Miracle-dz/UniFAR-FTUs huggingface dataset:
Epac2‐dependent mobilization of intracellular Ca2+ by glucagon‐like peptide‐1 receptor agonist exendin‐4 is disrupted in β‐cells of phospholipase C‐ɛ knockout mice

Calcium can be mobilized in pancreatic β‐cells via a mechanism of Ca2+‐induced Ca2+ release (CICR), and cAMP‐elevating agents such as exendin‐4 facilitate CICR in β‐cells by activating both protein kinase A and Epac2. Here we provide the first report that a novel phosphoinositide‐specific phospholipase C‐ɛ (PLC‐ɛ) is expressed in the islets of Langerhans, and that the knockout (KO) of PLC‐ɛ gene expression in mice disrupts the action of exendin‐4 to facilitate CICR in the β‐cells of these mice. Thus, in the present study, in which wild‐type (WT) C57BL/6 mouse β‐cells were loaded with the photolabile Ca2+ chelator NP‐EGTA, the UV flash photolysis‐catalysed uncaging of Ca2+ generated CICR in only 9% of the β‐cells tested, whereas CICR was generated in 82% of the β‐cells pretreated with exendin‐4. This action of exendin‐4 to facilitate CICR was reproduced by cAMP analogues that activate protein kinase A (6‐Bnz‐cAMP‐AM) or Epac2 (8‐pCPT‐2′‐O‐Me‐cAMP‐AM) selectively. However, in β‐cells of PLC‐ɛ KO mice, and also Epac2 KO mice, these test substances exhibited differential efficacies in the CICR assay such that exendin‐4 was partly effective, 6‐Bnz‐cAMP‐AM was fully effective, and 8‐pCPT‐2′‐O‐Me‐cAMP‐AM was without significant effect. Importantly, transduction of PLC‐ɛ KO β‐cells with recombinant PLC‐ɛ rescued the action of 8‐pCPT‐2′‐O‐Me‐cAMP‐AM to facilitate CICR, whereas a K2150E PLC‐ɛ with a mutated Ras association (RA) domain, or a H1640L PLC‐ɛ that is catalytically dead, were both ineffective. Since 8‐pCPT‐2′‐O‐Me‐cAMP‐AM failed to facilitate CICR in WT β‐cells transduced with a GTPase activating protein (RapGAP) that downregulates Rap activity, the available evidence indicates that a signal transduction ‘module’ comprised of Epac2, Rap and PLC‐ɛ exists in β‐cells, and that the activities of Epac2 and PLC‐ɛ are key determinants of CICR in this cell type.
Implementing Electronic Commerce in SMEs: Process and Barriers

Partwell Limited is a small to medium sized (SME) manufacturing and supply company based in the United Kingdom. This case study discusses the circumstances that led the company to consider the implementation of two Internet Web sites for the purpose of conducting Electronic Commerce (e-commerce). The history and culture of Partwell are described, as are the histories and characteristics of key personnel involved in this e-commerce project. Furthermore, the companyâ€™s previous experience with information and communication technology (ICT) is described. Following on from this the process by which e-commerce was introduced into the company is explained. This information provides the background for analyzing the case study. Finally, the case study goes on to show the importance of SMEs to the economy of the UK and identifies the main factors that inhibit SMEs from adopting e-commerce. The tangible benefits and consequences of this e-commerce project are identified.
A Robotic Exoskeleton for Treatment of Crouch Gait in Children With Cerebral Palsy: Design and Initial Application

Crouch gait, a pathological pattern of walking characterized by excessive knee flexion, is one of the most common gait disorders observed in children with cerebral palsy (CP). Effective treatment of crouch during childhood is critical to maintain mobility into adulthood, yet current interventions do not adequately alleviate crouch in most individuals. Powered exoskeletons provide an untapped opportunity for intervention. The multiple contributors to crouch, including spasticity, contracture, muscle weakness, and poor motor control make design and control of such devices challenging in this population. To our knowledge, no evidence exists regarding the feasibility or efficacy of utilizing motorized assistance to alleviate knee flexion in crouch gait. Here, we present the design of and first results from a powered exoskeleton for extension assistance as a treatment for crouch gait in children with CP. Our exoskeleton, based on the architecture of a knee-ankle-foot orthosis, is lightweight (3.2 kg) and modular. On board sensors enable knee extension assistance to be provided during distinct phases of the gait cycle. We tested our device on one six-year-old male participant with spastic diplegia from CP. Our results show that the powered exoskeleton improved knee extension during stance by 18.1° while total knee range of motion improved 21.0°. Importantly, we observed no significant decrease in knee extensor muscle activity, indicating the user did not rely solely on the exoskeleton to extend the limb. These results establish the initial feasibility of robotic exoskeletons for treatment of crouch and provide impetus for continued investigation of these devices with the aim of deployment for long term gait training in this population.
Detection times of marijuana metabolites in urine by immunoassay and GC-MS.

