Miracle-dz/UniFAR-FTUs huggingface dataset:
The Unpluggable in Pursuit of the Undruggable: Tackling the Dark Matter of the Cancer Therapeutics Universe

The notion that targeted drugs can unplug gain-of-function tumor pathways has revitalized pharmaceutical research, but the survival benefits of this strategy have so far proven modest. A weakness of oncogene-blocking approaches is that they do not address the problem of cancer progression as selected by the recessive phenotypes of genetic instability and apoptotic resistance which in turn arise from loss-of-function – i.e., undruggable – defects of caretaker (e.g., BRCA, MLH1) or gatekeeper (e.g., TP53, PTEN) suppressor genes. Genetic instability ensures that rapid cell kill is balanced by rapid selection for apoptotic resistance and hence for metastasis, casting doubt on the assumption that cytotoxicity (“response”) remains the best way to identify survival-enhancing drugs. In the absence of gene therapy, it is proposed here that caretaker-defective (high-instability) tumors may be best treated with low-lethality drugs inducing replicative (RAS-RAF-ERK) arrest or dormancy, causing “stable disease” rather than tumorilytic remission. Gatekeeper-defective (death-resistant) tumors, on the other hand, may be best managed by combining survival (PI3K-AKT-mTOR) pathway blockade with metronomic or sequential pro-apoptotic drugs.
B-type natriuretic peptide is predictive of postoperative events in orthopedic surgery.

BACKGROUND [Corrected] Clinical assessment is not always sufficient to predict postoperative (PO) cardiac complications. B-type natriuretic peptide (BNP) has an important prognostic value in patients with heart failure. Its value as a predictor of events in orthopedic surgeries has not yet been tested. OBJECTIVE To assess the value of BNP in predicting cardiac complications in the PO period of orthopedic surgeries. METHODS A total of 208 patients undergoing surgical treatment of femur fracture and hip or knee arthroplasty were prospectively evaluated. Of these, 149 (71.6%) were women and the mean age was 72.6 ± 8.8 years. In the preoperative period, the patients underwent conventional clinical assessment and their surgical risk was estimated according to the American Society of Anesthesiologists' (ASA) classification. BNP was determined in the preoperative period, and its ability to predict PO cardiac events (death; acute myocardial infarction; unstable angina; atrial fibrillation; ventricular tachycardia; or heart failure) was analyzed using multivariate logistic regression analysis. RESULTS Seventeen patients (8.0%) experienced cardiac events. Median BNP was significantly higher in these patients in comparison to those without cardiac events (93 [interquartile range 73-424] vs 26.6 [13.2-53.1], p = 0.0001). BNP was the main independent predictor of events (p = 0.01). The ASA classification was not an independent predictor. Analysis of the ROC curve demonstrated that for a cut-off point of 60 pg/mL, BNP showed sensitivity of 76.0% and specificity of 79.0% in the prediction of events, with an area under the curve of 83.0%. CONCLUSION BNP is an independent predictor of PO cardiac events in orthopedic surgeries.
Differences Between Part-Time and Full-Time Employees in the Financial Services Industry

Although part-time employees account for approximately 17% of the workforce, how, or if, they differ from full-time employees is still unknown. This study addresses the question of whether part-time and full-time employees differ on job satisfaction, organizational commitment, job involvement, role ambiguity, role conflict, and inclusion. Additionally, the respondents were from the financial services industry, which has been underrepresented in the part-time employment studies. Part-time employees were found to have lower levels of job involvement and inclusion.
Calculation of 2,3,7,8-TCDD equivalent concentrations of complex environmental contaminant mixtures

Sufficient toxicological data are now available to permit use of conventional risk assessment techniques to estimate the hazards associated with human exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). However, many real-world exposures involve complex mixtures of dibenzodioxins, dibenzofurans, and related compounds. Historical approaches to risk assessment on such mixtures have ranged from ignoring all compounds except 2,3,7,8-TCDD itself to assuming that all compounds have potencies equal to 2,3,7,8-TCDD. An alternative approach which uses existing literature data and analytical results to calculate the “2,3,7,8-TCDD equivalent” concentration of a mixture in order to “predict” its biological potency relative to 2,3,7,8-TCDD itself is advanced here. Previously reported in vivo acute and subchronic studies and some recently obtained analytical chemistry data are integrated here to clarify the utility of this important approach and to assess the uncertainties associated with its use. This predictive approach, and various conceptually similar ones, have now found wide applicability to the risk assessment process associated with exposure to complex mixtures of dioxins, dibenzofurans, and related compounds.
Higher education institution image: acorrespondence analysis approach

