cssi/SciSciGPT-SciSciNet huggingface dataset:
Poro-viscoelastic modeling of production from shale gas reservoir: An adaptive dual permeability model

Abstract In most simulations of gas production from shale reservoirs, only the elastic deformation of reservoir rock and fractures is modeled. However, many experimental studies and field investigations indicate shale experiences viscoelastic deformation. In this work, a numerical model is constructed by implementing a poro-viscoelastic model into a dual permeability model (DPM) by using finite element method (FEM), to investigate the coupled time-dependent viscoelastic deformation of shale, and fracture permeability evolution in response to compressible flow of gas and gas desorption. The viscoelastic effect is considered through both deviatoric and mean effective stresses to allow for the effect of shear strain localization. The geomechanical model is first verified against available analytical and numerical solutions. Then, the model is applied to a few synthetic production cases to investigate the geomechanical evolution of a fractured reservoir. Comparing the case of poroelasticity and poro-viscoelasticity shows that the pore pressure differences throughout the domain are small, however, the stress evolution is quite divergent, with higher fracture closure in the poro-viscoelastic case. Comparison of the cumulative gas productions for poroelastic and poro-viscoelastic cases shows that cumulative gas production predicted by the poro-viscoelastic case is always lower than that of the poroelastic one. The difference between the two cases increases for long production times, as the viscous deformation (creep) of the reservoir rock closes the fracture. Results of the numerical simulations suggest that viscous deformation-enhanced closure of natural fractures that feed the main propped fractures can have a critical role in production decline.
Glucose control and its implications for the general surgeon

In the face of these conflicting data, how should the practicing surgeon approach the issue of tight glucose control in their critically ill surgical patients? The answer to that question may well change over time as new data emerge. For now, however, it seems reasonable to conclude that tight glucose control to the normal range (80-110 mg/dL) in critically ill general surgery patients (i.e., the Van den Berghe model) is an intriguing but unproven hypothesis that needs to be confirmed by prospective randomized trials in different ICUs and in a relevant patient population. It is quite possible, and probably likely, that levels of hyperglycemia that were previously thought to be inconsequential (180-200 mg/dL) may be harmful when sustained over prolonged periods of time and that better glucose control in the ICU than previously practiced is merited. However, given the detrimental effects of hypoglycemia, great care must be exercised in trying to achieve better glucose control so as not to induce harm. Technical considerations such as differences in glucose measuring systems, use of morning versus all glucose values, and nutritional regimens all need to be considered. The ICU is by definition a complex environment involving multiple teams of consulting specialists whose orders for medications, dialysis treatments, radiographic studies, and interruptions of enteral nutrition may all disrupt the ability to establish stable blood glucose levels. These factors need to be accounted for in daily clinical practice and their roles need to be better understood in future clinical trials. At present, it seems reasonable to attempt to control blood glucose levels in critically ill general surgery patients to moderate levels that avoid deleterious hypoglycemia but have been associated with encouraging clinical results until better data emerge. Until that time, the clinician will need to attempt to balance the potentially detrimental effects of hyperglycemia with the risk of hypoglycemia carefully until future trials involving general surgery patients are completed to clarify this issue.
What We Have Learned from Patch Recordings of Cultured Cells

Dissociated neural cell cultures have been used as model systems to study a host of questions in neurobiology such as regulation of cell differentiation, interactions between cells, mechanisms of morphogenesis and synaptogenesis. Because culture systems are experimentally accessible to anatomical, biochemical, and pharmacological techniques, they provide the investigator with a great deal of information as well as the opportunity to correlate the knowledge obtained from various techniques. Until recently, these advantages of culture systems had not been exploited in studies of the gating properties of ion channels in the excitable membrane. The main reason is that cultured neuronal cells are usually quite small (<30 μm in diameter). Conventional voltage-clamp techniques, which have been used so successfully in nonmammalian preparations, such as squid axon and frog node, cannot be employed as effectively in cultured systems. Membrane potentials in cultured cells are commonly measured with microelectrodes. The tip resistance of microelectrodes used in these cells is usually high, ranging from 10 to 100 MΩ. This results in poor time resolution of the microelectrode voltage clamp. Moreover, electrode penetration often inflicts cell injury, and the ion composition of the cell interior cannot be controlled with this technique. Thus, electrophysiologists were reluctant to choose cultured cells as their preparations despite the successes of some research groups (Moolenaar and Spector, 1977, 1978; Nathan and DeHaan, 1979; Ebihara et al., 1980).
Applications of the Electrodynamic Tether to Interstellar Travel

After considering relevant properties of the local interstellar medium and defining a sample interstellar mission, this paper considers possible interstellar applications of the electrodynamic tether, or EDT. These include use of the EDT to provide on-board power and affect trajectory modifications and direct application of the EDT to starship acceleration. It is demonstrated that comparatively modest EDTs can provide substantial quantities of on-board power, if combined with a large-area electron-collection device such as the Cassenti toroidal-field ramscoop. More substantial tethers can be used to accomplish large-radius thrustless turns. Direct application of the EDT to starship acceleration is apparently infeasible.
Polyamine Interactions with Plant Hormones: Crosstalk at Several Levels

