cssi/SciSciGPT-SciSciNet huggingface dataset:
Intravital microscopy identifies selectins that regulate T cell traffic into allografts

T cell homing to sites of injury and inflammation is a critical step for adaptive immune responses. While much has been learned regarding T cell homing to lymphoid tissues, few studies have directly observed trafficking events during an effector response. In this study, we developed a model that uses intravital fluorescence videomicroscopy to determine the molecules critical to T cell rolling within skin allograft microvasculature during the effector phase of the rejection response. Additional studies were performed to quantify T cell infiltrates as rejection progressed. We found that P-selectin and E-selectin expressed on postcapillary venules play overlapping roles in the recruitment of activated T cells in a SCID reconstitution model of skin graft rejection and are important in T cell accumulation at the graft site. Surprisingly, we also found that naive T cells are recruited and accumulate via constitutive T cell L-selectin and upregulated L-selectin ligands on rejecting allograft vasculature. These data indicated that a specific retinue of molecules is upregulated during the rejection response, and they suggest potential future therapeutic targets.
Structural characteristics of nanoparticles produced by hydrothermal pretreatment of cellulose and their applications for electrochemical hydrogen generation

Abstract Hydrothermal pretreatment (HTP) of microcrystalline cellulose (MCC) and wood sawdust in water at 200 °C and 250 °C and at pressures up to about 600 psi for different heating times (≤60 min) is shown to produce nanoparticles of about 210 nm diameter. For the shorter treatment times of 15 min, only partial conversion is observed. Investigations of the post-HTP solid products by scanning electron microscopy show that the original size of cellulose particles is reduced by a factor of about 50 to yield spherical nanoparticles of about 210 nm size. In X-ray diffraction studies, the characteristic Bragg peaks of the parent MCC and sawdust are not present in the post-HTP products with only a broad halo being observed, indicating that the crystallinity of cellulose has broken down under HTP. Electron spin resonance (ESR) spectroscopy shows the observation of free radicals in the post-HTP products whereas the parent MCC, sawdust and glucose are ESR inert. FTIR spectroscopy shows the breakdown of the bonds between glucose units of the cellulosic structure. As an application, the pre- and post-HTP cellulose and sawdust were tested for the electrochemical production of hydrogen. Whereas the pre-HTP samples were found to be inactive, the post-HTP cellulose treated at 250 °C for 60 min was nearly as active as carbon BP2000 (surface area = 1500 m 2 /g) for producing H 2 at energy efficient voltages. A comparative energy analysis for the electrochemical production of hydrogen using carbons and post-HTP cellulose vis-a-vis water electrolysis is also presented.
Runoff nutrient loads as affected by residue cover, manure application rate, and flow rate

Manure is applied to cropland areas with varying surface cover to meet single-year or multiple-year crop nutrient requirements. The objectives of this field study were to: (1) examine runoff water quality characteristics following land application of manure to sites with and without wheat residue, (2) compare the water quality impacts of land application of manure to meet 0-, 1-, 2-, 4-, and 8-year P-based requirements for corn, and (3) evaluate the effects of varying runoff rates on runoff nutrient loads. Three 30-min simulated rainfall events, separated by 24 h intervals, were applied at an intensity of 70 mm h-1 to 0.75 m wide by 2.0 m long plots on which manure has been previously applied and incorporated. Runoff loads of dissolved phosphorus (DP), total phosphorus (TP), NO3-N, NH4-N, and total nitrogen (TN) were significantly greater on the plots with residue cover. Manure application rate significantly influenced runoff loads of DP, TP, NO3-N, NH4-N, and TN. No significant differences in runoff loads of DP and TP were found between sites where manure was applied to meet a 1-year or 2-year P requirement for corn. However, runoff loads of DP and TP were significantly greater on the sites where manure was applied to meet a 4-year rather than a 2-year P requirement. Each of the measured water quality parameters except electrical conductivity (EC) was significantly influenced by runoff rate. The application of manure to meet multiple-year crop nutrient requirements may increase nutrient loads in runoff.
Interaction of paraquat with the pulmonary microsomal fatty acid desaturase system.

Abstract Administration of paraquat (methyl viologen) to rats resulted in an acute inhibition of the pulmonary fatty acid desaturase enzyme system which may be explained by the anorexic effect of paraquat. However, this same enzyme system in paraquat-treated rat appears to be more strongly inhibited by in vitro addition of paraquat than control preparations. This effect does not appear to be related to an increased rate of microsomal hydrogen peroxide or superoxide production. This enzymatic sensitivity to paraquat is partially reversed by treatment of rats with phenobarbital which also mildly protects rats against the toxic effects of paraquat as expressed by a 50% increase in time to death at 35 mg/kg paraquat.
Tissue Expression of the Novel Serine Carboxypeptidase Scpep1

