Miracle-dz/UniFAR-FTUs huggingface dataset:
Exact minimum-width multi-row transistor placement for dual and non-dual CMOS cells

This paper proposes a minimum-width multi-row transistor placement method for CMOS cells in presence of non-dual P and N type transistors. This is the first exact multi-row transistor placement method which can be applied to CMOS cells with any types of structure. Non-dual CMOS cells occupy a major part of an industrial standard-cell library. To generate the exact minimum-width transistor placement of non-dual CMOS cells, we formulate the transistor placement problem into Boolean satisfiability (SAT) problem considering the P and N type transistors individually. Using the proposed method, the transistor placement problem of any types of CMOS cells can be solved exactly. Moreover, the proposed method uses more efficient gate connection style, and generates more area-efficient transistor placements than the conventional method. Experimental results show that the proposed method can generate the minimum width multi-row transistor placement of the cells with up to 26 transistors in reasonable time
Harnessing Local Immunity for an Effective Universal Swine Influenza Vaccine

Influenza A virus infections are a global health threat to humans and are endemic in pigs, contributing to decreased weight gain and suboptimal reproductive performance. Pigs are also a source of new viruses of mixed swine, avian, and human origin, potentially capable of initiating human pandemics. Current inactivated vaccines induce neutralising antibody against the immunising strain but rapid escape occurs through antigenic drift of the surface glycoproteins. However, it is known that prior infection provides a degree of cross-protective immunity mediated by cellular immune mechanisms directed at the more conserved internal viral proteins. Here we review new data that emphasises the importance of local immunity in cross-protection and the role of the recently defined tissue-resident memory T cells, as well as locally-produced, and sometimes cross-reactive, antibody. Optimal induction of local immunity may require aerosol delivery of live vaccines, but it remains unclear how long protective local immunity persists. Nevertheless, a universal vaccine might be extremely useful for disease prevention in the face of a pandemic. As a natural host for influenza A viruses, pigs are both a target for a universal vaccine and an excellent model for developing human influenza vaccines.
Distension of the Carotid Artery and Risk of Coronary Events: The Three-City Study

Objective—Arterial mechanical properties are of growing interest in the understanding of cardiovascular disease development. We aimed to determine the predictive value of carotid wall mechanics on coronary heart disease (CHD) in the Three-City study. Methods and Results—At baseline, 3337 participants aged ≥65 years underwent a carotid B-mode ultrasonography. During a median follow-up of 43.4 months, 128 CHD occurred. Increased carotid distension (relative stroke change in lumen diameter) was significantly associated with CHD risk. Comparison of subjects in tertile 3 versus those in tertile 1 (reference) showed a hazard ratio (HR) of 1.80 (95% CI, 1.17 to 2.75). Controlling for various confounders including age, heart rate, brachial (or carotid) pulse pressure, and common carotid intima-media thickness did not alter the association between carotid distension and CHD with a HR of 1.79 (95% CI, 1.12 to 2.86; tertile 3 versus tertile 1). Brachial and carotid pulse pressures were also independently associated with CHD. No association was found between CHD and carotid distensibility coefficient, cross-sectional compliance coefficient, Young’s elastic modulus, or &bgr; stiffness index. Conclusions—In the elderly, increased carotid distension was independently predictive of CHD. This simple and noninvasive parameter might be of particular interest for cardiovascular risk assessment.
Epstein–Barr virus‐specific T‐cell cytotoxicity is mediated through the perforin pathway in patients with lymphoproliferative disorders after allogeneic bone marrow transplantation

