cssi/SciSciGPT-SciSciNet huggingface dataset:
NMR Spectroscopy of Encapsulated Proteins Dissolved in Low Viscosity Fluids

The challenges to solution NMR spectroscopy originating from the slow tumbling of large proteins are reviewed and a novel solution based on a hydrodynamic approach is described. This solution is based on the effective decrease in tumbling time brought about by the encapsulation of the protein of interest in a protective reverse micelle assembly and its subsequent dissolution in a low viscosity fluid. The physical basis of the method is reviewed and a variety of technical issues are discussed. Recent advances that appear to validate the approach as a tool for structuralbiology are presented. Future applications and developments are also described.
Empire by Collaboration: Indians, Colonists, and Governments in Colonial Illinois Country

Review of: "Empire by Collaboration: Indians, Colonists, and Governments in Colonial Illinois Country," by Robert Michael Morrissey.
Measurement of Alcohol Levels in Body Fluids and Transdermal Alcohol Sensors

Blood or urine alcohol determination is routinely conducted in hospital laboratories, but many laboratories use enzymatic methods that can be easily adopted by automated chemistry analyzers. However, these methods may be subject to interference. For legal alcohol determination, headspace gas chromatography is the method of choice. In this chapter, various sources of errors in enzymatic alcohol determination are addressed. In addition, the in vitro production of alcohol in urine specimens due to the presence of bacteria and glucose (diabetic patients) along with approaches to circumvent such false-positive results, is discussed.
Effective discovery of rare variants by pooled target capture sequencing: A comparative analysis with individually indexed target capture sequencing.

Abstract Identification of all genetic variants associated with complex traits is one of the most important goals in modern human genetics. Genome-wide association studies (GWAS) have been successfully applied to identify common variants, which thus far explain only small portion of heritability. Interests in rare variants have been increasingly growing as an answer for this missing heritability. While next-generation sequencing allows detection of rare variants, its cost is still prohibitively high to sequence a large number of human DNA samples required for rare variant association studies. In this study, we evaluated the sensitivity and specificity of sequencing for pooled DNA samples of multiple individuals (Pool-seq) as a cost-effective and robust approach for rare variant discovery. We comparatively analyzed Pool-seq vs. individual-seq of indexed target capture of up to 960 genes in ∼1000 individuals, followed by independent genotyping validation studies. We found that Pool-seq was as effective and accurate as individual-seq in detecting rare variants and accurately estimating their minor allele frequencies (MAFs). Our results suggest that Pool-seq can be used as an efficient and cost-effective method for discovery of rare variants for population-based sequencing studies in individual laboratories.
The Impact of Meeting or Beating Analysts' Cash Flow Forecasts on a Firm's Cost of Debt

Our research examines the importance and influence of meeting or beating analysts’ cash flow forecasts on a firm’s cost of debt. We examine three important metrics related to a firm’s cost of debt: initial bond rating, bond yield, and subsequent changes in bond ratings. Our results indicate firms meeting/beating analysts’ cash flow forecasts have higher initial bond ratings as well as lower initial bond yields. We also find firms meeting or beating cash flow forecasts have a higher probability of receiving a debt rating upgrade and a lower probability of a ratings downgrade compared to firms missing cash flow forecasts. A direct comparison of the importance of meeting/beating cash flow versus earnings benchmarks indicates debt market participants appear to value both types of forecasts, but unlike previous equity market findings, neither forecast alone appears to be more important than the other for debt market participants.
Effects of Diets and Drugs on Biliary Cholesterol Secretion in Man

Cholesterol gallstones in human beings are frequently associated with supersaturated bile, i.e., bile that contains more cholesterol than can be solubilized by the bile acids and/or phospholipid content (1). Early studies on the mechanism of formation of supersaturated bile have shown that many patients with supersaturated bile have reduced pools of bile acids (2–3). Although a deficiency of bile acids in the enterohepatic circulation (EHC) therefore was postulated to be the cause of supersaturated bile, a somewhat different mechanism has been reported in American Indian women who have an extremely high incidence of cholesterol gallstones. Grundy, Metzger, and Adler (4) showed that Indian women with stones have two abnormalities leading to production of supersaturated bile: not only were bile acids secreted at a reduced rate by the liver, but also, outputs of biliary cholesterol were increased. Therefore, production of supersaturated bile in Indian women with gallstones was due to a combined defect in sterol metabolism. Furthermore, Grundy, et al (5) reported that increased hepatic secretion of cholesterol was the only detectable defect in production of supersaturated bile in young white women with cholesterol gallstones.
Energetic Consequences for a Northern, Range-Edge Lizard Population

Lizards at the northern, cool edge of their geographic range in the northern hemisphere should encounter environmental conditions that differ from those living near the core of their range. To better understand how modest climate differences affect lizard energetics, we compared daily feeding and metabolism rates of individual Sceloporus occidentalis in two populations during mid-summer. Chuckanut Beach (CB) was a cool, maritime climate in northern Washington State, and Sondino Ranch (SR) was a warmer, drier climate in southern, inland Washington. We found no difference between populations in daily energy expenditure (DEE), as calculated from doubly labeled water estimates. The CB population, however, had significantly higher prey availability and rate of daily energy intake (DEI) as estimated from fecal pellet masses. Consequently, CB lizards had higher size-adjusted body masses than lizards from SR. Within CB, during midsummer, DEE was similar to DEI. Within the SR population, DEE trended higher than DE...
Facilitating affective experiences to stimulate women’s entrepreneurship in rural India

