Lightweight Polymorphic Effects

Type-and-effect systems are a well-studied approach for reasoning about the computational behavior of programs. Nevertheless, there is only one example of an effect system that has been adopted in a wide-spread industrial language: Java’s checked exceptions. We believe that the main obstacle to using effect systems in day-to-day programming is their verbosity, especially when writing functions that are polymorphic in the effect of their argument. To overcome this issue, we propose a new syntactically lightweight technique for writing effect-polymorphic functions. We show its independence from a specific kind of side-effect by embedding it into a generic and extensible framework for checking effects of multiple domains. Finally, we verified the expressiveness and practicality of the system by implementing it for the Scala programming language

Renal histomorphology in dogs with pyometra and control dogs, and long term clinical outcome with respect to signs of kidney disease

<p>Abstract</p> <p>Background</p> <p>Age-related changes in renal histomorphology are described, while the presence of glomerulonephritis in dogs with pyometra is controversial in current literature.</p> <p>Methods</p> <p>Dogs with pyometra were examined retrospectively for evidence of secondary renal damage and persisting renal disease through two retrospective studies. In Study 1, light microscopic lesions of renal tissue were graded and compared in nineteen dogs with pyometra and thirteen age-matched control bitches. In Study 2, forty-one owners of dogs with pyometra were interviewed approximately 8 years after surgery for evidence ofclinical signs of renal failure in order to document causes of death/euthanasia.</p> <p>Results</p> <p>Interstitial inflammation and tubular atrophy were more pronounced in dogs with pyometra than in the control animals. Glomerular lesions classified as glomerular sclerosis were present in both groups. No unequivocal light microscopic features of glomerulonephritis were observed in bitches in any of the groups.</p> <p>Two bitches severely proteinuric at the time of surgery had developed end stage renal disease within 3 years. In five of the bitches polyuria persisted after surgery. Most bitches did not show signs of kidney disease at the time of death/euthanasia.</p> <p>Conclusion</p> <p>Tubulointerstitial inflammation was observed, but glomerular damage beyond age-related changes could not be demonstrated by light microscopy in the dogs with pyometra. However, severe proteinuria after surgery may predispose to development of renal failure.</p

Implementing Joins using Extensible Pattern Matching

Join patterns are an attractive declarative way to synchronize both threads and asynchronous distributed computations. We explore joins in the context of extensible pattern matching that recently appeared in languages such as F# and Scala. Our implementation supports join patterns with multiple synchronous events, and guards. Furthermore, we integrated joins into an existing actor-based concurrency framework. It enables join patterns to be used in the context of more advanced synchronization modes, such as future-type message sending and token-passing continuations

The relationship between educational level and bone mineral density in postmenopausal women

BACKGROUND: This study describes the influence of educational level on bone mineral density (BMD) and investigating the relationship between educational level and bone mineral density in postmenopausal women. METHODS: A total of 569 postmenopausal women, from 45 to 86 years of age (mean age of 60.43 ± 7.19 years) were included in this study. A standardized interview was used at the follow-up visit to obtain information on demographic, life-style, reproductive and menstrual histories such as age at menarche, age at menopause, number of pregnancies, number of abortions, duration of menopause, duration of fertility, and duration of lactation. Patients were separated into four groups according to the level of education, namely no education (Group 1 with 209 patients), elementary (Group 2 with 222 patients), high school (Group 3 with 79 patients), and university (Group 4 with 59 patients). RESULTS: The mean ages of groups were 59.75 ± 7.29, 61.42 ± 7.50, 60.23 ± 7.49, and 58.72 ± 7.46, respectively. Spine BMD was significant lower in Group 1 than that of other groups (p < 0.05). Trochanter and ward's triangle BMD were the highest in Group 4 and there was a significant difference between Group 1 and 4 (p < 0.05). The prevalence of osteoporosis showed an inverse relationship with level of education, ranging from 18.6% for the most educated to 34.4% for the no educated women (p < 0.05). Additionally, there was a significant correlation between educational level and spine BMD (r = 0.20, p < 0.01), trochanter BMD (r = 0.13, p < 0.01), and ward's BMD (r = 0.14, p < 0.01). CONCLUSIONS: The results of the study suggest that there is a significant correlation between educational level and BMD. Losses in BMD for women of lower educational level tend to be relatively high, and losses in spine and femur BMD showed a decrease with increasing educational level

Ligand-Induced Tyrosine Phosphorylation of Cysteinyl Leukotriene Receptor 1 Triggers Internalization and Signaling in Intestinal Epithelial Cells

Leukotriene D(4) (LTD(4)) belongs to the bioactive lipid group known as eicosanoids and has implications in pathological processes such as inflammation and cancer. Leukotriene D(4) exerts its effects mainly through two different G-protein-coupled receptors, CysLT(1) and CysLT(2). The high affinity LTD(4) receptor CysLT(1)R exhibits tumor-promoting properties by triggering cell proliferation, survival, and migration in intestinal epithelial cells. In addition, increased expression and nuclear localization of CysLT(1)R correlates with a poorer prognosis for patients with colon cancer

