Miracle-dz/UniFAR-FTUs huggingface dataset:
A semi-synthetic glycosaminoglycan analogue inhibits and reverses Plasmodium falciparum cytoadherence

A feature of mature Plasmodium falciparum parasitized red blood cells is their ability to bind surface molecules of the microvascular endothelium via the parasite-derived surface protein Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). This ligand is associated with the cytoadherence pathology observed in severe malaria. As pRBC treated with effective anti-malarial drugs are still able to cytoadhere, there is therefore a need to find an adjunct treatment that can inhibit and reverse the adhesion process. One semi-synthetic, sulfated polysaccharide has been identified that is capable of inhibiting and reversing sequestration of pRBC on endothelial cells in vitro under physiological flow conditions. Furthermore, it exhibits low toxicity in the intrinsic (APTT assay) and extrinsic (PT assay) clotting pathways, as well as exhibiting minimal effects on cell (HUVEC) viability (MTT proliferation assay). These findings suggest that carbohydrate-based anti-adhesive candidates may provide potential leads for therapeutics for severe malaria.
Mental Vulnerability as a Predictor of Early Mortality

Background: Studies have demonstrated that mental vulnerability (ie, a tendency to experience psychosomatic symptoms or inadequate interpersonal interactions) is associated with various diseases. The objective of our study is to evaluate whether mental vulnerability is a risk factor for early mortality. Methods: We conducted a prospective cohort study of 3 random samples of the population in Copenhagen County, Denmark selected in 1976, 1982–1984, and 1991 (n = 6435). Baseline data collection included measures of mental vulnerability, social factors, comorbidity, biologic risk markers (eg, blood pressure, lipid levels), and lifestyle factors. We determined vital status of the study sample through linkage to the Civil Registration System until 2001 and to the Cause of Death Registry until 1998. The mean follow-up time was 15.9 years for analysis of total mortality and 13.6 years for analysis of mortality as the result of natural causes. The association between mental vulnerability and survival was examined using Kaplan-Meir plots and Cox proportional-hazard models adjusting for possible confounding factors. Results: With respect to mental vulnerability, 79% of the sample was classified as not vulnerable, 13% as moderately vulnerable, and 8% as highly vulnerable. Compared with the nonvulnerable group, highly vulnerable persons showed increased total mortality (hazard ratio = 1.6; 95% confidence interval = 1.3–1.9) and increased mortality from natural causes (1.6; 1.2–2.0). The inclusion of the mental vulnerability score as a continuous variable gave similar results. Conclusions: Mental vulnerability may be an independent risk factor for premature mortality. The biologic mechanisms that may underlie this association need further exploration.
L2 gain analysis of actuator saturation for switched LPV systems and applications to aero-engines

This paper considers the L2 gain analysis problem for switched linear parameter-varying (LPV) systems in the presence of actuator saturation. The multiple parameter-dependent Lyapunov functions approach is used to design a state feedback law and parameter mode-dependent switching law without requiring the stability of each subsystem. A sufficient condition is obtained by a matrix optimization to guarantee the L2 gain of the switched systems. Based on a family of linearized models of an aero-engine, a switched LPV model is built. Simulation results show the effectiveness and validity of the proposed method.
Host range expansion of Autographa californica nuclear polyhedrosis virus (NPV) following recombination of a 0.6-kilobase-pair DNA fragment originating from Bombyx mori NPV

We have isolated hybrid baculoviruses of Bombyx mori nuclear polyhedrosis virus (BmNPV) and Autographa californica NPV (AcNPV) capable of replicating in both BmN (not susceptible to AcNPV) and SF-21 (not susceptible to BmNPV) cells (A. Kondo and S. Maeda, J. Virol. 65:3625-3632, 1991). Repeated backcross infection of one of these recombinant isolates with AcNPV generated eh-AcNPV, a virus with restriction endonuclease patterns of genomic DNA nearly identical to those of AcNPV but capable of replicating in both BmN and SF-21 cells, i.e., host range expanded. Expanded host range viruses were also isolated following cotransfection of AcNPV DNA with eh-AcNPV DNA cleaved with either HindIII or PstI. Subsequent cotransfection of AcNPV DNA with plasmids from an eh-AcNPV DNA fragment library identified an 11-kbp HindIII fragment that could expand the host range of AcNPV. Subcloning and cotransfection analyses localized a 572-bp SacI-HindIII fragment within this 11-kbp fragment which could alone expand the host range of AcNPV. Mapping and nucleotide sequencing analysis revealed that this fragment was identical to the corresponding 572-bp fragment (BmScH) of BmNPV. Furthermore, this fragment originated from the coding region of the putative DNA helicase gene. Cotransfection of AcNPV DNA with BmScH also generated a host range-expanded virus, eh2-AcNPV. These results indicated that the expanded host range characteristics of eh2-AcNPV were solely the result of recombination within the coding region of the putative DNA helicase gene.
Risk Factors for Cervical Precancer and Cancer in HIV-Infected, HPV-Positive Rwandan Women

