cssi/SciSciGPT-SciSciNet huggingface dataset:
A LABORATORY AND FIELD STUDY OF ICEBERG DETERIORATION

Vertical ice walls in warm sea water deteriorate from the action of natural convective boundary layers. A cooperative field study with the International Ice Patrol shows that in 4°C sea water melt-driven upwelling occurs adjacent to an iceberg. The effects of the iceberg on the water column were to lower the temperature and salinity by 3.0°C and 0.5°/00. In the laboratory this process was modeled using fresh water bubble-free ice sheets immersed in sodium chloride solutions of oceanic salinities and temperatures. The observed flow field next to the ice face was laminar at the bottom, then went through a region of transition and finally became fully turbulent further up the ice. The length of the laminar layer for oceanic conditions has a maximum length of 0.5 m, at which point the saline Grashof number reaches a critical value 2 × 108 and the flow becomes turbulent. Measurements of the melt rate and the ice/water interface temperature in the turbulent regime show uniform temperatures and a melting rate that varies slowly in the vertical; this greatly facilitates theoretical modeling of the flow. For subpolar water temperatures, 0° to 5°C, the experiments show the melt rate to be of the order 0.1 m day–1; for tropical water temperatures, 25°C, the melt rate is of the order 2.5 m day–1.
Synthesis and pharmacological characterization of functionalized 6-piperazin-1-yl-purines as cannabinoid receptor 1 (CB1) inverse agonists.

Abstract Antagonists of peripheral type 1 cannabinoid receptors (CB1) may have utility in the treatment of obesity, liver disease, metabolic syndrome and dyslipidemias. We have targeted analogues of the purine inverse agonist otenabant (1) for this purpose. The non-tissue selective CB1 antagonist rimonabant (2) was approved as a weight-loss agent in Europe but produced centrally mediated adverse effects in some patients including dysphoria and suicidal ideation leading to its withdrawal. Efforts are now underway to produce compounds with limited brain exposure. While many structure-activity relationship (SAR) studies of 2 have been reported, along with peripheralized compounds, 1 remains relatively less studied. In this report, we pursued analogues of 1 in which the 4-aminopiperidine group was switched to piperazine group to enable a better understanding of SAR to eventually produce compounds with limited brain penetration. To access a binding pocket and modulate physical properties, the piperazine was functionalized with alkyl, heteroalkyl, aryl and heteroaryl groups using a variety of connectors, including amides, sulfonamides, carbamates and ureas. These studies resulted in compounds that are potent antagonists of hCB1 with high selectivity for hCB1 over hCB2. The SAR obtained led to the discovery of 65 (Ki = 4 nM, >1,000-fold selective for hCB1 over hCB2), an orally bioavailable aryl urea with reduced brain penetration, and provides direction for discovering peripherally restricted compounds with good in vitro and in vivo properties.
Movement and perception recalibrate differently across multiple days of locomotor learning.

Error-based adaptation learning drives changes in movement and perception of movement. Are these changes across domains linked or simply coincidental? Here, we studied changes in movement and perce...
Gas pressure dependence of microwave pulses generated by laser-produced filament plasmas.

The plasma arising due to the propagation of a filamenting ultrafast laser pulse in air contains currents driven by the pulse that generate radiated electromagnetic fields. We report absolutely calibrated measurements of the frequency spectrum of microwaves radiated by the filament plasma from 2-40 GHz. The emission pattern of the electric field spectrum is mapped as a function of air pressure from atmosphere to 0.5 Torr. For fixed laser pulse energy, duration, and focal geometry, we observe that decreasing the air pressure by a factor of approximately 103 increases the amplitude of the electric field waveform by a factor of about 40. As the air pressure decreases, the lower frequency components ( 20 GHz). To the best of our knowledge, this behavior has not been observed before, is not predicted by existing theory, and implies the existence of a radiation mechanism in the plasma distinct from that which emits at terahertz frequencies.
A Bifunctional Role for the UHRF1 UBL Domain in the Control of Hemi-methylated DNA-Dependent Histone Ubiquitylation.

DNA methylation patterns regulate gene expression programs and are maintained through a highly coordinated process orchestrated by the RING E3 ubiquitin ligase UHRF1. UHRF1 controls DNA methylation inheritance by reading epigenetic modifications to histones and DNA to activate histone H3 ubiquitylation. Here, we find that all five domains of UHRF1, including the previously uncharacterized ubiquitin-like domain (UBL), cooperate for hemi-methylated DNA-dependent H3 ubiquitin ligation. Our structural and biochemical studies, including mutations found in cancer genomes, reveal a bifunctional requirement for the UBL in histone modification: (1) the UBL makes an essential interaction with the backside of the E2 and (2) the UBL coordinates with other UHRF1 domains that recognize epigenetic marks on DNA and histone H3 to direct ubiquitin to H3. Finally, we show UBLs from other E3s also have a conserved interaction with the E2, Ube2D, highlighting a potential prevalence of interactions between UBLs and E2s.
Adolescent Alcohol Exposure Epigenetically Suppresses Amygdala Arc Enhancer RNA Expression to Confer Adult Anxiety Susceptibility.

