Miracle-dz/UniFAR-FTUs huggingface dataset:
Coherence and Coupling Functions Reveal Microvascular Impairment in Treated Hypertension

The complex interactions that give rise to heart rate variability (HRV) involve coupled physiological oscillators operating over a wide range of different frequencies and length-scales. Based on the premise that interactions are key to the functioning of complex systems, the time-dependent deterministic coupling parameters underlying cardiac, respiratory and vascular regulation have been investigated at both the central and microvascular levels. Hypertension was considered as an example of a globally altered state of the complex dynamics of the cardiovascular system. Its effects were established through analysis of simultaneous recordings of the electrocardiogram (ECG), respiratory effort, and microvascular blood flow [by laser Doppler flowmetry (LDF)]. The signals were analyzed by methods developed to capture time-dependent dynamics, including the wavelet transform, wavelet-based phase coherence, non-linear mode decomposition, and dynamical Bayesian inference, all of which can encompass the inherent frequency and coupling variability of living systems. Phases of oscillatory modes corresponding to the cardiac (around 1.0 Hz), respiratory (around 0.25 Hz), and vascular myogenic activities (around 0.1 Hz) were extracted and combined into two coupled networks describing the central and peripheral systems, respectively. The corresponding spectral powers and coupling functions were computed. The same measurements and analyses were performed for three groups of subjects: healthy young (Y group, 24.4 ± 3.4 y), healthy aged (A group, 71.1 ± 6.6 y), and aged treated hypertensive patients (ATH group, 70.3 ± 6.7 y). It was established that the degree of coherence between low-frequency oscillations near 0.1 Hz in blood flow and in HRV time series differs markedly between the groups, declining with age and nearly disappearing in treated hypertension. Comparing the two healthy groups it was found that the couplings to the cardiac rhythm from both respiration and vascular myogenic activity decrease significantly in aging. Comparing the data from A and ATH groups it was found that the coupling from the vascular myogenic activity is significantly weaker in treated hypertension subjects, implying that the mechanisms of microcirculation are not completely restored by current anti-hypertension medications.
Absence of 4-1 BB Enhanced CD 4 T Cell Responsiveness in the Michael Croft

had enhanced cell division compared with wild-type cells and displayed augmented clonal expansion during the primary response. This was not due to a developmental defect as 4-1BB-deficient CD4 cells could respond normally to Ag in vitro. These results demonstrate that the absence of 4-1BB can make CD4 T cells hyperresponsive to protein Ag in vivo, suggesting a new unappre-ciated negative regulatory role of 4-1BB when expressed on a T cell. T cells need costimulation for activation, proliferation, and survival, which prevents the induction of tolerance and induces T cell immunity (1). Costimulatory molecules can be divided into two main groups: the Ig superfamily and the TNFR superfamily (2, 3). The 4-1BB (CD137), a member of the TNFR superfamily, was originally found on activated T cells, but has since been identified on other immune cells, including NK cells, monocytes, neutrophils, and dendritic cells (DC) 3 (4 –9). The 4-1BB ligand (4-1BBL) is largely expressed on APCs, such as B cells, macrophages, and DC (8, 10). The interaction of 4-1BB with 4-1BBL was proposed to preferentially costimulate CD8 T cells (11), but a number of studies have demonstrated that it also might play a role in CD4 T cell responses. Engaging 4-1BB on naive CD4 T cells with 4-1BBL-transfected fibroblast cells promoted proliferation and cell cycle progression and suppressed apoptosis (12). The 4-1BBL augmented primary responses of CD4 T cells in the absence of CD28 signaling, and 4-1BB agonistic Ab enhanced CD4 T cell responses in vitro and in vivo (13, 14). Moreover, 4-1BB ligation by single-chain Fv fragments of anti-4-1BB Ab on tumor cells promoted enhanced tumor rejection in a CD4 T cell-dependent manner (15). These results have therefore indicated a positive costimulatory role for 4-1BB on CD4 T cells. In contrast, it has been reported that 4-1BB ligation has either no specific role or even a negative role in regulating CD4 T cells. For example, 4-1BBL Ϫ/Ϫ mice generated normal CD4 T cell responses after lymphocytic choriomen-ingitis virus and influenza infection, although CD8 T cell responses were down-regulated in those mice (16, 17). In addition, 4-1BB agonistic Ab treatment unexpectedly led to suppressed pathogenic CD4 T cell responses in several autoimmune disease models, including experimental autoimmune encephalomyelitis, lupus, and collagen-induced arthritis (18 –21). Thus, the role of 4-1BB, especially in vivo, appears to be quite complex and may vary depending upon the inflammatory conditions. The 4-1BB Ϫ/Ϫ mice develop normally, …
Complete and partial fault tolerance of feedforward neural nets