Background Although cervical cancer is an AIDS-defining condition, infection with human immunodeficiency virus (HIV) may only modestly increase the risk of cervical cancer. There is a paucity of information regarding factors that influence the natural history of human papillomavirus (HPV) in HIV-infected women. We examined factors associated with cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) in Rwandan women infected with both HIV and HPV (HIV+/HPV+). Methods In 2005, 710 HIV+ Rwandan women ≥25 years enrolled in an observational cohort study; 476 (67%) tested HPV+. Each woman provided sociodemographic data, CD4 count, a cervical cytology specimen and cervicovaginal lavage (CVL), which was tested for >40 HPV genotypes by MY09/MY11 PCR assay. Logistic regression models calculated odds ratios (OR) and 95% confidence intervals (CI) of associations of potential risk factors for CIN3+ among HIV+/HPV+ women. Results Of the 476 HIV+/HPV+ women 42 (8.8%) were diagnosed with CIN3+. Factors associated with CIN3+ included ≥7 (vs. 0-2) pregnancies, malarial infection in the previous six months (vs. never), and ≥7 (vs. 0-2) lifetime sexual partners. Compared to women infected by non-HPV16 carcinogenic HPV genotypes, HPV16 infection was positively associated and non-carcinogenic HPV infection was inversely associated with CIN3+. CD4 count was significantly associated with CIN3+ only in analyses of women with non-HPV16 carcinogenic HPV (OR = 0.62 per 100 cells/mm3, CI = 0.40-0.97). Conclusions In this HIV+/HPV+ population, lower CD4 was significantly associated with CIN3+ only in women infected with carcinogenic non-HPV16. We found a trend for higher risk of CIN3+ in HIV+ women reporting recent malarial infection; this association should be investigated in a larger group of HIV+/HPV+ women.
Predicting Incentives to Change Among Adolescents with Substance Abuse Disorder

While interest in understanding the incentives to change amongindividuals with substance abuse disorders is growing, little is knownabout incentives among adolescents with substance abuse disorders whoare participating in formal services. The present research assesses thedegree and nature of motivation and treatment readiness amongadolescents admitted to substance abuse services, and whether suchfactors vary across significant subgroups of youth based on their social,legal, or clinical profiles. Data are based on interviews with 249 youthbetween 12 and 18 years of age who have been admitted to eitherinpatient, residential, or outpatient substance abuse treatment. Measuresare adapted from an instrument developed to assess multiple domains ofmotivation to change (e.g., intrinsic and extrinsic motivation, treatmentreadiness). Results suggest that the incentive to change amongadolescents with substance‐abusing behavior is modest at best,regardless of dimension. Nonetheless, ethnicity, type of substance use,and psychopathology significantly predict incentives to change, thoughthe predictors depend on which dimension is considered. The mostrobust predictor of incentives is the severity of negative consequencesassociated with youth's substance use—the greater the severity, thegreater the incentives. Findings underscore the need to examine theutility and dimensionality of incentive for treatment planning, while atthe same time, they identify factors that treatment planners can consideras they seek ways to enhance incentives and help adolescents withsubstance use disorders attain positive outcomes.
Change of shape due to dislocation climb

Abstract Abstract The geometry of the deformation produced by the climb of edge dislocations is defined and the conditions are determined under which dislocation climb, by itself or in conjunction with glide, can produce a general change of shape. The results are important in understanding the high-temperature deformation (T > 0.5Tm) of single crystals and polycrystals of materials with fewer than five independent slip systems. Some of these are discussed in detail. In particular the high-temperature creep of sapphire single crystals pulled parallel to (0001) is shown to be quantitatively consistent with Nabarro (Phil. Mag., 16, 231, 1967) creep by climbing dislocations.
Retrograde transport from the Golgi complex to the ER of both Shiga toxin and the nontoxic Shiga B-fragment is regulated by butyric acid and cAMP