Abstract Background Adolescent intermittent ethanol (AIE) exposure is an emerging risk factor for adult psychopathology, such as anxiety disorders. Enhancer RNAs (eRNAs) are short noncoding RNAs transcribed from enhancer regions that regulate synaptic plasticity–associated gene expression, including Arc, but their role in AIE-induced susceptibility to anxiety in adulthood is unknown. Methods Rats were exposed to AIE (ethanol exposure 2 days on/off) or intermittent normal saline during postnatal days 28 to 41 and allowed to grow to adulthood for analysis of behavior and biochemical measures. Some AIE rats and rats with intermittent normal saline exposure were exposed to an acute challenge with ethanol in adulthood. Cohorts of alcohol-naive adult rats were cannulated in the central nucleus of amygdala and infused with either Kdm6b small interfering RNA or an antisense locked nucleic acid oligonucleotide specific to Arc eRNA before behavioral and biochemical analysis. Results AIE adult rats displayed heightened anxiety and decreased Arc eRNA expression, which is regulated epigenetically through decreased Kdm6b expression. This triggered condensed chromatin at the synaptic activity response element site and promoter of the Arc gene, facilitating increased negative elongation factor binding to the Arc promoter and decreasing Arc expression in the amygdala. Knockdown of Kdm6b or Arc eRNA expression in the central nucleus of amygdala provoked anxiety in alcohol-naive adult rats and recapitulated the molecular and epigenetic phenotypes of AIE. Conclusions These data suggest that eRNA regulation via epigenetic reprogramming in the amygdala, particularly at the Arc synaptic activity response element site, contributes to adult anxiety after adolescent alcohol exposure.
High‐risk social drinkers and heavy drinkers display similar rates of alcohol consumption

Alcohol consumption is often assessed over weeks to months, but few attempts have been made to characterize alcohol consumption rates at the level of an individual drinking session. Here, we aimed to compare the rate of alcohol consumption in social drinkers at high risk for alcohol use disorder (AUD) and heavy drinkers. One hundred and sixty social drinkers and 48 heavy drinkers participated in an alcohol self-administration study. Social drinkers were classified as low risk or high risk for AUD based on sex, impulsivity, and family history of alcoholism. Participants received a priming dose of intravenous alcohol to assess alcohol-induced craving and completed a 125-minute intravenous alcohol self-administration session to assess rate of achieving a binge-level exposure (blood alcohol concentration greater than or equal to 80 mg%). There were no differences between rates of binging in high-risk and heavy drinkers (hazard ratio = 0.87; 95% CI, 0.48-1.56). Heavy drinkers reported higher levels of craving than high-risk and low-risk drinkers at baseline. However, following a priming dose of alcohol, there were no longer differences in craving between high-risk and heavy drinkers. These results indicate that high-risk social drinkers demonstrate binging behavior that is similar to heavy drinkers, which may be driven by alcohol-induced craving. Prospective studies are needed to elucidate whether these patterns of craving and consumption in high-risk social drinkers are predictive of future AUD.
The Voice Signal and Its Information Content—2

Information in the voice signal is embedded in both its time progression and in its spectral content, i.e. in its time domain and spectrographic domain respectively. Within these domains, information relevant to profiling may be present in the patterns exhibited by specific characteristics of the voice signal. The signal may however also have characteristics that are not evident in these domains, and must be searched for in other (derivative) mathematical domains where the relevant patterns become more tangible for measurement and analysis. This, however, is the subject of feature discovery—a subject that is discussed in Part II of this book. A third domain that reflects the information in the voice signal is that of physical or abstract models that simulate or explain the voice signal and the processes that generate it. We will refer to this as the model domain.
Quantifying and Exploring Elementary School Excellence Gaps Across Schools and Time

Despite considerable reform activity surrounding K-12 education over the past 20 years, racial and socioeconomic disparities among students who achieve at advanced levels have received little atten...
Microwave photonics

In the past few years there has been significant progress in photonic components and technology applicable to microwave (analog) systems. Notable advances include high-power lasers and amplifiers, low voltage modulators, and high-power photodetectors. The increase in component capability has led to many microwave photonic demonstrations ranging from high-performance wideband links to true time delay beamforming. These subsystems have strengthened interest in photonics as a viable alternative to conventional electrical techniques. This tutorial presents some of the basics, terminology, current capabilities, and limitations of photonics (primarily for wideband applications).
Image Processing Methods for Coronal Hole Segmentation, Matching, and Map Classification

The paper presents the results from a multi-year effort to develop and validate image processing methods for selecting the best physical models based on solar image observations. The approach consists of selecting the physical models based on their agreement with coronal holes extracted from the images. Ultimately, the goal is to use physical models to predict geomagnetic storms. We decompose the problem into three subproblems: (i) coronal hole segmentation based on physical constraints, (ii) matching clusters of coronal holes between different maps, and (iii) physical map classification. For segmenting coronal holes, we develop a multi-modal method that uses segmentation maps from three different methods to initialize a level-set method that evolves the initial coronal hole segmentation to the magnetic boundary. Then, we introduce a new method based on Linear Programming for matching clusters of coronal holes. The final matching is then performed using Random Forests. The methods were carefully validated using consensus maps derived from multiple readers, manual clustering, manual map classification, and method validation for 50 maps. The proposed multi-modal segmentation method significantly outperformed SegNet, U-net, Henney-Harvey, and FCN by providing accurate boundary detection. Overall, the method gave a 95.5% map classification accuracy.
The Need for Historical Perspective

Prometheus, the Titan, employed by Zeus to make men out of mud and water, stole fire from the heavens and gave its power to man. With the gift of fire, Prometheus fulfilled his destiny to be creative and a courageously original life-giver. With fire, man had the power to become toolmaker, explorer, and food grower. However, Zeus did not appreciate disobedience by a lesser god and punished Prometheus by chaining him to Mount Caucasus where an eagle came each day to eat out his liver, which Zeus renewed each night.
Microkinetic Modeling: A Tool for Rational Catalyst Design.

