Miracle-dz/UniFAR-FTUs huggingface dataset:
Experiences in case mix implementation: a case study

The health sector, being information-intensive, has tremendous potential for harnessing the power of information systems (IS). However, ironically, it is also one of the late-comers to the information-revolution. Only in the last two decades have UK hospitals started to become heavy investors in IS, led by Government initiatives to provide overarching information infrastructure and to make public sector organisations more accountable. One of these was the Resource Management Initiative, accompanied by the Case Mix IS - an organisation-wide system to provide clinical and management audit. Case Mix experiences in UK hospitals have typically been poorly documented, and those that have, paint a grim picture. This paper focuses on a detailed qualitative case study of a UK hospital that had relative success in implementation. As such, it provides a number of lessons learnt for other hospitals embarking on similar projects.
Cyclic coordinate descent: A robotics algorithm for protein loop closure

In protein structure prediction, it is often the case that a protein segment must be adjusted to connect two fixed segments. This occurs during loop structure prediction in homology modeling as well as in ab initio structure prediction. Several algorithms for this purpose are based on the inverse Jacobian of the distance constraints with respect to dihedral angle degrees of freedom. These algorithms are sometimes unstable and fail to converge. We present an algorithm developed originally for inverse kinematics applications in robotics. In robotics, an end effector in the form of a robot hand must reach for an object in space by altering adjustable joint angles and arm lengths. In loop prediction, dihedral angles must be adjusted to move the C‐terminal residue of a segment to superimpose on a fixed anchor residue in the protein structure. The algorithm, referred to as cyclic coordinate descent or CCD, involves adjusting one dihedral angle at a time to minimize the sum of the squared distances between three backbone atoms of the moving C‐terminal anchor and the corresponding atoms in the fixed C‐terminal anchor. The result is an equation in one variable for the proposed change in each dihedral. The algorithm proceeds iteratively through all of the adjustable dihedral angles from the N‐terminal to the C‐terminal end of the loop. CCD is suitable as a component of loop prediction methods that generate large numbers of trial structures. It succeeds in closing loops in a large test set 99.79% of the time, and fails occasionally only for short, highly extended loops. It is very fast, closing loops of length 8 in 0.037 sec on average.
NKX2-5 mutations causative for congenital heart disease retain functionality and are directed to hundreds of targets

We take a functional genomics approach to congenital heart disease mechanism. We used DamID to establish a robust set of target genes for NKX2-5 wild type and disease associated NKX2-5 mutations to model loss-of-function in gene regulatory networks. NKX2-5 mutants, including those with a crippled homeodomain, bound hundreds of targets including NKX2-5 wild type targets and a unique set of "off-targets", and retained partial functionality. NKXΔHD, which lacks the homeodomain completely, could heterodimerize with NKX2-5 wild type and its cofactors, including E26 transformation-specific (ETS) family members, through a tyrosine-rich homophilic interaction domain (YRD). Off-targets of NKX2-5 mutants, but not those of an NKX2-5 YRD mutant, showed overrepresentation of ETS binding sites and were occupied by ETS proteins, as determined by DamID. Analysis of kernel transcription factor and ETS targets show that ETS proteins are highly embedded within the cardiac gene regulatory network. Our study reveals binding and activities of NKX2-5 mutations on WT target and off-targets, guided by interactions with their normal cardiac and general cofactors, and suggest a novel type of gain-of-function in congenital heart disease. DOI: http://dx.doi. org/10.7554/eLife.06942. 001
Thermal characterisation of a lightweight mortar containing expanded perlite for underground insulation

This paper aims to investigate the use of expanded perlite in mortar, for further application of shotcrete to thermal insulation of underground mines. Mixes were designed according to the typical proportions of underground shotcrete, with the sand volumetrically substituted by expanded perlite. Tests of samples were conducted at four ages. Transient plane source technique was utilised to measure the thermal properties. The results showed reduced weight, decreased thermal conductivity, deteriorated thermal diffusivity, and sacrificed mechanical strength with perlite addition. Experimental data analysis and explanation in this paper would establish useful fundamentals for further application of expanded perlite to underground shotcrete.
Functional Heterogeneity in CD4+ T Cell Responses Against a Bacterial Pathogen