We previously identified a novel gene designated retinoid-inducible serine carboxypeptidase (RISC or Scpep1). Here we characterize a polyclonal antibody raised to Scpep1 and assess its localization in mouse cells and tissues. Western blot analysis revealed an immunospecific approximately 35-kDa protein corresponding to endogenous Scpep1. This protein is smaller than the predicted approximately 51-kDa, suggesting that Scpep1 is proteolytically cleaved to a mature enzyme. Immunohistochemical studies demonstrate Scpep1 expression in embryonic heart and vasculature as well as in adult aortic smooth muscle cells and endothelial cells. Scpep1 displays a broad expression pattern in adult tissues with detectable levels in epithelia of digestive tract and urinary bladder, islet of Langerhans, type II alveolar cells and macrophages of lung, macrophage-like cells of lymph nodes and spleen, Leydig cells of testis, and nerve fibers in brain and ganglia. Consistent with previous mRNA studies in kidney, Scpep1 protein is restricted to proximal convoluted tubular epithelium (PCT). Immunoelectron microscopy shows enriched Scpep1 within lysosomes of the PCT, and immunofluorescence microscopy colocalizes Scpep1 with lysosomal-associated membrane protein-2. These results suggest that Scpep1 is a widely distributed lysosomal protease requiring proteolytic cleavage for activity. The highly specific Scpep1 antibody characterized herein provides a necessary reagent for elucidating Scpep1 function.
Eating lowers defecation threshold in pigs through cholinergic pathways

The effect of atropine on defecation threshold was compared to placebo pre- and postprandially in four 20- to 30-kg pigs. Stepwise balloon distention was performed 10 cm from the anal verge with a 5-cm latex balloon. Volume was increased in steps of 10 ml up to 200 ml of air or until the balloon was defecated (defecation threshold). Dependent measures were balloon volume, rectal pressure, rectal compliance, and an index of distention-induced contractile activity. Under placebo conditions, the volume and pressure to elicit defecation were significantly lower after feeding (p < 0.05). The distention-induced contractile activity significantly increased near the defecation threshold, but pre- and postprandial conditions were not different. No differences were seen between pre- and postprandial rectal compliance curves. Atropine abolished the postprandial decrease in defecation threshold, but did not affect rectal compliance. The increase in contractile activity at defecation threshold seen with placebo was abolished by atropine. These results show that eating lowers the defecation threshold in terms of distention volume and rectal pressure, and demonstrate that these changes are mediated through cholinergic pathways.
Distributions of leptin receptor mRNA isoforms in the rat brain.

Leptin, secreted by white adipocytes, has profound feeding, metabolic, and neuroendocrine effects. Leptin acts on the brain, but the specific anatomic sites and pathways responsible for mediating these effects are still unclear. We have systematically examined distributions of mRNA of leptin receptor isoforms in the rat brain by using a probe specific for the long form and a probe recognizing all known forms of the leptin receptor. The mRNA for the long form of the receptor (OB-Rb) localized to selected nuclear groups in the rat brain. Within the hypothalamus, dense hybridization was observed in the arcuate, dorsomedial, ventromedial, and ventral premamillary nuclei. Within the dorsomedial nucleus, particularly intense hybridization was observed in the caudal regions of the nucleus ventral to the compact formation. Receptors were preferentially localized to the dorsomedial division of the ventromedial nucleus. Hybridization accumulated throughout the arcuate nucleus, extending from the retrochiasmatic region to the posterior periventricular region. Moderate hybridization was observed in the periventricular hypothalamic nucleus, lateral hypothalamic area, medial mammillary nucleus, posterior hypothalamic nucleus, nucleus of the lateral olfactory tract, and within substantia nigra pars compacta. Several thalamic nuclei were also found to contain dense hybridization. These groups included the mediodorsal, ventral anterior, ventral medial, submedial, ventral posterior, and lateral dorsal thalamic nuclei. Hybridization was also observed in the medial and lateral geniculate nuclei. Intense hybridization was observed in the Purkinje and granular cell layers of the cerebellum. A probe recognizing all known forms of the leptin receptor hybridized to all of these sites within the brain. In addition, intense hybridization was observed in the choroid plexus, meninges, and also surrounding blood vessels. These findings indicate that circulating leptin may act through hypothalamic nuclear groups involved in regulating feeding, body weight, and neuroendocrine function. The localization of leptin receptor mRNA in extrahypothalamic sites in the thalamus and cerebellum suggests that leptin may act on specific sensory and motor systems. Leptin receptors localized in nonneuronal cells in the meninges, choroid plexus, and blood vessels may be involved in transport of leptin into the brain and in the clearance of leptin from the cerebrospinal fluid. J. Comp. Neurol. 395:535–547, 1998. © 1998 Wiley-Liss, Inc.
An immunochemical analysis of the novel liver‐restricted LDH activity from cichlid fishes (Cichlidae: Teleostei) confirms its non‐orthology with piscine LDH‐C

