Miracle-dz/UniFAR-FTUs huggingface dataset:
Dual Endothelin-A/Endothelin-B Receptor Blockade and Cardiac Remodeling in Heart Failure With Preserved Ejection Fraction

Background—Despite the increasing prevalence of heart failure with preserved ejection fraction (HFpEF) in humans, there remains no evidence-based therapies for HFpEF. Endothelin-1 (ET-1) antagonists are a possibility because elevated ET-1 levels are associated with adverse cardiovascular effects, such as arterial and pulmonary vasoconstriction, impaired left ventricular (LV) relaxation, and stimulation of LV hypertrophy. LV hypertrophy is a common phenotype in HFpEF, particularly when associated with hypertension. Methods and Results—In the present study, we found that ET-1 levels were significantly elevated in patients with chronic stable HFpEF. We then sought to investigate the effects of chronic macitentan, a dual ET-A/ET-B receptor antagonist, on cardiac structure and function in a murine model of HFpEF induced by chronic aldosterone infusion. Macitentan caused LV hypertrophy regression independent of blood pressure changes in HFpEF. Although macitentan did not modulate diastolic dysfunction in HFpEF, it significantly reduced wall thickness and relative wall thickness after 2 weeks of therapy. In vitro studies showed that macitentan decreased the aldosterone-induced cardiomyocyte hypertrophy. These changes were mediated by a reduction in the expression of cardiac myocyte enhancer factor 2a. Moreover, macitentan improved adverse cardiac remodeling, by reducing the stiffer cardiac collagen I and titin n2b expression in the left ventricle of mice with HFpEF. Conclusions—These findings indicate that dual ET-A/ET-B receptor inhibition improves HFpEF by abrogating adverse cardiac remodeling via antihypertrophic mechanisms and by reducing stiffness. Additional studies are needed to explore the role of dual ET-1 receptor antagonists in patients with HFpEF.
Replication of Human Immunodeficiency Viruses Engineered with Heterologous Tat-Transactivation Response Element Interactions

ABSTRACT Human immunodeficiency viruses (HIVs) and the related bovine lentiviruses bovine immunodeficiency virus (BIV) and Jembrana disease virus (JDV) utilize the viral Tat protein to activate viral transcription. The arginine-rich RNA-binding domains of the Tat proteins bind to their cognate transactivation response element (TAR) RNA hairpins located at the 5′ ends of the viral mRNAs, resulting in enhanced processivity of RNA polymerase II. It has previously been shown that HIV type 1 (HIV-1) Tat requires the cellular cyclin T1 protein for high-affinity RNA binding whereas BIV Tat and JDV Tat bind with high affinity on their own and adopt distinct β-hairpin conformations when complexed to RNA. Here we have engineered the BIV and JDV Tat-TAR interactions into HIV-1 and show that the heterologous interactions support viral replication, correlating well with their RNA-binding affinities. Viruses engineered with a variant TAR able to bind all three Tat proteins replicate efficiently with any of the proteins. In one virus containing a noncognate Tat-TAR pair that neither interacts nor efficiently replicates (HIV-1 TAR and BIV Tat), viral revertants were isolated in which TAR had become mutated to generate a functional BIV Tat binding site. Our results support the view that incremental changes to TAR structure can provide routes for evolving new Tat-TAR complexes while maintaining active viral replication.
Comparing the in vivo and in vitro effects of hypoxia (3% O2) on directly derived cells from murine cardiac explants versus murine cardiosphere derived cells