Summary. The in vivo cytotoxic mechanism of Epstein–Barr virus (EBV)‐specific cytotoxic lymphocytes was examined in a patient who suffered with EBV‐associated lymphoproliferative disease (LPD) after bone marrow transplantation (BMT). His peripheral CD8+ T‐cell count was significantly increased and > 70% of these cells were EBV‐specific by fluorescence‐activated cell sorter (FACS) analysis for interferon‐γ production. Intracellular perforin expression was markedly increased in CD8+ T cells by FACS analysis. The lymphocytes from this patient had cytotoxic activity against autologous EBV+ lymphoblastoid cell lines which were completely inhibited by concanamycin A, an inhibitor of perforin, and a anti‐human leucocyte antigen (HLA)‐class I monoclonal antibody. These results suggest that the cytotoxicity was mediated by the perforin, in an HLA‐class I‐restricted manner. We performed serial intracellular perforin analyses in another patient who also showed endogenous expansion of EBV‐specific CD8+ T cells that coincided with an increased EBV‐DNA load. Perforin expression in the CD8+ and CD4+ T cells paralleled the EBV‐specific CD8+ T cells and EBV‐DNA load, which also suggests that perforin mediates EBV‐specific cytolysis in vivo and is responsible for effective immunosurveillance against EBV reactivation after BMT. Evaluation of host immunity against EBV by determining perforin expression in lymphocytes and EBV‐specific lymphocytes along with quantification of EBV‐DNA may be useful for predicting the clinical course of patients with EBV‐associated LPD after BMT.
Effect of artificial diet and culture systems on sensory quality of fried fish flesh of Indian major carps.

Two 90 days experimental trials were conducted to evaluate the effect of artificial diet (35% protein) on sensory quality of yearlings of Indian major carps (Labeo rohita, Cirrhinus mrigala and Catla catla). Experimental diet was given at 3% of fish wet body weight per day. After 90 days trial organoleptic study of fried fish was carried out by twelve panelists using hedonic scale for each species from treated and control ponds. In monoculture, Catla catla showed significantly higher score for flavour in treated ponds than control. Labeo rohita was found to be significantly different for juiciness and tenderness scores in treated ponds versus control. However, sensory scores of fried Cirrhinus mrigala did not exhibit any difference between treatments. In polyculture system, Cirrhinus mrigala was found to be significantly different with respect to sensory colour, tenderness, oiliness and over all acceptability in control than treated ponds. However, there were no differences in organoleptic quality of fried fish for Catla catla and Labeo rohita in polyculture system. It can be concluded from the present investigation that artificial diet can improve the sensory quality in monoculture system while in polyculture it has affected the flesh quality especially of bottom feeding fish (Cirrhinus mrigala) for various sensory attributes.
The biology of small, introduced populations, with special reference to biological control

Populations are introduced into novel environments in different contexts, one being the biological control of pests. Despite intense efforts, less than half introduced biological control agents establish. Among the possible approaches to improve biological control, one is to better understand the processes that underpin introductions and contribute to ecological and evolutionary success. In this perspective, we first review the demographic and genetic processes at play in small populations, be they stochastic or deterministic. We discuss the theoretical outcomes of these different processes with respect to individual fitness, population growth rate, and establishment probability. Predicted outcomes differ subtly in some cases, but enough so that the evaluating results of introductions have the potential to reveal which processes play important roles in introduced populations. Second, we attempt to link the theory we have discussed with empirical data from biological control introductions. A main result is that there are few available data, but we nonetheless report on an increasing number of well‐designed, theory‐driven, experimental approaches. Combining demography and genetics from both theoretical and empirical perspectives highlights novel and exciting avenues for research on the biology of small, introduced populations, and great potential for improving both our understanding and practice of biological control.
Boar sperm quality in lines of pigs selected for either ovulation rate or uterine capacity.

