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Alterations in coagulation factor X (FX) activation, mediated by the extrinsic VIIa/tissue factor (FVIIa/TF) or the intrinsic factor IXa/factor VIIIa (FIXa/FVIIIa) complexes, can result in hemorrhagic/prothrombotic tendencies. However, the molecular determinants involved in substrate recognition by these enzymes are poorly defined. Here, we investigated the role of arginine 386 (chymotrypsin numbering c202), a surface-exposed residue on the FX catalytic domain. The naturally occurring FX386Cys mutant and FX386Ala variant were characterized. Despite the unpaired cysteine, recombinant (r)FX386Cys was efficiently secreted (88.6 ± 21.3% of rFXwt) and possessed normal clearance in mice. rFX386Cys was also normally activated by FVIIa/TF and displayed intact amidolytic activity. In contrast, rFX386Cys activation by the FIXa/FVIIIa complex was 4.5-fold reduced, which was driven by a decrease in the k cat (1.6 ∗ 10 − 4 s − 1 vs 5.8 ∗ 10 − 4 s − 1 , rFXwt). The virtually unaltered K m (70.6 nM vs 55.6 nM, rFXwt) suggested no major alterations in the FX substrate exosite. Functional assays in plasma supplemented with rFX386Cys indicated a remarkable reduction in the thrombin generation rate and thus in coagulation efficiency. Consistently, the rFX386Ala variant displayed similar biochemical features suggesting that global changes at position 386 impact the intrinsic pathway activation. These data indicate that the FXArg386 is involved in FIXa/FVIIIa-mediated FX activation and help in elucidating the bleeding tendency associated with the FX386Cys in a rare FX deficiency case. Taking advantage of the unpaired cysteine, the rFX386Cys mutant may be efficiently targeted by thiol-specific ligands and represent a valuable tool to study FX structure–function relationships both in vitro and in vivo . [ABSTRACT FROM AUTHOR]

Broadcasting is an efficient and scalable way of transmitting data over wireless channels to an unlimited number of clients. In this paper the problem of allocating data to multiple channels is studied, assuming flat data scheduling per channel and the presence of unrecoverable channel transmission errors. The objective is that of minimizing the average expected delay experienced by the clients. Two different channel error models are considered: the Bernoulli model and the simplified Gilbert–Elliot one. In the former model, each packet transmission has the same probability to fail and each transmission error is independent from the others. In the latter one, bursts of erroneous or error-free packet transmissions due to wireless fading channels are modeled. Particular cases are detected where optimal solutions can be found in polynomial time. For general cases, simulations show that good sub-optimal solutions can be found on benchmarks whose item popularities follow Zipf distributions. [ABSTRACT FROM AUTHOR]

Broadcast is an efficient and scalable way of transmitting data to an unlimited number of clients that are listening to a channel. Cyclically broadcasting data over the channel is a basic scheduling technique, which is known as flat scheduling. When multiple channels are available, a data allocation technique is needed to assign data to channels. Partitioning data among channels in an unbalanced way, depending on data popularities, is an allocation technique known as skewed allocation. In this paper, the problem of data broadcasting over multiple channels is considered, assuming skewed data allocation to channels and flat data scheduling per channel, with the objective of minimizing the average waiting time of the clients. First, several algorithms, based on dynamic programming, are presented which provide optimal solutions for N data items and K channels. Specifically, for data items with uniform lengths, an 0(NK log N) time algorithm is proposed, which improves over the previously known 0(N2K) time algorithm. When K ≤ 4, a simpler 0(NlogN) time algorithm is exhibited which requires only 0(N) time if the data items are sorted. Moreover, for data items with nonuniform lengths, it is shown that the problem is NP-hard when K = 2 and strong NP-hard for arbitrary K. In the former case, a pseudopolynomial algorithm is discussed whose time is O(NZ), where Z is the sum of the data lengths. In the latter case, an algorithm is devised with time exponential in the maximum data length, which can optimally solve, in reasonable time, only small instances. For larger instances, a new heuristic is devised which is experimentally tested on some benchmarks whose popularities are characterized by Zipf distributions. Such experimental tests reveal that the new heuristic proposed here always outperforms the best previously known heuristic in terms of solution quality. [ABSTRACT FROM AUTHOR]

