Miracle-dz/UniFAR-FTUs huggingface dataset:
A practical, low-overhead, one-cycle correction design method for variation-tolerant digital circuits

: This paper presents a practical, low-overhead, one-cycle correction better-than-worst-case design method for ultra-low voltage digital circuits. Excessive design margin for PVT variation brought by traditional worst-case design method is eliminated. Proposed method is completely compatible with EDA tools. Considerable design e ﬀ orts are relaxed compared with other variation-tolerant techniques. We have implemented our proposed technique on a 16 bits × 16 bits pipelined multiplier in SIMC 55 nm CMOS process. The experimental results show that our proposed technique can get about 59% energy e ﬃ ciency improvements compared with operating in worst-case timing margin.
Thermodynamic limitation for Ca2+ handling contributes to decreased contractile reserve in rat hearts.

The free energy release from ATP hydrolysis (‖ΔG∼p‖) is decreased by inhibiting the creatine kinase (CK) reaction, which may limit the thermodynamic driving force for the sarcoplasmic reticulum (SR) Ca2+ pumps and thereby cause a decrease in contractile reserve. To determine whether a decrease in ‖ΔG∼p‖ results in decreased contractile reserve by impairing Ca2+ handling, we measured left ventricular pressure and cytosolic Ca2+concentration ([Ca2+]c; by indo 1 fluorescence) in isolated perfused rat hearts, with >95% inhibition of CK with 90 μmol iodoacetamide. Iodoacetamide did not directly alter SR Ca2+-ATPase activity, baseline left ventricular developed pressure, or baseline [Ca2+]c. When perfusate Ca2+ concentration was increased from 1.2 to 3.3 mM, LV developed pressure increased from 67 ± 6 to 119 ± 8 mmHg in control hearts ( P < 0.05) but did not significantly increase in CK-inhibited hearts. Similarly, the amplitude of the [Ca2+]ctransient increased from 548 ± 54 to 852 ± 140 nM in control hearts ( P < 0.05) but did not significantly increase in CK-inhibited hearts. We conclude that decreased ‖ΔG∼p‖ limits intracellular Ca2+ handling and thereby limits contractile reserve.
Vaping on Instagram: cloud chasing, hand checks and product placement

Introduction This study documented images posted on Instagram of electronic cigarettes (e-cigarette) and vaping (activity associated with e-cigarette use). Although e-cigarettes have been studied on Twitter, few studies have focused on Instagram, despite having 500 million users. Instagram's emphasis on images warranted investigation of e-cigarettes, as past tobacco industry strategies demonstrated that images could be used to mislead in advertisements, or normalise tobacco-related behaviours. Findings should prove informative to tobacco control policies in the future. Methods 3 months of publicly available data were collected from Instagram, including images and associated metadata (n=2208). Themes of images were classified as (1) activity, for example, a person blowing vapour; (2) product, for example, a personal photo of an e-cigarette device; (3) advertisement; (4) text, for example, ‘meme’ or image containing mostly text and (5) other. User endorsement (likes) of each type of image was recorded. Caption text was analysed to explore different trends in vaping and e-cigarette-related text. Results Analyses found that advertisement-themed images were most common (29%), followed by product (28%), and activity (18%). Likes were more likely to accompany activity and product-themed images compared with advertisement or text-themed images (p<0.01). Vaping-related text greatly outnumbered e-cigarette-related text in the image captions. Conclusions Instagram affords its users the ability to post images of e-cigarette-related behaviours and gives advertisers the opportunity to display their product. Future research should incorporate novel data streams to improve public health surveillance, survey development and educational campaigns.
Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) and Its Clinical Translation

