Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacogenetics of anticancer drug sensitivity in pancreatic cancer

Chemotherapy has produced unsatisfactory results in pancreas cancer and novel approaches, including treatment tailoring by pharmacogenetic analysis and new molecular-targeted drugs, are required. The scarcity of effective therapies may reflect the lack of knowledge about the influence of tumor-related molecular abnormalities on responsiveness to drugs. Advances in the understanding of pancreas cancer biology have been made over the past decade, including the discovery of critical mutations in oncogenes (i.e., K-Ras) as well as the loss of tumor suppressor genes, such as TP53 and p16INK4. Other studies showed the dysregulation of the expression of proteins involved in the control of cell cycle, proliferation, apoptosis, and invasiveness, such as Bcl-2, Akt, mdm2, and epidermal growth factor receptor. These characteristics might contribute to the aggressive behavior of pancreatic cancer and influence response to treatment. Indeed, the inactivation of p53 may explain the relative resistance to 5-fluorouracil, whereas Bcl-2 overexpression is associated with reduced sensitivity to gemcitabine. However, the future challenge of pancreas cancer chemotherapy relies on the identification of molecular markers that help in the selection of drugs best suited to the individual patient. Recent pharmacogenetic studies focused on genes encoding proteins directly involved in drug activity, showing the role of thymidylate synthase and human equilibrative nucleoside transporter-1 as prognostic factor in 5-fluorouracil- and gemcitabine-treated patients, respectively. Finally, inhibitors of signal transduction and angiogenesis are under extensive investigation, and several prospective trials have been devoted to this area. Pharmacogenetics is likely to play a central role in the personalization of treatment, to stratify patients based on their likelihood of response to both standard agents (i.e., gemcitabine/nucleoside transporters) and targeted treatments (i.e., epidermal growth factor receptor gene mutations and/or amplification and tyrosine kinase inhibitors), Thus, molecular analysis should be implemented in the optimal management of the patient affected by pancreatic adenocarcinoma. [Mol Cancer Ther 2006;5(6):1387–95] [Mol Cancer Ther 2006;5(6):1387-95]
Depolarization of end-plates by acetylcholine externally applied.

Surface potential of the excised toad's muscle, mostly sartorius, was recorded by a method similar to that used by Burns and Paton (1). Distribution of the surface potential along the length axis of muscle was demonstrated as a curve on a cathode-ray tube.1. Surface potential of an intact muscle is almost equal, demonstrating a difference of less than 1 mV. When 10-4-10-5 ACh chloride is applied, one or two negative peaks appear in the pattern of surface potential. This peak is due to ACh depolarization of the end-plate membrane. If a fine electrode is used, the shape of this peak becomes sharp.2. Actions of ACh in sodium-free media were studied. It was proven that ACh depolarization of the end-plate occurs in a sodium-free medium where sucrose Ringer and NH4+ Ringer are mixed at an even rate (table 1). After being soaked in this medium, the muscle tested shows ACh depolarization just as in the pre-treatment stage. A vigorous ACh contracture is also observed. The results seem to support strongly the short circuit theory of end-plate depolarization (2, 3, 5, 6, 7, 8). 3. Patterns of ACh depolarization were recorded in several different muscles other than the sartorius. Two types of patterns are found in ACh depolarization. In the first type, which is represented by the sartorius muscle, the peak is sharp and distinct. In the second type, which is represented by the rectus abdominis, the peak is flat. It is considered that muscles which belong to the latter group are composed mostly of tonus fibers.
Improvement of Semantic Search Results with Providing an Updatable Dynamic User Model

The current generation of search engines is severely limited in its understanding of the user's intent and the Web's content and consequently in matching the needs for information with the vast supply of resources on the web [10]. The search engines are evolving from the keyword matching search in general to conception match search personalized by user. In this article, is tried to use the semantic search engines to improve the efficiency level of personalization process. Since the general problem in the search results produced by semantic search is the overload information and the mismatch between the results and corresponding requirements needed by the user, so there is an attempt to troubleshoot the problems by applying user model to some extent. The research project at hand is oriented to collect personalized data to be displayed and create the user model. Models create a structure to display the information on the basis of the user’s priorities. The initial step to develop a user modeling is to collect and compile user’s interests. In this paper, is studied how to infer a user’s interest from the user’s search context and use the inferred implicit user model for personalized search.
Chronic Wasting Disease

