Miracle-dz/UniFAR-FTUs huggingface dataset:
KCNJ10 gene mutations causing EAST syndrome (epilepsy, ataxia, sensorineural deafness, and tubulopathy) disrupt channel function

Mutations of the KCNJ10 (Kir4.1) K+ channel underlie autosomal recessive epilepsy, ataxia, sensorineural deafness, and (a salt-wasting) renal tubulopathy (EAST) syndrome. We investigated the localization of KCNJ10 and the homologous KCNJ16 in kidney and the functional consequences of KCNJ10 mutations found in our patients with EAST syndrome. Kcnj10 and Kcnj16 were found in the basolateral membrane of mouse distal convoluted tubules, connecting tubules, and cortical collecting ducts. In the human kidney, KCNJ10 staining was additionally observed in the basolateral membrane of the cortical thick ascending limb of Henle's loop. EM of distal tubular cells of a patient with EAST syndrome showed reduced basal infoldings in this nephron segment, which likely reflects the morphological consequences of the impaired salt reabsorption capacity. When expressed in CHO and HEK293 cells, the KCNJ10 mutations R65P, G77R, and R175Q caused a marked impairment of channel function. R199X showed complete loss of function. Single-channel analysis revealed a strongly reduced mean open time. Qualitatively similar results were obtained with coexpression of KCNJ10/KCNJ16, suggesting a dominance of KCNJ10 function in native renal KCNJ10/KCNJ16 heteromers. The decrease in the current of R65P and R175Q was mainly caused by a remarkable shift of pH sensitivity to the alkaline range. In summary, EAST mutations of KCNJ10 lead to impaired channel function and structural changes in distal convoluted tubules. Intriguingly, the metabolic alkalosis present in patients carrying the R65P mutation possibly improves residual function of KCNJ10, which shows higher activity at alkaline pH.
Solution Structure of Human Cardiac Troponin C in Complex with the Green Tea Polyphenol, (−)-Epigallocatechin 3-Gallate*

Heart muscle contraction is regulated by Ca2+ binding to the thin filament protein troponin C. In cardiovascular disease, the myofilament response to Ca2+ is often altered. Compounds that rectify this perturbation are of considerable interest as therapeutics. Plant flavonoids have been found to provide protection against a variety of human illnesses such as cancer, infection, and heart disease. (−)-Epigallocatechin gallate (EGCg), the prevalent flavonoid in green tea, modulates force generation in isolated guinea pig hearts (Hotta, Y., Huang, L., Muto, T., Yajima, M., Miyazeki, K., Ishikawa, N., Fukuzawa, Y., Wakida, Y., Tushima, H., Ando, H., and Nonogaki, T. (2006) Eur. J. Pharmacol. 552, 123–130) and in skinned cardiac muscle fibers (Liou, Y. M., Kuo, S. C., and Hsieh, S. R. (2008) Pflugers Arch. 456, 787–800; and Tadano, N. , Yumoto, F. , Tanokura, M. , Ohtsuki, I. , and Morimoto, S. (2005) Biophys. J. 88, 314a). In this study we describe the solution structure of the Ca2+-saturated C-terminal domain of troponin C in complex with EGCg. Moreover, we show that EGCg forms a ternary complex with the C-terminal domain of troponin C and the anchoring region of troponin I. The structural evidence indicates that the binding site of EGCg on the C-terminal domain of troponin C is in the hydrophobic pocket in the absence of troponin I, akin to EMD 57033. Based on chemical shift mapping, the binding of EGCg to the C-terminal domain of troponin C in the presence of troponin I may be to a new site formed by the troponin C·troponin I complex. This interaction of EGCg with the C-terminal domain of troponin C·troponin I complex has not been shown with other cardiotonic molecules and illustrates the potential mechanism by which EGCg modulates heart contraction.
Primary Intimal Sarcoma of the Aorta Associated With a Dacron Graft and Resulting in Arterial Rupture