The design of heterogeneous catalysts relies on understanding the fundamental surface kinetics that controls catalyst performance, and microkinetic modeling is a tool that can help the researcher in streamlining the process of catalyst design. Microkinetic modeling is used to identify critical reaction intermediates and rate-determining elementary reactions, thereby providing vital information for designing an improved catalyst. In this review, we summarize general procedures for developing microkinetic models using reaction kinetics parameters obtained from experimental data, theoretical correlations, and quantum chemical calculations. We examine the methods required to ensure the thermodynamic consistency of the microkinetic model. We describe procedures required for parameter adjustments to account for the heterogeneity of the catalyst and the inherent errors in parameter estimation. We discuss the analysis of microkinetic models to determine the rate-determining reactions using the degree of rate control and reversibility of each elementary reaction. We introduce incorporation of Bronsted-Evans-Polanyi relations and scaling relations in microkinetic models and the effects of these relations on catalytic performance and formation of volcano curves are discussed. We review the analysis of reaction schemes in terms of the maximum rate of elementary reactions, and we outline a procedure to identify kinetically significant transition states and adsorbed intermediates. We explore the application of generalized rate expressions for the prediction of optimal binding energies of important surface intermediates and to estimate the extent of potential rate improvement. We also explore the application of microkinetic modeling in homogeneous catalysis, electro-catalysis, and transient reaction kinetics. We conclude by highlighting the challenges and opportunities in the application of microkinetic modeling for catalyst design.
Cats, cars, and crossings: The consequences of road networks for the conservation of an endangered felid

Abstract Encroaching urban development is a leading cause of habitat loss, replacing natural areas with anthropogenic infrastructure and road networks. Roadways can influence the spatial ecology and survival of mammalian carnivores, particularly felids, thereby threatening long-term persistence and conservation of sensitive populations. Ocelots (Leopardus pardalis) are a federally endangered felid in the United States with breeding populations restricted to the Lower Rio Grande Valley of South Texas, an area of extensive anthropogenic expansion. We evaluated the influence of road networks on ocelot survival using a long-term telemetry dataset (1982–2001, n = 59) and draw comparisons with a spatially referenced historical dataset of ocelot-vehicle collisions in the same area (1982–2020, n = 54). Vehicle collisions accounted for 40% of radio-collared ocelot fatalities. Annual survival rates were 0.90 (95% CI = 0.84–0.95) for resident ocelots and 0.66 (95% CI = 0.45–0.97) for transient ocelots. We evaluated biological and road-related factors that may influence ocelot survival using Cox proportional hazards regression. The top model included density of unpaved, low-volume, and high-volume roads within home ranges and resident-transient status. Mortality risk increased 16% with every 0.07 km/km2 increase of high-volume roads within annual home range, decreased 45% with every 1.12 km/km2 increase of unpaved roads, and decreased 276% for residents compared to transients. Further, probability of mortality specifically from vehicle collision increased with greater density of low-volume roads within ocelot home ranges. Within the historical dataset of ocelot-vehicle collisions, 46% occurred on low-volume roads while 39% occurred on high-volume roads. Our results highlight the necessity for mitigation strategies on low-volume roads which cause the most ocelot-vehicle collisions. In addition, continued attention towards high-volume roads is necessary to ocelot conservation. Understanding how road attributes affect the survival of species sensitive to urbanization and habitat fragmentation can aid in their conservation.
Statin Therapy and the Incidence of Thromboembolism and Vascular Events Following Liver Transplantation

Statin therapy may reduce the risk of venous thromboembolism (VTE), which may impact solid organ transplant outcomes. We evaluated the incidence of VTE and other complications after liver transplantation stratified by hyperlipidemia status and statin use using a retrospective cohort study approach from a high-volume liver transplant center. We reviewed all primary orthotopic liver transplant (OLT) records from January 2014-December 2019 from our center. Intraoperative deaths were excluded. Recipient and donor clinical and demographic data were collected. We developed risk-adjusted models to assess the effect of statin use on the occurrence of VTE, hepatic artery complications, graft failure, and death, accounting for clinical covariates and competing risks. 672 OLT recipients were included in the analysis. 11.9% (n=80) of this cohort received statin therapy. 47 patients (7.0%) had VTE events. Hepatic artery complications occurred in 40 patients (6.0%). 42 (6.1%) patients experienced graft loss while 9.1% (n=61) of the cohort died during the study interval. 268 (39.9%) OLT recipients had hyperlipidemia, of which 80 (29.8%) were treated with statins. Of those treated with statins, 0% of patients had VTE vs. 7.9% of those not on statins (p=0.01). Hepatic artery complications were identified in 1.2% of the statin group and 6.8% of the non-statin group. Untreated hyperlipidemia was associated with a 2.1-fold higher risk of hepatic artery complications vs no hyperlipidemia status patients (p=0.05). Statins were associated with significantly better risk-adjusted thromboembolic event-free survival (absence of DVT, PE, CVA, MI, HAC, and death) (90% statins vs. 73.9% untreated; HR =0.37, p = 0.01). These data indicate that statin therapy is correlated with a lower rate of VTE and hepatic artery complications after liver transplantation. Prospective studies are warranted.
CEDNIK syndrome, a rare neuro-cutaneous disorder (P1.6-050)

