Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic cystic fibrosis transmembrane regulator 4016insT D1152H compound heterozygosity and male infertility: an Italian case report

We report a case of a young subject without signs of cystic fibrosis (CF) presenting compound heterozygosity for two mutations of the cystic fibrosis transmembrane regulator (CFTR) gene, including the rare D1152H variant. A 30-year-old male from the Central Italian region of Lazio was referred to our laboratory for genetic screening of azoospermia factor region (AZF) microdeletions and CFTR mutations. The patient presented no history of pulmonary or pancreatic diseases. The genetic analyses were prescribed by an endocrinologist since the patient presented infertility due to severe oligospermia (data not reported). These tests were thus indicated for couple fertility pre-screening before an in vitro fertilization and embryo transfer (FIVET) procedure. The genetic test for AZF microdeletions was negative, whereas CFTR mutation screening identified compound heterozygosis for two rare CFTR mutations, namely 4016insT and D1152H. In addition, the patient exhibited genotype 7T/7T for intron 8 polymorphism screening. The genetic tests were performed using two commercially available kits, the INNO-LiPA CFTR Italian Regional kit for CFTR mutations (Innogenetics, Gent, Belgium) and an AB-Analitica kit (Padova, Italy) for AZF screening. The patient’s partner was not affected by any reproductive system diseases and results for all laboratory routine examinations were negative. To analyze the cis/trans configuration of these two mutations, we performed genetic CFTR tests on his
Critical perspectives on user involvement

In the UK, user involvement became an official policy through the health and social care system. But is this concept really established and accepted by all the parties concerned? Barnes and Cotterell deal with this question in a very inspiring way. With the collection ‘Critical Perspectives on User Involvement’, the editors assemble the knowledge and experience from more than 30 contributors from the scientific field, professionals as well as from the service users themselves.
Electrochemotherapy for cutaneous and subcutaneous tumor lesions: a novel therapeutic approach

Electroporation uses pulsed, high‐intensity electric fields to temporarily increase cell membrane permeability by creation of pores, through which small molecules, such as chemotherapeutic agents, can diffuse inside cells before they reseal. The combination of electroporation with the administration of otherwise low‐permeant cytotoxic drugs is known as electrochemotherapy (ECT). The two most commonly used drugs are bleomycin and cisplatin. ECT has already been proven to be effective in diverse tumor histotypes, including melanoma and basal and squamous cell carcinoma, Kaposi sarcoma, and breast cancer, also in those cases nonresponding to classical chemotherapies or other loco‐regional treatment modalities, with a good safety profile. ECT can be proposed as loco‐regional therapy for disseminated cutaneous and subcutaneous tumor lesions as alternative treatment modality to conventional therapies or as palliative care, in order to improve patients' quality of life.
Biologically inspired autoadaptive control of a knee prosthesis

This thesis describes the electronic control of a knee prosthesis for amputees. A microprocessor receives data from sensors, processes it and determines the proper level of rotary resistance for the joint. Control is maintained through one of two algorithms -one for a system with sensors only for knee angle and axial force and one that also senses bending moment at the knee base. The electronic knee can control stance stability, adapt to walking cadence and detect stairs and standing modes, all advantages over the conventional mechanical knee. It will also allow flexion during stancean important component of normal gait that most prostheses do not allow. Parameters for the knee are set automatically from observing the subject walk, rather then relying on the judgment of the prosthetist doing the fitting. As the subject moves, the output of the microprocessor changes and adapts to the actions of the subject, who might be walking faster, picking up a suitcase, or changing shoes. The algorithms were developed using five amputees with varying physical characteristics. Safety, comfort, and natural-appearing movement were considered in the project. Thesis Supervisor: Gill A. Pratt Title: Assistant Professor of Electrical Engineering and Computer Science, MIT
Aberrations of p16Ink4 and retinoblastoma tumour‐suppressor genes occur in distinct sub‐sets of human cancer cell lines