This paper aims to understand the nature of affective experiences that can help women to overcome perceived socio-cultural constraints and stimulate entrepreneurship. The paper focuses on rural poor women in India as they represent cultural contexts rich with impediments while also presenting an opportunity for socio-economic development.,A qualitative study with interpretative phenomenological analysis was conducted with participants from women-owned and -managed crafts-based cooperative entrepreneurial ventures from the state of Bihar in India.,Cooperative form of entrepreneurship and sisterhood among its members provides an environment for repeated affective experiences that inspire women to change the status quo. Sisterhood facilitates interactions with role models, mentee-driven mentoring and vicarious incentives, each producing positive affect, whereas cooperatives provide a work environment that fosters equality and helps women find their unique voice, generating affect. Together, the affect allows women to overcome fears associated with deviating from age-old traditions while engaging in entrepreneurial behaviors and sustaining them.,The paper advances knowledge on women entrepreneurship for non-Western cultural contexts, particularly the environments and experiences that stimulate entrepreneurship. The values of cooperative form of entrepreneurship and the homophily among sisters creates an environment which is relaxed and comfortable, where affective experiences can be naturally embedded in daily routines in contrast to those created through formal-structured training programmes. The paper findings are limited to cultural contexts of rural women in eastern states of India with high levels of poverty.,Policies for cooperative entrepreneurship and grassroots support to facilitate an environment to foster cooperatives’ values, and sisterhood can lead to affective experiences necessary for change that endures.,Entrepreneurship for pervasive social change, such as alleviating rural women from poverty, needs theory development, particularly a better understanding of the influence of macro socio-cultural contexts on women’s ability to be entrepreneurial. This paper provides an understanding of contextually relevant affective experiences conducive for rural women entrepreneurship.
RENEW: Programmable and Observable Massive MIMO Networks

Massive MIMO is one of the key technologies in 5G wireless broadband, capable of delivering substantial improvements in capacity of next-generation wireless networks. However, due to its inherent complexity, its operation, reconfiguration, and enhancement present significant challenges and risks. In this paper we present RENEW, a fully programmable and observable massive MIMO network. We present the architectural design for full programmability at every layer of the wireless stack, from the radio hardware, including PHY and MAC layer configurations, all the way up to the network core functionality using network function virtualization. We also present mechanisms to enable observability at every layer of the stack. These include various indicators in the radio and core access network, hence enabling effective monitoring, troubleshooting, and performance evaluation of the network at large.
Dopaminergic Effects of Major Bath Salt Constituents 3,4-Methylenedioxypyrovalerone (MDPV), Mephedrone, and Methylone Are Enhanced Following Co-exposure

Designer drug mixtures popularized as “bath salts” often contain the synthetic cathinones 3,4 methylenedioxypyrovalerone (MDPV), mephedrone, and methylone in various combinations. However, most preclinical investigations have only assessed the effects of individual bath salt constituents, and little is known about whether co-exposure to MDPV, mephedrone, and methylone produces significant neuropharmacological interactions. This study evaluated and compared how MDPV, mephedrone, and methylone influence discrete brain tissue dopamine (DA) levels and motor stimulant responses in mice when administered alone and as a ternary mixture. Male adolescent Swiss-Webster mice received intraperitoneal injections of saline or 1 or 10 mg/kg doses of MDPV, mephedrone, or methylone, or a cocktail of all three cathinones at doses of 1, 3.3, or 10 mg/kg each. The effect of each treatment on DA and DA metabolite levels in mesolimbic and nigrostriatal brain tissue was quantified 15 min after a single exposure using HPLC-ECD. Additionally, locomotor activity was recorded in mice after acute (day 1) and chronic intermittent (day 7) dosing. MDPV, mephedrone, and methylone produced dose-related increases in mesolimbic and nigrostriatal DA levels that were significantly enhanced following their co-administration. In addition, mice treated with the cathinone cocktail displayed decreased locomotor activity on day 1 that was exacerbated by day 7 and not observed with any of the drugs alone. Our findings demonstrate a significant enhanced effect of MDPV, mephedrone, and methylone on both DA, and these effects on DA result in significant alterations in locomotor activity.
Doppler-Derived Pulmonary Arterial Compliance (PAC) Correlates with Invasively Measured PAC in Patients with Advanced Heart Failure and Reduced Ejection Fraction

