cssi/SciSciGPT-SciSciNet huggingface dataset:
Tacrolimus Level Variability in Setting of Gastric Sleeve

Introduction While weight loss surgery can allow obese transplant (tx) candidates to meet body mass index (BMI) criteria for listing, it may impact immunosuppression (IS) exposure. IS pharmacokinetics (PK) are affected by alterations in the gastrointestinal tract and have been described in tx recipients receiving roux-en-y gastric bypass, gastrectomy and laproscopic gastric sleeves (LGS). We report a unique case with a patient with notable variability in IS exposure after LSG. Case Report Our patient is a 42 year old Black male deferred on the waitlist due to BMI >40 kg/m2. He received a LSG resulting in 19 kg weight loss and underwent heart tx 8 months later. IS immediately post-tx consisted of triple drug IS with immediate release tacrolimus (goal 10-13 ng/mL), mycophenolate mofetil and prednisone with posaconazole anti-fungal prophylaxis. Throughout the first 4 months levels were stable and monitored at least weekly. Then the patient began to have variable levels despite adherence and no dose changes leading to 2R rejection at 5 months. Tacrolimus levels continued to fluctuate with weekly labs despite adding CYP3A4 inhibitors (diltiazem, itraconazole) to help achieve therapeutic levels. Conversion to extended release (XR) tacrolimus [Envarsus] was done to reduce headaches, tremors and attempt for stable levels. Levels remained erratic on the XR formulation despite consistency in timing of administration and food consumption. A peak and trough of XR tacrolimus was measured in conjunction with a mycophenolic acid (MPA) mini area under the curve (AUC). The MPA mini AUC was unchanged from directly post tx (56.6 vs 43.2 mcg/mL). Tacrolimus PK was abnormal with identical trough and 3 hour peak levels (10.7 ng/mL). Summary To achieve goal tacrolimus levels (8-12 ng/mL) our adherent patient required doses from 8 to 38 mg/day (0.07 - 0.33 mg/kg/day). This variation contributed to rejection and neurotoxicity and may have been related to alterations in tacrolimus exposure after LSG. Patients with LSG warrant increased IS monitoring post tx.
When cells are down on their LUC7L2, alternative splicing rewires metabolism for OXPHOS

Daniels et al. (2021) and Jourdain et al. (2021) identify LUC7L2 as a component of the U1 snRNP capable of reprogramming cellular metabolism through changes in alternative pre-mRNA splicing.
Network-based integration of epigenetic landscapes unveils molecular programs underlying human T follicular helper cell differentiation

T follicular helper (Tfh) cells play a critical role in T-dependent humoral immune responses. While genetic programs controlling Tfh cell differentiation have been extensively studied using murine models, studies in humans have been hampered by the lack of a robust in vitro differentiation system for Tfh cells. We characterized epigenomic landscapes across stages of Tfh cell differentiation in a healthy human tonsil using ATAC-Seq and CUT&RUN for selected histone modifications. We combined these epigenomic datasets and integrated them with the reference human protein interactome using a novel network propagation approach. Our approach uncovered subnetworks integral to Tfh cell differentiation. These subnetworks captured known Tfh cell drivers to a greater extent than conventional gene-centric analyses would, and also revealed novel modules that may be required for Tfh cell differentiation. We find that human Tfh cell subnetworks are functionally associated with specific immune signaling cascades including cytokine receptor driven pathways. Analyses of transcriptomic data revealed that in addition to these immune pathways being significantly dysregulated in severe COVID-19, the corresponding Tfh cell subnetworks are also transcriptionally perturbed to a similar extent. This provides a molecular mechanistic basis for the previously observed impaired Tfh cell differentiation and loss of germinal centers in severe COVID-19.
X‐ray diffraction, differential scanning calorimetry and evolved gas analysis of aged plutonium tetrafluoride (PuF4)

A 30 year-old PuF4 sample consisting of brown powder (PuF4-b) and pink granules (PuF4-p) was analyzed. X-ray diffraction shows the bulk is comprised of three compounds: PuF4, PuO2, and PuF4·1.6H2O. Broadening of PuF4 XRD peaks suggests possible $$\upalpha$$ -damage. After annealing at 650 °C, crystalline PuF4 and PuO2 remain. Thermogravimetric analysis and differential scanning calorimetry—with simultaneous evolved gas analysis—of the separated PuF4-p and PuF4-b components reveal a distinct sequence of reactions. Dehydration occurs between ~ 90 and 300 °C. Exothermic annealing of the $$\upalpha$$ -damage occurs in two stages: at 350–355 °C and at 555–558 °C. Hydrofluoric acid, fluorine and helium desorb during the first exotherm. Above 700 °C, PuF4 reacts with PuO2, resulting in oxygen release and mass loss.
Feasibility of a virtual reality-based approach to improve behavioral weight management outcomes.

