cssi/SciSciGPT-SciSciNet huggingface dataset:
312 Three-year outcomes with first-line pembrolizumab for metastatic non–small-cell lung cancer (NSCLC) with a very high PD-L1 tumor proportion score (TPS) ≥ 90%

Background Although 1st-line PD-1 monotherapy has improved survival in patients with advanced NSCLC and a PD-L1 TPS ≥50%, responses occur in ~45% of patients. We have previously shown that among patients with NSCLC and PD-L1 expression of ≥50% treated with 1st-line pembrolizumab, clinical outcomes are significantly improved in those with a PD-L1 TPS of ≥90%.1 Here, we report the 3-year follow-up outcomes to 1st-line pembrolizumab in patients with a PD-L1 TPS ≥90% vs Methods Patients with stage IV EGFR/ALK wild type NSCLC and PD-L1 TPS ≥50% who received 1st-line pembrolizumab monotherapy at Dana-Farber Cancer Institute were included. Comprehensive tumor genomic profiling was performed to examine genomic correlates of a very high PD-L1 expression on an expanded cohort of NSCLC samples. Results Among 150 patients included, median age was 69 (range: 46–92), 55.3% were women, 91.9% were current smokers, and 34.0% had a KRAS mutation. At a median follow-up of 38.5 months, median progression-free (mPFS) and overall survival (mOS) in the entire cohort were 4.8 months, and 20.0 months, respectively. When compared to patients with a PD-L1 expression of 50–89% (N=81), those with PD-L1 TPS ≥90% (N=69) had a significantly longer mPFS (6.0 vs 3.9 months, HR 0.66, P=0.02), and longer mOS (27.0 vs 14.6 months, HR 0.63, P=0.03; figure 1). Kaplan-Meier estimates of the 3-year PFS and OS were 23.0% and 43.2% in the PD-L1 TPS ≥90% groups, and 8.6% and 24.0% in the PD-L1 TPS 50–89% group, respectively. A PD-L1 TPS ≥90% was confirmed to be an independent predictor of improved PFS (HR 0.58, P=0.02) and OS (HR 0.57, P=0.01) at multivariable analysis. Patients whose tumors had a PD-L1 TPS ≥90% were also significantly more likely to complete 35 cycles of therapy compared to those with PD-L1 TPS of 50–89% (17.4% vs 3.7%, P Conclusions Pembrolizumab monotherapy continues to demonstrate a meaningful long-term survival benefit at a 3-year follow-up in patients with advanced NSCLC and a PD-L1 TPS ≥90% vs 50–89%. NSCLCs with very high PD-L1 TPS have a more favorable genomic profile. These findings have implications for treatment selection and for clinical trial interpretation and design. Reference Aguilar EJ, Ricciuti B, Gainor JF, et al. Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression. Ann Oncol 2019 October 1;30(10):1653–1659
Germplasm Enhancement of Maize

Introduction The mission of the Germplasm Enhancement of Maize (GEM) Project is to effectively increase the diversity of U.S. maize germplasm utilized by producers, global end-users, and consumers. The mission will be achieved through a collaborative effort between USDA-ARS and both public and private research scientists by utilizing exotic, public, and proprietary maize germplasm. The resulting germplasm and associated knowledge, derived via the identification and incorporation of favorable alleles for prioritized traits from exotic sources, is utilized in private and public breeding programs and ultimately contributes to increased genetic diversity of maize grown by producers and improved product performance. In addition, the GEM project provides opportunities for training plant scientists in the enhancement and utilization of un-adapted germplasm. This contributes to the global sustainability of agricultural production, economic stability, and the nutrition and well-being of society.
Serotonin in Autism Spectrum Disorder: Insights from Human Studies and Animal Models

Increased blood serotonin in people with autism was first reported over 50 years ago, and this biogenic amine has remained a focus for the understanding, risk and treatment of Autism Spectrum Disorders (ASD). There is growing evidence that serotonergic transmission is altered by disparate genetic and environmental risk factors for ASD. This review will focus on recent developments regarding serotonin in ASD. Recent studies include epidemiology studies linking ASD with conditions that alter prenatal serotonin in the fetus, altered serotonin in diverse genetic and environmental animal models, and human pathology and molecular and functional brain imaging studies.
Hoop Tensile Characterization Of SiC/SiC Cylinders Fabricated From 2D Fabric

Tensile stress-strain properties in the hoop direction were obtained for 100-mm diameter SiC/SiC cylinders using ring specimens machined from the cylinder ends. The cylinders were fabricated from 2D balanced fabric with several material variants, including wall thickness (6, 8, and 12 plies), Sic fiber type (Sylramic, Sylramic-iBN, Hi-Nicalon, and Hi-Nicalon S), fiber sizing type, and matrix type (full CVI Sic, and partial CVI plus melt-infiltrated SiC-Si). Fiber ply splices existed in the all the hoops. Tensile hoop measurements were made at room temperature and 1200 C using hydrostatic ring test facilities. The hoop results are compared with in-plane data measured on flat panels using same material variants, but containing no splices.
The Devil's Invention: Asymptotic, Superasymptotic and Hyperasymptotic Series