In an electrophoretic survey of lactate dehydrogenase (LDH) isozymes in neotropical cichlid fishes (Perciformes: Cichlidae) several species were discovered in which a cathodal liver-restricted isozyme is expressed along with the highly anodal eye-restricted isozyme (LDH-C4) typically encountered in perciform fishes. Biochemical characterization of these two isozymes from the basketmouth cichlid, Acaronia nassa (Heckel), strongly suggested that they were non-orthologous and challenged the accepted view that eye- and liver-restricted LDH isozymes are alternative expressions of the same (LDH-C *) gene. In this study, antiserum raised against cypriniform (goldfish) liver-restricted LDH-C4 failed to cross-react with the basketmouth liver-restricted analogue while effectively titrating the eye-restricted, anodal isozyme and, at higher titres, the LDH-B4, heart-restricted isozyme from all cichlid species. Anti-serum raised against basketmouth muscle-restricted LDH-A4 failed to titrate any of the eye- and liver-restricted isozymes. These data confirm the orthology of eye- and liver-restricted LDH isozymes in Cypriniform and Perciform fishes as originally proposed, suggest that the liver-restricted isozyme of cichlid fishes is non-orthologous and further raise the question of identity and evolutionary origin of this anomalous LDH activity.
Chasms and bridges: Generativity in the space between educators' communities of practice

Abstract This article presents findings from an ethnographic study that explored how participation in an educator network contributed to the production of meaning, identity, and agency among the teachers and school district administrators involved. Prominent in this process were the differences between practice in the network, consisting of dialogue informed by theory, inquiry, and reflection on professional experience, and the practice of participants' workplace communities. I argue that identities afforded by multimembership in these very different communities, along with the bridges participants worked to build between the communities, hold promise for generating change in the field of education.
Symmetrical up-Diffused I2L

An up-diffused form of symmetrical cell Integrated Injection Logic (I2L) has been designed, modeled, fabricated, and demonstrated to be fully operating after 6 × 1014 neutrons/cm2. This technology is expected also to be capable of full operation after > 3 × 106 Rad(Si) ionizing radiation and immune to information upset at levels above 1 × 1010 Rad(Si)/s based on experience with related devices.
Apoptotic response to 5-fluorouracil treatment is mediated by reduced polyamines, non-autocrine Fas ligand and induced tumor necrosis factor receptor 2.

5-fluorouracil (5-FU) is the major chemotherapeutic agent for treatment of colorectal carcinoma, but the molecular mechanisms of response and resistance are not understood completely. We therefore studied the 5-FU dose response and time course of gene expression transcriptome changes in colon carcinoma cell lines that are relatively sensitive to or resistant to 5-FU (RKO and HT29, respectively. We identified cellular pathways and corroborated functions of selected pathways. Expression of genes for polyamine biosynthesis, i.e., ornithine decarboxylase (ODC) and spermine and spermidine synthases, was repressed in the sensitive line, while the biosynthesis-inhibiting gene ODC antizyme was induced in the resistant line. The rate-limiting gene in catabolism, spermine/spermidine acetyltransferase, was induced in both lines. Polyamine levels showed corresponding drastic decreases after 5-FU treatment, and polyamine replenishment interfered with 5-FU-induced apoptosis. In the sensitive cells which have wild-type p53, the p53 gene and its downstream genes including p21/WAF1, mdm2, Fas, mic-1, EphA2, and ferredoxin reductase as well as genes in the tumor necrosis factor (TNF) pathway including TNF receptor 2 (TNFR2) were induced, but not Fas ligand (FasL). Exposure to exogenous FasL increased 5-FU-induced apoptosis, and anti-TNFR2 antibody, but not anti-TNFR1, partially protected the sensitive cells. Our combination of gene expression profiling and corroborative functional studies revealed that reduced polyamine levels, non-autocrine FasL originating exogenous to tumor cells, and induced TNFR2 are all functional mediators of apoptosis caused by 5-FU in colon carcinoma cells.
Carotenoids need structural colours to shine

The bright colours of feathers are among the most striking displays in nature and are frequently used as sexual signals. Feathers can be coloured by pigments or by ordered tissue, and these mechanisms have traditionally been treated as distinct modes of display. Here we show that some yellow plumage colour is created both by reflection of light from white structural tissue and absorption of light by carotenoids. Thus, structural components of feathers contribute substantially to yellow 'carotenoid' displays, but the effect of variation in structural components on variation in colour displays is, to our knowledge, unstudied. The presence of structural colour in some carotenoid-based colour displays will have to be considered in studies of colour signalling.
Benzene-free synthesis of catechol: interfacing microbial and chemical catalysis.

The toxicity of aromatics frequently limits the yields of their microbial synthesis. For example, the 5% yield of catechol synthesized from glucose by Escherichia coli WN1/pWL1.290A under fermentor-controlled conditions reflects catechol's microbial toxicity. Use of in situ resin-based extraction to reduce catechol's concentration in culture medium and thereby its microbial toxicity during its synthesis from glucose by E. coli WN1/pWL1.290A led to a 7% yield of catechol. Interfacing microbial with chemical synthesis was then explored where glucose was microbially converted into a nontoxic intermediate followed by chemical conversion of this intermediate into catechol. Intermediates examined include 3-dehydroquinate, 3-dehydroshikimate, and protocatechuate. 3-Dehydroquinate and 3-dehydroshikimate synthesized, respectively, by E. coli QP1.1/pJY1.216A and E. coli KL3/pJY1.216A from glucose were extracted and then reacted in water heated at 290 °C to afford catechol in overall yields from glucose of 10% and 2...
Reactive eosinophilia and thrombosis.

