Miracle-dz/UniFAR-FTUs huggingface dataset:
Hemorheological Approach for Early Detection of Chronic Kidney Disease and Diabetic Nephropathy in Type 2 Diabetes.

BACKGROUND Hemorheologic alterations or changes in blood viscosity have been suggested to play a role in the pathogenesis of microvascular complications in diabetes. We measured various hemorheologic parameters in type 2 diabetes patients at different stages of chronic kidney disease (CKD) and assessed their possible role as early markers of diabetic nephropathy and renal insufficiency. SUBJECTS AND METHODS One hundred-five patients with type 2 diabetes were divided into four groups according to glomerular filtration rate (GFR), which represents the kidney function. Hemorheologic parameters, including erythrocyte deformability, fibrinogen/elongation index (EI), and aggregation index (AI) were measured using a microfluidic hemorheometer, and critical shear stress (CSS) was measured using a microfluidic technique. Various metabolic parameters were assessed from fasting blood samples, and the urine albumin-to-creatinine ratio (ACR) was calculated from first morning voided urine. RESULTS There were significant differences in red blood cell (RBC) deformability, AI, CSS, fibrinogen/EI, and ACR among patients in different stages of CKD (all P<0.05). RBC deformability and fibrinogen/EI significantly differed between normal (GFR >90 mL/min/1.73 m(2)) and CKD stage 2 (GFR 60-90 mL/min/1.73 m(2)) patients, whereas there was no such difference in ACR. In multiple regression analysis, fibrinogen/EI under a moderate shear stress of 3 Pa was an independent predictor of GFR (β=-0.328, P<0.05). Also, AI, CSS, and fibrinogen/EI were significantly different among patients at different stages of diabetic nephropathy, with a significant difference in fibrinogen/EI between normal and microalbuminuric patients (all P<0.05). CONCLUSIONS RBC deformability and fibrinogen/EI are sensitive parameters measured via point-of-care testing for detecting erythrocyte alterations in early CKD and nephropathy in patients with type 2 diabetes. Further studies are warranted to verify their use as screening tools for diabetic nephropathy and renal impairment.
Glucose Repression of STA1 Expression Is Mediated by the Nrg1 and Sfl1 Repressors and the Srb8-11 Complex

ABSTRACT In the yeast Saccharomyces diastaticus, expression of the STA1 gene, which encodes an extracellular glucoamylase, is negatively regulated by glucose. Here we demonstrate that glucose-dependent repression of STA1 expression is imposed by both Sfl1 and Nrg1, which serve as direct transcriptional repressors. We show that Nrg1 acts only on UAS1, and Sfl1 acts only on UAS2, in the STA1 promoter. When bound to its specific site, Sfl1 (but not Nrg1) prevents the binding to UAS2 of two transcriptional activators, Ste12 and Tec1, required for STA1 expression. We also found that Sfl1 contributes to STA1 repression by binding to the promoter and inhibiting the expression of FLO8, a gene that encodes a third transcriptional activator involved in STA1 expression. In addition, we show that the levels of Nrg1 and Sfl1 increase in glucose-grown cells, suggesting that the effects of glucose are mediated, at least in part, through an increase in the abundance of these repressors. NRG1 and SFL1 expression requires the Srb8-11 complex, and correspondingly, the Srb8-11 complex is also necessary for STA1 repression. However, our evidence indicates that the Srb8-11 complex does not associate with either the SFL1 or the NRG1 promoter and thus plays an indirect role in activating NRG1 and SFL1 expression.
How is self-management perceived by community living people after a stroke? A focus group study

