cssi/SciSciGPT-SciSciNet huggingface dataset:
Biomarkers and surrogate markers: an FDA perspective.

Interest is increasing rapidly in the use of surrogate markers as primary measures of the effectiveness of investigational drugs in definitive drug trials. Many such surrogate markers have been proposed as potential candidates for use in definitive effectiveness trials of agents to treat neurologic or psychiatric disease, but as of this date, there are no such markers that have been adequately “validated,” that is, shown to predict the effect of the treatment on the clinical outcome of interest. While the current law and regulations permit the United States Food and Drug Administration to base the approval of a drug product on a determination the effect of the drug on an unvalidated surrogate marker (that is, one for which it is not known that an effect on the surrogate actually predicts the desired clinical benefit), there are a number of difficulties in interpreting trials that use surrogate markers as primary measures of drug effect. In this article, the relevant regulatory context will be discussed, as well as the epistemological problems related to the interpretation of clinical trials in which unvalidated surrogate markers are used as primary outcomes.
Structure-based engineering of E. coli galactokinase as a first step toward in vivo glycorandomization.

Summary In vitro glycorandomization is a rapid chemoenzymatic strategy to diversify complex natural product scaffolds. The glycorandomization sugar activation pathway is dependent upon the efficient construction of diverse sugar-1-phosphate libraries. In the context of the previously evolved GalK Y371H "gatekeeper" mutation, the active site M173L mutation described herein presents a kinase with remarkably broadened substrate range to include 28 diverse natural and unnatural sugars. Among these new substrates, 6-azido-6-deoxy-galactose and 6-azido-6-deoxy-glucose present unique chemical probes to assess the utility of an E. coli Y371H/M173L-GalK-overproducing strain to generate unnatural sugar-1-phosphates in vivo. Remarkably, the in vivo conversion of both unnatural sugars rival that demonstrated in vitro. This notable in vivo success stands as the first step toward constructing short sugar-activation pathways in vivo and, ultimately, in vivo natural-product glycorandomization.
Environmental controls on the evolution of alluvial fans in Buena Vista Valley, North Central Nevada, during late Quaternary time

Abstract Alluvial fans in Buena Vista Valley, north-central Nevada, formed during at least four time periods during the late Quaternary as evidenced by four temporally and spatially constrained fan deposits: Qf1, Qf2, Qf3, and Qf4, from oldest to youngest. The stratigraphic relation between Qf3 and remnant beach ridge deposits of pluvial Lake Lahontan, the latter of which forms a paleoclimatic proxy for this region, indicate that climate and climatic change are primary controls on the evolution of fans. Qf3 deposition commenced during or immediately following the highstand of Lake Lahontan, between 13.5 and 12.5 ka, and continued as lake levels plummeted to levels below the sill elevation of the Buena Vista subbasin. We interpret Qf3 to be the result of a dynamic interplay between hillslope vegetation, soils, and hydrology as they are conditioned by climate and climatic change. Accelerated pedogenesis, because of aerosolic silts and clays from exposed lake sediments, coupled with decreased density of vegetation reduced infiltration capacity of the hillslope soils in interscrub areas. In contrast to fans in more arid climates, the increased runoff was not associated with increased coarse-grained sediment yield and major fan aggradation. Discharge from sediment-deficient basins entrenched older, proximal fan deposits and transported the sediment downfan to form secondary fans. The process–response of Qf3 to climatic change in north-central Nevada is especially illustrative of the impact of climate on landscapes in that: (1) it results from changes in basin sediment and/or water yield that occur in less than 500 years, and (2) it differs from responses in arid climates to the south and more semiarid climates to the north. The magnitude of vegetation change, including type and density of vegetation and the relative proportion of interscrub area, is particularly critical to water and sediment yield. Unit Qf2, an early late Pleistocene deposit, may also have been deposited during a transition from a wetter to drier climate. The synchronism of aggradation, stability, and entrenchment on all fans along the perimeter of Buena Vista Valley in the late Quaternary is further support for the dominance of climatic control on fan process; on the other hand, the impact of other extrinsic variables on fan process, including tectonism, base level, and basin lithology, all of which vary along the perimeter, is negligible.
Geochemical characteristics of oils from the Sirikit Oilfield, Phisanulok Basin, Thailand

Abstract Twelve oils from the Sirikit field of the Phisanulok Basin, Thailand, have been examined to determine the nature of their source materials, depositional environment, relative maturity and extent of biodegradation. The geochemical analyses performed in this study suggested that all of the oils were derived from similar types of organic source matter consisting of a mixture of bacterial, algal and higher plant material. The sterane contents of the oils were relatively low and conventional maturity parameters based on sterane ratios suggested the oils were relatively immature. Extensive strike/slip faults in the Phisanulok Basin may have led to rapid burial of the sediments during deposition preventing these ratios from having attained their equilibrium ratios.
Multi-layered unstructured mesh generation

Finite Element Mesh Generation is a critical component for many (bio-)engineering and science applications. In this project we will develop a novel framework for guaranteed quality mesh generation for 3D and 4D Finite Element (FE) analysis, able to scale to thousands of cores.
Chronic tolerance to the social consequences of ethanol in adolescent and adult Sprague-Dawley rats