Chronic wasting disease (CWD) is a unique transmissible spongiform encephalopathy (TSE) of mule deer (Odocoileus hemionus), white-tailed deer (O. virginianus), and Rocky Mountain elk (Cervus elaphus nelsoni). The natural history of CWD is incompletely understood, but it differs from scrapie and bovine spongiform encephalopathy (BSE) by virtue of its occurrence in nondomestic and free-ranging species. CWD has many features in common with scrapie, including early widespread distribution of disease-associated prion protein (PrPd) in lymphoid tissues, with later involvement of central nervous system (CNS) and peripheral tissues. This distribution likely contributes to apparent efficiency of horizontal transmission and, in this, is similar to scrapie and differs from BSE. Clinical features and lesions of CWD are qualitatively similar to the other animal TSEs. Microscopically, marked spongiform lesions occur in the central nervous system (CNS) after a prolonged incubation period and variable course of clinical disease. During incubation, PrPd can be identified in tissues by antibody-based detection systems. Although CWD can be transmitted by intracerebral inoculation to cattle, sheep, and goats, ongoing studies have not demonstrated that domestic livestock are susceptible via oral exposure, the presumed natural route of exposure to TSEs. Surveillance efforts for CWD in captive and free-ranging cervids will continue in concert with similar activities for scrapie and BSE. Eradication of CWD in farmed cervids is the goal of state, federal, and industry programs, but eradication of CWD from free-ranging populations of cervids is unlikely with currently available management techniques.
Guided antithrombotic therapy: current status and future research direction: report on a National Heart, Lung and Blood Institute working group.

The National Heart, Lung, and Blood Institute (NHLBI) convened a working group to develop a research agenda to enhance the understanding and effectiveness of antithrombotic therapy. The working group brought together cardiologists, hematologists, interventionalists, clinical trialists, genetic epidemiologists, basic scientists, and other stakeholders to review (1) coagulation, platelet activation and aggregation, and antithrombotic therapy; (2) issues surrounding antithrombotic therapy failure – how to define it, how to predict and diagnose it, available tests and how to optimize them; (3) the factors that affect the efficacy, safety, and predictability of antithrombotic therapies; (4) how to optimize antithrombotic therapy, improve on present interventions, and individually tailor therapy to increase efficacy and safety and to avoid failure; and (5) the clinical applicability and cost-effectiveness of individually tailored antithrombotic therapy based on functional and genetic testing. The working group characterized and discussed challenges for guided antithrombotic therapy in 4 domains: therapeutic strategies, antithrombotic metrics, pharmacology and pharmacogenetics, and stakeholders' roles. Overall, the working group identified and prioritized the most pressing clinical needs to focus future research and translational efforts. This report presents highlights of these reviews and a summary of suggested research directions. There has been tremendous progress in the field of thrombosis in the past 2 decades.1–5 The ramifications on cardiovascular care have been profound. A greater appreciation of the central role of platelets in atherothrombosis and an increased understanding of the receptors involved in platelet activation and aggregation have led to pivotal randomized controlled trials (RCTs) of novel agents.6 Many of these agents have been associated with substantial reductions in adverse cardiovascular outcomes. Simultaneously, an appreciation of the complexity of the coagulation cascade and the artificiality of separating it from cellular and platelet interactions has promoted a deeper understanding of thrombosis and, consequently, identification of pharmacological targets to …
Motion compensated prediction in transform domain Distributed Video Coding

The ongoing research in distributed video coding (DVC) for low complexity encoding is trying to shorten the substantial performance gap to well known state-of-the-art coders. One way of reducing this gap is to improve the quality of the motion compensated prediction. In this paper we investigate which motion estimation method to apply in DVC, comparing possible methods to produce a motion compensated prediction. We use interpolation as well as extrapolation methods. Our results show that even with a very simple DCT scheme for the Wyner Ziv frames, extrapolation can outperform the widely used interpolation.
New members in the upper scorpius association from the UKIRT infrared deep sky survey early data release