Polyamines play important roles in diverse plant growth and development processes, including seed germination, tissue lignification, organogenesis, flowering, pollination, embryogenesis, fruit development, ripening, abscission, senescence, and stress responses. In all these processes, synergistic and antagonistic interactions among various plant hormones have been shown. Although significant progress has been made in understanding the regulation of biosynthesis and signal transduction mechanisms for most of the plant hormones, inroads into the molecular mechanisms underlying polyamine (PA) action have just begun. Little is known or understood about the signal transduction pathways regulating a myriad of PA effects. We, therefore, embarked on evaluating and collating the information on changes in the transcriptome based on metabolic engineering of the PA pathway as well as mutants of PA biosynthesis. Also taken into consideration are the studies using exogenous application of PAs. Our analysis has revealed complex and differential relationships among the three main PAs—putrescine, spermidine and spermine—in regard to regulation of plant hormone biosynthesis and signaling. Putrescine was positively linked to the expression of genes regulating ABA biosynthesis but downregulated those of ethylene, jasmonates, and gibberellin biosynthesis, and the action of spermidine was found to be exactly opposite. Spermine, on the other hand, enhanced genes for ethylene and jasmonates biosynthesis but downregulated those for gibberellins and abscisic acid biosynthesis. In regard to hormone signaling pathways, spermidine positively regulated salicylic acid signaling genes, and those of auxin and cytokinins signaling genes were linked to spermine action. Putrescine was neutral to positive in regulating jasmonates signaling. PAs seem to be neutral in regard to brassinosteroids biosynthesis or signaling pathways.
Professional Discipline of Death Penalty Lawyers and Judges

On this, the fiftieth anniversary of Gideon v. Wainwright’s 1 broken promise, 2 I have been asked to propose guidelines that (a) provide professional discipline of lawyers who fail to provide competent representation in death penalty cases, but that (b) do not discourage good lawyers from taking death cases or from cooperating with successor counsel who is trying to show that the lawyers were ineffective at trial. It is a pointless exercise. And I have added another pointless exercise, drafting guidelines that will discipline judges who appoint lawyers in death cases whom the judges know or should know will give incompetent representation. The assignment is pointless, because we already have ample rules and guidelines to do the job. This is shown by a small number of disciplinary proceedings that have been brought. In general, however, disciplinary bodies are either inadequately equipped to enforce existing rules, or they prefer to let the “machinery of death” continue to grind on, defying due process and destroying lives. 3
Percentage of Philadelphia chromosome (Ph)-negative and Ph-positive cells found after autologous transplantation for chronic myelogenous leukemia depends on percentage of diploid cells induced by conventional- dose chemotherapy before collection of autologous cells

We collected peripheral blood mononuclear cells and bone marrow cells soon after recovery from conventional-dose chemotherapy-induced myelosuppression and transplanted these cells into advanced chronic myelogenous leukemia (CML) patients after treating these patients with 120 mg/kg cyclophosphamide, 750 mg/m2 VP-16, and 1,020 cGy of total body irradiation (TBI). Of the 10 late chronic-phase patients and the eight accelerated-phase CML patients evaluable posttransplant, 90% and 87%, respectively, remain alive posttransplant, whereas none of the three blast crisis CML patients given this therapy remain alive posttransplant. We measured the percentage of Philadelphia chromosome (Ph)-negative cells in the autologous cells collected after conventional-dose chemotherapy-induced myelosuppression before autologous transplant and in the marrow of these same CML patients after autologous transplantation of these cells into recipients treated with the cyclophosphamide, VP-16, and TBI. A direct correlation (correlation coefficient = 0.91) was observed between the level of Ph+ cells in the transplanted cells and the percentage of Ph+ marrow cells after transplant in 21 patients so transplanted. The data show that the chance of generating cytogenetic remissions post-transplant depends on the percentage of diploid cells in the preparations of autologous cells used for transplant and the stage of disease of the patients at the time of collection of the autologous cells.
Pyomyositis: A Complicated and Curious Case Report

Introduction: In the elderly (over the age of 50), the risk of urinary tract infections is estimated at 8% per year in men. Anatomic abnormalities such as prostatic hypertrophy, leading to urinary retention is considered as the main reason. Pyomyositis is an uncommon condition of optical urethrotomy, especially in patients who have received local radiation therapy in the past. Till date no cases of pectineus muscle abscess and only two cases of obturator externus muscle abscess have been reported in the literature, with only one developing as a result of genitourinary intervention such as urethrotomy. Case presentation: Here we are presenting a case of a very unusual and serious complication in an elderly man presenting with urosepsis several months after undergoing urethrotomy. Conclusion: Elderly men have an increased risk of sepsis, higher than that in women with UTI.
The isomiR-140-3p-regulated mevalonic acid pathway as a potential target for prevention of triple negative breast cancer

