Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional characterization of protein variants of the human multidrug transporter ABCC2 by a novel targeted expression system in fibrosarcoma cells

The multidrug resistance‐associated protein 2 (MRP2/ABCC2) is involved in the efflux of endogenous and xenobiotic substrates, including several anticancer and antiviral drugs. The functional consequences of ABCC2 protein variants remain inconsistent, which may be due to shortcomings of the in vitro assays used. To study systematically the functional consequences of nonsynonymous ABCC2 variants, we used a novel “Screen and Insert” (ScIn) technology to achieve stable and highly reproducible expression of 13 ABCC2 variants in HT1080 cells. Western blotting revealed lower (30–65%) ABCC2 expression for D333G, R1174H, and R1181L as compared with wild type (WT; 100%), whereas the linked variant V1188E/C1515Y resulted in higher expression (150%). R1174H caused mislocalization of ABCC2 to the cytoplasm with an endoplasmic reticulum‐like distribution. Variants N1244K and R1174H decreased transport of glutathione–methylfluorescein (GS–MF) and glutathione–monochlorobimane (GS–MCB) by 80% and 50%, respectively, whereas R1181L and P1291L reduced only GS–MCB transport by 50% as compared with WT. Contrary to protein data, the double variant V1188E/C1515Y decreased specific transport activity for GS–MF and GS–MCB by 40%. The ScIn approach is a feasible and reliable method to functionally characterize systematically ABCC2 variants. D333G, R1174H, R1181L, N1244K, P1291L, and double variant V1188E/C1515Y have been identified as most promising for further clinical evaluation. Hum Mutat 33:750–762, 2012. © 2012 Wiley Periodicals, Inc.
Architectural support for context-aware applications: from context models to services platforms

Context-awareness has emerged as an important and desirable feature in ubiquitous applications. This feature deals with the ability of applications to utilize information about the user’s environment (context) in order to tailor services to the user’s current situation and needs. This thesis aims at providing an integrated solution for the development of context-aware systems. The main objective is to facilitate the development of context-aware applications, focusing on two aspects: on offering context modelling abstractions and on providing infrastructural support by means of a context handling platform. The context modelling abstractions provide application developers with proper conceptual foundations that can be extended and specialized with specific application requirements. The context handling platform allows application functionality to be delegated to the platform, which reduces application development effort, time and, therefore, costs. This allows application developers to focus on their core business, instead of being bothered with application realization details.
X-ray structure of cyclodextrin glucanotransferase from alkalophilic Bacillus sp. 1011. Comparison of two independent molecules at 1.8 A resolution.

Cyclodextrin glucanotransferase (CGTase) is an enzyme which produces cyclodextrins by the degradation of starch. The enzyme from alkalophilic Bacillus sp. 1011, consisting of 686 amino acid residues, was crystallized from the solution containing 20% PEG 3000 and 20% 2-propanol at pH 5.6 adjusted with citrate buffer. The space group was P1 and the unit cell contained two molecules (V(m) = 2.41 A(3) Da(-1)). The structure was solved by the molecular replacement method and refined to a conventional R value of 0.161 (R(free) = 0.211) for the reflections in the resolution range 1.8-10 A by energy minimization combined with simulated annealing. The molecule consists of five domains, designated A-E, and its backbone structure is similar to the structure of other bacterial CGTases. The molecule has two calcium binding sites where calcium ions are coordinated by seven ligands, forming a distorted pentagonal bipyramid. The two independent molecules are related by a pseudotwofold symmetry and are superimposed with an r.m.s. deviation value of 0.32 A for equivalent C(alpha) atoms. Comparison of these molecules indicated the relatively large mobility of domains C and E with respect to domain A. The active site is filled with water molecules forming a hydrogen-bond network with polar side-chain groups. Two water molecules commonly found in the active center of both molecules link to several catalytically important residues by hydrogen bonds and participate in maintaining a similar orientation of side chains in the two independent molecules.
Inhaler devices for asthma: a call for action in a neglected field

