cssi/SciSciGPT-SciSciNet huggingface dataset:
Identification and overlapping expression of multiple unconventional myosin genes in vertebrate cell types.

Abstract Myosin diversity in the human epithelial cell line Caco-2BBe, the porcine epithelial cell line LLC-PK1 (CL-4), human peripheral blood leukocytes, and human liver was analyzed. PCR amplification yielded 8-11 putative myosins (depending on the cDNA source) representing six distinct myosin classes. Analysis of clones obtained by hybridization screening demonstrated that the original PCR products correspond to bona fide myosins, based on the presence of sequences highly conserved in other myosins. RNase protection analysis confirmed mRNA expression of 11 myosins in Caco-2BBe cells. Immunoblot analysis showed that at least 6 myosin immunogens are expressed in Caco-2BBe cells. The results reveal the existence of at least 11 unconventional human myosin genes, most of which are expressed in an overlapping fashion in different cell types. The abundance of myosins suggests that the myosin I vs. myosin II paradigm is inadequate to explain actin-based cellular motility.
Metamorphism of reduced granulites in low-CO 2 vapour-free environment

Pervasive flooding of CO2 has been proposed as the cause of granulite facies metamorphism that is capable of producing many distinctive characteristics of the deep continental crust: reduced water activity, orthopyroxene-bearing assemblages, depletion of large-ion lithophile (LIL) elements, and dehydration1–6. The calculations presented here of C–O–H fluid composition for conditions of granulite facies metamorphism show that oxygen fugacity (f O2) estimates from many terranes are sufficiently low that the addition of CO2-rich fluid causes graphite to precipitate. For values of pressure (P) and temperature (T) common to granulites, and with f O2 slightly below the quartz–fayalite–magnetite buffer (QFM), the addition of CO2 sufficient to grow 10 vol. % orthopyroxene requires the precipitation of 1.5 vol. % graphite. As 0.1 vol. % graphite is readily recognizable, but is not reported in most low f O2 granulites, these rocks have not been flooded by CO2, and low f H2O is probably due to extraction of a magma or recrystallization of an already dry rock7,8. Granulite terranes may thus result from a combination of these three processes and the dominance of any one cannot now be demonstrated on a regional basis.
Genome structural variation discovery and genotyping

Comparisons of human genomes show that more base pairs are altered as a result of structural variation — including copy number variation — than as a result of point mutations. Here we review advances and challenges in the discovery and genotyping of structural variation. The recent application of massively parallel sequencing methods has complemented microarray-based methods and has led to an exponential increase in the discovery of smaller structural-variation events. Some global discovery biases remain, but the integration of experimental and computational approaches is proving fruitful for accurate characterization of the copy, content and structure of variable regions. We argue that the long-term goal should be routine, cost-effective and high quality de novo assembly of human genomes to comprehensively assess all classes of structural variation.
Azimuth depolarization ambiguities in Synthetic Aperture Radar

Abstract The effects of target depolarization in measurements made by stationary microwave systems have been extensively investigated. The use of depolarized measurements can provide information not available in the like-polarized measurement alone. Depolarized measurements acquired by non-Doppler systems were susceptible to errors induced by the measurement antenna. We extend this previous research to non-stationary (Doppler) systems. In both stationary and Doppler systems, adequate antenna polarization isolation is required to allow high quality polarization (especially depolarized) measurements to be acquired. In the synthetic aperture radar (SAR) systems the effect of azimuth ambiguities caused by the pulse repetition frequency (prf) of the system must also be incorporated in the analysis. Normally the effects of PRF can be filtered by the azimuth spectrum processor, however when measuring the weak depolarized cross-section in the presence of the strong like-polarized cross-section the polarization is...
English in Albania: Contact and convergence

The status of English in Albania has changed as this formerly communist country has embarked on the road to a free market economy. This paper provides an overview of the current status and usage of English in Albania. By taking a historical approach, it outlines the Albanian sociolinguistic context in which such a change has taken place. It also presents evidence of the increasing contact areas of English and Standard Albanian under the new sociopolitical and economic circumstances after the downfall of communism. The paper concludes by drawing attention to the need for further research on English language planning and education in Albania.
Long-Lasting Neural Circuit Dysfunction Following Developmental Ethanol Exposure

Fetal Alcohol Spectrum Disorder (FASD) is a general diagnosis for those exhibiting long-lasting neurobehavioral and cognitive deficiencies as a result of fetal alcohol exposure. It is among the most common causes of mental deficits today. Those impacted are left to rely on advances in our understanding of the nature of early alcohol-induced disorders toward human therapies. Research findings over the last decade have developed a model where ethanol-induced neurodegeneration impacts early neural circuit development, thereby perpetuating subsequent integration and plasticity in vulnerable brain regions. Here we review our current knowledge of FASD neuropathology based on discoveries of long-lasting neurophysiological effects of acute developmental ethanol exposure in animal models. We discuss the important balance between synaptic excitation and inhibition in normal neural network function, and relate the significance of that balance to human FASD as well as related disease states. Finally, we postulate that excitation/inhibition imbalance caused by early ethanol-induced neurodegeneration results in perturbed local and regional network signaling and therefore neurobehavioral pathology.
What is the "right" intensity of care at the end of life and how do we get there?