The p16Ink4/MTSI/CDKN2 is a cell‐cycle regulatory inhibitor of cyclin‐dependent kinase 4 (cdk4), and a candidate tumour suppressor whose gene on chromosome band 9p21 is frequently deleted or mutated in diverse types of cancer. Cdk4 in association with its D‐type cyclin partners, together with p16Ink4, and the product of the retinoblastoma tumour‐suppressor gene (pRB), appear to constitute a G1‐phase‐controlling pathway which can become de‐regulated through oncogenic aberrations of any of the components. In an attempt to elucidate the underlying molecular mechanisms, we have now surveyed expression of p16Ink4, at the protein and the mRNA levels, in 21 human cell types expressing normal pRB, as compared with another series of 21 cell lines whose pRB is mutant and/or inactivated through sequestration by DNA tumour virus onco‐proteins. In contrast to aberrant lack of p16 expression in the majority of RB‐positive cell types, expression of apparently normal (as shown by electrophoretic mobility and/or the ability to form protein‐protein complexes with cdk4 in vivo) p16 was uniformly preserved in the cancer cell lines whose RB function was compromised. These data indicate that p16 operates upstream of pRB along the same pathway in G1. The results are discussed in view of the nature of a selective growth advantage potentially gained by cells through de‐regulation of this key cell‐cycle control mechanism. © 1995 Wiley‐Liss, Inc.
Predicting instructional effectiveness of cloud-based virtual learning environment

Purpose Cloud computing technology is advancing and expanding at an explosive rate. These advancements have further extended the capabilities of the virtual learning environment (VLE) to provide accessibility anywhere, anytime where educational resources can be saved, modified, retrieved and shared on the cloud. The purpose of this paper is to examine the predictors of instructional effectiveness of cloud computing VLE by extending the Self Determination and Channel Expansion Theory with external constructs of VLE interactivity, content design, school support, trust in website, knowledge sharing attitude and demographic variables. Design/methodology/approach Random sampling data were collected in two waves of nation-wide survey and analyzed with artificial neural network approach. Findings SDT, CET, content design, interactivity, trust in website, school support and demographics significantly predict instructional effectiveness. Research limitations/implications The study has provided a new paradigm shift from investigating the behavioral intention and continuance intention to the effectiveness of an information system. It advocates that quality of research may be improved by adhering to the basic research methodology starting from rigorous instrument development and validation to future research direction. Practical implications The research provides implications to Ministry of Education, the VLE content and service providers, scholars and practitioners. Social implications The findings of the study may further improve the quality of living of the society when the instructional effectiveness of the cloud-based VLE is further enhanced. Originality/value Existing grid computing VLE studies have focussed on the acceptance of students and teachers and not its instructional effectiveness. Unlike existing studies that examined extrinsic motivational factors (e.g. TAM, UTAUT), this study uses intrinsic motivational factors (e.g. relatedness, competence and autonomy) as well as perceived media richness. Malaysia is the first nation to implement the VLE at a national scale and the findings from this study will provide a new insight on the determinants of instructional effectiveness of the VLE system.
Triamcinolone acetonide-mediated oxidative injury in retinal cell culture: comparison with dexamethasone.

PURPOSE To investigate the cytotoxicity of triamcinolone acetonide (TA) and dexamethasone (DXM) in various types of cells in retinal cell culture. METHODS Primary rat retinal cell cultures were treated with 25 to 800 microg/mL TA (58 microM-1.8 mM) or DXM (48 microM-1.6 mM) for 12 to 24 hours. Cell survival and death were assessed chemically by measuring cellular DNA contents using DNA-binding fluorescent dye and morphologically by propidium iodide staining. Standard methods were used for immunocytochemistry, immunoblots, and ELISA measurements. Retinal cellular oxidative stress was measured under a fluorescence microscope using 5-(and-6)-carboxy-2',7'-difluorodihydrofluorescein diacetate. Changes in the level of several antioxidative proteins were investigated using immunoblots. RESULTS Exposure to 100 to 800 microg/mL TA (0.23-1.8 mM) or 800 microg/mL DXM (1.6 mM) for 24 hours caused a significant reduction in the number of retinal cells in culture, in a glucocorticoid receptor-independent manner. Of cell types in retinal cell cultures, astrocytes were most sensitive to TA and DXM. TA-induced cytotoxicity was mediated by oxidative stress. p38 kinase, c-Jun N-terminal kinase (JNK), caspase-1, and caspase-3 were involved in oxidative injury by TA. In addition, levels of antioxidative proteins increased after TA exposure. CONCLUSIONS TA induces oxidative injury to cultured retinal cells in a glucocorticoid receptor-independent manner. These results suggest that TA has a significantly higher toxic potential in retinal cell culture than more water-soluble DXM. For long-term anti-inflammatory effects, devices that are designed for the sustained release of water-soluble steroids may be safer.
Reducing Effect of a Combination of Phaseolus vulgaris and Cynara scolymus Extracts on Operant Self‐Administration of a Chocolate‐Flavoured Beverage in Rats