Reports of prolonged drug excretion have provided the basis for the common assumption that cannabinoid metabolites may he detected in urine for a week or longer. The accuracy, sensitivity, and specificity of immunoassays for the detection of cannabinoids and metabolites are unique for a specific assay and may change overtime. it is important that individuals who select assays and those who interpret test results be aware of qualitative and quantitative changes that occur. In the present study, detection times of cannabinoids in urine were determined using cannabinoid immunoassays with 20-, 50-, and 100-ng/mL cutoffs and using gas chromatography-mass spectrometry (GC-MS). Six subjects each smoked a single marijuana cigarette (placebo, 1.75, or 3.55% delta9-tetrahydrocannabinol [THC]) each week while residing on the clinical ward of the Addiction Research Center. Each urine specimen was analyzed under blind conditions by immunoassay according to the manufacturer's instructions. The following cannabinoid reagents were evaluated: EMIT d.a. u. 100, EMIT d.a. u. 50, EMIT d.a. u. 20, EMIT II 100, EMIT II 50, Abuscreen OnLine, and Abuscreen RIA, DRI, and ADx. All urine specimens were also analyzed for 11-nor-9-carboxy-delta9-THC by GC-MS using a 15-ng/mL cutoff. Urinary cannabinoid detection times varied substantially across assays, subjects, doses, and cutoff concentrations. Detection times were shorter than previously assumed. Mean detection times increased from a maximum of 0.5 days after the low dose to 1.5 days after the high dose using the 100-ng/mL cutoff. Mean detection times were less than 1 day following the low dose and less than 2 days following high-dose exposure using the 50-ng/mL cutoff. Mean detection times ranged from 1 to 5 days after the low dose and from 3 to 6 days after the high dose using the 20-ng/mL cutoff immunoassay. GC-MS detection times were approximately twice as long as mean detection times using an immunoassay with a cutoff of 50 ng/mL. Differences in sensitivity and specificity between the available immunoassay products affected the efficiency of detection of marijuana use. These results indicate that recent reductions in cannabinoid cutoffs by military and federally mandated programs will increase detection times and improve sensitivity, as expected. However, monitoring acute marijuana usage with a commercial cannabinoid immunoassay that has a 50-ng/mL cutoff concentration provides only a narrow window of detection of 1-2 days.
Orbital roof growing fractures: a report of four cases and literature review

Trivial injuries among paediatric patients are usually underestimated. Such injuries may account for delayed problems such as growing fractures of skull vault. Growing fracture of the orbital roof is rarely reported. Four cases of paediatric cranial trauma with growing orbital roof fractures are presented. Three cases required only dural repair, while the fourth patient underwent both duraplasty and cranioplasty, due to a large orbital roof defect. At follow-up, all had satisfactory outcome. Trivial injuries among children should be evaluated with caution. The development of orbital symptomatology should ask for a complete radiological survey. The orbital roof growing fractures are potentially important cause of orbital problems. The dural repair alone, usually provides satisfactory outcome, while calvarial bone graft may be of help in cases with large bony defects. Early diagnosis and management of such cases may prevent permanent neurological deficits.
Drug interactions as a cause of overanticoagulation on phenprocoumon or acenocoumarol predominantly concern antibacterial drugs

The risk of hemorrhage when coumarin anticoagulants are used sharply increases when the international normalized ratio (INR) is ≥6.0. Such overanticoagulation may be caused by drug interactions. We performed a case‐control study among previously stable outpatients of an anticoagulation clinic using phenprocoumon or acenocoumarol to identify changes in the use of potentially interacting drugs related to overanticoagulation.
Evolutionary design of multiclass support vector machines

Support Vector Machines constitute a Machine Learning technique originally designed for the solution of 2-class problems. For multiclass applications, several strategies divide the original problem into a set of binary subtasks, whose results are combined. This work introduces the use of Genetic Algorithms to determine binary decompositions of multiclass problems. Experimental results on benchmark and Bioinformatics multiclass datasets indicate the potential of the proposed approach, which is able to produce good multiclass solutions with the use of simple decompositions.
Non-homologous end joining: advances and frontiers.

