cssi/SciSciGPT-SciSciNet huggingface dataset:
New Insights into the Role of Conserved, Essential Residues in the GTP Binding/GTP Hydrolytic Cycle of Large G Proteins

The GTP hydrolytic (GTPase) reaction terminates signaling by both large (heterotrimeric) and small (Ras-related) GTP-binding proteins (G proteins). Two residues that are necessary for GTPase activity are an arginine (often called the "arginine finger") found either in the Switch I domains of the alpha subunits of large G proteins or contributed by the GTPase-activating proteins of small G proteins, and a glutamine that is highly conserved in the Switch II domains of Galpha subunits and small G proteins. However, questions still exist regarding the mechanism of the GTPase reaction and the exact role played by the Switch II glutamine. Here, we have characterized the GTP binding and GTPase activities of mutants in which the essential arginine or glutamine residue has been changed within the background of a Galpha chimera (designated alpha(T)*), comprised mainly of the alpha subunit of retinal transducin (alpha(T)) and the Switch III region from the alpha subunit of G(i1). As expected, both the alpha(T)*(R174C) and alpha(T)*(Q200L) mutants exhibited severely compromised GTPase activity. Neither mutant was capable of responding to aluminum fluoride when monitoring changes in the fluorescence of Trp-207 in Switch II, although both stimulated effector activity in the absence of rhodopsin and Gbetagamma. Surprisingly, each mutant also showed some capability for being activated by rhodopsin and Gbetagamma to undergo GDP-[(35)S]GTPgammaS exchange. The ability of the mutants to couple to rhodopsin was not consistent with the assumption that they contained only bound GTP, prompting us to examine their nucleotide-bound states following their expression and purification from Escherichia coli. Indeed, both mutants contained bound GDP as well as GTP, with 35-45% of each mutant being isolated as GDP-P(i) complexes. Overall, these findings suggest that the R174C and Q200L mutations reveal Galpha subunit states that occur subsequent to GTP hydrolysis but are still capable of fully stimulating effector activity.
COMBINED MEDICATION AND PSYCHOTHERAPY IN THE TREATMENT OF CHRONIC MOOD DISORDERS

As has been discussed in previous articles in this issue of The Psychiatric Clinics of North America , patients with chronic mood disorders are, by definition, those who suffer with their disorder for long periods. Because of their chronicity and treatment resistance, these patients represent a significant therapeutic challenge to the clinician. Other articles have discussed various pharmacologic and psychotherapeutic approaches to treating patients with chronic mood disorders. In this article, we focus on issues involved in combining medication and psychotherapies. At the outset, it is important to note that there are virtually no empirical data concerning the efficacy of combined treatments for patients with chronic mood disorders. Relatively few studies have explored the utility of combining treatments for unselected patients with major depression and even fewer have addressed these issues with chronically depressed patients. Thus, many of the points we make in this article are based on our clinical experience and extrapolation from the literature concerning major depression.
Charisma perception from text and speech

Charisma, the ability to attract and retain followers without benefit of formal authority, is more difficult to define than to identify. While we each seem able to identify charismatic individuals - and non-charismatic individuals - it is not clear what it is about an individual that influences our judgment. This paper describes the results of experiments designed to discover potential correlates of such judgments, in what speakers say and the way that they say it. We present results of two parallel experiments in which subjective judgments of charisma in spoken and in transcribed American political speech were analyzed with respect to the acoustic and prosodic (where applicable) and lexico-syntactic characteristics of the speech being assessed. While we find that there is considerable disagreement among subjects on how the speakers of each token are ranked, we also find that subjects appear to share a functional definition of charisma, in terms of other personal characteristics we asked them to rank speakers by. We also find certain acoustic, prosodic, and lexico-syntactic characteristics that correlate significantly with perceptions of charisma. Finally, by comparing the responses to spoken vs. transcribed stimuli, we attempt to distinguish between the contributions of ''what is said'' and ''how it is said'' with respect to charisma judgments.
The effects of acute oral glutamine supplementation on exercise-induced gastrointestinal permeability and heat shock protein expression in peripheral blood mononuclear cells

