Miracle-dz/UniFAR-FTUs huggingface dataset:
NDRG1 Is Necessary for p53-dependent Apoptosis*

Although a number of target genes for the tumor suppressor p53 have been described, the mechanism of p53-dependent apoptosis is incompletely understood. Thus, it is essential to identify and characterize additional target genes that could mediate apoptosis. In the study reported here, we isolated a p53-regulated gene named NDRG1 (N-Myc down-regulated gene 1). Its expression is induced by DNA damage in a p53-dependent fashion. The promoter region of the NDRG1 gene contains a p53 binding site that confers p53-dependent transcriptional activation via a heterologous reporter. RNA interference and inducible gene expression approaches suggest that NDRG1 is necessary but not sufficient for p53-mediated caspase activation and apoptosis. This report further supports the notion that p53 controls a network of genes that are required for its apoptotic function.
Perception of Object Length Via Manual Wielding in Children With and Without Developmental Coordination Disorder

ABSTRACT The authors compared haptic perception via active manual wielding in children with and without developmental coordination disorder (DCD). Forty-eight children, 11–12 years old, participated as volunteers. Twenty-four were typically developing children (TDC), and 24 had been diagnosed with DCD. Individually, children held and wielded unseen rods of five lengths (20, 45, 60, 75, or 90 cm). Based on this wielding, children judged the length of each rod. Judgments of rod length were shorter in the DCD group than in the TDC group. In addition, significant interactions revealed that the difference between the 2 groups was progressively greater for longer rods. The results provide support for the hypothesis that DCD includes deficits in the ability to use manual wielding in the perception of object length. In addition, the results suggest that the deficit is not general, but is greater for longer objects.
Efficient realization of logical execution times in legacy embedded software

The Logical Execution Time (LET) programming model has been recently employed as a parallel programming paradigm for multi-core platforms, in particular for porting large single-core applications to multi-core versions, which is a serious challenge faced in major industries, such as the automotive one. In this paper, we consider a transformation process from legacy single-core software to LET-based versions that are ready for multi-core, and focus on the problem of minimizing computational costs rooted in the additional buffering that is required to achieve the LET communication semantics, especially for parallel executions and in the presence of legacy event-driven functions that remain outside of the LET specifications. We propose a static analysis that proceeds top-down through successive layers of abstraction, where an optimal solution at a certain layer represents a minimal upper bound on the set of buffers determined in the next layer. We present a solution for the top layer, which is platform-independent and has no restrictions on executions of event-driven software. Furthermore, we derive optimal buffering for a second layer with a minimal platform configuration. We refer here to a three-layer implementation, which has been successfully applied to industrial automotive software, where further savings are achieved in the mapping from second layer buffers to memory locations. We also point to evaluation results, demonstrating the applicability of the approach in industrial settings.
Listeria monocytogenes infection in inflammatory bowel disease patients: case series and review of the literature

Background Listeria monocytogenes (LM) is a gram-positive intracellular bacillus that in immunodeficient patients, children, geriatric patients, pregnant women, and even in healthy individuals can cause central nervous system infection, bacteremia, and other clinical manifestations, becoming a relevant pathogen. Materials and methods From the Microbiology Service data of ‘Gregorio Marañón’ Hospital, we selected all positive biological sample cultures for LM from inflammatory bowel disease (IBD) patients, from January 1986 until January 2011. These cases were included in an SPSS database, analyzing several basal clinical characteristics and factors related to the infection. Results Three patients diagnosed with IBD had positive cultures for LM during this period. All of them were male, and also all of them had a diagnosis of Crohn’s disease. Every patient had a corticosteroid cumulated dose of more than 400 mg (equivalency in methylprednisolone doses), adding anti-tumor necrosis factor-&agr; treatment (certolizumab) in one patient. Prior colonoscopy with biopsy was performed in two patients. Clinical presentation of the infection was bacteremia in two patients, accompanied by central nervous system infection in one patient. One patient had isolated meningoencephalitis. Despite correct empiric treatment, one patient died from a cause related to the infection, that is, rombencephalitis. Increased incidence of LM bacteremia was found in IBD patients, compared with the general population (12.2 bacteremias/100 000 IBD patient-years, compared with 1.6 bacteremias/100 000 person-years), with an odds ratio of 7.4. Conclusion IBD patients may be at risk for more frequent and serious LM infection compared with the general population.
Model Uncertainty in Panel Vector Autoregressive Models

We develop methods for Bayesian model averaging (BMA) or selection (BMS) in Panel Vector Autoregressions (PVARs). Our approach allows us to select between or average over all possible combinations of restricted PVARs where the restrictions involve interdependencies between and heterogeneities across cross-sectional units. The resulting BMA framework can find a parsimonious PVAR specification, thus dealing with overparameterization concerns. We use these methods in an application involving the euro area sovereign debt crisis and show that our methods perform better than alternatives. Our findings contradict a simple view of the sovereign debt crisis which divides the euro zone into groups of core and peripheral countries and worries about financial contagion within the latter group.
The Phenomenology of Tourism Space