Prevention of triple-negative breast cancer (TNBC) is hampered by lack of knowledge about the drivers of tumorigenesis. To identify molecular markers and their downstream networks that can potentially be targeted for TNBC prevention, we analyzed small RNA and RNA sequencing of a cell line model that represent early stages of TNBC development. We have identified direct gene targets of isomiRNA-140-3p and by using cell-based and in vivo model systems we have demonstrated the utility of targeting downstream pathways for prevention of TNBC. These analyses showed that 5’isomiRNA of miR-140-3p (miR-140-3p-1) and its novel direct gene targets, HMG-CoA reductase (HMGCR) and HMG-CoA synthase 1(HMGCS1), key enzymes in the cholesterol biosynthesis pathway, were deregulated in the normal-to-preneoplastic transition. Upregulation in the cholesterol pathway creates metabolic vulnerability that can be targeted. Consistent with this hypothesis, we found direct targeting of miR-140-3p-1 and its downstream pathway by fluvastatin to inhibit growth of these preneoplastic MCF10.AT1 cells. However, although, fluvastatin inhibited the growth of MCF10.AT1-derived xenografts, histological progression remained unchanged. The cholesterol pathway is highly regulated, and HMGCR enzymatic activity inhibition is known to trigger a feedback response leading to restoration of the pathway. Indeed, we found fluvastatin-induced HMGCR transcript levels to be directly correlated with the degree of histological progression of lesions, indicating that the extent of cholesterol pathway suppression directly correlates with abrogation of the tumorigenic process. To block the HMGCR feedback response to statins, we treated resistant preneoplastic cells with an activator of AMP-activated protein kinase (AMPK), a brake in the cholesterol feedback pathway. AMPK activation by aspirin and metformin effectively abrogated the statin-induced aberrant upregulation of HMGCR and sensitized these resistant cells to fluvastatin. These results suggest the potential use of combined treatment with statin and aspirin for prevention of TNBC.
The Decision to Withdraw in Children With Ventricular Assist Devices

As ventricular assist devices (VADs), a form of mechanical circulatory support, become standard therapy for end-stage heart failure in children (O'Connor and Rossano 2014), there is ongoing discuss...
Nucleotide Analogues as Inhibitors of Viral Polymerases

Summary Coronaviruses such as the newly discovered virus from Wuhan, China, 2019-nCoV, and the viruses that cause SARS and MERS, have resulted in regional and global public health emergencies. Based on our molecular insight that the hepatitis C virus and the coronavirus use a similar viral genome replication mechanism, we reasoned that the FDA-approved drug EPCLUSA (Sofosbuvir/Velpatasvir) for the treatment of hepatitis C will also inhibit the above coronaviruses, including 2019-nCoV. To develop broad spectrum anti-viral agents, we further describe a novel strategy to design and synthesize viral polymerase inhibitors, by combining the ProTide Prodrug approach used in the development of Sofosbuvir with the use of 3’-blocking groups that we have previously built into nucleotide analogues that function as polymerase terminators.
An agent-based approach to optimizing modular vehicle fleet operation

Abstract Modularity in military vehicle designs facilitates assembly, disassembly, and the reconfiguration (ADR) of vehicles, which can be beneficial in promoting fleet adaptability and life cycle cost savings. This paper illustrates an agent-based approach to the optimal management of fleet operation and to control the resupply, demand prediction, and scheduling process. The agent-based approach is customized for modularized military vehicle fleets and applied to explore the feasibility and flexibility of modularity for various mission scenarios. Given deterministic field demands with operation stochasticity, we compare the performance of a modular fleet to a conventional fleet in equivalent operation strategies and also compare the fleet performance when driven by heuristic rules or optimization. Several indicators are selected to quantify fleet performance including operation costs, total resupplied resources, and fleet readiness. Then, the model is applied to the military Joint Tactical Transport System (JTTS). The results indicate that fleet modularity can reduce the total resources supplied without significant loss of fleet readiness. Additionally, the benefits of fleet modularity can be amplified through a real-time optimized operation strategy. A parametric study is performed to show the impact of ADR capacity on modular fleet performance. Finally, we provide practical suggestions for modular vehicle designs based on the analysis.
Bilayer graphene oxide membranes for a wearable hemodialyzer

2D nanomaterials have long been considered for development of ultra-high throughput membranes, due to their atomically thin nature and high mechanical strength. However, current processes have yet to yield a viable membrane for practical applications due to the lack of scalability and substantially improved performance over existing membranes. Herein, a graphene oxide (GO) bilayer membrane with a permeability of 1562 mL/hr.mmHg.m2, two orders of magnitude higher than existing nanofiltration membranes, and a tight molecular weight cut-off (MWCO) is presented. To build such a membrane, we have developed a new process involving self-assembly and optimization of GO nanoplatelets physicochemical properties. The process produced a highly organized mosaic of nanoplatelets enabling ultra-high permeability and selectivity with only three layers of GO. Performance of the membrane has been evaluated in a simulated hemodialysis application, where it presents a great value proposition. The membrane has a precise molecular cut-off size of 5 nm, adjusted using a molecular interlinker, designed to prevent loss of critical blood proteins. Urea, cytochrome-c, and albumin are used as representative test molecules. Urea and cytochrome-c sieving coefficients of 0.5 and 0.4 were achieved under physiological pressure conditions, while retaining 99% of albumin. Hemolysis, complement activation, and coagulation studies exhibit a performance on par or superior to the existing hemodialyzer materials.
Early experience with COVID-19 patients at academic hospital in Southwestern United States.