Adolescence is a time when experimentation with ethanol becomes normative, with high levels of use becoming apparent in some adolescents. Little is known, however, as to whether ethanol adaptations emerging in adolescents with repeated ethanol use are similar to those emerging in adults. The presents study used a rodent model to investigate the development of chronic tolerance to ethanol-induced alterations in social behavior. The study focused both on ethanol-induced social facilitations, typically evident in adolescents but not adult animals at low doses of ethanol, as well as the inhibition of social behavior occurring at higher doses in both adolescent and adult rats. Adolescent and adult male and female Sprague-Dawley rats were injected intraperitoneally with either isotonic saline or 1 g/kg ethanol for 7 consecutive days: postnatal day (P) 27-33 for adolescents and P62-68 for adults. Acute effects of ethanol (0, 0.25, 0.5, 0.75, and 1 g/kg) on social behavior, social motivation (measured in terms of social preference), and locomotor activity were assessed 48 h after the last chronic exposure using a modified social interaction test in a familiar environment. Adolescents chronically exposed to ethanol developed tolerance to ethanol-induced social facilitation. Animals of both ages likewise developed chronic tolerance to ethanol-induced social inhibition. Metabolic tolerance emerged in adults, as indexed by a decrease in blood ethanol concentrations after chronic ethanol at this age, whereas only functional tolerance was evident in adolescents. Unexpectedly, chronic ethanol diminished baseline levels of social preference in adolescents, but made them more responsive to ethanol-induced enhancement of social preference. Chronic ethanol exposure in adulthood, however, only induced tolerance to the suppressing effects of higher ethanol doses on social preference. Thus, whereas adolescents and adult both develop adaptations following repeated exposure to ethanol, adolescents are more vulnerable to the disruptive effects of chronic ethanol exposure on social preference than their more mature counterparts.
Energetics of Charged Particle-Induced Fission Reactions

Measurements with a semiconductor detector system and a two-dimensional analyzer have yielded information on the mass distributions and the details of the kinetic energy reiease from a series of charged particle-induced fission reactions. The fissioning compound nuclei range from thallium for which the mass distributions are symmetric, to plutonium for which the fission is predominantly asymmetric. In an intermediate region, the charged particle-induced fission of Ra/sup 226/ yields comparable contributions of symmetric and asymmetric fission. The results are quantitatively consistent with a two-mode hypothesis for the fission process and indicate that within each mode the distance between the charge centers of the two fragments at the scission point is approximately the same for all mass divisions. The results show a lower total kinetic energy release from symmetric fission than from asymmetric fission, indicating that the distance between the charge centers at the scission point is about 10% greater for the symmetric mode than for the asymmetric mode. (auth)
Diurnal hypercapnia in patients with neuromuscular disease

Summary Subjects with progressive neuromuscular diseases undergo a typical sequence of respiratory compromise, leading from normal unassisted gas exchange to nocturnal hypoventilation with normal daytime gas exchange, and eventually to respiratory failure requiring continuous ventilatory support. Several different abnormalities in respiratory pump function have been described to explain the development of respiratory failure in subjects with neuromuscular weakness. Early in the progression of respiratory failure, the use of nocturnal assisted ventilation can reverse both night- and day-time hypercapnia. Eventually, however, diurnal hypercapnia will persist despite correction of nocturnal hypoventilation. The likely beneficial effects of mechanical ventilatory support include resting fatigue-prone respiratory muscles and resetting of the central chemoreceptors to PaCO 2 . Recent experience shows that select patients who require daytime ventilation can be supported with non-invasive ventilation continuously to correct gas exchange abnormalities while avoiding detrimental aspects of tracheostomy placement.
The influence of 2,4-D and kinetin on leaf callus formation in different potato species.

Leaf segments ofSolanum tuberosum andS. acaule can proliferate callus. However, callus formation and growth for a specific species depends on different concentrations of 2,4-D and kinetin (6-furfurylamino purine) used in a medium. Large amounts of creamy white friable callus could be proliferated fromS. tuberosum when explants were cultured in media containing 3 mg of 2,4-D and 0.3 mg of kinetin per liter. WhenS. acaule explants were cultured in the similar medium, the segment tended to become yellow; however, when it was subcultured onto a similar fresh medium, friable and creamy white callus was then formed. In a medium containing 0.3 mg of 2,4-D and 1 mg of kinetin per liter, the compact callus could be directly proliferated fromS. acaule leaf segments. Segments incubated under light formed less callus than those incubated in darkness.
Clinical experience with low-dose continuous infusion of furosemide in acute heart failure: assessment of efficacy and safety.

