Miracle-dz/UniFAR-FTUs huggingface dataset:
TOWARDS A UNIFYING MECHANISM FOR CYP17 MUTATIONS THAT CAUSE ISOLATED 17, 20-LYASE DEFICIENCY

Cytochrome P450c17 (CYP17) is a single hemoprotein that catalyzes both the 17α-hydroxylase and 17, 20-lyase reactions in all species thus far examined. Severe defects in CYP17 cause classical 17-hydroxylase deficiency, but other defects result in partial or selective deficiency states. One such variant is the syndrome of isolated 17, 20-lyase deficiency. Recent detailed studies of the biochemical properties of the mutant CYP17 enzymes from patients with isolated 17, 20-lyase deficiency demonstrate that alterations in the interaction of CYP17 with its redox partner proteins P450-oxidoreductase and cytochrome b5 form the biochemical basis for these selective enzyme defects. Site-directed mutagenesis studies have confirmed that neutralization of any of several positive charges on the redox partner binding surface results in selective disruption of 17, 20-lyase activity. In one case diagnosed as isolated 17, 20-lyase deficiency, the identified mutation did not map to the redox partner binding surface; however, we have shown that this mutation cannot be the cause of isolated 17, 20-lyase deficiency in this patient. These consistent results have prompted us to propose a paradigm in which neutralization of positive charges in the redox partner binding surface of CYP17 may be the predominant if not sole mechanism leading to isolated 17, 20-lyase deficiency.
COMBINATION THERAPY FOR AGE-RELATED MACULAR DEGENERATION

Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis in age-related macular degeneration (AMD) and is a validated therapeutic target. However, combination of anti–VEGF agents with complementary inhibition of other mediators of angiogenesis, such as platelet-derived growth factor and integrin &agr;5&bgr;1, may result in enhanced visual acuity. Other concomitant treatments, such as inhibitors of inflammation, may generate an even stronger barrier to the progression of AMD than that now observed in individuals receiving anti–VEGF therapies alone. Experimental studies are providing support for the general principles of combination treatment in AMD.
COMPARING THE RELATION BETWEEN STAR FORMATION AND GALAXY MASS IN DIFFERENT ENVIRONMENTS

Analyzing 24 μm MIPS/Spitzer data and the [O ii]3727 line of a sample of galaxies at 0.4 ⩽ z ⩽ 0.8 from the ESO Distant Cluster Survey, we investigate the ongoing star formation rate (SFR) and the specific star formation rate (SSFR) as a function of stellar mass in galaxy clusters and groups, and compare these with results from field studies. As for the field, we find a decline in SFR with time, indicating that star formation (SF) was more active in the past, and a decline in SSFR as galaxy stellar mass increases, showing that the current SF contributes more to the fractional growth of low-mass galaxies than high-mass galaxies. However, we find a lower median SFR (by a factor of ∼1.5) in cluster star-forming galaxies than in the field. The difference is highly significant when all Spitzer and emission-line galaxies are considered, regardless of color. It remains significant at z > 0.6 after removing red emission-line galaxies, to avoid possible active galactic nucleus contamination. While there is overlap between the cluster and field SFR–mass relations, we find a population of cluster galaxies (10%–25%) with reduced SFR for their mass. These are likely to be in transition from star forming to passive. Separately comparing clusters and groups at z > 0.6, only cluster trends are significantly different from the field, and the average cluster SFR at a given mass is ∼two times lower than the field. We conclude that the average SFR in star-forming galaxies varies with galaxy environment at a fixed galaxy mass.
Algoritmo simulated annealing aplicado en la identificación de errores de difícil detección en estimación de estado.

