Miracle-dz/UniFAR-FTUs huggingface dataset:
K-RasV14I recapitulates Noonan syndrome in mice

Significance Noonan syndrome (NS) is a developmental disorder caused by germ-line mutations in various components of the RAS signaling pathway. The pathophysiological mechanisms underlying the clinical manifestations in NS patients and the basis for the observed phenotypic variability are poorly understood. To date, mouse models carrying mutations in Protein Tyrosine Phosphatase Non-Receptor type 11 (Ptpn11), Son of Sevenless homolog 1 (Sos1), and Raf1 loci have been described. The new model described here, induced by K-RasV14I expression, recapitulates most of the NS features including small size, craniofacial dysmorphism, cardiac defects, and myeloproliferative disorders, highly reminiscent of juvenile myelomonocytic leukemia. These mice should help us understand better the phenotypic variations of NS and serve as a preclinical tool to test forthcoming therapies based on the design of novel inhibitors of the RAS pathway. Noonan syndrome (NS) is an autosomal dominant genetic disorder characterized by short stature, craniofacial dysmorphism, and congenital heart defects. NS also is associated with a risk for developing myeloproliferative disorders (MPD), including juvenile myelomonocytic leukemia (JMML). Mutations responsible for NS occur in at least 11 different loci including KRAS. Here we describe a mouse model for NS induced by K-RasV14I, a recurrent KRAS mutation in NS patients. K-RasV14I–mutant mice displayed multiple NS-associated developmental defects such as growth delay, craniofacial dysmorphia, cardiac defects, and hematologic abnormalities including a severe form of MPD that resembles human JMML. Homozygous animals had perinatal lethality whose penetrance varied with genetic background. Exposure of pregnant mothers to a MEK inhibitor rescued perinatal lethality and prevented craniofacial dysmorphia and cardiac defects. However, Mek inhibition was not sufficient to correct these defects when mice were treated after weaning. Interestingly, Mek inhibition did not correct the neoplastic MPD characteristic of these mutant mice, regardless of the timing at which the mice were treated, thus suggesting that MPD is driven by additional signaling pathways. These genetically engineered K-RasV14I–mutant mice offer an experimental tool for studying the molecular mechanisms underlying the clinical manifestations of NS. Perhaps more importantly, they should be useful as a preclinical model to test new therapies aimed at preventing or ameliorating those deficits associated with this syndrome.
Some practical and theoretic concepts in the nutritional assessment of the cancer patient

Two patterns of response, that due to starvation or semistarvation and that due the stress, determine whether protein‐calorie malnutrition of the adult marasmus variety or hypoalbuminemic malnutrition will occur in any particular nomnalignant disease. The latter condition can have two major components, the neuroendocrine response to injury, which is in large measure mediated by hormones of the hypothalamus and adrenal gland, and the panoply of responses to interleukin‐1 production and release by macrophages and monocytes upon activation, usually by phagocytosis. In some cancer patients with weight loss there are many similarities to an interleukin‐1 response including increases in resting energy expenditure, whole‐body protein flux and synthesis and glucose flux and recycling, hypoalbuminemia and increased albumin catabolic rates, and an adaptive low T3 state that suggest a similar injury/infection response. Separation of cancer patients with malnutrition into those with an injury/infection response and those with simple starvation may explain the heterogeneous response to nutritional support among malnourished cancer patients and suggest new feeding regimens that may uniquely benefit the stress form of cancer malnutrition.
A primer for handling missing values in the analysis of education and training data

Abstract Quantitative research in vocational education and training (VET) is routinely affected by missing or incomplete information. However, the handling of missing data in published VET research is often sub-optimal, leading to a real risk of generating results that can range from being slightly biased to being plain wrong. Given that the growing availability of data from large-scale surveys and administrative collections offers exciting new opportunities for quantitative VET research, it is important that researchers follow best-practice approaches when using such data in their own work. Against this backdrop, we: (1) provide a primer on the use of appropriate missing data methods for quantitative VET research; and (2) illustrate the detrimental effects of inefficient methods on research results via a simulation study using real-world education and training data from the Longitudinal Surveys of Australian Youth (LSAY).
Differentially Private Publication of Sparse Data