The Brussels Declaration, published in the European Respiratory Journal in 2008 1, recognises the high prevalence of patients with poorly controlled asthma and calls for changes in asthma management across Europe. Prescribing an appropriate inhaler device for asthma, a device that the patient accepts and can handle correctly, is one key element in this process. Inhaler mishandling is very common in real-world clinical practice and can contribute to poor asthma control 2–5. The International Primary Care Respiratory Group (IPCRG) is committed to identifying reasons for poor asthma control and to promoting interventions to help patients achieve asthma control 6–9. An international panel of healthcare providers (HCPs), academics and a patient representative was convened under the auspices of IPCRG to discuss and challenge the science behind inhaler therapy, and to propose practical solutions to real-life problems related to inhaler choice and mishandling. The focus was on the problems confronting clinicians in prescribing a suitable inhaler for each individual and those confronting patients in using their inhalers. Until recently, inhaler therapy and devices have been marginal topics of clinical investigation and research in the field of asthma, mainly confined to a limited circle of experts, and lacking evidence for practical application. Thus, we propose this call for action, given: 1) the importance of inhaler technique for effective inhaled therapy; 2) the critical gaps in knowledge that need still to be addressed; and 3) the lack of solid evidence supporting HCPs in making clinical decisions regarding inhalers for asthma treatment. Correct inhaler technique is fundamental for effective inhaled therapy. Errors in inhaler technique are very common 10–13 and can impact drug delivery to the lungs, thereby compromising bronchodilation in the short term and asthma control in the long term, depending on the drug considered …
The effect of norepinephrine on visual cortical neurons in kittens and adult cats

The responses of visual cortical neurons during iontophoresis of norepinephrine (NE) were compared in kittens and adult cats. One type of neuronal “plasticity” (the ability of visual cortical neurons to have their response properties markedly altered during exposure to a restricted visual environment) normally occurs only in young kittens and has been hypothesized to depend on the presence of NE. We investigated this hypothesis in terms of a model of synaptic plasticity which suggested that NE would selectively enhance the evoked responses of neurons and that this enhancement might exist to a greater extent in kittens than in adult cats. The responses of 72% (43 of 60) of all neurons sampled decreased during NE iontophoresis, while the responses of only a few neurons (3 of 60) increased. Reduced activity occurred in roughly equal percentages of simple and complex cells. We also looked for differences in NE modulation of the “signal-to-noise” ratio of neurons. Most neurons had little spontaneous activity, but, of those that did, the signal-to-noise ratio increased in some instances and decreased in others. No difference in any of the effects of NE was observed between kittens and adult cats. The role of NE in cortical plasticity is discussed.
Defective β-Adrenergic Receptor Signaling Precedes the Development of Dilated Cardiomyopathy in Transgenic Mice with Calsequestrin Overexpression*

Calsequestrin is a high capacity Ca2+-binding protein in the junctional sarcoplasmic reticulum that forms a quaternary complex with junctin, triadin, and the ryanodine receptor. Transgenic mice with cardiac-targeted calsequestrin overexpression show marked suppression of Ca2+-induced Ca2+ release, myocyte hypertrophy, and premature death by 16 weeks of age (Jones, L. R., Suzuki, Y. J., Wang, W., Kobayashi, Y. M., Ramesh, V., Franzini-Armstrong, C., Cleemann, L., and Morad, M. (1998)J. Clin. Invest. 101, 1385–1393). To investigate whether alterations in intracellular Ca2+ trigger changes in the β-adrenergic receptor pathway, we studied calsequestrin overexpressing transgenic mice at 7 and 14 weeks of age. As assessed by echocardiography, calsequestrin mice at 7 weeks showed mild left ventricular enlargement, mild decreased fractional shortening with increased wall thickness. By 14 weeks, the phenotype progressed to marked left ventricular enlargement and severely depressed systolic function. Cardiac catheterization in calsequestrin mice revealed markedly impaired β-adrenergic receptor responsiveness in both 7- and 14- week mice. Biochemical analysis in 7- and 14-week mice showed a significant decrease in total β-adrenergic receptor density, adenylyl cyclase activity, and the percent high affinity agonist binding, which was associated with increased β-adrenergic receptor kinase 1 levels. Taken together, these data indicate that alterations in β-adrenergic receptor signaling precede the development of overt heart failure in this mouse model of progressive cardiomyopathy.
On Attaining the Multiple Solutions of Selective Harmonic Elimination PWM Three-Level Waveforms Through Function Minimization