Background Pulmonary arterial compliance (PAC), a marker of right ventricular (RV) afterload, represented as the ratio of stroke volume (SV) to pulmonary artery pulse pressure (PP), has been shown to be prognostic in heart failure populations. Prior work has shown that the ratio of right ventricular outflow tract pulsed-wave Doppler velocity time integral (RVOT-VTI; an echo-derived estimate of RV SV) and PA systolic pressure (PASP), correlates well with PAC obtained from invasive hemodynamics in patients with heart failure with preserved ejection fraction (HFpEF). We sought to explore this relationship in patients with heart failure with reduced ejection fraction (HFrEF) in a pre-left ventricular assist device (LVAD) cohort. Methods From a cohort of 196 patients with HFrEF awaiting LVAD implant at the Hospital of the University of Pennsylvania from 1/2008 to 2/2015, 72 patients underwent quantitative analysis of pre-implant echocardiogram by an independent reviewer (median days between echo and invasive hemodynamics were 3 [IQR 1-7]). We examined the relationship between RVOT-VTI/PASP with invasive PAC (calculated as SV/PP) using Pearson's rank coefficient and multivariate linear regression analysis. Results There were 42 patients (58%) with sufficient study quality to generate RVOT-VTI/PASP. The median RVOT-VTI/PASP was 0.16 cm/mmHg (IQR 0.11-0.23) and the median PAC was 1.61 ml/ mmHg (IQR 1.36-2.37). There was a modest but significant correlation between RVOT-VTI/PASP and PAC (r2 = 0.47; p=0.002) (Figure). In multivariate linear regression modeling, the relationship between RVOT-VTI/PASP and PAC was maintained (beta-coef 5.5, p=0.015) after adjusting for PCWP (beta-coef -0.016, p=0.5) and PVR (beta-coef -0.24, p=0.03). Conclusions In this small HFrEF cohort, RVOT-VTI/PASP, a proposed non-invasive metric of RV afterload that can be readily obtained on routine echocardiography, correlates with invasive PAC. Additional larger studies among patients with HFrEF are needed to determine if this relationship is maintained and is robust enough for the non-invasive estimation of PAC.
Music in mechanically ventilated stroke patients

Background: Music as a therapeutic intervention for critically ill stroke patients has not been adequately researched. This may be related to a limited number of tools being available to measure th...
In the eyes of others: Loneliness and relational meaning in life among Japanese college students:

In recent years, loneliness has become widely recognized as a public health issue that impacts negatively both on physical and on psychological health, even increasing the risk of mortality. This a...
The Benefits of Incorporating Human Anatomy into Apparel Design Coursework

Anatomy is defined as “the study of structure.” Students learn to base apparel design on some version of a body form: mannequin, two-dimensional sloper or pattern block to develop 3D products to approximate the body. A croquis, basic body outline, is often used as the basis for generating apparel sketches. All of these foundation forms focus on the external structure and surface of the body however, apparel is often designed to interface with the entire body, beyond its’ surface. Examples include bras, sport products and personal protective equipment. We propose that all apparel designer students should have working knowledge of the internal structures of the human body—the anatomy—that determines the external structure. Our motivation of this concept paper is to inspire conversation between ITAA members about the future needs of students studying apparel design, with the potential of workshop development for members in the organization regarding human anatomy.
13 – Presentation of cost accounting information

Publisher Summary This chapter discusses the presentation of cost accounting information. All accountants must be able to communicate. The prepared information must be presented to other members of the team in a way that is readily understandable. Before enquiries and the collection of information commence, it is essential to prepare a framework of investigation. Work can then proceed to a flexible plan that can be revised as necessary when fresh information becomes available. The plan should be based upon factors such as assessment of the likely difficulties, the time factor, amount of cooperation from employees or other managers, degree of confidentiality, possible repercussions from certain individuals or unions, and any special requirements of the report, such as legal or political implications. In the context of accounting reports, the information is derived from the accounting and book-keeping system, and the emphasis should be on the basis of ensuring that the information drops out readily with minimal need for reconciliations or analysis.
Investigating Performance Losses in High-Level Synthesis for Stencil Computations

With the aid of few directives and canonical forms, high-level synthesis (HLS) tools allow FPGA developers to describe their hardware designs in higher-level languages such as C or C++, thus enabling software engineers to exploit the powerful capabilities of FPGA-based accelerators. Hardware engineers may also benefit from automated RTL generation through HLS, as it can boost their productivity with shorter development cycles and simpler validation processes. However, the introduction of automation with its associated performance losses brings the viability of the current HLS-based approach into question: are we sacrificing the main advantage of FPGA designs, namely their performance, in return for higher productivity? This paper examines the performance-per-power penalties incurred in HLS designs in the context of stencil computations for fluid flow simulations, a prevalent class of applications that are difficult to accelerate because of their low arithmetic intensity. By using Xilinx’s Vivado HLS tool to replicate a hand-crafted RTL implementation of a solution of Laplace’s equation, this paper evaluates the impact of implicitly expressing parallelism, particularly if specific optimizations are not directly supported by the tool. In addition, by describing scenarios in which the HLS approach does and does not excel for stencil-based computations, this paper offers insights to assist hardware engineers in setting their expectations of the HLS approach and suggests alternative techniques to accomplish common tasks that fail or underperform using typical approaches.
ABCs of Chronic Pain Evaluation

