Miracle-dz/UniFAR-FTUs huggingface dataset:
Diagnostic and epidemiological implications of regional differences in serum concentrations of proteins observed in six Asian cities

Abstract The IFCC Committee on Plasma Proteins has been investigating regional differences for commonly assayed plasma proteins to determine whether universal reference intervals can be applied. As a part of this study, we launched an Asian project analyzing the concentrations of 13 serum proteins whose values are standardized to CRM470, and five newer analytes: retinol-binding protein (RBP), cystatin C (CysC), lightchain-κ (L-κ), and light-chain-λ (L-λ). In Tokyo, Seoul, Kuala Lumpur, Hong Kong, Taipei and Shanghai, serum samples were collected from 146 to 415 apparently healthy individuals with nearly equal gender ratios. All assays were performed in Tokyo on a Behring Nephelometer II (BN II). Seven chemical analytes (aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyltransferase (γGT), creatinine, total cholesterol (TC), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C)) were also measured. These results were used for excluding individuals with possible latent clinical disorders. Positive acute phase reactants were consistently lower, and negative ones were higher, in Tokyo than those in other cities. The most conspicuous difference was observed in C-reactive protein (CRP). There were no regional differences in transferrin, albumin, or CysC. Creatinine was much lower in Tokyo despite comparable CysC levels. ALT and γGT were higher in Shanghai, Taipei and Seoul; γGT and TG were higher in Shanghai; and HDL-C was higher in Tokyo. Gender-related differences in reference intervals were observed for immunoglobulin (Ig)M, haptoglobin, RBP, transferrin, α2-macroglobulin (A2M), transthyretin, α1-acid glycoprotein, CysC, and C4 in all cities. Slight age-related differences were observed, irrespective ofthe region, in IgA and ceruloplasmin (increase) and A2M (decrease). Environmental factors and lifestyle seem to have a great influence on many commonly measured analytes.
A Resource-Based View of Partnership Strategies in Health Care Organizations

Abstract The distribution of management structures in health care has been shifting from independent ownership to interorganizational relationships with other firms. A shortage of resources has been cited as one cause for such collaboration among health care entities. The resource-based view of the firm suggests that organizations differentiate between strategic alliances and acquisition strategies based on a firm's internal resources and the types of resources a potential partner organization possesses. This paper provides a review of the literature using the resource-based theory of the firm to understand what conditions foster different types of health care partnerships. A model of partnership alliances using the resource-based view is presented, strategic linkages are presented, managerial implications are outlined, and directions for future research are given.
Screening for Chronic Kidney Disease in Adult Males in Vojvodina: A Cross-sectional Study

Summary Background: Chronic kidney disease (CKD) is one of the most significant global health problems accompanied by numerous complicatons, with constant increase in the number of affected people. This number is much higher in early phases of disease and patients are mostly asymptomatic, so early detection of CKD is crucial. The aim was examination of the prevalence of CKD in the general population of males in Vojvodina, based on estimated glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (ACR), and exploring the determinants and awareness of CKD. Methods: This cross-sectional study included 3060 male examinees from the general population, over 18 years of age, whose eGFR and ACR were calculated, first morning urine specimen examined, arterial blood pressure measured and body mass index calculated. Standard biochemistry methods determined creatinine, urea, uric acid and glucose serum concentrations as well as albumin and creatinine urine levels. Results: Prevalence of CKD in the adult male population is 7.9%, highest in men over 65 years of age (46.7%), while in the other age groups it is 3.6-12.6%. The largest number of examinees with a positive CKD marker suffer from arterial hypertension (HTA) and diabetes mellitus (DM). Only 1.3% of examinees with eGFR<60 ml/min/1.73 m2 and/or ACR≥ 3 mg/mmol had been aware of positive CKD biomarkers. Conclusions: Obtained results show the prevalence of CKD in adult males is 7.9%, HTA and DM are the most important CKD risk factors and the level of CKD awareness is extremely low (1.3%) indicating the necessity for introduction of early stage disease recognition measures, including raising CKD awareness.
e-Restoration of Faces Appearing In Cultural Heritage Artefacts

Virtual restoration of Cultural Heritage (CH) artefacts is an important task that aims to re-create the original appearance of damaged items. In this paper we describe a method that can be used for virtual restoration of faces appearing in cultural heritage artefacts. Given a damaged face appearing in a 2D image we estimate the complete 3D shape of a face using data from the non-damaged face and we predict the texture of the damaged regions. As a result it is possible to generate a restored 3D model of the face which can be mapped back on the 2D image in order to complete the restoration process. Both visual and quantitative results prove the potential of the proposed method.
A family with congenital hypothyroidism caused by a combination of loss-of-function mutations in the thyrotropin receptor and adenylate cyclase-stimulating G alpha-protein subunit genes.