Coronary heart disease (CHD) is still one of the main causes of death in the world, despite significant advances in clinical treatments. Stem cell transplantation methods have the potential to improve cardiac function and patients’ outcome following heart attack, but optimal cell types, cell preparation methods and cell delivery routes are yet to be developed. Mammalian hearts contain a small fraction of progenitor cells which, in culture, migrate out of the cardiac explants, known as explant-derived cell (EDCs) and contribute to spheroids known as cardiospheres (Csphs). Following further culture and cell passaging, Csphs give rise to cardiosphere-derived cells (CDCs). EDCs, Csphs and CDCs show in vitro and in vivo angiogenesis and tissue regeneration in myocardial ischemia. However, CDC and Csph formation is time consuming, expensive and not always successful. Therefore, this study aims to compare EDCs with CDCs and assess the effect of hypoxic preconditioning on their pro-angiogenic potential. The data showed that preconditioning EDCs in hypoxic cell culture enhances cell growth, viability and expression of stem cell and pro-angiogenic markers more than CDCs. In vivo experiments using a sub-dermal matrigel plug assay showed that EDCs and CDCs alone have limited pro-angiogenic potential; however, hypoxic preconditioning of EDCs and CDCs significantly enhances this process. Further research will increase our understanding of cardiac stem cell mediated angiogenesis and improve clinical therapies for myocardial infarction (MI) patients.
Randomized algorithms for large-scale inverse problems with general Tikhonov regularizations

We shall investigate randomized algorithms for solving large-scale linear inverse problems with general Tikhonov regularizations. Our first approach transforms general form inverse problems into standard form, then we apply randomized algorithms to reduce large-scale systems of standard form to much smaller-scale systems and seek their regularized solutions in combination with some popular choice rules for regularization parameters. Our second approach involves a new random generalized SVD algorithm that can essentially reduce the sizes of the original large-scale ill-posed systems. The reduced systems can provide approximate regularized solutions with about the same accuracy as the ones by the classical generalized SVD, but they are much more stable and much less expensive as they need only to work on problems of much smaller sizes. Numerical results are presented to demonstrate the efficiency and accuracy of the algorithms.
Shape of the Central Sulcus and Disability After Subcortical Stroke: A Motor Reserve Hypothesis

Background and Purpose— Both brain and cognitive reserves modulate the clinical impact of chronic brain diseases. Whether a motor reserve also modulates the relationships between stroke and disability is unknown. We aimed to determine whether the shape of the central sulcus, a marker of the development of underlying motor connections, is independently associated with disability in patients with a positive history of small subcortical ischemic stroke. Methods— Shapes of central sulci were reconstructed from high-resolution magnetic resonance imaging and ordered without supervision according to a validated algorithm in 166 patients with a positive history of small subcortical ischemic stroke caused by CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy), a severe monogenic cerebral small vessel disease affecting young patients. Ordinal logistic regression modeling was used to test the relationships between modified Rankin scale, a disability scale strongly weighted toward motor disability, and sulcal shape. Results— Modified Rankin scale was strongly associated with sulcal shape, independent of age, sex, and level of education (proportional odds ratio =1.19, 95% confidence interval =1.06–1.35; P=0.002). Results remained significant after further adjustment for brain atrophy, volume of lacunes, and volume of white matter hyperintensities of presumed vascular origin. Conclusions— The severity of disability in patients with a positive history of small subcortical ischemic stroke caused by a severe cerebral small vessel disease is related to the shape of the central sulcus, independently of the main determinants of disability. These results support the concept of a motor reserve that could modulate the clinical severity in patients with a positive history of small subcortical ischemic stroke.
The crystallinity of ancient bone and dentine: new insights by transmission electron microscopy

We studied various archaeological and palaeontological bones and dentines from different burial environments by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and transmission electron microscopy (TEM), in the framework of a general study of diagenesis. FT-IR and XRD were used to evaluate the global preservation state of the bone and dentine mineral phase by determining a splitting factor (SF) or a crystallinity index (Cl), respectively. These data can be combined with studies on the nanometer scale made with TEM. This latter technique, coupled with electron microdiffraction, provides determination of dimensions and shapes of individual bone and dentine apatite nanocrystals as well as of secondary minerals formed during diagenesis. It enables us to distinguish between heat-induced recrystallization processes and crystal growth in solution occurring during diagenesis.
Spinal Processing of Noxious and Innocuous Cold Information: Differential Modulation by the Periaqueductal Gray