In this issue, Kelley and colleagues report that the intensity of end-of-life care is associated with several patient-level as well as regional factors. The editorialists discuss how the study exte...
Imaging of cervical spine trauma

Abstract The cervical spine, supporting such critical structures as the medulla, spinal cord, and cervical nerve roots, can be very challenging to image propertly because of its complex structural anatomy and superimposition of bony and soft tissue parts. In this article, the use and value of the various modalities that image the cervical spine are discussed. Plain radiography remains the best screening tool in the initial evaluation of the cervical spine after trauma. Additional views, such as swimmer's, pillar and lateral flexion, and extension, often are helpful in certain circumstances.
A High Spurious-Free Dynamic Range 4-bit ADC with Nyquist Signal Bandwidth for Wideband Communications

A 2.5-GS/s 4-bit flash ADC with high SFDR for wideband communication systems is designed using a standard 130 nanometer digital CMOS process. A new clocked digital comparator with dynamic offset suppression is proposed to improve ADC dynamic performance. In our simulation, SFDR of this 4-bit ADC achieve 36.88 dB at 9.766 MHz input signal. Near Nyquist frequency input signals, SFDR maintains above 19.81 dB, at up to 1.248 GHz. This ADC has a two-and-half clock cycle latency and a low input capacitance of 300 fF. The power consumption of ADC is 1.35 mW with 1.2-V voltage supply at a 2.5 GHz conversion rate.
A Dictionary for Transparency

There are many terms that are used in association with the U.S. Defense Threat Reduction Agency (DTRA) Transparency Project associated with the Mayak Fissile Materials Storage Facility. This is a collection of proposed definitions of these terms.
Identification of genomic targets downstream of p38 mitogen-activated protein kinase pathway mediating tumor necrosis factor-α signaling

Inhibition of p38 MAPK suppresses the expression of proinflammatory cytokines such as TNF-α and IL-1β in macrophages and fibroblast-like synoviocytes (FLS). However, there have been no genomewide studies on the gene targets of p38 MAPK signaling in synoviocytes. Microarray technology was applied to generate a comprehensive analysis of all genes regulated by the p38 MAPK signaling pathway in FLS. Gene expression levels were measured with Agilent oligonucleotide microarrays. Four independent sets of mRNA modulated by TNF-α and vehicle were used to measure the change of gene expression due to TNF-α, and three experiments were done to ascertain the effect of SB-203580, a p38 MAPK inhibitor, on TNF-α-induced genes. Microarray data were validated by RT-quantitative polymerase chain reaction. One hundred forty-one significantly expressed genes were more than twofold upregulated by TNF-α. Thirty percent of these genes were downregulated by the p38 inhibitor SB-203580, whereas 67% of these genes were not significantly changed. The SB-203580-inhibited genes include proinflammatory cytokines such as interleukins and chemokines, proteases including matrix metallopeptidases, metabolism-related genes such as cyclooxygenases and phosphodiesterase, genes involved in signal transduction, and genes encoding for transcription factors, receptors, and transporters. Approximately one-third of the TNF-α-induced genes in FLS are regulated by the p38 MAPK signal pathway, showing that p38 MAPK is a possible target for suppressing proinflammatory gene expressions in rheumatoid arthritis.
Photochemical Destruction of Tetrachloroethylene and Trichloroethylene from the Exhaust of an Air Stripper

A novel pilot-scale photochemical reactor is utilized to carry out vapor-phase tetrachloroethylene (PCE) and trichloroethylene (TCE) destruction experiments from the exhaust of a groundwater remediation air stripper. The cylindrical-shaped stainless steel photochemical reactor has an inner diameter of 32 cm and a length of 105 cm. Low-pressure mercury ultraviolet (UV) lamps are used as the photochemical energy source to initiate the destruction reaction within the reactor. A cylindrical-shaped air stripper with a volume of 15.7 L is constructed and utilized for transferring the contaminant from the aqueous phase to the vapor phase. Experiments are conducted using the air stripper to determine phase-transfer characteristics of PCE and TCE. The results show good contaminant phase transfer using clean airflow rates of 1.5 and 3.0 L/min. Next, groundwater remediation experiments are conducted with the air stripper exhaust flowing into the photochemical reactor for contaminant destruction. The first experiment use distilled water contaminated with dissolved PCE, the second experiment use distilled water contaminated with dissolved TCE, and the third experiment use distilled water contaminated with both dissolved PCE and TCE. All three experiments show excellent contaminant destruction efficiencies. This study demonstrates that the photochemical reactor should be included as part of an overall air-stripping PCE/TCE groundwater remediation scheme for complete contaminant destruction.
FLES Methods Courses Now?… Yes, More Than Ever!