Endocytosed Shiga toxin is transported from the Golgi complex to the endoplasmic reticulum in butyric acid-treated A431 cells. We here examine the extent of this retrograde transport and its regulation. The short B fragment of Shiga toxin is sufficient for transport to the ER. The B fragment of cholera toxin, which also binds to glycolipids, is transported to all the Golgi cisterns, but cannot be localized in the ER even after butyric acid treatment. Under all conditions the toxic protein ricin was found predominantly in the trans-Golgi network. There is no transport of endocytosed fluid to the Golgi apparatus or to the ER even after butyric acid treatment and in the presence of Shiga toxin, indicating that transport to the ER, through the trans-Golgi network and the cisterns of the Golgi apparatus, involves several sorting stations. Since Shiga toxin receptors (Gb3) in butyric acid- treated A431 cells seem to have a ceramide moiety with longer fatty acids than in untreated cells, the possibility exists that fatty acid composition of the receptor is important for sorting to the ER. Both retrograde transport and intoxication with Shiga toxin can also be induced by cAMP, supporting the idea that retrograde transport from the Golgi to the ER is required for intoxication. The data suggest that transport to the ER in cells in situ may depend on fatty acid composition and is regulated by physiological signals.
Amelogenins promote an alternatively activated macrophage phenotype in vitro

Amelogenins are extracellular matrix proteins used for the topical treatment of chronically inflamed tissues. The influence of amelogenins on human monocyte-derived macrophages was studied by measuring the concentrations of cytokines in culture supernatants. The interactions of cells and protein aggregates were visualised by transmission electron microscopy. The amelogenin treatment of macrophages increased several pro- and anti-inflammatory cytokines, including alternative macrophage activation marker AMAC-1 (p < 0.001) and vascular endothelial growth factor (VEGF; p < 0.001). The levels were independent of cytochalasin B, although amelogenin aggregates were ingested by macrophages. Amelogenin effect was compared with that of tyrosine-rich amelogenin peptide, which apart from augmented VEGF levels (p < 0.05), had no significant influence on the other cytokines analysed. In conclusion, amelogenins increased the macrophage release of key cell mediators involved in tissue repair. The effect was independent of phagocytosis, implying a receptor-mediated signal. The markedly increased levels of AMAC-1 suggest that amelogenins promote a reparative macrophage phenotype.
Neuromuscular treatments for speech and swallowing: a tutorial.

Despite the proliferation of oral motor therapies, much controversy exists regarding the application and benefit of neuromuscular treatments (NMTs) such as strength training for alleviating dysarthria and/or dysphagia. Not only is limited empirical support available to validate the use of NMTs, but clinicians may also lack the foundational information needed to judge the theoretical soundness of unstudied treatment strategies. This tutorial reviews the theoretical foundations for several NMTs, including active exercises, passive exercises, and physical modalities. It highlights how these techniques have been used to address neuromuscular impairments in the limb musculature and explores potential applications to the speech and swallowing musculature. Key issues discussed in relation to active exercise are the selection of treatment targets (e.g., strength, endurance, power, range of motion), specificity of training, progression, and recovery. Factors influencing the potential effectiveness of passive exercises and physical modalities are presented, along with discussion of additional issues contributing to the controversy surrounding oral motor therapies.
Evidence for the Involvement of RhoA Signaling in the Ethanol-Induced Increase in Intestinal Epithelial Barrier Permeability

In this work, we investigated the potential role of the small G protein RhoA in ethanol-induced tight junction (TJ) protein disassembly and increased intestinal epithelial barrier (IEB) permeability. Our study used Caco-2 cells as an in vitro IEB model and RhoA short hairpin RNA (shRNA) interference to establish whether RhoA plays a role in ethanol-induced TJ opening. RhoA shRNA interference partially inhibited epithelial leakage and restored normal transepithelial electrical resistance (TEER) values in the IEB. Moreover, RhoA shRNA interference prevented a shift in occludin distribution from insoluble to soluble fractions. Additionally, RhoA shRNA interference inhibited the ethanol-induced expression of zonula occludens-1 (ZO-1). Finally, RhoA shRNA interference inhibited an ethanol-induced increase in RhoA activity. The contributions of RhoA to an ethanol-induced increase in IEB permeability are associated with TJ disassembly.
Association between neutrophilic airway inflammation and airflow limitation in adults with asthma.

