Miracle-dz/UniFAR-FTUs huggingface dataset:
Contribution of the surface free energy perturbation to protein-solvent interactions.

Surface tension measurements were carried out at 20 degrees C by a capillary drop-weight method on aqueous solutions of sodium glutamate (NaGlu), lysine hydrochloride (LysHCl), potassium aspartate (KAsp), arginine hydrochloride (ArgHCl), lysylglutamate (LysGlu), argininylglutamate (ArgGlu), guanidinium sulfate, trehalose, trimethylamine N-oxide (TMAO), dimethyl sulfoxide, 2-methyl-2,4-pentanediol (hexylene glycol), and poly(ethylene glycol)s of molecular weights 200, 400, 600, and 1000. All of the salts and the sugar increased the surface tension of water, while the last four compounds decreased it, with 2-methyl-2,4-pentanediol lowering it most effectively and TMAO being the least effective. The preferential hydration of bovine serum albumin (BSA) and lysozyme was measured in KAsp, ArgHCl, LysGlu, and ArgGlu. The high values of preferential hydration found in all cases, except for BSA in ArgHCl, suggest that they should stabilize protein structure, as had been found for lysine hydrochloride and monosodium glutamate [Arakawa, T. , & Timasheff, S. N. (1984) J. Biol. Chem. 259, 4979-4986]. A correlation was found for both BSA and lysozyme in KAsp, NaGlu, LysHCl, ArgGlu, and LysGlu between the surface tension effect and the observed preferential interactions, indicating that the change in the surface free energy of the protein-containing cavity due to the surface tension increase for water by these amino acid salts contributes dominantly to the observed increase in the chemical potential of the protein by their addition. The lack of a correlation observed for BSA, but not lysozyme, in ArgHCl at low concentrations where preferential binding is close to zero suggests, however, that the surface tension effect is not the sole factor involved in the protein-solvent interactions in these amino acid salts. Binding of ArgHCl to BSA, probably through hydrogen bonds between the Arg guanidinium group and peptide bonds, was proposed to occur, the affinity of Arg+ being reduced by electrostatic repulsion when proteins carry a net positive charge, such as is the case with lysozyme. Since the four organic solvent additives also lead to protein preferential hydration, no correlation exists between their preferential interactions and the surface free energy perturbation. Therefore, in their case, the preferential hydration must be ascribed to other factors that overcome the preferential binding expected from the Gibbs adsorption isotherm. The surface tension results, however, are consistent with the binding of the organic solvents to proteins through hydrophobic interactions, explaining, at least in part, the observed concentration dependence of the interactions.
A pH-Dependent Colon-Targeted Oral Drug Delivery System Using Methacrylic Acid Copolymers. II. Manipulation of Drug Release Using Eudragit® L100 and Eudragit S100 Combinations

Tablets containing mesalazine as a model drug were coated using various combinations of two methacrylic acid copolymers, (Eudragit® L100 and Eudragit S100) by spraying from aqueous systems. The Eudragit L100–Eudragit S100 (w/w) combinations studied were 1:0, 4:1, 3:2, 1:1, 2:3, 1:4, 1:5, and 0:1. The coated tablets were tested in vitro for their suitability for pH-dependent colon-targeted oral drug delivery. The dissolution profiles of the drug obtained from the studied tablets demonstrate that the release of the drug could be manipulated by changing the Eudragit L100–Eudragit S100 ratios in the combinations within the pH range between 6.0 and 7.0 in which the individual polymers are soluble, and a coating formulation consisting of a combination of the two polymers can overcome the issue of high gastrointestinal (GI) pH variability among individuals. The results also demonstrate the feasibility of using aqueous dispersions of Eudragit L100–Eudragit S100 combinations for coating tablets for colon-targeted delivery of drugs, and that the formulation can be adjusted to deliver drug(s) at any other desirable site of the intestinal region of the GI tract in which pH of the fluid is within the range 6.0 to 7.0. For colon-targeted delivery of drugs, the proposed combination system is superior to tablets coated with either Eudragit L100 or Eudragit S100 alone.
Cognitive Effects and Sedation.