Abstract Although it is among the most frequently used notions in the study of tourism, the concept of tourism space is understood in a variety of ways. Similar to the term ‘geographical space’, it is often used intuitively, often in quite dissimilar contexts. This paper provides an analysis of the concept of ‘tourism space’ from the perspective of geography, based on a phenomenological approach.
Qualitative Corporate Disclosure and Credit Analysts’ Soft Rating Adjustments

Credit ratings are determined by both quantitative and qualitative inputs. While academics have extensively studied quantitative models of credit risk analysis, far less is known about credit analysts’ soft or qualitative adjustments to the outputs generated by their models. We examine whether and how credit analysts employ borrowers’ credit risk relevant qualitative disclosure in making their credit risk assessments. We provide evidence which suggests that credit analysts impound the information conveyed by borrowers’ qualitative disclosure in their credit ratings. Our results further indicate that the soft, but not hard, adjustments are the mechanism by which the information in borrowers’ qualitative disclosure is impounded into the rating. We next examine whether the efforts analysts expend to extract credit risk relevant information from qualitative disclosure affects the informativeness of credit ratings. We find that credit rating downgrades that involve soft adjustments or greater amounts of qualitative disclosure are more informative than those that do not; however, the increase in informativeness diminished after the Regulation Fair Disclosure exemption was repealed by the Dodd-Frank Act whereby legal liability for credit rating agencies increased.
Arthrogryposis multiplex congenita (amyoplasia): an orthopaedic perspective.

Arthrogryposis is a term that encompasses a group of rare but heterogeneous disorders affecting children in which there are at least 2 or more joint contractures in multiple body areas. There are 104 syndromes listed when using the search term arthrogryposis on the Web site "Online Mendelian In
Aqueous extracts of FBD, a Chinese herb formula composed of Poria cocos, Atractylodes macrocephala, and Angelica sinensis reverse scopolamine induced memory deficit in ICR mice

Herb formula FBD is composed of fu ling [or poria, or the sclerotium of the fungus of Poria cocos (Schw.) Wolf (Polyporaceae)], bai zhu [white atractylodes rhizome, or the rhizome of Atractylodes macrocephala Koidz. (Compositae)], and dang gui [or dong quai, Chinese angelica root, or the root of Angelica sinensis (Oliv.) Diels (Umbelliferae)], the three Chinese medicinal plants used traditionally to improve cognitive disorders. The present study aimed to observe the effects of dual doses of aqueous extracts of FBD (200 and 600 mg/kg) administered orally for 6 days on memory deficit induced by scopolamine, 4 mg/kg intraperitoneally (i.p.) in male imprinting control region (ICR) mice. Aqueous extracts of FBD markedly ameliorated scopolamine induced memory deficit in passive step-through avoidance test and passage water maze test, significantly inhibited acetylcholinesterase (AChE) activity in cortex and hippocampus, and circulating butyrylcholinesterase activity. Moreover, cortical AChE activity in vitro was suppressed in a dose-dependent manner by aqueous extracts of FBD at 50–200 μg crude herb/mL, in which dang gui extract exerted a stronger anti-AChE activity than that of fu ling or bai zhu. In contrast, no acute toxicity was observed within 14 days, after administration with FBD extracts at the maximal tolerable dose of 69 g/kg. These results suggested that FBD might be a potential and safe herbal agent for Alzheimer’s disease, and its nootropic action was mediated, in part, via enhancing the cholinergic nervous system.
Cytotoxic triplets plus a biologic: state-of-the-art in maximizing the potential of up-front medical treatment of metastatic colorectal cancer

Introduction: Up-front treatment of metastatic colorectal cancer (mCRC) has progressively become more complex during last few years. Nowadays, treatment options range from monotherapies with biologics or traditional chemotherapeutic agents to intensive combinations of chemotherapy plus targeted drugs. Areas covered: This review deals with the results of the most recent first-line trials in the medical treatment of mCRC, with a special focus on recently closed or ongoing trials of intensive concomitant combinations of all active cytotoxics plus a biologic agent. Expert opinion: Combinations of three cytotoxic drugs plus a biologic are under clinical investigation and therefore should not be recommended for routine use, nevertheless preliminary results are promising. The main challenges for the future are not only to demonstrate the real clinical usefulness of intensive approaches, but also to gain the ability of defining prior to treatment which patients will benefit most on the basis of clinical and molecular elements.
Assessment of Morphological and Immunohistological Alterations in Long-Term Keloid Skin Explants