BACKGROUND Resistance to thyrotropin (TSH) causes congenital hypothyroidism (CH). TSH receptor (TSHR) and adenylate cyclase-stimulating G alpha protein subunit (GNAS) loss-of-function mutations cause TSH resistance. We describe a family with TSH resistance and CH bearing a combination of inactivating mutations in TSHR and GNAS genes. We describe studies to determine the molecular mechanisms involved in TSH resistance in this family. METHODS DNA sequencing to identify TSHR and GNAS gene mutations was performed. In vitro effects of the mutations on cAMP production and TSH binding were investigated in COS7 cells. cAMP production was evaluated by transfecting a cAMP response element (CRE)-luciferase reporter with pSVL-TSHR and pSVK3-GNAS vectors. For binding studies, cells transfected with pSVL-TSHR vectors were incubated with iodine-125 bovine TSH ((125)IbTSH). RESULTS Family members with and without CH were heterozygous for the TSHR mutant p.E34K or the GNAS mutant c. 750_751insA (=GNASMut). The propositus had CH and he was heterozygous for TSHR p.E34K; his mother, also heterozygous for TSHR p.E34K, did not have CH. The euthyroid propositus' wife was heterozygous for GNASMut. The propositus' two daughters had CH, one was heterozygous for GNASMut and the other a compound heterezygous for TSHR p.E34K and GNASMut. Albright's hereditary osteodystrophy phenotype was present in those with GNASMut mutation but only the daughters had pseudohypoparathyroidism type 1a. Cells transfected with TSHRE34K had lower TSH affinity and less CRE-luciferase response than cells transfected with TSHR wild-type (WT). Cells transfected with GNASMut did not stimulate CRE-luciferase activity, but when cells were transfected with GNASMut plus GNASWT, a similar response to GNASWT alone was observed. The combination of TSHRWT and GNASWT showed higher CRE-luciferase response than TSHRWT and TSHRE34K with either GNASWT or GNASWT plus GNASMut. CONCLUSIONS CH was caused by loss-of-function mutations in TSHR and/or GNAS. The absence of CH in the propositus' mother argues against a role for TSHR p.E34K being the only cause of CH. The minimal thyroidal phenotypic differences between the sisters with pseudohypoparathyroidism type 1a and TSH resistance, both heterozygous for GNAS c. 750_751insA but only one bearing the TSHR p.E34K mutant, suggest that the main cause for CH was preferential expression of the mutated maternal GNAS allele in the thyroid gland.
How Germinal Centers Evolve Broadly Neutralizing Antibodies: the Breadth of the Follicular Helper T Cell Response

ABSTRACT Many HIV-1-infected patients evolve broadly neutralizing antibodies (bnAbs). This evolutionary process typically takes several years and is poorly understood as selection taking place in germinal centers occurs on the basis of antibody affinity. B cells with the highest-affinity receptors tend to acquire the most antigen from the follicular dendritic cell (FDC) network and present the highest density of cognate peptides to follicular helper T (Tfh) cells, which provide survival signals to the B cell. bnAbs are therefore expected to evolve only when the B cell lineage evolving breadth is consistently capturing and presenting more peptides to Tfh cells than other lineages of more specific B cells. Here we develop mathematical models of Tfh cells in germinal centers to explicitly define the mechanisms of selection in this complex evolutionary process. Our results suggest that broadly reactive B cells presenting a high density of peptides bound to major histocompatibility complex class II molecules (pMHC) are readily outcompeted by B cells responding to lineages of HIV-1 that transiently dominate the within host viral population. Conversely, if broadly reactive B cells acquire a large variety of several HIV-1 proteins from the FDC network and present a high diversity of several pMHC, they can be rescued by a large fraction of the Tfh cell repertoire in the germinal center. Under such circumstances the evolution of bnAbs is much more consistent. Increasing either the magnitude of the Tfh cell response or the breadth of the Tfh cell repertoire markedly facilitates the evolution of bnAbs. Because both the magnitude and breadth can be increased by vaccination with several HIV-1 proteins, this calls for experimental testing. IMPORTANCE Many HIV-infected patients slowly evolve antibodies that can neutralize a large variety of viruses. Such broadly neutralizing antibodies (bnAbs) could in the future become therapeutic agents. bnAbs appear very late, and patients are typically not protected by them. At the moment, we fail to understand why this takes so long and how the immune system selects for broadly neutralizing capacity. Typically, antibodies are selected based on affinity and not on breadth. We developed mathematical models to study two different mechanisms by which the immune system can select for broadly neutralizing capacity. One of these is based upon the repertoire of different follicular helper T (Tfh) cells in germinal centers. We suggest that broadly reactive B cells may interact with a larger fraction of this repertoire and demonstrate that this would select for bnAbs. Intriguingly, this suggests that broadening the Tfh cell repertoire by vaccination may speed up the evolution of bnAbs.
Grasping with the foot: Goal and motor expertise in action observation