Introduction:Clinical data are scarce for furosemide administered as a low-dose (<160 mg/24 hours) continuous intravenous infusion in acute heart failure (HF). Our purpose was to evaluate the effic...
Marine fungi (Ascomycetes) within and on tests of Foraminifera

Fruiting bodies of higher marine fungi occur within and on tests of foraminiferans on tropical beaches of the Pacific (Australia, Hawaii) and Atlantic Ocean (Belize, Mexico). Ascocarps (fruiting bodies ) of five intertidal species or varieties of the genera Arenariomyces, Corollospora and Lindra colonize foraminiferans in the natural habitat and may contribute to the eventual breakup of the tests. Fungal fruiting structures, which are normally subglobose when developing in other substrates, adjust to the shape of the foraminiferan chambers when growing within the tests. Pure cultures of L. thalassiae var. crassa yielded the same type of irregular fruiting bodies when grown at 30° C on foraminiferan tests as the sole source of nutrients.
The Structural Basis of Estrogen Receptor/Coactivator Recognition and the Antagonism of This Interaction by Tamoxifen

Ligand-dependent activation of transcription by nuclear receptors (NRs) is mediated by interactions with coactivators. Receptor agonists promote coactivator binding, and antagonists block coactivator binding. Here we report the crystal structure of the human estrogen receptor alpha (hER alpha) ligand-binding domain (LBD) bound to both the agonist diethylstilbestrol (DES) and a peptide derived from the NR box II region of the coactivator GRIP1 and the crystal structure of the hER alpha LBD bound to the selective antagonist 4-hydroxytamoxifen (OHT). In the DES-LBD-peptide complex, the peptide binds as a short alpha helix to a hydrophobic groove on the surface of the LBD. In the OHT-LBD complex, helix 12 occludes the coactivator recognition groove by mimicking the interactions of the NR box peptide with the LBD. These structures reveal the two distinct mechanisms by which structural features of OHT promote this "autoinhibitory" helix 12 conformation.
The spectrum of avulsion and avulsion-like injuries of the musculoskeletal system

Awareness of the radiographic appearances of various avulsion injuries helps the radiologist to arrive at an accurate diagnosis without unnecessary patient workup.
Requirement of macrophages and eosinophils and their cytokines/chemokines for mammary gland development

Epithelial/mesenchymal cell interactions are necessary for proper ductal morphogenesis throughout all stages of mammary gland development. Besides the well-established stromal components, such as adipocytes and fibroblasts, the mammary stroma is also infiltrated with migrating blood cells, mostly macrophages and eosinophils. The focus of this review is on the role of macrophages and their growth factor colony-stimulating factor 1 (CSF-1) in promoting branching morphogenesis during postnatal mammary gland development through to lactation. The more restricted role of eosinophils and their chemoattractant eotaxin during pubertal ductal morphogenesis is also discussed. A possible interaction between macrophages and eosinophils in ductal morphogenesis is considered, along with the roles of other chemokines. This role of macrophages in normal development also appears to be subverted by tumors of the mammary gland to promote the escape of the tumor cells from the local environment and enhance their rate of metastasis. These data emphasize the dual role of macrophages in the promotion of epithelial growth in normal and cancer states.
An architectural level test generator for a hierarchical design environment

Most state-of-the-art automatic test pattern generators (ATPGs) require a detailed gate level representation for the circuits under test, information that either does not exist or may not be available to the test engineers in a hierarchical design environment. An ATPG methodology working at an architectural level is proposed to exploit the hierarchy of the design and relieve the dependence on the gate level information. The test set for each high level primitive is pregenerated by any low-level sequential ATPG tool, based on any possible fault model. The test patterns in these test sets are justified and the fault effects are propagated at high level. Due to the fault collapsing effect, several data types have been defined for the manipulation of all possible fault effects. When conflict occurs and the backtracking mechanism is invoked, a novel tracing technique and an indexed backtracking technique are used to make high-level decisions. >
Development of an HPLC Method for Simultaneous Analysis of Five Antineoplastic Agents

Simultaneous analysis of common antineoplastic agents potentially hazardous to healthcare workers is of much interest for the evaluation of the overall health risk to these workers. Such analysis could be applied to both air and surface monitoring samples to provide a broader indication of risk to combinations of these agents. It was determined that the ability to simultaneously evaluate five frequently used, potentially hazardous agents was sufficient for general evaluation of exposures to healthcare workers. The approach used to select the five agents was to obtain a list of the agents used most frequently in both a cancer hospital and an outpatient cancer treatment center, then review the list to determine which agents were potentially more hazardous to human health. From these reviews, it was decided to attempt to develop an analytical method able to detect and quantify the presence of 5-fluorouracil, ifosfamide, cyclophosphamide, doxorubicin HCl, and paclitaxel. A reverse-phase high performance liqui...
Mismeasured Variables in Econometric Analysis: Problems from the Right and Problems from the Left

The effect of mismeasured variables in statistical and econometric analysis is one of the oldest known problems, dating from the 1870s in Adcock (1878). In the most straightforward regression analysis with a single regressor variable, the least squares estimate is downward biased in magnitude toward zero. 1 While a mismeasured right-hand side variable creates this problem, a mismeasured left-hand side variable under classical assumptions does not lead to bias. The only result is less precision in the estimated coefficient and a lower t-statistic. I will begin by reviewing these classical issues involving mismeasured variables. By the “classical mismeasurement assumptions,” I mean that the error of measurement is uncorrelated with the true variables and is uncorrelated with the stochastic disturbance in the regression specification. Then I will consider three recent developments for the effect of mismeasurement on econometric models. The first issue involves difficulties in using instrumental variables as a method of addressing the problem of mismeasured variables. A second involves the consistent estimators that have recently been developed for mismeasured nonlinear regression models. Finally, I return to mismeasured left-hand side variables, where I will focus on issues in binary choice models and duration models but also will point out some open issues in other models.
On two competing mechanisms for priority-based allocation problems