Selective harmonic elimination pulsewidth modulation techniques are some of the control methods used in voltage/current source converters. However, challenges such as the task of finding all the multiple sets of solutions of the switching angles for a given problem may be difficult to deal with. In this paper, a direct minimization of the nonlinear transcendental trigonometric Fourier functions in combination with a random search is discussed. The unipolar (three-level) waveform is used to illustrate the proposed method confirming its ability to find multiple sets of solutions, including a case where 51 angles are sought for single- and three-phase applications. A simple harmonic distortion factor is studied for each set of solutions to assess their performance against the noneliminated harmonics. The results presented both at theoretical and experimental level are in close agreement and confirm the robustness of the proposed approach.
Supporting polymorphism in xml data

The Extensible Markup Language (XML) is rapidly becoming the standard language for web data representation and exchange. XML data is structured as a hierarchy. Different users and organizations may adopt different hierarchies for their data. It often happens that the same information can be represented in different hierarchies in XML. We use the term polymorphism to characterize this property of the XML format. Polymorphism is very common in the practical use of XML data, yet there has been relatively little research on it. This dissertation examines issues important to the support for polymorphism in XML data. First, we examine the semantics of XML hierarchy. We formulate a semantics that captures the data modeling functionality of XML hierarchy. We then look at several applications in which polymorphism in XML data is of great significance and vast presence. These include XML compaction, XML restructuring, symmetric exploitation of XML data, and schema-less, semantics-based change detection for XML. Studying these issues is beneficial to the advancement of XML data management in general and to the understanding of XML data polymorphism in particular.
Lethal Obesity Associated with Sodium Valproate in a Brain-Injured Patient

A 34-year-old man developed posttraumatic epilepsy and a disinhibited orbitofrontal syndrome following severe head trauma at age 22. After an 11-year prison term marked by repeated impulsive aggression, he was transferred to a state psychiatric hospital. Replacement of phenytoin by valproic acid resulted in a 100-lb weight gain, exacerbation of sleep apnea, and right heart failure. Despite replacement of valproate with topiramate, he died of a cardiorespiratory arrest during a seizure. This case illustrates the potential risks associated with valproate therapy in the obese brain-damaged population.
Thermal and slip effects on rotor time constant in vector controlled induction motor drives

In this paper, the fast variation of rotor resistance due to winding temperature is shown. Thus, the rotor time constant in the vector controlled induction motor drives, in contrary to common belief, changes fast via temperature. Moreover, it depends on the motor slip. The slip dependency of rotor time constant is due to motor loss that is usually ignored. The iron and stray loss is introduced in the induction machine dynamic and static models and a new expression of the rotor time constant is derived, that contains the motor slip. Thus, the rotor time constant rapidly varies at load torque changes. A novel slip frequency calculation procedure is proposed that ensures the accurate and fast estimation of the valid machine rotor time constant. The above aspects have been verified by extensive simulation and experimental tests in a wide speed-torque range.
Trend of antibiotic resistance of Vibrio cholerae strains from East Delhi.

BACKGROUND & OBJECTIVE Epidemics of cholera caused by toxigenic Vibrio cholerae O1 and O139 (Bengal strain) represent a major public health problem in most developing countries. In view of the reported shift in epidemiology and pattern of antibiotic resistance in this was study carried out to assess the development of resistance to essential drugs like fluoroquinolones during treatment of cholera and cholera like cases in Delhi. METHODS Faecal specimens collected from 1184 patients with cholera and cholera like illness between 2001-2006 admitted to Guru Teg Bahadur hospital, East Delhi were subjected to culture isolation. Antimicrobial susceptibility testing of V. cholerae isolates was done by disc diffusion method. RESULTS Of the 1184 faecal samples examined, 670 (56.6%) were positive for V. cholera from 2001- 2006. V. cholerae El Tor Ogawa (54.6%) was more common than serotype Inaba (32.5%). During 2004-2006 V. cholerae Inaba emerged as the predominant serotype. Resistance to nalidixic acid, furazolidone and co-trimoxazole was constantly high (100%). Multiple antibiotic resistance (MAR) V. cholerae O1 Inaba isolates exhibited increased resistance to ciprofloxacin with MIC >4 microg/ml, but largely all remained susceptible to other antibiotics like, gentamicin, tetracycline and chloramphenicol. INTERPRETATION & CONCLUSION V. cholerae have a permanent existence in the environment and during the quiescent period, their survival in water bodies allows dissipation of resistance patterns to different serotypes or strains of V. cholerae O1 and therefore there is need for constant observation.
Immunopathologic study of fixed drug eruption