Action observation typically induces an online inner simulation of the observed movements. Here we investigate whether action observation merely activates, in the observer, the muscles involved in the observed movement or also muscles that are typically used to achieve the observed action goal. In a first experiment, hand and foot motor areas were stimulated by means of transcranial magnetic stimulation, while participants viewed a typical hand action (grasping) or a nonspecific action (stepping over an object) performed by either a hand or a foot. Hand motor evoked potentials (MEPs) increased for grasping and stepping over actions performed by the hand and for grasping actions performed by the foot. Conversely, foot MEPs increased only for actions performed by the foot. In a second experiment, participants viewed a typical hand action (grasping a pencil) and a typical foot action (pressing a foot‐pedal) performed by either a hand or a foot. Again, hand MEPs increased not only during the observation of both actions performed by the hand but also for grasping actions performed by the foot. Foot MEPs increased not only during the observation of grasping and pressing actions performed by the foot but also for pressing actions performed by the hand. This evidence indicates that motor activations by action observation occur also in the muscles typically used to perform the observed action, even when the action is executed by an unusual effector, hence suggesting a double coding of observed actions: a strict somatotopic coding and an action goal coding based on the observer's motor expertise. Hum Brain Mapp 35:1750–1760, 2014. © 2013 Wiley Periodicals, Inc.
NPHS2 mutation analysis shows genetic heterogeneity of steroid-resistant nephrotic syndrome and low post-transplant recurrence.

BACKGROUND Mutations of NPHS2 are causative in familial autosomal-recessive (AR) and sporadic steroid-resistant nephrotic syndrome (SRNS). This study aimed to determine the spectrum of NPHS2 mutations and to establish genotype-phenotype correlations. METHODS NPHS2 mutation analysis was performed in 338 patients from 272 families with SRNS: 81 families with AR SRNS, 172 patients with sporadic SRNS, and 19 patients with diffuse mesangial sclerosis (DMS). RESULTS Twenty-six different pathogenic NPHS2 mutations were detected, including 13 novel mutations. The mutation detection rate was 43% for familial AR and 10.5% for sporadic SRNS, confirming genetic heterogeneity. No pathogenic NPHS2 mutations were found in DMS patients. Age at onset in patients with two pathogenic mutations was earlier, especially in cases with frameshift, truncating, and the R138Q missense mutations. Patients with only one NPHS2 mutation or variant had late-onset NS. Triallelic inheritance was observed in one patient with a homozygous R138Q mutation and a de novo NPHS1 mutation. Among 32 patients with two NPHS2 mutations who underwent kidney transplantation, only one developed late recurrence of focal segmental glomerulosclerosis (FSGS). Among 25 patients with sporadic SRNS and post-transplantation recurrence, we detected a heterozygous NPHS2 mutation in one case, and heterozygous variants/polymorphisms in 3 cases. CONCLUSION Patients with two pathogenic NPHS2 mutations present with early-onset SRNS and very low incidence of post-transplantation recurrence. Heterozygous NPHS2 variants may play a role in atypical cases with mild, late-onset course, and recurrence after transplantation.
Chemical and X-ray analyses of five brands of dental gutta-percha cone.