One of the major impediments in keloid research is the lack of a keloid animal model that can mimic human keloid. This imposes investigative constraints on studying cellular interactions and biochemical processes that normally occur in vivo.Our main objective is to establish an in vitro model for maintaining long-term viable keloid dermal explants as a tool for investigating the pathogenesis of keloid scar formation. Explants of adult keloid scars were cultured in vitro by embedding them in enriched collagen gel matrix and maintaining them for up to 6 weeks, whereupon changes in tissue morphology and cellular differentiation were examined. The effects of medium enrichment, air versus liquid submersion, and different substrates on the explants were examined. Our results indicated that keloid explants embedded in a collagen gel matrix were morphologically better preserved than explants placed on a plastic substrate. Explants with epidermis at the air-liquid interface had better morphology than collagen-submerged explants, and there were no differences between serum-free and serum-supplemented explant cultures. Immunohistochemical and apoptotic analyses were performed to assess cellular viability and differentiation. In situ hybridization confirmed that keloid fibroblasts had sustained collagen type I gene expression throughout the 6 weeks in culture, thus validating the integrity of a long-term keloid culture system. In conclusion, the collagen-embedded skin explant system demonstrates that keloid tissues could be maintained for up to 6 weeks for long-term in vitro studies.
Review of a decision by the Medical Services Advisory Committee based on health technology assessment of an emerging technology: The case for remotely assisted radical prostatectomy

Objectives: In April 1998, the Medical Services Advisory Committee (MSAC) was established by the Australian federal government. Since that time, all new medical procedures must be evaluated for safety, effectiveness, and cost-effectiveness as a condition of the surgeon receiving public funding by means of the Medicare Benefits Schedule (MBS). Over these first 8 years, a significant number of applications for the public funding of new procedures have been given negative recommendations by the MSAC based on insufficient clinical evidence or lack of cost-effectiveness. In August 2006, after almost 2 years of processing, the MSAC made the decision to fund the new procedure, laparoscopic remotely assisted radical prostatectomy (LRARP). However, they stated that there was still uncertainty about the comparative cost-effectiveness. Methods: An observational study using provisional cost-utility data for LRARP based on a combination of costs taken from consecutive patients at the Epworth Hospital, Melbourne, Australia, and utilities from the prospectively collected data on all patients undergoing surgery for prostate cancer over a 4-year period at the Vattikuti Urology Institute, Michigan, United States. Results: The incremental cost for LRARP compared with the open surgery alternative is A$2,264 or A$24,457 per quality-adjusted life-year, well below the range accepted by the Australian pharmaceutical equivalent of the MSAC (the PBAC) of A$42,000 and A$76,000. This figure does not take into account additional benefits such as reduced time away from employment, reduced blood loss, reduced possibility of infection, and reduced scarring. Conclusions: This case study of LRARP demonstrates that there is sufficient crude evidence to show that this new procedure is likely to be superior to the existing procedure in terms of safety, effectiveness, and cost-effectiveness. The decision to allow MBS funding was correct and will allow for the collection of additional evidence, on both economic and clinical outcomes.
Immunologic thrombocytopenic purpura in human immunodeficiency virus--seropositive patients with hemophilia. Comparison with patients with classic autoimmune thrombocytopenic purpura, homosexuals with thrombocytopenia, and narcotic addicts with thrombocytopenia.

The immunologic platelet profile of 29 patients with hemophilia who had received multiple transfusions (14 had thrombocytopenia) was compared with profiles of 15 patients with classic autoimmune thrombocytopenia. Thrombocytopenic hemophiliacs who were seropositive for the human immunodeficiency virus (13 out of 14) had platelet-bound immunoglobulin G and C3C4 levels as well as circulating immune complexes that were 15.1-, 4.0-, and 2.4-fold greater, respectively, than normal control subjects' platelets and 3.4-, 2.6-, and 2.4-fold greater, respectively, than autoimmune thrombocytopenic patients' platelets. Hemophiliacs with normal platelet counts (nine out of 13 seropositive) had elevated values that were intermediate in level between those of thrombocytopenic hemophiliacs and those of classic autoimmune thrombocytopenic patients. The four seronegative hemophiliacs had normal values (except for one platelet-bound IgG measurement). An inverse correlation was noted between platelet count and platelet-bound IgG, r = -0.838, P less than 0.001. Serum antiplatelet reactivity (1:256 mean titer compared with control sera) resided predominantly in the 7S IgG fraction, and bound to autologous as well as homologous platelets at concentrations as low as 0.06 to 0.13 mg/ml. F(ab')2 fragments of the 7S IgG fraction inhibited binding of hemophilic IgG to normal platelets and bound to normal platelets at concentrations as low as 0.06 mg/ml. Antiplatelet IgG could be eluted from six of six hemophilic and eight of eight classic autoimmune thrombocytopenic patients. (ABSTRACT TRUNCATED AT 250 WORDS)
Interventions after Screening for Hearing Difficulties: A Retrospective Investigation of Interventions other than Hearing Aids