Treatment with a rational combination of standardized extracts of Phaseolus vulgaris and Cynara scolymus reduced food intake and glycemia in rats. The present study was designed to assess the effect of this extract combination and of each single extract in an experimental model of food craving, made up of rats displaying exaggerated seeking and taking behaviors for a chocolate‐flavoured beverage. After training to lever‐respond for the chocolate‐flavoured beverage, rats were treated with vehicle, Phaseolus vulgaris extract alone (200 mg/kg), Cynara scolymus extract alone (400 mg/kg), or combination of Phaseolus vulgaris (200 mg/kg) and Cynara scolymus (400 mg/kg) extracts. The Phaseolus vulgaris extract and the extract combination exerted similar and substantial decrements in the number of lever‐responses and amount of self‐administered chocolate‐flavoured beverage; conversely, the Cynara scolymus extract was totally ineffective. These results suggest that (i) the capacity of the extract combination to reduce the self‐administration of the chocolate‐flavoured beverage entirely relied on the Phaseolus vulgaris extract, (ii) Phaseolus vulgaris extract may interfere with the mechanisms regulating food‐related addictive‐like behaviors, and (iii) combinations of Phaseolus vulgaris and Cynara scolymus extracts may possess a broad spectrum of activities, from treatment of metabolic syndrome to overweight, obesity, and possibly food‐related addictive disorders. Copyright © 2012 John Wiley & Sons, Ltd.
Characterization of T–cell subclasses and NK–cells in lysosomal disorders by immuno–electron microscopy

Previous studies have shown that B and T lymphocytes are affected in lysosomal disorders. The aim of this study was to investigate the involvement of subclasses of T lymphocytes and natural killer cells in lysosomal diseases. CD4 +, CD8 +, and CD56+ cells were immunomagnetically separated from peripheral blood mononuclear cells in 10 patients with various lysosomal diseases – including one patient each with infantile, late infantile, and juvenile neuronal ceroid–lipfuscinoses, two patients with mucopolysaccharidosis (MPS) type I and four patients with MPS type HI, and one patient with mucolipidosis type II; all lymphocytes were studied by light and electron microscopy. Respective vacuolar or non–vacuolar lysosomal inclusions were identified in CD4 +, CD8 +, and CD56+ cells. Subclass–specific abnormal lysosomes could not be found. Both subclasses of T lymphocytes investigated showed nearly the same ratio of affected to non–affected cells. These results were obtained by studying a small number of different lysosomal disorders. Nevertheless, they suggest that lysosomal storage in these subclasses of immunocompetent cells might also be found in other forms of lysosomal disease.
Real‐time ventilation and perfusion distributions by electrical impedance tomography during one‐lung ventilation with capnothorax

Carbon dioxide insufflation into the pleural cavity, capnothorax, with one‐lung ventilation (OLV) may entail respiratory and hemodynamic impairments. We investigated the online physiological effects of OLV/capnothorax by electrical impedance tomography (EIT) in a porcine model mimicking the clinical setting.
TCR-Independent and Caspase-Independent Apoptosis of Murine Thymocytes by CD24 Cross-Linking1