Background: Fixed drug eruption (FDE) is a common drug induced dermatosis that can be caused by a variety of drugs. Although effector and regulatory T cells play a role in progression and resolution of FDE, little in vivo data exist regarding T cell dynamics in its pathogenesis. Objectives: To through light on the immunopathogenesis of FDE through studying the participation of CD8+, CD4+ T cells and HLA-DR antigen in the pathogenesis of lesions. The role of serum Ca was studied. Patients and methods: Thirty skin biopsy specimens from FDE skin lesions were used (16 active lesions& 14 healed lesions). Thirty biopsy specimens from thirty age and sex matched healthy subjects were used as a control group. Histopathological examination of hematoxylin& eosin- stained sections included analysis and scoring of histopathological parameters was done. Expression of CD4, CD8 and HLA-DR antigens was examined immunohistochemically. Blood samples were collected from patients and control subjects for assesment of serum calcium. Results: Active lesions showed interface dermatitis and dermal inflammatory infiltrate. Positive immunostaining was observed in both epidermis and dermis for HLA-DR, CD4 and CD8 antigens. Healed lesions showed epidermal atrophy and dermal inflammatory infiltrate. Positive immunostaining was observed in both epidermis and dermis for HLA-DR, CD4 and CD8 antigens. Such results were absent in control sections. Both total and ionized Ca2+ were significantly lower in patients than control subjects. Conclusions: Activation of T cells residing in resting FDE lesions by ingestion of the causative drug results in epidermal injury possibly through the production of IFN-a. (Iman Abd El Fattah Seleit, Mohamed Ahmed Basha, Nansy Youssef Asaad, Ola Ahmed Amin. Immunopathologic study of fixed drug eruption. Report and Opinion 2011;3(2):14-23). (ISSN: 1553-9873). http://www.sciencepub. net .
Effect of generalized joint hypermobility on knee function and muscle activation in children and adults

Introduction: We investigated muscle activation strategy and performance of knee extensor and flexor muscles in children and adults with generalized joint hypermobility (GJH) and compared them with controls. Methods: Muscle activation, torque steadiness, electromechanical delay, and muscle strength were evaluated in 39 children and 36 adults during isometric knee extension and flexion. Subjects performed isometric maximum contractions, submaximal contractions at 25% maximum voluntary contraction (MVC), and explosive contractions. Results: Agonist activation was reduced, and coactivation ratio was greater in GJH during knee flexion compared with controls. Torque steadiness was impaired in adults with GJH during knee flexion. No effect of GJH was found on muscle strength or electromechanical delay. Correlation analysis revealed an association between GJH severity and function in adults. Conclusions: The results indicate that muscle activation strategy and quality of force control were significantly affected in adults with GJH during knee flexion, whereas only muscle activation strategy was affected in children with GJH. Muscle Nerve 48:762–769, 2013
Rotavirus serotype G3 predominates in horses

Foal fecal group A rotavirus strains were characterized by electropherotype, serotype, and subgroup and shown to be distinctly different from rotaviruses of other mammals. Of 86 strains that were electropherotyped, 98% had similar profiles, with gene segments 3 and 4 close together and segments 7, 8, and 9 widely spaced. Of 70 strains that had sufficient detectable VP7 antigen to be serotyped by enzyme-linked immunosorbent assays (ELISAs), 63% were serotype G3 (39% were subtype G3A and 24% were subtype G3B), 4% were serotype G13, and 33% were untypeable. Serotypes G1, G2, G4, G5, G6, G9, G10, and G14 were not detected, although G5 and G14 strains have been identified among cultivable equine strains. Of 50 strains that had sufficient detectable VP6 antigen to be subgrouped by ELISAs, only 12% were able to be assigned to either subgroup I or II, with the remaining 88% belonging to neither subgroup.
Assessment of apixaban plasma levels by laboratory tests: suitability of three anti-Xa assays

