Miracle-dz/UniFAR-FTUs huggingface dataset:
Gene therapy strategies for hemophilia: benefits versus risks

Hemophilia is an inherited bleeding disorder caused by a deficiency of functional clotting factors VIII or IX in the blood plasma. The drawbacks of the classical protein substitution therapy fueled interest in alternative treatments by gene therapy. Hemophilia has been recognized as an ideal target disease for gene therapy because a relatively modest increase in clotting factor levels can result in a significant therapeutic benefit. Consequently, introducing a functional FVIII or FIX gene copy into the appropriate target cells could ultimately provide a cure for hemophilic patients. Several cell types have been explored for hemophilia gene therapy, including hepatocytes, muscle, endothelial and hematopoietic cells. Both nonviral and viral vectors have been considered for the development of hemophilia gene therapy, including transposons, γ‐retroviral, lentiviral, adenoviral and adeno‐associated viral vectors. Several of these strategies have resulted in stable correction of the bleeding diathesis in hemophilia A and B murine as well as canine models, paving the way towards clinical trials. Although clotting factor expression has been detected in hemophilic patients treated by gene therapy, the challenge now lies in obtaining prolonged therapeutic FVIII or FIX levels in these patients. This review highlights the benefits and potential risks of the different gene therapy strategies for hemophilia that have been developed. Copyright © 2010 John Wiley & Sons, Ltd.
Unemployment pre-dates symptoms of depression and anxiety resulting in medical consultation in young men.

BACKGROUND There is evidence to support a link between unemployment and lower levels of psychological well-being, but debate continues as to whether unemployment results in psychological morbidity, or whether the association is due to those who are more vulnerable to mental illness becoming unemployed. Here we assess the effect of recent and accumulated unemployment in young men on the risk of developing depression and anxiety leading to medical consultation. Adjustment was made for a measure of pre-existing tendency to depression, behavioural maladjustment, social class, qualifications and region of residence. METHODS Some 3241 men from the National Child Development Study (the 1958 British birth cohort) with data from birth to age 33 years, collected at birth and ages 7, 11, 16, 23 and 33 years were used in these analyses. The outcome measure was onset age of anxiety or depression between ages 24 and 33 years, that resulted in consultation with a GP or a specialist. This was used in Cox proportional hazards models where two measures of unemployment were modelled as time varying covariates. Pre-existing tendency to depression was measured by the Malaise Inventory prior to the experience of unemployment at age 23 years. Two measures of unemployment were investigated: any unemployment in the year prior to onset (recent unemployment) and all accumulated unemployment prior to onset (divided into four categories: 0, 1-12, 13-36 and 37+ months of unemployment). RESULTS After adjustment for potential confounding factors including pre-existing tendency to depression, the relative risk (RR) for developing symptoms resulting in consultation was 2.10 (95% CI: 1.21-3.63), when those who were unemployed in the year prior to onset were compared with those who were not. Accumulated unemployment was not statistically significantly related to onset of symptoms in all men after adjustment for the potential confounding factors: an RR of 1.63 (95% CI: 0.95-2.79) for men with 37+ months of accumulated unemployment when compared with none. However, exclusion of men with a pre-existing tendency to depression indicated by the Malaise Inventory score, increased the RR to 2.30 (95% CI: 1.44-3.65) for recent unemployment and 2.04 (95% CI: 1.17-3.54) for 37+ months of accumulated unemployment when compared with none. CONCLUSIONS Unemployment is a risk factor for psychological symptoms of depression requiring medical attention, even in those men without previous psychological vulnerability.
The intelligence of American children is still rising

Summary Children's intelligence increased in the United States by approxi-mately 3 IQ points per decade over the period 1932–78. New evidence shows that these increases have been sustained during the last 20 years. Two recent studies indicate that the rates of increase for 1972–89 and 1978–89 were 3·3 and 3·5 IQ points per decade respectively.
Inverse topological systems and compactness in abstract model theory

Abstract Given an abstract logic , generated by a set of quantifiers Qi, one can construct for each type τ a topological space Sτ, exactly as one constructs the Stone space for τ in first-order logic. Letting T be an arbitrary directed set of types, the set is an inverse topological system whose bonding mappings are naturally determined by the reduct operation on structures. We relate the compactness of to the topological properties of ST. For example, if I is countable then is compact iff for every τ each clopen subset of Sτ is of finite type and Sτ, is homeomorphic to limST, where T is the set of finite subtypes of τ. We finally apply our results to concrete logics.
Rapid response predicts 12-month post-treatment outcomes in binge-eating disorder: theoretical and clinical implications