We present the results of a 9.3-deg 2 infrared (ZYJHK) survey in the Upper Scorpius association extracted from the UKIRT Infrared Deep Sky Survey (UKIDSS) Galactic Cluster Survey Early Data Release. We have selected a total of 112 candidates from the (Z - J, Z) colour-magnitude diagram over the Z = 12.5-20.5 magnitude range, corresponding to M = 0.25-0.01 M ⊙ at an age of 5 Myr and a distance of 145 pc. Additional photometry in J and K filters revealed most of them as reddened stars, leaving 32 possible members. Among them, 15 have proper motion consistent with higher-mass members from Hipparcos and optical spectra with strong Ha in emission and weak gravity features. We have also extracted two lower-mass candidate members for which no optical spectra are in hand. Three members exhibit strong Ha equivalent widths (>20 A), suggesting that they could still undergo accretion, whereas two other dwarfs show signs of chromospheric activity. The likelihood of the binarity of a couple of new stellar and substellar members is discussed as well.
The dynamics of recycled acetylcholine receptors at the neuromuscular junction in vivo

At the peripheral neuromuscular junction (NMJ), a significant number of nicotinic acetylcholine receptors (AChRs) recycle back into the postsynaptic membrane after internalization to intermingle with not-yet-internalized `pre-existing' AChRs. However, the way in which these receptor pools are maintained and regulated at the NMJ in living animals remains unknown. Here, we demonstrate that recycled receptors in functional synapses are removed approximately four times faster than pre-existing receptors, and that most removed recycled receptors are replaced by new recycled ones. In denervated NMJs, the recycling of AChRs is significantly depressed and their removal rate increased, whereas direct muscle stimulation prevents their loss. Furthermore, we show that protein tyrosine phosphatase inhibitors cause the selective accumulation of recycled AChRs in the peri-synaptic membrane without affecting the pre-existing AChR pool. The inhibition of serine/threonine phosphatases, however, has no effect on AChR recycling. These data show that recycled receptors are remarkably dynamic, and suggest a potential role for tyrosine dephosphorylation in the insertion and maintenance of recycled AChRs at the postsynaptic membrane. These findings may provide insights into long-term recycling processes at less accessible synapses in the central nervous system in vivo.
Concerning the distribution of endogenous norepinephrine in the adventitial and media-intimal layers of the rabbit aorta and the capacity of these layers to bind tritiated norepinephrine.

Approximately 75% of the endogenous norepinephrine content of rabbit thoracic aorta resides in the adventitia; the remainder resides in the media-intimal layers. Approximately 75 to 90% of the capacity of sortie strips to bind tritiated norepinephrine resides in the adventitia and is sensitive to inhibition by cocaine. The remaining capacity to bind norepinephrine resides in the media-intimal layers and is not sensitive to inhibition by cocaine. Sham removal of the adventitia does not significantly alter the responsiveness of aortic strips to norepinephrine or tyramine. Actual removal of the adventitia drastically reduces the responsiveness of strips to tyramine and moderately reduces their responsiveness to norepinephrine. It is concluded that removal of the adventitia effectively denervates rabbit aorta. It is further concluded that the localization of the innervation of the rabbit aorta within the adventitia makes it unlikely that the innervation can effectively limit the concentration of norepinephrine throughout the entire media. The failure of the strips from which the adventitia has been removed to become hyperresponsive to norepinephrine supports this latter conclusion.
Cell-stiffness-induced mechanosignaling – a key driver of leukocyte transendothelial migration