To investigate how CD4+ T cells function against a bacterial pathogen, we generated a Listeria monocytogenes-specific CD4+ T cell model. In this system, two TCRtg mouse lines, LLO56 and LLO118, recognize the same immunodominant epitope (LLO190-205) of L. monocytogenes and have identical in vitro responses. However, in vivo LLO56 and LLO118 display vastly different responses during both primary and secondary infection. LLO118 dominates in the primary response and in providing CD8 T cell help. LLO56 predominates in the secondary response. We have also shown that both specific [T cell receptor (TCR)-mediated] and non-specific stimuli (bypassing the TCR) elicit distinct responses from the two transgenics, leading us to conclude that the strength of self-pMHC signaling during development tightly dictates the cell’s future response in the periphery. Herein, we review our findings in this transfer system, focusing on the contribution of the immunomodulatory molecule CD5 and the importance of self-interaction in peripheral maintenance of the cell. We also discuss the manner in which individual TCR affinities to foreign and self-pMHC contribute to the outcome of an immune response; our assertion is that there exists a spectrum of possible T cell responses to recognition of cognate antigen during infection, adding immense diversity to the immune system’s response to pathogens.
Actin cytoskeleton modulates ADMA-induced NF-kappaB nuclear translocation and ICAM-1 expression in endothelial cells

Summary Background Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS) inhibitor, increases the activity of NF-κB (NF-κB) and then induces the expression of intercellular adhesion molecule-1 (ICAM-1). However, the mechanisms regulating ADMA-induced NF-κB activation are unknown. This study investigated the function of actin cytoskeleton for ADMA-induced NF-κB activation and ICAM-1 expression in endothelial cells. Material/Methods Human umbilical vein endothelial cells (HUVEC) were cultured and left untreated or challenged for 24h with 100 μM ADMA in the absence and presence of 5 μM cytochalasin D (Cyt D), or 1 μM Jasplakinolide (Jas). The form of actin cytoskeleton, the translocation of NF-κB, NF-κB DNA binding activity, and the expression of ICAM-1 were determined. Results ADMA increased the formation of stress fiber in endothelial cells, and Cyt D clearly induced destabilization of the actin filaments. Either stabilizing or destabilizing the actin cytoskeleton prevented ADMA-induced NF-κB activation. It also showed that the inhibition of NF-κB activity was due to the impaired NF-κB nuclear translocation. Further, stabilizing or destabilizing the actin cytoskeleton inhibited the expression of the NF-κB target protein, ICAM-1. Conclusions Actin cytoskeleton may be engaged in modulated ADMA-induced NF-κB activation and thereby ICAM-1 expression in endothelial cells.
Intake of phytosterols from natural sources and risk of cardiovascular disease in the European Prospective Investigation into Cancer and Nutrition-the Netherlands (EPIC-NL) population