En este articulo se utiliza la tecnica de optimizacion Simulated Annealing con el fin de resolver el problema de estimacion de estado cuando este presenta errores de dificil deteccion. Es propuesto un algoritmo que combina la estimacion clasica con la teoria de puntos de apalancamiento y resuelto usando un metodo de optimizacion combinatorial denominado Simulated Annealing. Los resultados reportados presentan un mejor desempeno al ser comparados con los obtenidos por un estimador de estado tradicional y de igual calidad a los reportados con metodos de optimizacion combinatorial tales como Busqueda Tabu, Algoritmo Genetico de Chu- Beasley y Particulas Swarm.
Darwin and the divine experiment

In Denmark Darwin's theory of evolution was known early on and viewed with respect, but did not make immediate scientific converts. In the 1870s, when Darwinism was promoted by free thinkers, public debates began to flourish, but religious reactions were remarkably few and mostly undramatic. Since natural theology was not assumed by Lutheran theologians, the issue of design vs. chance was not prevalent. Discussions focused rather on scripture and the general challenge of naturalism, and if Darwin's name was included, the concern was human uniqueness and the social consequences of Darwinism. Religious responses thus targeted the materialism of semi-popular Darwinism more than the substance of Darwin's theory. Around 1900, however, many aspects of Darwin's theory were accepted. At that time, however, leading biologists found that Darwin's theory needed to be complemented by a Lamarckian emphasis on environment and adaptation. Theologians who were prepared to rethink Christianity in the light of evolution usually followed this trend. Darwin was domesticated, and brought home to the Danish public as part of the common cultural canon.
Transição do decreto-lei nº 319/91 para o 3/2008 no âmbito da educação especial - um estudo de caso

2 Agradecimentos 3 Indice de Anexos 5 Lista de Abreviaturas 6 Introducao 7 CAPITULO I Enquadramento Teorico 9 1. Necessidades Educativas e Inclusao 9 2. Dificuldades de Aprendizagem 10 3. As novas politicas de Educacao Especial em Portugal 12 4. Envolvimento Parental 17 Objetivos Especificos 23 CAPITULO II Metodologia 24 1. Introducao 24 2. Participantes 25 3. Instrumentos 25 4. Procedimentos de recolha de dados 5. Procedimento de analise de dados 27
Activin Signaling Pathways in Ovine Pituitary and LβT2 Gonadotrope Cells

Abstract In the pituitary, activin stimulates the synthesis and release of FSH. However, the activin receptor signaling pathways that mediate these effects are poorly known. We investigated these mechanisms in primary ovine pituitary cells (POP) and in the murine LβT2 gonadotrope cell line. POP cells and LβT2 cells express the different activin receptors (types IA, IB, IIA, and IIB) and the Smad proteins (Smad-2, -3, -4, and -7). In both POP and LβT2 cells, activin activated several signaling pathways: Smad-2, extracellular regulated kinase-1/2 (ERK1/2), p38, and phosphatidylinositol 3′-kinase (PI3K)/Akt. Phosphorylation of ERK1/2 and p38 were stimulated (3- to 6-fold) rapidly in 5 min, whereas activation of both Smad-2 and Akt (3- to 5-fold) occurred later, in 60 min. Activin also increased the association of activin receptor IIB with PI3K. Using specific inhibitors, we demonstrated that the activation of Smad-2 was partially blocked by the inhibition of PI3K but not by the inhibition of ERK1/2 or p38, suggesting a cross-talk between the Smad and PI3K/Akt pathways. In both POP and LβT2 cells, FSH expression and secretion in response to activin were not altered by the inhibition of PI3K/Akt, ERK1/2, or p38 pathways, whereas they were reduced by about 2-fold by expression of a dominant negative of Smad-2 or the natural inhibitory Smad-7 in LβT2 cells. These results indicate that activin activates several signaling pathways with different time courses in both POP and LβT2 cells, but only the Smad-2 pathway appears to be directly implicated in FSH expression and release in LβT2 cells.
Cigarette Smoking: A Modifier of Human Immunodeficiency Virus Type 1 Infection?

