Miracle-dz/UniFAR-FTUs huggingface dataset:
Many si/shRNAs can kill cancer cells by targeting multiple survival genes through an off-target mechanism

Over 80% of multiple tested siRNAs and shRNAs targeting CD95 or CD95 ligand (CD95L) induce a form of cell death characterized by simultaneous activation of multiple cell death pathways preferentially killing transformed and cancer stem cells. We now show these si/shRNAs kill cancer cells through canonical RNAi by targeting the 3’UTR of critical survival genes in a unique form of off-target effect we call DISE (death induced by survival gene elimination). Drosha and Dicer deficient cells, devoid of most miRNAs, are hypersensitive to DISE, suggesting cellular miRNAs protect cells from this form of cell death. By testing 4666 shRNAs derived from the CD95 and CD95L mRNA sequences and an unrelated control gene, Venus, we have identified many toxic sequences - most of them located in the open reading frame of CD95L. We propose that using specific toxic RNAi-active sequences present in the genome can kill cancer cells.
Cancer Biology and Signal Transduction MAPK Pathway Inhibition Enhances the Ef fi cacy of an Anti-Endothelin B Receptor Drug Conjugate by Inducing Target Expression in Melanoma

Therapies targeting the mitogen-activated protein (MAP) kinase pathway in melanoma have produced significant clinical responses; however, duration of response is limited by acquisition of drug resistance. Rational drug combinationsmay improve outcomes in this setting.We assessed the therapeutic combination of an antibody–drug conjugate (ADC) targeting the endothelin B receptor (EDNRB) with small-molecule inhibitors of the MAP kinase signaling pathway in melanoma. Cell lines and tumor models containing either mutant BRAF or NRAS, or wild-type for both, were exposed to small-molecule inhibitors of BRAF and MEK. Expression of EDNRB was analyzed and the therapeutic impact of combining the anti-EDNRB ADC with the BRAF and MEK inhibitors was assessed. Increased expression of EDNRB in response to inhibition of BRAF and/orMEKwas observed and augmented the antitumor activity of theADC. Enhanced target expression and ADC antitumor activity were realized irrespective of the response of the tumor model to the BRAF or MEK inhibitors alone and could be achieved inmelanomawithmutant NRAS, BRAF, or neithermutation. Cells that acquired resistance to BRAF inhibition through long-term culture retained drug-induced elevated levels of EDNRB expression. Expression of EDNRB was not enhanced in normal human melanocytes by inhibition of BRAF and the combination of the ADC with MAPK inhibitors was well-tolerated in mice. The anti-EDNRB ADC combines well with BRAF andMEK inhibitors and could have therapeutic use in the majority of human melanoma cases. Mol Cancer Ther; 13(6); 1599–610. 2014 AACR.
Single Image Spectral Reconstruction for Multimedia Applications

In this paper, we present a method which can perform spectral reconstruction and illuminant recovery from a single colour image making use of an unlabelled training set of hyperspectral images. Our method employs colour and appearance information to drive the reconstruction process subject to the material properties of the objects in the scene. The idea is to reconstruct the image spectral irradiance making use of a set of prototypes extracted from the training set. These spectra, together with a set of convolutional features are hence obtained using sparse coding so as to reconstruct the image irradiance. With the reconstructed spectra in hand, we proceed to compute the illuminant power spectrum using a quadratic optimisation approach. We provide a quantitative analysis for our method and compare to a number of alternatives. We also show sample results on illuminant substitution and transfer, film simulation and image recolouring using mood board colour schemes.
[18F]Fluorothymidine Positron Emission Tomography before and 7 Days after Gefitinib Treatment Predicts Response in Patients with Advanced Adenocarcinoma of the Lung