Background Phytosterols (PSs) are known to lower low-density lipoprotein cholesterol (LDL-C), an established risk factor for cardiovascular disease (CVD). Whether a high intake of PS reduces CVD risk is unknown. This observational study aimed to investigate the associations between intake of naturally occurring PSs, blood lipids and CVD risk. Methods The study included 35,597 Dutch men and women, participating in the European Prospective Investigation into Cancer and Nutrition-the Netherlands (EPIC-NL) study. At baseline, intakes of naturally occurring PSs were estimated with a validated food frequency questionnaire and non-fasting blood lipids were measured. Occurrence of CVD, coronary heart disease (CHD) and myocardial infarction (MI) was determined through linkage with registries. Results The average energy-adjusted PS intake at baseline was 296 mg/d (range: 83–966 mg/d). During 12.2 years of follow-up, 3047 CVD cases (8.6%) were documented. After adjustment for confounders, PS intake was not associated with risk of CVD, CHD or MI (p-value trend > 0.05); hazard ratios ranged from 0.90–0.99 for CVD, from 0.83–0.90 for CHD and from 0.80–0.95 for MI risk across quintiles of PS intake and were almost all non-significant. Higher PS intake was associated with lower total cholesterol (−0.06 mmol/l per 50 mg/d; p-value = 0.038) and lower LDL-C (−0.07 mmol/l; p-value = 0.007), particularly among men. In mediation analysis, LDL-C did not materially affect the association between PS intake and CVD risk. Conclusions In this population with a relatively narrow range of low naturally occurring PS intakes, intake of PS was not associated with reduced CVD risk despite lower LDL-C concentrations in men.
The Neuroprotective Effect of the Association of Aquaporin-4/Glutamate Transporter-1 against Alzheimer's Disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by memory loss and cognitive dysfunction. Aquaporin-4 (AQP4), which is primarily expressed in astrocytes, is the major water channel expressed in the central nervous system (CNS). This protein plays an important role in water and ion homeostasis in the normal brain and in various brain pathological conditions. Emerging evidence suggests that AQP4 deficiency impairs learning and memory and that this may be related to the expression of glutamate transporter-1 (GLT-1). Moreover, the colocalization of AQP4 and GLT-1 has long been studied in brain tissue; however, far less is known about the potential influence that the AQP4/GLT-1 complex may have on AD. Research on the functional interaction of AQP4 and GLT-1 has been demonstrated to be of great significance in the study of AD. Here, we review the interaction of AQP4 and GLT-1 in astrocytes, which might play a pivotal role in the regulation of distinct cellular responses that involve neuroprotection against AD. The association of AQP4 and GLT-1 could greatly supplement previous research regarding neuroprotection against AD.
Selection of Suitable Endogenous Reference Genes for Relative Copy Number Detection in Sugarcane

Transgene copy number has a great impact on the expression level and stability of exogenous gene in transgenic plants. Proper selection of endogenous reference genes is necessary for detection of genetic components in genetically modification (GM) crops by quantitative real-time PCR (qPCR) or by qualitative PCR approach, especially in sugarcane with polyploid and aneuploid genomic structure. qPCR technique has been widely accepted as an accurate, time-saving method on determination of copy numbers in transgenic plants and on detection of genetically modified plants to meet the regulatory and legislative requirement. In this study, to find a suitable endogenous reference gene and its real-time PCR assay for sugarcane (Saccharum spp. hybrids) DNA content quantification, we evaluated a set of potential “single copy” genes including P4H, APRT, ENOL, CYC, TST and PRR, through qualitative PCR and absolute quantitative PCR. Based on copy number comparisons among different sugarcane genotypes, including five S. officinarum, one S. spontaneum and two S. spp. hybrids, these endogenous genes fell into three groups: ENOL-3—high copy number group, TST-1 and PRR-1—medium copy number group, P4H-1, APRT-2 and CYC-2—low copy number group. Among these tested genes, P4H, APRT and CYC were the most stable, while ENOL and TST were the least stable across different sugarcane genotypes. Therefore, three primer pairs of P4H-3, APRT-2 and CYC-2 were then selected as the suitable reference gene primer pairs for sugarcane. The test of multi-target reference genes revealed that the APRT gene was a specific amplicon, suggesting this gene is the most suitable to be used as an endogenous reference target for sugarcane DNA content quantification. These results should be helpful for establishing accurate and reliable qualitative and quantitative PCR analysis of GM sugarcane.
Discrimination between two strains (types) of Herpes simplex virus by various modifications of the neutralization test.