The problem of privately releasing data is to provide a version of a dataset without revealing sensitive information about the individuals who contribute to the data. The model of differential privacy allows such private release while providing strong guarantees on the output. A basic mechanism achieves differential privacy by adding noise to the frequency counts in the contingency tables (or, a subset of the count data cube) derived from the dataset. However, when the dataset is sparse in its underlying space, as is the case for most multi-attribute relations, then the effect of adding noise is to vastly increase the size of the published data: it implicitly creates a huge number of dummy data points to mask the true data, making it almost impossible to work with. We present techniques to overcome this roadblock and allow efficient private release of sparse data, while maintaining the guarantees of differential privacy. Our approach is to release a compact summary of the noisy data. Generating the noisy data and then summarizing it would still be very costly, so we show how to shortcut this step, and instead directly generate the summary from the input data, without materializing the vast intermediate noisy data. We instantiate this outline for a variety of sampling and filtering methods, and show how to use the resulting summary for approximate, private, query answering. Our experimental study shows that this is an effective, practical solution, with comparable and occasionally improved utility over the costly materialization approach.
CONTRIBUTIONS TO THE PHYSIOLOGY OF THE CONDITIONED REFLEX

DEDICATION It is a joy and a privilege to be one of those participating in the Seventy Year Jubilee for Adolf Meyer. This article is proffered with a full sense of its shortcomings as a positive contribution to the psychobiology for which he stands. The choice of this limited material was based on the fact that it represents a group of completed and related experiments. The laboratory from which these data are reported owes its origin to Dr. Meyer; it is therefore fitting and with a deep sense of personal gratitude for his encouragement and guiding criticisms that this survey of completed work is dedicated to him. HISTORICAL REVIEW As early as 500 B. C. Pythagoras spoke of the brain as the central organ of the higher forms of activity, a view upheld by Hippocrates and Galen but denied by Aristotle. About the beginning of the nineteenth century the attention
Investigation of Diakoptics as a resourceful tool in power system analysis

The resourcefulness of Diakoptics as a tool with the potential ability to meet the challenges of modern power system analysis is outlined. The benefits include the generally accepted saving in computation time, but higher accuracy and the ability to use multicomputer configurations in analyses are highlighted. One of the reasons for the non-acceptance of Diakoptics as a universal tool is said to be the difficulty in understanding the concept. The concept is demonstrated using simple illustrative examples that are easy to understand and verify.
Differential effects of alcohol intoxication on S100B levels following traumatic brain injury.

BACKGROUND In an acute care setting, evaluation of traumatic brain injury (TBI) is often complicated by alcohol intoxication. The purpose of this study is to evaluate the clinical utility of the protein S100B as a biochemical marker for identifying brain injury in patients who are intoxicated at the time of injury. METHODS The study participants were 160 patients who presented to a large urban Level I Trauma Centre in Vancouver, Canada. Patients were classified into four clinical groups (medical controls, trauma controls, mild TBI, and definite TBI) and two day-of-injury alcohol intoxication groups (i.e., sober and intoxicated). Blood samples were collected via venipuncture in heparinized tubes within 8 hours of injury. Measures of S100B concentration were obtained using a commercially available assay kit (Sangtec 100 Elisa). RESULTS For those patients who were sober at the time of injury, higher S100B levels were associated with TBI when compared with other physical injuries and general medical complaints. However, for patients who were intoxicated at the time of injury, there were uniformly low S100B levels across all clinical groups. CONCLUSIONS Although there seems to be a strong association between S100B levels and TBI, further research is required to establish the clinical role of S100B in patients with suspected TBI, particularly in patients whose clinical presentation is complicated by alcohol intoxication.
Equitable partitioning with obstacles

We consider the problem of dividing a territory into sub-regions so as to balance the workloads of a collection of facilities or vehicles over that territory. We assume that the territory is a connected polygonal region, i.e. a simply connected polygon containing a set of simply connected obstacles. The territory also contains a collection of facilities, represented by a set of n fixed points in the territory. We give a fast analytic center cutting plane method that divides the territory into n compact, connected sub-regions, each of which contains a facility, such that the workloads in each sub-region are “balanced”. Our approach can also be used to design a control policy that allows us to design the sub-regions in a decentralized fashion.
Revisiting women managers and organisational acceptance

Purpose – The purpose of this paper is to revisit earlier predictions by Judi Marshall in 1991 to explore whether similar issues were evident in a sample of contemporary female managers.Design/methodology/approach – Qualitative data from six Australian female managers who had participated in a longitudinal study over a period of ten years were examined. Career advancement aspirations and outcomes were compared with those of male managers, and reflections on the managerial role, and organisational practices were sought.Findings – Examples of organisational resilience “to involve women in organisations on equal terms” were evident in all the six female managers in the study. In addition, even when levels of success were achieved, it could be questioned whether these women could be seen as “definers of meaning (or culture)”. Practical implications – Organisational culture appears to continue to create difficulties for contemporary women in management. A system of accountability is strongly recommended, based .
Another flew over the digital divide: internet usage in the Arab-Palestinian sector in Israel during municipal election campaigns, 2008