Chronic pain affects people all over the world. Effective treatment of chronic pain depends on a patient-centered approach to aim for a functional restoration and emotional rehabilitation of patient at an early stage. This chapter stresses the importance of complete patient evaluation including social and psychological evaluation. Any evaluation should not only include a detailed account of the patient’s pain, functional limitations, prior medications, prior procedures/interventions, substance abuse, and psychiatric disorders, but also social issues, and pain coping skills. Physical examination may not add much but goes a long way to develop trust with the patient. Blood tests in general are best left for the other specialists to order and interpret. Imaging tests have great value in ruling out stuff and reassuring patients to be active, while electrophysiological testing has a value in localizing nerve pathology and a prognostics value but not much value in the overall management of pain. Overall the evaluation should focus on finding a disease process that can be treated and if not present, effort should be made to minimize testing as it feed into a narrative that patient is not getting better.
Effect of Cleaning Multiple-Funnel Traps on Captures of Bark and Woodboring Beetles in Northeastern United States

Two experiments were conducted in mixed hardwood-conifer forests in the northeastern United States to test the effects of cleaning surfactant and non-surfactant treated multiple-funnel traps used to catch bark and woodboring beetles. Large amounts of pollen and other debris often form a crust on the interior of traps (personal observations). Such surface deposits may provide footholds for beetles to escape capture in traps. In one experiment, we tested cleaned surfactant and non-surfactant traps against non-cleaned surfactant and non-surfactant traps. In a second experiment, we tested field cleaning of modified multiple-funnel traps as an alternative to substituting clean traps on each collection visit. There was no effect of surfactant treated traps, cleaned or not, on total beetles or individual bark beetle species captured. However, in situ cleaned traps were statistically better at capturing total beetles, total bark beetles, and several bark beetle species than non-cleaned control traps. Surfactant-treated non-modified traps and cleaned modified traps had higher species richness and abundance than other treatments at the site level. Our results suggest that cleaning traps to remove accumulated pollen and debris may be helpful for some species but would have limited benefit for broad-scale trapping of bark and woodboring beetles in northeastern forests.
Ex Vivo Analysis of Primary Tumor Specimens for Evaluation of Cancer Therapeutics

The use of ex vivo drug sensitivity testing to predict drug activity in individual patients has been actively explored for almost 50 years without delivering a generally useful predictive capability. However, extended failure should not be an indicator of futility. This is especially true in cancer research where ultimate success is often preceded by less successful attempts. For example, both immune- and genetic-based targeted therapies for cancer underwent numerous failed attempts before biological understanding, improved targets, and optimized drug development matured to facilitate an arsenal of transformational drugs. Similarly, the concept of directly assessing drug sensitivity of primary tumor biopsies-and the use of this information to help direct therapeutic approaches-has a long history with a definitive learning curve. In this review, we will survey the history of ex vivo testing as well as the current state of the art for this field. We will present an update on methodologies and approaches, describe the use of these technologies to test cutting-edge drug classes, and describe an increasingly nuanced understanding of tumor types and models for which this strategy is most likely to succeed. We will consider the relative strengths and weaknesses of predicting drug activity across the broad biological context of cancer patients and tumor types. This will include an analysis of the potential for ex vivo drug sensitivity testing to accurately predict drug activity within each of the biological hallmarks of cancer pathogenesis.
Understanding interest, barriers, and preferences related to yoga practice among cancer survivors.

Despite growing evidence supporting the benefits of yoga for cancer-related symptom management, yoga usage among cancer survivors is low. To translate the evidence of yoga benefits into community practice, it is critical to understand interest in yoga as well as barriers and preferences that influence yoga usage among cancer survivors. We conducted a cross-sectional survey study among cancer survivors, 18 years or older, with a primary diagnosis of cancer, and receiving treatment or follow-up care at outpatient clinics at five regional academic cancer center sites. We collected data and performed bivariate and multivariable analyses on self-reported yoga usage and interest in and barriers to practicing yoga, as well as preferred location and time for yoga practice. Of 857 participants, 70.0% had never practiced yoga and 52.3% were interested in practicing yoga. Among those interested, 52.5% had never practiced yoga. Lower interest was independently associated with being male (odds ratio [OR] = 0.30, 95% confidence interval [CI] = 0.20–0.44, p < 0.001), unemployed (OR = 0.60, 95% CI = 0.39–0.91, p = 0.016), and white (OR = 0.42, 95% CI = 0.23–0.78, p = 0.005). Commonly cited barriers among those who were interested but had never practiced were not aware of yoga benefits (36.3%), difficulty motivating (28.7%), experiencing symptoms (22.9%), and not enough time (22.0%). Participants indicated “on-site and at a studio near home” (41.5%) as preferred location and evenings (3–8 pm, 34.0%) as preferred time for yoga practice. Although more than 50% of patients indicated interest in practicing yoga, use of yoga is low among cancer survivors. Barriers and patient preferences for yoga practice need to be addressed to design effective yoga programs for this population.
Shedding light on subungual digital mucous cysts.