Selection for 11 generations in swine for ovulation rate (OR) or uterine capacity (UC) resulted in significant changes in component traits of litter size. Our objective was to conserve the unique germplasm for the future and to characterize sperm quality as a correlated response to the selection criterion imposed compared to an unselected control line (CO). Boars representing genetic diversity available in all 3 lines were produced in 2 farrowing seasons. Season 1 was born in September 2005 and sampled for semen characteristics in October 2006. Season 2 was born in March 2006 and sampled for semen characteristics in February and March 2007. Each boar (n = 60) was collected twice. The sperm-rich fraction was obtained and volume and concentration of sperm cells were measured to estimate total sperm production. Each ejaculate was extended 1:3 vol/vol with Androhep Plus (Minitube, Verona, WI) and packed for shipping to the National Animal Germplasm Program laboratory for processing into frozen straws. Semen quality was measured by computer-assisted semen analysis at 3 semen processing points: fresh (FR), 24 h after extender added (E), and post-thaw (PT). A mixed model analysis of variance was applied to the data. Fixed effects of farrowing season, line and 2-way interactions were fitted. Random effect of boar (n = 60) within farrowing season and line was used to test line differences. Sperm concentration was not different (P = 0.18) among the lines (0.594 × 10(9), 0.691 × 10(9), and 0.676 × 10(9) cells/mL) for CO, OR, and UC lines, respectively. However, significance (P = 0.04) was detected for volume of the sperm-rich fraction, greatest for OR (86.4 mL), intermediate for UC (75.5 mL), and least for CO (70.2 mL). Line differences were thus detected (P = 0.02) for total sperm production per ejaculate, greatest for OR (54.9 × 10(9)), intermediate for UC (48.7 × 10(9)), and least for CO (40.5 × 10(9)). A larger percentage of progressively motile sperm and greater estimates of sperm velocity only at processing point E (P < 0.01) were detected in favor of CO. Estimates of motility, velocity, and other parameters of sperm movement measured on E processing points were positively correlated with the same estimates obtained PT but the magnitude was low to moderate (r range -0.03 to 0.23). Thus, selection for component traits of female reproduction had a favorable effect on total sperm production of boars.
Changes in Antihypertensive Prescribing During US Outpatient Visits for Uncomplicated Hypertension Between 1993 and 2004

Monitoring national patterns of antihypertensive drug therapy is essential to assessing adherence to treatment guidelines and the impact of major scientific publications on physician prescribing. We analyzed data from 2 US National Ambulatory Care Surveys to examine trends between 1993 and 2004 in the prescription of antihypertensive drug classes for uncomplicated hypertension and the association between thiazide and &bgr;-blocker prescribing and physician and patient characteristics. Diuretic prescriptions remained level through 2001 (39%; 95% CI: 34% to 44%) but increased to 53% (48% to 58%) in 2003, largely because of a 72% increase in thiazide prescriptions in the first quarter of 2003 (50%; 95% CI: 40% to 59%). However, these increases did not sustain in 2004. &bgr;-Blocker prescriptions increased modestly from 1993 (24%; 95% CI: 19% to 29%) to 2004 (33%; 95% CI: 28% to 39%). Prescription of calcium channel blockers and angiotensin-converting enzyme inhibitors declined significantly following the sixth Joint National Committee report, but both subsequently rebounded to prereport levels. Prescription of angiotensin II receptor blockers increased continuously from 1% in 1995 to 23% by 2004. Polytherapy prescriptions, particularly those involving ≥3 drug classes, became increasingly prevalent, accounting for 60% of antihypertensive drug visits by 2004. Prescriptions of thiazides and &bgr;-blockers were both more likely in 1998–2004 (versus 1993–1997). Blacks, women, and hospital outpatients were more likely to receive thiazides. Also, cardiologists were more likely to prescribe &bgr;-blockers. Evidence-based guidelines for antihypertensive drug therapy do impact physician prescribing, but the impact seems to be short lived. Future interventions are imperative for promoting long-term adherence to published guidelines.
Impact of the Centers for Disease Control's HIV Preexposure Prophylaxis Guidelines for Men Who Have Sex With Men in the United States.

BACKGROUND Preexposure prophylaxis (PrEP) is effective for preventing human immunodeficiency virus (HIV) infection among men who have sex with men (MSM) within trial settings. Population impact will depend on clinical indications for PrEP initiation, coverage levels, and drug adherence. No modeling studies have estimated the impact of clinical practice guidelines for PrEP issued by the Centers for Disease Control and Prevention (CDC). METHODS Mathematical models of HIV transmission among MSM were used to estimate the percentage of infections averted (PIA) and the number needed to treat (NNT) under behavioral indications of the CDC's PrEP guidelines. We modeled the contribution of these indications while varying treatment coverage and adherence. RESULTS At 40% coverage of indicated MSM over the next decade, application of CDC guidelines would avert 1162 infections per 100 000 person-years, 33.0% of expected infections. The predicted NNT for the guidelines would be 25. Increasing coverage and adherence jointly raise the PIA, but reductions to the NNT were associated with better adherence only. CONCLUSIONS Implementation of CDC PrEP guidelines would result in strong and sustained reductions in HIV incidence among MSM in the United States. The guidelines strike a good balance between epidemiological impact (PIA) and efficiency (NNT) at plausible scale-up levels. Adherence counseling could maximize public health investment in PrEP by decreasing the NNT.
A Large-Scale Initiative Inviting Patients to Share Personal Fitness Tracker Data with Their Providers: Initial Results