ABSTRACT The breaching of cellular and structural barriers by migrating cells is a driving factor in development, inflammation and tumor cell metastasis. One of the most extensively studied examples is the extravasation of activated leukocytes across the vascular endothelium, the inner lining of blood vessels. Each step of this leukocyte transendothelial migration (TEM) process is regulated by distinct endothelial adhesion receptors such as the intercellular adhesion molecule 1 (ICAM1). Adherent leukocytes exert force on these receptors, which sense mechanical cues and transform them into localized mechanosignaling in endothelial cells. In turn, the function of the mechanoreceptors is controlled by the stiffness of the endothelial cells and of the underlying substrate representing a positive-feedback loop. In this Commentary, we focus on the mechanotransduction in leukocytes and endothelial cells, which is induced in response to variations in substrate stiffness. Recent studies have described the first key proteins involved in these mechanosensitive events, allowing us to identify common regulatory mechanisms in both cell types. Finally, we discuss how endothelial cell stiffness controls the individual steps in the leukocyte TEM process. We identify endothelial cell stiffness as an important component, in addition to locally presented chemokines and adhesion receptors, which guides leukocytes to sites that permit TEM. Summary: Mechanosensing and -transduction is important for inflammation. This Commentary discusses the regulation of endothelial cell stiffness and its relevance for leukocyte adhesion, crawling and transendothelial migration.
Neurologic Interventions for Physical Therapy

Section 1: FOUNDATIONS 1. The Role of the Physical Therapist Assistant in Neurologic Rehabilitation 2. Neuroanatomy 3. Motor Control and Motor Learning 4. Motor Development Section 2: CHILDREN 5. Positioning and Handling To Foster Motor Function 6. Cerebral Palsy 7. Myelomeningocele 8. Genetic Disorders Section 3: ADULTS 9. Proprioceptive Neuromuscular Facilitation 10. Cerebrovascular Accidents 11. Traumatic Brain Injuries 12. Spinal Cord Injuries 13. Other Neurologic Disorders Answers to Review Questions Index
The role of androgens in fetal growth: observational study in two genetic models of disordered androgen signalling

Objective To examine the role of androgens on birth weight in genetic models of altered androgen signalling. Setting Cambridge Disorders of Sex Development (DSD) database and the Swedish national screening programme for congenital adrenal hyperplasia (CAH). Patients (1) 29 girls with XY karyotype and mutation positive complete androgen insensitivity syndrome (CAIS); (2) 43 girls and 30 boys with genotype confirmed CAH. Main outcome measures Birth weight, birth weight-for-gestational-age (birth weight standard deviation score (SDS)) calculated by comparison with national references. Results Mean birth weight SDS in CAIS XY infants was higher than the reference for girls (mean, 95% CI: 0.4, 0.1 to 0.7; p=0.02) and was similar to the national reference for boys (0.1, −0.2 to 0.4). Birth weight SDS in CAH girls was similar to the national reference for girls (0.0, −0.2 to 0.2) and did not vary by severity of gene mutation. Birth weight SDS in CAH boys was also similar to the national reference for boys (0.2, −0.2 to 0.6). Conclusion CAIS XY infants have a birth weight distribution similar to normal male infants and birth weight is not increased in infants with CAH. Alterations in androgen signalling have little impact on birth weight. Sex dimorphism in birth size is unrelated to prenatal androgen exposure.
LIKELIHOOD OF ANCESTOR STATES IN ADAPTIVE RADIATION

Theories of ecological diversification make predictions about the timing and ordering of character state changes through history. These theories are testable by “reconstructing” ancestor states using phylogenetic trees and measurements of contemporary species. Here we use maximum likelihood to estimate and evaluate the accuracy of ancestor reconstructions. We present likelihoods of discrete ancestor states and derive probability distributions for continuous ancestral traits. The methods are applied to several examples: diets of ancestral Darwin's finches; origin of inquilinism in gall wasps; microhabitat partitioning and body size evolution in scrubwrens; digestive enzyme evolution in artiodactyl mammals; origin of a sexually selected male trait, the sword, in platies and swordtails; and evolution of specialization in Anolis lizards. When changes between discrete character states are rare, the maximum‐likelihood results are similar to parsimony estimates. In this case the accuracy of estimates is often high, with the exception of some nodes deep in the tree. If change is frequent then reconstructions are highly uncertain, especially of distant ancestors. Ancestor states for continuous traits are typically highly uncertain. We conclude that measures of uncertainty are useful and should always be provided, despite simplistic assumptions about the probabilistic models that underlie them. If uncertainty is too high, reconstruction should be abandoned in favor of approaches that fit different models of trait evolution to species data and phylogenetic trees, taking into account the range of ancestor states permitted by the data.
Do GGA Adaptors Bind Internal DXXLL Motifs?