Background Behavioral weight loss interventions promote clinically significant weight loss over 12 months, but weight regain remains problematic and a substantial proportion of participants do not achieve long-term weight loss maintenance. Novel methods are needed that instill habit strength for sustaining weight control behaviors long term. Virtual reality (VR) has the potential to provide opportunities within behavioral treatment for patients to practice desired weight control behaviors in the frequency and magnitude necessary to build durable habits. A pilot randomized trial was done to test the feasibility integrating virtual reality (VR) into standard behavioral weight loss treatment. Methods Participants were 15 adults (43 years; 46.7% Hispanic), with overweight or obesity who were randomly assigned to a 4-week Standard Behavioral Weight Loss plus Non-Weight-Related VR app (i.e., Control Group) or Standard Behavioral Weight Loss plus Weight-Related VR app (i.e., Intervention Group). The Intervention's VR tool was designed to enable practice of behavioral skills taught in weekly group meetings, including managing social and home environmental cues for eating and activity. Results Participants were recruited over 3 months, and retention at the final assessment visit was high (86.6%). The VR footage and resulting app were rated as highly realistic (6.7 on a 10-point scale), and the VR program overall was rated as highly satisfactory (3.6 on a 4-point scale). Adverse effects of eye strain and motion sickness were minimal (~ 2 on a 7-point scale). As expected, the intervention and control groups both lost weight and unadjusted means (SD) averaged 3.4% (2.7) and 2.3% (3.6), respectively, over the 4 weeks. Overall, participants reported preferring a VR approach above traditional weight loss programs (rating of 5 on a 7-point scale). Conclusions Future research is needed to develop and test the feasibility of using VR for other weight control skills with a larger sample size and longer evaluation period to determine if VR can improve standard behavioral weight loss outcomes by intensifying practice opportunities and building habit strength for weight loss maintenance. Trial registration NCT04534088 ; date of registration: 09/01/2020, retrospectively registered.
The Perceptual and Cognitive Processes That Govern Egg Rejection in Hosts of Avian Brood Parasites

Hosts of avian brood parasites are under intense selective pressure to prevent or reduce the cost of parasitism. Many have evolved refined egg discrimination abilities, which can select for eggshell mimicry in their parasite. A classic assumption underlying these coevolutionary dynamics is that host egg recognition depends on the perceivable difference between their own eggs and those of their parasite. Over the past two decades, the receptor noise-limited (RNL) model has contributed to our understanding of these coevolutionary interactions by providing researchers a method to predict a host’s ability to discriminate a parasite’s egg from its own. Recent research has shown that some hosts are more likely to reject brown eggs than blue eggs, regardless of the perceived differences to their own. Such responses suggest that host egg recognition may be due to perceptual or cognitive processes not currently predictable by the RNL model. In this perspective, we discuss the potential value of using the RNL model as a null model to explore alternative perceptual processes and higher-order cognitive processes that could explain how and why some hosts make seemingly counter-intuitive decisions. Further, we outline experiments that should be fruitful for determining the perceptual and cognitive processing used by hosts for egg recognition tasks.
Carcinogenesis Risk Assessment Model for Environmental Chemicals

A Monte Carlo computer simulation model was created incorporating the pharmacokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the stochastic pharmacodynamics of resulting carcinogenesis. The animal model was the female Sprague-Dawley rat. The model was calibrated to the observed tumor formation probabilities from a carcinogenesis bioassay. TCDD tissue distribution was modeled with a four-compartment physiologically based pharmacokinetic model, using compartments of liver, fat, muscle/skin, and richly perfused tissue. The model includes TCDD binding to two liver compartment sites, a cytosolic receptor and a microsomal binding protein. The concentration bound to the cytosolic receptor was used as the basis for dose-response in a stochastic pharmacodynamic model. Using a Monte Carlo approach, the stochastic model was calibrated to the bioassay controls, and then to the bioassay high and medium dose data using a two parameter fitting function. Fitting to low dose results was impossible because the bioassay had an anomalous decreased response relative to controls. The overall model is capable of predicting human carcinogenesis in response to environmental TCDD exposure through substitution of human biological parameters for those of Sprague-Dawley rats.
Illicit psychotropic substances in the air: The state-of-art.

The occurrence of psychotropic substances (PSs) in the air is known since long time. Recently, attention was paid to illicit PS, with most investigations undertaken in Italy and Spain. In general, collection of illicit substances was performed through aspirating airborne particulates onto filters; afterwards, gas chromatography or high-performance liquid chromatography coupled with mass spectrometry were applied for the PS evaluation. Over twenty substances could be characterized simultaneously. Cocaine concentrations up to 17ngm(-3) were observed in Latin America, while this substance was absent (<0.003ngm(-3)) in Algiers (Algeria) and Pancevo (Serbia). Cannabinoids (comprising the psycho-active principle Δ(9)-tetrahydrocannabinol [THC]) were high in the winter and very low in the summer (up to 6ngm(-3) and <0.1ngm(-3), respectively). Many other substances (e.g., heroin, ephedrine and drug by-products) occurred less frequently and at lesser extents (<20pgm(-3)). In Rome (Italy), investigations were carried out in interiors of dwellings, schools, an office and a coffee bar, all sites resulting affected by drugs. Besides, solid phase microextraction methods were applied to detect ketamine and methamphetamine in interiors. The PS concentrations depended on substance, physical-chemical contour, and internal or external type of locations. Air monitoring allows detecting the drug consumption or preparation, because illicit substances prevail in sites frequented by abusers.
Scale-up and multiphase reaction engineering