To the Editor,The clinical expression of COVID-19 has been described in various part of the world. A recent report in journal of Beijing, China from 21 January to 9 March 2020, showed a spectrum of...
The impact of infected T lymphocyte burst rate and viral shedding rate on optimal treatment scheduling in a human immunodeficiency virus infection

We consider a mathematical model of human immunodeficiency virus (HIV) infection dynamics of T lymphocyte (T cell), infected T cell, and viral populations under reverse transcriptase inhibitor (RTI) andprotease inhibitor (PI) treatment. Existence, uniqueness, and characterization of optimal treatment profiles which minimize total amount of drug used, viral, and infected T cell populations, while maximizing levels of T cells are determined analytically. Numerical optimal control experiments are also performed to illustrate how burst rate of infected T cells and shedding rate of virions impact optimal treatment profiles. Finally, a sensitivity analysis is performed to detect how model input parameters contribute to output variance.
Terahertz characterization of two-dimensional low-conductive layers enabled by metal gratings.

While terahertz spectroscopy can provide valuable information regarding the charge transport properties in semiconductors, its application for the characterization of low-conductive two-dimensional layers, i.e., σs < < 1 mS, remains elusive. This is primarily due to the low sensitivity of direct transmission measurements to such small sheet conductivity levels. In this work, we discuss harnessing the extraordinary optical transmission through gratings consisting of metallic stripes to characterize such low-conductive two-dimensional layers. We analyze the geometric tradeoffs in these structures and provide physical insights, ultimately leading to general design guidelines for experiments enabling non-contact, non-destructive, highly sensitive characterization of such layers.
Eye-trackers, digital-libraries, and print-referencing: A single case study in CDKL5

Abstract Background Providing emergent literacy intervention and assessing outcomes for children with low-incidence, complex disabilities with concomitant physical, cognitive, sensory, and communication impairments presents a significant challenge to researchers, educators, clinicians, and families alike. Aims This study aimed to leverage advancements in commercially available eyetracking technologies to measure visual attention to print before and after a parentmediated print referencing intervention with a child with a severe, low incidence, congenital disability. Print referencing means drawing attention to the print on the page while reading. Methods and procedures The single case study investigated a mother-daughter dyad who completed the protocol using eye-gaze technology, digital children’s books, and a computer configured with software for observing and recording interactions that were shipped to the family’s home and set up by the mother with remote support from a researcher. Outcomes and results Results demonstrate that the eye-tracker successfully captured the participant’s eye-gaze. Furthermore, mean-level shifts in frequency of fixations demonstrates changes in visual attention to print after the parent introduced the print referencing strategy during reading. Conclusions and implications Commercially available eye-trackers and digital libraries were successfully used by the parent-child dyad to record visual attention. Furthermore, remote support from a trained researcher was sufficient to support the parent through set-up, calibration, intervention, and implementation.
Moderators of PTSD symptom change in group cognitive behavioral therapy and group present centered therapy.

Abstract To examine moderators of change during group-based intervention for Posttraumatic Stress Disorder (PTSD), multilevel models were used to assess trajectories of symptom clusters in male veterans receiving trauma focused Group Cognitive Behavioral Treatment (gCBT; N = 84) or non-trauma focused Group Present Centered Therapy (gPCT; N = 91; Sloan et al., 2018). Separate models were conducted for symptom clusters in each intervention, examining pre-treatment PTSD symptoms, pre-treatment depression severity, age, index trauma, and outcome expectancies as potential moderators. Unconditioned growth models for both gCBT and gPCT showed reductions in intrusions, avoidance, negative cognitions/mood, and arousal/reactivity (all p
Nb-Based Superconducting Silicon Interconnect Fabric for Cryogenic Computing Applications

As the number of qubits goes beyond one million, the I/O count and the interconnect wiring within a limited area become problematic. In this paper, we present a simple integration method (an Au interlayer) with a fine interconnect pitch (10 um) and close lateral die spacing (60 um) that can overcome the large I/O and high wiring level requirements of very large scale of quantum circuits. A System-on-Wafer(SoW) Superconducting Silicon Interconnect Fabric (Superconducting-IF) is proposed with the help of the mentioned Au interlayer technology. Through three testing structures, the Au interlayer integration technology is demonstrated to be fine pitch (≤10 um), Josephson-Junction-compatible ( 30 MPa) on various bonding areas, and electrically reliable at 2 K. It is one of the first demonstrations of the robust and reliable Au interlayer optimized for quantum applications. This work enables quantum computing to uncover its full strength through high-density (>10000 mm2 I/O and dense wiring) heterogeneous integration.
Ayurvedic Approach on Memory Stimulation in Guadeloupe: A Pilot Study

