Miracle-dz/UniFAR-FTUs huggingface dataset:
Improving drug delivery technology for treating neurodegenerative diseases

ABSTRACT Introduction: Neurodegenerative diseases (NDs) represent intricate challenges for efficient uptake and transport of drugs to the brain mainly due to the restrictive blood-brain barrier (BBB). NDs are characterized by the loss of neuronal subtypes as sporadic and/or familial and several mechanisms of neurodegeneration have been identified. Areas covered: This review attempts to recap, organize and concisely evaluate the advanced drug delivery systems designed for treating common NDs. It highlights key research gaps and opinionates on new neurotherapies to overcome the BBB as an addition to the current treatments of countering oxidative stress, inflammation and apoptotic mechanisms. Expert Opinion: Current treatments do not fully address the biological, drug and therapeutic factors faced. This has led to the development of vogue treatments such as nose-to-brain technologies, bio-engineered systems, fusion protein chaperones, stem cells, gene therapy, use of natural compounds, neuroprotectants and even vaccines. However, failure of these treatments is mainly due to the BBB and non-specific delivery in the brain. In order to increase neuroavailability various advanced drug delivery systems provide promising alternatives that are able to augment the treatment of Alzheimer’s disease and Parkinson’s disease. However, much work is still required in this field beyond the preclinical testing phase.
Estudo de novas ocorrências de argilas plásticas (ball clays) do nordeste do Brasil para uso em cerâmicas refratárias

A regiao nordeste do Brasil possui grandes depositos de argilas plasticas do tipo ball clay situados geralmente na Formacao Barreiras e sao usados em cerâmica branca e materiais refratarios. Essas argilas sao constituidas por caulinitas secundarias e materia orgânica, sendo muito plasticas e quando submetidas a elevadas temperaturas queimam com cores brancas e ocorrem transformacoes de fases, principalmente formacao de cristais de mulita e cristobalita. Este trabalho tem como objetivo estudar novos jazimentos de argilas plasticas visando utiliza-los na producao de materiais refratarios. As argilas foram caracterizadas por difracao a laser, difracao de raios X (DRX), fluorescencia de raios X, refratariedade, analise termica e microscopia eletronica de varredura (MEV). Os corpos de prova foram prensados e sinterizados a 1000, 1150, 1250, 1280 e 1400 °C. A caracterizacao apos queima foi realizada por DRX e MEV. Em seguida foram determinadas as propriedades fisico-mecânicas: absorcao, porosidade e tensao de ruptura a flexao. Os resultados evidenciaram que as argilas apresentaram a formacao de cristais de mulita com propriedades fisicas, quimicas e mineralogicas adequadas para uso em cerâmica refrataria.
Learning with sparsity and uncertainty by Difference of Convex functions optimization. (Apprentissage avec la parcimonie et sur des données incertaines par la programmation DC et DCA)

Dans cette these, nous nous concentrons sur le developpement des methodes d'optimisation pour resoudre certaines classes de problemes d'apprentissage avec la parcimonie et/ou avec l'incertitude des donnees. Nos methodes sont basees sur la programmation DC (Difference of Convex functions) et DCA (DC Algorithms) etant reconnues comme des outils puissants d'optimisation. La these se compose de deux parties : La premiere partie concerne la parcimonie tandis que la deuxieme partie traite l'incertitude des donnees. Dans la premiere partie, une etude approfondie pour la minimisation de la norme zero a ete realisee tant sur le plan theorique qu'algorithmique. Nous considerons une approximation DC commune de la norme zero et developpons quatre algorithmes basees sur la programmation DC et DCA pour resoudre le probleme approche. Nous prouvons que nos algorithmes couvrent tous les algorithmes standards existants dans le domaine. Ensuite, nous etudions le probleme de la factorisation en matrices non-negatives (NMF) et fournissons des algorithmes appropries bases sur la programmation DC et DCA. Nous etudions egalement le probleme de NMF parcimonieuse. Poursuivant cette etude, nous etudions le probleme d'apprentissage de dictionnaire ou la representation parcimonieuse joue un role crucial. Dans la deuxieme partie, nous exploitons la technique d'optimisation robuste pour traiter l'incertitude des donnees pour les deux problemes importants dans l'apprentissage : la selection de variables dans SVM (Support Vector Machines) et le clustering. Differents modeles d'incertitude sont etudies. Les algorithmes bases sur DCA sont developpes pour resoudre ces problemes.
Craving and Acute Effects of Alcohol in Youths’ Daily Lives: Associations With Alcohol Use Disorder Severity