Chronic glutamine supplementation reduces exercise-induced intestinal permeability and inhibits the NF-κB pro-inflammatory pathway in human peripheral blood mononuclear cells. These effects were correlated with activation of HSP70. The purpose of this paper is to test if an acute dose of oral glutamine prior to exercise reduces intestinal permeability along with activation of the heat shock response leading to inhibition of pro-inflammatory markers. Physically active subjects (N = 7) completed baseline and exercise intestinal permeability tests, determined by the percent ratio of urinary lactulose (5 g) to rhamnose (2 g). Exercise included two 60-min treadmill runs at 70 % of VO2max at 30 °C after ingestion of glutamine (Gln) or placebo (Pla). Plasma levels of endotoxin and TNF-α, along with peripheral blood mononuclear cell (PBMC) protein expression of HSP70 and IκBα, were measured pre- and post-exercise and 2 and 4 h post-exercise. Permeability increased in the Pla trial compared to that at rest (0.06 ± 0.01 vs. 0.02 ± 0.018) and did not increase in the Gln trial. Plasma endotoxin was lower at the 4-h time point in the Gln vs. 4 h in the Pla (6.715 ± 0.046 pg/ml vs. 7.952 ± 1.11 pg/ml). TNF-α was lower 4 h post-exercise in the Gln vs. Pla (1.64 ± 0.09 pg/ml vs. 1.87 ± 0.12 pg/ml). PBMC expression of IkBα was higher 4 h post-exercise in the Gln vs. 4 h in the Pla (1.29 ± 0.43 vs. 0.8892 ± 0.040). HSP70 was higher pre-exercise and 2 h post-exercise in the Gln vs. Pla (1.35 ± 0.21 vs. 1.000 ± 0.000 and 1.65 ± 0.21 vs. 1.27 ± 0.40). Acute oral glutamine supplementation prevents an exercise-induced rise in intestinal permeability and suppresses NF-κB activation in peripheral blood mononuclear cells.
Evolving Intergroup Techniques for Conflict Resolution: An Israeli-Palestinian Pilot Workshop

The problem-solving workshop is an approach to international conflict resolution based on intervention at the intergroup level and designed to provide inputs into policy processes. The pilot workshop described there included Israeli and Palestinian participants, meeting with a team of social scientists who served as a third party. Some of the features of the workshop included use of separate preworkshop sessions with each party to focus on internal group processes; induction of communication marked by an analytic, problem approach to the conflict to replace the legalistic, conflict-expressive approach that generally characterizes communication among conflicting parties; process observations from an intergroup (rather than interpersonal) perspective, linking ongoing interactions to the dynamics of the intergroup conflict; and emphasis on symbolic issues and questions of national identity. Among the issues discussed are definition of the parties to the conflict, characteristics of participants, the context for communication, relationships between intragroup and intergroup processes, nature of the third party and types of interventions, and the relationship of changes manifested in the workshop to changes transferred outside of that setting.
Nostalgia and Degeneration: The Moral Economy of Drinking in Navajo Society

This article focuses on how some members of Navajo society use narratives regarding alcohol and drinking to comment on cultural degeneration and the decay of the traditional Navajo moral economy. These narratives drinking are seldom solely about alcohol but refer to a host of distinct yet interrelated concerns involving moral values, individual and collective identities, underdevelopment, imagined histories, psychic conflict, and social contention. This article sheds light on how evaluations of alcohol and drinking problems, as encapsulated in narratives of degeneration, fit into the overall context of contemporary Navajo society. Narratives of degeneration juxtapose a degenerate present to a nostalgic past and in the process direct moral censure toward two primary groups in Navajo society, namely, young people and others who drink to excess, [drinking, Native Americans, Navajo, narrative, alcohol]
BORN–INFELD–DE SITTER GRAVITY: COLD, ULTRA-COLD AND NARIAI BLACK HOLES

In this paper, we have presented interesting properties of the static charged Born–Infeld–de Sitter black hole. They can have timelike as well as spacelike singularities depending on the parameters of the theory. The degenerate black holes lead to cold, ultra-cold and Nariai black holes. The geometry of such black holes is discussed. A comparison is done with the Reissner–Nordstrom–de Sitter black holes.
Salesperson Stereotypes, Consumer Emotions, and their Impact on Information Processing:

This study examines salesperson stereotypes and their effect on the selling environment. After reviewing relevant literature, the authors advance a hierarchical structure of salesperson stereotype categories. Experimental results suggest that stereotypes influence consumer emotions, and these emotions then mediate the relationship between stereotype activation and subsequent consumer cognitions.
Electrostatically actuated metal-droplet microswitches integrated on CMOS chip

The dominance of surface tension over inertia in microscale and favorable scale effect for electrostatic actuation allow electrostatically driven metal-droplet systems practical. Because of such potential advantages as low contact resistance, naturally bistable operation, and high switch density, the liquid-metal droplet switch is an excellent candidate for reconfigurable circuit interconnections. Following earlier droplet microswitch examples and related studies of metal-droplet behavior, we report the first functioning droplet switch directly integrated on top of a functional CMOS circuit. While the surface tension dominance makes the droplet switches practical as a mechanical system and also brings bistability, it also requires a high electric field to move the droplet. We implement the concept of physical surface modification to lower the driving voltage to a value that a commercial CMOS process can provide. Unlike previous droplet switches, the reported device is planar-processed to allow the integration with the underlying CMOS circuits. The integrated switch is made functional by such provisions as self-limiting actuation and by optimizing the electrostatic force in the planar configuration and avoiding liquid-metal "flooding" into surface patterns. A fabrication process for low driving voltage and high compatibility is developed to integrate the droplet switch on the custom-developed CMOS chip. A packaging method adapted from well-established microelectronic packaging isolates the active switch space from the surrounding environment. Low driving voltage (as low as 15 V) and millisecond switching speed are achieved by the current on-chip device. While the current device uses ~150 mum droplets for demonstration, additional theoretical and experimental results indicate that further miniaturization would lead to smaller devices and lower operation voltage
Metabolome-Proteome Differentiation Coupled to Microbial Divergence