Singular perturbation methods, such as the method of multiple scales and the method of matched asymptotic expansions, give series in a small parameter e which are asymptotic but (usually) divergent. In this survey, we use a plethora of examples to illustrate the cause of the divergence, and explain how this knowledge can be exploited to generate a 'hyperasymptotic' approximation. This adds a second asymptotic expansion, with different scaling assumptions about the size of various terms in the problem, to achieve a minimum error much smaller than the best possible with the original asymptotic series. (This rescale-and-add process can be repeated further.) Weakly nonlocal solitary waves are used as an illustration.
Vitamin D-3 Receptor as a Target for Breast Cancer Prevention

The vitamin D-3 receptor (VDR) is a nuclear receptor that modulates gene expression when complexed with its ligand 1-alpha,25-dihydroxycholecalciferol [1,25(OH)(2)-D(3)], which is the biologically active form of vitamin D-3. The cellular effects of VDR signaling include growth arrest, differentiation and/or induction of apoptosis, which indicate that the vitamin D pathway participates in negative-growth regulation. Although much attention has been directed in recent years toward the development of synthetic vitamin D analogs as therapeutic agents for a variety of human cancers including those derived from the mammary gland, studies on vitamin D as a chemopreventive agent for breast cancer have been quite limited. The VDR is expressed in normal mammary gland, where it functions to oppose estrogen-driven proliferation and maintain differentiation; this suggests that 1,25(OH)(2)-D(3) participates in negative-growth regulation of mammary epithelial cells. Furthermore, preclinical studies show that vitamin D compounds can reduce breast cancer development in animals, and human data indicate that both vitamin D status and genetic variations in the VDR may affect breast cancer risk. Collectively, findings from cellular, molecular and population studies suggest that the VDR is a nutritionally modulated growth-regulatory gene that may represent a molecular target for chemoprevention of breast cancer.
Neither castration nor steroid-replacement change the apparent molecular size of FSH in the sheep pituitary

Abstract Gonadal steroids alter the apparent molecular size of intrapituitary Follicle-Stimulating Hormone (FSH) in rats and monkeys as well as increase the percentage of acidic FSH isohormones in sheep. Hence, we hypothesized that the molecular size of ovine (o) FSH would be increased by gonadal steroids. Extracts of pituitaries from rams and wethers, as well as, from wethers which had been implanted with dihydrotestosterone (DHT), 17β-estradiol (E2) or both steroids (n=4–6 per treatment group) were subjected to analytical gel permeation chromatography using Sephadex G-100 Superfine. FSH concentrations in chromatographic fractions were determined by radioimmunoassays. Although FSH in pituitaries of non-implanted wethers eluted slightly earlier (i.e. larger) than FSH in pituitaries from E2-implanted wethers as evaluated by distribution coefficients (Kds) during chromatography (P 0.05). Thus, in contrast to rats and monkeys, neither castration nor steroid-replacement appears to alter the molecular size of FSH in the sheep pituitary as evaluated by analytical gel permeation chromatography.
Review: Structural determinants of pattern recognition by lung collectins.

Host defense roles for the lung collectins, surfactant protein A (SP-A) and surfactant protein D (SP-D), were first suspected in the 1980s when molecular characterization revealed their sequence homology to the acute phase reactant of serum, mannose-binding lectin. Surfactant protein A and SP-D have since been shown to play diverse and important roles in innate immunity and pulmonary homeostasis. Their location in surfactant ideally positions them to interact with air-space pathogens. Despite extensive structural similarity, the two proteins show many functional differences and considerable divergence in their interactions with microbial surface components, surfactant lipids, and other ligands. Recent crystallographic studies have provided many new insights relating to these observed differences. Although both proteins can participate in calcium-dependent interactions with sugars and other polyols, they display significant differences in the spatial orientation, charge, and hydrophobicity of their binding surfaces. Surfactant protein D appears particularly adapted to interactions with complex carbohydrates and anionic phospholipids, such as phosphatidylinositol. By contrast, SP-A shows features consistent with its preference for lipid ligands, including lipid A and the major surfactant lipid, dipalmitoylphosphatidylcholine. Current research suggests that structural biology approaches will help to elucidate the molecular basis of pulmonary collectin–ligand recognition and facilitate development of new therapeutics based upon SP-A and SP-D.
Leukocyte adhesion molecule expression and T cell naı̈ve/memory status following isoproterenol infusion

This study examined adhesion molecules on peripheral leukocytes following a 30-min infusion of the β-adrenergic agonist isoproterenol in 23 healthy subjects. In response to isoproterenol, the number of CD8+CD62L− T cells and both CD62L+ and CD62L− natural killer (NK) (CD3−CD16+56+) cells increased markedly in circulation (p<0.001). In addition, the surface density of CD62L was significantly lower on both CD8+ and CD4+ T cells (p<0.001). Plasma levels of soluble CD62L remained unchanged, arguing against an isoproterenol-induced shedding of L-selectin. In contrast to CD62L, the surface density of the β2 integrin LFA-1 (CD11a) was higher on circulating lymphocytes (p<0.001) (but not monocytes or lymphocytes) post-infusion. Isoproterenol also led to a mobilization of memory/activated CD8+CD29high T cells (p<0.01), but had no significant effect on the number of circulating CD8+CD45RA+CD62L+ naive T cells. β blockade with the non-specific antagonist propranolol eliminated these isoproterenol-induced effects.
Fracture study of aluminum composite coatings produced by the kinetic spray method