Primary arterial neoplasms are rare lesions which have been most frequently associated with local or constitutional symptomatology, and with distal embolization. Perirenal aortic disruption with pseudoaneurysm formation due to an intimal sarcoma adjacent to a previously placed prosthetic graft is reported in a 66-year-old man. This case supports the premise that the presence of a vascular prosthesis might result in the induction of an arterial wall malignancy. This should be considered when an intraluminal mass is identified in the absence of other arterial pathology. Although the prognosis of these tumors is poor, their preoperative recognition may enhance treatment outcomes.
Energy balance and its measurement in childhood disease

Under and overweight, usually secondary to energy imbalance, are common complications of childhood chronic disease. A simple energy balance paradigm has been helpful in understanding the etiology of underweight and overweight in chronic disease, including malignant disease, particularly when measurements of total energy expenditure have been made using the doubly labeled water method. Measurements of energy intake are usually insufficiently accurate and precise to be informative, and measurements of energy expended at rest alone provide an incomplete and potentially misleading assessment of energy expenditure and the causes of energy imbalance. In some diseases, such as acute lymphoblastic leukemia, the natural history and etiology of energy imbalance are now particularly well understood. Recent improvements in our understanding of etiology should lead to improved strategies for the prevention and treatment of underweight and overweight in chronic disease. In some diseases, cachectic processes drive the development of underweight: these are partly independent of energy balance, and strategies for prevention and treatment may require approaches aimed at modifying the cachectic process rather than attempting to modify energy balance directly. Pediatr Blood Cancer © 2007 Wiley‐Liss, Inc.
Structural and biochemical consequences of NF1 associated nontruncating mutations in the Sec14‐PH module of neurofibromin

Neurofibromatosis type 1 (NF1) is a common genetic disorder caused by alterations in the tumor suppressor gene NF1. Clinical manifestations include various neural crest derived tumors, pigmentation anomalies, bone deformations, and learning disabilities. NF1 encodes the Ras specific GTPase activating protein (RasGAP) neurofibromin, of which the central RasGAP related domain as well as a Sec14‐like (residues 1560–1699) and a tightly interacting pleckstrin homology (PH)‐like (1713–1818) domain are currently well defined. However, patient‐derived nontruncating mutations have been reported along the whole NF1 gene, suggesting further essential protein functions. Focusing on the Sec14‐PH module, we have engineered such nontruncating mutations and analyzed their implications on protein function and structure using lipid binding assays, CD spectroscopy and X‐ray crystallography. Although lipid binding appears to be preserved among most nontruncating mutants, we see major structural changes for two of the alterations. Judging from these changes and our biochemical data, we suggest the presence of an intermolecular contact surface in the lid‐lock region of the protein. Hum Mutat 32:1–7, 2011. © 2011 Wiley‐Liss, Inc.
Encountering Ambivalence – A Qualitative Study of Mental Health Nurses' Experiences with Dual Relationships

ABSTRACT Nurses are obliged to set professional boundaries in nurse–patient relationships. Relationships with patients that are pursued outside of working hours (dual relationships) are commonly prohibited by legislation and professional codes of ethics, but some nurses still engage in them. A thematic analysis of qualitative interviews revealed that the nurses experienced ambivalence regarding how they see the patients, their assessment of the dual relationships and how people around the nurses react to the relationships. Ambivalence was characterized by contradictory and indeterminate thoughts and attitudes toward patients and dual relationships. Results indicated that dual relationship decisions were complex and highly contextually dependent.
Growth fractions and estrogen receptors in human breast cancers as determined in situ with monoclonal antibodies.

The growth fraction (GF) and estrogen receptor (ER) status of 76 cases of breast cancer were investigated on frozen sections of the same tissue block by immunostaining with monoclonal antibodies (Ki-67 and anti ER antibody). In 55 cases of this series, the ER status was also determined by standard biochemical methods. Our study revealed an inverse correlation between GF and ER status. This negative relationship was most significant when both variables were determined immunohistologically in the same tissue block and less significant when GF was analyzed by immunohistology and ER status by biochemical methods. These data suggest that the immunohistologically assessed ER values characterize the receptor status of a given carcinoma better than the biochemical values, which leads to the conclusion that the immunohistologically determined close negative relationship between GF and ER reflects the actual in vivo situation of a given breast carcinoma case. However, the immunohistologic analysis also revealed that there is a proportion of exceptional cases, ie, those with a positive ER status and a large or moderately large GF. Because only half of the ER-positive breast carcinomas respond to endocrine therapy with objective remission. , it is hypothesized that it might be preferentially these mentioned exceptional cases that fail to positively respond to endocrine treatment protocols.
The role of information alignment and entrepreneurial traits on SME internationalization