![Figure][1] A 76-year-old female with chronic renal disease and dementia was admitted for acute chest pain. Physical examination showed no skin rash or wheezing. A CT scan for pulmonary embolism was positive and anticoagulation was started. Her blood tests showed white blood cells of 21.9
Type 2 diabetes mellitus is associated with multiple cardiometabolic risk factors.

The risk for cardiovascular disease (CVD) is multifactorial and includes such risk factors as diabetes, hypertension, smoking, and dyslipidemia. Thus, targeting the hyperglycemia in type 2 diabetes mellitus (DM) alone will not eliminate all of the excess cardiovascular risk; rather aggressive treatment is needed for all of the modifiable cardiometabolic risk factors. Therapeutic lifestyle change is considered primary therapy for hyperglycemia in type 2 DM. Currently, however, the focus in treatment is on preventing CVD rather than controlling glucose, lipid, or blood pressure (BP) levels. The American Diabetes Association guidelines identify low-density lipoprotein cholesterol as the first priority of lipid lowering, with optimal level set at 65% of patients with DM and hypertension will require 2 or more different antihypertensive drugs. Strategies that combine thiazolidinediones and statins may have complementary effects on cardiovascular risk-factor profiles in type 2 DM, in addition to controlling glycemia. Despite the range of treatment options available, therapeutic agents that target new steps in the progression of CVD are needed, as patients with type 2 DM remain at increased risk and many do not achieve therapeutic targets with the drugs available.
Divine Wisdom and Dolorous Mysteries: Habsburg Marian Devotion in Two Motets from Monteverdi's Selva morale et spirituale

Despite recent scholarly interest in Monteverdi9s Selva morale et spirituale (1641), many aspects of this large, complex print remain enigmatic, and the intended context for much of the music in the collection has long been a matter of pure conjecture. Yet two of the most anomalous features of the Selva morale , the solo motets Ab aeterno ordinata sum and Pianto della Madonna , can now be placed into the context of the Habsburg court in Vienna during the reign of Ferdinand III (1637––57). Both of these works play directly into the most important aspects of Habsburg Marian devotion. Ab aeterno is a setting of Proverbs 8:23––31, a text that although very rare for seventeenth-century motets would nonetheless have been widely understood as a celebration of the Immaculate Conception of the Blessed Virgin. The Pianto , a Latin contrafactum of Monteverdi9s celebrated Lamento d9Arianna , would have been perfectly suited for the Habsburgs9 Fifteen Mysteries Celebration, a Lenten devotion in praise of the Most Holy Rosary. Various types of evidence, including liturgical and other religious writings, Habsburg sermons, and additional musical works, support these interpretations of Monteverdi9s motets and reveal their importance to the imperial court. That the composer did indeed include the motets in his print with the Habsburg court in mind is further indicated by similarities between the Selva morale and an earlier publication stemming directly from Ferdinand III9s court: Giovanni Felice Sances9s Motetti a voce sola of 1638.
Error Models for Stilling Well - Float Type Tide Gages

Tidal measurements are subject to various errors. Because of the increasing emphasis on the accuracy of the data obtained by the Tide and National Water Level Network, the knowledge of these errors is of great importance. This paper summarizes the development of error models pertinent to tide measurement systems utilizing stilling wells and floats. The major error sources addressed include wind waves, water currents, float response, water density variation and marine fouling. Laboratory experiments including a wave tank, tow tank, and oscillatory water tunnel tests were also conducted to validate the wave, current and float response models. The error models developed can be useful tools for evaluating tide measurement systems utilizing stilling wells and floats and can also provide guidance to future design modifications to reduce tidal measurement errors.
Movement characteristics of American beavers (Castor canadensis)

Physiological states and foraging behaviors may shape movement patterns of animals. Optimal foraging theory and what we term the deliberate movement hypothesis predict that, to reduce predation risk, central place foragers should move faster with smaller turning angles the further they are from their central place. The complementary bimodal foraging trip hypothesis predicts that the distribution of foraging distances exhibited by central place foragers should be bimodal due to a trade-off between provisioning offspring and self-feeding. We used radio-telemetry to test these hypotheses for American beavers (Castor canadensis) in northern Alabama, United States. American beavers moved faster with increasing distance from lodges in wetland land cover but not in terrestrial land covers, partially supporting the deliberate movement hypothesis. Hourly distances moved from lodges were distributed bimodally during the breeding season, which supports the bimodal foraging trip hypothesis. Therefore, central place foraging may be a determinant of movement characteristics of American beavers.
Fast encoding algorithms for geometry-adaptive block partitioning