Background Personal fitness trackers (PFT) have substantial potential to improve healthcare. Objective To quantify and characterize early adopters who shared their PFT data with providers. Methods We used bivariate statistics and logistic regression to compare patients who shared any PFT data vs. patients who did not. Results A patient portal was used to invite 79,953 registered portal users to share their data. Of 66,105 users included in our analysis, 499 (0.8%) uploaded data during an initial 37-day study period. Bivariate and regression analysis showed that early adopters were more likely than non-adopters to be younger, male, white, health system employees, and to have higher BMIs. Neither comorbidities nor utilization predicted adoption. Conclusion Our results demonstrate that patients had little intrinsic desire to share PFT data with their providers, and suggest that patients most at risk for poor health outcomes are least likely to share PFT data. Marketing, incentives, and/or cultural change may be needed to induce such data-sharing.
Regulatory Domain Determinants That Control PKD1 Activity*

Background: PKD1 catalytic fragments accumulate during apoptosis; their cellular actions remain uncertain. Results: A PKD1 truncation mutant lacking the N-terminal portion of the regulatory domain does not phosphorylate protein substrates or activate PKD1-dependent cellular responses. Conclusion: The N-terminal portion of the regulatory domain (encompassing the C1 domain) is a positive regulator of PKD1 activity. Significance: Proteolysis limits the cellular actions of PKD1. The canonical pathway for protein kinase D1 (PKD1) activation by growth factor receptors involves diacylglycerol binding to the C1 domain and protein kinase C-dependent phosphorylation at the activation loop. PKD1 then autophosphorylates at Ser916, a modification frequently used as a surrogate marker of PKD1 activity. PKD1 also is cleaved by caspase-3 at a site in the C1-PH interdomain during apoptosis; the functional consequences of this cleavage event remain uncertain. This study shows that PKD1-Δ1–321 (an N-terminal deletion mutant lacking the C1 domain and flanking sequence that models the catalytic fragment that accumulates during apoptosis) and PKD1-CD (the isolated catalytic domain) display high basal Ser916 autocatalytic activity and robust activity toward CREBtide (a peptide substrate) but little to no activation loop autophosphorylation and no associated activity toward protein substrates, such as cAMP-response element binding protein and cardiac troponin I. In contrast, PKD1-ΔPH (a PH domain deletion mutant) is recovered as a constitutively active enzyme, with high basal autocatalytic activity and high basal activity toward peptide and protein substrates. These results indicate that individual regions in the regulatory domain act in a distinct manner to control PKD1 activity. Finally, cell-based studies show that PKD1-Δ1–321 does not substitute for WT-PKD1 as an in vivo activator of cAMP-response element binding protein and ERK phosphorylation. Proteolytic events that remove the C1 domain (but not the autoinhibitory PH domain) limit maximal PKD1 activity toward physiologically relevant protein substrates and lead to a defect in PKD1-dependent cellular responses.
Membrane Morphology Is Actively Transformed by Covalent Binding of the Protein Atg8 to PE-Lipids

Autophagy is a cellular degradation pathway involving the shape transformation of lipid bilayers. During the onset of autophagy, the water-soluble protein Atg8 binds covalently to phosphatdylethanolamines (PEs) in the membrane in an ubiquitin-like reaction coupled to ATP hydrolysis. We reconstituted the Atg8 conjugation system in giant and nm-sized vesicles with a minimal set of enzymes and observed that formation of Atg8-PE on giant vesicles can cause substantial tubulation of membranes even in the absence of Atg12-Atg5-Atg16. Our findings show that ubiquitin-like processes can actively change properties of lipid membranes and that membrane crowding by proteins can be dynamically regulated in cells. Furthermore we provide evidence for curvature sorting of Atg8-PE. Curvature generation and sorting are directly linked to organelle shapes and, thus, to biological function. Our results suggest that a positive feedback exists between the ubiquitin-like reaction and the membrane curvature, which is important for dynamic shape changes of cell membranes, such as those involved in the formation of autophagosomes.
Fluorescent in situ Detection of Encephalitozoon hellem Spores with a 6-Carboxyfluorescein-Labeled Ribosomal RNA-Targeted Oligonucleotide Probe