A method is proposed to estimate the fault tolerance (FT) of feedforward artificial neural nets (ANNs) and synthesize robust nets. The fault model abstracts a variety of failure modes for permanent stuck-at type faults. A procedure is developed to build FT ANNs by replicating the hidden units. It exploits the intrinsic weighted summation operation performed by the processing units to overcome faults. Metrics are devised to quantify the FT as a function of redundancy. A lower bound on the redundancy required to tolerate all possible single faults is analytically derived. Less than triple modular redundancy (TMR) cannot provide complete FT for all possible single faults. The actual redundancy needed to synthesize a completely FT net is specific to the problem at hand and is usually much higher than that dictated by the general lower bound. The conventional TMR scheme of triplication and majority voting is the best way to achieve complete FT in most ANNs. Although the redundancy needed for complete FT is substantial, the ANNs exhibit good partial FT to begin with and degrade gracefully. The first replication yields maximum enhancement in partial FT compared with later successive replications. For large nets, exhaustive testing of all possible single faults is prohibitive, so the strategy of randomly testing a small fraction of the total number of links is adopted. It yields partial FT estimates that are very close to those obtained by exhaustive testing. When the fraction of links tested is held fixed, the accuracy of the estimate generated by random testing is seen to improve as the net size grows.
The laboratory test utilization management toolbox

Efficiently managing laboratory test utilization requires both ensuring adequate utilization of needed tests in some patients and discouraging superfluous tests in other patients. After the difficult clinical decision is made to define the patients that do and do not need a test, a wealth of interventions are available to the clinician and laboratorian to help guide appropriate utilization. These interventions are collectively referred to here as the utilization management toolbox. Experience has shown that some tools in the toolbox are weak and other are strong, and that tools are most effective when many are used simultaneously. While the outcomes of utilization management studies are not always as concrete as may be desired, what data is available in the literature indicate that strong utilization management interventions are safe and effective measures to improve patient health and reduce waste in an era of increasing financial pressure.
Adenoviral Gizzard Erosion in Commercial Broiler Chickens

Pathologic and immunohistochemical changes caused by group I of the fowl adenovirus (FAV) serotype-1 99ZH strain, isolated from broiler chickens exhibiting gizzard erosion, were investigated in commercial broiler chickens. One hundred twenty-two chickens were inoculated with the strain by both oral and ocular routes at 1, 3, or 5 weeks of age and euthanatized for necropsy within 4–18 days of inoculation. Focal gizzard erosions were observed in the inoculated chickens of each age group. A histologically degenerative koilin layer, necrotic mucosa, intranuclear inclusion bodies in the glandular epithelial cells, inflammatory cell infiltrations in the lamina propria, submucosa, and a muscle layer were seen in the gizzards. Immunohistochemical staining showed evidence of FAV antigens in the intranuclear inclusion bodies. These findings were recognized regardless of their maternal antibody levels for FAV serotype-1. Gizzard lesions appeared later in the lower-dose-inoculated chickens than in the higher-dose–inoculated chickens. Numerous CD3-positive cells and IgY-positive plasma cells were seen in the gizzard lesions. In 5-week-old chickens the heterophil infiltrations in the lesions were milder than in younger chickens. Intranuclear inclusion bodies also were observed in the epithelial cells of the ileum or cecal tonsils of some chickens. Thus, this study shows that FAV-99ZH causes adenoviral gizzard erosion in broiler chickens without hepatic or pancreatic lesions and that cell infiltration is more severe than in dietary gizzard erosions.
Correlation between smoking history and molecular pathways in sporadic colorectal cancer: a meta-analysis.