Background We examined rapid response in obese patients with binge-eating disorder (BED) in a clinical trial testing cognitive behavioral therapy (CBT) and behavioral weight loss (BWL). Method Altogether, 90 participants were randomly assigned to CBT or BWL. Assessments were performed at baseline, throughout and post-treatment and at 6- and 12-month follow-ups. Rapid response, defined as ⩾70% reduction in binge eating by week four, was determined by receiver operating characteristic curves and used to predict outcomes. Results Rapid response characterized 57% of participants (67% of CBT, 47% of BWL) and was unrelated to most baseline variables. Rapid response predicted greater improvements across outcomes but had different prognostic significance and distinct time courses for CBT versus BWL. Patients receiving CBT did comparably well regardless of rapid response in terms of reduced binge eating and eating disorder psychopathology but did not achieve weight loss. Among patients receiving BWL, those without rapid response failed to improve further. However, those with rapid response were significantly more likely to achieve binge-eating remission (62% v. 13%) and greater reductions in binge-eating frequency, eating disorder psychopathology and weight loss. Conclusions Rapid response to treatment in BED has prognostic significance through 12-month follow-up, provides evidence for treatment specificity and has clinical implications for stepped-care treatment models for BED. Rapid responders who receive BWL benefit in terms of both binge eating and short-term weight loss. Collectively, these findings suggest that BWL might be a candidate for initial intervention in stepped-care models with an evaluation of progress after 1 month to identify non-rapid responders who could be advised to consider a switch to a specialized treatment.
Antioxidant properties, chemical composition and nutritional value of Terfezia boudieri (Chatin) from Turkey

Our objectives were to investigate the chemical composition, nutritive value and antioxidant activity potentials of Terfezia boudieri Chatin collected from different areas from Southeast of Turkey. The amounts of energy, protein, fat, carbohydrate, crude fibre, moisture and ash were 34.00–65.00 (kcal/100 g), 1.40–2.73, 0.86–1.71, 4.84–11.60, 80.86–90.33 (g/100 g, f.w.) and 1.02–1.98 g/100 g dry mass, respectively. Fatty acids and amino acids analyses revealed that linoleic acid and glutamic acid were, respectively the most abundant. Among the essential amino acids leucine was the highest amount and this was followed by threonine. Magnesium was the most abundant element with a concentration value of 182.30 mg/100 g dry mass. T. boudieri exhibited excellent antioxidant activity when compared with standard compounds. In total antioxidant and chelating effect on ferrous ions activity T. boudieri showed the highest activity against the standards. Additionally, at all studied tests antioxidant activity of the mushroom increased with increasing concentration. The total phenolic content of T. boudieri was found as 8.45 mg/g.
Adaptive Microphone Array System with Two-Stage Adaptation Mode Controller

In this paper, an adaptive microphone array system with a two-stage adaptation mode controller (AMC) is proposed for high-quality speech acquisition in real environments. The proposed system includes an adaptive array algorithm, a time-delay estimator and a newly proposed AMC. To ensure proper adaptation of the adaptive array algorithm, the proposed AMC uses not only temporal information, but also spatial information. The proposed AMC is constructed with two processing stages: an initialization stage and a running stage. In the initialization stage, a sound source localization technique is adopted, and a signal correlation characteristic is used in the running stage. For the adaptive array algorithm, a generalized sidelobe canceller with an adaptive blocking matrix is used. The proposed algorithm is implemented as a real-time man-machine interface module of a home-agent robot. Simulation results show 13 dB SINR improvement with the speaker sitting 2 m distance from the home-agent robot. The speech recognition rate is also enhanced by 32% when compared to the single channel acquisition system.
Isolation of Zymogen Granules from Rat Pancreas

This unit describes methods for preparing zymogen granules from rat pancreas. Zymogen granules are storage organelles in pancreatic acinar cells containing digestive enzymes that are released into the pancreatic duct. The protocols in this unit take advantage of the large size (up to 1 µm diameter) and high density (>1.20 g/cm3 on sucrose gradients) of the granules as compared to other cellular organelles. They use a combination of differential sedimentation and density gradient separation to accomplish the purification. Similar procedures can be used to isolate zymogen granules from mouse pancreas and canine pancreas. A protocol for preparing zymogen granules from dog pancreas is also included.
Software process improvement: best practices and lessons learned

1-How Do SPI Programs Produce Benefits. Common software problems and trends facing most segments of the software industry are reviewed. Three critical trends are reviewed that set the stage for understanding how SPI programs produce business benefits. These trends are the percentage of rework on projects in immature organizations, the cost of removing defects as a function of the phase in which they are discovered, and the comparative effects of different technologies and practices on productivity, quality, and time to market. Participants will be shown an example of a cost of quality analysis from a successful SPI program. This model demonstrates the dramatic change in business results when rework costs are eliminated. In addition a second area of dramatic productivity gains experienced by mature organizations that has only recently been discovered in the data will be discussed.
Molecular Analyses of Novel Methanotrophic Communities in Forest Soil That Oxidize Atmospheric Methane