Transillumination is a quick and easy way to diagnose digital mucous cysts and rule out other subungual masses.
It's Badging Time!: Permanence, Expiration, and Lifespan of Digital Badges

Digital badges, or virtual images that indicate skill or accomplishment of the earner, have been shown to be effective tools for supporting learning, credentialing, and other purposes. However, they are sometimes ineffective, demonstrating incompatibility between badging applications and purposes. To this end, recent research has become increasingly detailed in its examination of the specific design attributes of badges. This paper continues this trend by examining the topic of digital badging lifespan in order to create a common terminology for use in research and practice, and to lay a foundation for future discussion and research on badging lifespan, an area that has received little attention. This paper's primary contribution is the proposal of three types of badging lifespans: momentary badges, permanent badges, and semi-permanent badges. These types are not meant to be exhaustive, but can be used to more precisely describe badging system design and experimental manipulations in badging.
Chapter 3 The Use of Genetic Techniques to Analyze Protein Export in Escherichia coli

Publisher Summary This chapter discusses the use of genetic techniques to analyze protein export in Escherichia coli ( E. coli ), which lacks any kind of internal, membrane-bounded organelles. The task of localizing proteins to their correct, final destination is somewhat simpler than that faced by a eukaryotic cell. Various proteins are exported to one of three extracytoplasmic compartments: (1) the cytoplasmic or inner membrane includes a number of proteins involved in nutrient transport, energy metabolism, chemotaxis, lipid biosynthesis, and other processes; (2) the outer membrane contains relatively fewer proteins, but certain of these constitute major cellular proteins. Many outer membrane proteins function in the transport of various hydrophilic substances across this barrier by either active or passive mechanisms and were initially identified by their properties as receptors for different bacteriophages and/or colicins; (3) the periplasm, an aqueous space bounded by the cytoplasmic and outer membranes, contains two general classes of proteins. A classic genetic approach to the understanding of protein localization in E. coli calls for the isolation of mutants unable to export one or more proteins to their proper extracytoplasmic compartment. An analysis of such mutants could reveal (1) the properties inherent to extracytoplasmic proteins that facilitate correct localization, (2) the domains of these proteins within which such specific export signals are located, and (3) the nature of the cellular protein export machinery, if indeed any such specialized apparatus exists.
Regulation of T cell migration through formation of immunological synapses: the stop signal hypothesis.

The antigen specific immune response is initiated by molecular interactions in the nanometer scale gap between the T cell and antigen-presenting cell (APC). This specialized cell-cell junction has been aptly described as an immunological synapse (Norcross, 1984; Paul and Seder, 1994). The immunological synapse is the site of key signaling events that set thresholds for T cell activation. If these thresholds are appropriately set the T cell is defended against a wide array of pathogens and toxins. If these thresholds are incorrectly set the host is susceptible to pathogen escape, at one extreme, and destructive autoimmunity at the other extreme. The immunological synapse is the site of a sensitive molecular search where as few as 10-100 agonist MHC-peptide complexes are sufficient to activate a T cell (Peterson, et al., 1999). The immunological synapse is also the product of an extensive cellular search that brings the T cell and APC together in the secondary lymphoid tissues. The interaction of T cells agonist MHCpeptide complexes on an appropriate surface generates a robust stop signal (Dustin, et al., 1997; Dustin, et al., 1996; Negulescu, et al., 1996). The common characteristic of the stop signal is that the TCR signal appears to control the polarity of the T cell cytoskeleton and maintains a balance of integrin mediated traction forces to hold the T cell in place-an apparently delicate balance (Dustin, et al., 1997). Subsequent studies on the molecular interactions in the immunological synapse reveal a complex signaling landscape in which molecular topology and dynamic assemblies of cytoskeletal molecules and adhesion molecules create distinct supramolecular activation clusters (SMACs) in a bull’s eye pattern (Grakoui, et al., 1999;Monks, et al., 1998). The T cell receptor (TCR) and CD28 occupy the center of the bull’s eye, whereas the adhesion molecules LFA-1 and CD2 occupy the surrounding ring (Bromley, et al., 2001; Grakoui, et al., 1999; Monks, et al., 1998). The immunological synapse is formed through a distinct intermediate in which the6.
Dual flexible 7 DoF arm robot learns like a child to dance using Q-learning

Many attempts have been made by researchers and scholars to make people feel more conversant to robots. One such example is the dance performance of an Entertainment Robot. In most cases, the challenge to program dance motions for a robot and synchronize them has been too heavy. In addition, pre-programmed dance moves and synchronization information are useful only for a specific music track and are useless for any other. To solve these problems, we developed a new system that can make a robot learn dance moves according to the input music track. The system comprises of two main parts: the first is a beat extraction system for music track; and the second one is a system that learns dance motion for Baxter. In the first part, music track is analyzed using STFT and peak-to-peak time duration is computed. This gives the beats per minute (BPM) of the given music track. The second part takes the BPM and duration of track and feeds it to the developed Q-learning algorithm to make Baxter learn dance moves and synchronize dance motion to beat rate.
Functional Analysis of the Proximal 5′-Flanking Region of the N-Methyl-D-aspartate Receptor Subunit Gene, NMDAR1 (∗)