BACKGROUND Epidemiological studies have shown that smoking increases the risk for colorectal cancer (CRC). Evidence of the guiding significance of smoking history for molecular classification and molecular targeted anti-tumor therapy is not well established. AIMS To provide indirectly evidence, we conducted a systematic meta-analysis of association between smoking history and different molecular classification. METHODS We searched in multiple databases up to January 2014, and identified 27 eligible studies. All studies were divided into seven groups based on different molecular alteration categories, which are MSI, CIMP, and three molecular pathway-associated gene alterations (APC, KRAS, P53, BRAF mutation, and APC methylation). Crude odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated to evaluate the association. RESULTS Smoking showed a significantly positive correlation with P53 mutation (exons 4 to 8), BRAF (codon 600) mutation, MSI positivity, and CIMP positivity, with ORs of 1.25 (95% CI: 1.07-1.45), 1.41 (95% CI: 1.18-1.68), 1.28 (95% CI: 1.12-1.47), and 1.23 (95% CI: 1.01-1.50), respectively. However, smoking was not positively correlated with APC (mutation cluster region) and KRAS (codons 12 and 13) mutation in sporadic CRC patients. CONCLUSIONS These findings suggested smoking history occurred with P53 mutation, BRAF mutation, MSI positivity, and CIMP positivity in sporadic CRCs; and could guide those specifically therapeutic designs when molecular classification with genetic test was infeasible. More associated studies should be conducted for strengthening and renewing the current result.
Implementation of National Fire Plan treatments near the wildland–urban interface in the western United States

Because of increasing concern about the effects of catastrophic wildland fires throughout the western United States, federal land managers have been engaged in efforts to restore historical fire behavior and mitigate wildfire risk. During the last 5 years (2004–2008), 44,000 fuels treatments were implemented across the western United States under the National Fire Plan (NFP). We assessed the extent to which these treatments were conducted in and near the wildland–urban interface (WUI), where they would have the greatest potential to reduce fire risk in neighboring homes and communities. Although federal policies stipulate that significant resources should be invested in the WUI, we found that only 3% of the area treated was within the WUI, and another 8% was in an additional 2.5-km buffer around the WUI, totaling 11%. Only 17% of this buffered WUI is under federal ownership, which significantly limits the ability of federal agencies to implement fire-risk reduction treatments near communities. Although treatments far from the WUI may have some fire mitigation benefits, our findings suggest that greater priority must be given to locating treatments in and near the WUI, rather than in more remote settings, to satisfy NFP goals of reducing fire risk to communities. However, this may require shifting management and policy emphasis from public to private lands.
Protection from right- and left-sided colorectal neoplasms after colonoscopy: population-based study.

BACKGROUND Colonoscopy is used for early detection and prevention of colorectal cancer, but evidence on the magnitude of overall protection and protection according to anatomical site through colonoscopy performed in the community setting is sparse. We assessed whether receiving a colonoscopy in the preceding 10-year period, compared with no colonoscopy, was associated with prevalence of advanced colorectal neoplasms (defined as cancers or advanced adenomas) at various anatomical sites. METHODS A statewide cross-sectional study was conducted among 3287 participants in screening colonoscopy between May 1, 2005, and December 31, 2007, from the state of Saarland in Germany who were aged 55 years or older. Prevalence of advanced colorectal neoplasms was ascertained by screening colonoscopy and histopathologic examination of any polyps excised. Previous colonoscopy history was obtained by standardized questionnaire, and its association with prevalence of advanced colorectal neoplasms was estimated, after adjustment for potential confounding factors by log-binomial regression. RESULTS Advanced colorectal neoplasms were detected in 308 (11.4%) of the 2701 participants with no previous colonoscopy compared with 36 (6.1%) of the 586 participants who had undergone colonoscopy within the preceding 10 years. After adjustment, overall and site-specific adjusted prevalence ratios for previous colonoscopy in the previous 10-year period were as follows: overall, 0.52 (95% confidence interval [CI] = 0.37 to 0.73); cecum and ascending colon, 0.99 (95% CI = 0.50 to 1.97); hepatic flexure and transverse colon, 1.21 (95% CI = 0.60 to 2.42); right-sided colon combined (cecum to transverse colon), 1.05 (95% CI = 0.63 to 1.76); splenic flexure and descending colon, 0.36 (95% CI = 0.16 to 0.82); sigmoid colon, 0.29 (95% CI = 0.16 to 0.53); rectum, 0.07 (95% CI = 0.02 to 0.40); left colon and rectum combined (splenic flexure to rectum, referred to as left-sided elsewhere), 0.33 (95% CI = 0.21 to 0.53). CONCLUSION Prevalence of left-sided advanced colorectal neoplasms, but not right-sided advanced neoplasms, was strongly reduced within a 10-year period after colonoscopy, even in the community setting.
Acquisition of the H19 methylation imprint occurs differentially on the parental alleles during spermatogenesis.