Background: The necessity to prevent Alzheimer's disease prompted us to offer cognitive stimulation sessions. Objectives: The goals of our study are to evaluate the effectiveness of cognitive stimulation and also to estimate the influence of the three ayurvedic constitutional categories on the effectiveness of cognitive stimulation over three months. Methods: We looked at the ayurvedic categories, overall health perceptions, associative memory complaint and evolution in 28 healthy elderly people at T1 and T2 (three months later), as well as 12 healthy controls who weren't stimulated, using self-assessment questionnaires that included Prakriti and memory complaint, as well as several scales of perceived health (cognitive, physical, mental, and well-being/quality of life) and a test of associative memory. Results: Pitta-Kapha has the highest population representation. The severity of the cognitive and holistic status decreases between the two eras, but not on the physical health. The cognitive and memory issues are weak or non-existent. Regression models allow us to test our health perception and associative memory predictions. Conclusion: Cognitive stimulation is helpful, and ayurveda categories provide a useful framework for comprehending individual variances of cognitive functioning in healthy aged people.
Market Structure and the Speed of Price Adjustments: Evidence Of Non-Monotonicity

Rational distributed lag and partial adjustment models are used in this paper to analyze the speed of adjustment of consumer deposit rates. Dummy variables conditioned on market concentration are added to the rational distributed lag model to test for speed of adjustment differences across high, medium, and low concentration markets. The estimated model parameters suggest low, as well as high, concentration markets exhibit slower speed of adjustment (or more price rigidity) than the medium group. Thus, the results for the rational distributed lag model estimation provide empirical evidence of a possible non-monotonic relationship between market concentration and price rigidity. This relationship is further examined within the context of a partial adjustment model by estimating the speed of adjustment parameter as a non-linear (quadratic) function of market concentration. The results support the findings derived from the estimation of the rational distributed lag model. These findings have important implications for: (1) future research that attempts to empirically estimate relationships between market structure and price behavior, and (2) antitrust policies that assume reductions in market concentration will always lead to more competitive, presumably less rigid, pricing behavior.
Inborn errors of signal transduction: Mutations in G proteins and G protein-coupled receptors as a cause of disease

A vast array of neurotransmitters, polypeptide hormones and other extracellular signalling molecules utilize G protein-coupled pathways for transmembrane signalling. In recent years, mutations in G protein-coupled receptors and in G protein α subunits have been identified as the cause of a variety of human diseases. Both loss and gain of function mutations have been described in disorders such as Albright hereditary osteodystrophy, nephrogenic diabetes insipidus, McCune-Albright syndrome, and familial male precocious puberty. Identification of mutations in G protein-coupled receptors and in G proteins in human diseases has provided unique insights into G protein-coupled signal transduction, has important implications for diagnosis and potentially for treatment, and should stimulate the search for additional defects in G protein-coupled signal transduction in other diseases.
Cellular mechanisms of nephrotoxicity

Morphology of nephrotoxic injury _________________________________________ 65 Pathophysiology of cell injury _____________________________________________ 67 Disruption of energy production __________________________________________ 67 Mitochondrial dysfunction in acute renal failure ____________________________ 67 Defects in energy generation 67 Structural abnormalities 68 Endonuclease activation is the final common pathway of cell death __________ 68 Caspases and cell death __________________________________________________ 68 In vitro evidence of caspase activation in cytotoxicity 69 In vivo evidence of caspase activation in cytotoxicity 70 The Bcl-2 and the mitochondrial permeability transition: role in cell death _____ 70 The renal stress response determines whether cells survive or not ____________ 71 Molecular aspects 71 Signal transduction pathways in the stress response 71 Renal stress engages the cell cycle and is a determinant of cytotoxicity ________ 72 Summary _______________________________________________________________ 72 References ______________________________________________________________ 73
A 5.1-GHz CMOS PLL based integer-N frequency synthesizer with ripple-free control voltage and improved acquisition time

A 5.1-GHz integer-N CMOS phase locked loop (PLL) based frequency synthesizer is presented. A current mirror current source is used in designing the charge pump loop filter. A completely ripple-free VCO input control voltage is achieved using new mirror architecture in the charge pump loop filter. The acquisition time is improved by a factor of 1.62 using a new design methodology. The synthesizer operates from 4.92 to 5.1-GHz and achieves a phase noise of -121.9 dBc/Hz at 10-MHz offset frequency from the carrier for maximum oscillation frequency. The output rms jitter is 0.3% of the oscillator period. The total power consumption of this synthesizer is 10-mW. The PLL is designed and extracted in TSMC 0.18-/spl mu/m technology for GSM applications.
Effects of 5-bromodeoxyuridine on tumorigenicity, immunogenicity, virus production, plasminogen activator, and melanogenesis of mouse melanoma cells.