Purpose - – The paper aims to explore the internationalisation decision-making of small- and medium-sized enterprise (SME) owner/managers. Specifically, structural alignment theory (SAT) and regulatory focus theory (RFT) are utilised to examine the concept of opportunity recognition in the context of internationalisation choices. Design/methodology/approach - – This paper is conceptual in nature, and an integrative cognitive model of internationalisation choice decisions is developed based on SAT and RFT, underpinned by a critical review of the international entrepreneurship (IE) literature. Findings - – Scenarios are identified in which the structure of available information may affect the decision-evaluation process in terms of cognitive resource requirements. Further, the SME owner/manager’s motivational goal orientation is suggested to moderate the role of the information structure in line with IE literature. A conceptual model and propositions are presented. Research limitations/implications - – The conceptual model and the propositions arising from the discussion in this paper offer new directions of research to explore SME internationalisation. Originality/value - – This paper offers a cognitive perspective of SME internationalisation. This paper offers insights for policymakers, SME owner/managers, practitioners and researchers alike. For internationalisation decisions, this paper highlights the potential impact of the structure of information that is made available to SME owner/managers by industry or policy bodies; further, the moderating influence of motivational goal orientation may inform policy on how information should be presented to SME owner/managers to aid their decision-making.
New flavonol glycoside from Scabiosa prolifera L. aerial parts with in vitro antioxidant and cytotoxic activities

Abstract Phytochemical investigation of the chemical constituents of the aerial parts of Scabiosa prolifera L. led to the isolation of one new flavonol glycoside, kaempferol-3-O-(4″,6″-di-E-p-coumaroyl)-β-D-galactopyranoside (1), along with ten other known compounds including luteolin-7-O-(2″-O-ethyl-β-glucopyranoside), β-sitosterol, β-sitosterylglucoside, ursolic acid, corosolic acid, ursolic acid 3-O-β-D-arabinopyranoside, apigenin, methyl-α-D-glucopyranoside, luteolin-7-O-β-glucopyranoside and isoorientin. The structures of all isolated compounds were established using chemical methods and spectroscopic methods including IR, UV, NMR (1D and 2D) and HRESIMS. All compounds were isolated for the first time from the plant. The antioxidant and cytotoxic activities of compounds 1 and 2 were also investigated.
Relationship between Platelet Imidazoline Receptor‐Binding Peptides and Candidate Imidazoline‐1 Receptor, IRAS

Abstract: A candidate human imidazoline‐1 receptor, designated imidazoline receptor antisera‐selected (IRAS) protein, was cloned based on immunoreactivity with antiserum against a purified imidazoline receptor binding peptide (IRBP antiserum). Human IRAS is 167 kD in size, different from 33‐ to 85‐kD IRBP bands previously linked to the human platelet I1 receptor. To explore the possible relationship between IRAS and these smaller proteins, seven different epitope‐specific antisera against IRAS were raised in rabbits for comparison with IRBP antiserum. Focus was on antiserum227–241, corresponding to amino acids #227 to 241 in IRAS, because this antiserum was found uniquely able to immunoprecipitate non‐denatured 85‐kD and 170‐kD forms of IRAS from a human megakaryoblastoma cell line (MEG01), a model of platelet‐producing cells. Human platelets lacked the 170‐kD form of IRAS, but 33‐kD and 85‐kD bands were detectable and seemed to be possible fragments of full‐length IRAS. The intensity of the 85‐kD band detected by antiserum227–241 was significantly correlated (r 5 0.62, P 5 0.04) with the intensity of the 33‐kD band across 11 human platelet samples. A positive correlation between the intensities of the 33‐kD and 85‐kD bands is consistent with both being fragments of IRAS.
Analysis of TDMP Algorithm of LDPC Codes Based on Density Evolution and Gaussian Approximation