SummaryTwo hundred and two homosexual men enrolled in a prospective cohort study of AIDS risk were assessed for differences in the occurrence and progression of human immunodeficiency virus type 1 (HIV-1) infection with respect to cigarette smoking. Among subjects who were initially seronegative, smokers were more likely than nonsmokers to become HIV-1 seropositive (p = 0.03). After seroconversion, serum β2-microglobulin and CD4+ lymphocyte levels were elevated in cigarette smokers relative to nonsmokers (p = 0.02 for both comparisons), but both of these differences disappeared within 2 years. There was no detectable difference in the risk of AIDS or Pneumocystis carinii pneumonia with respect to smoking. Our data suggest that cigarette smoking may alter the immune response to HIV-1 infection, but it appears to have no marked effect on clinical outcome. They also suggest that cigarette smoking may be a surrogate marker for continued high-risk sexual behavior in homosexual men.
Localization of measles virus nucleic acid sequences in infected cells by in situ hybridization

Vero cells were infected with measles virus and hybridized in situ to a cloned DNA fragment containing specific sequences for measles nucleocapsid protein. The DNA was labelled with tritium by nick‐translation. The viral RNA were detected in the cytoplasm 21 hrs after infection. In many cells, the probe hybridized to nuclear structures, and in several mitotic cells, to chromosomes. After 36 hrs of infection, hybridization sites were found both in the center and in many nuclei of all the polykaryons. These results indicate that cellular distribution of viral RNA molecules varies in the course of infection. They further suggest that the nucleus plays a more active role than expected in measles virus transcription and replication.
A Multi-Model Approach to Failure Detection in Uncertain Sampled-Data Systems

In this paper we propose a methodology for active failure detection for sampled-data systems in the presence of model uncertainty. Active failure detection consists of injecting a signal (called an auxiliary signal) into the system. Using a multi-model framework to represent normal and failed behaviors of the system,we develop algorithms for the design of optimal auxiliary signals and online detection tests. The tests give guaranteed detection. Any conservatism inherited from the multi-model framework increases the size of the test signal and is not reflected in missed failures or false alarms as with several other approaches.
Two novel substrate integrated waveguide filters in LTCC technology

In this paper, two novel substrate integrated waveguide (SIW) elliptic filters based on low-temperature co-fired ceramic (LTCC) technology are proposed. Different coupling structures are used to implement electric and magnetic couplings and then a useful Schematic topology of filter based on LTCC is offered. A new input/output coupling structure is then proposed. Two Ku-band fourth-order cross-coupled band-pass filters with different input/output couplings using both positive and negative coupling mechanisms between cavities located in different lays are given and verified by experiments. A good agreement between the simulated and measured results is observed, which has also validated the proposed concept of design with the SIW technology.
New NO‐Donors with Antithrombotic and Vasodilating Activities, I: 3‐Arylalkyl‐N‐nitroso‐5‐sydnone Imines

Nine nitrosimino title compounds were prepared. They inhibit the aggregation of human platelets induced by collagen with an IC50 = 0.7 ‐ 33 μmol/L. The most active substance is the 3‐phenylethyl derivative 6b. The in vitro effect is mediated by an active metabolite which is formed by a photochemical reaction in the aggregometer. As the corresponding and so far unknown sydnone‐5‐cyanimines have no effect on platelets the metabolite is most certainly a NO‐species. The activity of the sydnone‐5‐nitrimine 5b is in the same order of magnitude (IC50 = 7.5 μmol/L) as in the nitrosimines of type 6. The most active compound 6b was investigated for antithrombotic properties in a thrombosis model, where the thrombus formation was induced by a laserbeam. 2 h after oral administration of 60 mg/kg of 6b to rats in venoles a 28% inhibition of thrombin formation was found. In arterioles this effect is more evident and a 48% inhibition is seen (the thrombus formation index is 2.6 and 3.9, respectively). These results suggest that the active metabolite is formed as well in vivo.
Metal Hypersensitivity and Total Knee Arthroplasty