Publisher Summary This chapter discusses the effects of 5-bromodeoxyuridine (BrdU) on tumorigenicity, immunogenicity, virus production, plasminogen activator, and melanogenesis of mouse melanoma cells. Tumorigenicity and expression of PA appeared to be immediately affected by these changes; there was a lag in the time course of reduction and subsequent regaining of tyrosinase activity. The effects of BrdU on total RNA or protein synthesis or on plating efficiency appear insufficient to account for the degree of suppression of function observed. Investigations on the suppression of tumorigenicity by BrdU reveal separate components involved in the tumorigenic potential of melanoma cells. Both reduction in the intrinsic ability of the cells to grow in vivo and changes evoking host defense mechanisms appear to operate in the reduction of tumorigenicity by BrdU treatment. Host response may depend on antigenic changes, some of which may be related to the induction of C-type virus in BrdU-treated cells. The untreated melanoma cells grow in a manner suggestive of transformed cells. The suppression of melanogenesis by BrdU occurs through a coordinated effect on the structural and enzymic proteins required for melanin synthesis. These results are consistent with cessation of synthesis of tyrosinase and melanosomal structural proteins in BrdU-treated cells, and indicate that there may be a “program” of gene activity for melanogenesis, which is regulated as a unit.
Data Monitoring Committees including Operational Issues

Data Monitoring Committees, also known as Data and Safety Monitoring Boards, are often established as a component of clinical trial oversight to review interim data of the ongoing trial so that safety concerns or problematic operational issues can be identified rapidly and corrective measures can be undertaken. Such committees may be independent of the trial sponsor and investigator to ensure recommendations are as objective as possible and unaffected by conflicts of interest. Federal funding and regulatory agencies have issued policy documents concerning the establishment and operation of Data Monitoring Committees, but substantial variation exists in committee processes. Keywords: clinical trial; interim analysis; safety; oversight
Mechanism of coupling between Cl− and OH− transport in renal brush-border membranes

The coupling mechanism for Cl- and H+/OH- transport in renal brush-border vesicles was examined from intravesicular pH changes following imposed H+ and Cl- gradients. Vesicles were loaded with 6-carboxyfluorescein and exposed to H+ gradients and Cl-, gluconate, or sulfate gradients, each with and without a K+/valinomycin voltage clamp. Parallel experiments were performed with vesicles equilibrated with 10 mM HCO3- or 5 mM formate. Rate of H+/OH- transport was determined from the initial rate of change in 6-carboxyfluorescein fluorescence, vesicle buffer capacity and the relationship between fluorescence and vesicle pH. In contrast to gluconate or sulfate, Cl- caused enhanced H+/OH- transport under all conditions. This difference was eliminated with voltage clamping in the presence of gluconate, SO4(2-), or HCO3-, but not in the presence of formate. These findings were not affected by the method of preparation of the vesicles. Electrically coupled Cl-/OH- transport was not inhibited by 100 microM DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonate) or 100 microM DBDS (4,4'-dibenzamidostilbene-2,2'-disulfonate). SITS (4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonate) was found to be a protonophore at concentrations greater than 500 microM. As a control for the method, we demonstrated amiloride inhibitable, electroneutral Na+-H+ exchange (H+ flux = 107 +/- 9 nmol/s per mg, 100 mM Na+) and electroneutral, DBDS inhibitable Cl(-)-HCO3- exchange in sealed human red blood cell ghosts. Therefore, electroneutral Cl(-)-OH- or HCO3- exchange does not measurably contribute to Cl- transport in the proximal tubule brush border. Cl(-)-formate exchange with formic acid recycling appears to be the only electroneutral coupling mechanism between Cl- and OH- transport demonstrable in renal brush-border membrane vesicles.
Demonstration of distinct corticotropin releasing factor--containing neuron populations in the bed nucleus of the stria terminalis. A light and electron microscopic immunocytochemical study in the rat.

Immunocytochemical light and electron microscopic studies revealed two distinct populations of corticotropin releasing factor (CRF) — containing neurons, a dorsolateral and ventrolateral group, located in the bed nucleus of the stria terminalis (BST) of the rat brain. CRF neurons of the dorsolateral group had a smaller diameter and more primary dendrites than those of the ventrolateral group. CRF neurons in the dorsolateral BST had both somatic and dendritic spines, smooth contoured nuclei, and many dense and alveolate vesicles in their cytoplasm. Whereas, CRF neurons in the ventrolateral BST had only dendritic spines, irregularly-shaped indented nuclei and contained only alveolate vesicles in their cytoplasm.
Structural organization of the cerebral cortex (motor area) in human chromosomal aberrations. A golgi study. I. D1 (13–15) trisomy, patau syndrome