Identifying factors associated with the progression from recreational to pathological drinking in youth holds high clinical and theoretical importance. The present study tested cross-sectional associations of alcohol use disorder (AUD) severity with putative mechanisms of AUD progression among youth ages 15–24 years, namely acute subjective effects of alcohol and craving. Male (n = 44) and female (n = 42) youth completed ecological momentary assessments when not drinking, just before drinking, and while drinking in the natural environment via handheld wireless devices. Youth were recruited from the community and were frequent and heavy drinkers, the majority (93%) with at least 1 AUD symptom (M = 3.4, SD = 2.4). Findings from youths’ daily lives suggested that how youth feel while they drink depends, in part, on their severity of AUD pathology. In support of hypotheses, youths with more progressed drinking pathology (i.e., those with more symptoms of AUD) reported greater reductions in craving and tension while drinking, relative to nondrinking times. In partial support of hypotheses, males with greater AUD symptomatology reported marginally attenuated increases in stimulatory states while drinking; however, contrary to hypotheses, females with greater AUD symptomatology reported enhanced increases in stimulation while drinking. This research leveraged ecological momentary assessment methods to study subjective responses to alcohol and craving in youths’ daily lives and to cross-sectionally test putative associations with AUD etiology. This work adds to literature supporting subjective responses to alcohol in the pathogenesis of alcoholism, specifically by highlighting their importance during the period in life when alcohol problems typically first emerge.
Matching with Text Data: An Experimental Evaluation of Methods for Matching Documents and of Measuring Match Quality

Matching for causal inference is a well-studied problem, but standard methods fail when the units to match are text documents: the high-dimensional and rich nature of the data renders exact matching infeasible, causes propensity scores to produce incomparable matches, and makes assessing match quality difficult. In this paper, we characterize a framework for matching text documents that decomposes existing methods into (1) the choice of text representation and (2) the choice of distance metric. We investigate how different choices within this framework affect both the quantity and quality of matches identified through a systematic multifactor evaluation experiment using human subjects. Altogether, we evaluate over 100 unique text-matching methods along with 5 comparison methods taken from the literature. Our experimental results identify methods that generate matches with higher subjective match quality than current state-of-the-art techniques. We enhance the precision of these results by developing a predictive model to estimate the match quality of pairs of text documents as a function of our various distance scores. This model, which we find successfully mimics human judgment, also allows for approximate and unsupervised evaluation of new procedures in our context. We then employ the identified best method to illustrate the utility of text matching in two applications. First, we engage with a substantive debate in the study of media bias by using text matching to control for topic selection when comparing news articles from thirteen news sources. We then show how conditioning on text data leads to more precise causal inferences in an observational study examining the effects of a medical intervention.
UHRF1 epigenetically down-regulates UbcH8 to inhibit apoptosis in cervical cancer cells

ABSTRACT UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) is an important epigenetic regulator that plays a part in DNA methylation, protein methylation and ubiquitination. It is also frequently overexpressed in many types of cancers, including cervical cancer, which is caused by human papillomavirus (HPV). In this study, we showed that UHRF1 was up-regulated in HPV oncogene E7 expressing cells and HPV-positive cervical cancer cells. We demonstrated that UHRF1 down-regulated the expression of UBE2L6 gene that encodes the ISG15-conjugating enzyme UbcH8. Overexpression of UHRF1 reduced UBE2L6 while knockdown UHRF1 elevated the expression of UBE2L6. We showed that UHRF1 regulated UBE2L6 gene by promoter hypermethylation in cervical cancer cells. Consistent with the functions of UHRF1, restored expression of UbcH8 induced apoptosis. These findings establish UBE2L6 as a novel target of UHRF1 that regulates the apoptosis function of UHRF1. Our studies suggest that UHRF1/ UbcH8 can be manipulated for therapy in cervical cancer.
Serological survey of mumps antibodies in adults in the Czech Republic and the need for changes to the vaccination strategy

ABSTRACT Mumps outbreaks, especially in adolescents and young adults, have been reported in the Czech Republic. The aim of the presented study was to determine the seroprevalence of specific IgG antibodies against mumps in the adult population of the Czech Republic. The study was designed as a multicenter serological survey of adults aged 18 years and over. Specific IgG antibodies against mumps were detected in blood samples using an enzyme-linked immunosorbent assay (ELISA). A total of 1,911 serum samples were examined. The overall seropositivity reached 55.3%. In individual age groups, the highest seropositivity 63% (63.5–65.2%) was recorded in adults aged 40 years and over; the lowest seropositivity was found in adults aged 18–29 years (27.4%). The difference in seropositivity rate between the 18–29 years age group and the 40 years and over age groups was statistically significant (p < 0.001). Only the 18–29 years age group included both vaccinated and unvaccinated (born in the pre-vaccine era) individuals. In vaccinated individuals, seropositivity was reported in only 19.1% of persons; in unvaccinated individuals, seropositivity reached 48.2%. Our results demonstrate the long-term persistence of antibodies following natural infection and the decrease in seropositivity that occurs after vaccination over time. This immunity waning may account for the higher susceptibility of adolescents and young adults to mumps. Therefore, the current vaccination program in the Czech Republic could be considered as less effective. It will be modified with the shifting of the second dose of vaccine from two years of age to the preschool age.
Mineral surfaces and soil organic matter