ABSTRACT Forest and other upland soils are important sinks for atmospheric CH4, consuming 20 to 60 Tg of CH4 per year. Consumption of atmospheric CH4 by soil is a microbiological process. However, little is known about the methanotrophic bacterial community in forest soils. We measured vertical profiles of atmospheric CH4 oxidation rates in a German forest soil and characterized the methanotrophic populations by PCR and denaturing gradient gel electrophoresis (DGGE) with primer sets targeting thepmoA gene, coding for the α subunit of the particulate methane monooxygenase, and the small-subunit rRNA gene (SSU rDNA) of all life. The forest soil was a sink for atmospheric CH4 in situ and in vitro at all times. In winter, atmospheric CH4was oxidized in a well-defined subsurface soil layer (6 to 14 cm deep), whereas in summer, the complete soil core was active (0 cm to 26 cm deep). The content of total extractable DNA was about 10-fold higher in summer than in winter. It decreased with soil depth (0 to 28 cm deep) from about 40 to 1 μg DNA per g (dry weight) of soil. The PCR product concentration of SSU rDNA of all life was constant both in winter and in summer. However, the PCR product concentration of pmoAchanged with depth and season. pmoA was detected only in soil layers with active CH4 oxidation, i.e., 6 to 16 cm deep in winter and throughout the soil core in summer. The same methanotrophic populations were present in winter and summer. Layers with high CH4 consumption rates also exhibited more bands of pmoA in DGGE, indicating that high CH4oxidation activity was positively correlated with the number of methanotrophic populations present. The pmoA sequences derived from excised DGGE bands were only distantly related to those of known methanotrophs, indicating the existence of unknown methanotrophs involved in atmospheric CH4 consumption.
Classification of Kangaroo Habitat Distribution Using Three GIS Models

Abstract In this paper, we compare three techniques for mapping wildlife habitat, termed BIOCLIM, CART and a new classification method based on nonparametric techniques. These techniques model dependent map layers of species distributions, where the areas to be mapped are large and the plot data is sparse. The techniques recognise pattern in the (independent) plot data, available to natural resource managers. In this case, the independent data set comprised 12 climate surfaces, that attempt to represent the range of temperature and precipitation important in determining the habitat of kangaroos across Australia. With this particular data set, the CART (decision tree) model was most accurate, but more time consuming to initialise. The relative performance of these models depends on the quality of the data set, and skill of the GIS analyst. Where possible, GIS analysts should implement all available methods, and compare output.
Development and characterization of microsatellite primers for Chamaecyparis obtusa (Cupressaceae)1

Premise of the study: Although several microsatellite markers of Chamaecyparis obtusa (Cupressaceae) have been reported in previous studies, we newly developed and evaluated polymorphic microsatellite markers of C. obtusa, an economically important species in Korea as a major forestation tree species, for further genetic studies. Methods and Results: Microsatellite-enrichment libraries were constructed according to the selective hybridization method. From this output, we obtained 10 polymorphic and five monomorphic microsatellite markers for C. obtusa. Five of these developed markers were successfully amplified for C. pisifera, a related species. Conclusions: These microsatellite markers can be valuable tools for further genetic studies of C. obtusa, and gathered genetic information may be useful for breeding program management.
Design, testing and optimization of a micropump for cryogenic spot cooling applications

The performance of two micropumps with different electrode designs in liquid N/sub 2/ was investigated in this study. One of the experimental challenges was developing a method for measuring the flow rate of the liquid N/sub 2/. By combining a numerical model of the non-isothermal flow of the liquid N/sub 2/ around the loop and the experimental measurements of the temperatures around the flow loop, the liquid N/sub 2/ flow rates could be determined accurately enough to compare the pumping performance of these micropumps. The first tested micropump had an electrode spacing of 20 /spl mu/m and an electrode pair spacing of 80 /spl mu/m, while the second pump had an electrode spacing of 50 /spl mu/m and electrode-pair spacing of 200 /spl mu/m. The results showed that both micropumps pumped sufficient liquid N/sub 2/ to cool a typical superconductive sensor or other low power device. For both pumps, the pumping capacities increased with increasing EHD voltage. The pump with the smaller electrode spacing generated a higher flow rate at a lower applied voltage. This pump generated flow rates as high as 10 mL/min at an applied voltage of 500 V.
IPDMA : Individual Patient / Participant Data Meta-Analysis