Tandem high-throughput proteomics and metabolomics were employed to functionally characterize natural micro- bial biofilm communities. Distinct molecular signatures exist for each analyzed sample. Deconvolution of the high-resolution molecular data demonstrates that identified proteins and detected metabolites exhibit organism-specific correlation patterns. These patterns are reflective of the functional differentiation of two bacterial species that share the same genus and that co-occur in the sampled microbial communities. Our analyses indicate that the two species have similar niche breadths and are not in strong competition with one another. IMPORTANCE Natural microbial assemblages represent dynamic consortia that exhibit extensive complexity at all levels. In the present study, we demonstrate that correlations between protein and metabolite abundances allow the deconvolution of com- plex molecular data sets into shared and organism-specific contingents. We demonstrate that evolutionary divergence is associ- ated with the restructuring of cellular metabolic networks, which in turn allows bacterial species to occupy distinct ecological niches. The apparent lack of interspecific competition may explain the extensive population-level genetic heterogeneity observed extensively within microbial communities. The reportedfindings have broad implications for the in-depth investigation of the ecology and evolution of distinct microbial community members and for leveraging the solution of cryptic metabolic processes in the future.
Improving Global Seismic Event Locations using Source-Receiver Reciprocity

The leading source of error in seismic event locations is travel-time perturbations caused by three-dimensional Earth structure. The reciprocity of travel times between sources and receivers provides a method for testing the effectiveness of empirical methods for improving event locations that rely on nearby calibration events of known location. We apply this approach to travel-time residuals obtained by Engdahl et al. (1998) for almost 100,000 teleseismic events. By analyzing the residual patterns at thousands of seismic stations of known location, we characterize the spatial coherence of station/event mislocation vectors. We find that, on average, calibration events are likely to improve locations only if they are located within 100–150 km of the target events. For 84 events of known location, we find that applying source-receiver reciprocity can significantly reduce location errors by correcting for the teleseismic residual pattern observed at stations close to the target events. These results have implications for efforts to improve event locations for nuclear explosion monitoring purposes.
Selection of cables and connectors for 100BaseTX Ethernet for defense/aerospace environment EMI compliance

100BaseTX Ethernet is a popular method of high-speed data transfer using copper wire in the residential, commercial and industrial environments. Through proper circuit design and printed wiring board layout, IEEE 802.3 100BaseTX Ethernet systems can be made to comply with the applicable FCC Part 15 class B radiated emissions requirements and the European Union's radiated and conducted immunity EMI compliance requirements using unshielded twisted pair wiring. Because of the tremendous off-the-shelf availability of hardware and software, there are many advantages to using 100BaseTX Ethernet on defense/aerospace platforms to quickly and cost effectively increase system capability. This paper provides methods of determining expected emissions and immunity with respect to defense/aerospace equipment EMI requirements when 100BaseTX Ethernet is used with various cable/connector systems. Data and analysis are presented for cable/connector system that will allow various defense/aerospace EMI requirements to be met.
A sequential dynamic pricing model and its applications

Consider a sequential dynamic pricing model where a seller sells a given stock to a random number of customers. Arriving one at a time, each customer will purchase one item if the product price is lower than her personal reservation price. The seller's objective is to post a potentially different price for each customer in order to maximize the expected total revenue. We formulate the seller's problem as a stochastic dynamic programming model, and develop an algorithm to compute the optimal policy. We then apply the results from this sequential dynamic pricing model to the case where customers arrive according to a continuous-time point process. In particular, we derive tight bounds for the optimal expected revenue, and develop an asymptotically optimal heuristic policy. © 2004 Wiley Periodicals, Inc. Naval Research Logistics, 2004.
Structural design for obtaining desired eigenfrequencies by using the topology and shape optimization method

Abstract A topology and shape optimization method is presented for structural eigenfrequency optimization problems using the concept of Optimal Material Distribution (OMD). First, a mean-eigenvalue corresponding to the multiple eigenfrequencies of a structure is defined. Three optimization problems are then considered for obtaining the desired eigenfrequencies using this mean-eigenvalue: maximization of the specified structural eigenfrequencies, maximization of the distances of the specified structural eigenfrequencies from a given frequency or frequencies, and optimization of the structure for obtaining prescribed eigenfrequencies. Several examples are presented to demonstrate the capability of this new technique which can be used to deal with a wide range of practical design problems for improving the dynamic nature of a structure.
EntomoModel: Understanding and Avoiding Performance Anomaly Manifestations