The NMDAR1 receptor subunit is a common subunit of N-methyl-D-aspartate receptors. We have previously characterized 3 kilobases (kb) of 5′-flanking sequence of the NMDAR1 gene and now report on the ability of this region to direct transcription of a reporter gene and on its interaction with nuclear proteins. The sequence 356 base pairs (bp) 5′ of the first nucleotide of codon 1 was sufficient to express a luciferase reporter gene in rat PC12 pheochromocytoma cells. Additional sequences upstream of nucleotide −356 influenced the activity approximately 2-fold. A labeled 112-bp fragment (position −356 to −245) formed six complexes (C1A and -B, C2A and -B, and C3A and -B), grouped as three double bands, with nuclear extracts from PC12 cells. Competition with Sp1 oligonucleotides abolished formation of C2A and -B and C3A and -B complexes. Sp1 antibody recognized the C3A complex in supershift experiments. Prior immunoprecipitation of nuclear extracts with Sp1 antibody abolished formation of C2A and -B and C3A and -B complexes. Purified Sp1 protein alone did not form a C3A complex but potentiated its formation when PC12 nuclear extract was added. A GC-rich sequence in this fragment was protected from DNase I digestion by nuclear extract. These results suggest that a 356-bp sequence comprises the NMDAR1 basal promoter, and that NMDAR1 gene expression may be regulated by Sp1-like nuclear factors.
A 3.4 ns 0.8 /spl mu/m BiCMOS 53/spl times/53 b multiplier tree

A 53/spl times/53 b multiplier tree with 3.4 ns latency, 10 mm/sup 2/ active area, and 5 W power dissipation at 200 MHz and 3.6 V supply is implemented in 0.8 /spl mu/m n-well BiCMOS with 115 /spl Aring/ gate oxide, 0.45 /spl mu/m effective channel length, and 4 levels of metal. This 3.4ns low-latency multiplier is for a floating-point unit (FPU) on a BiCMOS RISC processor capable of performing IEEE double precision multiply-add operations in three pipelined stages at 200MHz (15ns latency, 5ns throughput, 400MFLOPs peak rate) using multiply-add fused dataflow. >
Regional differences in nerve terminal Na+ channel subtype expression and Na+ channel‐dependent glutamate and GABA release in rat CNS

We tested the hypothesis that expression of pre-synaptic voltage-gated sodium channel (Na(v)) subtypes coupled to neurotransmitter release differs between transmitter types and CNS regions in a nerve terminal-specific manner. Na(v) coupling to transmitter release was determined by measuring the sensitivity of 4-aminopyridine (4AP)-evoked [(3)H]glutamate and [(14)C]GABA release to the specific Na(v) blocker tetrodotoxin (TTX) for nerve terminals isolated from rat cerebral cortex, hippocampus, striatum and spinal cord. Expression of various Na(v) subtypes was measured by immunoblotting using subtype-specific antibodies. Potencies of TTX for inhibition of glutamate and GABA release varied between CNS regions. However, the efficacies of TTX for inhibition of 4AP-evoked glutamate release were greater than for inhibition of GABA release in all regions except spinal cord. The relative nerve terminal expression of total Na(v) subtypes as well as of specific subtypes varied considerably between CNS regions. The region-specific potencies of TTX for inhibition of 4AP-evoked glutamate release correlated with greater relative expression of total nerve terminal Na(v) and Na(v)1.2. Nerve terminal-specific differences in the expression of specific Na(v) subtypes contribute to transmitter-specific and regional differences in pharmacological sensitivities of transmitter release.
Aground and Aloft

I fly in deep river canyons and come to rest where flat land is scarce. My day is a hopscotch route, up and down, up and down. For the dwellers of remote outposts I am a taxi service, mail carrier and delivery van. On occasion I am called on to be an ambulance driver, an emergency outlet arcing over the granite peaks. Once I have been a hearse of last resort, bearing out the body of a drowned river run ner as cargo in the tail, cinched up tight in his sleeping bag. But these are details that don't change my waking day. I attend to the variables around me: the steep slopes, the jutting trees, updrafts and crosswinds and density altitude. My importance doesn't lie in what I carry or where I go. I am responsible for my skill with the yoke, a knowledge of flaps and throttle, an eye for the condition of the air. It is my task to settle the machine to the earth in impossible places, like alighting at the bottom of a soup bowl. I make runs out of Cascade, where I work for Chimp Atherton. His name is on the hangar and the planes. My husband, Ron, and I hired on eighteen years ago, when it was just the three of us. Today there are four pilots, Chimp not included, as well as two mechan ics and three women who run the office and take radio calls. Now, in the summer, is our busiest season. Every pilot and every plane will work steady through until the aspen groves turn yellow and quaky. Then we will bolt skis to a couple of the Cessnas and deliver groceries and mail to some of the ranches that get snowed-in. But the work is slower in winter. Two of the summer pilots head down to Arizona and run a flight school, and then appear again when the rivers here are high with snowmelt. I prefer the taxi and supply flights, ferrying cargo around, travel ing routes I can see in my sleep. Chimp likes some of the fancy flying, chartering for the Forest Service Aerial Fire Attack when the ridges start to burn. Powell, a moustache with a man attached, likes to get up there and tool around for hours, so he volunteers for the Fish and Wildlife trips to monitor gray wolves they have marked with radio collars. I'm not much for adventure these days, though.
STIM1 elevation in the heart results in aberrant Ca2+ handling and cardiomyopathy