The kinetic spray process is a low temperature method for producing coatings. This process allows one to formulate various mixtures of metals, ceramics, polymers, etc., and combine them with a ductile material (as the matrix), to produce composite coatings. The low temperatures involved result in little oxidation or reaction between the parent materials of the composite coating. This report deals with the study of fractured surfaces of aluminum composites using a matrix of aluminum with reinforcing particles of diamond, tungsten, silicon carbide or aluminum nitride. Fracture surfaces were examined with the SEM microscope for evidence of bonding.
Photoelectron Counter Dead Time Effects on Direct Detection Optical Communication Systems

The effects of photon counter dead time on a direct detection binary pulse position modulation optical communication system are computed for both a free space optical channel and an atmospheric channel subject to clear air turbulence. The degradation in the performance of an optimum receiver structure due to dead time losses was found to be typically 1 dB for the free space channel and less than 1 dB for the atmospheric fading channel, even at the large value of the ratio of counter dead time to counting interval length of ten percent.
Study of a dual‐band packaged patch antenna on a PC card for 5–6 GHz wireless LAN applications

A study of a dual-band PC card mounted folded microstrip patch antenna is presented for use with a laptop computer. The antenna operates in the wireless local area network (WLAN) bands from 5.15–5.35 GHz and from 5.725–5.825 GHz within 2.5:1 VSWR. Three cases are considered. First, the PC-card-mounted antenna is studied without a laptop. Next, it is attached externally to a laptop and its characteristics are analyzed. Finally the antenna is studied as packaged within a laptop. Detailed antenna characteristics, including current distribution, VSWR, radiation pattern, and gain, are given. © 2003 Wiley Periodicals, Inc. Microwave Opt Technol Lett 37: 423–428, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10938
Automation Complacency: Using Non-Invasive Brain Stimulation to Change Attention Allocation

Automation complacency has been considered by some to result from a state of mindlessness. An attentional framework offered by Parasuraman and Manzey (2010) has suggested that automation bias and complacency may be overlapping functions of the same central cognitive process, with attentional resources as the shared mechanism. Non-invasive brain stimulation methods present novel ways to manipulate attentional resources and influence operator allocation of attention. Study results indicate that positive stimulation affects complex task performance, although not necessarily evenly across task function. Stimulation effects on complacency potential may be modulated by an operator’s automation bias. This has broad implications for interface design, as well cognitive theory of human-automation interaction.
A progressive code digital quantizer

The analog-to-digital converter described receives analog information obtainable from a graph reader or other analog source and gives a corresponding numerical indication. A progressive coding scheme is used to lessen chances of wrong readings. Several circuits are given for obtaining digital indication, the basic principle being based on comparing the analog voltage with the sum of a finite geometric series. A readout circuit is described for converting the coded digital indication to conventional decimal form for visual reading or for punching International Business Machines (IBM) cards.
Preemptive analgesia with lidocaine prevents Failed Back Surgery Syndrome

Abstract Failed Back Surgery Syndrome (FBSS) is commonly encountered in pain-treatment settings in the United States. We tested whether potential key factors in this syndrome, such as extracellular concentrations of excitatory amino acids (EAAs), are increased in the dorsal horn by synaptic release due to unintentional stretch and/or deformation/compression/transection of dorsal spinal structures during surgery. We hypothesized that pharmacological nerve block as a form of preemptive analgesia prior to any insult to dorsal root neurons will prevent an abnormally high increase in extracellular concentrations of EAAs in the dorsal horn and ultimately the establishment of central sensitization during back surgery. The L4 and L5 dorsal roots were cut bilaterally near the spinal cord to provide an adequate model to test for preemptive analgesia. Amino acid concentrations were measured by dorsal horn microdialysis sampling; EAAs aspartate and glutamate were significantly increased by 80% and 65% respectively, as were other amino acids compared to sham control values. Topical application of 1% Lidocaine ® , a voltage-gated Na + channel blocker, for 10 min prior to L4 and L5 bilateral dorsal rhizotomy (BDR) significantly attenuated the increase in EAA concentrations such that their values were not different from sham controls. Behavioral tests demonstrated significant hindlimb mechanical allodynia after BDRs that was significantly attenuated by Lidocaine® pretreatment. Thus, Lidocaine® pretreatment could offer a safe measure for prevention of chronic pain for back surgical procedures if given by intramuscular injection, topical administration onto spinal nerves and/or the dorsal spinal surface during surgical procedures that include nerve entrapment release, intervertebral disc modification and laminectomies.
Fostering spatial skill acquisition by general chemistry students