Subtle implementation errors or mis-configurations in complex Internet services may lead to performance degradations without causing failures. These undiscovered performance anomalies afflict many of today’s systems, causing violations of service-level agreements (SLAs), unnecessary resource over provisioning, or both. In this paper, we re-inserted realistic anomaly causes into a multi-tier Internet service architecture and studied their manifestations. We observed that each cause had certain workload and management parameters that were more likely to trigger manifestations, hinting that such parameters could be effective classifiers. This observation held even when anomaly causes manifested differently in combination than in isolation. Our study motivates EntomoModel, a framework for depicting performance anomaly manifestations. EntomoModel uses decision tree classification and a design-driven performance model to characterize the workload and management policy settings under which manifestations are likely. EntomoModel enables online system management that avoids anomaly manifestations by dynamically adjusting system management parameters. Our trace-driven evaluations show that manifestation avoidance based on EntomoModel, or entomophobic management, can reduce 98th percentile SLA violations by 67% compared to an anomaly oblivious adaptive approach. In a cloud computing scenario with elastic resource allocation, our approach uses less than half of the resources needed in static over-provisioning.
Highly linear InP phase modulator for high dynamic range RF/photonic links

The optical phase locked loop (OPLL) photonic integrated circuit (PIC) is a key element for the emerging linear coherent RF-photonic links. One of the main challenges for the OPLL-PIC is the nonlinearity of the Indium Phosphide (InP)-based phase modulator. In this paper, we report the experimental results from a multi-quantum well phase modulator fabricated on an InP substrate that is specially designed for the OPLL-PIC. The phase modulator shows low optical loss and good linearity performance. In particular, at a reverse bias voltage of 5.6 V, its phase IP3 and insertion loss per unit length are ∼2.8p/mm and 1.2 dB/mm, respectively.
Ion Exchange of Protons by Coinage Metals to Give Gold and Silver Encapsulation within a Pseudo‐D2d Distorted Face‐Capped Pd14 Cubic Kernel: [(μ14‐M)Pd22(CO)20(PEt3)8]+ (M=Au, Ag)

Heart of gold (or silver): The pseudo-D2d distorted MPd14 cubic kernel of [(μ14-M)Pd22(CO)20(PEt3)8](+) cations, with M = Au (1), Ag (2), has an encapsulated M atom (see picture; yellow) coordinated to eight cubic corner (black) and six face-capping Pd atoms (gray). Compounds 1 and 2 were obtained (28-60 % yields) from two-step/one-pot reactions of a Pd10 precursor with CF3CO2 H followed by coinage-metal ion exchange of protons.
Inflammatory bowel disease: Etiology and pathogenesis

The field of gastroenterology offers many challenges to both the clinician and the investigator, but few are as complex and enigmatic as inflammatory bowel disease (IBD). Crohn’s disease (CD) and ulcerative colitis (UC) have been known for well over one half a century, but why affected individuals spend their lives with a chronic inflammatory process that relentlessly destroys their bowel remains a mystery. Advances, although unequal in different areas, have been plentiful in the last decade when the combined power of cellular and molecular biology began to unveil the enigmas of IBD. No single agent or distinct mechanism is the sine qua non motive that explains all aspects of IBD, and several distinguishing factors are likely necessary to result in either CD or UC (Table 1). This review will attempt to discuss those that currently appear important.
Genetics of alcohol dehydrogenase and aldehyde dehydrogenase from Monodelphis domestica cornea: further evidence for identity of corneal aldehyde dehydrogenase with a major soluble protein.

A didelphid marsupial, the gray short-tailed opossum ( Monodelphis domestica ), was used as a model species to study the biochemical genetics of alcohol dehydrogenases (ADHs) and aldehyde dehydrogenase (ALDH) in corneal tissue. Isoelectric point variants of corneal ALDH (designated ALDH3) and a major soluble protein in corneal extracts were observed among eight families of animals used in studying the genetics of these proteins. Both phenotypes exhibited identical patterns following PAGE-IEF and were inherited in a normal Mendelian fashion, with two alleles at a single locus ( ALDH3 ) showing codominant expression. The data provided evidence for genetic identity of corneal ALDH with this major soluble protein, and supported biochemical evidence, recently reported for purified bovine corneal ALDH, that this enzyme constitutes a major portion of soluble corneal protein (Abedinia et al. 1990). Isoelectric point variants for corneal ADH were also observed, with patterns for the two major forms (ADH3 and ADH4) and one minor form (ADH5) being consistent with the presence of two ADH subunits (designated γ and δ), and variant phenotypes existing for the γ subunit. The genetics of this enzyme was studied in the eight families, and the results were consistent with codominant expression of two alleles at a single locus (designated ADH3 ). It is relevant that a major detoxification function has been proposed for corneal ADH and ALDH, in the oxidoreduction of peroxidic aldehydes induced by available oxygen and UV-B light (Holmes & VandeBerg, 1986 a ). In addition, a direct role for corneal ALDH as a UV-B photoreceptor in this anterior eye tissue has also been proposed (Abedinia et al. 1990).
Tool integration for flexible simulation of distributed algorithms

