Miracle-dz/UniFAR-FTUs huggingface dataset:
CURRENT AND EXPERIMENTAL THERAPEUTICS FOR THE TREATMENT OF OPIOID ADDICTION

Currently, numerous effective pharmacologic and behavioral therapies are available for the treatment of opioid addiction, and these two types of therapies often are combined to optimize patient management. Newer therapeutic options may take various forms. For example, methadone maintenance is an established treatment modality, whereas the use of buprenorphine and naloxone in an office-based setting represents a new variation on that theme. Clonidine has been used extensively to ameliorate opioid withdrawal signs, whereas lofexidine is a structural analogue that appears to have less hypotensive and sedating effects. The depot dosage form of naltrexone, currently under development, may increase compliance with a medication that has been an effective opioid antagonist but that has been underused secondary to patient nonacceptance. In almost every treatment episode using pharmacotherapy, it is combined with some type of psychosocial or behavioral treatment. Recent research has documented the value of these additional treatments and has provided insight into the ones that are the most effective. This chapter reviews current and experimental treatments for opioid addiction with an emphasis on some of the newer, more promising, and interesting therapies.
MOOCs: striking the right balance between facilitation and self-determination

Recent research suggests that a growing proportion of formal learning occurs outside formal educational settings, where information and learning opportunities are mediated by technology. The rise of massive open online courses (MOOCs) in the last few years bears witness to this phenomenon. This contribution considers whether MOOCs afford a collaborative environment in which participants can develop the necessary literacy skills to become successful self-directed learners and members of online communities. It also discusses the extent to which self-determination and participatory literacy might be relevant for success in different types of MOOCs. The paper draws on data from OT12, an 8-week MOOC on open translation tools and practices run in 2012 by the Department of Languages of The Open University in the United Kingdom. The data consist of pre- and post-course surveys covering learners' backgrounds and prior experience of translation, expectations and challenges envisaged, and evaluation of outcomes. The authors conclude that to conceive of MOOCs as environments where individuals coalesce around a common endeavor is to raise a series of under-explored challenges. For organizers, the challenge lies in learning design and facilitation, and the extent to which their assumptions about the participants match the learners' capabilities. For learners, the challenge rests in self-determination and participatory literacy skills.
The optimization of auxiliary poles of IPM synchronous machine

The interior permanent magnet (IPM) machine, which enjoys advantages such as high efficiency and torque, is widely used not only in home application like air conditioners but also in electric vehicles. Its leakage flux is bigger than surface mounted permanent magnet (SPM), however, because the magnetization direction of permanent magnet is plumb to axes of air gap flux and far away from air gap. In order to reduce leakage flux and improve air gap flux density, we may add auxiliary poles in rotor structure. This paper adopts the vector magnetism potential to calculate machines field, and aim at model of 4 kinds, compare the relation between leakage flux of permanent magnet beside the shaft and equivalent air gap when auxiliary poles are existent and non-existent, respectively. Then, discusses the influence of auxiliary poles in different positions on air gap flux density when pole pairs are different, point out placement position of auxiliary poles and optimizes thickness of rare earth magnet in that position. At same time, the paper analyzes the influence of the thickness of auxiliary poles on the air gap flux density as pole pairs vary
Practically realizable digital transmission significantly below the Nyquist bandwidth

A practically realizable digital signaling scheme is proposed that requires a bandwidth significantly less than the Nyquist limit and at the same time achieves the same asymptotic performance as memoryless pulse-amplitude modulation (PAM). A three-step iterative procedure for constructing such schemes is presented, and examples that occupy down to about 60% of the Nyquist bandwidth are demonstrated using this simple procedure. A practical receiver structure using an adaptive breath-first trellis search algorithm is also discussed. <<ETX>>
Involuntary Monitoring of Sound Signals in Noise Is Reflected in the Human Auditory Evoked N1m Response