Abstract Purpose: Self-management has become an important concept in stroke rehabilitation; however, the way that people post-stroke reflect on the concept of self-management has not yet been studied. This qualitative study explored the reflections of persons post-stroke on self-management, readiness and needs in self-management support. Methods: Focus group interviews were conducted with 16 community living stroke survivors (53–84 years of age). Both verbal questions and photo elicitations were used to collect data. A constant comparative framework was used for the analysis. Result: Participants described their self-management as a complex, long-term, personal learning process. Post-discharge, participants were not ready to self-manage. Aside from individual self-management, participants also mentioned co-management with relatives. Relatives could provide support, but they also limited the development of participants’ self-management skills. Participants missed having professional support post-discharge and would have appreciated additional psychological and emotional support in their process of self-management. Conclusion: Self-management post-stroke is complex. Stroke self-management programmes may be optimised when integrating role and emotional management in addition to medical management. Although readiness to self-manage differs among individuals, support should start as soon as possible and continue post-discharge in people’s personal environments. Self-management programmes should not only focus on self-management of stroke survivors but also on co-management with relatives. Implications for Rehabilitation This study suggests that health care professionals should pay attention to the way patients understand the word and concept of self-management, and need to stress that self-management is not “do-it-yourself”, but is about managing life and health in collaboration with relatives and professionals. Self-management programmes become more meaningful for patients if valued activities and roles are the points of departure of the assessment, goal-setting and coaching throughout the process post-stroke. Stroke self-management programmes should be delivered in people’s own environments.
Scintillation Screen Studies for High-Dose Ion Beam Applications

Scintillating screens are commonly used at accelerator facilities. However, their imaging qualities are not well understood, especially for high-current ion beam operation. Several types of inorganic scintillators were investigated for various ion species and energies of 4.8 and 11.4 MeV/u. For ion beam applications, the exact reproduction of the beam profile is of great importance. Due to the impact by ions, the dose rate during beam delivery is more than 10 orders of magnitude higher as for other applications of scintillators in typical nuclear physics experiments. To validate the imaging quality of the scintillators, different profile measurement methods are compared. Ceramic Al2O3 showed the best results compared to other ceramics like ZrO2 :Y or quartz glass Herasil 102. The imaging properties of the materials can depend significantly on the ion energy. For Al2O3 irradiated with a Ca beam the of 4.8 MeV/u, the results agree with the reference methods. However, for 11.4 MeV/u, the screen image does not reflect the beam distribution, which cannot be attributed to material degradation. A model is under development taking into account the radial dose distribution along the ion track as well as the overlap of tracks. For Al2O3 , this model can describe the observed saturation effect and is able to reconstruct saturated images. The basics and applications of this model are discussed. Detailed spectroscopic investigations were performed to determine the influence of the ion beam intensity on the luminescence spectra emitted by the materials. No significant dependence on the spectra with respect to the beam intensity was found for most of the scintillators.
Portfolio selection using the Riskiness Index

PurposeThe purpose of this paper is to increase the accuracy of the efficient portfolios frontier and the capital market line using the Riskiness Index.Design/methodology/approachThis paper will develop the mean-riskiness model for portfolio selection using the Riskiness Index.FindingsThis paper’s main result is establishing a mean-riskiness efficient set of portfolios. In addition, the paper presents two applications for the mean-riskiness portfolio management method: one that is based on the multi-normal distribution (which is identical to the MV model optimal portfolio) and one that is based on the multi-normal inverse Gaussian distribution (which increases the portfolio’s accuracy, as it includes the a-symmetry and tail-heaviness features in addition to the scale and diversification features of the MV model). Research limitations/implicationsThe Riskiness Index is not a coherent measurement of financial risk, and the mean-riskiness model application is based on a high-order approximation to the portfolio’s rate of return distribution.Originality/valueThe mean-riskiness model increases portfolio management accuracy using the Riskiness Index. As the approximation order increases, the portfolio’s accuracy increases as well. This result can lead to a more efficient asset allocation in the capital markets.
Backbone dynamics of the regulatory domain of calcium vector protein, studied by 15N relaxation at four fields, reveals unique mobility characteristics of the intermotif linker