This review focuses on the cognitive neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) based on functional magnetic resonance imaging (fMRI) studies and on recent clinically relevant applications such as fMRI-based diagnostic classification or neuromodulation therapies targeting fMRI deficits with neurofeedback (NF) or brain stimulation. Meta-analyses of fMRI studies of executive functions (EFs) show that ADHD patients have cognitive-domain dissociated complex multisystem impairments in several right and left hemispheric dorsal, ventral and medial fronto-cingulo-striato-thalamic and fronto-parieto-cerebellar networks that mediate cognitive control, attention, timing and working memory (WM). There is furthermore emerging evidence for abnormalities in orbital and ventromedial prefrontal and limbic areas that mediate motivation and emotion control. In addition, poor deactivation of the default mode network (DMN) suggests an abnormal interrelationship between hypo-engaged task-positive and poorly “switched off” hyper-engaged task-negative networks, both of which are related to impaired cognition. Translational cognitive neuroscience in ADHD is still in its infancy. Pattern recognition analyses have attempted to provide diagnostic classification of ADHD using fMRI data with respectable classification accuracies of over 80%. Necessary replication studies, however, are still outstanding. Brain stimulation has been tested in heterogeneously designed, small numbered proof of concept studies targeting key frontal functional impairments in ADHD. Transcranial direct current stimulation (tDCS) appears to be promising to improve ADHD symptoms and cognitive functions based on some studies, but larger clinical trials of repeated stimulation with and without cognitive training are needed to test clinical efficacy and potential costs on non-targeted functions. Only three studies have piloted NF of fMRI-based frontal dysfunctions in ADHD using fMRI or near-infrared spectroscopy, with the two larger ones finding some improvements in cognition and symptoms, which, however, were not superior to the active control conditions, suggesting potential placebo effects. Neurotherapeutics seems attractive for ADHD due to their safety and potential longer-term neuroplastic effects, which drugs cannot offer. However, they need to be thoroughly tested for short- and longer-term clinical and cognitive efficacy and their potential for individualized treatment.
New Insights into the Role of Zinc Acquisition and Zinc Tolerance in Group A Streptococcal Infection

ABSTRACT Zinc plays an important role in host innate immune function. However, the innate immune system also utilizes zinc starvation (“nutritional immunity”) to combat infections. Here, we investigate the role of zinc import and export in the protection of Streptococcus pyogenes (group A Streptococcus; GAS), a Gram-positive bacterial pathogen responsible for a wide spectrum of human diseases, against challenge from host innate immune defense. In order to determine the role of GAS zinc import and export during infection, we utilized zinc import (ΔadcA ΔadcAII) and export (ΔczcD) deletion mutants in competition with the wild type in both in vitro and in vivo virulence models. We demonstrate that nutritional immunity is deployed extracellularly, while zinc toxicity is utilized upon phagocytosis of GAS by neutrophils. We also show that lysosomes and azurophilic granules in neutrophils contain zinc stores for use against intracellular pathogens.
Lercanidipine effect on circulating CD34+ progenitor cells in elderly patients: a randomized study

Abstract Objective: This randomized study evaluates the effects of lercanidipine – as well as its antihypertensive efficacy – on the number of circulating endothelial progenitor cells (EPCs) in elderly patients with hypertension. Research design and methods: In total, 61 patients with hypertension were randomly assigned to lercanidipine 10 mg/day or to other antihypertensive treatments (control group). Main outcome measures: Cytometry analysis was conducted at baseline, at 12 weeks and at 24 weeks. Routine clinical examination was also performed. Results: Overall, the number of circulating EPCs had already significantly increased with lercanidipine, compared with baseline values, after 12 weeks; this increase was sustained until the end of the study. On the other hand, the number of circulating EPCs remained stable in the control group throughout the study period. At 12 weeks, a significant reduction in blood pressure, compared with baseline values, was observed in both groups. Regression analysis showed a significant negative correlation between systolic blood pressure and the number of circulating EPCs. Conclusions: Although the limited number of patients and the short follow-up hamper the analysis, this study suggests that lercanidipine may increase EPC concentration independently from its anti-hypertensive effect.
Escape from vasopressin-induced antidiuresis: role of vasopressin resistance of the collecting duct.