OBJECTIVE Cognitive effects and sedation (CES) are prevalent in chronic nonmalignant pain populations receiving long-term opioid therapy and are among the most common reasons patients discontinue opioid use. In this narrative review, we describe the phenomenology, epidemiology, mechanisms, assessment, and management of opioid-related CES. DESIGN We reviewed the empirical and theoretical literature on CES in opioid-treated populations with chronic pain. Data on long-term opioid therapy (≥ 3 months in duration) in chronic nonmalignant pain patients were sought. RESULTS The phenomenology of CES includes: inattention, concentration difficulties, memory deficits, psychomotor dysfunction, perceptual distortions, and executive dysfunction and somnolence, sleep disorders, and lethargy. Deficits may be caused by unrelieved pain or opioid therapy alone, or from a combination of these and other factors. Mechanisms include central nervous system effects, for example, direct toxic effects on neurons resulting in decreased consciousness; direct effects on processing and reaction resulting in cognitive or psychomotor impairment, and inhibitory effects on cholinergic activity. Pharmacological management approaches may include opioid dose reduction and rotation or psychostimulant use. Nonpharmacological approaches may include cognitive-behavioral therapy, mindfulness-based stress reduction, acupuncture, exercise, and yoga. CONCLUSIONS The most prevalent CES include: memory deficits (73-81%), sleep disturbance (35-57%), and fatigue (10%). At its most severe, extreme cognitive dysfunction can result in frank delirium and decreased alertness can result in coma. Emotional distress, sleep disorders, and other comorbidities and treatments can worsen CES, particularly among the elderly. Conclusions about the neuropsychological domains affected by opioids are limited due to the heterogeneity of studies and methodological issues.
New Strategies for Cultivation and Detection of Previously Uncultured Microbes

ABSTRACT An integrative approach was used to obtain pure cultures of previously uncultivated members of the divisions Acidobacteria and Verrucomicrobia from agricultural soil and from the guts of wood-feeding termites. Some elements of the cultivation procedure included the following: the use of agar media with little or no added nutrients; relatively long periods of incubation (more than 30 days); protection of cells from exogenous peroxides; and inclusion of humic acids or a humic acid analogue (anthraquinone disulfonate) and quorum-signaling compounds (acyl homoserine lactones) in growth media. The bacteria were incubated in the presence of air and in hypoxic (1 to 2% O2 [vol/vol]) and anoxic atmospheres. Some bacteria were incubated with elevated concentrations of CO2 (5% [vol/vol]). Significantly more Acidobacteria were found on isolation plates that had been incubated with 5% CO2. A simple, high-throughput, PCR-based surveillance method (plate wash PCR) was developed. This method greatly facilitated detection and ultimate isolation of target bacteria from as many as 1,000 colonies of nontarget microbes growing on the same agar plates. Results illustrate the power of integrating culture methods with molecular techniques to isolate bacteria from phylogenetic groups underrepresented in culture.
Effect of porcine conceptus secretory proteins on interestrous interval and uterine secretion of prostaglandins.

Porcine conceptus secretory proteins (pCSP) were obtained from medium in which pig conceptuses, collected on Day 15 of pregnancy, were cultured for 30 h. Culture medium was pooled, dialyzed, and concentrated by Amicon ultrafiltration for intrauterine infusion. Serum proteins (SP) were obtained from blood collected from a Day 15 pregnant gilt and diluted for intrauterine infusion. Catheters were placed into both uterine horns and the inferior vena cava of cyclic (Day 8) gilts. Single blood samples were collected at 0800 h on Days 9, 10, and 11. On Day 11, all gilts received 1 mg estradiol-17 beta (E2) i.m. at 0800 h. Protein infusions commenced on Day 12 and continued through Day 15, twice daily at 0800 h and 2000 h. Protein infusions per uterine horn were (1) 4.0 mg pCSP + 4.0 mg SP (pCSP, 4 gilts) and (2) 8.0 mg SP (SP, 4 gilts). Blood samples were collected every 15 min on Days 12 through 17 between 0805 h and 1100 h. Single blood samples were collected at 0800 h after Day 17 until gilts exhibited estrus. Concentrations of prostaglandin (PG) E, 13,14-dihydro-15-keto-PGF2 alpha (PGFM), and progesterone (P4) were measured by specific radioimmunoassays. Interestrous intervals for pCSP-treated (18.2 days) and SP-treated (18.0 days) gilts were not different (SEM = 0.8 days) and temporal changes in concentrations of P4 in plasma did not differ between pCSP-treated (29.2 ng/ml) and SP-treated (31.2 ng/ml) gilts. (ABSTRACT TRUNCATED AT 250 WORDS)
Network Size and Connectivity in Mobile and Stationary Ad Hoc Networks