State-of-the-art video compression technologies, such as MPEG-4 AVC/H.264 or the new HEVC standard being developed by ISO MPEG and ITU-T VCEG, make use of tree-structured block partitioning for motion compensation. Such motion partitioning only captures horizontal and vertical motion boundaries. To better match actual motion frontiers, Geometry adaptive block partitioning (GEO) has been explored for several years. GEO enables splitting a block using non-horizontal or non-vertical line. Although noticeable coding efficiency gains can be obtained, GEO involves a significant increase of the number of modes to be tested with therefore a high impact on encoding complexity. This paper presents fast algorithms aiming at controlling the complexity while saving the coding efficiency gains of GEO. Experimental results are provided on top of the HEVC standard, demonstrating first the efficiency of the GEO tool. Simplified versions, offering noticeable complexity reduction with limited rate-distortion performance loss, are also demonstrated and compared.
Observations of tidal temperature and wind perturbations in the mesopause region above Urbana, IL (40°N, 88°W)

Na lidar and MF radar measurements of temperature and horizontal winds were conducted simultaneously during several continuous 24 h periods in March and April 1996 at the Urbana Atmospheric Observatory. The data are used to determine the amplitude and phase profiles of the 24 and 12 h tides in the mesopause region between about 82 and 100 km. The measured amplitudes and phases of the tidal components of the horizontal winds are generally consistent with the predictions of the global-scale wave model (GSWM). The measured 24 h temperature amplitude is comparable to the GSWM predictions between 85 and 96 km but is significantly larger than GSWM above 96 km. The measured phase progression is downward below 94 km with an inferred vertical wavelength of 14±1 km. Above 94 km the temperature phase progression is upward with a vertical wavelength of 12±1 km. The measurements suggest the presence of a diurnal heat source in the lower thermosphere which is generating a strong downwardly propagating 24 h wave.
Application of GPS for transportation related engineering surveys

The Texas State Department of Highways and Public Transportation(SDHPT) has been usingGPS for over two years to establish primary geodetic reference points for engineering projects and mapping control. In accordance with a Five YearGPS Implementation Plant developed in 1982, fourGPS, unmanned, automatic Regional Reference Point(RRP) stations will be installed by September 1, 1986. Five additional stations are planned as justified. EachRRP will consist of a dual frequencyGPS receiver that will ultimately track the satellites continuously. Operation of the receiver, telecommunications and other station keeping chores will be handled by a microcomputer. TheRRP station network will be controlled through another centrally located microcomputer which is also interfaced with a larger mainframe system. EachRRP is designed to service an area bounded by a200 KM radius and will act as the “other” receiver for roving field units operating in aGPS differential measurement mode. In order to meet the installation schedule, early decisions are being made concerning satellite tracking rates, operational scenarios, and telecommunications to facilitate development of the basic hardware and software systems. A period of continual enhancement to hardware, software andRRP operational procedures is expected asGPS technology expands.
Stereotactic body radiation therapy for abdominal and pelvic oligometastases: Dosimetric targets for safe and effective local control

Abstract Purpose To investigate correlates and predictors of outcomes of stereotactic body radiation therapy (SBRT) for patients with abdominal and pelvic oligometastases from different primary tumors. Methods and materials We evaluated outcomes of 38 consecutive patients with 44 unresectable nodal and soft-tissue oligometastases in the abdominal pelvic region who were treated with SBRT between November 2008 and April 2014. Thirty-two patients had solitary lesions and 6 patients had 2 lesions. The median prescription dose was 40 Gy (24-50 Gy) delivered in 4-5 fractions. The median gross tumor volume was 18.7 mL (0.7-194.1 mL). We evaluated tumor response, local control (LC), and overall survival (OS) rates as well as acute and chronic toxicities. Results At a median follow-up of 19 months (0.9-53.4 months), tumor responses were: complete response 31.8%, partial response 38.6%, standard deviation 20.5%, and progressive disease 9.1%. The overall 1- to 2-year LC and OS rates were 100%/75.1% (95% confidence interval [CI], 54.4%-88.4%) and 95.2% (95% CI, 82.8%-98.8%)/88.9% (95% CI, 68.1%-95.1%), respectively. On univariate analysis, increasing SBRT dose, smaller gross tumor volume, and asymptomatic lesions were associated with improved LC ( P = .01, P P = .01, respectively). On multivariate analysis, advanced original primary disease stage predicted for worse OS ( P = .001). One patient developed a colovesicular fistula at 20.9 months in the setting of local tumor progression with a volume of bowel receiving 20 Gy (V 20Gy ) = 26.9 mL. The overall mean bowel V 20Gy achieved was 16 ± 22.9 mL. Another patient had grade 2 proctitis at 13 months after SBRT. Pain relief was achieved in 81.8% of patients with symptomatic lesions (N = 11). Conclusions Our results suggest that SBRT doses 40-50 Gy in 5 fractions (biological effective dose 72-100 Gy 10 ) with bowel V 20Gy ≤20 mL are efficacious and associated with minimal toxicity for abdominal pelvic nodal and soft-tissue oligometastases. Palliation of symptoms is achievable in most patients with symptomatic lesions. SBRT for oligometastases may be a good alternative to systemic therapy in selected patients.
Association between β2-glycoprotein I gene polymorphisms and pediatric SLE and antiphospholipid antibodies