SUMMARY Over the last two decades, considerable research has been done in distributed operating systems, which can be attributed to faster processors and better communication technologies. A distributed operating system requires distributed algorithms to provide basic operating system functionality like mutual exclusion, deadlock detection, etc. A number of such algorithms have been proposed in the literature. Traditionally, these distributed algorithms have been presented in a theoretical way, with limited attempts to simulate actual working models. This paper discusses our experience in simulating distributed algorithms with the aid of some existing tools, including OPNET and Xplot. We discuss our efforts to define a basic model-based framework for rapid simulation and visualization, and illustrate how we used this framework to evaluate some classic algorithms. We have also shown how the performance of different algorithms can be compared based on some collected statistics. To keep the focus of this paper on the approach itself, and our experience with tool integration, we only discuss some relatively simple models. Yet, the approach can be applied to more complex algorithm specifications. Copyright  2001 John Wiley & Sons, Ltd.
Inventory technology: ‘ebb tides’, ‘flash floods’ and ‘whirlpools’

Abstract The development and implementation of inventory techniques are cyclic. For a long while, our inventory procedures in the USDA Forest Service have been rather stable. Now, given new information requirements and an onslaught of new technology, our needs, capabilities, and methodologies are rapidly changing. This paper reviews past (‘ebb tides’) and emerging techniques (‘flash floods’). It also lists some of the problems (‘whirlpools’) we will encounter in implementing the changes. While the paper addresses resource inventories within the USDA Forest Service, the potential and problems are applicable to the inventory of any ecosystem including the forested wetlands. Lastly, some thoughts for follow-up global actions are presented.
Feasibility of Matching Wind and Wave Energy Conversion for an Integrated Design Concept

Wave and wind modeling software were used to evaluate a combined resource availability of wave and wind along the California coast. A potential for an integrated wave and wind platform was evaluated and found that the resource increases in the northern direction. An integrated platform for wave and wind was proposed and modelled with estimates of implementation cost. The constructed platform was rated at 584 kW producing over 4,500,000 kWh/yr. This would lead to a yearly income of $599,022 resulting in an 8.8 year simple payback at 2014 currency value. This cost can change depending on several aspects such as the design details of the wind turbines as well as the wave platform, and the rate at which electricity can be sold.Copyright © 2015 by ASME
Chapter 1 Aspartyl proteinases

Publisher Summary The aspartyl proteinases represent one of the four known main classes of enzymes that act at interior peptide bonds of proteins and oligopeptides (endopeptidases); the other classes are denoted serine proteinases, cysteine proteinases, and metalloproteinases. Because of their optimal action at pH 1.5–5, the aspartyl proteinases were previously named “acid proteinases.” With the recognition that particular carboxyl groups in these enzymes are essential for catalysis, the term “carboxyl proteinase” was then used. The identification of these groups as belonging to aspartyl residues in several members of this class has led to the currently-preferred terminology. The term “aspartyl proteinase” is more appropriate than “acid proteinase” because several enzymes now known to belong to this class act optimally on their substrates near pH 7. Pepsin is considered as the prototype of the unorganized ferments as distinct from the organized ferments responsible for such processes as the fermentation of sugar by yeast.
Conceptions of Community: Past and Present

The concept of community in sociology has its origin in Ferdinand F. Tonnies’ theory of Gemeinschaft and Gesellschaft (Community and Society) in 1887 (Loomis, 1957; Sorokin, 1940). But the idea of community was evident much earlier in Confucius’ theory of the five fundamental relationships (Bahm, 1992). Confucius contrasted Small Tranquility with Great Similarity in the same way Tonnies compared the mentality of Gemeinschaft with its opposite Gesellschaft. Contrasting societal typologies were evident in the work of Plato (the Ideal Republic versus the Oligarchic Society), Aristotle, and Cicero’s ideas of true and false friendship, St. Augustine’s concepts of the City of God versus the Society of Man, and many other social thinkers before and after Tonnies.
It is the Moral Obligation of the State to Provide Basic Health Care for its Citizens

In this paper, I present a case for universal health care in the United States by arguing that government policies related to employee health care, payment system and regulation on health care insurance are the main reasons that contribute to skyrocketing cost of health care. I also argue that the health of a work force whose earnings are the main drivers for tax revenue is crucial to the well being of a nation. A universal health care system is also one that will create a fair playing field for all its citizens.
Abstract 330: Endothelial JNK Is Critically Required for Native Collateral Artery Development