The study of chemistry requires the understanding and use of spatial relationships, which can be challenging for many students. Prior research has shown that there is a need to develop students' spatial reasoning skills. To that end, this study implemented guided activities designed to strengthen students' spatial skills, with the aim of improving their understanding of spatial relationships that exist within and between molecules. Undergraduate STEM majors, taking the second semester of a two-semester general chemistry course, engaged in these activities. This study followed a quasi-experimental design, in which the experimental (n = 209) and the control group (n = 212) were administered a pre-test. At the completion of the semester, both groups participated in a post-test designed to measure spatial skill acquisition. A one-way ANOVA confirmed that student performance differed significantly between the three interventions and the control group. Students who completed three activities scored higher than those who completed only two, suggesting continuity is an important feature of spatial training. In particular, our results show improvement in three skill areas: symmetry plane identification, visualization of molecules and translation between 2D and 3D representations. The results of this study show that spatial skills can be successfully enhanced through the use of relevant guided activities designed to improve student understanding of external representations. Our findings show that the use of activities which require students to sketch molecular models from different perspectives, locate a plane of symmetry on a 3D model and on a 2D sketch of the same molecule, as well as position physical models to match 2D sketches containing dash/wedge cues is an effective approach to the teaching and learning of spatial skills in general chemistry.
Sexual Serosorting among Women with or at Risk of HIV Infection

Serosorting, the practice of selectively engaging in unprotected sex with partners of the same HIV serostatus, has been proposed as a strategy for reducing HIV transmission risk among men who have sex with men (MSM). However, there is a paucity of scientific evidence regarding whether women engage in serosorting. We analyzed longitudinal data on women’s sexual behavior with male partners collected in the Women’s Interagency HIV Study from 2001 to 2005. Serosorting was defined as an increasing trend of unprotected anal or vaginal sex (UAVI) within seroconcordant partnerships over time, more frequent UAVI within seroconcordant partnerships compared to non-concordant partnerships, or having UAVI only with seroconcordant partners. Repeated measures Poisson regression models were used to examine the associations between serostatus partnerships and UAVI among HIV-infected and HIV-uninfected women. The study sample consisted of 1,602 HIV-infected and 664 HIV-uninfected women. Over the follow-up period, the frequency of seroconcordant partnerships increased for HIV-uninfected women but the prevalence of UAVI within seroconcordant partnerships remained stable. UAVI was reported more frequently within HIV seroconcordant partnerships than among serodiscordant or unknown serostatus partnerships, regardless of the participant’s HIV status or types of partners. Among women with both HIV-infected and HIV-uninfected partners, 41% (63 HIV-infected and 9 HIV-uninfected) were having UAVI only with seroconcordant partners. Our analyses suggest that serosorting is occurring among both HIV-infected and HIV-uninfected women in this cohort.
The ideal magnet—fully controllable permanent magnets for power and transport

Electromagnets wound on the pole-plates of suitable high-coercivity magnets give complete flux control without loss of permanence. This principle has wide uses in power controls and both road and rail transport, as recently proved by the author with work on safe lifting magnets for ton loads.
Dynamic programming estate transfer model—The closely held farm business

Abstract A dynamic programming solution procedure is described which incorporates probabilistic returns and the most recent laws which govern estate and gift taxation in the United States. The objective is to maximize the expected value of the transferred estate over a specified planning horizon through gifts from the parents to the heirs. Returns are derived through simulation of the life and death events of the parents over the planning horizon. The simulations involve firm growth and estate transfer through gifts and inheritance. Empirical results are described and discussed.
A multiscale coupling method for the modeling of dynamics of solids with application to brittle cracks

We present a multiscale model for numerical simulations of dynamics of crystalline solids. The method combines the continuum nonlinear elasto-dynamics model, which models the stress waves and physical loading conditions, and molecular dynamics model, which provides the nonlinear constitutive relation and resolves the atomic structures near local defects. The coupling of the two models is achieved based on a general framework for multiscale modeling - the heterogeneous multiscale method (HMM). We derive an explicit coupling condition at the atomistic/continuum interface. Application to the dynamics of brittle cracks under various loading conditions is presented as test examples.
Clear Cell Sarcoma Shows Immunoreactivity for Microphthalmia Transcription Factor: Further Evidence for Melanocytic Differentiation

Microphthalmia transcription factor, a melanocytic nuclear protein critical for the embryonic development and postnatal viability of melanocytes, is a master regulator in modulating extracellular signals. Recently, microphthalmia transcription factor expression was shown to be both a sensitive and specific marker of epithelioid melanoma. We investigated the sensitivity of D5, an anti-microphthalmia transcription factor antibody, for diagnosis of clear cell sarcoma (also known as malignant melanoma of soft parts). Immunoreactivity in a nuclear pattern for D5 was present in 8 of 12 (75%) tumors. D5 staining was strong in three tumors, moderate in two, and weak in three. S-100 protein expression was seen in all 12 cases that had clear cell sarcoma examined. HMB-45 staining was seen in 11 of 12 (92%) tumors. Focal Melan-A positivity was seen in 3 of 7 (43%) tumors. Although D5 was shown in a previous study to be a highly sensitive and specific marker for epithelioid melanomas, the results of this study expand the spectrum of tumors showing immunoreactivity for D5. D5 immunoreactivity in clear cell sarcoma provides further evidence for melanocytic differentiation in this unusual tumor.
Experimental evaluation method for determination of friction characteristics and performance of cold heading coatings