BACKGROUND There is debate about the mechanisms of persistent airflow limitation in patients with asthma. Chronic inflammation is assumed to be important, although there is limited and contradictory information about the relationship between airway inflammation and postbronchodilator FEV1. METHODS We have assessed the cross-sectional relationship between prebronchodilator and postbronchodilator FEV1 and measures of airway inflammation after allowing for the effects of potential confounding factors. Multivariate analysis was performed on data collected from 1,197 consecutive patients with asthma seen at the respiratory outpatient clinic at Glenfield Hospital between 1997 and 2004. Relationships between induced sputum total neutrophil and differential eosinophil cell counts, and prebronchodilator and postbronchodilator lung function were examined. RESULTS Sputum total neutrophil but not differential eosinophil count was associated with lower postbronchodilator FEV1. Both differential eosinophil and total neutrophil count were associated with lower prebronchodilator FEV1. These effects were independent after adjustment for age, smoking, ethnicity, asthma duration, and inhaled corticosteroid use. A 10-fold increase in neutrophil count was associated with a 92 mL reduction (95% confidence interval, 29 to 158; p = 0.007) in postbronchodilator FEV1. CONCLUSIONS In this large heterogeneous population of adults with asthma, we have shown that prebronchodilator FEV1 is associated with neutrophilic and eosinophilic airway inflammation, whereas sputum total neutrophil counts alone are associated with postbronchodilator FEV1. This supports the hypothesis that neutrophilic airway inflammation has a role in the progression of persistent airflow limitation in asthma and raises the possibility that this progression and the development of COPD share a common mechanism.
present in TALs , where they seem to be involved in NKCC 2 trafficking and NaCl absorption

Ortiz, Pablo A. cAMP increases surface expression of NKCC2 in rat thick ascending limbs: role of VAMP. Am J Physiol Renal Physiol 290: F608 –F616, 2006. First published September 6, 2005; doi:10.1152/ajprenal.00248. 2005. —NaCl absorption by the thick ascending limb of Henle’s loop (TAL) is mediated by the apical Na-K-2Cl cotransporter NKCC2. cAMP increases NaCl absorption in the TAL by stimulating NKCC2. In oocytes, cAMP increases NKCC2 activity by regulating its trafficking. However, the mechanism by which cAMP stimulates NKCC2 in TALs is not clear. We hypothesized that cAMP increases surface expression of NKCC2 and NaCl absorption in TALs and that vesicle-associated membrane protein (VAMP) is involved in this mechanism. We used surface biotinylation of rat medullary TALs (mTAL) to examine surface and total NKCC2 levels. When mTAL suspensions were treated with dibutyryl cAMP (db-cAMP) or forskolin plus IBMX for 20 min, surface NKCC2 expression increased by 126 23 and 92 17% above basal, respectively (P 0.03). No changes in total NKCC2 expression were observed, suggesting that cAMP increased translocation of NKCC2. We studied the role of VAMP in NKCC2 translocation and found that incubating mTALs with tetanus toxin (30 nM), which inhibits vesicle trafficking by inactivating VAMP-2 and -3, completely blocked the stimulatory effect of db-cAMP on surface NKCC2 expression (tetanus toxin 100% vs. tetanus toxin db-cAMP 102 21% of control; not significant). We studied VAMP-2 and -3 expression and localization in isolated perfused TALs by confocal microscopy and found that both of them were located in the subapical space of the TAL. Finally, in isolated perfused mTALs, db-cAMP increased net Cl absorption by 95.0 34.8% (P 0.03), and pretreatment of TALs with tetanus toxin blocked the stimulation of Cl absorption (from 110.9 15.9 to 109.7 15.6 pmol min 1 mm ; not significant). We concluded that cAMP increases NKCC2 surface expression by a mechanism involving VAMP and that NKCC2 trafficking to the apical membrane is involved in the stimulation of TAL NaCl absorption by cAMP.
Peroxisome Proliferator Activator Receptor (PPAR)-γ Ligand, but Not PPAR-α, Ameliorates Cyclophosphamide-Induced Oxidative Stress and Inflammation in Rat Liver