In a previous article in KT Update (Dijkers, 2014), the development of meta-analysis (MA) was sketched from (1) meta-analysis of individual study findings (e.g., means and standard deviations, correlations) reported in the literature, to (2) meta-analysis of individual subject data harvested from the published literature, to (3) merging of datasets from multiple studies that share subject population (but not the same individuals) and have similar variables, to (4) creation of common data elements (CDEs) to standardize the variables in related studies, to (5) trialists’ collaborations, which offer a mechanism to prospectively combine related studies into a single dataset. Of the above, 2, 3, 4, and 5 all require or offer opportunities for individual patient/participant (data) MA, or IPDMA. The major differences between IPDMA and a secondary analysis of a single-site or multi-site dataset is the need to acquire data or datasets, carefully develop a common coding scheme for all variables, and in the analysis address any issues resulting from the origin of the data (e.g., clustering). How much of this painstaking work needs to be done depends largely on the source of one’s data – differences between 2, 3, 4 or 5 above, essentially. IPDMA is most closely associated with 3 above: synthesizing information resulting from a re-analysis of the data produced by two or more studies. Alternative names that have been proposed for this process are “mega-analysis” and “integrative data analysis. ” These have not caught on; even though one might ask whether for a one-stage IPDMA (explained below), the term “meta” may be appropriate.
Transcriptional Regulation of Human CD5: Important Role of Ets Transcription Factors in CD5 Expression in T Cells1

CD5 is a surface receptor constitutively expressed on thymocytes and mature T and B-1a cells. CD5 expression is tightly regulated during T and B cell development and activation processes. In this study we shown that the constitutive expression of CD5 on human T cells correlates with the presence of a DNase I-hypersensitive (DH) site at the 5′-flanking region of CD5. Human CD5 is a TATA-less gene for which 5′-RACE analysis shows multiple transcriptional start sites, the most frequent of which locates within an initiator sequence. Luciferase reporter assays indicate that a 282-bp region upstream of the initiation ATG displays full promoter activity in human T cells. Two conserved Ets-binding sites (at positions −239 and −185) were identified as functionally relevant to CD5 expression by site-directed mutagenesis, EMSAs, and cotransfection experiments. A possible contribution of Sp1 (−115 and −95), c-Myb (−177), and AP-1-like (−151) motifs was also detected. Further DH site analyses revealed an inducible DH site 10 kb upstream of the human CD5 gene in both T and B CD5+ cells. Interestingly, a 140-bp sequence showing high homology with a murine inducible enhancer is found within that site. The data presented indicate that the 5′-flanking region of human CD5 is transcriptionally active in T cells, and that Ets transcription factors in conjunction with other regulatory elements are responsible for constitutive and tissue-specific CD5 expression.
Population pulsations and nondegenerate four-wave mixing in semiconductor lasers and amplifiers

The theory of nondegenerate four-wave mixing (NDFWM) in semiconductor lasers and amplifiers is presented with particular emphasis on the physical processes that lead to population pulsations. In the case of nearly degenerate four-wave mixing, modulation of the carrier density at the beat frequency Ω of the pump and probe waves creates a dynamic population grating whose effectiveness is governed by the spontaneous carrier lifetime τs. Such a grating affects both the gain and the refractive index of the probe wave. In particular, the probe gain exhibits features analogous to those observed in a detuned atomic system arising from the optical Stark effect. Both the gain grating and the index grating contribute to NDFWM, with the dominant contribution coming from the index grating. For detunings such that Ωτs ≫ 1, population pulsations correspond to modulation of the intraband population arising from spectral hole burning. Our results show that NDFWM is then limited by the phase-mismatch effects governed by the transit time τ rather than by the intraband population-relaxation time T1. Significant NDFWM is expected to occur for detunings up to about 300 GHz for typical transit-time values of 3 psec in semiconductor lasers.
Role of bacteriophage SPP1 tail spike protein gp21 on host cell receptor binding and trigger of phage DNA ejection

Bacteriophages recognize and bind specific receptors to infect suitable hosts. Bacteriophage SPP1 targets at least two receptors of the Bacillus subtilis cell envelope, the glucosylated wall teichoic acids and the membrane protein YueB. Here, we identify a key virion protein for YueB binding and for the trigger of DNA ejection. Extracts from B. subtilis‐infected cells applied to a YueB affinity matrix led to preferential capturing of gp21 from SPP1. To assess the significance of this interaction, we isolated mutant phages specifically affected in YueB binding. The mutants exhibited a very low inactivation rate and a strong defect to eject DNA when challenged with YueB. The phenotype correlated with presence of a single amino acid substitution in the gp21 carboxyl terminus, defining a region involved in YueB binding. Immunoelectron microscopy located the gp21 N‐terminus in the SPP1 cap and probably in the adjacent tail spike region whereas the gp21 C‐terminus was mapped further down in the spike structure. Antibodies against this part of gp21 interfered with the interaction of YueB with SPP1 and triggered DNA ejection. The gp21 C‐terminal region thus plays a central role in two early key events that commit the virus to deliver its genome into host cells.