Based on density evolution analysis of the existing belief propagation (BP) algorithm, the Turbo Decoding Message Passing (TDMP) algorithm was analyzed from the perspective of density evolution and Gaussian approximation, and the theoretical analysis process of TDMP algorithm was given. When calculating the prior message of each layer of the TDMP algorithm, the check message of the previous iteration should be subtracted. Therefore, the result will not be convergent, if the TDMP algorithm is directly analyzed based on density evolution and Gaussian approximation. We researched the TDMP algorithm based on the symmetry conditions to obtain the convergent result. When using density evolution (DE) and Gaussian approximation to analyze the decoding convergence of the TDMP algorithm, we can provide a theoretical basis for proving the superiority of the algorithm. Then, based on the DE theory, we calculated the probability density function (PDF) of the check-to-variable information of TDMP and its simplified algorithm, and then gave it a calculation based on the process of the normalization factor. Simulation results show that the decoding convergence speed of the TDMP algorithm was faster and the iterations were smaller compared to the BP algorithm under the same conditions.
Indices de formes et de textures. Application au classement de noyaux de cellules

This paper present a study on the diagnoses of blood cell nuclei from patients affected by the Progeria disease. Nuclei are characterized with various methods that analyze them shape and texture, and subsequently classify them by learning techniques. These methods extract "measures" from nuclei, which are used for the computation of a set of values named "indexes". These indexes are function bringing up real or discrete values that give information about geometrical, morphological and textural features of nuclei. A description model of nuclei is built based on this data, that is used to classify nuclei.
Applying Overlapping Community Detection Based on Data Field Theory For Twitter Audiences Classification

Recent years have witnessed the increasing development of Twitter. Given a specific target, all the followers and other participants who have interactions such as mentions with target, are called audiences of the target. As one of the significant applications in social media marketing, classifying Twitter audiences is inherently equivalent to potential customer classification. In this paper, we propose to employ community discovering methods as a solution. On one hand, the significance and influence range of nodes are different, and the influence can be radiated among non-connected nodes as well. To this end, we propose to introduce data field theory to measure the strength between nodes. On the other hand, to minimize parameter selection and settings, we propose a multi-step method by first determining initial clusters based on potentials, and then applying a rough clustering algorithm to detect overlapping communities. Moreover, we collect real world Twitter dataset for the evaluation of proposed method.
O-Antigen-Deficient Francisella tularensis Live Vaccine Strain Mutants Are Ingested via an Aberrant Form of Looping Phagocytosis and Show Altered Kinetics of Intracellular Trafficking in Human Macrophages

We examined the uptake and intracellular trafficking of F. tularensis Live Vaccine Strain (LVS) and LVS with disruptions of wbtDEF and wbtI genes essential for synthesis of the O antigen of lipopolysaccharide. Unlike parental bacteria, O-antigen-deficient LVS is efficiently killed by serum with intact complement but not by serum lacking terminal complement components. Opsonization of O-antigen-deficient LVS in serum lacking terminal complement components allows efficient uptake of these live bacteria by macrophages. In the presence of complement, whereas parental F. tularensis LVS is internalized within spacious pseudopod loops, mutant LVS is internalized within tightly juxtaposed multiple onion-like layers of pseudopodia. Without complement, both parental and mutant LVSs are internalized within spacious pseudopod loops. Thus, molecules other than O antigen are important in triggering dramatic pseudopod extensions and uptake by spacious pseudopod loops. Following uptake, both parental and mutant LVSs enter compartments that show limited staining for the lysosomal membrane glycoprotein CD63 and little fusion with secondary lysosomes. Subsequently, both parental and mutant LVSs lose their CD63 staining. Whereas the majority of parental LVS escapes into the cytosol by 6 h after uptake, mutant LVS shows a marked lag but does escape by 1 day after uptake. Despite the altered kinetics of phagosome escape, both mutant and parental strains grow to high levels within human macrophages. Thus, the O antigen plays a role in the morphology of uptake in the presence of complement and the kinetics of intracellular growth but is not essential for escape, survival, altered membrane trafficking, or intramacrophage growth.
Reducing contact resistance of macro-scale separable electrical contacts with single-layer graphene coatings