Objective: NA Background: CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis and keratoderma) syndrome is a rare autosomal recessive neuro-cutaneous disorder characterized by mutation in Synaptosomal-associated protein 29 (SNAP29) gene. We present a patient with alteration in SNAP29. Design/Methods: Case report. Results: A 26-month old male born to non-consanguineous parents without any prenatal complications, had severe retrognathia at birth requiring G-tube placement and mandibular enhancement procedure. He had severe developmental delay with inability to sit, no speech development, severe cognitive issues and seizures developed at 9 months. Examination showed bilateral epicanthic folds with mid-facial hypoplasia, generalized icthyosis and diffuse hypotonia. MRI showed multiple brain malformations including partial agenesis of corpus callosum and diffuse polymicrogyria. A sequencing panel showed two mutations, a homozygous pathogenic frame shifts sequence change in the SNAP29 gene, associated with the CEDNIK syndrome. He has continued to have profound developmental delay and at 2 years is functioning in the 4–6 month range. Conclusions: Our patient’s DNA analysis of SNAP29 gene demonstrated a homozygous one base pair duplication in exon 2, c.354dup. This pathogenic sequence change results in an amino acid frameshift and creates a premature stop codon 14 amino acids downstream of the mutation, p.Leu119Alafs*15. This pathogenic change is predicted to result in an abnormal transcript, causing truncated SNAP29 protein with abnormal function. SNAP proteins are t-SNARE proteins that function in intracellular vesicle fusion. SNAP29 has been determined to bind to a broad range of syntaxin fusion proteins and is involved in a number of intracellular transport steps and would impact a variety of neuroectodermal tissues. Recent study suggest that SNAP has additional role as a negative modulator of neurotransmitter release by slowing the recycling of the SNARE-associated fusion machinery and synaptic vesicle turnover. This may be related to the severe neurologic al manifestations shown by patients with CEDNIK syndrome. Disclosure: Dr. Tiwana has nothing to disclose. Dr. Raymond has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Viking Therapeutics and Bluebird bio. Dr. Kumar has received research support from Marathon and Sarepta Therapeutics.
Additive manufacturing of multimaterial and multifunctional structures via ultrasonic embedding of continuous carbon fiber

Abstract Multimaterial and multifunctional parts were fabricated using an ultrasonic embedding technology in combination with 3D printing of thermoplastic. Continuous carbon fiber (CF) bundles were impregnated with polycarbonate solution (7 wt.%) prior to use in the embedding process. Using an ultrasonic embedding tool, a single layer of CF bundle was embedded into 3D printed polycarbonate parts containing one of three raster angles (RA): 0°, +45/-45°, and 90° RA. In tensile testing, the highest ultimate tensile stress (UTS) was found in samples printed with +45/-45° RA (75% higher UTS when compared to neat samples having the same RA), followed by those printed with 0° RA (60% UTS increase). Samples printed with 90° RA and containing a single layer (bundle) of embedded CF yielded the least UTS improvement (13%). Statistical t-test results showed that +45/-45° RA samples with embedded CF had superior mechanical strength while exhibiting less variation. Flexural testing of +45/-45° RA specimens with embedded CF showed an average flexural strength increase of 7%, and an average modulus increase of 7% when compared to the neat specimen. In addition to the mechanical reinforcement, multilayer CF embedding using ultrasonic energy was demonstrated. In addition, the change in electrical resistance in embedded CF layers was measured during mechanical loading to demonstrate structural health monitoring functionality.
A Study on Brexit: Correlations and Tail Events Distribution of Liquidity Measures

Liquidity describes the degree to which an asset or security can be quickly bought or sold in the market without affecting the asset's price. In this study, some of the existing liquidity measures are studied and analyzed during Brexit. We examine Utilities Select Sector SPDR Fund (Exchange-Traded Fund) components in this study. The time period covers June 16, 2016 to June 30, 2016 which includes Brexit event day. We use high-frequency tick level Trade data, Quote data, and Limit Order Book data. We study the sample of Trade and Quote liquidity measures (TAQL) and Limit Order Book liquidity measures (LOBL). Our study shows that the correlations between these two liquidity groups (TAQL & LOBL) have significant relationship with the returns of the underlying ETF components. Furthermore, the analysis shows that low correlation between TAQL and LOBL indicates high probability of large price change. Finally, we study the empirical distributions, which implies that Brexit generated fatter tails on liquidity measures distributions. This indicates that infrequent (low) liquidity condition occurs more frequently during Brexit.
Static Deformations of Solids