Purpose: To evaluate the usefulness of 3′-deoxy-3′-[18F]fluorothymidine (FLT)-positron emission tomography (PET) for predicting response and patient outcome of gefitinib therapy in patients with adenocarcinoma of the lung. Experimental Design: Nonsmokers with advanced or recurrent adenocarcinoma of the lung were eligible. FLT-PET images of the thorax were obtained before and 7 days after the start of gefitinib (250 mg/d) therapy, the maximum standardized uptake values (SUVmax) of primary tumors were measured, and the percent changes in SUVmax were calculated. After 6 weeks of therapy, the responses were assessed by computed tomography of the chest. Results: Among 31 patients who were enrolled, we analyzed 28 patients for whom we had complete data. Chest computed tomography revealed partial response in 14 (50%), stable disease in 4 (14%), and progressive disease in 10 (36%) after 6 weeks of treatment. Pretreatment SUVmax of the tumors did not differ between responders and nonresponders. At 7 days after the initiation of therapy, the percent changes in SUVmax were significantly different (−36.0 ± 15.4% versus 10.1 ± 19.5%; P < 0.001). Decrease of >10.9% in SUVmax was used as the criterion for predicting response. The positive and negative predictive values were both 92.9%. The time to progression was significantly longer in FLT-PET responders than nonresponders (median, 7.9 versus 1.2 months; P = 0.0041). Conclusion: FLT-PET can predict response to gefitinib 7 days after treatment in nonsmokers with advanced adenocarcinoma of the lung. The change in tumor SUVmax obtained by FLT-PET seems to be a promising predictive variable.
Interferon-γ responses to Plasmodium falciparum vaccine candidate antigens decrease in the absence of malaria transmission

Background Malaria elimination campaigns are planned or active in many countries. The effects of malaria elimination on immune responses such as antigen-specific IFN- γ responses are not well characterized. Methods IFN- γ responses to the P. falciparum antigens circumsporozoite protein, liver stage antigen-1, thrombospondin-related adhesive protein, apical membrane antigen-1, MB2, and merozoite surface protein-1 were tested by ELISA in 243 individuals in highland Kenya in April 2008, October 2008, and April 2009, after a one-year period of interrupted malaria transmission from April 2007 to March 2008. Results While one individual (0.4%) tested positive for P. falciparum by PCR inOctober 2008 and another two (0.9%) tested positive in April 2009, no clinical malaria cases were detected during weekly visits. Levels of IFN-γ to all antigens decreased significantly from April 2008 to April 2009 (all P < 0.001). Discussion Naturally acquired IFN- γ responses to P. falciparum antigensare short-lived in the absence of repeated P. falciparum infection. Even short periods of malaria interruption may significantly decrease IFN-γ responses to P. falciparum antigens.
Resetting of pressure-dependent renin release by intrarenal alpha 1-adrenoceptors in conscious dogs.

We investigated the influence of a stimulation of intrarenal alpha 1-adrenoceptors on the relationship between renin release and renal artery pressure in 8 conscious, chronically instrumented dogs receiving a normal salt diet. Renin stimulus-response curves were determined by a stepwise reduction of renal artery pressure down to 70 mm Hg (1) under control conditions, (2) during a bilateral common carotid occlusion combined with an intrarenal prazosin infusion, and (3) during an intrarenal methoxamine infusion. Both drug infusions did not alter resting renal blood flow. (1) The control renin stimulus-response curve revealed a flat portion (plateau-level) around and above the resting blood pressure and a very steep portion (slope) below a well-defined threshold pressure 10-15 mm Hg below the resting blood pressure. (2) An intrarenal alpha 1-adrenoceptor blockade by prazosin prevented the resetting of the threshold pressure which is regularly observed during bilateral common carotid occlusion. (3) An intrarenal infusion of the alpha 1-adrenoceptor agonist methoxamine increased the threshold pressure. We suggest that the neural control of renin release within the autoregulatory range of renal blood flow involves two independent mechanisms: the direct release of renin from juxtaglomerular granular cells by beta 1-adrenoceptors, and the modulation of the threshold pressure of pressure-dependent renin release by intrarenal alpha 1-adrenoceptors. The small changes in renal nerve activity necessary to reset the threshold pressure and the close relationship between the threshold pressure and resting blood pressure imply an important function of intrarenal alpha 1-adrenoceptors in the regulation of renin release. (ABSTRACT TRUNCATED AT 250 WORDS)
A study of platelet activation in atrial fibrillation and the effects of antithrombotic therapy.