In addition to cold being an important behavioral drive, altered cold sensation frequently accompanies pathological pain states. However, in contrast to peripheral mechanisms, central processing of cold sensory input has received relatively little attention. The present study characterized spinal responses to noxious and innocuous intensities of cold stimulation in vivo and established the extent to which they are modulated by descending control originating from the periaqueductal gray (PAG), a major determinant of acute and chronic pain. In lightly anesthetized rats, hindpaw cooling with ethyl chloride, but not acetone, was sufficiently noxious to evoke withdrawal reflexes, which were powerfully inhibited by ventrolateral (VL)-PAG stimulation. In a second series of experiments, subsets of spinal dorsal horn neurons were found to respond to innocuous and/or noxious cold. Descending control from the VL-PAG distinguished between activity in nociceptive versus non-nociceptive spinal circuits in that innocuous cold information transmitted by non-nociceptive class 1 and wide-dynamic-range class 2 neurons remained unaltered. In contrast, noxious cold information transmitted by class 2 neurons and all cold-evoked activity in nociceptive-specific class 3 neurons was significantly depressed. We therefore demonstrate that spinal responses to cold can be powerfully modulated by descending control systems originating in the PAG, and that this control selectively modulates transmission of noxious versus innocuous information. This has important implications for central processing of cold somatosensation and, given that chronic pain states are dependent on dynamic alterations in descending control, will help elucidate mechanisms underlying aberrant cold sensations that accompany pathological pain states.
Adaptive 2-D Wavelet Transform Based on the Lifting Scheme With Preserved Vanishing Moments

In this paper, we propose novel adaptive wavelet filter bank structures based on the lifting scheme. The filter banks are nonseparable, based on quincunx sampling, with their properties being pixel-wise adapted according to the local image features. Despite being adaptive, the filter banks retain a desirable number of primal and dual vanishing moments. The adaptation is introduced in the predict stage of the filter bank with an adaptation region chosen independently for each pixel, based on the intersection of confidence intervals (ICI) rule. The image denoising results are presented for both synthetic and real-world images. It is shown that the obtained wavelet decompositions perform well, especially for synthetic images that contain periodic patterns, for which the proposed method outperforms the state of the art in image denoising.
Those Who Most Ignore, Least Escape

Are minds subject to laws of physics? Are the laws of physics computable? Are conscious thought processes computable? Currently there is little agreement as to what are the right answers to these questions. Penrose ([41], p. 644) goes one step further and asserts that: a radical new theory is indeed needed, and I am suggesting, moreover, that this theory, when it is found, will be of an essentially non-computational character. The aim of this paper is three fold: 1) to examine the incompatibility between the hypothesis of strong determinism and computability, 2) to give new examples of uncomputable physical laws, and 3) to discuss the relevance of Gödel’s Incompleteness Theorem in refuting the claim that an algorithmic theory—like strong AI—can provide an adequate theory of mind. Finally, we question the adequacy of the theory of computation to discuss physical laws and thought processes.
Fast and accurate thermal modeling and optimization for monolithic 3D ICs

In this paper, we present a comprehensive study of the unique thermal behavior in monolithic 3D ICs. In particular, we study the impact of the thin inter-layer dielectric (ILD) between the device tiers on vertical thermal coupling. In addition, we develop a fast and accurate compact full-chip thermal analysis model based on non-linear regression technique. Our model is extremely fast and highly accurate with an error of less than 5%. This model is incorporated into a thermal-aware 3D-floorplanner that runs without significant runtime overhead. We observe up to 22% reduction in the maximum temperature with insignificant area and performance overhead.
Pathogenesis of venous thrombosis.