Successful scale-up of new multiphase reactions from the laboratory into practical processes is important to all sectors of the process industry. Business demands that process technologies involving molecular transformations maintain high profitability and operate safely within existing environmentally regulations. Current societal expectations and regulations require that all process technology should be environmentally responsible [ 1 ]. One key question to be answered is whether or not these expectations can be met in the foreseeable future with the current approaches to scale-up and technological workforce. In addition, advances in chemistry, physics, materials, and biology will continue to generate new potential reaction pathways for more efficient utilization of non-renewable and renewable resources. Another key question is whether the current methods for process scale-up incorporate the relevant scientific advances to ensure ‘green technologies’, or are they just extensions of previous largely empirical approaches having limited utility and reliability? Evidence suggests that only a science-based scale-up methodology can substantially reduce the risk of new process commercialization and provide reliable estimates of both profitability and environmental impact. We review briefly here the historical approach to scale-up and opine on the challenges of implementing improved approaches.
Targeted disruption of the epidermal growth factor receptor impairs growth of squamous papillomas expressing the v-ras(Ha) oncogene but does not block in vitro keratinocyte responses to oncogenic ras.

Abstract We have assessed the role of epidermal growth factor receptor (EGFR) signaling in biological responses to the v- ras Ha oncogene using primary keratinocytes from Egfr -/- mice and wild-type littermates. On the basis of several criteria, Egfr -/- keratinocytes were unresponsive to either acute or chronic exposure to several EGFR ligands but were stimulated to proliferate in response to several other mitogens. Although conditioned medium from primary keratinocytes transduced with v- ras Ha retrovirus (v- ras Ha keratinocytes) was a potent mitogen for wild-type but not Egfr -/- keratinocytes, v- ras Ha transduction of primary keratinocytes of either genotype resulted in a strong mitogenic response, arguing against an obligatory role for EGFR activation in v- ras Ha -mediated stimulation of keratinocyte proliferation. Infection with high-titer v- ras Ha retrovirus altered the keratin expression pattern in keratinocytes of both genotypes, suppressing differentiation-specific keratins K1 and K10 while activating aberrant expression of K8 and K18. In wild-type but not Egfr -/- cultures, K1 and K10 were also suppressed following infection at lower retroviral titers, presumably as a result of paracrine EGFR activation on uninfected cells present in these cultures. Squamous papillomas produced by grafting Egfr -/- v- ras Ha keratinocytes onto nude mice were only 21% of the size of wild-type v- ras Ha tumors, and a striking redistribution of S-phase cells was detected by immunostaining for bromodeoxyuridine. In Egfr -/- v- ras Ha papillomas, the fraction of total labeled nuclei detected in suprabasal layers was increased from 19 to 39%. In contrast, the basal layer labeling index of Egfr -/- papillomas was reduced to 34%, compared to 43% in wild-type tumors. Our results indicate that, although autocrine EGFR signaling is not required for keratinocyte responses to oncogenic ras in culture or benign tumor formation in nude mouse grafts, disruption of this pathway impairs growth of v- ras Ha papillomas by a mechanism that may involve alterations in keratinocyte cell cycle progression and/or migration in vivo .
A systematic framework for unearthing the missing links: measurements and impact

The lack of an accurate representation of the Internet topology at the Autonomous System (AS) level is a limiting factor in the design, simulation, and modeling efforts in inter-domain routing protocols. In this paper, we design and implement a framework for identifying AS links that are missing from the commonly-used Internet topology snapshots. We apply our framework and show that the new links that we find change the current Internet topology model in a non-trivial way. First, in more detail, our framework provides a large-scale comprehensive synthesis of the available sources of information. We cross-validate and compare BGP routing tables, Internet Routing Registries, and traceroute data, while we extract significant newinformation from the less-studied Internet Exchange Points (IXPs). We identify 40% more edges and approximately 300% more peer-to-peer edges compared to commonly used data sets. Second, we identify properties of the new edges and quantify their effects on important topological properties. Given the new peer-to-peer edges, we find that for some ASes more than 50% of their paths stop going through their ISP providers assuming policy-aware routing. A surprising observation is that the degree of a node may be a poor indicator of which ASes it will peer with: the two degrees differ by a factor of four or more in 50% of the peer-to-peer links. Finally, we attempt to estimate the number of edges we may still be missing.
Excision repair of uracil during replication of ØX174 DNA in vitro

Abstract Each of the stages in the replication of OX174 DNA in vitro , e. g., conversion of circular single stranded parental DNA to the duplex replicative form (SS → RF), replication of the closed circular duplex form (RF → RF), and synthesis of circular single stranded progeny DNA (RF →SS), may be affected by a reduced level of dUTPase. Thus, in enzyme preparations from mutant strains defective in dUTPase ( dut −), the complementary strand synthesized in the SS → RF reaction is abnormally short (7–8S vs. 14S), and the extent of RF replication is decreased 10-fold. Preferential removal of dUTPase during fractionation of enzyme preparations from wild type ( dut +) cells may produce comparable effects. In particular, the single stranded circular DNA synthesized in the RF → SS reaction by a set of highly purified enzymes is rapidly degraded upon incubation with the less pure enzymes required for its conversion to RF. All of these effects are plausibly accounted for by the incorporation into DNA of uracil from dUTP, possibly present as a contaminant in one or more components of the reaction, followed by excision of the uracil and phosphodiester bond cleavage at the resulting apyrimidinic site.
Measurements of Ultrasonic Scattering from Near-Surface Flaws