DNA double-strand breaks (DSBs) are the most serious form of DNA damage. In human cells, non-homologous end joining (NHEJ) is the major pathway for the repair of DSBs. Different types of DSBs result in different subsets of NHEJ repair strategies. These variations in NHEJ repair strategies depend on numerous elements, such as the flexible recruitment of NHEJ-related proteins, the complexity of the DSB ends, and the spatial- and temporal-ordered formation of the multi-protein complex. On the one hand, current studies of DNA DSBs repair focus on the repair pathway choices between homologous recombination and classic or alternative NHEJ. On the other hand, increasing researches have also deepened the significance and dug into the cross-links between the NHEJ pathway and the area of genome organization and aging. Although remarkable progress has been made in elucidating the underlying principles during the past decades, the detailed mechanism of action in response to different types of DSBs remains largely unknown and needs further evaluation in the future study.
SEBOCYSTOMATOSIS: A CLINICAL VARIANT OF STEATOCYSTOMA MULTIPLEX

A thirty-year-old man was evaluated for multiple papules and nodules on the forehead and scalp. The lesions had first appeared on his scalp at the age of 25 years, and since then they had slowly increased in size and number and had spread onto the forehead and cheeks (Fig. 1). The patient also had congenital alopecia on the frontal scalp. Physical examination revealed many yellowish firm, freely movable small and large papules and nodules with cystic firmness on his forehead and scalp. There were no similar lesions below the neck area of the body. His family history was noncontributory and the results of routine laboratory investigation were within normal limits. Histopathologic findings showed multiple round cysts in the midand deep dermis. The walls of the cysts were composed of three or five layers of squamous epithelium without granular layer and the cysts contained small amounts of keratinous materials and no vellus hairs. Undulatory eosinophilic homogenous cuticles irregularly protruded into the luman and mature sebaceous lobules were located near the cysts (Fig. 2). We diagnosed this case as steatocystoma multiplex (SM) histopathologically, because of undulatory eosinophilic homogenous cuticles that are characteristic of SM.
Intrathecal pathogenic anti–aquaporin‐4 antibodies in early neuromyelitis optica

The serum of most neuromyelitis optica (NMO) patients contains autoantibodies (NMO‐IgGs) directed against the aquaporin‐4 (AQP4) water channel located on astrocyte foot processes in the perivessel and subpial areas of the brain. Our objectives were to determine the source of central nervous system (CNS) NMO‐IgGs and their role in disease pathogenesis.
Numerical methods of computation of singular and hypersingular integrals

In solving numerous problems in mathematics, mechanics, physics, and tech- nology one is faced with necessity of calculating different singular integrals. In analytical form calculation of singular integrals is possible only in unusual cases. Therefore approximate methods of singular integrals calculation are an active develop- ing direction of computing in mathematics. This review is devoted to the optimal with respect to accuracy algorithms of the calculation of singular integrals with fixed singu- larity, Cauchy and Hilbert kernels, polysingular and many-dimensional singular integrals. The isolated section is devoted to the optimal with respect to accuracy algorithms of the calculation of the hypersingular integrals.
Stability and instability in evolution.

In this paper we propose a mechanism which tries to explain the presence of periods of stability and instability which occur during the evolution of living forms. According to the Gaia hypothesis there are feedback mechanisms which stabilise the biosphere. Adding the presence of parameters which are out of control of the biosphere and of different time-scales, we propose a model which might explain the periods of instability.
Investigation of sludge viscosity and its effects on the performance of a vacuum rotation membrane bioreactor