We consider the priority-based allocation problem: there is a set of indivisible objects with multiple supplies (e.g., schools with seats) and a set of agents (e.g., students) with priorities over objects (e.g., proximity of residence area). We study two well-known and competing mechanisms. The agentoptimal stable mechanism (AOSM) allots objects via the deferred acceptance algorithm. The top trading cycles mechanism (TTCM) allots objects via Gale’s top trading cycles algorithm. We show that the two mechanisms are equivalent, or TTCM is fair (i.e., respects agents’ priorities), or resource monotonic ,o rpopulation monotonic, if and only if the priority structure is acyclic. Furthermore, if AOSM fails to be efficient (consistent) for a problem, TTCM also fails to be fair (consistent) for it. However, the converse is not necessarily true.
Discrete in vivo roles for the MutL homologs Mlh2p and Mlh3p in the removal of frameshift intermediates in budding yeast

Abstract The DNA mismatch repair machinery is involved in the correction of a wide variety of mutational intermediates. In bacterial cells, homodimers of the MutS protein bind mismatches and MutL homodimers couple mismatch recognition to downstream processing steps [1]. Eukaryotes possess multiple MutS and MutL homologs that form discrete, heterodimeric complexes with specific mismatch recognition and repair properties. In yeast, there are six MutS (Msh1–6p) and four MutL (Mlh1–3p and Pms1p) family members [2,3]. Heterodimers comprising Msh2p and Msh3p or Msh2p and Msh6p recognize mismatches in nuclear DNA [4,5] and the subsequent processing steps most often involve a Mlh1p–Pms1p heterodimer [6,7]. Mlh1p also forms heterodimeric complexes with Mlh2p and Mlh3p [8], and a minor role for Mlh3p in nuclear mismatch repair has been reported [9]. No mismatch repair function has yet been assigned to the fourth yeast MutL homolog, Mlh2p, although mlh2 mutants exhibit weak resistance to some DNA damaging agents [10]. We have used two frameshift reversion assays to examine the roles of the yeast Mlh2 and Mlh3 proteins in vivo . This analysis demonstrates, for the first time, that yeast Mlh2p plays a role in the repair of mutational intermediates, and extends earlier results implicating Mlh3p in mismatch repair.
Ikaros, a lymphoid-cell-specific transcription factor, contributes to the leukemogenic phenotype of a mink cell focus-inducing murine leukemia virus.

Mink cell focus-inducing (MCF) viruses induce T-cell lymphomas in AKR/J strain mice. MCF 247, the prototype of this group of nonacute murine leukemia viruses, transforms thymocytes, in part, by insertional mutagenesis and enhancer-mediated dysregulation of cellular proto-oncogenes. The unique 3′ (U3) regions in the long terminal repeats of other murine leukemia viruses contain transcription factor binding sites known to be important for enhancer function and for the induction of T-cell lymphomas. Although transcription factor binding sites important for the biological properties of MCF 247 have not been identified, pathogenesis studies from our laboratory suggested to us that binding sites for Ikaros, a lymphoid-cell-restricted transcriptional regulator, affect the biological properties of MCF 247. In this report, we demonstrate that Ikaros binds to predicted sites in U3 sequences of MCF 247 and that site-directed mutations in these sites greatly diminish this binding in vitro. Consistent with these findings, ectopic expression of Ikaros in murine cells that do not normally express this protein significantly increases transcription from the viral promoter in transient gene expression assays. Moreover, site-directed mutations in specific Ikaros-binding sites reduce this activity in T-cell lines that express Ikaros endogenously. To determine whether the Ikaros-binding sites are functional in vivo, we inoculated newborn mice with a variant MCF virus containing a mutant Ikaros-binding site. The variant virus replicated in thymocytes less efficiently and induced lymphomas with a delayed onset compared to the wild-type virus. These data are consistent with the hypothesis that the Ikaros-binding sites in the U3 region of MCF 247 are functional and cooperate with other DNA elements for optimal enhancer function in vivo.
Anal HIV DNA is associated with high-risk HPV genotypes in anal cytology specimens obtained for anal neoplasia screening

Purpose High-grade anal neoplasia (AN) is associated with highrisk human papillomavirus (HPV) genotypes and is the precursor to anal cancer. Individuals infected with human immunodeficiency virus type 1 (HIV) continue to be at increased risk for AN even while on effective antiretroviral therapy (ART) with undetectable HIV RNA levels. The study was undertaken to assess HIV DNA from anal cytology specimens to determine if HIV DNA copy number was a factor for presence of high risk HPV genotypes.
Introduction to special series on college students with ADHD: psychosocial issues, comorbidity, and treatment