Previously, we demonstrated that escape from vasopressin-induced antidiuresis ("vasopressin escape") in rats is associated with a large, selective decrease in whole kidney expression of aquaporin-2, the vasopressin-regulated water channel. Here, we show that isolated perfused inner medullary collecting ducts (IMCDs) from vasopressin-escape rats {desamino-[d-arginine]vasopressin (DDAVP)/water-loaded} have dramatically reduced vasopressin-dependent osmotic water permeabilities [46% of control rats (DDAVP alone)], which coincides with a fall in inner medullary aquaporin-2 protein abundance as measured by immunoblotting in the opposite kidney. Furthermore, we demonstrate in IMCD suspensions that cAMP accumulation in response to DDAVP is substantially reduced in the vasopressin-escape rats both in the presence and absence of the phosphodiesterase inhibitor IBMX. By immunoblotting, we show that the abundance of two proteins important in cAMP generation: the stimulatory heterotrimeric G protein subunit Gsα and adenylyl cyclase type VI, do not change. We conclude that vasopressin escape is associated with relative vasopressin resistance of the collecting duct cells manifested by decreased intracellular cAMP levels. The decreased cAMP levels can contribute to the demonstrated decrease in collecting duct water permeability in two ways: 1) by causing a decrease in aquaporin-2 expression and 2) by limiting the acute action of vasopressin to increase collecting duct water permeability.
Exploring Cost Constraints on Stem Elongation in Plants Using Phenotypic Manipulation

Negative associations between individual life-history traits of an organism are referred to as life-history trade-offs (Stearns 1992; Zera et al. 1998). The existence of costly trade-offs is thought to have favored the evolution of phenotypic plasticity as a mechanism through which organisms can account for environmental heterogeneity while modulating costs and benefits incurred by fixed allocation to competing functions (Bradshaw 1965; Stearns 1992; Sultan 1995; Dudley and Schmitt 1996; Pigliucci 1996). In plants, the ability to modify stem elongation in response to environmental cues appears to be a classic form of adaptive phenotypic plasticity (Sultan 1995; Gedroc et al. 1996). Plastic increases or decreases in stem elongation rate in plants can be triggered by light-quality and lightquantity cues (Smith 1982; Ballare et al. 1989, 1990; Rajapakse and Kelly 1995; Petit and Thompson 1997) and exposure to mechanical stimuli (e.g., wind) (Gartner 1991; Jaffe and Forbes 1993; Emery et al. 1994; Cipollini 1997b). Increased stem elongation in response to light cues can enable plants to escape shading by neighbors and capitalize on heterogenous resources, while reduced elongation in response to mechanical cues can enable plants to resist mechanical damage (Ballare et al. 1991, 1995; Jaffe and Forbes 1993). The best-studied plastic stem response in plants is the “shade avoidance” response, cued by altered red : far-red
RBC Adherence of Immune Complexes Containing Botulinum Toxin Improves Neutralization and Macrophage Uptake

In the paralytic disease botulism, the botulinum neurotoxin (BoNT) passes through the bloodstream to reach and inactivate neuromuscular junctions. Monoclonal antibodies (mAbs) may be useful BoNT countermeasures, as mAb combinations can rapidly clear BoNT from the blood circulation. We have previously shown that the BoNT-neutralizing potency of mAbs can be improved through red blood cell (RBC) immunoadherence. For example, a fusion protein (FP) that adheres biotinylated mAbs to the RBC surface enabled a pair of mAbs to neutralize 5000 LD50 BoNT/A in the mouse protection assay. Here, we added two mAbs to that combination, creating a 4-mAb:FP complex that neutralized 40,000 LD50 BoNT/A in vivo, and analyzed functional correlates of neutralization. The FP enhanced potency of BoNT/A immune complexes, providing the greatest magnitude of benefit to the 4-mAb combination. RBC binding of a BoNT/A complexed with 4-mAb:FP exhibited a bi-phasic clearance process in vivo. Most of the complexes were cleared within five minutes; the rest were cleared gradually over many hours. Peritoneal macrophages showed better uptake of the 4-mAb complex than the 3-mAb complex, and this was not affected by the presence of the FP. However, the addition of RBCs to the 4-mAb:FP BoNT/A doubled macrophage uptake of the complexes. Lastly, the 4-mAb:FP BoNT/A complex synergistically induced M2 macrophage polarization, as indicated by IL-10 expression, whether or not RBCs were present. RBC-targeted immunoadherence through the FP is a potent enhancer of mAb-mediated BoNT/A neutralization in vivo, and can have positive effects on BoNT/A sequestration, immune complex uptake, and macrophage activation.
Gomisin G Inhibits the Growth of Triple-Negative Breast Cancer Cells by Suppressing AKT Phosphorylation and Decreasing Cyclin D1