AIM To determine the chemical composition of five commercially available nonstandardized gutta-percha points. METHODOLOGY The organic fraction (gutta-percha polymer and wax/resin) of nonstandardized gutta-percha points (Dentsply, Tanari, Konne, Obtura Spartan and Analytic Endodontics) was separated from the inorganic fraction (ZnO and BaSO4) by dissolution in chloroform. Gutta-percha polymer was precipitated with acetone. Zinc oxide was partially separated from barium sulphate by reaction with HCl. Energy-dispersive X-ray microanalysis and X-ray diffraction were employed to identify the chemical elements and compounds (barium sulphate and zinc oxide). The barium sulphate content was calculated by percentage of sulphur from elemental microanalysis. All analyses were repeated three times. RESULTS The means and standard deviations of the percentage by weight of gutta-percha in the points were: Dentsply (14.5 +/- 0.70%), Tanari (15.6 +/- 0.66%), Obtura (17.7 +/- 0.35%), Konne (18.9 +/- 0.32%) and Analytic (20.4 +/- 0.40%). The mean and SD of the zinc oxide content were: Dentsply (84.3 +/- 0.50%), Tanari (82.0 +/- 0.72%), Obtura (69.5 +/- 0.21%), Konne (78.0 +/- 0.05%) and Analytic (66.5 +/- 0.50%). CONCLUSIONS The method was appropriate to quantify gutta-percha and resin/wax components of gutta-percha points, but not barium sulphate and zinc oxide. An alternative procedure to determine barium sulphate and zinc oxide contents has been proposed based on elemental microanalysis of sulphur. Some brands of gutta-percha did not contain barium sulphate.
Efficient flow cytometric assay for platelet-leukocyte aggregates in whole blood using fluorescence signal triggering.

BACKGROUND Platelet-leukocyte aggregates (PLAs) may be important in thrombotic and inflammatory disease states, but accurate assessment of PLA formation in vivo is hampered by the propensity for in vitro artefacts caused by sample manipulation. A whole blood flow cytometric assay for circulating PLAs, based on minimal sample manipulation, was thus developed. METHODS Citrated whole blood was labeled with a RPE-CD45 MAb (leukocyte marker) and an FITC-CD42a (GPIX) MAb (platelet marker). The latter was used to avoid possible influences of platelet glycoprotein proteolysis by neutrophil-derived proteases. The samples were mildly fixed with 0.5% formaldehyde saline. The cytometer was triggered by RPE-CD45 fluorescence. Leukocyte subpopulations were separated according to their typical light scattering and CD45 expression. RESULTS Minimal sample manipulation and mild sample fixation resulted in minor in vitro artefacts and good sample stability. Fluorescence triggering increased the efficiency of the flow cytometric analysis approximately 5-fold compared with triggering with light scatter, and allowed discrimination of leukocyte subpopulations. The majority of PLAs involved monocytes and neutrophils, rather than lymphocytes, both without and with in vitro stimulation by ADP or thrombin. A cocktail of blocking MAbs to CD62P, CD15, GPIIb/IIIa and the CD11b/CD18 complex had no effect on unstimulated samples, whilst totally inhibiting aggregation induced by 10(-5) M ADP, suggesting that the PLAs in unstimulated blood were preformed in vivo. CONCLUSIONS This whole blood flow cytometric assay for PLAs is simple and efficient, and appears to reflect closely platelet-leukocyte aggregates in circulating blood in vivo.
Structure of a quinohemoprotein amine dehydrogenase with an uncommon redox cofactor and highly unusual crosslinking

The crystal structure of the heterotrimeric quinohemoprotein amine dehydrogenase from Paracoccus denitrificans has been determined at 2.05-Å resolution. Within an 82-residue subunit is contained an unusual redox cofactor, cysteine tryptophylquinone (CTQ), consisting of an orthoquinone-modified tryptophan side chain covalently linked to a nearby cysteine side chain. The subunit is surrounded on three sides by a 489-residue, four-domain subunit that includes a diheme cytochrome c. Both subunits sit on the surface of a third subunit, a 337-residue seven-bladed β-propeller that forms part of the enzyme active site. The small catalytic subunit is internally crosslinked by three highly unusual covalent cysteine to aspartic or glutamic acid thioether linkages in addition to the cofactor crossbridge. The catalytic function of the enzyme as well as the biosynthesis of the unusual catalytic subunit is discussed.
Automated test case generation for the stress testing of multimedia systems