Metal hypersensitivity in patients with a total knee arthroplasty (TKA) is a controversial topic. The diagnosis is difficult, given the lack of robust clinical validation of the utility of cutaneous and in vitro testing. Metal hypersensitivity after TKA is quite rare and should be considered after eliminating other causes of pain and swelling, such as low-grade infection, instability, component loosening or malrotation, referred pain, and chronic regional pain syndrome. Anecdotal observations suggest that two clinical presentations of metal hypersensitivity may occur after TKA: dermatitis or a persistent painful synovitis of the knee. Patients may or may not have a history of intolerance to metal jewelry. Laboratory studies, including erythrocyte sedimentation rate, C-reactive protein level, and knee joint aspiration, are usually negative. Cutaneous and in vitro testing have been reported to be positive, but the sensitivity and specificity of such testing has not been defined. Some reports suggest that, if metal hypersensitivity is suspected and nonsurgical measures have failed, then revision to components fabricated of titanium alloy or zirconium coating can be successful in relieving symptoms. Revision should be considered as a last resort, however, and patients should be informed that no evidence-based medicine is available to guide the management of these conditions, particularly for decisions regarding revision. Given the limitations of current testing methods, the widespread screening of patients for metal allergies before TKA is not warranted.
Drotrecogin alfa (activated) administration across clinically important subgroups of patients with severe sepsis

ObjectiveTo assess the effects of drotrecogin alfa (activated) therapy, a recombinant human activated protein C, across clinically relevant subpopulations in a randomized, phase 3, placebo-controlled study of patients with severe sepsis (recombinant human activated protein C worldwide evaluation in severe sepsis [PROWESS]). DesignUnivariate and multivariable analysis of prospectively defined subgroups from the PROWESS study. SettingA total of 164 medical centers in 11 countries. PatientsA total of 1,690 patients with severe sepsis. Measurements and Main ResultsWe report observed 28-day mortality rates for drotrecogin alfa (activated) and placebo patients for subgroups prospectively defined by demographic data, surgical status, type and site of infection, and clinical and biochemical measures of disease severity. We performed subgroup analyses to explore the consistency of the mortality benefit observed in the overall population and performed tests for both quantitative and qualitative interactions. To examine the magnitude of the treatment benefit with drotrecogin alfa (activated) across the underlying predicted risk of mortality spectrum, we used stepwise logistic regression on PROWESS placebo patients to generate a predicted risk of mortality model that simultaneously included many clinical and biochemical markers of mortality risk. Because drotrecogin alfa (activated) has anticoagulant properties, we also present analyses of bleeding and thrombotic events. Actual mortality rates were lower with drotrecogin alfa (activated) compared with placebo for nearly all prospectively defined subgroups. Both univariate and multivariable regression analyses showed a consistent relative risk reduction in 28-day mortality rates for drotrecogin alfa (activated). Larger absolute risk reductions were found with drotrecogin alfa (activated) in patients with a higher baseline predicted risk of mortality, and actual mortality rates were lower with drotrecogin alfa (activated) in all subgroups defined by disease severity measures where a ≥20% placebo mortality was observed. Although discriminatory power was limited by few observed events, the increased absolute risk of experiencing a serious bleeding event with treatment did not seem to vary according to the baseline predicted risk of mortality. ConclusionsThe administration of drotrecogin alfa (activated) to patients with severe sepsis was associated with a significant survival benefit that tended to increase with higher baseline likelihood of death. Current data suggest that the increased risk of bleeding does not vary according to likelihood of death.
Context-aware service composition and delivery in NGSONs over SDN

NGSON is an IEEE sponsored effort to standardize an open service ecosystem where different stakeholders may cooperate to satisfy users' ever changing requirements by composing and delivering services dynamically across different service providers and network operators' domains. A main distinguishing feature of NGSON is context awareness, that is, the capability of collecting, processing, and using context information to drive the interactions of the NGSON overlay nodes with service and network operators' infrastructures for guaranteeing an optimal user experience. Recent advances in network control and management technologies, such as SDN, NFV, and service-oriented networking paradigms, are expected to make the network effectively able to cope with application service requirements in a more flexible, timely, and agile manner. In this article we discuss how NGSON, which already incorporates several aspects of virtualization, could take advantage of network virtualization mechanisms and programmable traffic steering capabilities to enhance and effectively support context-aware service composition along with adaptive service delivery. We propose an architectural model for NGSON that leverages these novel network service control capabilities and illustrate through a use case how this model could effectively be put into operation.
Hair as a diagnostic tool in dysmorphology