Summary The organic carbon content of soil is positively related to the specific surface area (SSA), but large amounts of organic matter in soil result in reduced SSA as determined by applying the Brunauer– Emmett–Teller (BET) equation to the adsorption of N2. To elucidate some of the controlling mechanisms of this relation, we determined the SSA and the enthalpy of N2 adsorption of separates with a density > 1.6 g cm � 3 from 196 mineral horizons of forest soils before and after removal of organic matter with NaOCl. Likewise, we investigated these characteristics before and after sorption of increasing amounts of organic matter to four mineral soil samples, oxides (amorphous Al(OH)3, gibbsite, ferrihydrite, goethite, haematite), and phyllosilicates (kaolinite, illite). Sorption of organic matter reduced the SSA, depending on the amount sorbed and the type of mineral. The reduction in SSA decreased at larger organic matter loadings. The SSA of the mineral soils was positively related to the content of Fe oxyhydroxides and negatively related to the content of organic C. The strong reduction in SSA at small loadings was due primarily to the decrease in the micropores to which N2 was accessible. This suggests preferential sorption of organic matter at reactive sites in or at the mouths of micropores during the initial sorption and attachment to less reactive sites at increasing loadings. The exponential decrease of the heat of gas adsorption with the surface loading points also to a filling or clogging of micropores at early stages of organic matter accumulation. Desorption induced a small recovery of the total SSA but not of the micropore surface area. Destruction of organic matter increased the SSA of all soil samples. The SSA of the uncovered mineral matrix related strongly to the amounts of Fe oxyhydroxides and the clay. Normalized to C removed, the increase in SSA was small in topsoils and illuvial horizons of Podzols rich in C and large for the subsoils containing little C. This suggests that micropores preferentially associate with organic matter, especially at small loadings. The coverage of the surface of the soil mineral matrix as calculated from the SSA before and after destruction of organic matter was correlated only with depth, and the relation appeared to be linear. We conclude that mineralogy is the primary control of the relation between surface area and sorption of organic matter within same soil compartments (i.e. horizons). But at the scale of complete profiles, the surface accumulation and stabilization of organic matter is additionally determined by its input.
Stereo Viewing Modulates Three-Dimensional Shape Processing During Object Recognition: A High-Density ERP Study

The role of stereo disparity in the recognition of 3-dimensional (3D) object shape remains an unresolved issue for theoretical models of the human visual system. We examined this issue using high-density (128 channel) recordings of event-related potentials (ERPs). A recognition memory task was used in which observers were trained to recognize a subset of complex, multipart, 3D novel objects under conditions of either (bi-) monocular or stereo viewing. In a subsequent test phase they discriminated previously trained targets from untrained distractor objects that shared either local parts, 3D spatial configuration, or neither dimension, across both previously seen and novel viewpoints. The behavioral data showed a stereo advantage for target recognition at untrained viewpoints. ERPs showed early differential amplitude modulations to shape similarity defined by local part structure and global 3D spatial configuration. This occurred initially during an N1 component around 145–190 ms poststimulus onset, and then subsequently during an N2/P3 component around 260–385 ms poststimulus onset. For mono viewing, amplitude modulation during the N1 was greatest between targets and distracters with different local parts for trained views only. For stereo viewing, amplitude modulation during the N2/P3 was greatest between targets and distracters with different global 3D spatial configurations and generalized across trained and untrained views. The results show that image classification is modulated by stereo information about the local part, and global 3D spatial configuration of object shape. The findings challenge current theoretical models that do not attribute functional significance to stereo input during the computation of 3D object shape.
Molecular Characterization of Host-Specific Biofilm Formation in a Vertebrate Gut Symbiont