CaVP is a calcium‐binding protein from amphioxus. It has a modular composition with two domains, but only the two EF‐hand motifs localized in the C‐terminal domain are functional. We recently determined the solution structure of this regulatory half (C‐CaVP) in the Ca2+‐saturated form and characterized the stepwise ion binding. This paper reports the 15N nuclear relaxation rates of the Ca2+‐saturated C‐CaVP, measured at four different NMR fields (9.39, 11.74, 14.1, and 18.7 T), which were used to map the spectral density function for the majority of the amide HN‐N vectors. Fitting the spectral density values at eight frequencies by a model‐free approach, we obtained the microdynamic parameters characterizing the global and internal movements of the polypeptide backbone. The two EF‐hand motifs, including the ion binding loops, behave like compact structural units with restricted mobility as reflected in the quite uniform order parameter and short internal correlation time (< 20 nsec). Comparative analysis of the two Ca2+ binding sites shows that site III, having a larger affinity for the metal ion, is generally more rigid, and the amide vector in the second residue of each loop is significantly less restricted. The linker fragment is animated simultaneously by a larger amplitude fast motion and a slow conformational exchange on a microsecond to millisecond time scale. The backbone dynamics of C‐CaVP characterized here is discussed in relation with other well‐characterized Ca2+‐binding proteins.
Prodrug activation enzymes in cancer gene therapy

Among the broad array of genes that have been evaluated for tumor therapy, those encoding prodrug activation enzymes are especially appealing as they directly complement ongoing clinical chemotherapeutic regimes. These enzymes can activate prodrugs that have low inherent toxicity using both bacterial and yeast enzymes, or enhance prodrug activation by mammalian enzymes. The general advantage of the former is the large therapeutic index that can be achieved, and of the latter, the non‐immunogenicity (supporting longer periods of prodrug activation) and the fact that the prodrugs will continue to have some efficacy after transgene expression is extinguished. This review article describes 13 different prodrug activation schemes developed over the last 15 years, two of which – activation of ganciclovir by viral thymidine kinase and activation of 5‐fluorocytosine to 5‐fluorouracil – are currently being evaluated in clinical trials. Essentially all of these prodrug activation enzymes mediate toxicity through disruption of DNA replication, which occurs at differentially high rates in tumor cells compared with most normal cells. In cancer gene therapy, vectors target delivery of therapeutic genes to tumor cells, in contrast to the use of antibodies in antibody‐directed prodrug therapy. Vector targeting is usually effected by direct injection into the tumor mass or surrounding tissues, but the efficiency of gene delivery is usually low. Thus it is important that the activated drug is able to act on non‐transduced tumor cells. This bystander effect may require cell‐to‐cell contact or be mediated by facilitated diffusion or extracellular activation to target neighboring tumor cells. Effects at distant sites are believed to be mediated by the immune system, which can be mobilized to recognize tumor antigens by prodrug‐activated gene therapy. Prodrug activation schemes can be combined with each other and with other treatments, such as radiation, in a synergistic manner. Use of prodrug wafers for intratumoral drug activation and selective permeabilization of the tumor vasculature to prodrugs and vectors should further increase the value of this new therapeutic modality. Copyright © 2000 John Wiley & Sons, Ltd.
URANIUM DEPOSITION AND RETENTION IN A USTUR WHOLE BODY CASE