ABSTRACT Despite the fact that so few FLES programs are in existence, colleges should offer a FLES methods course. When there was a demand for FLES, we were unprepared to fill many positions with qualified teachers, and the results did not further the cause of FLES. A first-hand experience in FLES can benefit any foreign language teacher. Many foreign language teachers know very little about FLES or the special satisfaction of teaching it. A necessary component of a FLES methods course is teaching experience with young children. Through this contact, foreign language teachers encounter typical favorable and unfavorable situations with administrators and classroom teachers. The methods course should provide techniques, materials, and assistance with ongoing problems. Readings, discussions, demonstrations, resource people, and films should also be included. From this exposure, secondary school foreign language teachers become enthusiastic about the merits of FLES and tend to focus more on arousing interest, being more creative, and introducing new techniques into their regular classes. They also come to understand FLES and are willing to support it rather than compete with it. A backlog of teachers trained in FLES can then be available for use in bilingual, ESL, and future FLES programs.
Group and Individual Treatment Strategies for Distress in Cancer Patients

Many cancer patients experience distress during the course of their illness. Recently, the National Comprehensive Cancer Network recommended that all cancer patients receive evaluation and treatment of distress as a routine part of their care. For some patients, psychosocial interventions may be helpful, but which patients benefit from what type of psychosocial interventions is unclear. To highlight the importance of this problem, this article examines the prevalence of distress in cancer patients and reviews the evidence that supports that cancer patients benefit from group and individual treatment strategies. Several randomized studies have examined the effects of group or individual therapy on both the emotional and the physiological well-being of cancer patients. Both individual and group interventions that are structured have proved effective in reducing distress. Clearly, more investigation is warranted and future research is needed to advance the understanding of structured interventions, to examine support groups, and to tailor psychological interventions to meet individual needs of distressed cancer patients.
Exploration of switching activity behavior of addition algorithms

Total energy consumption of a micro-architecture directly depends on the switching factors of the internal nodes. Weinberger and Ling are the most widely used binary addition algorithms that are used in microprocessor adders. In this paper, the switching activity behaviors of those well known addition recurrence structures are explored. The formulae for estimation of switching activity rates of signals given the probabilities of input signals are derived. The results reveal that the preference of one addition algorithm to other one in terms of switching factors depends on the statistical properties of the input signals as well. The addition algorithms are examined on Kogge-Stone structure and it is possible to save energy up to 20% by selection of the proper addition algorithm in 64-bit adders.
How Diverse—CD4 Effector T Cells and their Functions

CD4 effector T cells, also called helper T (Th) cells, are the functional cells for executing immune functions. Balanced immune responses can only be achieved by proper regulation of the differentiation and function of Th cells. Dysregulated Th cell function often leads to inefficient clearance of pathogens and causes inflammatory diseases and autoimmunity. Since the establishment of the Th1–Th2 dogma in the 1980s, different lineages of effector T cells have been identified that not only promote but also suppress immune responses. Through years of collective efforts, much information was gained on the function and regulation of different subsets of Th cells. In this review, we attempt to sample the essence of what has been learnt in this field over the past two decades. We will discuss the classification and immunological functions of effector T cells, the determinants for effector T cell differentiation, as well as the relationship between different lineages of effector T cells.
A full bit prefetch architecture for synchronous DRAM's

A high performance data path circuit design for Synchronous DRAM's (SDRAM's) is described. Data lines by second-level of metal above memory cells achieve a low power and area efficient full bit prefetch capability. An experimental 3.3-V 16-Mb SDRAM is developed based on this architecture. Since the full burst read data are latched in I/O sense amplifiers by a single CAS access, a precharge operation can start as early as two clocks before the data burst cycles begin. The early precharge function allows next RAS and CAS accesses during burst reads of the previous data. With a burst length of eight, a seamless read operation is possible for any row addresses even within the same bank. The full bit prefetch architecture enables low active power data burst operations because high frequency clock driven circuits are limited to the data path only. The SDRAM with a 1M/spl times/16-b configuration dissipates a 65-mA active current at a 100-MHz full page mode operation. >
Phosphorus soil testing: Innovations for water quality protection

Abstract Modern agricultural management practices for phosphorus (P), including soil testing, can no longer focus exclusively on soil fertility and agricultural productivity but must also address the role of agricultural P in nonpoint source pollution of surface waters. The eutrophication of streams, rivers, lakes, and bays as a result of P loss from soil to water points to the need for advances in soil testing that can contribute to water quality protection. A concerted research effort to modify, refine, and advance soil testing for P to achieve environmental as well as agronomic objectives has been underway for the past decade; unfortunately, little of this research has been adopted by soil testing programs in the United States. The intent of this paper is two‐fold. First, to briefly review some of this research, illustrating its potential value in soil P management programs that, by necessity, must today have both agronomic and environmental components. And second, to provide recommendations as to how ...
Evaluation of accuracy and efficiency of some simulation and sampling methods in structural reliability analysis