An experimental method was designed to evaluate wire coatings for the cold-heading process. Coatings are employed to increase material formability and to reduce wear on tooling. Typically, evaluation of frictional properties proves to be difficult because of problems instrumenting machine tooling and both the complexity and number of stages in the forming process. The proposed test is a cold extrusion process utilizing a selected trapped-forward extrusion die, where load versus stroke data is collected. Three different coating ratings are generated based upon maximum extrusion force, standard deviation of the force, and the characteristic shape of the extrusion curve. Coating performance interpretations for the curve characteristics are discussed.
Coating-induced wave-front aberrations: On-axis astigmatism and chromatic aberration in all-reflecting systems

The coatings used on telescope mirrors and other optical interfaces can have a marked effect on an optical system's image quality. We describe the wave-front aberrations, particularly the defocus and on-axis astigmatism, that are induced by the s- and p-phase shifts of coatings. These coating-induced wave-front aberrations are very small, particularly near the design wavelengths of the coatings, but they can under certain circumstances overshadow the geometric wave-front aberrations of the system. The wave-front aberrations that are induced by reflection-enhanced coatings on an A/1.5 Cassegrain telescope are numerically evaluated as an example. A theory of coating-induced on-axis astigmatism and chromatic aberration is presented, and a simple algorithm that uses polarization ray tracing to calculate coating-induced defocus and astigmatism coefficients in radially symmetric systems is provided.
On the condition number of some gram matrices arising from least squares approximation in the complex plane

This paper analyses the growth of the condition number of a class of Gram matrices that arise when computing least squares polynomials in polygons of the complex plane. It is shown that if the polygon is inserted between two ellipses then the condition number of the (n+1)×(n+1) Gram matrix is bounded from above by 4m(n+1)2(k)2n wherem is the number of edges of the polygon, andk≥1 is a known ratio which is close to one if the two ellipses are close to each other.
Normal Spastin Gene Dosage Is Specifically Required for Axon Regeneration

Axon regeneration allows neurons to repair circuits after trauma; however, most of the molecular players in this process remain to be identified. Given that microtubule rearrangements have been observed in injured neurons, we tested whether microtubule-severing proteins might play a role in axon regeneration. We found that axon regeneration is extremely sensitive to levels of the microtubule-severing protein spastin. Although microtubule behavior in uninjured neurons was not perturbed in animals heterozygous for a spastin null allele, axon regeneration was severely disrupted in this background. Two types of axon regeneration-regeneration of an axon from a dendrite after proximal axotomy and regeneration of an axon from the stump after distal axotomy-were defective in Drosophila with one mutant copy of the spastin gene. Other types of axon and dendrite outgrowth, including regrowth of dendrites after pruning, were normal in heterozygotes. We conclude that regenerative axon growth is uniquely sensitive to spastin gene dosage.
Holocene environmental changes in the alpine zone, northern San Juan Mountains, Colorado: Evidence from bog stratigraphy and palynology

Cores from five high alpine basins in the northern San Juan Mountains show several fluctuations in lithology. Typically, peats are interbedded with coarser clastic sediments or else woody peats alternate with fibrous peat. Twenty 14C dates provide radiometric control. Sediment rates averaged about 2.5 cm/100 yr but varied at the different sites between 1.19 and 50 cm/100 yr. Rates were lower during the middle of the Holocene. Basal radiocarbon dates indicate that these high (ca. 3600 m a.s.l.) northeasterly facing cirques were icefree by 9000 BP. There is some evidence in the cores for a short climatic reversal sometime between 8000 and 7000 BP. A major change occurred in the high basins very close to 5000 BP and thereafter there are several intervals of increased clastic sedimentation which may be related to Neoglacial climatic fluctuations. Analysis of a 2.15 m core near Hurricane Basin indicates significant fluctuation of pollen and macrofossils occurred during the 9000 ± year record. The Picea/Pinus ratios are used to delimit changes in the apparent elevation of the site: the ratios indicate that a short drop of “treeline” occurred about 8000 BP and then remained near present level until about ≥1800 BP when the apparent elevation of the site rose. Macrofossils indicate that spruce was present in the Hurricane Basin (and others) at specific periods and confirms the general results of the Picea/Pinus ratios. The San Juan Mountains do not possess a glacial Neoglacial record but the stratigraphy of these high cirque basins can be used to define glacial stades (cf. Jardine, 1972). The interpreted climatic response record on vegetation and sediment flux has both similarities and differences from other records in the western mountains of North America.
Josquin as Classic: Qui habitat, Memor esto, and Two Imitations Unmasked

Further progress in Josquin research and in the study of the music of the whole age will largely depend on detailed inquiry into the catalogue of the authentic works of the master. This will probably be the most burning problem, for how should the scholar pursue serious studies of Josquin's music, and how should the amateur find an approach to this outstanding musician, unless they know that the composition in their hands is really by Josquin?'
Cobalt(II) halide complexes ofN-2-(4-picolyl)-,N-2-(6-picolyl)-andN-2-(4,6-lutidyl)-N′-phenylthioureas

CoII complexes of various stoichiometries have been isolated from reactions of the metal chlorides and bromides withN-2-(4-picolyl)-,N-2-(6-picolyl)- andN-2-(4,6-lutidyl)-N′-phenylthioureas.
Tumor Necrosis Factor-related Weak Inducer of Apoptosis Augments Matrix Metalloproteinase 9 (MMP-9) Production in Skeletal Muscle through the Activation of Nuclear Factor-κB-inducing Kinase and p38 Mitogen-activated Protein Kinase A POTENTIAL ROLE OF MMP-9 IN MYOPATHY