Abstract A fluorescent in situ hybridization assay has been developed for the detection of the human-pathogenic microsporidian, Encephalitozoon hellem in water samples using epifluorescence microscopy. The assay employs a 19-nucleotide species-specific 6-carboxyfluorescein-labeled oligonucleotide probe, HEL878F, designed to be complementary to the nucleic acid sequence 878–896, a highly variable segment of the 16S ribosomal RNA of E. hellem spores. The specificity of this probe for its ribosomal RNA target site was confirmed using RNA degradation, ribosomal RNA target site competition, and nucleotide base mismatch control probe assays. Furthermore, the specificity of the HEL878F oligonucleotide probe for E. hellem spores was established when it was evaluated on spores from all three species of the genus Encephalitozoon that had been seeded in reagent water and environmental water concentrates. The specificity of the HEL878F oligonucleotide probe was further corroborated when tested on algae, bacteria, and protozoa commonly found in environmental water. The study demonstrates the applicability of a fluorescent in situ hybridization assay using a species-specific fluorescent-labeled oligonucleotide probe for the detection of E. hellem spores in water samples.
Lactobacillus reuteri I5007 Modulates Intestinal Host Defense Peptide Expression in the Model of IPEC-J2 Cells and Neonatal Piglets

Modulation of the synthesis of endogenous host defense peptides (HDPs) by probiotics represents a novel antimicrobial approach for disease control and prevention, particularly against antibiotic-resistant infections in human and animals. However, the extent of HDP modulation by probiotics is species dependent and strain specific. In the present study, The porcine small intestinal epithelial cell line (IPEC-J2) cells and neonatal piglets were used as in-vitro and in-vivo models to test whether Lactobacillus reuteri I5007 could modulate intestinal HDP expression. Gene expressions of HDPs, toll-like receptors, and fatty acid receptors were determined, as well as colonic short chain fatty acid concentrations and microbiota. Exposure to 108 colony forming units (CFU)/mL of L. reuteri I5007 for 6 h significantly increased the expression of porcine β-Defensin2 (PBD2), pBD3, pBD114, pBD129, and protegrins (PG) 1-5 in IPEC-J2 cells. Similarly, L. reuteri I5007 administration significantly increased the expression of jejunal pBD2 as well as colonic pBD2, pBD3, pBD114, and pBD129 in neonatal piglets (p < 0.05). This was probably associated with the increase in colonic butyric acid concentration and up-regulating expression of Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) and G Protein-Coupled Receptor 41 (GPR41) (p < 0.05), but not with stimulation of Pattern-Recognition Receptors. Additionally, supplementation with L. reuteri I5007 in the piglets did not affect the colonic microbiota structure. Our findings suggested that L. reuteri I5007 could modulate intestinal HDP expression and improve the gut health of neonatal piglets, probably through the increase in colonic butyric acid concentration and the up-regulation of the downstream molecules of butyric acid, PPAR-γ and GPR41, but not through modifying gut microbiota structure.
HLA-B27-mediated protection in HIV and hepatitis C virus infection and pathogenesis in spondyloarthritis: two sides of the same coin?

Purpose of reviewHLA-B27 is associated with low viral load and long-term nonprogression in HIV infection as well as spontaneous clearance of hepatitis C virus (HCV) infection. This review summarizes mechanisms that have been suggested to be involved in this protective effect of HLA-B27, and highlights possible lessons for the role of HLA-B27 in spondyloarthritis. Recent findingsRecent studies linked protection by HLA-B27 in HIV and HCV infection to virological mechanisms such as a complicated pathways of viral escape from immunodominant HLA-B27-restricted virus-specific CD8+ T-cell epitopes. In addition, several immunological mechanisms have been proposed, including CD8+ T-cell polyfunctionality and functional avidity, thymic selection of CD8+ T-cell precursors, specific T-cell receptor repertoires and clonotypes, efficient antigen processing, and evasion from regulatory T-cell-mediated suppression. SummaryMultiple virological and immunological mechanisms have been suggested to contribute to HLA-B27-mediated protection in HIV and HCV infection. Some of these mechanisms may also be involved in HLA-B27-associated pathogenesis in spondyloarthritis.