The imprinted mouse H19 gene is hypomethylated on the expressed maternal allele and hypermethylated on the silent paternal allele. A 2-kb region of differential methylation located from -2 to -4 kb relative to the H19 transcriptional start site has been proposed to act as the imprinting mark since hypermethylation in this region is inherited from sperm and retained on the paternal allele throughout development. Here, we describe a temporal analysis of the methylation patterns at the H19 locus during postnatal male germ cell development. The 2-kb region is methylated on the paternal allele throughout spermatogenesis, suggesting that methylation is acquired in this region prior to the resumption of mitosis in postnatal male mice. Likewise, more than half of the maternal alleles are hypermethylated prior to the resumption of mitosis. However, the remaining maternal alleles are not hypermethylated until the completion of meiosis I, indicating that de novo methylation in this region is a continuous process. Sequences proximal to the H19 promoter, which are methylated in spermatozoa and on the paternal allele in somatic cells, are differentially methylated in diploid, mitotic spermatogonia. The maternal allele becomes hypermethylated in this region during meiotic prophase. Thus, the parental H19 alleles acquire methylation differentially in the male germline.
Characterisation of the First Enzymes Committed to Lysine Biosynthesis in Arabidopsis thaliana

In plants, the lysine biosynthetic pathway is an attractive target for both the development of herbicides and increasing the nutritional value of crops given that lysine is a limiting amino acid in cereals. Dihydrodipicolinate synthase (DHDPS) and dihydrodipicolinate reductase (DHDPR) catalyse the first two committed steps of lysine biosynthesis. Here, we carry out for the first time a comprehensive characterisation of the structure and activity of both DHDPS and DHDPR from Arabidopsis thaliana. The A. thaliana DHDPS enzyme (At-DHDPS2) has similar activity to the bacterial form of the enzyme, but is more strongly allosterically inhibited by (S)-lysine. Structural studies of At-DHDPS2 show (S)-lysine bound at a cleft between two monomers, highlighting the allosteric site; however, unlike previous studies, binding is not accompanied by conformational changes, suggesting that binding may cause changes in protein dynamics rather than large conformation changes. DHDPR from A. thaliana (At-DHDPR2) has similar specificity for both NADH and NADPH during catalysis, and has tighter binding of substrate than has previously been reported. While all known bacterial DHDPR enzymes have a tetrameric structure, analytical ultracentrifugation, and scattering data unequivocally show that At-DHDPR2 exists as a dimer in solution. The exact arrangement of the dimeric protein is as yet unknown, but ab initio modelling of x-ray scattering data is consistent with an elongated structure in solution, which does not correspond to any of the possible dimeric pairings observed in the X-ray crystal structure of DHDPR from other organisms. This increased knowledge of the structure and function of plant lysine biosynthetic enzymes will aid future work aimed at improving primary production.
Decision-making about the use of hormone therapy among perimenopausal women.