A type of breast cancer with a defect in three molecular markers such as the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor is called triple-negative breast cancer (TNBC). Many patients with TNBC have a lower survival rate than patients with other types due to a poor prognosis. In this study, we confirmed the anti-cancer effect of a natural compound, Gomisin G, in TNBC cancer cells. Treatment with Gomisin G suppressed the viability of two TNBC cell lines, MDA-MB-231 and MDA-MB-468 but not non-TNBC cell lines such as MCF-7, T47D, and ZR75-1. To investigate the molecular mechanism of this activity, we examined the signal transduction pathways after treatment with Gomisin G in MDA-MB-231 cells. Gomisin G did not induce apoptosis but drastically inhibited AKT phosphorylation and reduced the amount of retinoblastoma tumor suppressor protein (Rb) and phosphorylated Rb. Gomisin G induced in a proteasome-dependent manner a decrease in Cyclin D1. Consequently, Gomisin G causes cell cycle arrest in the G1 phase. In contrast, there was no significant change in T47D cells except for a mild decrease in AKT phosphorylation. These results show that Gomisin G has an anti-cancer activity by suppressing proliferation rather than inducing apoptosis in TNBC cells. Our study suggests that Gomisin G could be used as a therapeutic agent in the treatment of TNBC patients.
Longitudinal associations between outpatient medical care use and substance use among rural stimulant users

ABSTRACT Background: Negative views toward substance use treatment among some rural substance users and limited treatment resources in rural areas likely affect substance use utilization. It is therefore important to determine whether accessing healthcare options other than substance use treatment, specifically outpatient medical care (OMC), is associated with reductions in substance use. Objectives: We examined whether use of OMC was associated with reductions in substance use among rural substance users over a three-year period. We also explored whether substance user characteristics, including substance-use severity and related-problems, moderated this potential relationship. Methods: Data were collected from an observational study of 710 (61% male) stimulant users using respondent-driven sampling. Participants were recruited from rural counties of Arkansas, Kentucky, and Ohio. Results: We found a significant main effect of having at least one OMC visit (relative to none) on fewer days of alcohol, crack cocaine, and methamphetamine use over time. Fewer days of alcohol, crack cocaine, and methamphetamine use were reported in participants with at least one OMC visit (relative to those with none) among those reporting higher Addiction Severity Index employment and psychiatric severity scores, and low education, respectively. Conclusion: Our findings extend the results from prior studies with urban substance users to show that contact with an outpatient medical care clinic is associated with reductions in substance use over time among rural substance users with especially poorer functioning. These findings highlight the potential importance of OMCs in addressing unhealthy substance use in rural communities.
Physiological regulation of epithelial tight junctions is associated with myosin light-chain phosphorylation.

Tight junctions serve as the rate-limiting barrier to passive movement of hydrophilic solutes across intestinal epithelia. After activation of Na+-glucose cotransport, the permeability of intestinal tight junctions is increased. Because previous analyses of this physiological tight junction regulation have been restricted to intact mucosae, dissection of the mechanisms underlying this process has been limited. To characterize this process, we have developed a reductionist model consisting of Caco-2 intestinal epithelial cells transfected with the intestinal Na+-glucose cotransporter, SGLT1. Monolayers of SGLT1 transfectants demonstrate physiological Na+-glucose cotransport. Activation of SGLT1 results in a 22 ± 5% fall in transepithelial resistance (TER) ( P< 0.001). Similarly, inactivation of SGLT1 by addition of phloridzin increases TER by 24 ± 2% ( P < 0.001). The increased tight junction permeability is size selective, with increased flux of small nutrient-sized molecules, e.g., mannitol, but not of larger molecules, e.g., inulin. SGLT1-dependent increases in tight junction permeability are inhibited by myosin light-chain kinase inhibitors (20 μM ML-7 or 40 μM ML-9), suggesting that myosin regulatory light-chain (MLC) phosphorylation is involved in tight junction regulation. Analysis of MLC phosphorylation showed a 2.08-fold increase after activation of SGLT1 ( P< 0.01), which was inhibited by ML-9 ( P < 0.01). Thus monolayers incubated with glucose and myosin light-chain kinase inhibitors are comparable to monolayers incubated with phloridzin. ML-9 also inhibits SGLT1-mediated tight junction regulation in small intestinal mucosa ( P < 0.01). These data demonstrate that epithelial cells are the mediators of physiological tight junction regulation subsequent to SGLT1 activation. The intimate relationship between tight junction regulation and MLC phosphorylation suggests that a critical step in regulation of epithelial tight junction permeability may be myosin ATPase-mediated contraction of the perijunctional actomyosin ring and subsequent physical tension on the tight junction.
Effect of pear apple and date fibres incorporation on the physico-chemical, sensory, nutritional characteristics and the acceptability of cereal bars