Numerous simulation and sampling methods can be used to estimate reliability index or failure probability. Some point sampling methods require only a fraction of the computational effort of direct simulation methods. For many of these methods, however, it is not clear what trade-offs in terms of accuracy, precision, and computational effort can be expected, nor for which types of functions they are most suited. This study uses nine procedures to estimate failure probability and reliability index of approximately 200 limit state functions with characteristics common in structural reliability problems. The effects of function linearity, type of random variable distribution, variance, number of random variables, and target reliability index are investigated. It was found that some methods have the potential to save tremendous computational effort for certain types of limit state functions. Recommendations are made regarding the suitability of particular methods to evaluate particular types of problems.
Immediate or early cord clamping vs delayed clamping

Over the past 40 years, there have been a number of review articles attempting to rationalise cord clamping practice. Early cord clamping was originally thought to be important in active management of the third stage of labour, but this was never evidence based. Without an evidence base to justify it, early cord clamping in clinical practice has remained very variable. There is good evidence that early cord clamping leads to hypovolaemia, anaemia and low iron stores in the neonate. We review all the evidence and discuss possible reasons why some obstetricians and midwives persevere with early clamping. We explain how a variable definition, defective education, deferred responsibility between obstetrician and paediatrician, variable guidelines and a lack of appreciation for the potential harm of the intervention, have all contributed. This study describes how the need for early cord clamping can be avoided in practically all clinical complications of birth.
Cobalt limitation and uptake in Prochlorococcus

Processes that enable marine phytoplankton to acquire trace metals are fundamental to our understanding of primary productivity and global carbon biogeochemical cycling. Here we show that the abundant marine cyanobacterium, Prochlorococcus strain MED4-Ax, has an absolute cobalt requirement and that zinc cannot substitute for cobalt in the growth medium, as is the case in some other phytoplankton species. When resuspended into fresh medium, uptake of cobalt into the cell occurs as free cobalt (Co 21 ). In contrast, cultures augmented with conditioned medium assimilated cobalt significantly faster than those in fresh medium, leading to the hypothesis that Prochlorococcus produced organic cobalt ligands in the conditioned medium. This work suggests that the availability of cobalt might influence the composition of phytoplankton assemblages in the open ocean.
Kinship Asymmetries and the Divided Self

Imprinted genes are predicted to affect interactions among relatives. Therefore, variant alleles at imprinted loci are promising candidates for playing a causal role in disorders of social behavior. The effects of imprinted genes evolved in the context of patterns of asymmetric relatedness that existed within social groups of our ancestors.
Application of the compatibility factor to the design of segmented and cascaded thermoelectric generators

Using thermoelectric compatibility, efficient thermoelectric generators are rationally designed. With examples, compatible and incompatible systems are explained and materials proposed for targeted development.
Research Note---An Investigation of the Appropriation of Technology-Mediated Training Methods Incorporating Enactive and Collaborative Learning

The growth in the application of information technology to student and employee learning underscores the need to understand the impact of technology-mediated learning TML methods. Using previous developed TML models, based on social cognitive theory and adaptive structuration meta-theory, the effectiveness of three training methods were examined in this study: technology mediated using both vicarious and enactive learning, and collaborative and combined collaborative plus technology mediated. The study also focused on the learning process. The experimental study results showed a significant positive influence of enactive learning enabled TML and collaborative training on specific training outcomes, and the combined training method shows positive results on all training outcomes. The study results also showed that faithful appropriation of the training methods during the learning process has a moderator effect on training outcomes. The study provides important research implications for theory and practice.
The small RNA SgrS: roles in metabolism and pathogenesis of enteric bacteria.

Bacteria adapt to ever-changing habitats through specific responses to internal and external stimuli that result in changes in gene regulation and metabolism. One internal metabolic cue affecting such changes in Escherichia coli and related enteric species is cytoplasmic accumulation of phosphorylated sugars such as glucose-6-phosphate or the non-metabolizable analog α-methylglucoside-6-phosphate. This “glucose-phosphate stress” triggers a dedicated stress response in γ-proteobacteria including several enteric pathogens. The major effector of this stress response is a small RNA (sRNA), SgrS. In E. coli and Salmonella, SgrS regulates numerous mRNA targets via base pairing interactions that result in alterations in mRNA translation and stability. Regulation of target mRNAs allows cells to reduce import of additional sugars and increase sugar efflux. SgrS is an unusual sRNA in that it also encodes a small protein, SgrT, which inhibits activity of the major glucose transporter. The two functions of SgrS, base pairing and production of SgrT, reduce accumulation of phosphorylated sugars and thereby relieve stress and promote growth. Examination of SgrS homologs in many enteric species suggests that SgrS has evolved to regulate distinct targets in different organisms. For example, in Salmonella, SgrS base pairs with sopD mRNA and represses production of the encoded effector protein, suggesting that SgrS may have a specific role in the pathogenesis of some γ-proteobacteria. In this review, we outline molecular mechanisms involved in SgrS regulation of its target mRNAs. We also discuss the response to glucose-phosphate stress in terms of its impact on metabolism, growth physiology and pathogenesis.
Normal Immune Development and Glucocorticoid-Induced Thymocyte Apoptosis in Mice Deficient for the T-Cell Death-Associated Gene 8 Receptor