We now have enough machinery to begin to find solutions to problems involving the static deformation of elastic solids. In Chap. 7 we will discuss the dynamic behavior of solids. Most of our discussion will be restricted to the discussion of linear, isotropic solids, characterized by two material constants (we will mostly use the Young’s modulus E and Poisson’s ratio v, but one could just as well use the two Lame constants λ and μ). Extensions to the treatment of general linear elastic solids, using the 6 × 6 stiffness matrix c or the compliance matrix s, are possible, but involve such intricate manipulations of complex differential equations that such problems are usually relegated to numerical solutions. We will illustrate some of the differences between isotropic and non-isotropic solids in the examples.
Cases on information technology management in modern organizations

Information systems educators, professionals and students can best learn from the experience of others. The successes and failures of others can help the information systems community to further develop and flourish. An effective means of conveying these experiences and lessons learned is through case studies. This is a compilation of original cases that describe information technology experience in both domestic and international organizations. Each case has been carefully structured to provide background information, project description, current status of the case/project, successes and failures, epilogue and lessons learned, and a series of questions for discussion. This should be useful as a case book for undergraduate MIS courses or for introductory MIS courses at the MBA or MS level.
Envejecimiento y salud en México: un enfoque integrado

The aim of this article is to present a conceptual framework for studying the health of the elderly population and to discuss the need to undertake integrated studies for this purpose. It also contains a summary of a new project, the National Study on Health and Aging in Mexico (ENASEM) and mentions other d-bases that could contribute to these studies.
Automated modeling and control synthesis using the MACSYN toolbox

This paper describes the Modeling and Control Synthesis (MACSYN) Toolbox, which is an integrated software package for system identification, modeling, and robust control. Using MACSYN, the plant is identified in state-space form, and modeling errors are characterized in terms of norm-bounded weighting functions in a form that can be used with modern robust control design software packages. An automated framework simplifies the modeling and control design procedure, and enables robust high-performance feedback designs for systems which would be otherwise difficult to control reliably. MACSYN is implemented as programmable M-files in MATLAB.
Plasma Levels of Soluble Interleukin-2 Receptor α Associations With Clinical Cardiovascular Events and Genome-Wide Association Scan

Objective—Interleukin (IL) -2 receptor subunit α regulates lymphocyte activation, which plays an important role in atherosclerosis. Associations between soluble IL-2Rα (sIL-2Rα) and cardiovascular disease (CVD) have not been widely studied and little is known about the genetic determinants of sIL-2Rα levels. Approach and Results—We measured baseline levels of sIL-2Rα in 4408 European American (EA) and 766 African American (AA) adults from the Cardiovascular Health Study (CHS) and examined associations with baseline CVD risk factors, subclinical CVD, and incident CVD events. We also performed a genome-wide association study for sIL-2Rα in CHS (2964 EAs and 683 AAs) and further combined CHS EA results with those from two other EA cohorts in a meta-analysis (n=4464 EAs). In age, sex- and race- adjusted models, sIL-2Rα was positively associated with current smoking, type 2 diabetes mellitus, hypertension, insulin, waist circumference, C-reactive protein, IL-6, fibrinogen, internal carotid wall thickness, all-...
Functional genomics of systemic complement activation in AMD

Purpose To describe the current status of genetic variants associated with age-related macular degeneration (AMD) and present functional genomic association studies demonstrating that systemic complement activation is inlfuenced by haplotypes in AMD risk loci and increases the risk of having age-related macular degeneration. Methods A genome wide association study using the Illumina 370 Beadchip on over 3000 subjects was performed. Focused genetic association and haplotype studies investigating the genetic mechanisms increasing AMD risk in complement and non-complement AMD risk loci were performed using standard methods. Functional genomic association studies relating genetic risks for AMD to plasma complement levels measured using ELISA assays were performed. Results The collaborative genome-wide association study revealed novel pathways increasing the risk of AMD and will be discussed. The established genetic variants in the CFH, CFHR, FI, ARMS2 (10q26), and ApoE loci will be reviewed with a focus on insights from genetic studies on functional consequences. The proteogenomic association study showed that haplotypes in complement genes associated with AMD altered plasma levels of complement substrates, regulators, and activation by-products. The majority of the difference between case and control levels of complement proteins in plasma was explained by the genetic variants associated with AMD. Conclusion Multiple independent pathways leading to AMD have been identified using the genetic approach. Detailed genetic studies and functional genomic studies are beginning to suggest mechanisms through which AMD risk is increased. Commercial interest
Modulation of cis-platinum renal toxicity by the radioprotective agent WR 2721.