Destruction of skeletal muscle extracellular matrix is an important pathological consequence of many diseases involving muscle wasting. However, the underlying mechanisms leading to extracellular matrix breakdown in skeletal muscle tissues remain unknown. Using a microarray approach, we investigated the effect of tumor necrosis factor-related weak inducer of apoptosis (TWEAK), a recently identified muscle-wasting cytokine, on the expression of extracellular proteases in skeletal muscle. Among several other matrix metalloproteinases (MMPs), we found that the expression of MMP-9, a type IV collagenase, was drastically increased in myotubes in response to TWEAK. The level of MMP-9 was also higher in myofibers of TWEAK transgenic mice. TWEAK increased the activation of both classical and alternative nuclear factor-κB (NF-κB) signaling pathways. Inhibition of NF-κB activity blocked the TWEAK-induced production of MMP-9 in myotubes. TWEAK also increased the activation of AP-1, and its inhibition attenuated the TWEAK-induced MMP-9 production. Overexpression of a kinase-dead mutant of NF-κB-inducing kinase or IκB kinase-β but not IκB kinase-α significantly inhibited the TWEAK-induced activation of MMP-9 promoter. The activation of MMP-9 also involved upstream recruitment of TRAF2 and cIAP2 proteins. TWEAK increased the activity of ERK1/2, JNK1, and p38 MAPK. However, the inhibition of only p38 MAPK blocked the TWEAK-induced expression of MMP-9 in myotubes. Furthermore the loss of body and skeletal muscle weights, inflammation, fiber necrosis, and degradation of basement membrane around muscle fibers were significantly attenuated in Mmp9 knock-out mice on chronic administration of TWEAK protein. The study unveils a novel mechanism of skeletal muscle tissue destruction in pathological conditions.
A computerized method of analyzing and playing back vibratory animal signals

In water striders or other animals that communicate with vibratory or oscillatory signals, surface wave signals can be recorded, analyzed in digital form by computer, then played back accurately by oscillating a magnet, glued to the animal, with electromagnetic fluctuations from a coil driven by the computer. Signals can be played with great flexibility through a normally behaving animal, in laboratory or field.
Crystallographic evidence for doxorubicin binding to the receptor-binding site in Clostridium botulinum neurotoxin B.

The neurotoxins of Clostridium botulinum and tetanus bind to gangliosides as a first step of their toxin activity. Identifying suitable receptors that compete with gangliosides could prevent toxin binding to the neuronal cells. A possible ganglioside-binding site of the botulinum neurotoxin B (BoNT/B) has already been proposed and evidence is now presented for a drug binding to botulinum neurotoxin B from structural studies. Doxorubicin, a well known DNA intercalator, binds to the neurotoxin at the receptor-binding site proposed earlier. The structure of the BoNT/B–doxorubicin complex reveals that doxorubicin has interactions with the neurotoxin similar to those of sialyllactose. The aglycone moiety of the doxorubicin stacks with tryptophan 1261 and interacts with histidine 1240 of the binding domain. Here, the possibility is presented of designing a potential antagonist for these neurotoxins from crystallographic analysis of the neurotoxin–doxorubicin complex, which will be an excellent lead compound.
Comparison of Somatostatin and Its Highly Potent Hexa- and Octapeptide Analogs on Exocrine and Endocrine Pancreatic Secretion:

The effects on pancreatic responses of highly potent cyclic hexapeptide (cyclo (N-Me-Ala-Phe-D-Trp-Lys-Thr-Phe)) (Veber analog) and octapeptide analogs of somatostatin such as D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol (SMS 201-995), D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121), and D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) have been compared with somatostatin tetradecapeptide (SS-14) and atropine. The parameters evaluated were pancreatic responses to secretin and meat feeding in conscious dogs with chronic pancreatic fistula and amylase release from the dispersed pancreatic acini. The analogs were administered intravenously or intraduodenally. The cyclic hexapeptide and octapeptide analogs, given iv in graded doses against a constant background stimulation with secretin, produced similar and dose-dependent inhibition of pancreatic HCO3- and protein secretion. Analogs RC-121, RC-160, and the Veber analog were about two to four times more active than SS-14 in suppressing HCO3- secretion and equipotent in reducing protein secretion, but SMS 201-995 was only about half as potent as somatostatin in inhibiting HCO3-. RC-160 was effective in inhibiting secretin-induced protein secretion at lower doses than other analogs. In tests with feeding, SMS 201-995, the Veber analog, RC-121, and RC-160 were more potent inhibitors of exocrine pancreatic secretion of HCO3- and protein and exhibited more prolonged inhibitory effects than SS-14. The Veber analog, RC-121, and RC-160 were also more effective after intraduodenal administration. Atropine also caused significant inhibition of both HCO3- and protein responses to secretin and meal feeding. All four analogs decreased the postprandial insulin and pancreatic polypeptide release to a similar degree as SS-14. Neither SS-14 nor the analogs tested significantly affected basal or caerulein-, gastrin-, secretin-, or bethanechol-stimulated amylase release from the dispersed canine pancreatic acini. Atropine reduced amylase release induced by bethanechol, but not that stimulated by caerulein, gastrin, or secretin. This indicated that the analogs, as somatostatin, are ineffective as secretory inhibitors in vitro. We conclude that cyclic hexapeptide and octapeptide analogs are more potent and longer acting inhibitors of pancreatic secretion than somatostatin-14 in vivo.
We choose to go to the membrane