This article is part of a pioneering study which analyses Internet usage by some 600 candidates for heads of 156 local authorities in Israel in the municipal campaigns of 2008. Despite the importance attributed to the municipal elections in the Arab-Palestinian sector in Israel, the high turnout rate, the competitiveness of the elections and the continuing penetration of the Internet, it was scarcely used by candidates, compared to about 50% usage by candidates who competed in municipalities with Jewish populations. Interviews suggest that beyond access gaps, additional obstacles impede the usage of the Internet as an effective political tool in the Arab-Palestinian sector.
Topic modeling for spoken document retrieval using word- and syllable-level information

Topic modeling for information retrieval (IR) has attracted significant attention and demonstrated good performance in a wide variety of tasks over the years. In this article, we first present a comprehensive comparison among various topic modeling approaches, including the so-called document topic models (DTM) and word topic models (WTM), for Chinese spoken document retrieval (SDR). Moreover, in order to lessen SDR performance degradation when using imperfect recognition transcripts, we also leverage different levels of indexing features for topic modeling, including words, syllable-level units and their combinations. All the experiments are performed on the TDT Chinese collection.
Native American Ethnicity and Childhood Maltreatment as Variables in Perceptions and Adjustments to Boot Camp vs. “Traditional” Correctional Settings

Abstract A sample of 302 juveniles confined in two separate correctional facilities in a Western plains state was assessed to examine the relationship between child maltreatment and other delinquency risk factors, and Native American ethnicity on perceptions of the institutional environments and psychological adjustment in a boot camp and traditional facility. The results indicate few differences between Native and non-Native American youth's perceptions of institutional environments. Youth institutionalized in the boot camp, however, differed significantly from those in the traditional facility in their perceptions of institutional activity, control, justice, and freedom. Child maltreatment and other risk factors were related to psychological adjustment for all youth. In addition, the boot camp facility significantly reduced anxiety for Native American youth. The implications of this research for boot camps and juvenile justice policy are discussed.
Coping with prescription drug cost sharing: knowledge, adherence, and financial burden.

OBJECTIVE Assess patient knowledge of and response to drug cost sharing. STUDY SETTING Adult members of a large prepaid, integrated delivery system. STUDY DESIGN/DATA COLLECTION Telephone interviews with 932 participants (72 percent response rate) who reported knowledge of the structures and amounts of their prescription drug cost sharing. Participants reported cost-related changes in their drug adherence, any financial burden, and other cost-coping behaviors. Actual cost sharing amounts came from administrative databases. PRINCIPAL FINDINGS Overall, 27 percent of patients knew all of their drug cost sharing structures and amounts. After adjustment for individual characteristics, additional patient cost sharing structures (tiers and caps), and higher copayment amounts were associated with reporting decreased adherence, financial burden, or other cost-coping behaviors. CONCLUSIONS Patient knowledge of their drug benefits is limited, especially for more complex cost sharing structures. Patients also report a range of responses to greater cost sharing, including decreasing adherence.
Outcome of inflammatory response after normothermia during cardiopulmonary bypass surgery in infants with isolated ventricular septal defect

Purpose A recent study analyzing several cytokines reported that long cardiopulmonary bypass (CPB) time and long aortic cross clamp (ACC) time were accompanied by enhanced postoperative inflammation, which contrasted with the modest influence of the degree of hypothermia. In this present study, we aimed to examine the effect of CPB temperature on the clinical outcome in infants undergoing repair of isolated ventricular septal defect (VSD). Methods Of the 212 infants with isolated VSD who underwent open heart surgery (OHS) between January 2001 and December 2010, 43 infants were enrolled. They were classified into 2 groups: group 1, infants undergoing hypothermic CPB (26℃-28℃; n=19) and group 2, infants undergoing near-normothermic CPB (34℃-36℃; n=24). Results The age at the time of the OHS, and number of infants aged<3 months showed no significant differences between the groups. The CPB time and ACC time in group 1 were longer than those in group 2 (88 minutes vs. 59 minutes, P=0.002, and 54 minutes vs. 37 minutes, P=0.006 respectively). The duration of postoperative mechanical ventilation was 1.6 days in group 1 and 1.8 days in group 2. None of the infants showed postoperative neurological and developmental abnormalities. Moreover, no postoperative differences in the white blood cell count and C-reactive protein levels were noted between two groups. Conclusion This study revealed that hypothermic and near-normothermic CPB were associated with similar clinical outcomes and inflammatory reactions in neonates and infants treated for simple congenital heart disease.
Therapeutic Process and Outcome: The Interplay of Research