Stromal interaction molecule 1 (STIM1) is a Ca(2+) sensor that partners with Orai1 to elicit Ca(2+) entry in response to endoplasmic reticulum (ER) Ca(2+) store depletion. While store-operated Ca(2+) entry (SOCE) is important for maintaining ER Ca(2+) homeostasis in non-excitable cells, it is unclear what role it plays in the heart, although STIM1 is expressed in the heart and upregulated during disease. Here we analyzed transgenic mice with STIM1 overexpression in the heart to model the known increase of this protein in response to disease. As expected, STIM1 transgenic myocytes showed enhanced Ca(2+) entry following store depletion and partial co-localization with the type 2 ryanodine receptor (RyR2) within the sarcoplasmic reticulum (SR), as well as enrichment around the sarcolemma. STIM1 transgenic mice exhibited sudden cardiac death as early as 6weeks of age, while mice surviving past 12weeks of age developed heart failure with hypertrophy, induction of the fetal gene program, histopathology and mitochondrial structural alterations, loss of ventricular functional performance and pulmonary edema. Younger, pre-symptomatic STIM1 transgenic mice exhibited enhanced pathology following pressure overload stimulation or neurohumoral agonist infusion, compared to controls. Mechanistically, cardiac myocytes isolated from STIM1 transgenic mice displayed spontaneous Ca(2+) transients that were prevented by the SOCE blocker SKF-96365, increased L-type Ca(2+) channel (LTCC) current, and enhanced Ca(2+) spark frequency. Moreover, adult cardiac myocytes from STIM1 transgenic mice showed both increased diastolic Ca(2+) and maximal transient amplitude but no increase in total SR Ca(2+) load. Associated with this enhanced Ca(2+) profile was an increase in cardiac nuclear factor of activated T-cells (NFAT) and Ca(2+)/calmodulin-dependent kinase II (CaMKII) activity. We conclude that STIM1 has an unexpected function in the heart where it alters communication between the sarcolemma and SR resulting in greater Ca(2+) flux and a leaky SR compartment.
Wnt signalling in development and disease. Max Delbrück Center for Molecular Medicine meeting on Wnt Signaling in Development and Disease

Figure 1. A meeting on Wnt Signaling in Development and Disease took place between 12 and 15 September 2007, in the Max Delbruck Center for Molecular Medicine in Berlin‐Buch, Germany, and was organized by W. Birchmeier (Berlin, Germany) and T. Holstein (Heidelberg, Germany). Wnt signalling is implicated in numerous aspects of development, cell biology and physiology. This meeting brought together several leading scientists in the Wnt signalling field, who discussed their latest research in this rapidly growing discipline. The expanding number of diseases that are the consequence of mutations in components of the Wnt signalling pathway also attracted researchers with a more clinical interest. Many new insights were presented into the mechanics of Wnt signalling and the role of Wnts in development, regeneration, stem cells and cancer, which we have attempted to summarize in this meeting report. In the absence of Wnt ligands, β‐catenin is phosphorylated by a destruction complex that contains the scaffolding proteins axin and adenomatous polyposis coli (Apc), and the glycogen synthase kinase 3β (Gsk3β). Phosphorylated β‐catenin is recognized by the E3 ubiquitin ligase β‐TrCP and targeted for proteasomal degradation. Wnt signalling is initiated at the plasma membrane by the binding of Wnt ligands to the receptors Frizzled (Fz) and Arrow/LRP. The signal is then relayed in the cytoplasm through Dishevelled (Dsh/Dvl) and leads to inhibition of the destruction complex. Unphosphorylated β‐catenin can then localize to the nucleus where it binds to Tcf/Lef proteins and activates transcription through the recruitment of various cofactors (see Clevers (2006) and the Wnt homepage (http://www.stanford.edu/~rnusse/wntwindow.html) for reviews on Wnt signalling). The binding of Wnt to Fz/LRP leads to the phosphorylation of LRP6 by Gsk3β and casein kinase Iγ (CkIγ), which is necessary for correct Wnt signalling, presumably because axin can then dock to the phosphorylated residues. At the same time, Dvl is recruited …
Adhesion to fibronectin regulates Hippo signaling via the FAK–Src–PI3K pathway

The Hippo pathway is involved in the regulation of contact inhibition of proliferation and responses to various physical and chemical stimuli. Recently, several upstream negative regulators of Hippo signaling, including epidermal growth factor receptor ligands and lysophosphatidic acid, have been identified. We show that fibronectin adhesion stimulation of focal adhesion kinase (FAK)-Src signaling is another upstream negative regulator of the Hippo pathway. Inhibition of FAK or Src in MCF-10A cells plated at low cell density prevented the activation of Yes-associated protein (YAP) in a large tumor suppressor homologue (Lats)–dependent manner. Attachment of serum-starved MCF-10A cells to fibronectin, but not poly-d-lysine or laminin, induced YAP nuclear accumulation via the FAK–Src–phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K) signaling pathway. Attenuation of FAK, Src, PI3K, or PDK1 activity blocked YAP nuclear accumulation stimulated by adhesion to fibronectin. This negative regulation of the Hippo pathway by fibronectin adhesion signaling can, at least in part, explain the effects of cell spreading on YAP nuclear localization and represents a Lats-dependent component of the response to cell adhesion.
A re-evaluation of X-ray diffraction patterns of DNA

Concentric circular lines are present on X-ray diffraction patterns of DNA. They cannot be accounted for by the double helix model. It is suggested that they may indicate the presence of double helical side chains.
β‐ENDORPHIN: SYNTHESIS AND RADIORECEPTOR BINDING ACTIVITY OF βh‐ENDORPHIN‐(1–27) AND ITS ANALOGS