T-cell death-associated gene 8 (TDAG8) is a G-protein-coupled receptor transcriptionally upregulated by glucocorticoids (GCs) and implicated by overexpression studies in psychosine-mediated inhibition of cytokinesis and in GC-induced apoptosis. To examine the physiological function of TDAG8, we generated knockout (KO) mice by homologous recombination. An enhanced green fluorescent protein reporter was knocked into the disrupted tdag8 locus to allow the analysis of TDAG8 expression in living cells. Interestingly, we found that during thymocyte development, TDAG8 expression resembled the dynamic regulation described for known modulators of GC-induced apoptosis, including Bcl-2, Notch1, and GC receptor. TDAG8 was expressed in double-negative cells, was downregulated at the double-positive transition, and was upregulated in single-positive thymocytes. However, despite this striking expression pattern, maturation and selection of thymocytes, as well as major immune functions, were not affected in TDAG8 KO mice. In contrast to previous overexpression results, TDAG8 was dispensable for psychosine-induced formation of multinucleated cells. Furthermore, TDAG8 KO thymocytes showed normal apoptosis following in vivo and in vitro GC treatment. These results, while establishing a useful reporter strain to study T-lymphocyte maturation, argue against a critical role for TDAG8 in immune development, psychosine-mediated inhibition of cytokinesis, and GC-induced cell death.
Net energy analysis of Bakken crude oil production using a well-level engineering-based model

Abstract Since 2005, production of oil from the Bakken formation of North Dakota has increased substantially, and the region now supplies about 1.5% of global oil output. This study presents a first engineering-based assessment of the energy intensity of Bakken crude oil production and computes the resulting NER (net energy return) from Bakken hydrocarbon production. The energy required to drill, produce, and process Bakken oil and gas is estimated for over 7000 wells using open-source drilling and production assessment models. The largest energy uses are from drilling and processing of produced fluids (crude/water emulsions and gas). Fluid lifting and injection and embodied energy are also important energy needs. Median energy consumption equals ≈3.4% of net crude and gas energy content, while mean energy consumption equals ≈3.9% of hydrocarbon energy. The median NER is 29.3 MJ/MJ. The interquartile range is 24.3–35.7 MJ/MJ, while the 5%–95% range is 13.3–52.0 MJ/MJ. NERs have declined in recent years, with a decline in median NER of 23% between 2010 and 2014. Results are most sensitive to modeled estimated ultimate recovery, and embodied energy.
Endosonographers’ approach to delivering a diagnosis of pancreatic cancer: obligated but undertrained

Background and study aims: No data are available on the practice patterns of endosonographers as they pertain to the disclosure of a pancreatic cancer diagnosis. We sought to understand the current practice and coping strategies of physicians who perform endoscopic ultrasound (EUS) procedures in patients with suspected pancreatic cancer. Methods: This study used a nonexperimental, cross-sectional survey design. A total of 707 endosonographers were contacted and asked to complete an online survey encompassing both demographic and practice data. In addition, participants had the option to complete a second survey assessing common coping strategies. Results: A total of 152 physicians (22 %) participated in the study. The sample was split between community (47 %) and academic centers (53 %). A total of 92 % of the respondents felt an obligation to share a cancer diagnosis when it was available to them; however, only 45 % felt they were adequately trained to do so. Comfort levels were higher in those who performed more than 200 EUS procedures annually and in those practicing for longer than 5 years (P = 0.044). A total of 98 physicians (64.5 %) also completed the Brief COPE questionnaire, and the results indicated that the more experienced endosonographers were less likely to experience emotional distress when disclosing a cancer diagnosis. Conclusion: The comfort level for disclosing a pancreatic cancer diagnosis after EUS appears to be higher in experienced endosonographers (> 5 years in practice) and in those who conduct a higher volume of procedures. Although the majority of endosonographers feel obligated to disclose a cancer diagnosis, the lack of time and proper training is limiting. Formal communication skills training within a gastrointestinal fellowship should be considered.
Integrated Investigation of Dynamic Drainage Volume and Inflow Performance Relationship (Transient IPR) to Optimize Multistage Fractured Horizontal Wells in Tight/Shale Formations

This study presents an integrated approach to evaluate the efficiency of fracturing stimulation and predict well production performance. As the pressure disturbance propagates throughout the reservoir during long-time transient flow regimes, it will shape an expanding drainage volume. A macroscopic “compressible tank model (CTM)” using weak (integral) form of mass balance equation is derived to relate dynamic drainage volume (DDV) and average reservoir pressure to production history in extremely shale reservoirs. Fluids and rock compressibility, desorption parameters (for shale or coal gas), and production rates control the speed at which the boundaries advance. After the changes of average reservoir pressure within the expanding drainage volume are obtained, a new empirical inflow performance relationship (transient IPR) correlation is proposed to describe well performance during long transient flow periods in shale reservoirs. This new empirical correlation shows better match performance with field data than that of conventional Vogel-type IPR curves. The integrated approach of both CTM model and transient IPR correlation is used to determine and predict the optimal fracturing spacing and the size of horizontal section for few wells from one of shale oil plays in U.S. The results suggest the existence of optimal fracture spacing and horizontal well length for multistage fractured horizontal wells in shale oil reservoirs. In practice, this paper not only provides an insight in understanding the long transient flow production characteristics of shale reservoirs using concept of expanding drainage volume. Neither methods require comprehensive inputs for the strong form (differential) nor any prior knowledge about the sophisticated shale reservoir features (shape, size, etc.), the ultimate drainage volume, the ultimate recovery, optimal fracture spacing, and the length of horizontal section for each well can also be easily obtained by this new integrated analytical method.
Disposition of 3-Hydroxyquinidine in Patients Receiving Initial Intravenous Quinidine Gluconate for Electrophysiology Testing of Ventricular Tachycardia