Abstract From Freud through to modern times researchers have aimed to develop a clearer understanding of therapeutic processes and outcomes. Despite this continued interest in the field, the representation of psychotherapy processes and the applicability of research findings and recommendations to the therapeutic field continue to prove difficult. Quantitative and qualitative studies each purport to provide answers, however, they differ greatly in their research methods and underlying ontological and epistemological views. Efficacy and effectiveness studies and the measures of statistical significance and clinical significance are explored with their inherent strengths and weaknesses highlighted. This paper presents the view that research into psychotherapy should enhance the experiences of both the therapist and client. For this to be achieved it is recommended that quantitative and qualitative data, or objective and subjective experiences, should collude rather than collide.
Pupillometric evidence for the locus coeruleus-noradrenaline system facilitating attentional processing of action-triggered visual stimuli

It has been argued that attentional processing of visual stimuli is facilitated by a voluntary action that triggers the stimulus onset. However, the relationship between action-induced facilitation of attention and the neural substrates has not been well established. The present study investigated whether the locus coeruleus-noradrenaline (LC-NA) system is involved in this facilitation effect. A rapid serial visual presentation paradigm was used to assess the dynamics of transient attention in humans. Participants were instructed to change a digit stream to a letter stream by pressing a button and specifying successive targets of four letters. Pupil dilation was measured as an index of LC-NA function. Accuracy of target identification was better when the temporal delay between participants’ key press and target onset was 800 ms than when targets appeared just after the key press or when targets appeared without key press. Accuracy of target identification was positively correlated with both the peak amplitude of pupil dilation and the pupil size at the time of the key press. These results indicate that target identification in the visual task is closely linked to pupil dilation. We conclude that the LC-NA system plays an important role in the facilitation of transient attention driven by voluntary action.
The Effectiveness of Bone Mineral Density as Supplementary Tool for Evaluation of the Osteogenic Potential in Patients with Spinal Fusion

Study Design Retrospective study. Purpose This study was designed to determine the effectiveness of bone mineral density measurement as a supplementary tool for evaluation of osteogenic potential in patients with spinal fusion. To this end, we correlated bone mineral density (BMD) with osteogenic potential from cultured mesenchymal stem cells (MSCs). Overview of Literature Many studies have correlated osteogenic potential of in vitro cultured MSCs with aging or osteoporosis. Methods We studied twenty-five individuals with harvested bone marrow from the ilium during lumbar spinal surgery. The BMD of the femoral neck was measured using dual energy X-ray absorptiometry prior to bone marrow aspiration, and the osteoporotic group was classified as those with T-scores below-2.5. After MSCs were isolated from bone marrow, in vitro induction of osteogenesis was performed. We analyzed the patient's osteogenic potential from cultured MSCs such as mineral deposition stain, bone alkaline phosphatase (ALP) activity and osteoblast-specific gene expression in RT-PCR. Results On mineral staining, the osteoporotic group had a scanty matrix mineral deposition in contrast to the non-osteoporotic group. The expression of osteocalcin in the osteoporotic group was 1.5 to 3 times less than in the non-osteoporotic group. At the 3rd week after the induction of osteogenesis, the activity of ALP of cultured MSCs in the osteoporotic group was lower than in the control group (mean, 45±19 u/L, in osteoporotic group vs 136±7 u/L in non-osteoporotic), and there was a statistically significant and positive correlation between BMD & ALP (r=0.487, p=0.013). Conclusions There is a positive correlation between BMD and osteogenic potential derived from MSCs. The measurement of BMD can provide supplementary data for evaluating osteogenic potential clinically.
Security Issues in Wireless Distance Vector Routing Protocols

Most of the ad-hoc wireless network routing protocol assume a trusted environment, mainly because securing communications between routers using conventional authentication methods (asymmetric cryptography, digital signatures, use of symmetric cryptography) are resource consuming. Secure routing protocols become of critical importance and have a lot of proposals to improvement security mechanisms. In this paper we will present the main security issues encountered in these environments and make a comparative study of the proposed mechanisms for securing the communication between wireless router nodes. Different kind of attack have different solution, and we try to select them to be combine in one solution without exceed de routing node capacities.