In ultrasonic NDE measurements the detection of subsurface flaws is of practical importance, especially flaws too far from the surface to be detected by eddy current methods and yet close enough to the surface for the flaw-surface interaction to be important. In this paper we report experimental results of ultrasonic scattering measurements of subsurface flaws in the presence of a fluid-solid interface and compare these results with theoretical calculations of subsurface flaw scattering. Comparison of the absolute value of the scattering amplitude in terms of frequency, flaw-to-surface distance, ultrasonic mode and scattering angle will be made for an oblate spheroidal void in the interior of bulk titanium and for a spherical inclusion near the surface of a thermoplastic sample. Results of applying the one-dimensional inverse Born algorithm to the sizing of near-surface flaws are also reported.
Pars and pedicle fracture and screw loosening associated with cortical bone trajectory: a case series and proposed mechanism through a cadaveric study.

Abstract Background Context Cortical bone trajectory (CBT) technique for pedicle screw placement in the lumbar spine has become more popular since its introduction in 2009. The distinct advantages of using the CBT technique involve increased screw purchase within the cortical bone and reduced surgical dissection. However, contrary to several favorable biomechanical results, there were anecdotal reports of clinical complications associated with CBT. Purpose This study aimed (1) to report on two unique pars and pedicle fracture cases involving the use of the CBT technique and (2) to perform a cadaveric pilot study to determine the possible mechanism for this fracture pattern. Study Design/Setting A case report and cadaveric study were carried out. Methods After presenting two clinical cases, 19 fresh-frozen lumbar vertebrae were obtained from 8 cadavers. Pedicle screws were instrumented on each level using CBT under video recording. After the instrumentation, X-ray images were obtained, and anatomical dissections were performed. Results To be able to reach a necessary angle for medial to lateral CBT trajectory, 13 out of 19 (68%) spinous processes had to be removed. There were a total of seven complications. One pars and pedicle fracture out of 37 trajectories (2.7%) and 6 out of 37 trajectory deviations (16.2%), which resulted in gross loosening, were observed. Conclusions The head of the pedicle screw impinging on the base of spinous process and lamina was observed in our cadaveric model. This mechanism could potentially explain both screw loosening and fractures associated with the CBT technique.
Species Specificity in Major Urinary Proteins by Parallel Evolution

Species-specific chemosignals, pheromones, regulate social behaviors such as aggression, mating, pup-suckling, territory establishment, and dominance. The identity of these cues remains mostly undetermined and few mammalian pheromones have been identified. Genetically-encoded pheromones are expected to exhibit several different mechanisms for coding 1) diversity, to enable the signaling of multiple behaviors, 2) dynamic regulation, to indicate age and dominance, and 3) species-specificity. Recently, the major urinary proteins (Mups) have been shown to function themselves as genetically-encoded pheromones to regulate species-specific behavior. Mups are multiple highly related proteins expressed in combinatorial patterns that differ between individuals, gender, and age; which are sufficient to fulfill the first two criteria. We have now characterized and fully annotated the mouse Mup gene content in detail. This has enabled us to further analyze the extent of Mup coding diversity and determine their potential to encode species-specific cues. Our results show that the mouse Mup gene cluster is composed of two subgroups: an older, more divergent class of genes and pseudogenes, and a second class with high sequence identity formed by recent sequential duplications of a single gene/pseudogene pair. Previous work suggests that truncated Mup pseudogenes may encode a family of functional hexapeptides with the potential for pheromone activity. Sequence comparison, however, reveals that they have limited coding potential. Similar analyses of nine other completed genomes find Mup gene expansions in divergent lineages, including those of rat, horse and grey mouse lemur, occurring independently from a single ancestral Mup present in other placental mammals. Our findings illustrate that increasing genomic complexity of the Mup gene family is not evolutionarily isolated, but is instead a recurring mechanism of generating coding diversity consistent with a species-specific function in mammals.
Hippocampus, amygdala, and basal ganglia morphometrics in children after moderate-to-severe traumatic brain injury

While closed head injury frequently results in damage to the frontal and temporal lobes, damage to deep cortical structures, such as the hippocampus, amygdala, and basal ganglia, has also been reported. Five deep central structures (hippocampus, amygdala, globus pallidus, putamen, and caudate) were examined in 16 children (eight males, eight females; aged 9-16y), imaged 1 to 10 years after moderate-to-severe traumatic brain injury (TBI), and in 16 individually-matched uninjured children. Analysis revealed significant volume loss in the hippocampus, amydala, and globus pallidus of the TBI group. Investigation of relative volume loss between these structures and against five cortical areas (ventromedial frontal, superomedial frontal, lateral frontal, temporal, and parieto-occipital) revealed the hippocampus to be the most vulnerable structure following TBI (i.e. greatest relative difference between the groups). In a separate analysis excluding children with focal hippocampal abnormalities (e.g. lesions), group differences in hippocampal volume were still evident, suggesting that hippocampal damage may be diffuse rather than focal.
Effect of Mucosal Removal on the Response of the Feline Bladder to Pharmacological Stimulation