Summary While laboratory monitoring is not required in patients treated with apixaban, a direct factor-Xa inhibitor, assessment of its concentration is useful in some critical situations. However, few data are available on its effect on coagulation tests and on the suitability of anti-Xa assays for its quantification. It was the objective of this study to identify laboratory tests suitable for apixaban concentration assessment. Coagulation tests – PT and aPTT- and anti-Xa assays were performed in apixaban-spiked plasma samples. To evaluate the sensitivity of PT and aPTT to apixaban, we conducted a first monocenter part, with a wide range of concentrations (50–1,000 ng/ml), a large panel of reagents (20 reagents), and two coagulometers (STAR®, Stago and ACL TOP®, IL), and a second multicenter part involving 13 laboratories using either a common PT reagent (RecombiPlastin2G®) or the local PT and aPTT reagents. In the multicentre part, five blinded apixaban-spiked plasma samples (0/100/200/400/800 ng/ml – checked by HPLC-MS/MS) were used; apixaban concentrations were measured with three anti-Xa assays, apixaban calibrators and controls (Stago). PT and aPTT tests using a large panel of reagents displayed a low sensitivity to a wide range of apixaban concentrations. The concentrations to double PT ranged from 400 to >1,000 ng/ml with the 10 reagents. With the three anti-Xa assays, interlaboratory precision and accuracy were below 11% and 12%, respectively. In conclusion, whereas PT and aPTT tests were not sensitive enough to detect apixaban, the three anti-Xa assays tested using lyophilised apixaban calibrators and controls allowed to reliably quantify a wide range of apixaban concentrations.
Reasons for urban trail use predict levels of trail-related physical activity.

BACKGROUND Efforts to increase community levels of physical activity through the development of multiuse urban trails could be strengthened by information about factors predicting trail use. This study examined whether reasons for trail use predict levels of physical activity on urban trails. METHODS Adults (N = 335) living within a 1-mile buffer zone of urban trails in Chicago, Dallas, and Los Angeles completed a self-report measure assessing demographics, reason for trail use, and physical activity on the trail. Accelerometers measured total daily moderate-to-vigorous physical activity (MVPA). Environmental features of the urban trail were assessed with the Systematic Pedestrian and Cyclist Environmental Scan for trails measure. Multivariate regression analyses were conducted that accounted for clustering of individuals within trail segments. RESULTS After controlling for demographic and environmental factors and total daily MVPA, reasons for trail use significantly predicted recreational but not transportation activity. Recreational trail activity was greater for participants who reported exercise and health reasons for trail use as compared with other reasons (ie, social interaction, enjoying nature, walking pets) for recreational trail use. CONCLUSIONS To increase the use of urban trails, it may be useful to promote the health and exercise benefits of recreational trail use.
46,XY/47,XY,+ 17p+ mosaicism in amniocytes associated with fetal abnormalities despite normal fetal blood karyotype

46,XY/47,XY, + 17p + mosaicism was found in two primary amniotic fluid cultures (AFCs). Fetal blood karyotype was normal, but ultrasonography revealed Dandy‐Walker malformation and bilateral choroid plexus cysts. Following termination of pregnancy, fetal examination revealed post‐axial polydactyly and neuroblastoma‐in‐situ affecting both adrenals in addition to the cerebellar abnormalities. Mosaicism for the aberrant cell line was confirmed in all fetal tissues sampled and in the placenta.
Dysregulation of the immune system in Aicardi-Goutières syndrome: another example in a TREX1-mutated patient

Aicardi-Goutières syndrome (AGS) is a rare genetic encephalopathy characterized by neurological and extraneurological involvement. A clinical overlap between AGS and systemic lupus erythematosus (SLE) has been reported. We describe an AGS patient who developed autoimmune manifestations: thyroiditis, cANCA positivity, antiphospholipid antibodies and cerebral ischemia. This first description of antiphospholipid syndrome in a TREX1-mutated patient further expands the clinical spectrum of AGS. Although the clinical overlap with SLE may indicate common pathogenic mechanisms, the autoimmune manifestations in AGS are so extensive that we suggest they should be considered a clinical feature of the disease, rather than a sign of coexistent SLE.