Increasing empirical attention has been focused on college students with ADHD in recent years. In this special series, five studies are included that address psychosocial issues, comorbidity, and treatment of college students with ADHD. The nature and results of each study are briefly described. This special series of articles significantly advances our knowledge of critical issues with respect to psychosocial functioning, alcohol/substance use, comorbidity, and treatment of ADHD in college students.
Preparation and Characterization of Coenzyme Q10–Eudragit® Solid Dispersion

A solid dispersion of Coenzyme Q10 and Eudragit L 100-55 was prepared using solvent evaporation method. Solid dispersion, physical mixture, and pure compound were then characterized using differential scanning calorimetry and powder x-ray diffraction. Solubility of CoQ10 in different surfactant media was measured, and a suitable dissolution medium was developed to compare the dissolution patterns of the solid dispersion, physical mixture, and the pure compound. Combining labrasol with different surfactants in dissolution media demonstrated an additive effect on CoQ10 solubility. The solubility of CoQ10 in a 4% Labrasol/2% Cremophor EL solution was 562 microg/ml, which was five times higher than the combined solubility in 5% Labrasol (91 microg/ml) and 5% Cremophor EL (7.8 microg/ml). Moderate change in the crystalline pattern of CoQ10 was observed, which was attributed to solvent displacement rather than the degree of crystallinity change. The dissolution test indicated that the in-vitro release of Coenzyme Q10 from its solid dispersion was much faster than its physical mixture, which in turn was faster than the pure drug. The amount of drug released in 12 hours from solid dispersion, physical mixture, and the pure drug was 100, 26.5 and 12.5% respectively. CoQ10 was photostable throughout the dissolution experiments.
Breaking all the invariants: Anomalous electron radiation belt diffusion by pitch angle scattering in the presence of split magnetic drift shells

Relativistic electron observations near geostationary orbit routinely show pitch angle distributions peaked away from 90 degrees. These “butterfly” distributions are consistent with magnetic drift shell splitting combined with a radial flux gradient. During magnetic storms, nature adds pitch angle scattering to split drift shells, breaking all three adiabatic invariants of the particle's motion. Therefore, some degree of anomalous radial diffusion is likely, and cross terms between the gyration and drift invariants and between the bounce and drift invariants arise. Using typical assumptions about the pitch angle scattering and the magnetic field topology, we calculate these anomalous diffusion coefficients near geostationary orbit. We show that the anomalous radial diffusion can exceed that due to more traditional drift-resonant wave-particle interactions. We also show that the neglected cross terms, particularly the bounce-drift cross term, can be significant. These results suggest necessary additions to some global electron radiation belt simulations.
Investigating γ-secretase protein interactions in live cells using active site-directed clickable dual-photoaffinity probes

We have developed a suite of clickable γ-secretase active site-directed dual-photoaffinity probes possessing photoactivatable benzophenones that are located within the inhibitor scaffold as well as spaced away from the core by a linker. Through photoactivation of these dual photoprobes and subsequent click chemistry mediated conjugation of a reporter group, we have been able to specifically label PS1-N-terminal fragment (PS1-NTF), PS1-C-terminal fragment (PS1-CTF) and nicastrin and form a pseudo-full length PS1 through crosslinks between PS1-NTF and PS1-CTF. Probe-mediated protein–protein crosslinks were confirmed by in-gel fluorescence, western blotting and LC-MS/MS detection of tryptic peptides of the electrophoretically separated proteins.
Effectiveness of Laser Application for Periodontal Surgical Therapy: Systematic Review and Meta‐Analysis

Background: Evidence has shown some improved clinical outcomes and morbidity reduction with the use of lasers for non-surgical periodontal therapy due to ablation, vaporization, hemostasis, and field sterilization. The purpose of this systematic review is to evaluate and compare studies involving lasers as monotherapy or adjunctive to surgical periodontal treatment.Methods: Electronic and manual searches were conducted by two independent reviewers in several databases for articles written in English up to December 2014. Articles were included in this review if they reported outcomes of surgical periodontal therapy with and without the use of lasers. The primary outcome was probing depth (PD), and secondary outcomes were measured changes in clinical factors such as clinical attachment level (CAL) and gingival recession (GR). For the comparative studies included, the pooled weighted mean difference (WMD) and 95% confidence interval (CI) of each variable were calculated using random-effects meta-analysis.Res...
Continuing the Dialogue: Reducing Minimum Legal Drinking Age Laws from 21 to 18

The purpose of this paper is to examine both sides of the debate revolving around the issue of reducing the minimum legal drinking age law from age 21 to 18 years of age. Ethical considerations surrounding the issue are offered. The current 1984 National Minimum Drinking Age Act (MLDA 21) has been shown to save lives. However, in 2008 the major supporters of reducing the minimum legal drinking age laws from 21 to 18 issued a call to dialogue. The Amethyst Initiative and Choose Responsibility have spearheaded opposition to MDLA 21. They call for a public dialogue about the ineffectiveness of MLDA 21 laws; whereas proponents of MLDA 21 laws provide evidence-based data that the MLDA 21, laws save lives. The authors provide arguments in opposition to reducing the age requirements of the MLDA 21 laws and present ethical considerations that represent both sides of the issues. The authors conclude that in view of the adverse consequences of alcohol-related traffic injuries/fatalities among youth ages 15–20, cont...
The Role of Si-H Functionality in Oxycarbide Glass Synthesis