AbstractThe urothelium plays an important role in the maintenance of normal bladder function. It provides a nonpermeable barrier to the contents of urine. The urothelium is directly involved in the transduction of both intravesical pressure and intravesical volume information to the afferent nerve fibers located within the lamina propria area. A third function may be to modulate bladder contractile function through local secretion of bioactive substances into the muscularis layers adjacent to the urothelium. To test this last hypothesis, the following experiments were performed: Strips of female cat bladders were isolated from the bladder body, base and urethra. The mucosa of alternate adjacent strips was removed, and the contractile response to field stimulation (FS), bethanechol (body), phenylephrine (base, urethra) and KCl was determined.For the bladder body, the strips without mucosa responded to FS, bethanechol, adenosine triphosphate (ATP) and KCl significantly greater than the strips with mucosa in...
Ignition and flash‐fire studies of cellulosic materials

Various celloulosic materials were evaluated for ignitability and flash-fire propensity, using screening test methods developed at the University of San Francisco. Time to ignition, using radiation from a high-temperature radiant source without a pilot flame, appeared to be primarily a function of heat flux and material density, rather than of type of wood or celloulosic board. At heat flux levels from 5.8 to 10.5 W cm−2, time to ignition was shortest for cellulose fiberboard with a density of 0.2225 g ml−1, followed by western red cedar at 0.314 g ml−1, eastern white pine at 0.348 g ml−1, southern yellow pine at 0.422 g ml−1, Douglas fir at 0.565 g ml −1, and longest for hardboard at 0.878 g ml−1. For the cotton and rayon woven-pile upholstery fabrics, time to ignition appeared to increase with increasing fabric weight. For Cellulose insulation treated with boron-containing additives, flash-fire magnitude decreased with increasing additive content. Flash-fire magnitude decreased more that could be accounted for by decreasing weight loss alone, indication reduction in the combustibility of the volatiles produced. Reduction in flash-fire propensity of cotton bating by treatment with boron-containing additives was also observed.
412 CHRONIC NON-SPECIFIC DIARRHEA: ROLE OF DIETARY MANAGEMENT IN CONTROL

Chronic non-specific diarrhea (CNSD) still represents the most common cause (85%) of chronic diarrhea in childhood. Although self-limited, this condition has been a therapeutic enigma for gastroenterologists. In an attempt to control this problem, we have assessed the association of CNSD with altered dietary intake due to either iatrogenic measures used to treat post-infectious diarrhea or due to dietary idiosyncrasies within families. Of 86 consecutive patients referred with chronic diarrhea, 48 were classified as having CNSD (Davidson's criteria) after a negative mala, sorption workup including lactose tolerance test. Duration of symptoms ranged from 3 weeks to 6 months. When a complete dietary history was obtained on 23 patients, 19 reported a low fat ( 50%) intake. Fourteen additional patients gave histories suggestive of similar intakes. When placed on diets with increased levels of fat (>50%) and with lower carbohydrate levels (<20%), 19 of 23 patients demonstrated normalization of stool frequency and consistency within 5 days to 2 weeks. In addition, 4 patients with a normal dietary intake also responded to an increase in dietary fat. These observations suggest that iatrogenic changes in diet to treat diarrhea (low fat, high carbohydrate) may account for chronicity in numerous instances and an increased fat intake may decrease bowel motility.
On the detection of lunar volatile emissions

This letter shows that the Apollo lunar-surface Suprathermal Ion Detection Experiment (SIDE) instruments lack the sensitivity to detect even large emissions of radiogenic gases from the moon if the venting of these gases occurs primarily at a few-well-defined sites of lunar transient phenomena (LTPs). It is suggested that specific flight instruments for the proposed ESA Polar Orbiting Lunar Observatory (POLO) mission, which could detect active venting, would help determine the energy source for LTPs and would increase knowledge of lunar geophysics. A critical-velocity model for the LTP energy source is briefly discussed.
Identification of novel compounds that increase SMN protein levels using an improved SMN2 reporter cell assay.

Spinal muscular atrophy (SMA) is a neurodegenerative disorder that is characterized by progressive loss of motor neuron function. It is caused by the homozygous loss of the SMN1 (survival of motor ...
Disease models provide insights into post-Golgi protein trafficking, localization and processing

Over the past two years, the use of in vitro systems and the identification of autoantibodies to Golgi proteins have provided important new tools for analyzing vesicle and cargo trafficking in the distal secretory pathway. In addition, the phenotypic characterization of mice with knockouts of various prohormone convertases has led to significant progress in understanding the biological relevance of prohormone processing in post-Golgi compartments.
Influence of an aggressive early enteral nutrition protocol on nitrogen balance in critically ill children.