With the advancement in network bandwidth and computing power, multimedia systems have become a popular means for information delivery. However, general principles of system testing cannot be directly applied to testing of multimedia systems on account of their stringent temporal and synchronization requirements. In particular, few studies have been made on the stress testing of multimedia systems with respect to their temporal requirements under resource saturation. Stress testing is important because erroneous behavior is most likely to occur under resource saturation. This paper presents an automatable method of test case generation for the stress testing of multimedia systems. It adapts constraint solving techniques to generate test cases that lead to potential resource saturation in a multimedia system. Coverage of the test cases is defined upon the reachability graph of a multimedia system. The proposed stress testing technique is supported by tools and has been successfully applied to a real‐life commercial multimedia system. Although our technique focuses on the stress testing of multimedia systems, the underlying issues and concepts are applicable to other types of real‐time systems. Copyright © 2002 John Wiley & Sons, Ltd.
Identifying Feasible Physical Activity Programs for Long-Term Care Homes in the Ontario Context

Background Structured exercise programs for frail institutionalized seniors have shown improvement in physical, functional, and psychological health of this population. However, the ‘feasibility’ of implementation of such programs in real settings is seldom discussed. The purpose of this systematic review was to gauge feasibility of exercise and falls prevention programs from the perspective of long-term care homes in Ontario, given the recent changes in funding for publically funded physiotherapy services. Method Six electronic databases were searched by two independent researchers for randomized controlled trials that targeted long-term care residents and included exercise as an independent component of the intervention. Results A total of 39 studies were included in this review. A majority of these interventions were led by physiotherapist(s), carried out three times per week for 30–45 minutes per session. However, a few group-based interventions that were led by long-term care staff, volunteers, or trained non-exercise specialists were identified that also required minimal equipment. Conclusion This systematic review has identified ‘feasible’ physical activity and falls prevention programs that required minimal investment in staff and equipment, and demonstrated positive outcomes. Implementation of such programs represents cost-effective means of providing long-term care residents with meaningful gains in physical, psychological, and social health.
Silicon-organic (SOH) and plasmonic-organic (POH) hybrid integration: Extending the capabilities of silicon photonics and plasmonics

Summary form only given. Silicon photonics offers tremendous potential for inexpensive high-yield photonic-electronic integration by enabling fabless fabrication and joint processing of photonic and electronic circuitry. Besides conventional dielectric waveguides, plasmonic structures can also be efficiently realized on the silicon photonic platform, thereby reducing the device footprint by more than an order of magnitude. Silicon and metals, however, fall short of certain optical properties that are indispensable for high-performance photonic devices. In particular, neither material exhibits an appreciable second-order optical nonlinearity, thereby making efficient electro-optic modulators challenging. These deficiencies can be overcome by the concepts of silicon-organic hybrid (SOH) and plasmonic-organic hybrid (POH) integration, which combine silicon-on-insulator (SOI) waveguides and plasmonic nanostructures with organic electro-optic materials. In this paper, we give an overview of our recent progress in the field of SOH [1][8] and POH [9] photonics. Our work covers basic material aspects and device concepts of highly efficient phase modulators [1], [2] and phase shifters [3]. We demonstrate Mach-Zehnder and Inphase-Quadrature(IQ-)modulators [4], [5] having energy consumptions down to a few fJ/bit [2], as well as high-speed transmission experiments using advanced modulation formats such as 16QAM at symbol rates (bit rates) of up to 40 GBd (160 Gbit/s) [6]. We further show that the extraordinarily low operating voltage of SOH modulators allows to drive them directly from standard output ports of field-programmable gate arrays (FPGA), without the need for external amplifiers and analog-to-digital converters. Such schemes can be used even if high-order modulation formats such as 16QAM are to be generated [7]. Moreover, we use SOH devices for generating broadband frequency combs, which are well suited as optical multi-wavelength sources for terabit/s transmission [8]. POH integration finally enables ultra-short phase modulators of less than 30 μm length, operating at data rates of 40 Gbit/s [9]. The POH modulators feature a flat frequency response up to at least 65 GHz, and potentially open the route for modulation at THz frequencies.