The formation rate constant and elimination rate constant for 3-hydroxyquinidine were determined in eight patients with ventricular tachycardia. These two parameters (mean +/- SD) were found to be 0.784 +/- 0.202 and 0.042 +/- 0.058 h-1, respectively. Coefficients of determination for the computer-generated line of best fit for serum concentration-time data were 0.986 +/- 0.008. Patients received two infusions of quinidine gluconate 5 mg/kg over 30 minutes separated by a 20-30 minute electrophysiologic testing period. Unbound and total 3-hydroxyquinidine concentrations were also determined. Among the eight patients, 3-hydroxyquinidine was 61.9 percent bound. Studies in healthy volunteers had shown 50 percent binding. Linear regression of unbound and total 3-hydroxyquinidine was described by the equation Y = 0.3814X-1.448, r = 0.813. Although half-lives of 3.5-12.4 hours had been reported in healthy volunteers, prolonged half-lives were observed in all but two of our arrhythmia patients.
Molecular Pathways Mediating Metastases to the Brain via Epithelial-to-Mesenchymal Transition: Genes, Proteins, and Functional Analysis

Background: Brain metastases are the leading cause of morbidity and mortality among patients with disseminated cancer. The development of metastatic disease involves an orderly sequence of steps enabling tumor cells to migrate from the primary tumor and colonize at secondary locations. In order to achieve this complex metastatic potential, a cancer cell is believed to undergo a cellular reprogramming process involving the development of a degree of stemness, via a proposed process termed epithelial-to-mesenchymal transition (EMT). Upon reaching its secondary site, these reprogrammed cancer stem cells submit to a reversal process designated mesenchymal-to-epithelial transition (MET), enabling establishment of metastases. Here, we examined the expression of markers of EMT, MET, and stem cells in metastatic brain tumor samples. Materials and Methods: Immunohistochemical analyses were performed to establish the markers of EMT and MET. Co-expression of these markers was determined by immunofluorescence analysis. Gene-expression analysis was conducted using tissues from brain metastases of primary adenocarcinoma of the lung compared to non-metastatic tissue. Cell proliferation was carried out using 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide S-phase entry analysis, by determining the 5-ethynyl-2’-deoxyuridine incorporation. Scratch wound and chemotactic migration assays were performed in an astrocytic setting. Results: Metastatic brain tumor samples displayed expression of epithelial markers (zinc finger protein SNAI1 and Twist-related protein-1), as well as the mesenchymal marker vimentin. The stem cell marker CD44 was also highly expressed. Moreover, co-expression of the epithelial marker E-cadherin with the mesenchymal marker vimentin was evident, suggesting a state of transition. Expression analysis of transcription factor genes in metastatic brain tumor samples demonstrated an alteration in genes associated with neurogenesis, differentiation, and reprogramming. Furthermore, tumor cells grown in astrocytic medium displayed increased cell proliferation and enhanced S-phase cell-cycle entry. Additionally, chemotactic signaling from the astrocytic environment promoted tumor cell migration. Primary tumor cells and astrocytes were also shown to grow amicably together, forming cell-to-cell interactions. Conclusion: These findings suggest that cellular reprogramming via EMT/MET plays a critical step in the formation of brain metastases, where the cerebral milieu provides a microenvironment suitable for the development of metastatic disease.
Ontogeny of basolateral membrane lipid composition and fluidity in small intestine

To evaluate physicochemical properties of the small intestinal basolateral cell surface during postnatal development, membranes were isolated from suckling (14-17 days) and weanling-mature (35-49 days) rabbit jejunal and ileal enterocytes at 30- to 40-fold purification (based on Na+-K+-ATPase specific activity) and with limited contamination from coisolated cellular elements. Membrane lipid analysis demonstrated age-dependent reductions and proximal to distal increases in total lipid (per milligram protein). Postnatal increases in membrane total cholesterol of jejunum (suckling vs. mature, 0.18 vs. 0.26 mumol/mg protein; P less than 0.01) and ileum (0.18 vs. 0.31 mumol/mg protein; P less than 0.01) resulted in markedly higher cholesterol-to-phospholipid molar ratios (jejunum, 0.43 vs. 0.73; ileum, 0.43 vs. 0.72 mumol/mg protein; P less than 0.01). Membranes from mature animals had higher relative sphingomeylin and phosphatidylcholine content and, in both age groups, fatty acyl saturation was increased in ileum compared with jejunum. By utilization of the fluorophores 1,6-diphenyl-1,3,5-hexatriene and DL-12-(9-anthroyl)stearic acid, the fluidity of basolateral membranes and liposomes prepared from extracted membrane lipid decreased markedly in mature rabbits. Arrhenius plots demonstrated higher apparent thermotropic transition temperatures of mature membrane lipid. These data therefore demonstrate significant changes in small intestinal basolateral membrane lipid composition and fluidity that occur during the weaning period. Possible relationships to ontogenesis of membrane protein function are discussed.
Structural characterization of the virulence factor Sda1 nuclease from Streptococcus pyogenes