Arterial occlusive diseases are major causes of morbidity and mortality in industrialized countries and represent a huge economic burden. The extent of the native collateral circulation is considered to be the most important determinant of the magnitude of tissue damage and subsequent functional impairment that ensues following an arterial occlusive event. Therefore, understanding the mechanisms responsible for collateral artery development may provide avenues for the design of strategies to enhance the collateral circulation in patients at risk for arterial occlusive diseases. Here, we identify a critical requirement for cJun-NH2-Terminal Kinase (JNK) in collateral artery development. Indeed, using immunofluorescence, microfil perfusion and three dimensional high resolution micro computed tomography (μCT) imaging techniques, we demonstrate that mice with compound JNK-deficiency in the vascular endothelium display abnormal collateral arteries, which are unable to restore blood perfusion following occlusion of a major artery leading to severe tissue necrosis in animal models of femoral and coronary artery occlusion. Furthermore, employing constitutive and inducible conditional deletion strategies, we demonstrate that JNK acts during the initial development of collateral arteries to ensure proper patterning and connectivity, but is, for the most part, dispensable for angiogenic and arteriogenic responses in adult mice. The defects in collateral artery development may reflect an enhanced sensitivity of JNK-deficient endothelial cells to cell death in specific contexts. This study introduces JNK as a major regulator of vascular development and highlights the crucial importance of the collateral circulation as the main defining factor in reducing the severity of tissue damage and functional impairment following arterial occlusive events.
Structure-based prediction of drug side effects using a novel classification algorithm

In silico prediction of drug side-effects in early stage of drug development is becoming more popular now days, which reduces the time for drug design and drug development costs. In this paper, we propose an ensemble approach to predict drug side-effects of drug molecules based on their chemical structure. We applied our approach to 1385 side-effects in the SIDER database for 888 drugs. Results show that our approach outperformed previous approaches and standard classifiers. Furthermore, we apply our method to a number of uncharacterised drug molecules in DrugBank database and predict their side-effects for future usage. Results from various sources confirm that our method is able to predict the side-effects for uncharacterised drugs. Finally, we use our models to identify key chemical substructures that may cause different side-effects. Therefore this method can be useful to predict side-effects in drug design in an early stage to reduce experimental cost and time.
Developmental Biology of the Leafhopper, Scaphytopius nitridus (Homoptera: Cicadellidae), with Notes on Distribution, Hosts, and Interspecific Breeding

The developmental biology of Scaphytopius nitridus DeLong, a vector of Spiroplasma citri, the causative organism of stubborn disease of citrus in California and Arizona, was studied in the greenhouse. Nymphs required 40.02 days or 15,460 heat units to complete development. The mean number of nymphs produced per female was 113.6; the maximum was 353. Adults produced progeny up to 77 days and lived as long as 156 days. Population of S. nitridus and S. californiensis Hepner failed to interbreed, indicating that the two species are distinct. New distribution and host records are provided.
Seasonal Shifts in Thyroid Function in the Cotton Rat (Sigmodon hispidus)

Cotton rats ( Sigmodon hispidus ) were captured in southwestern Missouri in summer and winter, several thyroid parameters were measured, and utilization rates of thyroxine (T4) and triiodothyronine (T3) were calculated. In addition, resting metabolic rates were measured seasonally. Animals captured in winter had significantly lower concentrations of serum T4 and greater volumes of distribution than summer-caught rats. The resultant utilization of T4 was lower in winter, while the thyroxine efficiency (oxygen consumed per thyroxine used) was greater. The latter suggests an improved T4-to-T3 deiodination and is consistent with the markedly higher serum T3 observed in winter. Winter cotton rats also had shorter T3 half-lives, greater volumes of T3 distribution, and higher T3 utilization rates. Because resting metabolism was not significantly higher, it is concluded that, while winter may stimulate an increased T4-to-T3 deiodination, the excess T3 is removed from circulation before affecting metabolic rate.
THE THYMUS; CURRENT CONCEPTS.

Recent experimental studies have related the thymus and other “central lymphoid tissue” to the ontogenetic development of immunologic capacity, to lymphomagenesis, and to maintenance of adaptive immunity in mammals. Clinically the thymus has been clearly implicated in myasthenia gravis, and a link between the thymus and other auto-immune diseases has been suggested. A high incidence of lymphocytic and reticular malignancy has been observed in certain diseases marked by immunologic deficiency, namely, ataxia-telangiectasia, congenital sex-linked recessive agammaglobulinemia, and also primary acquired agammaglobulinemia.
Effects of different irrigation methods on grain quality of japonica rice in Huanghuai District of China

To clarify the effects of different irrigation treatments in paddy field on rice gain quality,three irrigation methods,moistening irrigation( 0 cm water depth),shallow water irrigation( 1-2cm water depth) and deep water irrigation( 5- 6 cm water depth),were established under field condition. In the experiment,rice gain physiochemical parameters including grain length,width,area and perimeter,amylose and protein contents and RVA profile characteristics of 3 rice cultivars( Shengdao 14,Shengdao 2572,Shengdao 18) with excellent quality were evaluated. Results showed that grain length,area and perimeter were significantly enhanced under shallow water irrigation when compared with the other two irrigation methods,while chalky rice rate and chalkiness performed conversely. Of all irrigation methods,moistening irrigation produced the highest peak viscosity and hot viscosity values,but deep irrigation produced the lowest peak viscosity,hot viscosity and final viscosity values. The breakdown,setback,consistence values and amylose content of rice grains of 3 varieties displayed disparate responses to the 3 irrigation treatments,largely due to the difference of genotypes. Shengdao 14 had the best eating quality under moistening irrigation and Shengdao 18 under deep irrigation. Correlation analysis indicated that RVA profile parameters were significantly related with apparent and physiochemical parameters. The relationship between apparent and eating quality was quantified by regression and pathway analyses,suggesting that grain area,perimeter and the ratio of grain length to width were the main factors controlling breakdown,the ratio of grain length to width was for setback,and grain protein and amylose contents for consistence.
Multivariate evaluation of criteria for differentiating cut marks created from steel and lithic implements