One of the assumptions behind tactical mobile ad hoc networks (MANETs) is that routes consisting of multiple hops will be available to connect those nodes that lack line-of sight connectivity. The practical utility of MANET depends on this assumption being true and, for a mobile network, remaining true during mobility. In previous work, we showed that average node-to-node direct connectivity and the rate at which direct links break over time while moving through a given terrain can be characterized approximately using average terrain measures that are location and distance insensitive. Here, we exploit that result and extend our previous work to characterize the rate at which line-of-sight links and end-to-end shortest paths appear and disappear for mobile networks of various sizes in various terrains.
Clinical Research: A Novel Approach to the Analysis of Repeated Measures

In current clinical research, repeated measures in a single subject are common. The problem with repeated measures is that they are closer to one another than unrepeated measures. If this is not taken into account, then data analysis will lose power. In the past decade, user-friendly statistical software programs such as SAS and SPSS have enabled the application of mixed models as an alternative to the classical general linear model for repeated measures with, sometimes, better sensitivity. The objective was to assess whether in studies with repeated measures, designed to test between-subject differences, the mixed model performs better than does the general linear model. In a parallel group study of cholesterol-reducing treatments with 5 evaluations per patient, the mixed model performed much better than did the general linear model with P values of 0.0001 and 0.048, respectively. In a crossover study of 3 treatments for sleeplessness, the mixed model and general linear model performed similarly well with P values of 0.005 and 0.010. Mixed models do, indeed, seem to produce better sensitivity of testing, when there are small within-subject differences and large between-subject differences and when the main objective of your research is to demonstrate between- rather than within-subject differences. The novel mixed model may be more complex. Yet, with modern user-friendly statistical software, its use is straightforward, and its software commands are no more complex than they are with standard methods. We hope that this article will encourage clinical researchers to make use of its benefits more often.
Auto Adaptive Identification Algorithm Based on Network Traffic Flow

Traffic identification is a key task for any Internet Service Provider (ISP) or network administrator. Machine learning method is an important researchmethod on traffic identification, while impact of the asymmetry router on the traffic identification is considered, so this paper analyzes the impact of asymmetry routing on traffic identification, and proposes an effective method to decrease the impact, and experimental results show the auto adaptive algorithm can improve the traffic identification.
Effect of breastfeeding and formula feeding on transmission of HIV-1: a randomized clinical trial.