Sludge characteristics of a full-scale vacuum rotation membrane (VRM) bioreactor having plate-type membranes with 0.038 μm nominal pore size and 540 m2 surface area were investigated. The VRM plant is composed of an aeration tank and a filtration chamber. The sludge floc size distribution, as determined microscopically, was mainly between 0 and 100 μm in the filter chamber with very little difference in size distribution between summer (20–25°C) and winter (10–15°C) seasons. Small floc size encountered in the filtration chamber was evident due to excessive shear administered by the rotation action and vigorous agitation by the scouring air. The mixed liquor suspended solids (MLSS) was variable between 5.23 and 14.10 g/L in the VRM tank and sludge behaved plastic. Viscosity ranged between 2.39 and 30 cP in the VRM tank in relation with MLSS concentration and temperature. Above 20 cP inter-plate spaces rapidly clogged leading to major clean-up.
Subclinical Lesions and Donor-Specific Antibodies in Kidney Transplant Recipients Receiving Tacrolimus-Based Immunosuppressive Regimen Followed by Early Conversion to Sirolimus

Background There is no evidence on the incidence of subclinical inflammation and scaring lesions in patients receiving tacrolimus (TAC) minimization and elimination immunosuppressive regimens. Methods This study analyzed preimplantation, 3 and 24 months protocol biopsies and anti-HLA donor-specific antibodies (DSA) in 140 low immunological risk kidney transplant recipients receiving reduced TAC exposure, prednisone, and mycophenolate, randomized at 3 months to be converted or not to sirolimus (SRL). Results Mean TAC concentrations were 6.0 ± 2.4 ng/mL and 5.8 ± 2.2 ng/mL at 3 and 24 months. The incidence of subclinical inflammation lesions at 3 months was 9.3%. The incidence of (interstitial fibrosis) IF/(tubular atrophy) TA at month 24 was 57.6%, higher in SRL compared to TAC group (68.8 vs 44.4%; P = 0.022). Patients converted to SRL showed higher incidence of acute rejection (7.3% vs 0%), proteinuria (59.6% vs 25%; P = 0.001), and DSA (17.8% vs 7.3%; P = 0.201), respectively. Biopsy-proven acute rejection (odds ratio [OR] 2.32, 95% confidence interval [95% CI], 0.979-5.518, P = 0.056), subclinical inflammation lesions at 3 months (OR, 11.75; 95% CI, 1.286-107.474; P = 0.029) and conversion to SRL (OR, 2.72; 95% CI, 1.155-6.383; P = 0.022) were associated with IF/TA at month 24. Black ethnicity (OR, 0.22; 95% CI, 0.058-0.873; P = 0.031), donor age (OR, 2.74; 95% CI, 1.329-5.649; P = 0.006), and conversion to SRL (OR, 2.34; 95% CI, 1.043-5.267; P = 0.039) were associated with inferior renal function at 24 months. Conclusions In kidney transplant recipients receiving reduced TAC exposure, subclinical inflammation lesions at 3 months were associated with IF/TA at 24 months. Conversion from TAC to SRL was associated with inferior renal function, higher incidence of IF/TA, and trends to higher incidence of DSA at 24 months.
Phase III trial of interferon alfa-2a with or without 13-cis-retinoic acid for patients with advanced renal cell carcinoma.

PURPOSE A randomized phase III trial was conducted to determine whether combination therapy with 13-cis-retinoic acid (13-CRA) plus interferon alfa-2a (IFNalpha2a) is superior to IFNalpha2a alone in patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS Two hundred eighty-four patients were randomized to treatment with IFNalpha2a plus 13-CRA or treatment with IFNalpha2a alone. IFNalpha2a was given daily subcutaneously, starting at a dose of 3 million units (MU). The dose was escalated every 7 days from 3 to 9 MU (by increments of 3 MU), unless >/= grade 2 toxicity occurred, in which case dose escalation was stopped. Patients randomized to combination therapy were given oral 13-CRA 1 mg/kg/d plus IFNalpha2a. Quality of life (QOL) was assessed. RESULTS Complete or partial responses were achieved by 12% of patients treated with IFNalpha2a plus 13-CRA and 6% of patients treated with IFNalpha2a (P =.14). Median duration of response (complete and partial combined) in the group treated with the combination was 33 months (range, 9 to 50 months), versus 22 months (range, 5 to 38 months) for the second group (P =.03). Nineteen percent of patients treated with IFNalpha2a plus 13-CRA were progression-free at 24 months, compared with 10% of patients treated with IFNalpha2a alone (P =.05). Median survival time for all patients was 15 months, with no difference in survival between the two treatment arms (P =.26). QOL decreased during the first 8 weeks of treatment, and a partial recovery followed. Lower scores were associated with the combination therapy. CONCLUSION Response proportion and survival did not improve significantly with the addition of 13-CRA to IFNalpha2a therapy in patients with advanced RCC. 13-CRA may lengthen response to IFNalpha2a therapy in patients with IFNalpha2a-sensitive tumors. Treatment, particularly the combination therapy, was associated with a decrease in QOL.
Association between exposure to Neospora caninum and milk production in dairy cows.