Abstract The identification of cut marks has been integral to expanding the understanding of hominin behavior ranging from the origins of meat consumption to the role of human hunting in megafaunal extinctions and the timing of the peopling of the Americas. Paleoanthropological and archaeological research demonstrates cut mark placement can be indicative of activity, but cut mark morphology is more complex and influenced by multiple variables such as raw material, tool shape, and bone density. Significant overlap in the ‘classic’ features of cut marks, such as V-shaped cross-sections, has also been recognized in numerous processes including carnivore gnawing and trampling. Before researchers can refer to modified animal remains as proxies for a hominin presence, diagnostic patterns representative of past human behavior in the archaeological record must first be identified and distinguished from modern cultural processes. This paper develops an empirical multivariate and probabilistic approach for differentiating cut marks created by lithics from those by steel. The results identify no single diagnostic attribute of cut marks produced by lithics. However, an approach which includes excavation history, stratigraphic context, location, orientation, and mark color significantly improve the likelihood with which cut marks are identified accurately.
Successful implantation of a deep brain stimulator for essential tremor in a patient with a preexisting cochlear implant: surgical technique: technical case report.

Objective Deep brain stimulation (DBS) has become routine for the treatment of Parkinson's disease and essential tremor. Because both of these disorders are common in patients older than the age of 60, neurosurgeons are likely to encounter increasing numbers of patients who require DBS surgery but who already have another electronic medical implant such as a cardiac pacemaker/defibrillator or intrathecal infusion pump, raising the concern that one device might interfere with the performance of the other. Clinical presentation Herein we report a modification of surgical technique resulting in the successful use of thalamic DBS to treat disabling essential tremor in a man with a previously implanted cochlear implant. Intervention and technique The presence of the cochlear implant necessitated a number of modifications to our standard surgical technique including surgical removal of the subgaleal magnet that holds the receiver to the scalp and the use of computed tomography instead of magnetic resonance imaging to target the thalamus. More than a year after surgery, the patient is enjoying continued tremor suppression and an enhanced quality of life. The presence of the DBS device has not interfered with the proper functioning of his cochlear implant. Conclusion DBS can be used successfully in patients with a previously implanted cochlear implant. The operating neurosurgeon should be aware of the limitations of intraoperative imaging and the need to coordinate with an otologic surgeon for maximum patient benefit.
Abstract 3726: Predicting cellular response to small molecule Mcl-1 antagonists

Myeloid cell leukemia -1 (Mcl-1) is an anti-apoptotic member of the Bcl-2 protein family which many cancers overexpress and depend on for survival. Mcl-1 inhibits apoptosis by binding to Bax and Bak, inhibiting the effectors of apoptosis from oligomerizing at the outer membrane of the mitochondria to promote cell death. Due to its role in cancer and resistance development to conventional chemotherapies, efforts to potently and specifically target MCL-1 have been ongoing. We have discovered novel small molecule inhibitors that selectively disrupt Mcl-1-Bim binding in the sub-nanomolar range. Anti-proliferative activities of our leading Mcl-1 inhibitors were assessed in a panel of hematological and solid cancer cell lines. We found that our compound promoted apoptosis in a subset of cell lines tested. As there was a variable response, we used BH3 profiling, which is a functional assay that rapidly measures dependence on any of the anti-apoptotic Bcl-2 family proteins for an individual sample to predict in vitro sensitivity to our Mcl-1 antagonists. Using the MS1 peptide, a known potent and selective Mcl-1 binder as a positive control in the BH3 profiling assay, we found a correlation between the BH3 profiling measurement of anti-apoptotic dependence to Mcl-1 and increased cytotoxicity caused by our compounds. These studies demonstrate that our compounds promote apoptosis through a selective inhibition of Mcl-1 mechanism of action and supports further investigation of our compounds in in vivo models of cancer. Citation Format: Leah Hogdal, John Sensintaffar, Allison Arnold, Craig Goodwin, Zhiguo Bian, Subrata Shaw, Chris Tarr, Taekyu Lee, Edward Olejniczak, Stephen Fesik. Predicting cellular response to small molecule Mcl-1 antagonists. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3726.
Forest clearcutting effects on trace metal concentrations: spatial patterns in soil solutions and streams