“Create an image for your company or your competitors will do it for you. ” In the higher education sector this statement by Keever is equally true; as competition for students increases and funding decreases universities and technikons need to create and maintain a distinctive image in the market place. Higher education institutions are becoming increasingly aggressive in their marketing activities to convey an image that is favourable to their public, be they prospective students, employers, funders etc. Investigates how marketing is used to convey higher education institution type image in the UK and South Africa. Using correspondence analysis, shows the unique positionings that have been created by the old UK universities, the new UK universities, South African universities and technikons. Also identifies which marketing tools these institution types use in conveying their institutional image.
Effect of Carotid Artery Ligation on Regional Cerebral Blood Flow in Normotensive and Spontaneously Hypertensive Rats

Regional cerebral blood flow (rCBF) was measured in normotensive rats (NTR) and spontaneously hypertensive rats (SHR), in a lightly anesthetized state and with control of Pacos by artificial ventilation. Without carotid artery ligation, NTR and SHR showed almost identical rCBF values and distribution, despite s gnificantly elevated levels of blood pressure in SHR. Bilateral carotid artery ligation, however, caused much more pronounced decreases of rCBF (ischemia) in SHR than NTR, in regions supplied by the carotid artery. The reduction of rCBF in SHR was rather homogenous and symmetrical. Mechanisms causing the differences between NTR and SHR are discussed.
An effective level set image segmentation by Joint local kernelized model and global Chan-Vese model

This study presents a novel level set method for image segmentation by means of local kernel mapping and piecewise constant modeling of the image data to deal with image segmentation with intensity non-homogeneity problem. The proposed method adopts local kernel mapping to enhance the discriminative ability to delineate nonlinear decision boundaries between classes. In addition, our approach method embeds a Chan-Vese model into the energy function, which not only can enhance the robustness against noise but also make our approach less sensitive to the localization of the initial contour. We verified the results of the method by a comparative study over a large number of experiments on synthetic and real images. The experiments demonstrate that our method is efficient and robust for segmenting images with intensity inhomogeneity, noise images and texture images.
D'un droit de propriété intellectuelle sur le vivant aux firmes de génomique: vers une marchandisation de la connaissance scientifique sur le génome humain

[fre] Cet article analyse les conditions d’emergence aux Etats-Unis d’une nouvelle generation de firmes de biotechnologies qui, specialisees dans la decouverte de genes humains -activite scientifique jusque-la promue par les systemes de recherche publique -vise la commercialisation de ces decouvertes. L’article montre que, saisie dans la dynamique de developpement du secteur des biotechnologies specifique au contexte nord-americain, la condition majeure de cette emergence tient a l’instauration d''un droit de propriete intellectuelle sur le vivant dont l’evolution a conduit au basculement des decouvertes scientifiques dans le champ des brevets. L’article conclut sur les consequences de la diffusion de ce basculement, notamment a l’Europe, et sur l’essor de ces firmes de genomique sur le changement de statut de la connaissance scientifique. [eng] From Intellectual Property Rights on Living Matter to Genomics Firms : towards Selling Scientific Knowledge of the Human Genome. This article analyses the conditions underlying the emergence of a new generation of biotechnology firms on the American market specialised in the discovery of human genes -a scientific activity previously promoted by public research systems -and the sale of these discoveries. The article shows that, within the specific growth dynamics of the biotechnology sector in the North-American context, the main factor behind the emergence of these firms has been the creation of intellectual property rights on living matter. The development of these rights has led to the patenting of scientific discoveries. The last part of the article discusses the consequences of disseminating the use of patents, particularly in Europe, and the change in status of scientific knowledge triggered by the rise of genomics firms.
A Hyperlexic-Like Reading Style Is Associated With Increased Autistic Features in Girls With ADHD

Objective: Hyperlexic-like reading (defined as word decoding much better than comprehension) has been associated with autism spectrum disorder (ASD). Here we study correlates of a hyperlexic-like reading style (HPL) in ADHD, a condition known to co-occur both with reading difficulties and ASD. Method: We compared 10 girls with an ADHD diagnosis plus HPL with 26 with ADHD minus HPL. Results: Girls with HPL scored marginally lower in reading comprehension but did not differ from non-HPL girls in IQ, vocabulary, or in the severity of ADHD ratings. However, in addition to scoring much better on word decoding, HPL readers also displayed higher levels of social-communication deficits on the ADOS-G and the ADI-R. Moreover, correlation analysis in the full sample revealed an association between increasing autistic features and word reading. Conclusion: The study underscores the heterogeneity of reading skills in ADHD, and shows the relevance of subclinic autistic features for understanding this variability.
Inhalant Abuse: A Call for Attention

The percentage of youth inhaling volatile substances is on the rise in the United States. The professional literature has been critical of the helping professions for not doing enough to address this problem adequately. This article attempts to heighten the awareness of the mental health professional by defining inhalant abuse, its consequences, and strategies for prevention and intervention. Suggestions for further research are also provided.
Subsequent Suicide in Depressed In-Patients