The objective was to determine stress related factors and nutritional indices affecting the nitrogen balance (NB) and the creatinine height index (CHI) in critically ill children on early enteral nutrition (EEN). Seventy-one consecutively enrolled critically ill children aged 2 to 204 months, requiring prolonged mechanical ventilation, were studied. All patients were on early intragastric nutrition (Nutrison Pediatric or Standard) from day 1 (energy intake equal to 1/2, 1, 5/4, 6/4 and 6/4 of the predicted basal metabolic rate on days 1-5, respectively). Nitrogen balance and CHI changes determined efficacy. Study patients had severe depletion of somatic protein status on stress day 1 (CHI 80%, p <.004). On day 1, none of the patients had positive NB but after 5 days of EEN, 44 (62%) had positive NB and only 27 (38%) had negative NB (p <.0001). Multivariate stepwise regression analysis showed that only the difference of daily given-recommended dietary allowances protein and the total repleted energy were positively correlated (r(2) =.47, p <.001 and r(2) = 34, p =.003, respectively) and multiple organ system failure negatively correlated with the NB (r(2) = -.24, p <.03) on the 5th day of the EEN protocol. Our data suggest that achievement of positive protein and energy balance in relation to the basic metabolic rate using an aggressive EEN protocol improves NB during the acute phase of stress in 2/3 of critically ill children.
Finite element analysis of cut-growth in sheets of highly elastic materials

Abstract The Rivlin-Thomas criterion for the tearing of rubber vulcanizates is discussed in terms of Rice's path-independent J integral. It is shown that the R - T criterion can be stated in an alternative form where the growth of a cut is governed by this integral. The J criterion is then used to predict the critical load that causes a cut to grow in the uniaxial stretching of nicked rubber vulcanizate strips. Calculation of the J integral is accomplished with the use of a finite element procedure for highly elastic materials. It is shown that the predicted critical loads agree fairly closely with existing experimental data.
Incorporation of middleware and grid technologies to enhance usability in Computational Chemistry applications

High performance computing, storage, visualization, and database infrastructures are increasing in complexity as scientists move towards grid-based computing. This evolution of computing infrastructure has the effect of pushing breakthrough computational capabilities beyond the reach of domain scientists. In this work, we discuss a workflow management system that allows portal construction that is fully integrated with emerging grid standards but can be dynamically reconfigured. By defining an XML schema to describe both resources, application codes and interfaces, we will enable a ''pluggable'' event-driven model where grid-enabled services can be composed to form elaborate pipelines of simulation, and visual analysis.
Efficient Trojan Detection via Calibration of Process Variations

In this paper we present an efficient method to detect hardware Trojans under high levels of process variations, by measuring delays for vectors generated using a minimally delay-invasive Trojan model. Our method focuses on various sources of process variations and significantly reduces the effects of variations on delays by calibrating delays measured on each fabricated chip. Using test structures and additional measurements on these, our approach significantly reduces the number of chips that we need to test to detect minimally-invasive Trojans with a desired level of confidence. Our approach for tackling high levels of process variations can be used in conjunction with any other type of parametric Trojan detection strategy to significantly improve its efficiency.
Toward a Global Consumer “Eco-orientation” Model: A Cross-national Perspective

ABSTRACTA third-order global consumer eco-orientation model is developed that captures similarities among cross-national consumers with different cultural and economic backgrounds. Two second-order constructs emerge. The first second-order construct, eco-notions, is conceptualized to capture intangible environmental notions. The other second-order construct, eco-actions, is conceptualized to capture tangible environmental actions. The systematic specification of the model sheds light on universal environmental concerns at the consumer level of three economy types. The model adds understanding of the value that cross-national consumers place on the environment. In the process of model specification, the foundational perspective of the properties associated with the multifactor eco-scale is challenged. The result is a new third-order, multidimensional model characterizing ecological concerns of cross-national consumers.
Expectancy confirmed again: A computer investigation of expectancy theory

Abstract A computerized attempt to replicate Aronson and Carlsmith's test of expectancy theory was conducted. Generally, subjects performed consistent with their expectancy, although the effect of expectancy was strongly attentuated by an overall achievement orientation. The results contradict the hypotheses that experimenter bias, demand characteristics, or differential recall of performance mediate the effects of expectancy upon performance.
Synaptic Vesicles Caught Kissing Again

In this issue of Neuron, Harata et al. use a novel quenching technique to provide compelling evidence that kiss-and-run is the dominant mode of vesicle fusion at hippocampal synapses and that the prevalence of kiss-and-run can be modulated by stimulus frequency. The increased incidence of kiss-and-run at lower frequencies may ensure that vesicles are available for use during periods of high demand.
Analyzing Topical Oral Biographies of Old People The Case of Friendship

In order to gain understanding of friendship in the context of individuals' lives, over 60 chronologically old informants were asked to relate their biographies to an interviewer using friendship as the constant referent. The strengths and weaknesses for the data obtained in this way are discussed and three frameworks for analysis are specfied. These data have the potential to provide insight into cultural aspects of friendship in American society, the process of friendship through the life course, and social actors' organization of their friendships. The "topical oral biographies method" is suggested as a way to pursue research questions about the relationship between individuals and societies.
gossypol inhibits growth and promotes apoptosis of human head and neck squamous cell carcinoma in vivo.