CD24, also referred to as the heat-stable Ag, is a T cell differentiation Ag that is highly expressed on both CD4−CD8− double negative and CD4+CD8+ double positive thymocytes. Here, we report that CD24 ligation by a new anti-CD24 Ab, mT-20, induced the apoptosis of both double negative and double positive thymocytes, as well as the Scid.adh thymic lymphoma cell line, in the absence of TCR/CD3 engagement. CD24-mediated apoptosis of mouse thymocytes and its signaling pathway appeared not to be associated with p53, CD95, TNFR, or caspases. Furthermore, we found that cell death was blocked by the addition of scavengers of reactive oxygen species or by Bcl-2 overexpression, implying the role of CD24 signaling in the mitochondrial regulation. In this study, we suggest that CD24 ligation induced the apoptosis of immature thymocytes independently of both caspase and TCR.
The economic efficiency of apple production in terms of post‑harvest technology

This study analyses how the level of postharvest technology’s development influences the economic efficiency of apple production with the help of a deterministic simulation model based on primary data gathering in producer undertakings. To accomplish our objectives and to support our hypotheses three processing plant types are included in the model: firstly apple production with no postharvest and prompt sale after the harvest, secondly parallel production and storage combined with an extended selling period and thirdly production and entire postharvest infrastructure (storage, sorting-ranking, packing) with the highest level of goods production and continuous sales. Based on our results it can be stated that the parallel production (plantation) and cold storage, so the second case is proved to be totally inefficient, considering that the establishment of a cold storage carries enormously high costs with resulting a relative low plus profit compared to the first type of processing plant. The reason for this is that this type is selling bulk goods without sorting-grading or packaging; storage itself – as a means of continuously servicing the market – is not covered properly by the consumers. Absolute efficiency ranking cannot be established regarding the other two processing plants: plantation without post-harvest infrastructure resulting lower NPV, but a more favourable IRR, DPP and PI as developing a plantation and a whole post-harvest infrastructure.
Nearly four million California adults are victims of intimate partner violence.

Nearly 1 in 6 adults in California, about 3.7 million persons, report experiencing physical intimate partner violence (IPV) as adults, according to the authors of this policy brief. Using data from the 2007 California Health Interview Survey, the authors found that over one million Californians were forced to have sex by an intimate partner during adulthood and17.2% of adults-—nearly four million Californians-—report being a victim of physical and/or sexual IPV as an adult. The brief also looks at patterns of reported IPV during adulthood by race ethnicity as well as gender and sexual orientation.
A novel Chk1/2–Lats2–14-3-3 signaling pathway regulates P-body formation in response to UV damage

Proper response to DNA damage is essential for maintaining the integrity of the genome. Here we show that in response to ultraviolet (UV) radiation, the Lats2 tumor suppressor protein is phosphorylated predominantly by Chk1 and weakly by Chk2 at S408 in vivo, and that this process occurs at all stages of the cell cycle and leads to phosphorylation of 14-3-3γ on S59 by Lats2. Interaction of Lats2 and 14-3-3γ in vivo was confirmed by immunoprecipitation and western blot analysis. Phosphorylated 14-3-3γ translocates to the P-body, where mRNA degradation, translational repression and mRNA surveillance take place. Depletion of Lats2 or 14-3-3γ by siRNA inhibits P-body formation in response to UV, newly implicating Lats2 and 14-3-3 as regulators of P-body formation. By contrast, siRNA-mediated depletion of Lats1, a mammalian paralog of Lats2, showed no such effect. On the basis of these findings, we propose that the Chk1/2–Lats2–14-3-3 axis identified here plays an important role in connecting DNA damage signals to P-body assembly.
Avian apolipoprotein A-V binds to LDL receptor gene family members Published, JLR Papers in Press, March 30, 2007.