The assessment of suicidal intent is one of the most important problems of clinical psychiatry. An earlier study (Robin, Brooke and Freeman-Browne, 1968) has confirmed the high incidence of suicide in admissions diagnosed at first contact as suffering from affective disorders, and found that 8 per cent. male in-patients and 5 per cent. female in-patients so diagnosed committed suicide during a follow-up of 6–11 years. It was also shown that in male patient suicides unemployment at the time of first admission and a previous history of self-poisoning or self-inflicted injury occurred more often than in matched controls, while a history of more than one suicidal attempt was found more often in female suicides than in matched controls. Female suicides were treated less often with E.C. T. than their controls, and more often with tranquillizers.
PACAP regulates immediate catecholamine release from adrenal chromaffin cells in an activity‐dependent manner through a protein kinase C‐dependent pathway

Adrenal medullary chromaffin cells are a major peripheral output of the sympathetic nervous system. Catecholamine release from these cells is driven by synaptic excitation from the innervating splanchnic nerve. Acetylcholine has long been shown to be the primary transmitter at the splanchnic‐chromaffin synapse, acting through ionotropic nicotinic acetylcholine receptors to elicit action potential‐dependent secretion from the chromaffin cells. This cholinergic stimulation has been shown to desensitize under sustained stimulation, yet catecholamine release persists under this same condition. Recent evidence supports synaptic chromaffin cell stimulation through alternate transmitters. One candidate is pituitary adenylate cyclase activating peptide (PACAP), a peptide transmitter present in the adrenal medulla shown to have an excitatory effect on chromaffin cell secretion. In this study we utilize native neuronal stimulation of adrenal chromaffin cells in situ and amperometric catecholamine detection to demonstrate that PACAP specifically elicits catecholamine release under elevated splanchnic firing. Further data reveal that the immediate PACAP‐evoked stimulation involves a phospholipase C and protein kinase C‐dependant pathway to facilitate calcium influx through a Ni2+ and mibefradil‐sensitive calcium conductance that results in catecholamine release. These data demonstrate that PACAP acts as a primary secretagogue at the sympatho‐adrenal synapse under the stress response.
A framework to model and translate clinical rules to support complex real-time analysis of physiological and clinical data

We present a framework to model and translate clinical rules to support complex real-time analysis of both synchronous physiological data and asynchronous clinical data. The framework is demonstrated through a case study in a neonatal intensive care context showing how a clinical rule for detecting an apnoeic event is modeled across multiple physiological data streams in the Artemis environment, which employs IBM's InfoSphere Streams middleware to support real-time stream processing. Initial clinical hypotheses for apnoea detection are modeled using UML activity diagrams which are subsequently translated into Stream's SPADE code to be deployed in Artemis to deliver real-time decision support. Our aim is to provide a Clinical Decision Support System capable of identifying and detecting patterns in physiological data streams indicative of the onset of clinically significant conditions that that may adversely affect health outcomes. Benefits associated with our approach include: 1) reduced time and effort on the clinician's part to assess health data from multiple sources; 2) the ability to allow clinicians to control the rules-engine of Artemis to enhance clinical care within their unique environments; 3) the ability to apply clinical alerts to both synchronous and asynchronous data; and 4) the ability to continuously process data in real-time.
Increased Expression of the Sodium Transporter BSC-1 in Spontaneously Hypertensive Rats

The purpose of this study was to compare the expression of BSC-1 (bumetanide-sensitive Na+-K+-2Cl– cotransporter) in kidneys of spontaneously hypertensive rats (SHR) versus Wistar-Kyoto (WKY) rats by immunoblotting and reverse transcription-polymerase chain reaction. To determine the specificity of any observed changes in BSC-1 expression, we also compared expression of the thiazide sensitive Na+-Cl– cotransporter (TSC), the type-3 Na+-H+ exchanger (NHE-3), Na+-K+-ATPase-α1, the inwardly rectifying K+ channel (ROMK-1), the type-1 \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{Na}^{+}\mathrm{-}\mathrm{HCO}_{3}^{-}\) \end{document} cotransporter (NBC-1), aquaporin-1, and aquaporin-2. Analyses were performed on outer cortex, outer medulla, and inner medulla. BSC-1 protein was detected in outer medulla and was markedly (6-fold) higher in SHR. TSC protein was detected in the cortex and was not overexpressed in SHR. Aquaporin-1 protein was detected in all three regions and was not overexpressed in SHR. Aquaporin-2 and ROMK-1 proteins were detected in all three regions, but were moderately elevated (2-fold) only in the SHR inner medulla. Na+-K+-ATPase and NHE-3 proteins were detected in all three regions. Na+-K+-ATPase-α1 was modestly (25%) increased in SHR outer and inner medulla, whereas NHE-3 was moderately (2-fold) increased in the SHR cortex and inner medulla. NBC-1 protein was detected only in the cortex and was higher (2-fold) in SHR. mRNA levels of BSC-1, aquaporin-2, and ROMK-1 were not elevated in SHR, indicating a post-translational mechanism of protein overexpression. High-dose furosemide increased fractional sodium excretion more in SHR than WKY (3-fold). We conclude that increased expression of BSC-1, and to a lesser extent, aquaporin-2, ROMK-1, NHE-3, and NBC-1 may contribute to the pathogenesis of hypertension in the SHR.
Objective conjugation and medialisation