Beta h-Endorphin-(1-27) (I), [Ac-Tyr1]-beta h-endorphin-(1-27) (II), [Gln8]-beta h-endorphin-(1-27) (III), and [Ac-Tyr1, Gln8]-beta h-endorphin-(1-27) (IV) were synthesized by the solid-phase method. The binding potency of I-IV to rat brain membrane preparations was measured by radioreceptor binding assay. The relative potencies were: beta h-endorphin, 100; I, 30; II, 0.04; III, 90; IV, 0.07.
Distribution of tumor necrosis factor receptor messenger RNA in normal and herpes simplex virus infected trigeminal ganglia in the mouse.

Abstract Purpose: to investigate the distribution of p55 and p75 tumor necrosis factor (TNF) receptor mRNA in normal murine trigeminal ganglia, and in murine trigeminal ganglia acutely infected with McKrae strain herpes simplex virus (HSV). Methods: in situ hybridization with antisense 35S-labeled riboprobes for mRNA encoding both the p55 and p75 TNF receptor (TNFR) subtypes was used in normal and HSV-infected murine trigeminal ganglia. Sense riboprobes were used as controls. Results: in situ hybridization with both p55 and p75 riboprobes produced a strong autoradiographic signal over many, but not all, trigeminal sensory neurons. Signal for mRNA encoding both TNFR subtypes was also present over the arachnoid layers surrounding trigeminal ganglia. Acute ocular HSV infection was accompanied by an intense leukocytic infiltrate into the ophthalmic portion of the trigeminal ganglia, and, in this setting, increased p55 and p75 mRNA signal was closely related to the location and number of infiltrating white blood cells. The distribution and number of trigeminal sensory neurons expressing mRNA for the two TNFR subtypes did not appear to change following infection. Signal over control sections hybridized with sense p55 and p75 TNFR cRNA probes was comparable to background. Conclusions: the observed distribution of p55 and p75 TNFR mRNA over trigeminal sensory neurons and over the arachnoid layers surrounding trigeminal ganglia supports suggestions that TNF has a direct effect on neurons, either as a neuromodulator or neurotrophic factor, and that TNF may play a central role in blood-brain barrier regulation. Increased signal for TNFR mRNA in acutely infected trigeminal ganglia appears to reflect infiltration by receptor-bearing white blood cells.
Weighted Wilcoxon Estimators in Nonlinear Regression

Summary In this paper, we consider the estimation of parameters of a general near regression model. An estimator that minimises the weighted Wilcoxon dispersion function is considered and its asymptotic properties established under mild regularity conditions similar to those used in least squares and least absolute deviations estimation. As in linear models, the procedure provides estimators that are robust and highly efficient. The estimates depend on the choice of a weight function and diagnostics which differentiate between nonlinear fits are provided along with appropriate benchmarks. The behavior of these estimates is discussed on a real data set. A simulation study verifies the robustness, efficiency and validity of these estimates over several error distributions including the normal and a family of contaminated normal distributions.
Herder's Nineteenth Century

I begin this essay epigrammatically with song, with a single song that came to tell an historical tale of the nineteenth century (Fig. 1, p. 3). We know this single song in many versions, though it is perhaps the second version that most musicians and scholars of the nineteenth century, more accustomed to playing or hearing the keyboard music of Johannes Brahms than singing Child ballads, know best (Ex. 1). In the Brahms setting, the first of his op. 10 Balladen for solo piano, it may perhaps no longer be a song at all, for its narrative has been stripped of words.
N-Oxidation of Quinoline and Isoquinoline by Cunninghamella elegans

Abstract Sutherland, J. B., Freeman, J. P., Williams, A. J., and Cerniglia, C. E. 1994. N-oxidation of quinoline and isoquinoline by Cunninghamella elegans. Experimental Mycology 18: 271-274. Cultures of Cunninghamella elegans were grown for 7 days in liquid Sabouraud medium containing 1.9m M quinoline or isoquinoline. The spent culture media were extracted with ethyl acetate; metabolites were purified by high-performance liquid chromatography (HPLC) and thin-layer chromatography. The major metabolite produced from each compound was identified by the HPLC elution time, ultraviolet/visible absorption spectrum, and mass spectrum. Under similar conditions, approximately 65% of the added quinoline and 3% of the added isoquinoline were metabolized to quinoline N -oxide and isoquinoline N -oxide, respectively.
The Effect of Surface Impurities on the Thermal Accommodation of Rare Gases on a Tungsten Surface

A rather comprehensive experimental examination of the effect of surface impurities (potassium and cesium) on the thermal accommodation of rare gases on a tungsten surface has been made by Roach and Thomas. The present work examines these effects from a theoretical viewpoint with particular emphasis on the effect on the thermal accommodation of helium on a tungsten surface caused by the adsorption of cesium ions and/or atoms. For this examination, the theory of Allen and Feuer has been utilized using reasonable values of the interaction parameters for helium with the adsorbate as well as the force constant for the adsorbate-substrate bond. Resulting values of the accommodation coefficients are compared with experimental values.