OBJECTIVES Women reaching menopause must make a controversial decision about whether to use hormone therapy (HT). The theory of planned behaviour (TPB) was the organizing framework. The objectives were to determine if (1) influence of different TPB constructs varied with stage of menopause and HT use, (2) women with diabetes were influenced in significantly different ways from women without, (3) the overall perceived behavioural control (PBC) and self-efficacy (SE) have independent effects on intention, and (4) physician influence was mediated by subjective norm (SN). DESIGN Cross-sectional survey of women from a managed care organization. METHODS Multiple regression analysis was used to analyse 765 responses (230 from women with diabetes) and separately four main subgroups: (1) early menopause stage and never used HT, (2) late menopause stage and never used HT, (3) late menopause stage and previously used HT, and (4) late menopause stage currently using HT. RESULTS For the entire sample, the model explains 68% of variance in intention, where SE, physicians' influence, self-identification with menopause as a natural part of ageing, self-identification as someone who wants to delay menopause, HT status, menopause status, and diabetes were added to the TPB. For the entire sample, SE added 2% to the explained variance and the physician determinant added 7%. CONCLUSIONS An augmented TPB is useful for understanding women's HT use decisions. The theory explains more variance in intention before a behaviour is enacted than after, and decision structure changes over time. PBC and SE have independent effects on intention.
Exposure to Celebrity-Endorsed Small Cigar Promotions and Susceptibility to Use among Young Adult Cigarette Smokers

Small cigar smoking among young adult cigarette smokers may be attributed to their exposure to its advertisements and promotions. We examined the association between exposure to a celebrity music artist's endorsement of a specific brand of small cigars and young adult cigarette smokers' susceptibility to smoking that brand. Venue-based sampling procedures were used to select and survey a random sample of 121 young adult cigarette smokers, aged 18–35. Fourteen percent reported exposure to the artist's endorsement of the small cigar and 45.4% reported an intention to smoke the product in the future. The odds of small cigar smoking susceptibility increased threefold for those who reported exposure to the endorsement compared to those not exposed (OR = 3.64, 95% CI 1.06 to 12.54). Past 30-day small cigar use (OR = 3.30, 95% CI 1.24 to 8.74) and past 30-day cigar use (OR = 5.08, 95% CI 1.23, 21.08) were also associated with susceptibility to smoke a small cigar. An association between young adult cigarette smokers' exposure to the music artist's small cigar endorsement and their susceptibility to smoke small cigars was found. This association underscores the importance of monitoring small cigar promotions geared toward young people and their impact on small cigar product smoking.
To explore or to exploit: An entropy-driven approach for evolutionary algorithms

An evolutionary algorithm is an optimization process comprising two important aspects: exploration discovers potential offspring in new search regions; and exploitation utilizes promising solutions already identified. Intelligent balance between these two aspects may drive the search process towards better fitness results and/or faster convergence rates. Yet, how and when to control the balance perceptively have not yet been comprehensively addressed. This paper introduces an entropy-driven approach for evolutionary algorithms. Five kinds of entropy to express diversity are presented; and the balance between exploration and exploitation is adaptively controlled by one kind of entropy and mutation rate in a metaprogramming fashion. The experimental results of the benchmark functions show that the entropy-driven approach achieves explicit balance between exploration and exploitation and hence obtains even better fitness values and/or convergence rates.
The effects of washing on the ultrastructure and cytochemistry of ram spermatozoa.

some spermatozoa. The proportion of spermatozoa with broken plasma membranes over the acrosome increased with the number of washes. Washing once to achieve a dilution rate of 10-fold was sufficient to remove from spermatozoa all the substrate available for NADPH diaphorase and probably glucose-6-phosphate dehydrogenase, but not quite all the substrate for succinic dehydrogenase. A 10-fold dilution was also sufficient to remove glucose-6-phosphate dehydrogenase from a considerable proportion of spermatozoa, but even three washes to achieve a dilution rate of 1000-fold had little effect on succinic dehydrogenase and NADPH diaphorase activity in spermatozoa. The effects of washing could not be attributed to repeated centrifugation of spermatozoa during the process.