Abstract Pretreatment with the radioprotective thiol compound WR 2721 resulted in amelioration of renal histologic damage induced at 5 and 31 days in rats by a single exposure to cis -dichlorodiammineplatinum II ( cis -Pt), an anticancer agent. Renal histopathologic changes 5 days after exposure consisted of tubular epithelial necrosis at the corticomedullary junction, while after longer time intervals, nuclear hypertrophy, anisonucleosis, and diminished tubular diameters were evident. The degree of histologic change at 5 days was inversely correlated with the amount of WR 2721 administered. At 31 days after a single cis -Pt dose following pretreatment with 200 mg/kg WR 2721, the dose reduction factor (treated/control) was 1.5–1.6.
Kinetic characteristics of ammonium-oxidizer communities in a California oak woodland-annual grassland

Abstract We must have information on the kinetic characteristics of soil biological processes if we are accurately to predict how environmental change will affect soil nutrient cycles. Little information is available on the characteristics of NH 4 + -oxidizing bacteria in uncultivated soils. In addition, little is known about how much physiological diversity occurs in NH 4 + -oxidizer communities within a single ecosystem. Therefore, we evaluated how NH 4 + -oxidizer communities from an oak woodland-annual grass ecosystem in north-eastern California respond to changes in temperature, osmotic potential and substrate concentrations. We used nitrification potential assays to determine the effects of temperature and osmotic potential on rates of NH 4 + oxidation in two soil depths, under two types of vegetative cover and during two seasons. We determined the kinetics of substrate utilization using soil slurries and enrichment cultures. In slurries, NH 4 + oxidation rates were measured using 15 N-isotope dilution to avoid confounding the effects of NO 3 − consumption with NO 3 − production. Ammonium-oxidizer communities beneath the canopies of oaks had lower temperature optima, greater activities and greater seasonal fluctuations in activity than communities in open grassy interspaces. Temperature optima of communities beneath oak canopies (31.8°C) and in open grassy interspaces (35.9°C) were as different as those reported for communities from tropical and temperate climatic zones. Ammonium-oxidizer communities from beneath oak canopies and open interspaces showed no difference in tolerance of low osmotic potential. The effect of substrate concentration on NH 4 + oxidation rates in slurries were best described by the Michaelis-Menten equation. Rates in liquid cultures were best described by the Haldane equation because of substrate inhibition. The half-saturation constant ( K m ) for NH 4 + oxidation in these soils averaged 15 μ m NH 4 + (=0.012 μ m NH 3 ), which is substantially lower than values reported in the literature for agricultural soils, sediments and sewage sludge. Enrichment cultures were inhibited by lower substrate concentrations (1600 μ m NH 4 + or 1.3 μ m NH 3 ) than reported for isolates from sewage systems. These results suggest that NH 4 + -oxidizer communities in uncultivated soils are more oligotrophic in nature, and thus kinetic parameters reported in the literature for agricultural soils, sediments and sewage sludge are not appropriate for describing NH 4 + oxidation rates in these soils.
Raman scattering and attenuated-total-reflection studies of surface-plasmon polaritons.

We have made in situ measurements of attenuated total reflection (ATR) and Raman scattering from a layered structure consisting of a glass prism, a thin silver film, an ${\mathrm{MgF}}_{2}$ spacer, and a liquid mixture whose refractive index is matched to that of ${\mathrm{MgF}}_{2}$. When the incident angle of the laser beam coincides with the ATR angle, the surface-plasmon polariton (SPP) of the silver film is excited resonantly and the Raman scattering intensity of the liquid shows a maximum. The same effect is observed at the frequency of the Stokes scattered light. By measuring the decrease of the Raman scattering intensity of the liquid with increase of the thickness of the ${\mathrm{MgF}}_{2}$ spacer layer, we have determined the decay length (${l}_{d}$) of the SPP field into the liquid. The measured value of ${l}_{d}$=1539 A\r{} agrees with the calculated value, 1534 A\r{}.
Biomechanical comparison of screw-in suture anchor-suture combinations used for Bankart repair.

Bankart repair laxity may contribute to pathologic joint instability. This biomechanical study compared two screw-in suture anchor–suture combinations under tensile loads. Twelve pairs of scapulae were implanted with either a 3 mm diameter, 14 mm long poly-l/d-lactide suture anchor with a suture eyelet (Group 1) or a 3.1 mm diameter, 11 mm long polylactide suture anchor with a molded eyelet (Group 2). Constructs were cyclically loaded between 25 and 50 N with a 25 N load increase every 25 cycles. Group 2 displayed greater displacement at failure, had more specimens with ≥2 mm displacement by the 50 N interval (P = 0.014), and had displaced more by 100 N (P ≤ 0.046). Group 1 displayed a stronger load–displacement at failure relationship than Group 2 (r 2 = 0.67 vs. r 2 = 0.37). Construct differences may influence decisions regarding the required number of suture anchor–suture loops, the rehabilitation timetable, and the timing of return to unrestricted activities.
Interaction maps for kinase inhibitors.

The specificity of kinase inhibitors can be rapidly determined with a new in vitro competition assay.
A three state model for alamethicin conductance in bilayer membranes.