Resistance to chemotherapy is a common problem encountered in the treatment of head and neck squamous cell carcinoma (HNSCC). Chemoresistant HNSCC tumors frequently overexpress antiapoptotic proteins, such as Bcl-x(L). (-)-gossypol, the negative enantiomer of a cottonseed polyphenol, binds to Bcl-x(L) and was recently been shown to inhibit HNSCC proliferation in vitro. In this study, we assessed the in vivo efficacy of (-)-gossypol in an orthotopic xenograft model of HNSCC, using two human HNSCC cell lines with high Bcl-x(L) expression levels. Both produced tumors in a murine floor-of-mouth model that mimics human HNSCC, exhibiting growth and invasion into adjacent tissues. Mice were randomized into three groups: vehicle control and two daily intraperitoneal (-)-gossypol treatment groups (5 and 15 mg/kg). Tumors were measured twice weekly. In the control group, tumors grew progressively, whereas in (-)-gossypol treatment groups, tumor growth was significantly suppressed. The mitotic rate in tumors from (-)-gossypol-treated animals was significantly lower than that in controls, and an increase in the percentage of apoptotic cells was observed in treated tumors versus controls. Residual tumors remained growth-suppressed for 2 weeks after cessation of (-)-gossypol treatment. Our results demonstrate that (-)-gossypol can inhibit tumor growth in an orthotopic model of aggressive HNSCC.
ERG Proteins and Functional Cardiac IKr Channels in Rat, Mouse, and Human Heart

The voltage-gated K(+) channel (Kv) pore forming alpha subunit, ERG1 (KCNH2), has been identified as the locus of mutations in one type of inherited long QT syndrome, LQT2. Heterologous expression of ERG1 reveals rapidly activating and inactivating K(+) currents, characterized by marked inward rectification at potentials positive to 0 mV, which are similar to the rapid component of cardiac delayed rectification I(Kr). There are, however, marked differences in the properties of expressed ERG1 and endogenous cardiac I(Kr), suggesting that functional I(Kr) channels reflect the coassembly of full-length ERG1 with splice variants and /or accessory subunits. Consistent with these hypotheses, N- and C-terminal variants of ERG1 have been identified, and it has been demonstrated that heterologously expressed ERG1 and minK (or MiRP1) coimmunoprecipitate. Recent biochemical studies, however, suggest that only full-length ERG1 is expressed in adult mouse, rat, or human heart. Clearly, further studies, focused on identifying the subunits that coassemble with ERG1 in vivo, as well as on post-translational processing of the full-length ERG1 protein will be necessary to define the molecular composition of functional cardiac I(Kr) channels.
Review Of High Efficiency Silicon Solar Cells

High efficiency is the key to large scale applicability of photovoltaic systems. Detailed cost analysis done by Electric Power Research Institute (EPRI) indicates that greater than 15% efficient modules will be required at a cost of less than 50c/watt in order for PV to compete with conventional energy sources. There are various approaches being investigated for a commercially viable PV product including low cost, low efficiency thin film approach using amorphous silicon and CnInSe2, and high cost, high efficiency approach using GaAs material and sophisticated tandem and concentrator cell designs. Silicon solar cells, which are the focus of this paper, provide an intermediate path for achieving the cost and efficiency goals. It has been more than thirty years since silicon solar cells were first discovered, but the drive for high efficiency has only recently become intense due to the balance of system (BOS) cost. Figure 1 shows a road map of silicon cell efficiency improvement since 1950, when the cell efficiency was only 5%. During the period 1960-1975, only a small improvement in cell efficiency was realized because major emphasis was on radiation hardness and space applications. Drive for terrestrial applications started in 1975 with the initial emphasis on low cost, therefore, only a moderate improvement in cell efficiency was observed during 1975-1980. In the early 1980s, when the importance of balance of system cost was recognized, the emphasis shifted to high efficiency and since then the progress in silicon cell efficiency has been phenomenal (Figure 1). Five years ago, 20% efficient cells seemed unattainable, but today we have already seen 22% (AM1) efficient silicon cells. Major advances in cell efficiency in the 1980s came from the emphasis on improving V c and optical design of I silicon cells. Improved material quality also contributed a ot to the current rapid progress. The purpose of this paper is to review and summarize some of those approaches that resulted in AM1 silicon cell efficiencies in the range of 18-22%.
Field-effect modulation of thermoelectric properties in multigated silicon nanowires

Electric-field-induced charge carriers typically exhibit greater mobility over carriers contributed by chemical dopants and offer a powerful mechanism for thermoelectric power factor enhancement. We fabricate multigated silicon nanowires (Si NWs) and demonstrate significant modulation of electrical conductivity and the Seebeck coefficient with gate bias. Because of the higher mobility of field-effect charge carriers, we demonstrate that power factor for the gated Si NWs is similar to the highest values reported for n-type Si nanostructures despite charge transport only occurring at the NW surface. Field-effect doping is a promising strategy for optimizing power factor and may result in significant power factor enhancement in smaller diameter Si NWs where high average carrier densities can be obtained with induced surface charge.
Disruption of actin-myosin interactions results in the inhibition of focal adhesion assembly in Xenopus XR1 glial cells.