BACKGROUND Platelet function may be abnormal in patients with atrial fibrillation (AF) and could be related to abnormal thrombogenesis. The aim of this cross-sectional study was to investigate new aspects of platelet biology in AF, predominantly focusing on platelet activation and the effects of concomitant antiplatelet and anticoagulant therapy. PATIENTS AND METHODS The study group of 238 patients were (i). 93 patients on no antithrombotic therapy, (ii). 60 patients taking 75-325 mg aspirin/day, and (iii). 85 patients on dose-adjusted warfarin (International Normalised Ratio [INR] range 2.0-3.0). Results were compared with those from 50 age- and sex-matched normal subjects. Platelet markers (plasma beta-thromboglobulin, soluble glycoprotein V [both ELISA]), coagulation markers (fibrin D-dimer [ELISA] and fibrinogen [Clauss]), and platelet aggregation in response to standard platelet agonists were studied. RESULTS beta-thromboglobulin (P=0.01), soluble glycoprotein V (P<0.001) and fibrin D-dimer (P=0.002) were higher in untreated AF patients compared to healthy controls. AF patients on warfarin had lower fibrin D-dimer (P<0.001) when compared to AF patients on no therapy. Plasma fibrinogen and platelet aggregation was no different between patients with AF and healthy controls. Aspirin use was associated with reduced platelet aggregation response to epinephrine (P=0.01), whilst patients established on warfarin had significantly lower plasma fibrin D-dimer levels. CONCLUSION AF patients exhibit changes in plasma markers of platelet function but no significant abnormalities of platelet aggregation. However, treatment with warfarin or aspirin failed to demonstrate any significant benefit on platelet activation, although warfarin use was associated with reduced thrombogenesis (fibrin D-dimer). We suggest that platelet activation may not play an important role in the pathogenesis of thromboembolism in AF.
17 Cognitive and Behavioural Changes After Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson ’ s Disease

In patients with Parkinson’s disease, cognitive impairment is common, may be detectable in early disease stages, even in young patients, and may progress to overt dementia. In addition, a variety of psychiatric and behavioural symptoms may occur in Parkinsonian patients, including depression, apathy, anxiety, visual hallucinations, sleep disorders, impulse control disorders, punding and the dopamine dysregulation syndrome. The cognitive and behavioural symptoms observed in these patients may be part of the non-motor symptoms of Parkinson’s disease, which can appear in various phases of the disease course.
Learning to Ground Fact Symbols in Behavior-Based Robots

A robot running a hybrid control system (its architecture comprising a deliberative and a reactive part) must permanently update its symbolic situation model to allow its ongoing deliberation to operate. Previous work has shown that this update can be improved by using, possibly among other sources, the robot's sensor information as filtered through recent activation value histories of robot behaviors. In that work, characteristic patterns in groups of behavior activation values are used to define chronicles, which allow true facts about the current situation to be hypothesized. Chronicle definitions are hand-crafted as part of the domain modeling. In this paper, we demonstrate that analogs of chronicle definitions can be learned. We use an echo state network, which is a particular type of recurrent neural network. To train it, the same activation value data are used as before in chronicle definitions. The training process is fast. The detection process is cheap to run on-line on board the robot. The new method is demonstrated on data from a robot simulator. It provides the robot programmer an alternative tool for getting recent symbolic situation fact hypotheses.
Torpid mixing of local Markov chains on 3-colorings of the discrete torus