CONTEXT Transmission of human immunodeficiency virus type 1 (HIV-1) is known to occur through breastfeeding, but the magnitude of risk has not been precisely defined. Whether breast milk HIV-1 transmission risk exceeds the potential risk of formula-associated diarrheal mortality in developing countries is unknown. OBJECTIVES To determine the frequency of breast milk transmission of HIV-1 and to compare mortality rates and HIV-1-free survival in breastfed and formula-fed infants. DESIGN AND SETTING Randomized clinical trial conducted from November 1992 to July 1998 in antenatal clinics in Nairobi, Kenya, with a median follow-up period of 24 months. PARTICIPANTS Of 425 HIV-1-seropositive, antiretroviral-naive pregnant women enrolled, 401 mother-infant pairs were included in the analysis of trial end points. INTERVENTIONS Mother-infant pairs were randomized to breastfeeding (n = 212) vs formula feeding arms (n = 213). MAIN OUTCOME MEASURES Infant HIV-1 infection and death during the first 2 years of life, compared between the 2 intervention groups. RESULTS Compliance with the assigned feeding modality was 96% in the breastfeeding arm and 70% in the formula arm (P<.001). Median duration of breastfeeding was 17 months. Of the 401 infants included in the analysis, 94% were followed up to HIV-1 infection or mortality end points: 83% for the HIV-1 infection end point and 93% to the mortality end point. The cumulative probability of HIV-1 infection at 24 months was 36.7% (95% confidence interval [CI], 29.4%-44.0%) in the breastfeeding arm and 20.5% (95% CI, 14.0%-27.0%) in the formula arm (P = .001). The estimated rate of breast milk transmission was 16.2% (95% CI, 6.5%-25.9%). Forty-four percent of HIV-1 infection in the breastfeeding arm was attributable to breast milk. Most breast milk transmission occurred early, with 75% of the risk difference between the 2 arms occurring by 6 months, although transmission continued throughout the duration of exposure. The 2-year mortality rates in both arms were similar (breastfeeding arm, 24.4% [95% CI, 18.2%-30.7%] vs formula feeding arm, 20.0% [95% CI, 14.4%-25.6%]; P = .30). The rate of HIV-1-free survival at 2 years was significantly lower in the breastfeeding arm than in the formula feeding arm (58.0% vs 70.0%, respectively; P = .02). CONCLUSIONS The frequency of breast milk transmission of HIV-1 was 16.2% in this randomized clinical trial, and the majority of infections occurred early during breastfeeding. The use of breast milk substitutes prevented 44% of infant infections and was associated with significantly improved HIV-1-free survival.
Nuclear factor-κB as a hormonal intracellular signaling molecule: focus on angiotensin II-induced cardiovascular and renal injury

Purpose of reviewNuclear factor-κB (NF-κB) has recently emerged as a novel intracellular signaling molecule for hormones, cytokines, chemokines, and growth factors. The purpose of this article is to highlight the role of NF-κB as an intracellular signaling for angiotensin II and clinical perspectives of targeting NF-κB signaling in treating hypertensive and renal diseases. Recent findingsA selective review of recently published work provides strong evidence that activation of NF-κB signaling by angiotensin II mediates the detrimental effects of angiotensin II on the transcription of cytokines, chemokines and growth factors. Angiotensin II stimulates AT1 receptors to activate NF-κB signaling via both canonical (classical) and noncanonical (alternative) pathways. Intracellular angiotensin II may also induce NF-κB activation and transactivation of target genes. Nearly 800 NF-κB inhibitors have been described, but none has advanced to clinical trials. However, angiotensin converting enzyme inhibitors and AT1 blockers are beneficial in treating angiotensin II-induced hypertensive and renal injury in part by inhibiting NF-κB activation. SummaryAngiotensin II induces the transcription of cytokines, chemokines and growth factors, leading to target organ injury. These responses to angiotensin II are caused primarily by AT1 receptor-activated NF-κB signaling. Targeting NF-κB signaling with angiotensin converting enzyme inhibitors, AT1 blockers, and specific NF-κB inhibitors may represent a novel approach in treating angiotensin II-induced hypertensive and renal diseases.
Role of the Sympathetic Autonomic Nervous System in Hypoxic Remodeling of the Fetal Cerebral Vasculature

Abstract: Fetal hypoxia triggers compensatory angiogenesis and remodeling through mechanisms not fully elucidated. In response to hypoxia, hypoxia-inducible factor drives expression of cytokines that exert multiple effects on cerebral structures. Among these, the artery wall is composed of a heterogeneous cell mix and exhibits distinct patterns of cellular differentiation and reactivity. Governing these patterns are the vascular endothelium, smooth muscle (SM), adventitia, sympathetic perivascular nerves (SPN), and the parenchyma. Although an extensive literature details effects of nonneuronal factors on cerebral arteries, the trophic role of perivascular nerves remains unclear. Hypoxia increases sympathetic innervation with subsequent release of norepinephrine (NE), neuropeptide-Y (NPY), and adenosine triphosphate, which exert motor and trophic effects on cerebral arteries and influence dynamic transitions among SM phenotypes. Our data also suggest that the cerebrovasculature reacts very differently to hypoxia in fetuses and adults, and we hypothesize that these differences arise from age-related differences in arterial SM phenotype reactivity and proximity to trophic factors, particularly of neural origin. We provide an integration of recent literature focused on mechanisms by which SPN mediate hypoxic remodeling. Our recent findings suggest that trophic effects of SPN on cerebral arteries accelerate functional maturation through shifts in SM phenotype in an age-dependent manner.
Cerebellar Direct Current Stimulation Enhances On-Line Motor Skill Acquisition through an Effect on Accuracy