Systems in applications ranging from aerospace, automotive, to power distribution are all crucially comprised of electrical connectors. Every system with removable electrical components will have electrical connectors, and likewise these systems will be susceptible to the contact losses and failure modes of these connections. Corrosion is one of the largest causes of failure for electrical connectors and costs the electrical power distribution system in the United States hundreds of millions of dollars annually. This study demonstrates the viability graphene as a protective coating for copper connectors to mitigate corrosion and improve electrical contact performance. Graphene, which is constituted of single layers of hexagonally-oriented carbon atoms, is inherently ultra-thin, chemically and thermally stable, gas impermeable (a property which can inhibit corrosion), highly electrically conductive, and made from an abundant and low-cost components, making it an ideal candidate for implementation as a protective coating on electrical contacts. In this work, single-layer graphene was deposited on copper used in commercially-available electrical connectors. In static tests the electrical contact resistance of the graphene-coated copper contact was two orders of magnitude lower than the contact resistance of the bare copper, and performed similarly to a benchmark gold/nickel coating that is a widely-used anticorrosive coating, demonstrating graphene's protective utility.
Electrochemical Determination of Carbofuran in Tomatoes by a Concanavalin A (Con A) Polydopamine (PDA)-Reduced Graphene Oxide (RGO)-Gold Nanoparticle (GNP) Glassy Carbon Electrode (GCE) with Immobilized Acetylcholinesterase (AChE)

Abstract A new biosensor method was developed to determine residual carbofuran in tomatoes in a rapid and convenient fashion based on immobilizing acetylcholinesterase (AChE) on an electrode modified by concanavalin A (Con A)/polydopamine (PDA)-reduced graphene oxide (RGO)-gold nanoparticle (GNP) nanocomposites. The specific binding between Con A and AChE was investigated by the Ellman method and cyclic voltammetry (CV). The synthesis of nanocomposites was monitored by ultraviolet-visible absorption spectroscopy, scanning electron microscopy (SEM), and electrochemical impedance spectroscopy (EIS). The results showed that, due to the specific binding and good electrical conductivity, the biosensor had 2.2 times higher bioactivity, leading to high sensitivity with a low Michaelis constant of 0.10 mM. Parameters that affect the response of the biosensor, such as the pH, enzyme loading, ionic concentration, and inhibition time, were optimized. When used for the detection of carbofuran, this biosensor showed a wide range of applicability from 5 µg/kg to 40 µg/kg with a detection limit of 0.012 µg/kg. In addition, the biosensor demonstrated good recovery values of 101% and 90% for 10 µg/kg and 100 µg/kg of the analyte, good stability, high repeatability, and a rapid detection time of 20 min for carbofuran in tomatoes, which provides significant advantages for future analysis.
On the reliability of peptide nonplanarity seen in ultra‐high resolution crystal structures

Ultra‐high resolution protein crystal structures have been considered as relatively reliable sources for defining details of protein geometry, such as the extent to which the peptide unit deviates from planarity. Chellapa and Rose (Proteins 2015; 83:1687) recently called this into question, reporting that for a dozen representative protein structures determined at ∼1 Å resolution, the diffraction data could be equally well fit with models restrained to have highly planar peptides, i.e. having a standard deviation of the ω torsion angles of only ∼1° instead of the typically observed value of ∼6°. Here, we document both conceptual and practical shortcomings of that study and show that the more tightly restrained models are demonstrably incorrect and do not fit the diffraction data equally well. We emphasize the importance of inspecting electron density maps when investigating the agreement between a model and its experimental data. Overall, this report reinforces that modern standard refinement protocols have been well‐conceived and that ultra‐high resolution protein crystal structures, when evaluated carefully and used with an awareness of their levels of coordinate uncertainty, are powerful sources of information for providing reliable information about the details of protein geometry.