DNA Methylation Analysis Identifies Loci for Blood Pressure Regulation

Genome-wide association studies have identified hundreds of genetic variants associated with blood pressure (BP), but sequence variation accounts for a small fraction of the phenotypic variance. Epigenetic changes may alter the expression of genes involved in BP regulation and explain part of the missing heritability. We therefore conducted a two-stage meta-analysis of the cross-sectional associations of systolic and diastolic BP with blood-derived genome-wide DNA methylation measured on the Infinium HumanMethylation450 BeadChip in 17,010 individuals of European, African American, and Hispanic ancestry. Of 31 discovery-stage cytosine-phosphate-guanine (CpG) dinucleotides, 13 replicated after Bonferroni correction (discovery: N = 9,828, p &lt; 1.0 × 10−7; replication: N = 7,182, p &lt; 1.6 × 10−3). The replicated methylation sites are heritable (h2 &gt; 30%) and independent of known BP genetic variants, explaining an additional 1.4% and 2.0% of the interindividual variation in systolic and diastolic BP, respectively. Bidirectional Mendelian randomization among up to 4,513 individuals of European ancestry from 4 cohorts suggested that methylation at cg08035323 (TAF1B-YWHAQ) influences BP, while BP influences methylation at cg00533891 (ZMIZ1), cg00574958 (CPT1A), and cg02711608 (SLC1A5). Gene expression analyses further identified six genes (TSPAN2, SLC7A11, UNC93B1, CPT1A, PTMS, and LPCAT3) with evidence of triangular associations between methylation, gene expression, and BP. Additional integrative Mendelian randomization analyses of gene expression and DNA methylation suggested that the expression of TSPAN2 is a putative mediator of association between DNA methylation at cg23999170 and BP. These findings suggest that heritable DNA methylation plays a role in regulating BP independently of previously known genetic variants

Integrative omics identifies conserved and pathogen-specific responses of sepsis-causing bacteria

Even in the setting of optimal resuscitation in high-income countries severe sepsis and septic shock have a mortality of 20–40%, with antibiotic resistance dramatically increasing this mortality risk. To develop a reference dataset enabling the identification of common bacterial targets for therapeutic intervention, we applied a standardized genomic, transcriptomic, proteomic and metabolomic technological framework to multiple clinical isolates of four sepsis-causing pathogens: Escherichia coli, Klebsiella pneumoniae species complex, Staphylococcus aureus and Streptococcus pyogenes. Exposure to human serum generated a sepsis molecular signature containing global increases in fatty acid and lipid biosynthesis and metabolism, consistent with cell envelope remodelling and nutrient adaptation for osmoprotection. In addition, acquisition of cholesterol was identified across the bacterial species. This detailed reference dataset has been established as an open resource to support discovery and translational research

Crowding Alone Cannot Account for Cosolute Effect on Amyloid Aggregation

Amyloid fiber formation is a specific form of protein aggregation, often resulting from the misfolding of native proteins. Aimed at modeling the crowded environment of the cell, recent experiments showed a reduction in fibrillation halftimes for amyloid-forming peptides in the presence of cosolutes that are preferentially excluded from proteins and peptides. The effect of excluded cosolutes has previously been attributed to the large volume excluded by such inert cellular solutes, sometimes termed “macromolecular crowding”. Here, we studied a model peptide that can fold to a stable monomeric β-hairpin conformation, but under certain solution conditions aggregates in the form of amyloid fibrils. Using Circular Dichroism spectroscopy (CD), we found that, in the presence of polyols and polyethylene glycols acting as excluded cosolutes, the monomeric β-hairpin conformation was stabilized with respect to the unfolded state. Stabilization free energy was linear with cosolute concentration, and grew with molecular volume, as would also be predicted by crowding models. After initiating the aggregation process with a pH jump, fibrillation in the presence and absence of cosolutes was followed by ThT fluorescence, transmission electron microscopy, and CD spectroscopy. Polyols (glycerol and sorbitol) increased the lag time for fibril formation and elevated the amount of aggregated peptide at equilibrium, in a cosolute size and concentration dependent manner. However, fibrillation rates remained almost unaffected by a wide range of molecular weights of soluble polyethylene glycols. Our results highlight the importance of other forces beyond the excluded volume interactions responsible for crowding that may contribute to the cosolute effects acting on amyloid formation

Efeito do genótipo e da idade de ovinos na reatividade medida em pista de venda

Objetivou-se avaliar o comportamento de ovinos e relacionar aspectos comportamentais com a raça e idade dos animais. Foram observados 5.971 animais divididos em 181 lotes quanto às raças – Corriedale (n = 2.731), Ideal (n = 1.574), Merino (n = 168), Texel (n = 717), Suffolk (n = 247) e 6 mestiços (n = 534) – e quanto à idade – cordeiras (1,5 ano, n = 3.021), ovelhas (acima de 1,5 ano, n = 2457) e cordeiras dente-de-leite (média de 6 meses de idade, n = 493). O comportamento médio dos lotes foi avaliado pela atribuição de escores de movimentação e resistência à condução na entrada, permanência e saída da pista de comercialização. Os animais das raças mais especializadas para produção de carne (Suffolk e Texel) e os animais jovens foram os mais agitados e apresentaram maior resistência à condução pelo homem em comparação àqueles das raças produtoras de lã e aos mais velhos. Os escores comportamentais foram positivamente relacionados entre si, o que permite a escolha de qualquer um deles para medir o comportamento dos ovinos. O comportamento de ovinos em pista de venda é influenciado pela idade e raça.The objective of this work was to evaluate behavior of sheep and to relate behavioral aspects with breed and age of animals. It was observed 5,971 animals distributed in 181 plots regarded to: breed - Corriedale (n=2,731), Ideal (n=1,574), Merino (n=168), Texel (n=717), Suffolk (n=247) and six crossbreds (n=534); age - yearlings (1.5 year, n=3,021), ewes (above 1.5 year, n =2,457) and lambs (average 6 months of age, n=493). Average behavior of plots was evaluated by attributing scores of movement and resistance to conduction at entrance, permanence and exit from the market auction. Animals from more specialized breeds for meat production (Sulfock and Texel) and young animals were the most agitated and they showed more resistance to human conduction compared to those wool producer breeds and to the older ones. Behavior scores positively correlated among each other, allowing to choose any of them to measure sheep behavior. Sheep on market auction behavior is influenced by age and breed