We study local Markov chains for sampling 3-colorings of the discrete torus <i>T<inf>L, d</inf></i> = {0, . , <i>L</i>--1}<sup><i>d</i></sup>. We show that there is a constant ρ ≈ . 22 such that for all even <i>L</i> ≥ 4 and <i>d</i> sufficiently large, certain local Markov chains require exponential time to converge to equilibrium. More precisely, if <i>M</i> is a Markov chain on the set of proper 3-colorings of <i>T<inf>L, d</inf></i> that updates the color of at most ρ<i>L</i><sup><i>d</i></sup> vertices at each step and whose stationary distribution is uniform, then the convergence to stationarity of <i>M</i> is exponential in <i>L</i><sup><i>d</i>-1</sup>. Our proof is based on a conductance argument that builds on sensitive new combinatorial enumeration techniques.
MojaveFS : A Transactional Distributed File System

MojaveFS is a key component of an infrastructure supporting distributed transactional computing. It is closely tied to the Mojave Compiler Collection, which provides high-level programming language constructs for reliable distributed programming. Among the most important features of the system are transparency, consistency, and fault-tolerance. We use group communication systems to ensure the consistency and serializability of all operations. The file system provides a global uniform namespace which allows for mobile computing. Transactions are supported through a journalling mechanism, and replication provides fault tolerance. The design provides a UNIX-style file system.
Rise of the Machines

Until recently, sequencing the entire genome of an organism was a major endeavor. New technologies are transforming this task into routine practice and launching a new assault on whole-genome sequencing. It is more than 30 years since Sir Fred Sanger and colleagues published their method for sequencing DNA [1]. This Nobel Prize–winning work formed the basis of the vast majority of subsequent sequencing methodologies, albeit with some crucial technical innovations. Despite the great utility of Sanger sequencing, its scalability is inherently limited, and therefore the creation of warehouse-sized facilities was required to accomplish whole-genome sequencing projects. As a result, sequencing more than a few kilobases of DNA—a requirement for all but the simplest genomes—has long remained the province of a few dedicated sequencing centers. Within the last year, however, things have begun to change in dramatic ways. New sequencing technologies are emerging, announced in an assortment of reports, conference presentations, and press releases. In this issue of PLoS Genetics, Srivatsan et al. [2] report the resequencing of several genomes of the bacterium Bacillus subtilis using one of these new technologies. A new battle at the frontier of DNA sequencing has commenced.
Optimum Communication Spanning Trees

Given a set of nodes $N_i (i = 1,2, \cdots ,n)$ which may represent cities and a set of requirements $r_{ij} $ which may represent the number of telephone calls between $N_i $ and $N_j $, the problem is to build a spanning tree connecting these n nodes such that the total cost of communication of the spanning tree is a minimum among all spanning trees. The cost of communication for a pair of nodes is $r_{ij} $ multiplied by the sum of the distances of arcs which form the unique path connecting $N_i $ and $N_j $ in the spanning tree. Summing over all $\begin{pmatrix} n \\ 2 \ \end{pmatrix}$ pairs of nodes, we have the total cost of communication of the spanning tree. Note that the problem is different from the minimum spanning tree problem solved by Kruskal and Prim.
Gauze packing of open surgical wounds: empirical or evidence-based practice?

INTRODUCTION Most surgical wounds are closed primarily, but some are allowed to heal by secondary intention. This usually involves repeated packing and dressing of the raw wound surfaces. Although the long-term care of such wounds has devolved to the care of nurses in the community or out-patient setting, the initial wound dressing or cavity packing is done by the surgeon in the operating theatre. Many surgeons are unaware of the growth of the discipline of wound care, and still use traditional soaked gauze for dressing and packing open surgical wounds and cavities. RESULTS This review summarises the some of the modern alternatives available and the evidence--or the lack of it--for their use in both the acute and chronic setting.
Combining multiple translation systems for Spoken Language Understanding portability

We are interested in the problem of learning Spoken Language Understanding (SLU) models for multiple target languages. Learning such models requires annotated corpora, and porting to different languages would require corpora with parallel text translation and semantic annotations. In this paper we investigate how to learn a SLU model in a target language starting from no target text and no semantic annotation. Our proposed algorithm is based on the idea of exploiting the diversity (with regard to performance and coverage) of multiple translation systems to transfer statistically stable word-to-concept mappings in the case of the romance language pair, French and Spanish. Each translation system performs differently at the lexical level (wrt BLEU). The best translation system performances for the semantic task are gained from their combination at different stages of the portability methodology. We have evaluated the portability algorithms on the French MEDIA corpus, using French as the source language and Spanish as the target language. The experiments show the effectiveness of the proposed methods with respect to the source language SLU baseline.
Increased availability of tryptophan in brain as common pathogenic mechanism for anorexia associated with different diseases.