Cereal bars are nutritious food composed of several ingredients including dry raw and agglutinative ingredients. The objective of this study was to evaluate the effect of pear apple and date fibres, from cooked fruit co-product, addition on the physico-chemical textural and sensory properties of cereal bars. First, five formulations containing an amount of 10% of co-products and commercial fibre, used as a reference, were elaborated and their physico-chemical composition was determined. Second, to determine the acceptability of consumer, apple fibre co-products were added (6, 10 and 14%). Products were evaluated for their texture using a texturometer and sensory characteristics using an acceptance test. Results showed that physico-chemical composition of cereal bars elaborated with co-products was slightly different compared to those elaborated with commercial fibre. All bars have low water activity levels (∼0.470) and interesting energy (300 kcal/100 g bar). External appearance revealed a darker colour (L*:∼42/a*:∼8/b*:∼20). There were no significant differences (P > 0.05) in texture values (hardness: 40.8 N; cohesiveness: 0.34; springiness: 0.60; chewiness: 8.30 N) between cereal bars prepared with pear co-product and wheat bran. Acceptance test confirms the formulation used for cereals bars and showed that incorporation of 10% of co-product produced cereal bars with the highest acceptability. Sensory characteristics revealed that appearance is the limiting factor for consumer acceptability, essentially for cereal bars containing pear co-product. Apple, pear and date co-products could be used successfully as a food ingredient to develop new formulations of cereal bars.
Formulation of influenza T cell peptides : in search of a universal influenza vaccine

Current seasonal influenza vaccines rely on the induction of antibodies to neutralize the virus. However, influenza viruses frequently undergo genetic mutations due to antigenic drift and shift, altering the surface proteins hemagglutinin and neuraminidase to which antibodies usually bind. This could render vaccine-induced antibody responses ineffective, resulting in an ineffective influenza vaccine. Influenza vaccines based on the induction of T cell responses might be cross-reactive, since they target conserved influenza epitopes that do not tend to mutate. However, the peptide antigens that are able to induce such T cell responses are often poorly immunogenic. In this thesis, several formulation strategies are described that could improve the immunogenicity of influenza T cell peptide antigens. Using combinations of delivery systems and immunostimulators, the peptide antigens were able to induce influenza-specific T cell responses in mice. Furthermore, a model was developed that could predict the in vitro adjuvanticity of liposomes according to the liposomal lipid composition. In addition, the recent advances in influenza vaccine development are discussed. Finally, an alternative delivery system, the Bioneedle, was evaluated for the delivery of several influenza vaccines.
Influence of altered tongue contour and position on deglutitive pharyngeal and UES function.

The potential influence of altered lingual position and contour during the bolus loading phase of the swallow in mediating the swallowed bolus volume-dependent regulation of upper esophageal sphincter (UES) relaxation and opening was studied in 15 healthy volunteers using simultaneous videoradiography and manometry. A maxillary dental splint modulated tongue deformity during the early oral phase of deglutition. We examined the effect of the splint and swallowed bolus density on bolus volume-dependent changes in the timing of events in the swallow sequence and on hypopharyngeal intrabolus and midpharyngeal pressures. Peak midpharyngeal pressure ( P = 0.001) and hypopharyngeal intrabolus pressure ( P = 0.04) were significantly reduced by the splint. The normal volume-dependent earlier onset of sphincter relaxation and opening was preserved with the splint in situ. The splint significantly delayed the onset of hyoid motion and UES relaxation and opening without influencing transit times or total swallow duration. Alterations in tongue contour and position reduce intrabolus pressure and pharyngeal contraction without influencing normal bolus volume-dependent regulation of timing of UES relaxation and opening.