In the field of protein folding, the membrane is uncharted territory. The energetic factors that govern the folding and stability of a protein in the hydrophobic lipid bilayer are sparsely understood. To probe these thermodynamic influences, several energy scales have been determined that measure the energy to transfer an amino acid into a membrane-like environment: the Wimley-White (WW) scale (1, 2), which measures residue partitioning between water and octanol, and the translocon scale, which measures the partitioning of residues on an α-helical segment from the translocon machinery into the membrane (3). Although these hydrophobicity scales provide energetic benchmarks, they do not convey the actual equilibrium change in free energy (ΔGo) of transferring a residue from the water into a real membrane core, in the context of a membrane protein structure.
Synthese und Struktur eines chiralen, C3‐symmetrischen Monophosphans

Synthese a partir du bromo-2 phenol ou du di-t-butyl-4,6 bromo-2 phenol et de POCl 3 et PCl 3
Another look at depressive symptoms and antiretroviral therapy adherence: The role of treatment self-efficacy:

Depression has been strongly associated with poor HIV treatment adherence, but little research has explored how individuals manage to follow their regimens despite symptoms of major depression. Using a sample of antiretroviral therapy patients with clinically significant depressive symptoms (n = 84), we examined whether patients with optimal adherence differed from those with suboptimal adherence in terms of the types of depressive symptoms experienced and treatment self-efficacy. There were no significant differences between participants with regard to types of depressive symptoms. Findings indicate that patients with high treatment self-efficacy were more likely to report optimal levels of adherence than patients with low self-efficacy.
SOLID PHASE SYNTHESIS OF 2,4,5-TRISUBSTITUTED THIOMORPHOLIN-3-ONES

Abstract The solid phase synthesis of 2,4,5-trisubstituted thiomorpholin-3-ones is described. Starting from a resin-bound protected cysteine, and employing reductive alkylation and amide formation, thiomorpholin-3-one derivatives have been synthesized through intramolecular thioether formatiom in good yield and high purity.
Immunological identification of two adenovirus 2-induced early proteins possibly involved in cell transformation.

HUMAN adenovirus 2(Ad2), a DNA tumour virus that replicates in the nucleus of permissive human cells1,2, transforms non-permissive or semipermissive cultured rodent cells, but does not induce tumours in newborn hamsters (oncogenic group C). The constant functioning of protein product(s) from Ad2 ‘transforming gene(s)’ is probably responsible for the transformed phenotype, although this has not been proved. Identification and functional characterisation of ‘transforming protein(s)’ are important for the understanding of cell transformation and growth control. We describe here immunoprecipitation studies made with antisera against presumptive Ad2 ‘transforming protein(s)’, that identify two candidate transforming proteins of 53,000 (53k) and 15kdaltons.
An alternate approach to developing a total celebrity endorser rating model using the analytic hierarchy process

Using the analytic hierarchy process to develop an overall rating of a celebrity is a new approach to enhance procedures such as the Q-Rating currently in practice. The Q-rating approach has received criticism on its usefulness because it essentially only considers familiarity and likeability of the celebrity. Using the AHP model approach allows users to input judgments as to how they feel about one celebrity compared to another with a specific set of criteria in mind. The model is an improvement over the Q-rating system because it includes a more complete set of attributes and, more importantly, has the ability to capture and analyse trade-offs among those attributes. Another improvement is that as situations change or evolve, the model can be easily updated to capture new information. This allows for celebrities' ratings to change over time and be more accurate given all available information.
Play as a mechanism of working through medical trauma for children with medical illnesses and their siblings

Children’s reactions to medical trauma have been recorded through play. In this study, participants were 15 children with medical illnesses, 14 siblings of children with a medical illness, and 6 ch...
Maintenance cortisone in severe bronchial asthma

Abstract 1.1. Six patients with severe bronchial asthma have been cleared with cortisone. 2.2. It has been possible to maintain these patients free of asthma for months with suitable daily doses of cortisone. 3.3. No untoward pharmacologic effects of cortisone have been noted to date. 4.4. Cortisone does seem to precipitate clumping of the cellular elements of the blood of the bulbar conjunctiva and to cause edema to appear in these areas.
A generalized model for network survivability

The high expectation of network to be available and perform at all time has created growing concerns between network operators and engineers all over the globe. Network should be available to users whenever they want to use them. In the wake of an attack, network should be also able to recover as soon as possible. A survivable network is one that can provide services in the presence of an attack or failure and be able to recover fully in a timely manner. Designing a model for network survivability basically involves the understanding of three key issues, i.e, how the system will function in the wake of failures, what will be the impact of failures on the user, and how to overcome these failures. To achieve these goals, this paper proposes a quantitative approach to evaluate the network survivability in terms of using a generalized model; we consider a more complex system with several faults to study the survivability of a network using Markov chain. In presenting a better survivability performance, some numerical comparisons for the network availability, failure frequency and survivability is also developed.
Oral contraception and the risk of hepatocellular carcinoma.