Abstract— This report describes a whole body donation from a person with a documented occupational intake of uranium. USTUR Case 1002 was an adult male who died from an acute cerebellar infarct at the age of 83. He worked as a power operator, utility operator, and metal operator for 28 years in a facility that processed and handled radioactive materials. Although he suffered a number of burns from hot metal and acids, cuts, abrasions, and puncture wounds during his many years of work, there were no corresponding health physics or medical records to indicate that these occurrences needed or required excision or decontamination due to the suspicion of the deposition of radioactive material. Over the course of his employment, USTUR Case 1002 submitted numerous urine samples for uranium, plutonium, and fission product analysis. The highest single uranium value measured during this time period was ∼30 &mgr;g L−1 recorded during the second year of his employment. A urinary bioassay sample taken before termination of employment measured 4.3 &mgr;g L−1. The mean urinary uranium concentration per liter per year calculated from the employee’s bioassay records covering the first eleven years of monitoring averaged less than 3 &mgr;g L−1. The ratio of 234/238U activity in the lung tissue was about 1, the same as that found in natural uranium. The highest concentration of uranium was found in a tracheobronchial lymph node. The uranium content in the various tissues of the body followed a rank order lung > skeleton > liver > kidney. Concentration of uranium in the kidney tissue was ∼1.98 ng g−1, about 3 orders of magnitude less than the generally accepted threshold level for permanent kidney damage of 3 &mgr;g U g−1 and roughly equal to the 1.4 ng g−1 reported for Reference Man. The autopsy disclosed findings not uncommon in the aged: severe atherosclerosis, areas of sclerotic kidney glomeruli with stromal fibrous scarring, and moderate to severe arterionephrosclerosis. Lung sections contained parenchymal areas of acute vascular congestion and a mild degree of anthracosis.
Targeting of HER2-Expressing Tumors Using 111In-ABY-025, a Second-Generation Affibody Molecule with a Fundamentally Reengineered Scaffold

Overexpression of the human epidermal growth factor receptor type 2 (HER2) in breast carcinomas predicts response to trastuzumab therapy. Affibody molecules based on a nonimmunoglobulin scaffold have demonstrated a high potential for in vivo molecular imaging of HER2-expressing tumors. The reengineering of the molecular scaffold has led to a second generation of optimized Affibody molecules that have a surface distinctly different from the parental protein domain from staphylococcal protein A. Compared with the parental molecule, the new tracer showed a further increased melting point, stability, and overall hydrophilicity and was more amenable to chemical peptide synthesis. The goal of this study was to assess the potential effects of this extensive reengineering on HER2 targeting, using ABY-025, a DOTA-conjugated variant of the novel tracer. Methods: 111In-ABY-025 was compared with previously evaluated parent HER2-binding Affibody tracers in vitro and in vivo. The in vivo behavior was further evaluated in mice bearing SKOV-3 xenografts, rats, and cynomolgus macaques (Macaca fascicularis). Results: 111In-ABY-025 bound specifically to HER2 in vitro and in vivo. Direct comparison with the previous generation of HER2-binding tracers showed that ABY-025 retained excellent targeting properties. Rapid blood clearance was shown in mice, rats, and macaques. A highly specific tumor uptake of 16.7 ± 2.5 percentage injected activity per gram of tissue was seen at 4 h after injection. The tumor-to-blood ratio was 6.3 at 0.5 h and 88 at 4 h and increased up to 3 d after injection. γ-camera imaging of tumors was already possible at 0.5 h after injection. Furthermore, the repeated intravenous administration of ABY-025 did not induce antibody formation in rats. Conclusion: The biodistribution of 111In-ABY-025 was in remarkably good agreement with the parent tracers, despite profound reengineering of the nonbinding surface. The molecule displayed rapid blood clearance in all species investigated and excellent targeting capacity in tumor-bearing mice, leading to high tumor-to-organ-ratios and high-contrast imaging shortly after injection.
Reduced anxiety‐like and depression‐related behavior in neuropeptide Y Y4 receptor knockout mice

Neuropeptide Y (NPY) acting through Y1 receptors reduces anxiety‐ and depression‐like behavior in rodents, whereas Y2 receptor stimulation has the opposite effect. This study addressed the implication of Y4 receptors in emotional behavior by comparing female germ line Y4 knockout (Y4−/−) mice with control and germ line Y2−/− animals. Anxiety‐ and depression‐like behavior was assessed with the open field (OF), elevated plus maze (EPM), stress‐induced hyperthermia (SIH) and tail suspension tests (TST), respectively. Learning and memory were evaluated with the object recognition test (ORT). In the OF and EPM, both Y4−/− and Y2−/− mice exhibited reduced anxiety‐related behavior and enhanced locomotor activity relative to control animals. Locomotor activity in a familiar environment was unchanged in Y4−/− but reduced in Y2−/− mice. The basal rectal temperature exhibited diurnal and genotype‐related alterations. Control mice had temperature minima at noon and midnight, whereas Y4−/− and Y2−/− mice displayed only one temperature minimum at noon. The magnitude of SIH was related to time of the day and genotype in a complex manner. In the TST, the duration of immobility was significantly shorter in Y4−/− and Y2−/− mice than in controls. Object memory 6 h after initial exposure to the ORT was impaired in Y2−/− but not in Y4−/− mice, relative to control mice. These results show that genetic deletion of Y4 receptors, like that of Y2 receptors, reduces anxiety‐like and depression‐related behavior. Unlike Y2 receptor knockout, Y4 receptor knockout does not impair object memory. We propose that Y4 receptors play an important role in the regulation of behavioral homeostasis.
Gait switches in deep-diving beaked whales: biomechanical strategies for long-duration dives