Constant sound sequencing as operationalized by repeated stimulation with tones of the same frequency has multiple effects. On the one hand, it activates mechanisms of habituation and refractoriness, which are reflected in the decrease of response amplitude of evoked responses. On the other hand, the constant sequencing acts as spectral cueing, resulting in tones being detected faster and more accurately. With the present study, by means of magnetoencephalography, we investigated the impact of repeated tone stimulation on the N1m auditory evoked fields, while listeners were distracted from the test sounds. We stimulated subjects with trains of either four tones of the same frequency, or with trains of randomly assigned frequencies. The trains were presented either in a silent or in a noisy background. In silence, the patterns of source strength decline originating from repeated stimulation suggested both, refractoriness as well as habituation as underlying mechanisms. In noise, in contrast, there was no indication of source strength decline. Furthermore, we found facilitating effects of constant sequencing regarding the detection of the single tones as indexed by a shortening of N1m latency. We interpret our findings as a correlate of a bottom-up mechanism that is constantly monitoring the incoming auditory information, even when voluntary attention is directed to a different modality.
Efficient Verification of Distributed Protocols Using Stateful Model Checking

This paper presents efficient model checking of distributed software. Key to the achieved efficiency is a novel stateful model checking strategy that is based on the decomposition of states into a relevant and an auxiliary part. We formally show this strategy to be sound, complete, and terminating for general finite-state systems. As a case study, we implement the proposed strategy within Basset/MP-Basset, a model checker for message-passing Java programs. Our evaluation with actual deployed fault-tolerant message-passing protocols shows that the proposed stateful optimization is able to reduce model checking time and memory by up to 69% compared to the naive stateful search, and 39% compared to partial-order reduction.
Numerical modeling of the mechanical response of basalt plain woven composites under high strain rate compression

The compression behaviors of 2D plain woven basalt/vinyl ester resin composites along the thickness direction under high strain rates have been investigated experimentally and by use of finite element analyses. The compression stress–strain curves, compressive damage, and rate sensitivity of the compressive behaviors was obtained experimentally. The dynamic responses including the compression stress–strain curves, compression damages, and energy absorptions of the plain woven composite samples were predicted based on finite element analyses at the microstructure level. From the finite element analyses results, it was concluded that the plain woven fabric structure and the rate dependent behaviors of the matrix were the key factors which affect the strain rate sensitivity of the compressive properties. The plain woven fabric structure distortion, instability of woven architecture, and matrix crack were the main failure modes of the plain woven composites under high strain rate compression. The compressive behaviors of plain woven composite could be improved with better design of the woven fabric structures and superior matrix properties.
A consensus-based criterion standard for trauma center need

BACKGROUND In civilian trauma care, field triage is the process applied by prehospital care providers to identify patients who are likely to have severe injuries and immediately need the resources of a trauma center. Studies of the efficacy of field triage have used various measures to define trauma center need because no “criterion standard” exists, making cross-study comparisons difficult. This study aimed to develop a consensus-based functional criterion standard definition of trauma center need. METHODS Local and national experts were recruited for participation. Blinded key informant interviews were conducted in order of availability until no new themes emerged. Themes identified during the interviews were used to develop a Modified Delphi survey, which was electronically delivered via Survey Monkey. The trauma center need criteria were refined iteratively based on participant responses. Participants completed additional surveys until there was at least 80% agreement for each criterion. RESULTS Fourteen experts were recruited. Five participated in key informant interviews. A Modified Delphi survey was administered five times (four modifications based on the expert’s responses). After the fifth round, there was at least 82% agreement on each criterion. The final definition included 10 time-specific indicators: major surgery, advanced airway, blood products, admission for spinal cord injury, thoracotomy, pericardiocentesis, cesarean delivery, intracranial pressure monitoring, interventional radiology, and in-hospital death. CONCLUSION We developed a consensus-based functional criterion standard definition of needing the resources of a trauma center, which may help to standardize field triage research and quality assurance in trauma systems as well as allow for cross study comparisons.
Depletion of cellular brassinolide decreases embryo production and disrupts the architecture of the apical meristems in Brassica napus microspore-derived embryos