There have been a number of studies on screening of hearing in adult populations. Despite the high importance of interventions following screening for hearing (Wilson and Jungner, 1968) there is a dearth of information on the nature of interventions following such screening, other than hearing aid fitting (HA) or referral to audiology/ENT departments (Pronk et al., 2011). In the late 1980s and early 1990s four studies were performed in Wales, which offered such other interventions to those individuals indicating hearing disabilities in screening questionnaires (eg Stephens et al., 1990; Davis et al., 1992). The majority of the patient notes from these studies were still accessible and have been examined to extract the following information: - what interventions were used other than hearing aids? - who received these interventions? - would they have been more appropriate than HAs for some of those fitted? The aim of this paper is to list the interventions provided in these studies and relate them to the initial complaints of those indicating hearing problems.
Dynamics of the Hck‐SH3 domain: Comparison of experiment with multiple molecular dynamics simulations

Molecular dynamics calculations provide a method by which the dynamic properties of molecules can be explored over timescales and at a level of detail that cannot be obtained experimentally from NMR or X‐ray analyses. Recent work (Philippopoulos M, Mandel AM, Palmer AG III, Lim C, 1997, Proteins 28:481–493) has indicated that the accuracy of these simulations is high, as measured by the correspondence of parameters extracted from these calculations to those determined through experimental means. Here, we investigate the dynamic behavior of the Src homology 3 (SH3) domain of hematopoietic cell kinase (Hck) via 15N backbone relaxation NMR studies and a set of four independent 4 ns solvated molecular dynamics calculations. We also find that molecular dynamics simulations accurately reproduce fast motion dynamics as estimated from generalized order parameter (S 2) analysis for regions of the protein that have experimentally well‐defined coordinates (i.e., stable secondary structural elements). However, for regions where the coordinates are not well defined, as indicated by high local root‐mean‐square deviations among NMR‐determined structural family members or high B‐factors/low electron density in X‐ray crystallography determined structures, the parameters calculated from a short to moderate length (less than 5–10 ns) molecular dynamics trajectory are dependent on the particular coordinates chosen as a starting point for the simulation.
Six-Month Survival of Microencapsulated Pig Islets and Alginate Biocompatibility in Primates: Proof of Concept

Background. Pig islets xenotransplantation remains associated with a strong humoral and cellular xenogeneic immune responses. The aim of this study was to assess the long-term biocompatibility of alginate encapsulated pig islets after transplantation in primates Methods. Adult pig islets encapsulated in alginate under optimal conditions (n=7) or not (n=5) were transplanted under the kidney capsule of nondiabetic Cynomolgus maccacus. Additional primates received empty capsules (n=1) and nonencapsulated pig islets (n=2) as controls. Capsule integrity, cellular overgrowth, pig islet survival, porcine C-peptide and anti-pig IgM/IgG antibodies were examined up to 6 months after implantation Results. Nonencapsulated islets and islets encapsulated in nonoptimal capsules were rapidly destroyed. In seven primates receiving perfectly encapsulated pig islets, part of the islets survived up to 6 months after implantation without immunosuppression. Porcine C-peptide was detected after 1 month in 71% of the animals. The majority of grafts (86%) were intact and completely free of cellular overgrowth or capsule fibrosis. Explanted capsules, after 135 (n=2/2) and 180 (n=2/3) days, demonstrated residual insulin content and responses to glucose challenge (stimulation index of 2.2). Partial islet survival was obtained despite an elicited anti-pig IgG humoral response Conclusions. Optimal alginate encapsulation significantly prolonged adult pig islet survival into primates for up to 6 months, even in the presence of antibody response.
Technological Improvements for Linear Ion Trap Experiments

Laser-cooled, trapped ions are a highly controlled experimental system that allows one to engineer novel quantum states of both fundamental and practical interest. For a string of ions in a linear radio frequency (RF) Paul trap, the linear-zigzag structural phase transition is an intriguing system to investigate quantum dynamics near the critical point of a prototype second-order phase transition, including the preparation of superposition states of different structural configurations. This thesis focuses on two technological improvements required for studying the linear-zigzag structural phase transition in the quantum regime. The first is the development of a compact and cost-effective RF synthesizer setup to provide multiple modulation sources for the laser manipulation of ion strings. The functionality and limitations of a prototype design, based on Direct Digital Synthesizer (DDS) development boards with a microcontroller interface, are evaluated and future improvements are identified. The second part of this thesis focuses on the stabilization of the secular trap frequencies in a linear Paul trap, which is necessary to obtain a stable critical point for the studies of the linear-zigzag transition. To this end, this thesis presents the implementation of a Ramsey spectroscopic technique to measure the secular frequencies and presents the preliminary results from the stability tests.