Two strains (or types) of Herpesvirus hominis, HF and HPF, have been shown to be immunologically related but antigenically distinct by a number of modifications of the neutralization test. Various types of neutralization tests distinguished between the two strains (or types) equally well under the conditions described. The tests differed, however, in ease of performance and capacity for comparative expression of results. The multiplicity neutralization test with 50% plaque reduction and pN value determinations was preferable in most instances. Neutralization of artificial mixtures of the two types of herpesvirus by antiserum to one or the other type was useful in detecting antigenic differences and similarities. Each virus was neutralized in artificial mixtures as though the other was not present. This test merits further consideration in studying viral genetics and mechanisms of cross-neutralization as well as in differentiation of related viruses. In the kinetic neutralization test, antiserum which was either too concentrated or too dilute failed to discriminate between HF and HPF, suggesting the possibility of an optimal serum concentration for most effective discrimination between viruses by an antiserum. Antiserum titers were decreased in tests requiring dilution of virus-antiserum mixtures, a four- to eightfold reduction in titer resulting from dilution to 10-4. This effect was noted with both homologous virus-antiserum and heterologous virus-antiserum mixtures so that differentiation between the two strains or types could still be accomplished despite dilution. The change in titer upon dilution was thought to be related to the “dilution effect” described in the 1920's and 1930's in which infectious virus was released by dilution of virus-antiserum mixtures.
Principle of Partial Participation and Individualized Adaptaiions in Educational Programs for Severely Handicapped Students1,2

This article defines the principle of partial participation and individualized adaptations and describes their use to generate functional school and nonschool curricula / or severely handicapped students. An eight-phase strategy is discussed for incorporating partial participation and adaptations. In addition, an example of the use of the eight-phase strategy is provided along with cautions for optimal utilization.
Epigallocatechin-3-gallate rescues LPS-impaired adult hippocampal neurogenesis through suppressing the TLR4-NF-κB signaling pathway in mice

Adult hippocampal dentate granule neurons are generated from neural stem cells (NSCs) in the mammalian brain, and the fate specification of adult NSCs is precisely controlled by the local niches and environment, such as the subventricular zone (SVZ), dentate gyrus (DG), and Toll-like receptors (TLRs). Epigallocatechin-3-gallate (EGCG) is the main polyphenolic flavonoid in green tea that has neuroprotective activities, but there is no clear understanding of the role of EGCG in adult neurogenesis in the DG after neuroinflammation. Here, we investigate the effect and the mechanism of EGCG on adult neurogenesis impaired by lipopolysaccharides (LPS). LPS-induced neuroinflammation inhibited adult neurogenesis by suppressing the proliferation and differentiation of neural stem cells in the DG, which was indicated by the decreased number of Bromodeoxyuridine (BrdU)-, Doublecortin (DCX)- and Neuronal Nuclei (NeuN)-positive cells. In addition, microglia were recruited with activatingTLR4-NF-κB signaling in the adult hippocampus by LPS injection. Treating LPS-injured mice with EGCG restored the proliferation and differentiation of NSCs in the DG, which were decreased by LPS, and EGCG treatment also ameliorated the apoptosis of NSCs. Moreover, pro-inflammatory cytokine production induced by LPS was attenuated by EGCG treatment through modulating the TLR4-NF-κB pathway. These results illustrate that EGCG has a beneficial effect on impaired adult neurogenesis caused by LPSinduced neuroinflammation, and it may be applicable as a therapeutic agent against neurodegenerative disorders caused by inflammation.
Cerebral perfusion changes in migraineurs: a voxelwise comparison of interictal dynamic susceptibility contrast MRI measurements

Introduction: The increased risk of cerebro- and cardiovascular disease in migraineurs may be the consequence of a systemic condition affecting whole body vasculature. At cerebrovascular level, this may be reflected by interictal global or regional cerebral perfusion abnormalities. Whether focal perfusion changes occur during interictal migraine has not been convincingly demonstrated. Methods: We measured brain perfusion with dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) in 29 interictal female migraineurs (12 migraine with aura (MA), 17 migraine without aura (MO)), and 16 female controls. Perfusion maps were compared between these groups with a voxelwise (p < 0.001, uncorrected, minimum cluster size 20 voxels) and a region-of-interest approach. Results: In whole brain voxelwise analyses interictal hyperperfusion was observed in the left medial frontal gyrus in migraineurs and in the inferior and middle temporal gyrus in MO patients, in comparison with controls. Hypoperfusion was seen in the postcentral gyrus and in the inferior temporal gyrus in MA patients and in the inferior frontal gyrus in MO patients. Additional focal sites of hyperperfusion were noted in subgroups based on attack frequency and disease history. Region-of-interest analyses of the pons, hypothalamus, occipital lobe, and cerebellum did not show interictal perfusion differences between migraineurs and controls. Conclusions: We conclude that interictal migraine is characterized by discrete areas of hyper- and hypoperfusion unspecific for migraine pathophysiology and not explaining the increased vulnerability of particular brain regions for cerebrovascular damage.
Task relevance differentially shapes ventral visual stream sensitivity to visible and invisible faces