Hepatoprotective potential of peroxisome proliferator activator receptor (PPAR)-α and -γ agonists, fenofibrate (FEN), and pioglitazone (PIO), respectively, against cyclophosphamide (CP)-induced toxicity has been investigated in rat. FEN and PIO (150 and 10 mg/kg/day, resp.) were given orally for 4 weeks. In separate groups, CP (150 mg/kg, i.p.) was injected as a single dose 5 days before the end of experiment, with or without either PPAR agonist. CP induced hepatotoxicity, as it caused histopathological alterations, with increased serum alanine and aspartate transaminases, total bilirubin, albumin, alkaline phosphatase and lactate dehydrogenase. CP caused hepatic oxidative stress, indicated by decrease in tissue reduced glutathione, with increase in malondialdehyde and nitric oxide levels. CP also caused decrease in hepatic antioxidant enzyme levels, including catalase, superoxide dismutase, glutathione peroxidase, and glutathione S-transferase. Furthermore, CP increased serum and hepatic levels of the inflammatory marker tumor necrosis factor (TNF)-α, evaluated using ELISA. Preadministration of PIO, but not FEN, prior to CP challenge improved hepatic function and histology, and significantly reversed oxidative and inflammatory parameters. In conclusion, activation of PPAR-γ, but not PPAR-α, conferred protection against CP-induced hepatotoxicity, via activation of antioxidant and anti-inflammatory mechanisms, and may serve as supplement during CP chemotherapy.
The effect of Nd:YAG laser treatment of posterior capsule opacification on anterior chamber depth and refraction in pseudophakic eyes

Purpose This was a prospective descriptive study to determine the changes in intraocular lens (IOL) position after neodymium-doped yttrium–aluminum–garnet (Nd:YAG) laser posterior capsulotomy by measuring anterior chamber depth (ACD) and refraction, including the spherical equivalent (SE) and cylinder. Materials and methods Forty-seven pseudophakic eyes with posterior capsule opacification of 29 patients were included. Nd:YAG laser posterior capsulotomy was performed. Patients’ ACD and refraction were measured before the treatment, as well as after the treatment at 1 week and 3 months. IOLMaster® and an automated refractometer were used at the Department of Ophthalmology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Results There were no statistically significant differences in ACD and SE before and after laser treatment at 1 week and 3 months (repeated analysis of variance, P=0.582 and P=0.269, respectively). Both backward IOL movement (number [n]=29) and forward IOL movement (n=18) were found. Some changes in cylindrical refraction were found at 1 week, but decreased at 3 months after capsulotomy (baseline cylinder: −1.16; cylinder at 1 week and 3 months: −1.00 and −1.14, respectively; P=0.012). These changes were the same with one-piece and three-piece IOLs. Conclusion Nd:YAG laser posterior capsulotomy did not significantly change ACD and SE. It led to cylinder change at 1 week after laser, but the effect decreased at 3 months. This effect was small and may not be clinically significant.
Emotional face recognition deficit in amnestic patients with mild cognitive impairment: behavioral and electrophysiological evidence

Amnestic mild cognitive impairment (MCI) has been conceptualized as a transitional stage between healthy aging and Alzheimer’s disease. Thus, understanding emotional face recognition deficit in patients with amnestic MCI could be useful in determining progression of amnestic MCI. The purpose of this study was to investigate the features of emotional face processing in amnestic MCI by using event-related potentials (ERPs). Patients with amnestic MCI and healthy controls performed a face recognition task, giving old/new responses to previously studied and novel faces with different emotional messages as the stimulus material. Using the learning-recognition paradigm, the experiments were divided into two steps, ie, a learning phase and a test phase. ERPs were analyzed on electroencephalographic recordings. The behavior data indicated high emotion classification accuracy for patients with amnestic MCI and for healthy controls. The mean percentage of correct classifications was 81.19% for patients with amnestic MCI and 96.46% for controls. Our ERP data suggest that patients with amnestic MCI were still be able to undertake personalizing processing for negative faces, but not for neutral or positive faces, in the early frontal processing stage. In the early time window, no differences in frontal old/new effect were found between patients with amnestic MCI and normal controls. However, in the late time window, the three types of stimuli did not elicit any old/new parietal effects in patients with amnestic MCI, suggesting their recollection was impaired. This impairment may be closely associated with amnestic MCI disease. We conclude from our data that face recognition processing and emotional memory is impaired in patients with amnestic MCI. Such damage mainly occurred in the early coding stages. In addition, we found that patients with amnestic MCI had difficulty in post-processing of positive and neutral facial emotions.