The cerebellum is involved in the update of motor commands during error-dependent learning. Transcranial direct current stimulation (tDCS), a form of noninvasive brain stimulation, has been shown to increase cerebellar excitability and improve learning in motor adaptation tasks. Although cerebellar involvement has been clearly demonstrated in adaptation paradigms, a type of task that heavily relies on error-dependent motor learning mechanisms, its role during motor skill learning, a behavior that likely involves error-dependent as well as reinforcement and strategic mechanisms, is not completely understood. Here, in humans, we delivered cerebellar tDCS to modulate its activity during novel motor skill training over the course of 3 d and assessed gains during training (on-line effects), between days (off-line effects), and overall improvement. We found that excitatory anodal tDCS applied over the cerebellum increased skill learning relative to sham and cathodal tDCS specifically by increasing on-line rather than off-line learning. Moreover, the larger skill improvement in the anodal group was predominantly mediated by reductions in error rate rather than changes in movement time. These results have important implications for using cerebellar tDCS as an intervention to speed up motor skill acquisition and to improve motor skill accuracy, as well as to further our understanding of cerebellar function.
The Influence of BRCA1/BRCA2 Mutations on Toxicity Related to Chemotherapy and Radiotherapy in Early Breast Cancer Patients

Objective: The presence of BRCA gene mutation and low expressions of BRCA proteins are associated with a greater sensitivity of tumor cells to ionizing radiation and to cytostatics damaging the DNA of the cells. The purpose of this study was to estimate the rate of adverse events in BRCA1/2-associated breast cancer patients receiving anthracycline-based chemotherapy compared to patients without mutation. The authors also compared radiotherapy toxicity in these 2 groups. Methods: The analysis included 270 early-stage breast cancer patients treated between 2006 and 2012. All patients were examined for the presence of BRCA1/2 mutations. Results:BRCA mutation was detected in 41 (15%) patients. Toxicity grade 3, especially nausea and vomiting, was observed more often in noncarriers (7 vs. 13%, p = 0.0008). Neutropenia was detected more frequently in patients with BRCA1/2 mutation (32 vs. 10%), but only after 1 cycle of chemotherapy (p = 0.0007). There was increased radiation toxicity in BRCA1/2 patients who underwent mastectomy and neoadjuvant chemotherapy (p = 0.016). Conclusions:BRCA1/2 mutation carriers seemed to be more at risk of neutropenia after the first cycle of the treatment. In terms of other side effects, there was a lack of increased toxicity in this group. Mastectomy and neoadjuvant chemotherapy were risk factors for radiation toxicity in mutation carriers.
Side impact reliability of micro-switches

In this study, a novel side-impact test method is developed for shearing-off miniature electromechanical devices from the printed wiring boards (PWBs) of portable products. The test method is implemented by modifying a commercial IZOD pendulum impact test setup. The key modification is the replacement of the instrumented pendulum impactor with an instrumented “striker-bar” design. The pendulum instrumented with the “striker-bar” allows high impact velocity up to 3.54E+3 mm/s, and is specially designed for testing components with very low profile. In this study, this setup is used to test a miniaturized electromechanical devices, such as a micro-switch, whose low profile presents a significant challenge to repeatable side-impact testing. Both overstress impact tests and repetitive impact fatigue tests are conducted, to evaluate the interaction of the different parts of the entire electromechanical assembly, including the solder joints, pins, through-holes and housing of the package. Failure modes are documented and failure envelopes are developed by relating the measured durability to the impact parameters like impact velocity, fracture energy and force impulse.