Alamethicin is an antibiotic which produces voltage gated channels in lipid bilayer membranes. Recently completed studies of the pressure dependence of alamethicin conductance have shown that its onset following application of a suprathreshold voltage step at a pressure of 100 MPa (1000 atm) is markedly slowed relative to that observed at ambient pressure. Furthermore, the time course of the onset of conductance becomes distinctly sigmoidal at elevated pressure, a condition which is not evident at atmospheric pressure. The decay of alamethicin conductance upon removal of suprathreshold applied voltage is also slowed by application of hydrostatic pressure, but it follows a single exponential time course at all pressures. In addition, kinetic parameters characterizing the onset and decay of conductance show distinctly different pressure dependences. These observations cannot be explained by a two state model in which alamethicin moves reversibly between nonconducting and conducting states. Therefore we re-examine critically a hypothesis made by previous workers, namely that alamethicin, in monomeric or aggregate form, moves upon application of suprathreshold voltage first from a nonconducting surface state to a nonconducting preassembly, or precursor state, and then finally into a conducting state. Parameters of this three state model are related to a geometric factor which measures the degree of sigmoidal conductance response and which can be evaluated directly from experimental data. An alternative aggregation-type analysis, equivalent to that applied by Hodgkin & Huxley to the potassium conductance in squid axon, is also considered in the context of this same geometric factor. The possibility of distinguishing between these analyses on the basis of experimental data is discussed.
Potassium transport in the maturing kidney.

The distal nephron and colon are the primary sites of regulation of potassium (K+) homeostasis, responsible for maintaining a zero balance in adults and net positive balance in growing infants and children. Distal nephron segments can either secrete or reabsorb K+ depending on the metabolic needs of the organism. In the healthy adult kidney, K+ secretion predominates over K+ absorption. Baseline K+ secretion occurs via the apical low-conductance secretory K+ (SK) channel, whereas the maxi-K channel mediates flow-stimulated net urinary K+ secretion. The K+ retention characteristic of the neonatal kidney appears to be due not only to the absence of apical secretory K+ channels in the distal nephron but also to a predominance of apical H-K-adenosine triphosphatase (ATPase), which presumably mediates K+ absorption. Both luminal and peritubular factors regulate the balance between K+ secretion and absorption. Perturbation in any of these factors can lead to K+ imbalance. In turn, these factors may serve as effective targets for the treatment of both hyper-and hypokalemia. The purpose of this review is to present an overview of recent advances in our understanding of mechanisms of K+ transport in the maturing kidney.
Interaction of transmembrane helices in ATP synthase subunit a in solution as revealed by spin label difference NMR

Abstract Subunit a in the membrane traversing F0 sector of Escherichia coli ATP synthase is known to fold with five transmembrane helices (TMHs) with residue 218 in TMH IV packing close to residue 248 in TMH V. In this study, we have introduced a spin label probe at Cys residues substituted at positions 222 or 223 and measured the effects on the Trp ɛNH indole NMR signals of the seven Trp residues in the protein. The protein was purified and NMR experiments were carried out in a chloroform–methanol–H2O (4:4:1) solvent mixture. The spin label at positions 222 or 223 proved to broaden the signals of W231, W232, W235 and W241 located at the periplasmic ends of TMH IV and TMH V and the connecting loop between these helices. The broadening of W241 would require that the loop residues fold back on themselves in a hairpin-like structure much like it is predicted to fold in the native membrane. Placement of the spin label probe at several other positions also proved to have broadening effects on some of these Trp residues and provided additional constraints on folding of TMH IV and TMH V. The effects of the 223 probes on backbone amide resonances of subunit a were also measured by an HNCO experiment and the results are consistent with the two helices folding back on themselves in this solvent mixture. When Cys and Trp were substituted at residues 206 and 254 at the cytoplasmic ends of TMHs IV and V respectively, the W254 resonance was not broadened by the spin label at position 206. We conclude that the helices fold back on themselves in this solvent system and then pack at an angle such that the cytoplasmic ends of the polypeptide backbone are significantly displaced from each other.
NSC23925, Identified in a High-Throughput Cell-Based Screen, Reverses Multidrug Resistance

Author(s): Duan, Zhenfeng; Choy, Edwin; Hornicek, Francis J | Abstract: BackgroundMultidrug resistance (MDR) is a major factor which contributes to the failure of cancer chemotherapy, and numerous efforts have been attempted to overcome MDR. To date, none of these attempts have yielded a tolerable and effective therapy to reverse MDR; thus, identification of new agents would be useful both clinically and scientifically.Methodology/principal findingsTo identify small molecule compounds that can reverse chemoresistance, we developed a 96-well plate high-throughput cell-based screening assay in a paclitaxel resistant ovarian cancer cell line. Coincubating cells with a sublethal concentration of paclitaxel in combination with each of 2,000 small molecule compounds from the National Cancer Institute Diversity Set Library, we identified a previously uncharacterized molecule, NSC23925, that inhibits Pgp1 and reverses MDR1 (Pgp1) but does not inhibit MRP or BCRP-mediated MDR. The cytotoxic activity of NSC23925 was further evaluated using a panel of cancer cell lines expressing Pgp1, MRP, and BCRP. We found that at a concentration of g10 microM NSC23925 moderately inhibits the proliferation of both sensitive and resistant cell lines with almost equal activity, but its inhibitory effect was not altered by co-incubation with the Pgp1 inhibitor, verapamil, suggesting that NSC23925 itself is not a substrate of Pgp1. Additionally, NSC23925 increases the intracellular accumulation of Pgp1 substrates: calcein AM, Rhodamine-123, paclitaxel, mitoxantrone, and doxorubicin. Interestingly, we further observed that, although NSC23925 directly inhibits the function of Pgp1 in a dose-dependent manner without altering the total expression level of Pgp1, NSC23925 actually stimulates ATPase activity of Pgp, a phenomenon seen in other Pgp inhibitors.Conclusions/significanceThe ability of NSC23925 to restore sensitivity to the cytotoxic effects of chemotherapy or to prevent resistance could significantly benefit cancer patients.
Maximal Exercise Tolerance in Chronic Congestive Heart Failure: Relationship to Resting Left Ventricular Function