Antibodies against phospholipids (PL) and PL-binding proteins have been causally implicated in antiphospholipid syndrome (APS). Mutations in the fifth domain of the β2-glycoprotein I (β2GPI) protei...
Hypothesis Generation and Evaluation in Clinical Trial Design

We are developing and implementing novel applications of knowledge representation, ontology development and natural language processing to address issues within the pharmaceutical industry. It is well-documented that the pharmaceutical industry is experiencing significant difficulties in maintaining its historical record of drug approvals and financial achievement because of failures in moving compounds from the discovery pipeline to regulatory approval and commercial success. The critical link in this transition is the clinical trial, heavily regulated and monitored for patient safety and drug efficacy. At present, only about 9% of drugs entering clinical trials succeed in being approved by the regulatory bodies, and unfortunately, that, alone, does not guarantee commercial success as a significant number of approved drugs fail upon introduction into the marketplace. Our approach evaluates and refines the hypothesis upon which these trials are based, establishes a comprehensive approach to an early go/no go decision, identifies risk and improves the probability for success.
Adsorption, desorption and oxidation of arsenic affected by clay minerals and aging process

Adsorption/desorption and oxidation/reduction of arsenic at clay surfaces are very important to the natural attenuation of arsenic in the subsurface environment. Although numerous studies have concluded that iron oxides have high affinities for the adsorption of As(V), very little experimental work has addressed the arsenic attenuation capacities of different clay minerals and aging process affecting the transformation of arsenic. The abundance of clay minerals in a variety of geochemical environments and their influence on adsorption of contaminants suggests a need for more experimental work to characterize the adsorption desorption, and oxidation of arsenic on clay minerals. In this investigation three types of clay mineral were studied: the 1 : 1 layer clays [halloysite (IN), sedimentary M-kaolinite, and weathered EPK-kaolinite]; the 2 : 1 layer clays [illite (MT) and illite/montmorillonite (MT)]; the 2 :>: 1 layer clay [chlorite (CA)]. The halloysite and the chlorite had much greater As(V) adsorption (25–35 folds) than the other clay minerals. The clay minerals had lower As(III) adsorption than As(V) adsorption, and the adsorption was affected by pH. Desorption of arsenic from the clay minerals was significantly influenced by the aging process. The quantities of extractable As(III) and As(V) decreased with increasing aging time. The results demonstrated that oxidation of As(III) to As(V) occurred on the clay surfaces, whereas reduction of As(V) to As(III) was not found in any of the clay minerals studied. The oxidation of As(III) was affected by the types of clay and aging time.
Glutamate receptors: Mechanistic twists and turns

Ionotropic glutamate receptors are ligand-gated ion channels that mediate excitatory neurotransmission, which is crucial for memory and learning. New cryo-electron microscopy structures of these receptors trapped in distinct functional states provide remarkable insight into conformational changes triggered by agonist binding.
Periodicity and self‐actualization in women

Studied the relationship between menstrual cycle phase and self-actualization as measured by the Personal Orientation Inventory (POI). In classroom testing sessions, 160 high school students completed the POI and personal data sheets, which gave information about their menstrual cycle phase. Premenstrual, menstrual, and midcycle groups of 20 Ss each were formed from those girls eligible for inclusion in each condition. Three one-by-three analyses of variance were run using the TC, I, and TC + I scores of the POI, which were selected as the best overall measures of self-actualization. A significant (p less than .05) difference on TC + I was found; subsequent t-tests revealed that the menstrual group's TC + I score was significantly (p less than .02) higher than that of the midcycle group. The difference between menstrual and premenstrual Ss on TC + I, though not significant, lay in the same direction and was of the same order of magnitude. Possible explanations for the results and implications for future testing that involves females are presented briefly.
Mineralogy and stable isotope geochemistry of hydrothermally altered oceanic rocks

Mineralogical and isotopic variations observed in altered glassy and crystalline rocksfrom the East Pacific Rise and the Mid-Atlantic Ridge provide information about the temperatures of alteration and seawater/rock ratios for various hydrothermal regimes within the oceanic crust. A systematic increase in alteration temperature is evident for the glassy rocksin the sequence: (1) nontronite and celadonite vesicle fillings (35°C), (2) saponite-rich pillow breccias ( 130–170°C), (3) calcite-rich greenstone breccias and epidote-rich greenstone (200–350°C). Theseresults include the highest temperatures thus far reported for saponite formation. The “seawater-dominated” hydrothermal alteration process that formed the saponite-rich pillow breccias is characterized by high water/rock ratios (>0:1), low to moderate temperatures, a seawater origin of most of the carbon in vein calcites (δ 13 C≈0) and the predominance of Fe-rich saponite and calcite as secondary phases. Greenstones (chlorite-quartz-epidote) and greenstone breccias (chlorite-quartz-albite-calcite) are altered in a “rock-dominated” system with lower water/rock ratios (50:1 to 13 C≈−4). The crystalline rocks (diabase, gabbro, and metagabbro) are affected to varying degrees by pervasive high-temperature seawater interactions that commence soon after solidification, producing varying proportions of fine-grained secondary minerals including talc, smectite, chlorite, vermiculite, actinolite, and sodicplagioclase. Hydrothermal solutions, derived from alteration of the crystalline rocks, are of the appropriate temperature and isotopic composition to alter the overlying glassy rocks to the observed mineralogies as well as being the source of metal-rich deposits associated with the oceanic spreading centers.
The use of time‐limited relationship therapy with borderline patients