The classification problem transforms a set of N numbers in such a way that none of the first N/2 numbers exceeds any of the last N/2 numbers. A comparator network that solves the classification problem on a set of r numbers is commonly called an r-classifier. This paper shows how the well-known Leighton's Columnsort algorithm can be modified to solve the classification problem of N = rs numbers, with 1 ≤ s ≤r, using an r-classifier instead of an r-sorting network. Overall, the r-classifier is used O(s) times, namely, the same number of times that Columnsort applies an r-sorter. A hardware implementation is proposed that runs in optimal O(s + log r) time and uses an O(r log r(s + log r)) work. The implementation shows that, when N = r log r, there is a classifier network solving the classification problem on N numbers in the same O(log r) time and using the same O(r log r) comparators as an r-classifier, thus saving a log r factor in the number of comparators over an (r log r)-classifier. [ABSTRACT FROM AUTHOR]

Background: High plasma levels of coagulation factor VII have been suggested to be predictors of death due to coronary artery disease. Since polymorphisms in the factor VII gene contribute to variations in factor VII levels, such polymorphisms may be associated with the risk of myocardial infarction, which is precipitated by thrombosis.Methods: We studied a total of 444 patients, 311 of whom had severe, angiographically documented coronary atherosclerosis. Of these 311 patients, 175 had documentation of a previous myocardial infarction. As a control group, 133 patients with normal coronary arteriograms were also included. We measured the levels of activated factor VII and assessed three polymorphisms in the factor VII gene, one involving the promoter (A1 and A2 alleles), one involving the catalytic region (R353Q), and one involving intron 7.Results: Each of the polymorphisms influenced factor VII levels. Patients with the A2A2 and QQ genotypes had the lowest levels of activated factor VII (66 percent and 72 percent lower, respectively, than the levels in patients with the wild-type genotypes). The frequencies of the various genotypes in the patients free of coronary artery disease were similar to those in the entire population of patients with coronary artery disease. In the latter group, there were significantly more heterozygotes and homozygotes for the A2 and Q alleles among those who had not had a myocardial infarction than among those who had had an infarction (P=0.008 for the presence of the promoter polymorphism and P=0.01 for the presence of the R353Q polymorphism by chi-square analysis). The adjusted odds ratio for myocardial infarction among the patients with the A1A2 or RQ genotype was 0.47 (95 percent confidence interval, 0.27 to 0.81).Conclusions: Our findings suggest that certain factor VII genotypes have a role in protection against myocardial infarction. This may explain why some patients do not have myocardial infarction despite the presence of severe coronary atherosclerosis. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the effects of antimicrobial photodynamic therapy (aPDT) consisting of toluidine blue (TBO) and light-emitting diode (LED) on dermatophytosis caused by Trichophyton rubrum. A murine model was assessed based on histopathology of the skin, fungal burden in potato agar, and myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) activity, intraperitoneal macrophages, intracellular formation of hyphae and oxidative burst (ROS), and phagocytosis assay.

A letter to the editor regarding inhibitors to factor VII in congenital factor VII deficiency is presented.