Clinical diagnosis in dysmorphology is made by the recognition of a specific pattern of malformations and through an analytic search for discrete features.We present our personal experience regarding the usefulness of hair morphology as a tool for diagnosis in some metabolic and malformation syndromes. These cases represent only a few illustrative examples; an exhaustive review of the topic can be found elsewhere ( 1 ).
CHEMICAL COMPOSITION AND SENSORY EVALUATION OF TEA (CAMELLIA SINENSIS) COMMERCIALIZED IN PAKISTAN

The quality of black and green commercial tea samples was accessed by physicochemical analysis, mineral analysis and sensory evaluation. Significant variations in physicochemical and organoleptic parameters were observed. The moisture, protein, fat, crude fiber, water extracts and ash contents of the commercial tea samples were found to be in the range of 2.467. 47, 0.87-1.141, 0.94-2.15, 11.23-17.21, 32.34-53.61, and 3.29-5.86%, respectively while caffeine and catechin were found in the range of 2.34-4.33% and 0-7.44%, respectively. The highest percentage of moisture, protein, fat, and crude fiber contents were observed in green tea samples while highest percentage of ash and water extracts were observed in black tea samples. Calcium, magnesium, sodium, potassium and manganese were found to be in the range of 1.47-3.84 mg/l, 2.975. 66 mg/l, 0.39-1.83 mg/l, 3.01-4.00 mg/l. , 1.09-2.43 mg/l, respectively with maximum amounts found in green tea as compared to black tea.
Simian foamy virus infection in a blood donor

BACKGROUND: Infections with simian foamy virus (SFV) are widely prevalent in nonhuman primates. SFV infection was confirmed in a worker, occupationally exposed to nonhuman primates, who donated blood after the retrospectively documented date of infection. Human‐to‐human transmission of SFV through trans‐ fusion and its pathogenicity have not been studied.
Random projection design for scalable implicit smoothing of randomly observed stochastic processes

Standard methods for multi-variate time series analysis are hampered by sampling at random timestamps, long range dependencies, and the scale of the data. In this paper we present a novel estimator for cross-covariance of randomly observed time series which identifies the dynamics of an unobserved stochastic process. We analyze the statistical properties of our estimator without the assumption that observation timestamps are independent from the process of interest and show that our solution does not suffer from the corresponding issues affecting standard estimators for cross-covariance. We implement and evaluate our statistically sound and scalable approach in the distributed setting using Apache Spark and demonstrate its ability to identify interactions between processes on simulations and financial data with tens of millions of samples.
More frequent cloud‐free sky and less surface solar radiation in China from 1955 to 2000

Newly available data from extended weather stations and time period reveal that much of China has experienced significant decreases in cloud cover over the last half of the Twentieth century. This conclusion is supported by the analysis of the more reliably observed frequency of cloud‐free sky and overcast sky. The total cloud cover and low cloud cover have decreased 0.88% and 0.33% per decade, respectively, and cloud‐free days have increased 0.60% and overcast days decreased 0.78% per decade in China from 1954–2001. Meanwhile, both solar radiation and pan evaporation have decreased in China, with solar radiation decreasing 3.1 W/m2 and pan evaporation decreasing 39 mm per decade. Combining these results with findings of previous studies, we speculated that increased air pollution may have produced a fog‐like haze that reflected/absorbed radiation from the sun and resulted in less solar radiation reaching the surface, despite concurrent increasing trends in cloud‐free sky over China.
Revisión bibliográfica: Implementación del vector de park para la detección de fallas en máquinas rotativas

In this paper we present a literature review, techniques for fault detection in induction motor stator on three-phase using the spatial vector. We focus on these techniques because it allows to verify the extent of the failure and its class, with the advantage of using non-invasive techniques that allow us to check the status of an engine without the aggravation of having to take out it of service. We especially like that the progress in the last decade, using the technique of Park's vector and the geometric characteristics of the vector for detect the fault and size of the fault.