Abstract Top-down modulations of the visual cortex can be driven by task relevance. Yet, several accounts propose that the perceptual inferences underlying conscious recognition involve similar top-down modulations of sensory responses. Studying the pure impact of task relevance on sensory responses requires dissociating it from the top-down influences underlying conscious recognition. Here, using visual masking to abolish perceptual consciousness in humans, we report that functional magnetic resonance imaging (fMRI) responses to invisible faces in the fusiform gyrus are enhanced when they are task-relevant, but suppressed when they are task-irrelevant compared to other object categories. Under conscious perceptual conditions, task-related modulations were also present but drastically reduced, with visible faces always eliciting greater activity in the fusiform gyrus compared to other object categories. Thus, task relevance crucially shapes the sensitivity of fusiform regions to face stimuli, leading from enhancement to suppression of neural activity when the top-down influences accruing from conscious recognition are prevented.
Calderon inverse Problem for the Schrodinger Operator on Riemann Surfaces

On a fixed smooth compact Riemann surface with boundary $(M_0,g)$, we show that the Cauchy data space (or Dirichlet-to-Neumann map $\mc{N}$) of the Schr\"odinger operator $\Delta +V$ with $V\in C^2(M_0)$ determines uniquely the potential $V$. We also discuss briefly the corresponding consequences for potential scattering at 0 frequency on Riemann surfaces with asymptotically Euclidean or asymptotically hyperbolic ends.
Development of a Direct Tensile Test for Compacted Earth Blocks Reinforced with Natural Fibers

Many thousands of years after its development, unburnt earth block masonry continues to offer an environmentally sustainable and cost-effective alternative to other conventional wall building materials, such as concrete blocks and clay fired bricks, in both developing and developed countries. However, earth is a brittle building material with low tensile strength, and as a consequence tensile cracks in response to external actions or restrained shrinkage are often observed. Ductility and tensile strength may be improved by adding binders or natural fibers to the soil mixture. In this technical note, initial findings of an ongoing study of the tensile characteristics of compacted earth blocks reinforced with natural fibers is reported. The pre- and postcracking characteristics of compacted earth blocks in direct tension were determined using a test procedure developed for this work.
When amnesic patients perform well on recognition memory tests.

Extended exposure to study material can markedly improve subsequent recognition memory performance in amnesic patients, even the densely amnesic patient H.M. To understand this phenomenon, the severely amnesic patient E.P., 3 other amnesic patients, and controls studied pictorial material and then were given either a yes-no (Experiment 1) or a 2-alternative, forced-choice (Experiment 2) recognition test. The amnesic patients and controls benefited substantially from extended exposure, but patient E.P. consistently performed at chance. Furthermore, confidence ratings corresponded to recognition accuracy. The results do not support the idea that the benefit of extended study time is due to some kind of familiarity process made available through nondeclarative memory. It is likely that amnesic patients benefit from extended study time to the extent that they have residual capacity for declarative memory.
Type 2 diabetes in Brazil: epidemiology and management

Type 2 diabetes mellitus (T2DM) is one of the most important epidemic diseases in the world this century, and accounts for 90% of cases of diabetes globally. Brazil is one of the most important examples of the alarming picture of T2DM in emergent societies, being the country with the fourth largest number of people with diabetes. The aim of this paper is to review the literature on diabetes in Brazil, specifically looking at the epidemiology and management of T2DM. A literature search was conducted using PubMed and LILACS to identify articles containing information on diabetes in Brazil. Official documents from the Brazilian government, World Health Organization, and International Diabetes Federation were also reviewed.