Apolipoprotein A-V (apoA-V) affects plasma triglyceride (TG) levels; however, the properties of apoA-V that mediate its action(s) are still incompletely understood. It is unclear how apoA-V, whose plasma concentration is extremely low, can affect the pronounced TG differences observed in individuals with various apoA-V dysfunctions. To gain novel insights into apoA-V biology, we expanded our previous studies in the chicken to this apolipoprotein. First, we characterized the first avian apoA-V, revealing its expression not only in liver and small intestine but also in brain, kidney, and ovarian follicles and showing its presence in the circulation. Second, we demonstrate directly that galline apoA-V binds to the major LDL receptor family member (LR) of the laying hen and that this interaction does not depend on the association of the apolipoprotein with lipid or lipoproteins. We propose that a direct interaction with LRs may represent a novel, additional mechanism for the modulation of TG levels by apoA-V.
Use of space and its impact on the welfare of laying hens in a commercial free-range system.

The aim of this study was to explore the factors influencing patterns of space use of commercial free-range laying hens and their relation to welfare indicators. Three free-range laying hen flocks were studied during one production cycle by collecting spatial locations on 150 individually tagged hens per flock. At the end of production, welfare and morphometric measures were collected. The results indicated that use of the outdoor area was lower during midday (P < 0.05), but remained stable across age periods (P > 0.05). Tagged hens were classified according to their use of the outdoor area (heavy, medium, light, or never) per age period. A total of 49.5% were never observed using the outdoor area, which was higher than any other category (P < 0.05). In addition, the early experience of the hens using the outdoor area during the first 16 wk (20 to 36 wk) determined the level of use of the outdoor area at later ages (P < 0.05). Most use of space parameters did not vary according to age period (P > 0.05); only activity center indoors increased (P < 0.05), while mean distance from the hen house tended to increase (P = 0.053). However, birds with a higher frequency of use of the outdoor area had larger home ranges and activity centers (r = 0.956, r = 0.964 P < 0.05, respectively) and showed lower plumage damage (r = -0.337, P < 0.05) and a lower incidence of footpad dermatitis (r = -0.307, P < 0.05). On the contrary, birds showing higher total walked distance indoors showed a higher incidence of footpad dermatitis (r = 0.329, P < 0.01). We conclude that there exist individual differences in the use of the outdoor area, with early experience (20 to 36 weeks) during the production period being the most relevant factor affecting outdoor area use. Birds visiting the outdoor area more frequently also used larger areas. In addition, individual patterns of space use had some relevance on the incidence on foot pad dermatitis and plumage condition.
Review article: diagnosis and treatment of non‐alcoholic fatty liver disease

Background Non‐alcoholic fatty liver disease (NAFLD) is an increasingly prevalent condition affecting adults and children, leading to significant morbidity. It is often associated with the metabolic syndrome, although multiple pathogenetic mechanisms have been suggested. In the coming decades, it promises to be the leading cause of liver disease in industrial countries.
Enterprise resource planning: An integrative review

Enterprise resource planning (ERP) system solutions are currently in high demand by both manufacturing and service organisations because they provide a tightly integrated solution to an organisation's information system needs. During the last decade, ERP systems have received a significant amount of attention from researchers and practitioners from a variety of functional disciplines. In this paper, a comprehensive review of the research literature (1990‐2003) concerning ERP systems is presented. The literature is further classified and the major outcomes of each study are addressed and analysed. Following a comprehensive review of the literature, proposals for future research are formulated to identify topics where fruitful opportunities exist.
Grid-connected topology of PMSG wind power system based on VSC-HVDC

As the wind power generation technique is improved greatly, permanent magnet synchronous generator (PMSG) is paid more and more attention because of its multiple advantages. Nevertheless, conventional directly-drive PMSG wind generation system is connected to the grid by AC transmission. This paper introduces the DC connection structure of wind farm based on PMSG. According to VSC-HVDC (Voltage Source Converter based HVDC) transmission, the topology of series-parallel DC generation units is proposed. Regarding to the control strategy of the power generation and transmission system mentioned above, the DC voltage is controlled on generator-side for achieving the purpose of seriesparallel, and on grid-side active and reactive power decoupling method is applied to track maximum wind power by controlling the d-axis and q-axis current of the grid. The models of singlegenerator, series connection and parallel connection system are established on the PSCAD/EMTDC platform. Simulation results prove the validity of the topology scheme and the corresponding control strategy.