Infection by Group A Streptococcus pyogenes (GAS) is a leading cause of severe invasive disease in humans, including streptococcal toxic shock syndrome and necrotizing fasciitis. GAS infections lead to nearly 163,000 annual deaths worldwide. Hypervirulent strains of S. pyogenes have evolved a plethora of virulence factors that aid in disease-by promoting bacterial adhesion to host cells, subsequent invasion of deeper tissues and blocking the immune system's attempts to eradicate the infection. Expression and secretion of the extracellular nuclease Sda1 is advantageous for promoting bacterial dissemination throughout the host organism, and evasion of the host's innate immune response. Here we present two crystal structures of Sda1, as well as biochemical studies to address key structural features and surface residues involved in DNA binding and catalysis. In the active site, Asn211 is observed to directly chelate a hydrated divalent metal ion and Arg124, on the putative substrate binding loop, likely stabilizes the transition state during phosphodiester bond cleavage. These structures provide a foundation for rational drug design of small molecule inhibitors to be used in prevention of invasive streptococcal disease.
Micropuncture studies of the transport of individual amino acids by the Necturus proximal tubule.

Micropuncture studies of the transport of individual amino acids by the Necturus proximal tubule. Absorption of amino acids by the Necturus proximal tubule was measured under free-flow conditions. The coexistence of proximal tubular amino acid influx was determined by infusing saline into tubular lumens by the stopped-flow microperfusion technique. Under free-flow conditions, fractional absorption of individual amino acids ranged from 0.30 ± 0.18 (glutamic acid) to 0.96 ± 0.02 (proline), with 14 of 19 values greater than 0.75. The transport avidity for a given amino acid bore no relationship to its molecular weight, transport class, or plasma concentration. The values obtained for tubular fluid/plasma (TF/P) were very comparable to those reported for the rat. In stopped-flow microperfusion experiments, samples of isotonic saline residing in tubule lumens for 20min were found to contain all the amino acids present in plasma (filtrate). The concentrations of all except the acidic anionic pair, glutamic acid and aspartic acid, were remarkably similar to those obtained by collection of end proximal samples in free-flow studies. The very high concentrations of the acidic amino acids may reflect their passive distribution across the luminal cell membrane, active absorption having been impaired by the absence of some substance normally present in glomerular filtrate. Etude par microponction du transport individuel des acides amines par le tube proximal de Necturus. L'absorption des acides amines par le tube proximal de Necturus a ete mesuree dans des conditions de flux libre. La co-existence d'un influx d'acides amines dans le tube proximal a ete determinee par la perfusion, avec du solute sale, des lumieres tubulaires par la technique de la microperfusion stationnaire. Dans les conditions de flux libre, l'absorption fractionnelle des acides amines varie de 0,30 ± 0,18 (acide glutamique) a 0,96 ± 0,02 (proline), des valeurs superieures a 0,75 sont obtenues pour 14 a 19 acides amines. L'avidite du transport d'un acide amine n'a aucune relation avec son poids moleculaire, sa classe de transport ou sa concentration plasmatique. Les valeurs du rapport fluide tubulaire/plasma obtenues sont tres comparables avec celles observees chez le rat. Au cours des experiences de microperfusion stationnaire, les echantillons de solute sale isotonique qui ont sejourne dans les lumieres tubulaires pendant 20 minutes, contiennent tous les acides amines presents dans l'ultrafiltrat du plasma. Toutes les concentrations, a l'exception de la paire anionique, acide glutamique et acide aspartique, sont remarquablement semblables a celles obtenues au cours des experiences en flux libre a la fin du tube proximal. Les concentrations tres elevees des acides amines acides peuvent refleter leur distribution passive a travers la membrane cellulaire luminale, l'absorption active ayant ete empechee par l'absence d'une substance normalement presente dans le filtrat glomerulaire.
Alcohol Expectancies Mediate the Relationship Between Age of First Intoxication and Drinking Outcomes in College Binge Drinkers

ABSTRACTBackground: While prior research has shown that age of first intoxication (AI) is associated with negative alcohol outcomes, limited research has examined factors accounting for this relationship. Alcohol expectancies, or beliefs about the effects of alcohol, may explain such associations as both positive and negative expectancies have been shown to be key predictors of drinking outcomes. Objective: The present study examined expectancies as mediators between early AI and alcohol-related outcomes. Method: Data collection occurred in 2012 and 2013. Participants were college students (N = 562, 65.8% women) who completed an online survey including measures of alcohol use history, alcohol expectancies, typical alcohol consumption, and alcohol-related problems. Structural equation modeling was used to test the hypothesized model. Results: Our findings support a model whereby AI is associated with drinking through its influence on both positive and negative expectancies. Specifically, an earlier AI was ...
Surface-Functionalization-Dependent Optical Properties of II–VI Semiconductor Nanocrystals