To the Editor. — The authors wish to thank Matzger for his letter "Pathogenesis of Venous Thrombosis" ( 215 :799, 1971). Our agreement with Matzger is complete— the problem of thromboembolism is by no means resolved. However, we do not share his opinion that this subject is cloaked in mystery. It is our firm conviction that the inability to date to control this dreaded complication in hospital patients should not be cause for despair but rather should spur us on to continuous, diligent studies and research until the ultimate conquest is achieved. In his hurried attempt to build a case, Matzger overlooked several pertinent facts. Unquestionable reduction of the venous pool of the calf (both deep and superficial veins) was repeatedly and amply demonstrated in our illustrations and fully explained under Phlebograms . Angiography while not entirely free from pitfalls is the choice tool available to us for the delineation of vascular forms
Inference of concise regular expressions and DTDs

We consider the problem of inferring a concise Document Type Definition (DTD) for a given set of XML-documents, a problem that basically reduces to learning concise regular expressions from positive examples strings. We identify two classes of concise regular expressions—the single occurrence regular expressions (SOREs) and the chain regular expressions (CHAREs)—that capture the far majority of expressions used in practical DTDs. For the inference of SOREs we present several algorithms that first infer an automaton for a given set of example strings and then translate that automaton to a corresponding SORE, possibly repairing the automaton when no equivalent SORE can be found. In the process, we introduce a novel automaton to regular expression rewrite technique which is of independent interest. When only a very small amount of XML data is available, however (for instance when the data is generated by Web service requests or by answers to queries), these algorithms produce regular expressions that are too specific. Therefore, we introduce a novel learning algorithm crx that directly infers CHAREs (which form a subclass of SOREs) without going through an automaton representation. We show that crx performs very well within its target class on very small datasets.
Glycosylated hemoglobin as a screening test for hyperglycemia in antipsychotic-treated patients: a follow-up study

Purpose To assess the point prevalence of undetected prediabetes (preDM) and diabetes mellitus (DM) in patients treated with antipsychotics and to compare metabolic parameters between patients with normoglycemia (NG), preDM, and DM. Furthermore, conversion rates for preDM and DM were determined in a 1-year follow-up. Patients and methods In a naturalistic cohort of 169 patients, fasting glucose (FG) and hemoglobin A1c (HbA1c) criteria were applied at baseline and at follow-up after 1 year. A distinction was made between baseline patients diagnosed according to FG (B-FG) and those diagnosed according to HbA1c (B-HbA1c). Conversion rates in the 1-year follow-up were compared between B-FG and B-HbA1c. Results At baseline, preDM and DM were present in 39% and 8%, respectively. As compared to patients with NG, metabolic syndrome was significantly more prevalent in patients with preDM (62% vs 31%). Although the majority of patients were identified by the FG criterion, HbA1c contributed significantly, especially to the number of patients diagnosed with preDM (32%). Regarding the patients with preDM, conversion rates to NG were much higher in the B-FG group than in the B-HbA1c group (72% vs 18%). In patients diagnosed with DM, conversion rates were found for B-FG only. Conclusion PreDM and DM are highly prevalent in psychiatric patients treated with antipsychotic drugs. HbA1c was shown to be a more stable parameter in identifying psychiatric patients with (an increased risk for) DM, and it should therefore be included in future screening instruments.
Uncovering Genes with Divergent mRNA-Protein Dynamics in Streptomyces coelicolor

Many biological processes are intrinsically dynamic, incurring profound changes at both molecular and physiological levels. Systems analyses of such processes incorporating large-scale transcriptome or proteome profiling can be quite revealing. Although consistency between mRNA and proteins is often implicitly assumed in many studies, examples of divergent trends are frequently observed. Here, we present a comparative transcriptome and proteome analysis of growth and stationary phase adaptation in Streptomyces coelicolor, taking the time-dynamics of process into consideration. These processes are of immense interest in microbiology as they pertain to the physiological transformations eliciting biosynthesis of many naturally occurring therapeutic agents. A shotgun proteomics approach based on mass spectrometric analysis of isobaric stable isotope labeled peptides (iTRAQ™) enabled identification and rapid quantification of approximately 14% of the theoretical proteome of S. coelicolor. Independent principal component analyses of this and DNA microarray-derived transcriptome data revealed that the prominent patterns in both protein and mRNA domains are surprisingly well correlated. Despite this overall correlation, by employing a systematic concordance analysis, we estimated that over 30% of the analyzed genes likely exhibited significantly divergent patterns, of which nearly one-third displayed even opposing trends. Integrating this data with biological information, we discovered that certain groups of functionally related genes exhibit mRNA-protein discordance in a similar fashion. Our observations suggest that differences between mRNA and protein synthesis/degradation mechanisms are prominent in microbes while reaffirming the plausibility of such mechanisms acting in a concerted fashion at a protein complex or sub-pathway level.
A Type-2 Fuzzy Ontology and Its Application to Personal Diabetic-Diet Recommendation