Silicon oxycarbide gels and glasses were synthesized using various ratios of methyldimethoxysilane and TEOS. These gels and glasses were compared with those made from methyltrimethoxysilane and TEOS. The effect of the Si-H functionality in the methyldimethoxysilane was of primary interest. Hydrolysis and condensation processes were monitored using 1H and 29Si-NMR spectroscopy. The structures and the oxycarbide fractions of the glasses, obtained after heating the gels to 900°C in flowing argon, were investigated with 29si-MAS NMR. The total carbon and silicon contents of the glasses were determined using chemical analysis. The glasses covered the range of carbon concentration from ~1 to 15%, while the silicon concentrations were constant at about 40%. The concentration of the oxycarbide species was enhanced in the glasses synthesized with the Si-H functionality in the precursor.
The Relationship Between Creativity and Behavior Problems Among Underachieving Elementary and High School Students

Understanding the role creative potential may play in the underachievement of some students could help schools and parents understand underachievers. This study examined whether there is a relationship between creativity and behavior problems among underachievers. Forty-one elementary and 89 high school students and 4 teachers in Korea participated in this study. The principal study involved comparing all of the students' scores on the 3 measures of creative potential (Torrance Tests of Creative Thinking-Figural [TTCT], Runco Ideational Behavior Scale [RIBS], and Scales for Rating the Behavioral Characteristics of Superior Students-Revised Edition [SRBCSS-R]), with their scores on a measure of behavior problems reported by their teachers. The results indicated that, among underachievers, there is a relationship between behavioral problems and students' scores on the 3 measures of creative potential. An understanding of these students and their behavior will help us promote creative students' academic and ...
Atrial natriuretic peptide suppresses osmostimulated vasopressin release in young and elderly humans.

Atrial natriuretic peptide (ANP) may suppress vasopressin release, but the dynamics of this interaction as well as the influence of age have not been defined. We studied six or seven young (19-40 yr old) and seven elderly volunteers (65-83 yr old) under two circumstances: 1) after infusion of 5% saline (0.04 ml.kg-1.min-1) for 2 h and 2) after the same infusion given with simultaneous synthetic human ANP (0.05 micrograms.kg-1.min-1). Hypertonic saline alone produced a progressive rise in plasma vasopressin with increasing serum sodium. During hypertonic saline alone, vasopressin levels began to rise at an increment in serum sodium of 1.67 +/- 0.35 mM in the young and 1.43 +/- 0.32 mM in the elderly and rose linearly with increasing serum sodium. When ANP was infused with hypertonic saline (with peak ANP levels of approximately 1,000 pM), vasopressin levels began to rise at an increment in serum sodium of 4.43 +/- 0.67 mM in the young and 4.57 +/- 0.43 mM in the elderly (P less than 0.01 vs. saline alone). Furthermore, the vasopressin response for any given serum sodium was significantly reduced in both young and elderly subjects, resulting in a rightward displacement of the curve relating vasopressin response to sodium concentration (P less than 0.001). In conclusion, ANP not only suppresses vasopressin but raises the threshold for release of vasopressin in response to osmotic stimulation in both young and elderly individuals. High circulating ANP levels may be responsible in part for the suppression of vasopressin levels and water diuresis seen during states of volume expansion.
Immunology: A bacterial nudge to T-cell function

The epithelial cells that line the intestine have been found to sense tight attachment of bacteria, and to respond by producing proteins that shape the effector functions of the immune system's TH17 cells.
Headache and Facial Pain in Sickle Cell Disease

Children and adolescents with sickle cell disease (SCD) have a high prevalence of recurrent headaches (24.0-43.9 %). Acute presentation with headache can be diagnostically challenging, as the clinician must consider evaluation of several potentially devastating conditions including vascular diseases (stroke, hemorrhage, venous sinus thrombosis, moyamoya, posterior reversible encephalopathy syndrome), facial and orbital bone infarcts, dental pain, and osteomyelitis. Patients with SCD and primary headache disorders may benefit from comprehensive headache treatment plans that include abortive therapy, prophylactic therapy, and non-pharmacological modalities. Although there is limited data in adults, those with SCD are at risk for medication overuse headache secondary to frequent opioid use. Addressing headache in patients with SCD may help to reduce their use of opioids and disability and improve pain and quality of life.
A Simplified model of mutually inhibitory sleep-active and wake-active neuronal populations employing a noise-based switching mechanism

Infant rats switch randomly between the sleeping and waking states; during early infancy (up to postnatal day 8), sleep and wake bouts are random, brief (with means on the order of several seconds) and exponentially distributed, with the length of a particular bout independent of the length of prior bouts. As the rat ages during this early period, mean sleep and wake bout lengths gradually increase, though sleep and wake bouts remain exponentially distributed. Additionally, sleep and wake bouts are regulated independently of each other - alterations in the development of sleep (wake) bouts has no impact on the regulation wake (sleep) bouts. Sleep and wake bout behavior is associated with the activity of mutually inhibitory sleep-active and wake-active brainstem populations. In this work, I employ a simplified biophysical model of two mutually inhibitory populations consisting of ten integrate-and-fire neurons each and a noise-based switching mechanism. I show that such a noise-based switching mechanism naturally accounts for the experimentally observed features of sleep-wake switching during early infancy - random alternating activity bouts occur as a consequence of noise (provided inhibition is strong relative to excitation), bout durations are exponential (due to a lack of memory within the system), and cross-population inhibition or intrapopulation excitatory coupling provide mechanisms for changing and independently regulated sleep and wake bout means.
Inclusion body myositis.