We report a study of the surface-functionalization-dependent optical properties of II–VI zinc-blende semiconductor nanocrystals on the basis of ligand-exchange chemistry, isomaterial core/shell growth, optical spectroscopy, transmission electron microscopy, and X-ray powder diffraction. Our results show that the transition energy and extinction coefficient of the 2Sh3/21Se excitonic band of these nanocrystals can be strongly modified by their surface ligands as well as ligand associated surface atomic arrangement. The oleylamine exchange of oleate-capped zinc-blende II–VI nanocrystals narrows the energy gap between their first and second excitonic absorption bands, and this narrowing effect is size-dependent. The oleylamine exchange results in the quenching, subsequent recovery, and even enhancing of the photoluminescence emission of these II–VI semiconductor nanocrystals. In addition, the results from our X-ray powder diffraction measurements and simulations completely rule out the possibility that oleat...
Adrenal Gland Responses to Experimental Manipulations of Captive Pocket Gophers (Thomomys umbrinus)

The responses of the adrenal gland in two populations of the pocket gopher, Thomomys umbrinus , held in captivity were gauged after (1) holding individuals singly in captivity; (2) placing them together in various sex and numerical combinations and (3) surgical removal of the left adrenal gland. Animals held singly in captivity showed only slight increases in adrenal weight, apparently due to nodular increase of the zona fasciculata. Unilaterally adrenalectomized animals (kept singly) showed a marked compensatory hypertrophy of the remaining right adrenal gland due to both cortical and medullary changes. Animals held together in “pairs” normally reacted to each other by violent threats and attacks reflected in frequent wounding and death and in pronounced medullary changes. Populations of 2, 4 and 8 individuals held in outdoor pens with “natural” food and cover showed striking antagonisms at the higher levels, including death to half the test population at level eight, but did not show adrenal gland differences consonant with the extent of wounding, weight loss and death. Cellular changes in the adrenal gland were chiefly medullary. In view of the unusual gland responses observed we suggest that the pocket gopher depends on medulla-mediated antagonisms to maintain territory reinforced by ecological isolation. Apparently little dependence is placed on adrenopituitary interactions. The pocket gopher seemingly has lost, or has never developed, dependence on this axis so important in more social mammals.
Factors limiting populations of arid-land darkling beetles (Coleoptera; Tenebrionidae): predation by rodents

The role of rodent predation as a limiting factor in the abundance of sixspecies of darkling beetles (Tenebrionidae) was examined in a sagebrush–steppe ecosystem (Kemmerer, Wyo.). Rodent predators were identified in feeding experiments using captive rodents and darkling beetles. Grasshopper mice ( Onychomys ) and deer mice ( Peromyscus ) successfully captured and consumed Eleodes extricatus Say. Ground squirrels ( Spermophilus ) and pocket mice ( Perognathus ) initially fed upon E. extricatus but developed an aversion to them after several exposures. Subsequent experiments demonstrated that the chemical aerosol produced by E. extricatus as an antipredator defense was effective in providing escape time during deer mouse attacks but not during grasshopper mouse attacks. A replicated field experiment, employing 10 rodent exclosures (15 by 15 m) and 10 control plots, showed that the removal of rodent predators resulted in population increases in five of the six species of darkling beetles ( Coniontis ovalis, E. extricatus, E. pimelioides, E. rileyi , and Helops difficilis ). The total population of beetles exhibited a 63% increase in abundance following rodent removal. Based on 1986 field density measurements of rodents (8/ha) and beetles (4,931/ha), an average daily consumption of fewer than two beetles per rodent was calculated to be sufficient to produce the observed differences in darkling beetle populations on the site. Therefore, it is concluded that rodent predation functioned as a significant limiting factor on darkling beetle populations in the sagebrush–steppe study area.
Changing Places: Where Will We Be with Our Patients? A Perspective from the Keystone IV Conference

Dr. Stephens knew a lot about place-his place within family medicine and the place of family medicine as a catalyst for change in our communities. In "G. Gayle Stephen's Festschrift," the evolution of our profession is mirrored by Dr. Stephen's seminal contributions to practice and service to his discipline. He describes our place as healers, teachers, scholars, builders, moral agents, professionals, and reformers. Stephen's place-changing career and ethos pave the way for our place as advocates for our patients and change agents for family medicine in this newest millennium.
A Preliminary Investigation of the Predilection for Adaptive Behavior and Sales Success

The issue of salesperson adaptivity has become an important part of current theoretical research. A crucial unresolved issue at this time is whether a salesperson has a predilection to alter their behavior. Adaptation requires the examination of internal as well as external activity. This study exams the relationship between self-consciousness and two different performance measurements. Results of this preliminary study identify that a relationship between a predilection to adaptive behavior and successful selling exists; although the type of sales interaction affects the direction of the self-consciousness characteristics.