The fibrillar-neuronal organization of the cerebral motor cortex (area 4) of a newborn girl with 13–15 trisomy (Patau syndrome) has been studied, for the first time, utilizing both hematoxylin and eosin and rapid Golgi preparations. A variety of structural abnormalities considered to be sufficient to explain and possibly capable of causing some degree of cortical dysfunction have been found in the motor cortex of this infant. The significance of these findings becomes obvious in view of the fact that mental retardation is a prominent feature of infants with this chromosomal defect who survive to an age in which neuronal dysfunction can be reasonably judged. The motor cortex of this infant is characterized by a generalized hypocellularity which includes both a reduction in the number of neurons and glial cells. The possibility that the primordial cortical plate in this chromosomal defect may be primarily hypocellular is suggested. Cortical neurogenesis, neuronal migration, formation of the different cortical layers and development of the different neuronal types and systems of afferent fibers are considered to evolve normally in this chromosomal disorder. The neurons of the motor cortex of this infant depict a mild degree of delayed structural and functional maturation. The number of spines (postsynaptic components of the axo-spinodendritic synapses) is reduced and their distribution along the apical dendrite of the layer V pyramidal neurons is abnormal. The apical dendrite of these neurons received an inadequate amount of information along the dendritic segments which cross the cortical territories of layers III and II. In view of these findings, it is postulated that poor motor coordination and possible inadequate intercortical association should be prominent features in the type of mental retardation encountered in this chromosomal disorder. In addition, the dendritic spines depict structural abnormalities considered also to be capable of causing functional inadequacy of the axospinodendritic synapses. This study demonstrates that abnormal structure (spine anomalies) may be directly related to abnormal function (mental retardation). Also, it demonstrates and emphasizes the need to study further the fibrillar-neuronal organization of the cerebral cortex of infants with any type of mental retardation including those infants with the so-called minimal brain damage (MBD) with specialized neurohistological techniques (e.g., rapid Golgi method) in addition to the routine methods.
The socioecology of fission-fusion sociality in Orangutans

Fission-fusion systems can have the group or the individual as their primary unit. In group-based fission-fusion systems, predation risk reduction is the major benefit to grouping, in the individual-based ones the benefits are likely to be primarily social. Orangutans, like chimpanzees, are examples of an individual-based fission-fusion species. The orangutans inhabiting a Sumatran swamp forest (Suaq Balimbing) are more likely than elsewhere to form travel parties. As elsewhere, the main benefits of grouping are social: mating opportunities, protection from harassment and socialization of infants. Most animals also incur costs, but these are relatively low at Suaq Balimbing due to the high productivity of the swamp. Costs seem to be disproportionately high for females with mid-sized infants, who avoid parties.
Growth, structure, and morphology of TiO2 films deposited by molecular beam epitaxy in pure ozone ambients

TiO"2 films were grown using a reactive molecular beam epitaxy system equipped with high-temperature effusion cells as sources for Ti and an ozone distillation system as a source for O. The growth mode, characterized in-situ by reflection high-energy electron diffraction (RHEED), as well as the phase assemblage, structural quality, and surface morphology, characterized ex-situ by X-ray diffraction and atomic force microscopy (AFM), depended on the choice of substrate, growth temperature, and ozone flux. Films deposited on (100) surfaces of SrTiO"3, (La"0"."2"7Sr"0"."7"3)(Al"0"."6"5Ta"0"."3"5)O"3, and LaAlO"3 grew as (001)-oriented anatase. Both RHEED and AFM indicated that smoother surfaces were observed for those grown at higher ozone fluxes. Moreover, while RHEED patterns indicated that anatase films grown at higher temperatures were smoother, AFM images showed presence of large inclusions in these films.
Assessment of Quality of Outcomes within a Local United Way Organization: Implications for Sustaining System Level Change

This paper provides a historical case study of efforts to implement and sustain "outcomes based funding" in a large United Way system in Central Ohio. The case study describes how community practitioners employed specific strategies to promote sustainability. The use of these strategies corresponds to several techniques suggested in the sustainability literature. This case study is offered as a means of considering how practitioners helped sustain the shift to outcomes based funding within the United Way system. In addition, this case study demonstrates how skills related to implementation and sustainability might be transferred to other situations where practitioners are interested in promoting change within large organizations and/or communities. The authors suggest that skills related to implementation and sustainability are essential to community practice.
A brief statement of schema theory

Schema theory has recently been extended, coupled with suitable stimulus generating, procedures, and shown to have some predictive utility. A concise summary of extended schema theory is here presented, with provisional definitions of key terms and a statement of the basic suppositions. A distinction is made between the single schema condition and the mixed schema conditions; suppositions about schema learning are offered for both cases.
Microvascular Endothelial Cell Seeding of Small-Diameter Dacron|2TM|0 Vascular Grafts

One obstacle to the clinical implementation of endothelial cell seeding of vascular prostheses is the difficulty in derivation of large numbers of autologous endothelial cells from blood vessels of patients requiring vascular grafting. Capillary endothelial cells obtained from fat have been suggested as an abundant alternative to large-vessel endothelium for graft seeding. The object of this study was to evaluate the performance of 4-mm internal diameter (ID) Dacron™ Microvel grafts seeded with omentally derived microvascular endothelial cells. Six-cm lengths of the test grafts were implanted bilaterally into canine carotid arteries. One of each pair of grafts was seeded with endothelial cells (x = 8.4 × 106) derived from collagenase digestion of autologous omental fat samples. The contralateral graft of each pair was nonseeded. At 5 weeks postoperatively, the grafts were harvested and evaluated. The mean patencies of both the seeded and nonseeded grafts were 89 percent. The mean thrombus-free surface are...
A computer-based approach for assessing dietary supplement use in conjunction with dietary recalls.