(1967). The use of time‐limited relationship therapy with borderline patients. Smith College Studies in Social Work: Vol. 37, No. 2, pp. 127-141.
A HIDDEN POPULATION OF MASSIVE STARS WITH CIRCUMSTELLAR SHELLS DISCOVERED WITH THE SPITZER SPACE TELESCOPE

We have discovered a large number of circular and elliptical shells at 24 μm around luminous central sources with MIPS on board the Spitzer Space Telescope. Our archival follow-up effort has revealed 90% of these circumstellar shells to be previously unknown. The majority of the shells is only visible at 24 μm, but many of the central stars are detected at multiple wavelengths from the mid- to the near-IR regime. The general lack of optical counterparts, however, indicates that these sources represent a population of highly obscured objects. We obtained optical and near-IR spectroscopic observations of the central stars and find most of these objects to be massive stars. In particular, we identify a large population of sources that we argue represents a narrow evolutionary phase, closely related or identical to the luminous blue variable stage of massive stellar evolution.
A more efficient message-optimal algorithm for distributed termination detection

Termination detection is a fundamental problem in distributed computing. Many algorithms have been proposed, but only the S. Chandrasekaran and S. Venkatesan (CV) algorithm (1990) is known to be optimal in worst-case message complexity. This optimal algorithm, however, has several undesirable properties. First, it always requires M'+2* mod E mod +n-1 control messages, whether it is worst case or best case, where M' is the number of basic messages issued by the underlying computation after the algorithm starts, mod E mod is the number of channels in the system, and n is the number of processes. Second, its worst-case detection delay is O(M'). In a message-intensive computation, that might not be tolerable. Third, the maximum amount of space needed by each process is O(M'), a quantity not known at compile time, making it necessary to use the more expensive dynamic memory allocation. Last, it works only for FIFO channels. This paper remedies these drawbacks, while keeping its strength. The authors propose an algorithm that requires M'+2(n-1) control messages in the worst case, but much fewer on the average, and in the best case, it uses only 2(n-1) control messages, no matter how large M' is. >
A novel predictive inductor multiplier for integrated circuit DC-DC converters in portable applications

While the large passive elements of power converters are in the way of converging walls of shrinking cell phones and cameras, the new capabilities these devices flaunt are creating additional burdens and making it difficult to meet specifications without even bigger elements. Active circuits that enhance the effects of passive elements will allow power converters to handle larger loads and get smaller at the same time. This paper presents a predictive inductor multiplier circuit that amplifies the effective inductance in a Buck converter. The output ripple of the simulated converter is so small that the converter appears to have an inductance thirty-eight times the value actually used. Compensating for small inductors introduces new power losses, but it is discovered that linear regulators and faster switching converters can be even less efficient.
Evaluation of a radioimmunoassay for histamine measurement in biologic fluids

A new radioimmunoassay for the measurement of histamine in biologic fluids was evaluated. Assay selectivity and specificity were achieved by "succinyl-glycinamide derivatization" of histamine in samples to mimic the immunogen used to generate the monoclonal antibody. The assay exhibits a linear response from 0.1 to 5.0 ng/ml of histamine and the monoclonal antibody used has partial recognition of only N-methylhistamine (other than histamine). With minimal modifications, the assay can accurately measure histamine in plasma, urine, and buffer. Normal ranges for human subjects were established: plasma levels are 0.193 +/- 0.08 ng/ml (n = 40) and urine levels are 20.9 +/- 11.2 micrograms histamine/gm creatinine (n = 10).
One-Sided Cross-Validation

Abstract A new method of selecting the smoothing parameters of nonparametric regression estimators is introduced. The method, termed one-sided cross-validation (OSCV), has the objectivity of cross-validation and statistical properties comparable to those of a plug-in rule. The new method may be viewed as an application of the prequential model selection method of Dawid. As such, our results identify a situation in which the prequential method is a more efficient model selector than cross-validation. An example, simulations, and theoretical results demonstrate the utility of OSCV when used with local linear and kernel estimators.
Analysis of Residue Integration Sampling With Improved Jitter Immunity

The improved jitter immunity of window residue sampling (WRS) is analyzed in this brief. We build a mathematical model for WRS and compare the signal-to-noise ratio performance with the conventional impulse and integration sampling methods. Simulation results show that WRS has better jitter immunity of approximately 3 dB compared with conventional impulse sampling at the Nyquist input frequency.
Towards feasibility and scalability of text search in peer-to-peer systems

