of glutathione S-transferases in developing mouse liver

The hepatic glutathione S-transferases (Gsts) are critical phase II enzymes in protecting cellular macromolecules against electrophiles and oxidative stress. Little is known about the ontogeny of Gsts and the underlying regulatory mechanisms during liver development. Therefore, in this study, the ontogeny and the regulatory mechanisms of 19 known Gst isoforms were investigated in mouse liver from 2 days before birth to postnatal day 45. With the exception of Gstm5 and MGst2 that showed a progressive decline in postnatal messenger RNA (mRNA) expression, most other Gst isoforms showed a progressive increase in postnatal mRNA expression. Two-way hierarchical clustering revealed three distinct expression patterns of these Gsts isoforms: perinatal, adolescent, and adult enriched. The expression signatures of certain Gst isoforms showed positive association with the ontogeny of critical xenobiotic-sensing transcription factors, including aryl hydrocarbon receptor, pregnane X receptor (PXR), constitutive androstane receptor, peroxisome proliferator-activated receptor alpha, and NF-E2-related factor-2. Specifically, genome-wide chromatin immunoprecipitation coupled with the next generation sequencing technology (ChIP-Seq) revealed direct PXR-binding sites to the Gsta, Gstm, Gstt, and Gstp polycistron clusters as well as to the Mgst1 gene locus. Chromatin immunoprecipitation-on-chip analysis demonstrated that DNA methylation and histone H3K27-trimethylation (H3K27me3), two-gene expression-suppressing epigenetic marks, were consistently low around the Gstz1 gene locus. In contrast, enrichment of histone H3K4-dimethylation (H3K4me2), a hallmark for gene activation, increased 60% around the Gstz1 gene locus from prenatal to the young adult period. Regression analysis revealed a strong correlation between the enrichment of H3K4me2 and Gstz1 mRNA expression (r = 0.76). In conclusion, this study characterized three distinct ontogenic expression signatures of the 19 Gst isoforms and examined some genetic and epigenetic mechanisms inducing their transcription during liver development.
Understanding the Electron

Whether it is the crack and snap of an electric shock on a cold winter day or the boom and crash of a lightning bolt on a stormy summer afternoon, we are familiar with electrons because they influence us. Similarly, scientists know about electrons because they influence their measurement equipment .
Culture of Impunity

For a state to make progress in ending impunity, it must not only secure criminal convictions and a commitment to the rule of law, but also restore public confidence in the functioning of the criminal justice system. This is because effective investigations and prosecutions are contingent upon victims reporting crimes to the police and witnesses testifying in court. Such cooperation first requires that victims and witnesses have confidence in the criminal justice system. Witnesses must feel that reported crimes will be properly investigated, that cases will be fairly and impartially adjudicated and that their security (and that of their families) will be guaranteed at all times. Where witnesses do not feel confident in these matters, they will be less likely to report and testify, thereby making investigations and prosecutions even more challenging and contributing to a ‘cycle of impunity’. The breaking of this cycle may only occur when steps are taken that have the effect of restoring public confidence in the criminal justice system. This chapter considers the extent to which the OTP’s strategy of complementarity contributed to such a restoration of public confidence in Kenya and thereby helped in ending the country’s ‘culture of impunity’.