In response to the need to assess both food and supplemental sources of nutrients, we have expanded the capabilities of nutrition data system for research (NDSR) software to allow for assessing dietary supplement use. A Dietary Supplement Assessment Module allows for the automated collection and coding of dietary supplement use. The module is designed for use in conjunction with the software's 24-hour dietary recall features. The medication inventory method, commonly used in pharmaceutical research, served as the basis for the module's assessment approach. In adapting this approach for use in our software we designed a tiered structure that involves first screening for use of dietary supplements, then collecting product detail (e.g. full name of product, number of times taken, etc.), and finally reviewing the information with the participant. Results from a demonstration study conducted to evaluate the module indicate the assessment approach is acceptable to both participants and interviewers. Collecting dietary supplement use information significantly increases interview time, especially for those using multiple products. A validation study is needed to determine whether the new method results in accurate estimation of nutrient intake from supplemental sources.
Prevalence of viral erythrocytic necrosis in pacific herring and epizootics in Skagit Bay, Puget Sound, Washington.

Abstract Epizootics of viral erythrocytic necrosis (VEN) occurred among juvenile Pacific herring Clupea pallasii in Skagit Bay, Puget Sound, Washington, during 2005–2007 and were characterized by high prevalences and intensities of cytoplasmic inclusion bodies within circulating erythrocytes. The prevalence of VEN peaked at 67% during the first epizootic in October 2005 and waned to 0% by August 2006. A second VEN epizootic occurred throughout the summer of 2007; this was characterized by disease initiation and perpetuation in the age-1, 2006 year-class, followed by involvement of the age-0, 2007 year-class shortly after the latter's metamorphosis to the juvenile stage. The disease was detected in other populations of juvenile Pacific herring throughout Puget Sound and Prince William Sound, Alaska, where the prevalences and intensities typically did not correspond to those observed in Skagit Bay. The persistence and recurrence of VEN epizootics indicate that the disease is probably common among juvenile P...
New Developments in Employee Training

In order to accommodate the rapid technological changes, employees must master increasingly complex technical skills. Five major forces behind training becoming so important and central to any firm′s operations are as follows: global and domestic competition; changes in technology; mergers, acquisitions and divestitures causing realignment of structures and functions of companies; better educated workforce;.
Energetics of radiation damage in natural zircon (ZrSiO4)

Transposed temperature drop calorimetry at 1000 °C was performed on natural zircons (ZrSiO4) from Sri Lanka that were partially to completely metamict due to α-decay event damage (0.06 to 11.7×1015α-decay events/mg). The enthalpy of annealing at room temperature (ΔHanneal) varies sigmoidally as a function of radiation dose. ΔHanneal reaches a saturation plateau at radiation doses greater than 5×1015α-decay events/mg. The annealing of several samples to a crystalline structure with broadened diffraction peaks does not significantly affect the enthalpy of annealing. The large magnitude of the enthalpy of annealing plateau, −59±3 kJ/mol, suggests that the damage to the structure is pervasive on the scale of Angstroms, consistent with the loss of mid-range order characteristic of a glass. The energetics are consistent with, but do not require, chemical heterogeneity caused by micro-domains of amorphous SiO2-rich and ZrO2-rich regions in the metamict state.
The incorporation of a purified, membrane-bound form of guanylate cyclase into phospholipid vesicles and erythrocytes.

Abstract The purified membrane-bound form of guanylate cyclase was incorporated into artificial unilamellar phospholipid vesicles. The rate and extent of enzyme incorporation into the vesicles was dependent upon the phospholipid concentration and the time period of incubation. The enzyme was incorporated at a significantly faster rate after removal of carbohydrate with endoglycosidase H. The incorporation of the enzyme led to a 10-fold decrease in the apparent maximal velocity and a 2-fold increase in the apparent Michaelis constant for MnGTP. Extraction of liposomes containing guanylate cyclase with 0.2% Lubrol PX resulted in the recovery of 85% of the original amount of added activity, suggesting that the decrease in maximal velocity was not due to enzyme denaturation. Phosphatidylcholine liposomes differentially effected the activity of the membrane-form of guanylate cyclase, dependent on the nature of the fatty acid present on the phospholipid. Specific activities ranged between 458 nmol/min per mg and 2.6 μmol/min per mg, dependent upon the fatty acids present. Liposomes containing the membrane-bound form of guanylate cyclase were subsequently fused with erythrocytes using poly(ethylene glycol) 4000 in attempts to introduce the enzyme into intact cells. The enzyme was successfully introduced into the erythrocytes; greater than 90% of the enzyme activity was subsequently shown to be associated with erythrocyte membranes. Cyclic GMP concentrations of erythrocytes increased from essentially nondetectable to 4 pmol/10 9 cells after introduction of the enzyme. These results demonstrate that guanylate cyclase can be incorporated into liposomes in an active state and that such liposomes can be used to introduce the enzyme into cells where it can subsequently function to generate cyclic GMP.