In the present study we have investigated the role of actin-myosin interactions in regulating focal adhesion assembly in Xenopus XR1 glial cells. Actin- myosin interactions, stress fiber formation, and focal adhesion assembly are thought to allow cells to exert tension in the surrounding extracellular matrix, a process essential during morphogenesis and wound healing. Immunocytochemical analysis has revealed that myosin heavy chain-A (MHC-A), the predominant isoform in XR1 cells, was distributed in a filamentous pattern in the central region but was more diffuse towards the cell periphery. Myosin heavy chain-A-like immunoreactivity (IR) partially colocalized with phalloidin stained F-actin microfilaments in XR1 cells but not with microtubules. Furthermore, MHC-A-IR colocalized with immunoreactivity for b1 integrin receptors and vinculin at focal adhesions located more centrally along the ventral surface of the cells. The partial colocalization of MHC-A with the F-actin cytoskeleton, as well as at focal adhesions, provides evidence that actin-myosin interactions may be involved in regulat- ing focal adhesion assembly and stabilization. To examine this possibility, we have used drugs shown to inhibit cell contractility: the kinase inhibitors H7 and HA100, and 2,3-butanedione 2-monoxime (BDM), which inhibits muscle and nonmuscle ATPase activity. Compared to control cultures, those treated with the inhibitors exhibited a dose-dependent decrease in the percentage of cells that displayed focal adhesions. In addition, these cells also displayed disrupted actin cytoskeletons and a similar disruption in myosin filaments. Taken together, these results provide evidence for an important role of actin-myosin generated forces during focal adhesion assembly in glial cells. GLIA 26:245-259, 1999. r 1999 Wiley-Liss, Inc.
Constant Domain-regulated Antibody Catalysis

Some antibodies contain variable (V) domain catalytic sites. We report the superior amide and peptide bond-hydrolyzing activity of the same heavy and light chain V domains expressed in the IgM constant domain scaffold compared with the IgG scaffold. The superior catalytic activity of recombinant IgM was evident using two substrates, a small model peptide that is hydrolyzed without involvement of high affinity epitope binding, and HIV gp120, which is recognized specifically by noncovalent means prior to the hydrolytic reaction. The catalytic activity was inhibited by an electrophilic phosphonate diester, consistent with a nucleophilic catalytic mechanism. All 13 monoclonal IgMs tested displayed robust hydrolytic activities varying over a 91-fold range, consistent with expression of the catalytic functions at distinct levels by different V domains. The catalytic activity of polyclonal IgM was superior to polyclonal IgG from the same sera, indicating that on average IgMs express the catalytic function at levels greater than IgGs. The findings indicate a favorable effect of the remote IgM constant domain scaffold on the integrity of the V-domain catalytic site and provide a structural basis for conceiving antibody catalysis as a first line immune function expressed at high levels prior to development of mature IgG class antibodies.
Arrhythmia Risk Associated with Sleep Disordered Breathing in Chronic Heart Failure

The intersecting relationships of sleep disordered breathing (SDB), arrhythmogenic risk and chronic heart failure (HF) are complex and most likely multi-directional and synergistic. Autonomic dysfunction is a common pathophysiological feature of each of these entities. Intermittent hypoxia, hypercapnia, mechanical cardiac influences due to upper airway obstruction and rostral fluid shifts are SDB-specific mechanisms which may trigger, perpetuate and exacerbate HF and arrhythmogenesis. Specific pathophysiological mechanisms will vary according to the predominance of central as compared to obstructive sleep apnea. The risk of cardiac arrhythmias and HF attributable to SDB may be considerable given the high prevalence of SDB and its likely physiologic burden. The current review focuses on the data, which have accrued elucidating the specific contributory mechanisms of SDB in cardiac arrhythmias and HF, highlighting the clinical relevance and effects of standard SDB treatment on these outcomes, and describing the role of novel therapeutics.
Purification and characterization of rhodobactin: a mixed ligand siderophore from Rhodococcus rhodochrous strain OFS

The siderophore produced by Rhodococcus rhodochrous strain OFS, rhodobactin, was isolated from iron-deficient cultures and purified by a combination of XAD-7 absorptive/partition resin column and semi-preparative HPLC. The siderophore structure was characterized using 1D and 2D (1)H, (13)C and (15)N NMR techniques (DQFCOSY, TOCSY, NOESY, HSQC and LR-HSQC) and was confirmed using ESI-MS and MS/MS experiments. The structural characterization revealed that the siderophore, rhodobactin, is a mixed ligand hexadentate siderophore with two catecholate and one hydroxamate moieties for iron chelation. We further investigated the effects of Fe concentrations on siderophore production and found that Fe limiting conditions (Fe concentrations from 0.1 microM to 2.0 microM) facilitated siderophore excretion. Our interests lie in the role that siderophores may have in binding metals at mixed contamination sites (containing metals/radionuclides and organics). Given the broad metabolic capacity of this microbe and its Fe scavenging ability, R. rhodochrous OFS may have a competitive advantage over other organisms employed in bioremediation.