Introduction Breast cancer is a public health problem in Brazil. This is due to the difficulty of primary prevention (eliminating risk factors or to diagnose and treat precursor lesions), with a consequent increase in the incidence and mortality from this cancer. The current challenge arises from the lack of access to a few specialized centers, which in turn are not always qualified for diagnosis and prompt treatment. Objective To develop a strategic plan aimed at two management priorities: resolubility diagnostic and fast treatment of women with clinical or secondary changes to mammographic screening. Methodology The Oswaldo Cruz Alemão Hospital (OCAH) in partnership with the Ministry of Health of Brazil has developed and deployed in the region of the Mooca - City of St. Paul the Integrated Program for Breast Cancer Control (IPBCC), which begins in the primary prevention (health education and removal of factors risk), continues with the mammographic detection and early diagnosis, modern instrumental in a Center for Diagnostic Detection and Tracking (CDDT), and culminates in the surgical and radiotherapy, ad juvant chemotherapy and hormone therapy or not, according to a standardized protocol. The care is coordinated in single query by mastologists trained in resolving service, with the participation of radiologists, oncologists, social workers, psychologists, nutritionists and health educators. Results From January 2010 to December 2011 were met 12266 women, mean age 58 years (range, 22-89) of which 100 were diagnosed with breast cancer and the proportion of carcinomas was of 8 per 1000. The detection rate mammography, ultrasound, and by both methods were: 0.30, 0.30 and 0.25, respectively. Forty-one percent of cancers corresponded to stages Tis N0M0 (3%) and T1N0M0 (38%) predominantly in women aged less than 50 years (38% of the sample). The average time between diagnosis and recorded start of surger y or chemotherapy was 42 days (range 19-68). As for quality of care, satisfaction was 99% (n = 12143). Conclusions The experience in resolving service provided a significant increase in the number of initial cases showing detection rates per image consistent with the age distribution of population. It is expected that the tracking time and quality of service, allow the prevalent cancers cease to be diagnosed, privileging the incidents. The median time to diagnosis and early treatment of patients with cancer was significantly lower the average of 120 days recorded in some public reference services. [ABSTRACT FROM AUTHOR]

Abstract: Background: The present study examines the hand movements of children with cerebral palsy during functional tests and compares the childrens'' performance with and without the aid of an orthosis that provides wrist extension and thumb abduction. Methods: The range of motion of the trapeziometacarpal joint was assessed for 32 participants via a reflexive markers image system. Observed motions included flexion–extension and abduction–adduction motions performed in the course of four tests for manual ability; the rest position, lateral and tripod pinches and cylindrical grasp. Muscle strength and manual ability were evaluated using dynamometry and the Jebsen–Taylor test. Findings: The range of motion tests for the rest position, lateral and tripod pinches and cylindrical grasp demonstrated improvements from 17% to 42% (P <0.001) for flexion/extension and from 36% to 54% for abduction/adduction (P <0.001) with the use of the orthosis. Dynamometry measurements showed that the improvement in muscle strength obtained through use of the orthosis was 50% (P <0.001). Improvements in the time required to perform the movements as determined using the Jebsen–Taylor test varied from 13% to 24% (P <0.01) for the four considered tests of manual ability. Interpretation: The orthosis improved the range of motion of the trapeziometacarpal joint, muscle strength and manual ability. The combination of the three techniques may provide the basis for a quantitative assessment of hand dysfunction/improvement in cerebral palsy that will ultimately guide health professionals in their clinical interventions. [Copyright &y& Elsevier]

Determines the strategies for mapping in parallel memory systems. Complexity of the memory addressing scheme; Occurrence of memory conflicts; Structures of data-parallelism in memory accesses.

This paper describes a model of integrated reproductive health care services for women at the primary health care level, put into practice at the Perola Byington Hospital, Sao Paulo, Brazil, from 1991 to 1998. Some 2,000 women from poor social strata, whose health condition was poor, were being seen every day in the last two years of the programme, including new consultations and women with a previous attendance returning. Women were attended first by nurse-assistants, who had been trained to screen for the most frequent gynaecological problems, and then a physician. Because doctors spent less time with each patient, four times as many women could be seen. Programmes were set up for the diagnosis and treatment of gynaecological cancers, STDs, HIV/AIDS, hypertension and other degenerative disorders such as diabetes. Screening and treatment programmes for cervical and breast cancer achieved significant improvements in the stage at which a diagnosis was made, allowing more lives to be saved. This model also succeeded in decreasing the costs for these health services per woman seen. [ABSTRACT FROM AUTHOR]