OBJECTIVE To determine association between exposure to Neospora caninum and milk production in dairy cows. DESIGN Prospective observational study. ANIMALS 565 Holstein cows. PROCEDURE Cows were classified as seropositive or seronegative to N. caninum within 7 days after calving by use of a kinetic ELISA. Milk production was compared between seropositive and seronegative cows. RESULTS On the basis of 305-day mature equivalent milk production data, seropositive cows produced less milk (2.8 lb/cow per day) than did seronegative cows. In addition, analysis of results throughout the first 300 days of lactation revealed that after adjusting for effects of lactation number, calving season, clinical mastitis, and lameness, milk weight of seropositive cows was 2.5 lb/cow per day less than that of seronegative cows. CONCLUSIONS AND CLINICAL RELEVANCE Exposure to N. caninum was associated with a 3 to 4% decrease in milk production. A decrease in milk production of 800 lb/cow for a typical 305-day lactation represents a loss of $128/cow.
Docetaxel, oxaliplatin, and capecitabine (TEX regimen) for patients with metastatic gastric cancer: Interim results from a phase II trial by the German AIO Group.

4554 Background: Combination regimens of 3 drugs have shown promising activity as treatment for patients (pts) with metastatic gastric cancer (GC). Docetaxel combined with cisplatin and 5-FU (CF) improved overall survival and response rates when compared to standard CF. However, the identification of less toxic and more convenient variants of this regimen is still important. We have previously established a regimen with docetaxel (T) combined with oxaliplatin (E) and capecitabine (X) in a phase I trial [Grothe et al., Proc. ASCO 2006]. Results of a preplanned interim analysis of subsequent multicenter phase II trials of the TEX regimen are presented here. METHODS Pts with metastatic or locally advanced GC, adequate organ function, ECOG PS 0-2, and no prior chemotherapy for advanced disease (adjuvant allowed) were enrolled. TEX regimen was administered as defined: T 35 mg/m2 and E 70 mg/m2 on days (d) 1 and 8, with X 800 mg/m2 bid on d1-14 every 22 days Toxicity assessment was done 3-weekly while CT scans were repeated 9-weekly. RESULTS 35 of 48 pts were enrolled until 06/08: 28 male / 7 female, median age 59 (36-81) years, ECOG PS 0/1/2 69%/31%/0%, gastric / gastroesophageal cancer 60%/40%, distant metastases 96%, tumor in situ 37%. The most common toxicities reported were (CTC grade [gr] 3/4): diarrhea 20%/3%, vomiting 11%/3%, asthenia and neurotoxicity each 9%/0%. Mucositis and hand-foot-syndrome were observed in (grade 1+2 / grade 3) 29%/0% and 26%/3%, respectively. Hematoxicity was mild with grade 3 anemia in 10% and no other grade 3/4 toxicity except one episode of febrile neutropenia . Of 25 pts evaluable so far, first tumor response assessment revealed (RECIST criteria) partial response in 36% and stable disease in 40% of patients. CONCLUSIONS TEX is a safe and tolerable regimen for patients with metastatic gastric cancer. Preliminary efficacy results indicate promising activity. Mature data including progression free survival will be presented at the meeting. [Table: see text].
Myths about nutrition in pregnancy

Abstract Many women have incorrect knowledge about nutrition in pregnancy owing to false beliefs derived from popular practices. More than 90% of our cohort of pregnant women during early pregnancy (<12 weeks of gestational age) gave at least one incorrect answer to the five questions relative to common myths about nutrition in pregnancy. Education was inversely associated with the percentage of incorrect answers, and the lowest percentage of any mistakes was found in the small number of women who received nutritional information by a dietician. In conclusion, the usual sources of information about nutrition in pregnancy are not adequate to overcome the false beliefs acquired by traditions.