The relationship between maximal exercise tolerance and resting radionuclide indexes of left ventricular systolic and diastolic function were evaluated in 20 ischemic and 44 idiopathic cardiomyopathy patients with New York Heart Association class 2-4 chronic congestive heart failure. Left ventricular ejection fraction, peak systolic ejection rate, peak diastolic filling rate, time to peak filling from end-systolic volume, and fractional filling in early diastole were measured from the radionuclide ventriculogram. All patients underwent symptom-limited exercise testing with on-line measurement of oxygen consumption. In the ischemic group, all of the radionuclide indexes correlated poorly with maximal exercise oxygen consumption (VO2max) except the peak systolic ejection rate which correlated modestly (r = 0.58, p 14 mL/kg/min). In the idiopathic group, none of the radionuclide indexes correlated well with VO2max; and all indexes were similar in patients with and without marked exercise intolerance. These data suggest that (1) resting left ventricular ejection fraction poorly predicts maximal exercise capacity in both ischemic and idiopathic cardiomyopathy and (2) resting peak systolic ejection rate, peak diastolic filling rate, and fractional filling in early diastole may predict exercise tolerance in ischemic but not idiopathic cardiomyopathy.
Properties of CaSO4: Mn Phosphor under Vacuum Ultraviolet Excitation

The properties of a manganese-activated CaS${\mathrm{O}}_{4}$ phosphor were investigated in connection with its use as a detector of extreme ultraviolet solar radiation in upper atmosphere research. The luminescence of particular interest was a long-period phosphorescence which is excited by wavelengths in the range 1350A to gamma-rays. The energy stored in the phosphor after exposure to short ultraviolet was released by heating and measured by means of a photomultiplier. The stored energy was given by the integrated multiplier response and was independent of the form of the heating cycle. It was also nearly independent of the exposure temperature (-30 to +70\ifmmode^\circ\else\textdegree\fi{}C) and humidity. There was a useful exposure range of ${10}^{4}$ over which the stored energy was directly proportional to the exposure intensity and time; for higher exposures, saturation set in. The excitation spectrum of the stored energy was measured and the maximum quantum efficiency (5 to 10 percent) was found to lie at 1030A. At room temperature, the long-period phosphorescence decay was of the hyperbolic type. Fluorescence in addition to phosphorescence was excited by wavelengths shorter than 1350A, and an additional excitation band of fluorescence only was found in the region 1400-1600A. The emission spectrum extended from 4480 to 5790A.
Species Difference in GI Motor Response to Somatostatin

Acute experiments were performed on overnight fasted chloralose-urethan anesthetized dogs, cats, rabbits, and rats. Under these conditions, somatostatin practically abolished gastric contractions and decreased GI tonus in all species examined. The canine duodenum, jejunum, and ileum exhibited only a contractile response to somatostatin, whereas motor activities of the small intestines of the cat, rabbit, and rat were inhibited. In all instances and at all dosages, both the inhibitory and excitatory effects showed suggestions of tachyphylaxis. The data also indicate that excitatory or inhibitory effects were not dependent on the presence of long arc pathways. It is concluded that somatostatin exerts a direct stimulatory effect on the canine small intestine that is mediated by the muscularis mucosa.
Virtual-Intelligence Applications in Petroleum Engineering: Part 2—Evolutionary Computing

The goal of this second article is to provide an overview of evolutionary computing, its potential combination with neural networks to produce powerful intelligent applications, and its applications in the oil and gas industry. The most succesful intelligent applications incorporate several virtual-intelligence tools in a hybrid manner. Virtual-intelligence tools complement each other and are able to amplify each other's effectiveness. This article also presents the background of evolutionary computation as related to Darwinian evolution theory. This is followed by a more detailed look at genetic algorithms, the primary evolutionary-computing paradigm currently used. The article concludes by exploring application of a hybrid neural network/genetic algorithm system to a petroleum-engineering-related problem.
Relativistic Magnetron Research

We present preliminary results of a longer pulse (200 ns) relativistic magnetron experiment. This experiment demon-strated the excitation of pr. mode besides the usual 27r mode through voltage variation and through magnetic field tuning, and reconfirmed the importance of voltage stability in achieving the mode stability and power output stability required by phase locking conditions. The experiment also indicated the possibility of using velvet as the cathode material for achieving long microwave pulses (200 ns). The long pulse behavior of graphite cathodes with varying cathode locations was found to be similar to the short pulse case. These experimental results aid in the understanding of the high-current magnetron under long pulse operation which is crucial for conducting the long pulse phase locking experiment. We also describe the design and construction of our long pulse, high repetition rate (1 ps, 4 pps) relativistic magnetron system (700 kV, 770 A) with the stability and pulse duration suitable for studying phase locking.