Publisher Summary This chapter discusses inclusion body myositis (IBM). It is usually a slowly progressive myopathy that causes considerable morbidity but does not directly cause mortality. The lack of any effective treatments makes it a challenge to manage. Inclusion-body myopathy is usually of late onset with more than 80% of cases occurring over the age of 50 years. Nearly all cases of IBM are sporadic. Cases have been described of siblings and twins with a phenotype identical to sporadic inclusion body myositis and with inflammation in their muscle biopsies. The presentation of typical IBM reflects the insidious onset and progression of the disease and the often stereotyped pattern of muscle involvement. The first symptom is often one of sudden, unprovoked falls without loss of consciousness. Despite the lack of facial symptoms in a third of cases examination shows mild weakness of eyelid or lip closure that is not a feature of inflammatory myopathies such as polymyositis and dermatomyositis. Muscle biopsy is essential for a definitive diagnosis of IBM. The diagnosis of IBM is based upon a combination of clinical, laboratory, and histological data. The increasing understanding of the degenerative aspects of IBM opens up a further range of therapeutic options.
Confirmatory Analysis of Aggregate Hierarchical Market Structures: Inferences from Brand-Switching Behavior

A probabilistic model is developed for testing hypothesized hierarchical market structures at the aggregate level using brand-switching data. Each hypothesized structure is represented by a directe...
How ocean currents are studied

How infinite and boundless the ocean must have seemed to the first man to set foot upon its shore. Kind or stern, shallow or steep, the ocean’s shores have always held a peculiar fascination for man. The moist warm breath of wide expanses of water forces the winter cold to retreat and, in coastal waters, teeming with life, one can always find sustenance. The ever-changing beauty of the sea shore has helped to enrich man’s spiritual life. Ancient people could only ponder upon the mystery of existence as they watched inexplicable oceanic phenomena that at times could be very hostile and threatening. How was it possible for capes and distant shores to withstand this great surge, these huge storm waves and tornadoes sweeping across the sky? Only a boundless element could give rise to such phenomena.
Outsider Indigenous Research: Dancing the Tightrope Between Etic and Emic Perspectives

In diesem Beitrag beschreibe ich, wie ich in einer eigene Studie versucht habe, etische und emische Perspektiven so zu variieren, dass indigenes (Insider-) Wissen besser berucksichtigt werden konnte. Ich habe hierzu ein iteratives methodologisches Modell konzipiert, das etische und emische Ansatze in methodische Praktiken zu uberfuhren versucht. Kern dieses Modells ist das Konzept der methodologischen Flexibilitat (Methoden, die hinreichend "weich" sind, um Insider-Perspektiven fassen zu konnen). Das zu leistende Reframing, d.h. das Balancieren etischer und emischer Perspektiven im Rahmen dieses Modells verfolgt, dem Konzept der methodologischen Flexibilitat genugend, zwei Ziele: Erstens unterstutzt es die Reflexivitat der Forschenden. Und zweitens eroffnet es die Moglichkeit zur Diskussion praktischer Anpassungen, die emischen Perspektiven in allen Phasen des Forschungsprozesses (Design, Datenerhebung, Datenanalyse) zu einem besseren Ausdruck verhelfen sollen. Im Weiteren beschreibe ich, wie ich in meiner eigenen Studie, die ich in Yucatan (Mexiko) mittels eines Mixed-Methods-Ansatzes durchgefuhrt habe, die Balance zwischen den dort tendenziell polaren Perspektiven zu halten versucht habe. Konkrete methodische Vorschlage sollen Forschenden helfen, die als "Outsider" Forschung in indigenen Kontexten betreiben wollen. URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs160364
Abstract B080: Noninvasive imaging of antitumor responses as a possible predictive tool