Exogenous applications of brassinolide (BL) increased the number and quality of microspore-derived embryos (MDEs) whereas treatments with brassinazole (BrZ), a BL biosynthetic inhibitor, had the opposite effect. At the optimal concentration (4×10−6 M) BrZ decreased both embryo yield and conversion to less than half the value of control embryos. Metabolic studies revealed that BL levels had profound effects on glutathione and ascorbate metabolism by altering the amounts of their reduced forms (ASC and GSH) and oxidized forms [dehydroascorbate (DHA), ascorbate free radicals (AFRs), and GSSG]. Applications of BL switched the glutathione and ascorbate pools towards the oxidized forms, thereby lowering the ASC/ASC+DHA+AFR and GSH/GSH+GSSG ratios. These changes were ascribed to the ability of BL to increase the activity of ascorbate peroxidase (APX) and decrease that of glutathione reductase (GR). This trend was reversed in a BL-depleted environment, effected by BrZ applications. These metabolic alterations were associated with changes in embryo structure and performance. BL-treated MDEs developed zygotic-like shoot apical meristems (SAMs) whereas embryos treated with BrZ developed abnormal meristems. In the presence of BrZ, embryos either lacked a visible SAM, or formed SAMs in which the meristematic cells showed signs of differentiation, such as vacuolation and storage product accumulation. These abnormalities were accompanied by the lack or misexpression of three meristem marker genes isolated from Brassica napus (denoted as BnSTM, BnCLV1, and BnZLL-1) homologous to the Arabidopsis SHOOTMERISTEMLESS (STM), CLAVATA 1 (CLV1), and ZWILLE (ZLL). The expression of BnSTM and BnCLV1 increased after a few days in cultures in embryos treated with BL whereas an opposite tendency was observed with applications of BrZ. Compared with control embryos where these two genes exhibited abnormal localization patterns, BnSTM and BnCLV1 always localized throughout the subapical domains of BL-treated embryos in a zygotic-like fashion. Expression of both genes was often lost in the SAM of BrZ-treated embryos. The results suggest that maintenance of cellular BL levels is required to modulate the ascorbate and glutathione redox status during embryogenesis to ensure proper development of the embryos and formation of functional apical meristems.
Structural Basis for Activation and Inhibition of Class I Phosphoinositide 3-Kinases

The regulatory interactions between PI3Ks and their binding partners could be exploited for therapies. Phosphoinositide 3-kinases (PI3Ks) phosphorylate a hydroxyl group on phosphoinositide lipids. The 3-phosphorylated inositol lipids act as membrane-resident second messengers, recruiting downstream signaling components that control cell growth, proliferation, differentiation, survival, and motility. The best studied of the PI3Ks, the class I enzymes, are heterodimers with a catalytic and a regulatory subunit and have been implicated in many human diseases. Class I PI3Ks can be stimulated downstream of receptor tyrosine kinases and heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors as well as small G proteins of the Ras superfamily. Both the catalytic and regulatory subunits have a multidomain organization. Crystal structures, biochemical analysis, and oncogenic mutations in PI3Ks have shown that interdomain interactions are not static but undergo regulated conformational cycles, resulting in enzyme activation or inhibition. This Review, which contains 7 figures and 104 references, highlights the molecular details of how their regulatory partners selectively inhibit and activate PI3K isoforms. Phosphoinositide 3-kinases (PI3Ks) are implicated in a broad spectrum of cellular activities, such as growth, proliferation, differentiation, migration, and metabolism. Activation of class I PI3Ks by mutation or overexpression correlates with the development and maintenance of various human cancers. These PI3Ks are heterodimers, and the activity of the catalytic subunits is tightly controlled by the associated regulatory subunits. Although the same p85 regulatory subunits associate with all class IA PI3Ks, the functional outcome depends on the isotype of the catalytic subunit. New PI3K partners that affect the signaling by the PI3K heterodimers have been uncovered, including phosphate and tensin homolog (PTEN), cyclic adenosine monophosphate–dependent protein kinase (PKA), and nonstructural protein 1. Interactions with PI3K regulators modulate the intrinsic membrane affinity and either the rate of phosphoryl transfer or product release. Crystal structures for the class I and class III PI3Ks in complexes with associated regulators and inhibitors have contributed to developing isoform-specific inhibitors and have shed light on the numerous regulatory mechanisms controlling PI3K activation and inhibition.
New tests of cumulative prospect theory and the priority heuristic: Probability-outcome tradeoff with branch splitting