Changes in brain serotonin and tryptophan concentrations probably represent one of the most important mechanisms in the regulation of eating behavior both in experimental animals and in humans. Anorexia, which accompanies numerous diseases, e.g., cancer, liver cirrhosis, and uremia, may recognize an increased brain availability of tryptophan as a common pathogenic mechanism. This will lead to a rise in brain serotonin synthesis, which, in turn, is responsible for a reduction in food intake. According to this hypothesis, the anorexia observed in various diseases could be improved either by a decrease in the cerebral synthesis of serotonin or by a reduction in the entry of tryptophan into the brain.
Morphology Evolution of γ′ Precipitates during Isothermal Exposure in Wrought Ni-Based Superalloy Inconel X-750

The morphological evolution of γ′ precipitates and lattice misfit with isothermal aging were closely investigated in wrought Ni-based superalloy Inconel X-750. The γ′ morphology dramatically changes in terms of shape, distribution, coalescence and coherency at the γ/γ′ interface. These processes and their dependence on temperature are summarized as a γ′ morphology map together with a time–temperature–precipitation (TTP) diagram through quantifying relevant morphological parameters. The lattice misfit was measured by X-ray diffraction and is positive; it decreases from 0.6% at room temperature to 0.1% at the aging temperature. These results suggest that the morphological changes of the γ′ precipitates are attributable to very low lattice misfit, the interaction of the elastic field, the volume fraction of the precipitates and incoherence in γ/γ′ interface.
Oxygen uptake in one-legged and two-legged exercise.

PURPOSE The purpose of this study was to determine the primary factors causing the differential oxygen uptake (VO2) response at submaximal intensities between one-legged and two-legged exercise, and whether peak oxygen uptake (VO2peak) increases in proportion to the increase in active muscle mass. METHODS Two different types of exercise were used for this experiment, each requiring a different movement, a different method of stabilizing posture, and, finally, a different limiting VO2peak. In experiment 1, nine male subjects performed one-legged cycling (OLC) and two-legged cycling exercise (TLC) at a pedaling rate of 80 rpm. The exercise intensity was first set at 80 W and was increased by 40 W every 3 min until exhaustion. In experiment 2, six healthy male subjects performed one-legged knee-extension (OKE) and two-legged knee-extension (TKE) exercise at a rate of 50 contractions per minute. The knee-extension exercise was done at constant work rates for a 3-min session in OKE or a 4-min session in TKE. The exercise bouts were performed intermittently at four to seven different submaximal intensities and VO2 was determined at each intensity in all exercises. RESULTS At submaximal intensities, VO2 in relation to work rate of one-legged exercise was more steep than those of two-legged exercise, and the mean values of VO2 were significantly higher in one-legged exercise than those in two-legged exercise in both knee extension and cycling exercise. Mean values of VO2peak for two-legged exercise were significantly higher than that for one-legged exercise (P < 0.01); however, it was much lower than two times of that for one-legged exercise even in knee extension exercise where the VO2peak would be limited peripherally. CONCLUSION The findings of this study suggest that the differential VO2 response between one-legged and two-legged exercise would be attributed not only to the difference in force application throughout the exercise movement and to the effect of a postural component but also to the inhibited circulatory response caused by the multiple limb exercise. In addition, it was supposed that VO2peak does not increase in proportion to the exercising muscle mass even during smaller muscle activity where the cardiac pumping capacity has not reached its upper limit.