ABSTRACT Diving animals modulate their swimming gaits to promote locomotor efficiency and so enable longer, more productive dives. Beaked whales perform extremely long and deep foraging dives that probably exceed aerobic capacities for some species. Here, we use biomechanical data from suction-cup tags attached to three species of beaked whales (Mesoplodon densirostris, N=10; Ziphius cavirostris, N=9; and Hyperoodon ampullatus, N=2) to characterize their swimming gaits. In addition to continuous stroking and stroke-and-glide gaits described for other diving mammals, all whales produced occasional fluke-strokes with distinctly larger dorso-ventral acceleration, which we termed ‘type-B’ strokes. These high-power strokes occurred almost exclusively during deep dive ascents as part of a novel mixed gait. To quantify body rotations and specific acceleration generated during strokes we adapted a kinematic method combining data from two sensors in the tag. Body rotations estimated with high-rate magnetometer data were subtracted from accelerometer data to estimate the resulting surge and heave accelerations. Using this method, we show that stroke duration, rotation angle and acceleration were bi-modal for these species, with B-strokes having 76% of the duration, 52% larger body rotation and four times more surge than normal strokes. The additional acceleration of B-strokes did not lead to faster ascents, but rather enabled brief glides, which may improve the overall efficiency of this gait. Their occurrence towards the end of long dives leads us to propose that B-strokes may recruit fast-twitch fibres that comprise ∼80% of swimming muscles in Blainville's beaked whales, thus prolonging foraging time at depth. Highlighted Article: A new method for estimating the biomechanical parameters of swimming strokes from tag data reveals that beaked whales may increase efficiency by switching gaits during different phases of deep dives.
Resistance to Diet-Induced Obesity and Improved Insulin Sensitivity in Mice With a Regulator of G Protein Signaling–Insensitive G184S Gnai2 Allele

OBJECTIVE—Guanine nucleotide binding protein (G protein)–mediated signaling plays major roles in endocrine/metabolic function. Regulators of G protein signaling (RGSs, or RGS proteins) are responsible for the subsecond turn off of G protein signaling and are inhibitors of signal transduction in vitro, but the physiological function of RGS proteins remains poorly defined in part because of functional redundancy. RESEARCH DESIGN AND METHODS—We explore the role of RGS proteins and Gαi2 in the physiologic regulation of body weight and glucose homeostasis by studying genomic “knock-in” mice expressing RGS-insensitive Gαi2 with a G184S mutation that blocks RGS protein binding and GTPase acceleration. RESULTS—Homozygous Gαi2G184S knock-in mice show slightly reduced adiposity. On a high-fat diet, male Gαi2G184S mice are resistant to weight gain, have decreased body fat, and are protected from insulin resistance. This appears to be a result of increased energy expenditure. Both male and female Gαi2G184S mice on a high-fat diet also exhibit enhanced insulin sensitivity and increased glucose tolerance despite females having similar weight gain and adiposity compared with wild-type female mice. CONCLUSIONS—RGS proteins and Gαi2 signaling play important roles in the control of insulin sensitivity and glucose metabolism. Identification of the specific RGS proteins involved might permit their consideration as potential therapeutic targets for obesity-related insulin resistance and type 2 diabetes.