Previous tests of cumulative prospect theory (CPT) and of the priority heuristic (PH) found evidence contradicting these two models of risky decision making. However, those tests were criticized because they had characteristics that might “trigger” use of other heuristics. This paper presents new tests that avoid those characteristics. Expected values of the gambles are nearly equal in each choice. In addition, if a person followed expected value (EV), expected utility (EU), CPT, or PH in these tests, she would shift her preferences in the same direction as shifts in EV or EU. In contrast, the transfer of attention exchange model (TAX) and a similarity model predict that people will reverse preferences in the opposite direction. Results contradict the PH, even when PH is modified to include a preliminary similarity evaluation using the PH parameters. New tests of probability-consequence interaction were also conducted. Strong interactions were observed, contrary to PH. These results add to the growing bodies of evidence showing that neither CPT nor PH is an accurate description of risky decision making.
Study on the Relationship Between Crystalline Structures and Physical Properties of Polyamide‐6

A small amount of styrene‐maleic anhydride (SMA) copolymer was blended with polyamide‐6 (PA‐6). Polarized‐light microscope (PLM) observation and small angle light scattering (SALS) tests showed that the spherulite size of PA‐6/SMA was smaller than that of PA‐6. Differential scanning calorimetry (DSC) study showed that the crystallization process changed from thermal nucleation for PA‐6 to athermal nucleation for PA‐6/SMA. It was found in wide angle X‐ray diffraction (WAXD) tests that PA‐6/SMA tended to form α form crystals. Due to the smaller spherulite size and the stable crystal form, PA‐6/SMA had a lower water absorption rate, lower equilibrium water absorption, higher impact strength, and higher tensile strength than did virgin PA‐6. In addition, PA‐6/SMA showed higher melt elasticity and viscosity in rheology tests.
Therapeutics , Targets , and Chemical Biology Contribution of Bcl-2 Phosphorylation to Bak Binding and Drug Resistance

Bcl-2 is phosphorylated on Ser after treatment of cells with spindle poisons. On the basis of effects observed in cells overexpressing Bcl-2 S70E or S70A mutants, various studies have concluded that Ser phosphorylation either enhances or diminishes Bcl-2 function. In the present study, the ability of phosphorylated Bcl-2, as well as the S70E and S70Amutants, to bind and neutralize proapoptotic Bcl-2 family members under cell-free conditions and in intact cells was examined in an attempt to resolve this controversy. Surface plasmon resonance indicated that phosphorylated Bcl-2, Bcl-2 S70E, and Bcl-2 S70A exhibit enhanced binding to Bim and Bak compared with unmodified Bcl-2. This enhanced binding reflected a readily detectable conformation change in the loop domain of Bcl-2. Furthermore, Bcl-2 S70E and S70A bound more Bak and Bim than wild-type Bcl-2 in pull-downs and afforded greater protection against several chemotherapeutic agents. Importantly, binding of endogenous Bcl-2 to Bim also increased during mitosis, when Bcl-2 is endogenously phosphorylated, and disruption of this mitotic Bcl-2/Bim binding with navitoclax or ABT-199, like Bcl-2 downregulation, enhanced the cytotoxicity of paclitaxel. Collectively, these results provide not only a mechanistic basis for the enhanced antiapoptotic activity of phosphorylated Bcl-2, but also an explanation for the ability of BH3 mimetics to enhance taxane sensitivity. Cancer Res; 73(23); 6998–7008. 2013 AACR.
Cells and Humoral Immunity in Atherosclerosis