The GGA family of clathrin adaptor proteins mediates the intracellular trafficking of transmembrane proteins by interacting with DXXLL‐type sorting signals on the latter. These signals were originally identified at the carboxy‐termini of the transmembrane cargo proteins. Subsequent studies, however, showed that internal DXXLL sorting motifs occur within the N‐ or C‐terminal cytoplasmic domains of cargo molecules. The GGAs themselves also contain internal DXXLL motifs that serve to auto‐regulate GGA function. A recent study challenged the notion that internal DXXLL signals are competent for binding to GGAs. Since the question of whether GGA adaptors interact with internal DXXLL motifs is fundamental to the identification of bona fide GGA cargo, and to an accurate understanding of GGA regulation within cells, we have extended our previous findings. We now present additional evidence confirming that GGAs do interact with internal DXXLL motifs. We also summarize the recent reports from other laboratories documenting internal GGA binding motifs.
Compiler and runtime support for enabling reduction computations on heterogeneous systems

A trend that has materialized, and has given rise to much attention, is of the increasingly heterogeneous computing platforms. Presently, it has become very common for a desktop or a notebook computer to come equipped with both a multi‐core CPU and a graphics processing unit (GPU). Capitalizing on the maximum computational power of such architectures (i.e., by simultaneously exploiting both the multi‐core CPU and the GPU), starting from a high‐level API, is a critical challenge. We believe that it would be highly desirable to support a simple way for programmers to realize the full potential of today's heterogeneous machines. This paper describes a compiler and runtime framework that can map a class of applications, namely those characterized by generalized reductions, to a system with a multi‐core CPU and GPU. Starting with simple C functions with added annotations, we automatically generate the middleware API code for the multi‐core, as well as CUDA code to exploit the GPU simultaneously. The runtime system provides efficient schemes for dynamically partitioning the work between CPU cores and the GPU. Our experimental results from two applications, for example, k‐means clustering and principal component analysis, show that, through effectively harnessing the heterogeneous architecture, we can achieve significantly higher performance compared with using only the GPU or the multi‐core CPU. In k‐means clustering, the heterogeneous version with eight CPU cores and a GPU achieved a speedup of about 32.09x relative to one‐thread CPU. When compared with the faster of CPU‐only and GPU‐only executions, we were able to achieve a performance gain of about 60%. In principal component analysis, the heterogeneous version attained a speedup of 10.4x relative to the one‐thread CPU version. When compared with the faster of CPU‐only and GPU‐only versions, the heterogeneous version achieved a performance gain of about 63.8%. Copyright © 2011 John Wiley & Sons, Ltd.
Breaking Audio CAPTCHAs

CAPTCHAs are computer-generated tests that humans can pass but current computer systems cannot. CAPTCHAs provide a method for automatically distinguishing a human from a computer program, and therefore can protect Web services from abuse by so-called "bots. " Most CAPTCHAs consist of distorted images, usually text, for which a user must provide some description. Unfortunately, visual CAPTCHAs limit access to the millions of visually impaired people using the Web. Audio CAPTCHAs were created to solve this accessibility issue; however, the security of audio CAPTCHAs was never formally tested. Some visual CAPTCHAs have been broken using machine learning techniques, and we propose using similar ideas to test the security of audio CAPTCHAs. Audio CAPTCHAs are generally composed of a set of words to be identified, layered on top of noise. We analyzed the security of current audio CAPTCHAs from popular Web sites by using AdaBoost, SVM, and k-NN, and achieved correct solutions for test samples with accuracy up to 71%. Such accuracy is enough to consider these CAPTCHAs broken. Training several different machine learning algorithms on different types of audio CAPTCHAs allowed us to analyze the strengths and weaknesses of the algorithms so that we could suggest a design for a more robust audio CAPTCHA.