Immunotherapy has produced durable remissions across a spectrum of malignancies. However, predicting and monitoring therapeutic outcomes remains a challenge. Techniques to achieve these goals without multiple biopsies or other invasive methods will be critical to further improve on immunotherapy. Noninvasive imaging of immune responses is therefore a highly desirable goal. The abundance, movement and expansion of relevant cell types may yield reproducible patterns in responders and nonresponders that could help understand, if not predict, the failure or success of a therapy. To enable noninvasive imaging of the targeted cell populations, we isolated camelid-derived single domain antibody fragments (VHHs) against CD8, PD-L1, CTLA, Class II MHC, and CD11b markers. We also developed a method to site-specifically label VHHs with 18F, 64Cu or 89Zr. Radiolabeled VHHs rapidly clear the circulation (t1/2≈15-30 min) and clearly visualize their targets. Through PET imaging using radiolabeled VHHs, we can monitor and explore patterns of responses in the tumor microenvironment, as such or in response to therapy. Early results suggest that infiltration of a tumor by CD8 T cells may be used as a prognostic criterion. Tumors homogenously infiltrated by CD8-T cells appear more likely to respond than tumors that have heterogeneous CD8-T cell infiltration. Important next questions to be explored by PET imaging include the following. What is the role of regulatory T cells (Tregs) and macrophages? How does the CD8-T cell/Treg-cell ratio change in response to treatment? Is it possible to stratify responders from non-responders soon after starting therapy, and how would this affect treatment strategies? Because the basic methodology proposed here is in principle translatable to a human setting, this approach may ultimately find clinical application. Citation Format: Mohammad Rashidian, Hidde Ploegh. Noninvasive imaging of antitumor responses as a possible predictive tool [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B080.
Seizure onset zone localization from many invasive EEG channels using directed functional connectivity

In this study we investigated how directed functional connectivity can be used to localize the seizure onset zone (SOZ) from ictal intracranial EEG (iEEG) recordings. First, simulations were conducted to investigate the performance of two directed functional connectivity measures, the Adaptive Directed Transfer Function (ADTF) and the Adaptive Partial Directed Coherence (APDC), in combinations with two graph measures, the out-degree and the shortest path, to localize the SOZ. Afterwards the method was applied to the seizure of an epileptic patient, recorded with 113-channel iEEG and localization was compared with the subsequent resection that rendered the patient seizure free. We found both in simulations and in the patient data that the ADTF combined with the out-degree and shortest path resulted in correct SOZ localization. We can conclude that ADTF combined with out-degree or shortest path are most optimal to localize the SOZ from a high number of iEEG channels.
Biologics for Adult Lumbar Scoliosis

Adult scoliosis, arising either as a sequelae of untreated adolescent idiopathic scoliosis or as a de novo degenerative deformity, has been estimated in as much as 68 % of adults over the age of 60 [1]. Anwar et al. further reported that adult lumbar scoliosis in particular was significantly underreported, particularly in scoliotic curves 30–40° are commonly considered for operative treatment [3, 5]. The Lenke-Silva Treatment Levels I–VI matrix offers distinct procedural options for lumbar scoliosis indications, which range from decompression only to decompression with instrumentation utilizing varying surgical approaches, construct lengths, and need for osteotomy inclusion [3].
Peritoneal drainage is associated with higher survival rates for necrotizing enterocolitis in premature, extremely low birth weight infants.

Abstract Background To evaluate peritoneal drainage (PD) and laparotomy ± resection/ostomy (LAP) as initial approaches to the surgical management of necrotizing enterocolitis (NEC) in premature, extremely low birth weight (ELBW) infants. Methods Kids' Inpatient Database (2003-2012) was searched for cases of NEC (International Classification of Diseases, ninth revision, Clinical Modification [ICD-9-CM] 777.5x) in premature ( Results On PS-matched comparison, PD had higher survival versus LAP, P = 0.0009. LOS and cost were higher for PD versus LAP, P Conclusions A risk-adjusted PS-matched analysis of operative management in premature, ELBW infants with NEC found higher survival rates associated with PD placement versus LAP, whether PD was used as definitive treatment or with subsequent LAP even after controlling for potential contributors to selection bias (i.e., stability influencing management preference).
City and regional planning: a primer for public health officials.

Recognizing that planners’ decisions affect the public’s health, some public health officials are becoming more involved in city and regional planning. This article describes city and regional planning fundamentals to help public health practitioners better understand plan making and plan implementation, including the development project review process; provides examples of how three local public health agencies are currently involved in planning; and discusses general strategies for such participation. With this information, public health officials could increase their influence on local planning with consequent public health benefits.
Can microbial cells develop resistance to oxidative stress in antimicrobial photodynamic inactivation

Infections have been a major cause of disease throughout the history of humans on earth. With the introduction of antibiotics, it was thought that infections had been conquered. However, bacteria have been able to develop resistance to antibiotics at an exponentially increasing rate. The growing threat from multi-drug resistant organisms calls for intensive action to prevent the emergence of totally resistant and untreatable infections. Novel, non-invasive, non-antibiotic strategies are needed that act more efficiently and faster than current antibiotics. One promising alternative is antimicrobial photodynamic inactivation (APDI), an approach that produces reactive oxygen species when dyes and light are combined. So far, it has been questionable if bacteria can develop resistance against APDI. This review paper gives an overview of recent studies concerning the susceptibility of bacteria towards oxidative stress, and suggests possible mechanisms of the development of APDI-resistance that should at least be addressed. Some ways to potentiate APDI and also to overcome future resistance are suggested.
The Welfare Effects of Ethanol and Biodiesel Mandates on Edible Oil Uses in the United States

The purpose of this study is to analyze the welfare effects of the ethanol and biodiesel mandates on edible oil, gasoline and corn uses in the United States, as well as potential price increase caused by such mandates and policies. Despite all the claims that the federal mandates and policies have caused the prices of corn and vegetable oils to increased, the literature lacks the evidence and information needed to deduce any results and arrive in a an inclusive conclusion.