Atherosclerosis is a chronic inflammatory disease of largeand medium-sized arteries. It is characterized by the deposition and trapping of low-density lipoproteins (LDLs) in the artery wall, which then undergo a variety of changes, both enzymatic and nonenzymatic, that lead to a cascade of inflammatory responses followed by the recruitment of mostly macrophages and T cells. The accumulation of LDL in the subendothelial space makes it susceptible to oxidation by various processes, and the resultant formation of oxidized LDL (OxLDL) has been suggested to be the key event in driving the subsequent inflammation that characterizes atherosclerosis. Infiltrating macrophages take up OxLDL via scavenger receptors leading to the formation of lipid-laden foam cells, which are the hallmark cells of atherosclerotic lesions. With plaque progression, many foam cells undergo apoptosis resulting in the formation of an acellular necrotic core that is full of lipid gruel and cellular debris. Once the fibrous cap covering the necrotic core erodes or ruptures, allowing contact between the exposed material and the circulating coagulation system, thrombus formation is triggered, resulting in clinical events such as stroke and myocardial infarction, which are leading causes of death globally. Inflammation is the response of the immune system to the presence of exogenous and endogenous antigens, and it is now widely accepted that immune mechanisms are involved in all phases of lesion development. However, knowledge Review
NEURAL NETWORK MODELING OF LAKE SURFACE CHLOROPHYLL AND SEDIMENT CONTENT FROM LANDSAT TM IMAGERY

Concentrations of chlorophyll and suspended sediment are two important optically active parameters of inland water quality. In the open ocean, these two parameters can be effectively quantified by empirical algorithms relating remote sensor radiances to surface concentrations. In inland waters, however, the task becomes difficult due to the presence of suspended sediment and dissolved organic matters in high concentrations, often varying independently of each other and overwhelming the signature of chlorophyll. Thus, the transfer function becomes non-linear in nature. Moreover, broad band sensors have to be used in inland waters as the present aquatic satellite sensors lack adequate spatial resolution for monitoring in these waters. In the process, conventional algorithms fail to estimate the water quality parameters effectively. Neural networks has been regarded as a relatively simpler tool to implement with proven success in modeling various nonlinear geophysical transfer functions. In this study, back-propagation neural network is used to model the transfer function between chlorophyll concentration and suspended solid, and sensor-received radiances at the first four bands of LandsatTM. Study area is lake Kasumigaura of Japan, a shallow eutrophic lake with heavy sedimentation. Neural network with only one hidden layer could model both the water quality parameters better than conventional regression techniques from LandsatTM imagery. Root Mean Square Errors(RMSE) in estimating chlorophyll-a were 1. 53μg/l(R 2 : 0.93) and 4. 39μg/l(R 2 : 0.31) for neural networks and regression respectively. In estimating suspended sediments, RMSE for regression was 1.47mg/l(R 2 :0.92) while for neural network the same was 2.14mg/l(R 2 :0.85). Neural network- derived map of chlorophyll-a shows that, the lake is eutrophic even in the low productivity season.
Thirty-year trends of physical activity in relation to age, calendar time and birth cohort in Finnish adults.

BACKGROUND The aim of this article was to investigate time trends 1972-2002 in leisure time, occupational and commuting physical activity across birth cohorts in Finnish adults. METHODS The study population comprised 59 028 men and women aged 25-64 years who participated in the FINRISK Study. The first birth cohort was born in 1913 and the last in 1977. Prevalence of physical activity was reported across birth cohorts and study years and change in the prevalence was tested using log-linear regression analysis. RESULTS The prevalence of leisure-time physical activity increased between 1972 and 2002 from 66% to 77% in men and from 49% to 76% in women. In each study year, the younger people were more active than the older ones. However, within the birth cohorts, physical activity tended to increase with age. The prevalence of physically demanding work decreased from 60% to 38% in men and from 47% to 25% in women and the prevalence of daily commuting activity decreased from 30% to 10% in men and from 34% to 22% in women, in the same time period. In the 1970s and the 80s, the older people had more physically demanding work than the younger ones, but within the birth cohorts, occupational activity decreased with age. CONCLUSION During the past 30 years, the prevalence of leisure-time physical activity has increased, while the prevalence of occupational and commuting physical activity has decreased. The cross-sectional association of age with different types of physical activity was different from that assessed within the birth cohorts.