Backgrounds/Aims We performed a meta-analysis of observational epidemiological studies to examine the association between oral contraceptives (OC) and hepatocellular carcinoma (HCC). Methods Two independent researchers conducted PubMed searches followed by systematic abstraction of studies that compared OC use between patients with HCC and a group of controls. Pooling of ORs was conducted using a random effects model. Heterogeneity and publication bias among studies were examined. Results Twelve case-control studies that included 739 cases and 5223 controls met the inclusion and exclusion criteria. The pooled estimate of ORs (age- and sex-matched only) from all 12 studies was 1.57 (95% CI = 0.96–2.54, p = 0.07) with a heterogeneity of I 2 = 39.9. Exclusion of one large multi-national European study decreased the heterogeneity to I 2 = 16.9 and increased the pooled OR to 1.70 (95% CI = 1.12–2.59, p = 0.01). Eight studies reported adjusted ORs (in addition to age and sex); the pooled estimate was 1.45 (95% CI = 0.93–2.27, p = 0.11) with a heterogeneity of I 2 = 20.4. Only few studies identified or adjusted for other HCC risk factors. Six studies showed a significant 2- to 20-fold increase in HCC risk with longer durations of OC use; however, the reporting was too inconsistent to allow meta-analysis. Conclusions The evidence is inconclusive to establish a relation between oral contraceptives and the risk of hepatocellular carcinoma. Future studies should focus on the duration, intermittency, and recency of OC use.
Determination of Griseofulvin in Skin, Plasma, and Sweat

Abstract A procedure is described for the quantitative determination of griseofulvin in skin, plasma, and sweat. Griseofulvin is extracted with ether from skin and is measured quantitatively by GLC and an electron‐capture detector, using diazepam as an internal standard. Griseofulvin from plasma and sweat is extracted with ether and measured spectrophotofluorometrically.
Impact of residential PV adoption on Retail Electricity Rates

The price of electricity supplied from home rooftop photo voltaic (PV) solar cells has fallen below the retail price of grid electricity in some areas. A number of residential households have an economic incentive to install rooftop PV systems and reduce their purchases of electricity from the grid. A significant portion of the costs incurred by utility companies are fixed costs which must be recovered even as consumption falls. Electricity rates must increase in order for utility companies to recover fixed costs from shrinking sales bases. Increasing rates will, in turn, result in even more economic incentives for customers to adopt rooftop PV. In this paper, we model this feedback between PV adoption and electricity rates and study its impact on future PV penetration and net-metering costs. We find that the most important parameter that determines whether this feedback has an effect is the fraction of customers who adopt PV in any year based solely on the money saved by doing so in that year, independent of the uncertainties of future years. These uncertainties include possible changes in rate structures such as the introduction of connection charges, the possibility of PV prices dropping significantly in the future, possible changes in tax incentives, and confidence in the reliability and maintainability of PV.
The characterization of TEOS oxides used in the isolation module of high-speed bipolar and BiCMOS circuits

Abstract A furnace, CVD TEOS-based oxide, and a plasma enhanced TEOS-based oxide were evaluated for use as spacer oxides in a deep trench. The deep trench is combined with a thermally-grown field oxide to form the isolation module of a pair of high performance integrated circuits. The films were evaluated based on their step coverage of the trench sidewall, their deposition uniformity, the effect of the density of trenches on the deposition uniformity, the fixed charge in the films, the junction leakage current of diodes isolated by these trenches, and the trench sidewall inversion threshold voltage. The uniformity and conformality of the furnace TEOS films were superior. The fixed charge in the furnace TEOS film was also less than the charge in the PETEOS film after annealing. The leakage current and threshold voltage for the two films were comparable. The furnace TEOS film was chosen as the preferred film for use as the spacer oxide.
Monitoring the cure of a composite matrix resin with microdielectrometry

Abstract : Solvent free resin was prepared from a MY720-DDS prepreg solution by evaporation in a vacuum oven. This material was cured under vacuum by a ramp-hold-ramp to cure temperature cycle and the temperature and dielectric loss factor at 5 frequencies were measured every four minutes for the duration of the cure cycle. At selected times during the cure, small samples of the reacting mixture are removed and quenched and subsequently analyzed for Tg. At frequencies of 1 and 10 Hz, the ionic conductivity dominates the loss factor and the logarithmic derivative of the loss factor with respect to time equals the logarithmic derivative of the conductivity with respect to time. This derivative is then related to the derivative of Tg with respect to time by a WLF equation. Keywords: Conductivity, Thermosetting polymers, Williams-Landel-Ferry equation, Glass transition temperature, Epoxy resins, Amine hardener, Network structure, Microdielectrometry, Differential scanning calorimetry, Loss factor.
On the alleged connection between moral evil and human freedom

Those who advance the traditional argument from human freedom presume that human freedom provides an adequate explanation of moral evil. I argue that this presumption is erroneous. An adequate explanation of our capacity to make choices that produce moral evil must be distinguished from an adequate explanation of the actuality of such choices. Human freedom may account for our ability to make choices that issue in moral evil. It cannot, by itself, account for our actually making such choices. Something more than our potential for choices that produce moral evil is required to adequately explain the profusion of moral evil that we actually find in the world.