It has been widely pointed out that classical ontology is not sufficient to deal with imprecise and vague knowledge for some real-world applications like personal diabetic-diet recommendation. On the other hand, fuzzy ontology can effectively help to handle and process uncertain data and knowledge. This paper proposes a novel ontology model, which is based on interval type-2 fuzzy sets (T2FSs), called type-2 fuzzy ontology (T2FO), with applications to knowledge representation in the field of personal diabetic-diet recommendation. The T2FO is composed of 1) a type-2 fuzzy personal profile ontology ( type-2 FPPO); 2) a type-2 fuzzy food ontology ( type-2 FFO); and 3) a type-2 fuzzy-personal food ontology (type-2 FPFO). In addition, the paper also presents a T2FS-based intelligent diet-recommendation agent ( IDRA), including 1) T2FS construction; 2) a T2FS-based personal ontology filter; 3) a T2FS-based fuzzy inference mechanism; 4) a T2FS-based diet-planning mechanism; 5) a T2FS-based menu-recommendation mechanism; and 6) a T2FS-based semantic-description mechanism. In the proposed approach, first, the domain experts plan the diet goal for the involved diabetes and create the nutrition facts of common Taiwanese food. Second, the involved diabetics are requested to routinely input eaten items. Third, the ontology-creating mechanism constructs a T2FO, including a type-2 FPPO, a type-2 FFO, and a set of type-2 FPFOs. Finally, the T2FS-based IDRA retrieves the built T2FO to recommend a personal diabetic meal plan. The experimental results show that the proposed approach can work effectively and that the menu can be provided as a reference for the involved diabetes after diet validation by domain experts.
Transfusion transmitted infections – A retrospective analysis from the National Blood Transfusion Service in Eritrea

Background The emergence of transfusion transmitted infection (TTI) especially HIV/AIDS has created a huge obstacle in ensuring blood safety. To assess the situation in Eritrea, we carried out a retrospective study of 29,501 blood donors for the prevalence of TTI's i.e. HIV, HBV, HCV and Syphilis. Methods The study population included all donors who donated blood from January 2006 to November 2009. The data was collected from the National Blood Transfusion Services (NTBS) of Eritrea and includes category of donor and result for TTI markers. Results A total of 29,501 units of blood were collected from 23,385(79%) voluntary blood donors and the rest 6,116(21%) units were collected from family replacement donors. The over all prevalence of TTI's were 3.8% with 3.5% in voluntary blood donors and 5.1% in family replacement donors. The sero-prevalence for TTI markers were 0.18% HIV, 2.58% HBV, 0.57% HCV and 0.49% Syphilis. Conclusion In conclusion, even if the TTI prevalence rate among Eritrean blood donors is low, ensuring blood safety has a long way to go.
DELETION STATUS AND INTELLECTUAL IMPAIRMENT IN DUCHENNE MUSCULAR DYSTROPHY

The authors collected Verbal, Performance and Full‐scale IQs for 74 patients in whom complete analysis of the dystrophin gene for deletions and duplications had been performed. There was a significant difference in the mean Full‐scale IQ between patients with deletions at the 5' and 3' ends of the gene, with no patients with 5' deletions having mental retardation. No relationship was established between mental retardation and the presence or absence of deletions or length of deletions, and similar deletions were observed in the presence and absence of mental retardation. Although distal deletions were more commonly associated with mental retardation, there was no clear evidence for a particular region of the dystrophin gene being specifically responsible for IQ. The intellectual deficit seen in DMD may be a consequence of cerebral hypoxia, due to malfunction of smooth muscle dystrophin.