In this paper, we introduce a search engine, Dgoogle, designed for large scale P2P systems. Dgoogle is purely text- based, does not organize documents based on pre-defined keywords or based on their semantics. It is simple to implement and can tolerate variations in the wording of text queries. Compared to existing proposals, such as Inverted Indices, Dgoogle does not stress network bandwidth and offers an order of magnitude of savings in storage overhead and in the response time to user queries. Furthermore, Dgoogle's performance is not affected by long queries or by processing popular query words. Simulation results validate the efficacy of our proposal.
Duodenal infusion of stool is more effective than vancomycin in patients with recurrent Clostridium difficile

Commentary on: Van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 2013;368:407–15.[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Clostridium difficile infection (CDI) is increasing in both inpatients and outpatients. CDI accounted for approximately 336 600 inpatient hospitalisations in the USA in 2009.1 Recurrent CDI (RCDI) occurs in 15–30% of patients after the initial infection and in 40–65% with subsequent infections.1 Guidelines recommend that for mild disease, a first recurrence can be treated with the same initial antibiotic regimen; however, severe recurrent disease should be treated with vancomycin.2 Stool transplant or faecal microbiota transplantation (FMT) has been recommended in a recent gastrointestinal (GI) guideline for RCDI.3 This was the first open-label non-blinded … [1]: {openurl}?query=rft.jtitle%253DN%2BEngl%2BJ%2BMed%26rft.volume%253D368%26rft.spage%253D407%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa1205037%26rft_id%253Dinfo%253Apmid%252F23323867%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMoa1205037&link_type=DOI [3]: /lookup/external-ref?access_num=23323867&link_type=MED&atom=%2Febmed%2F18%2F6%2F220.atom [4]: /lookup/external-ref?access_num=000314215400005&link_type=ISI
A retrospective review of digit span-related effort indicators in probable Alzheimer's disease patients.

There has been extensive research on the use of both stand-alone and embedded measures of effort in neuropsychological testing; however, relatively few studies have reported on their utility in the context of dementia. Previous studies that have examined the specificity of traditionally used cut-scores on embedded measures of effort with dementia samples have largely found high rates of false positive errors. The present study examined the specificity of several Digit Span derived embedded measures of effort in a large clinical sample of patients with probable Alzheimer's disease stratified by level of dementia severity. Of the measures that were examined, only the Vocabulary – Digit Span score demonstrated promising specificity through the moderate level of dementia severity. All of the remaining indices, including Reliable Digit Span, Digit Span Age-Corrected Scaled Score, and Longest Digits Forward (1 & 2 Trials), yielded unacceptable rates of false positive errors as dementia severity increased. The i...
HIGH TIMES FOR HATE CRIMES: EXPLAINING THE TEMPORAL CLUSTERING OF HATE‐MOTIVATED OFFENDING

This research explains the temporal clustering of hate crimes. It is hypothesized that many hate crimes are retaliatory in nature and tend to increase, sometimes dramatically, in the aftermath of an antecedent event that results in one group harboring a grievance against another. Three types of events are used to test and refine the argument: 1) contentious criminal trials involving interracial crimes, 2) lethal terrorist attacks, and 3) appellate court decisions concerning same-sex marriage. The results from time-series analyses indicate that contentious trial verdicts and lethal domestic terrorist attacks precede spikes in racially or religiously motivated hate crimes, whereas less evidence is found for antigay hate crimes after appellate court rulings that grant rights to same-sex partners. The model put forth in this article complements prior work by explaining in part the timing of hate crime clusters. Language: en
Cyanobacteria as biological drivers of lake nitrogen and phosphorus cycling

Here we draw attention to the potential for pelagic bloom-forming cyanobacteria to have substantial effects on nutrient cycling and ecosystem resilience across a wide range of lakes. Specifically, we hypothesize that cyanobacterial blooms can influence lake nutrient cycling, resilience, and regime shifts by tapping into pools of nitrogen (N) and phosphorus (P) not usually accessible to phytoplankton. The ability of many cyanobacterial taxa to fix dissolved N2 gas is a well-known potential source of N, but some taxa can also access pools of P in sediments and bottom waters. Both of these nutrients can be released to the water column via leakage or mortality, thereby increasing nutrient availability for other phytoplankton and microbes. Moreover, cyanobacterial blooms are not restricted to high nutrient (eutrophic) lakes: blooms also occur in lakes with low nutrient concentrations, suggesting that changes in nutrient cycling and ecosystem resilience mediated by cyanobacteria could affect lakes across a gradient of nutrient concentrations. We used a simple model of coupled N and P cycles to explore the effects of cyanobacteria on nutrient dynamics and resilience. Consistent with our hypothesis, parameters reflecting cyanobacterial modification of N and P cycling alter the number, location, and/or stability of model equilibria. In particular, the model demonstrates that blooms of cyanobacteria in low-nutrient conditions can facilitate a shift to the high-nutrient state by reducing the resilience of the low-nutrient state. This suggests that cyanobacterial blooms warrant attention as potential drivers of the transition from a low-nutrient, clear-water regime to a high-nutrient, turbid-water regime, a prediction of particular concern given that such blooms are reported to be increasing in many regions of the world due in part to global climate change.