Increased concentrations of solutes in drainage waters following forest clearcutting may affect downstream water quality. The objective of this study was to evaluate some of the processes regulating concentrations of trace metals and Fe in soil solutions and streamwater in a clearcut watershed by determining changes in metal release by soil horizon, stand vegetation and elevation. Commercial whole-tree harvesting of a watershed at the Hubbard Brook Experimental Forest, NH, U.S.A. resulted in increased loss of NO inf3 sup− from the study watershed. This N0 inf3 sup− loss resulted in acidification of soil solutions, which was associated with release of Mn and Zn from mineral soil to soil solutions and streamwater. Significant correlations of Pb and Fe with dissolved organic C (DOC) suggested that mobilization of these metals was linked to DOC transfer. However, there was little evidence of increased release of DOC, Fe, or Pb following the whole-tree harvest, except in a high elevation spruce-fir zone with shallow soils.
Validation of wax deposition models with recent laboratory scale flow loop experimental data

Abstract Experimental data at various conditions are important for improving wax deposition prediction and upscaling efforts. This study consolidates several single-phase wax deposition data acquired in recent years and validates several wax deposition models for a comprehensive range of experimental conditions. The film mass transfer (FMT), equilibrium (EM), Matzain (1999), and Venkatesan (2004) models were tested against 70 experimental data points (19 sets of initial operating conditions), obtained with four different oils and flow loop facilities. Uncertainty propagation analysis was performed to estimate reasonable ranges of error in the prediction that may be caused by fluid properties or standard correlations instead of the model formulation itself. The FMT model regularly over-predicts the deposition rate, which is consistent with previous theoretical, experimental, and visualization studies. It is observed that EM does not necessarily serves as the lower bound of deposition rate, suggesting that some form of flux reduction effects may exist. Sherwood number analysis was performed to validate conclusions from FMT and EM model assessment. A fix set of shear coefficient values in Venketasan's model is not sufficient to achieve acceptable accuracy in general, indicating that the shear coefficients are likely to be oil and flow conditions dependent. Matzain's model delivers relatively superior performance on deposit wax mass and flux predictions among the four models, although it is still unable to predict aging mechanistically and the deposition trends as a whole. In conclusion, more mechanistically rigorous wax deposition models and experimental data are still needed.
Repeated sedimentation and exposure of glacial Lake Missoula sediments: A lake-level history at Garden Gulch, Montana, USA

Abstract Glaciolacustrine sediments record lake transgression, regression, and subaerial modification of the silty lake-bottom of glacial Lake Missoula in the Clark Fork River valley. The sequence preserved at Garden Gulch, MT documents lake-level fluctuations at >65% of its full-pool volume. Twelve sedimentary cycles fine upwards from (1) very fine-grained sandy silt to (2) silt with climbing ripples to (3) rhythmically laminated silt and some clay. The cycles are fine-grained turbidites capped locally by thin layers of angular gravel derived from local bedrock outcrops. The gravels appear to be the toes of mass wasting lobes carried onto the exposed lakebed surface during repeated lake-level lowerings. Periglacial wedges, small rotational faults, involutions, and clastic dikes deform the tops of eleven cycles. The wedges are 10–30 cm wide, penetrate 30–70 cm deep, are spaced The lowest five cycles are thicker and display more periglacial modification at their tops than the upper seven cycles. The Garden Gulch section may represent as few as seven and as many as twelve substantial fillings and partial to complete drainings of glacial Lake Missoula.
Weighted Ensemble Simulation: Review of Methodology, Applications, and Software

The weighted ensemble (WE) methodology orchestrates quasi-independent parallel simulations run with intermittent communication that can enhance sampling of rare events such as protein conformational changes, folding, and binding. The WE strategy can achieve superlinear scaling—the unbiased estimation of key observables such as rate constants and equilibrium state populations to greater precision than would be possible with ordinary parallel simulation. WE software can be used to control any dynamics engine, such as standard molecular dynamics and cell-modeling packages. This article reviews the theoretical basis of WE and goes on to describe successful applications to a number of complex biological processes—protein conformational transitions, (un)binding, and assembly processes, as well as cell-scale processes in systems biology. We furthermore discuss the challenges that need to be overcome in the next phase of WE methodological development. Overall, the combined advances in WE methodology and software ...
The Missing Self in Scientific Psychiatry

Various traditions in mental health care, such as phenomenological, and existential and cognitive-behavioral psychotherapy, implicitly or explicitly acknowledge that a disruption of the self, or the person, or the agent (often using these three concepts synonymously) is among the common denominators of different mental disorders. They often emphasize the importance of understanding patients as reasonsresponsive, in their full mental health relevant complexity, if their mental disorder is to be treated successfully. The centrality of the concept of the self is not mirrored in the mainstream scientific approaches in psychiatry however; the self has rarely been considered as the object of scientific research, the empirical investigation of which might yield successful explanations of and interventions in mental disorders. Thus, even though self-related phenomena are clinically relevant in so far as they give important information about a mental disorder to the clinician and help the development of effective interventions, they are not considered among the scientifically relevant properties of mental disorders. Leaving the self-related phenomena out of the scientific research on mental disorders can be attributed to the presupposition that the self is not empirically tractable and its use will hinder psychiatry’s goal to be scientific. In this paper, taking issue with this, I argue the self is empirically tractable, and its use as a target of research will not hinder psychiatry’s scientific commitments.