This paper is concerned with the origins and the function of the objective verbal conjugation especially in Hungarian but with an eye to general typology and Uralic. Previous attempts at solving problems associated with it are given a critical survey. The author argues that since objective conjugation is neither specific to Hungarian nor to its relatives, whether close or distant, but is found in various language families and language types all over the world, one should seek explanations in universal tendencies rather than giving ad hoc accounts. The universal tendency of medialisation is pointed out here-especially in the first and second persons of the paradigm-, which differentiated what is now called the (unmarked) general or indefinite conjugation from the original unitary conjugation. It is here proposed that what now functions as the objective conjugation results historically from a reinterpretation of the original paradigm as in contrast with the medial (then general) paradigm. This explains the .
Prompts, Goal Setting and Feedback to Increase Suggestive Selling

Suggestive selling has been demonstrated to increase sales in comparison designs in a variety of settings. Similarly prompts have increased suggestive selling in comparison designs. In the present study, prompts, goal-setting, feedback, and praise were used to increase red and white wine sales in a multiple baseline design. This combination increased suggestive selling when applied to each wine. Prompts with just goal-setting and praise produced largely temporary effects. Prompts with feedback and praise tripled the percent of checks containing wine sales; however, these increases were not maintained after the feedback, praise, and prompts were discontinued.
The effectiveness of Talking Mats® with people with intellectual disability

Accessible summary • It is hard for the views of people with learning disability to be listened to. • Talking Mats uses pictures to help people say what they feel about their lives. • This study asked 48 people with learning disability to use Talking Mats to find out how well it works. • The study found that most people found Talking Mats helped them to understand and to say what they feel. • Talking Mats is a useful tool to help find out what people with learning disability feel about their lives. Summary People with intellectual disability have significant difficulties in ensuring their voice is heard. Talking Mats is a low tech communication resource which helps understanding and supports expression. This study examined the effectiveness of the resource for people with intellectual disability. A mixed method quantitative and qualitative study involving 48 people at four levels of comprehension was designed to compare the effectiveness of Talking Mats with the individual’s main communication method. Thirty of the 48 participants were identified as using Talking Mats effectively. Effective use of Talking Mats was associated with functional comprehension. The study found that scores on all indicators of communication effectiveness were higher when using Talking Mats compared to main communication methods. This study identified that Talking Mats can be an effective communication resource for many people with intellectual difficulty and can help them express their views by increasing both the quantity and quality of information communicated.
Review Article: Media Literacy and Public Citizens

Despite the existence of numerous introductory titles already available in media studies and the sociology of culture, these three recent texts are primarily directed at undergraduate students. They have been written by scholars from different countries (UK, US, Norway) and deal with media studies from various perspectives, disciplines and approaches, namely social history, cultural sociology and media theory. Each one raises fundamental questions about key concepts not only in the sociology of culture, media studies and cultural theory, but also more specifically in the study of public opinion and the public sphere. In a quite useful way, British historians Asa Briggs and Peter Burke have written a very readable book that summarizes what you would need to know about media history since the early modern period (from the ‘print revolution’, around 1450) in order to understand some of the key issues and new challenges in contemporary communications research. The first half of their book encompasses the period from the 15th to the 19th centuries, while the second half is mainly concerned with 20th-century events, concentrating on radio, television, and to a much lesser extent the film industry (pp. 167–73). The last chapter deals with issues related to media ownership, concentration, the Internet and other new technologies (pp. 320–33). We often hear nowadays that communications have become enormously fast, particularly since the advent of cyberspace; even the definition of what communication is all about has changed much in less than half a century. Briggs and Burke note in their conclusion that
A new approach of coding to improve speed and noise tolerance of on-chip busses

This paper introduces a new coding scheme that faces simultaneously different issues of interconnection design (power, noise and crosstalk). Based on skewing signals on the link, its implementation is very simple and area-efficient. This scheme permits to double bandwidth and to improve noise tolerance through the use of two error detecting codes. The first one uses temporal redundancy and the second one is a parity-based detecting code. This noise tolerance property enables to decrease the power supply voltage to reduce power consumption.