Although vertebrates harbor bacterial communities in their gastrointestinal tract whose composition is host-specific, little is known about the mechanisms by which bacterial lineages become selected. The goal of this study was to characterize the ecological processes that mediate host-specificity of the vertebrate gut symbiont Lactobacillus reuteri, and to systematically identify the bacterial factors that are involved. Experiments with monoassociated mice revealed that the ability of L. reuteri to form epithelial biofilms in the mouse forestomach is strictly dependent on the strain's host origin. To unravel the molecular basis for this host-specific biofilm formation, we applied a combination of transcriptome analysis and comparative genomics and identified eleven genes of L. reuteri 100-23 that were predicted to play a role. We then determined expression and importance of these genes during in vivo biofilm formation in monoassociated mice. This analysis revealed that six of the genes were upregulated in vivo, and that genes encoding for proteins involved in epithelial adherence, specialized protein transport, cell aggregation, environmental sensing, and cell lysis contributed to biofilm formation. Inactivation of a serine-rich surface adhesin with a devoted transport system (the SecA2-SecY2 pathway) completely abrogated biofilm formation, indicating that initial adhesion represented the most significant step in biofilm formation, likely conferring host specificity. In summary, this study established that the epithelial selection of bacterial symbionts in the vertebrate gut can be both specific and highly efficient, resulting in biofilms that are exclusively formed by the coevolved strains, and it allowed insight into the bacterial effectors of this process.
Seasonal Effects of Habitat on Sources and Rates of Snowshoe Hare Predation in Alaskan Boreal Forests

Survival and predation of snowshoe hares (Lepus americanus) has been widely studied, yet there has been little quantification of the changes in vulnerability of hares to specific predators that may result from seasonal changes in vegetation and cover. We investigated survival and causes of mortalities of snowshoe hares during the late increase, peak, and decline of a population in interior Alaska. From June 2008 to May 2012, we radio-tagged 288 adult and older juvenile hares in early successional and black spruce (Picea mariana) forests and, using known-fate methods in program MARK, evaluated 85 survival models that included variables for sex, age, and body condition of hares, as well as trapping site, month, season, year, snowfall, snow depth, and air temperature. We compared the models using Akaike’s information criterion with correction for small sample size. Model results indicated that month, capture site, and body condition were the most important variables in explaining survival rates. Survival was highest in July, and more generally during summer, when alternative prey was available to predators of hares. Low survival rates coincided with molting periods, breeding activity in the spring, and the introduction of juveniles to the sample population in the fall. We identified predation as the cause of mortality in 86% of hare deaths. When the source of predation could be determined, hares were killed more often by goshawks (Accipiter gentilis) than other predators in early successional forest (30%), and more often by lynx (Lynx canadensis) than other predators in black spruce forest (31%). Great horned owls (Bubo virginianus) and coyotes (Canis latrans) represented smaller proportions of hare predation, and non-predatory causes were a minor source (3%) of mortality. Because hares rely on vegetative cover for concealment from predators, we measured cover in predation sites and habitats that the hares occupied and concluded that habitat type had a greater influence on the sources of predation than the amount of cover in any given location within a habitat. Our observations illustrate the vulnerability of hares to predators in even the densest coniferous habitat available in the boreal forest, and indicate strong seasonal changes in the rates and sources of predation.
An Investigation of Rotorcraft Stability-Phase Margin Requirements in Hover

A cooperative study was performed to investigate the handling quality effects from reduced flight control system stability margins, and the trade-offs with higher disturbance rejection bandwidth (DRB). The piloted simulation study, performed on the NASA-Ames Vertical Motion Simulator, included three classes of rotorcraft in four configurations: a utility-class helicopter; a medium-lift helicopter evaluated with and without an external slung load; and a large (heavy-lift) civil tiltrotor aircraft. This large aircraft also allowed an initial assessment of ADS-33 handling quality requirements for an aircraft of this size. Ten experimental test pilots representing the U.S. Army, Marine Corps, NASA, rotorcraft industry, and the German Army (WTD 61), evaluated the four aircraft configurations, for a range of flight control stabilitymargins and turbulence levels, while primarily performing the ADS-33 Hover and Lateral Reposition MTEs. Pilot comments and aircraft-task performance data were analyzed. The preliminary stability margin results suggest higher DRB and less phase margin cases are preferred as the aircraft increases in size. Extra care will need to be taken to assess the influence of variability when nominal flight control gains start with reduced margins. Phase margins as low as 20-23 degrees resulted in low disturbanceresponse damping ratios, objectionable oscillations, PIO tendencies, and a perception of an incipient handling qualities cliff. Pilot comments on the disturbance response of the aircraft correlated well to the DRB guidelines provided in the ADS-33 Test Guide. The ADS-33 mid-term response-to-control damping ratio metrics can be measured and applied to the disturbance-response damping ratio. An initial assessment of LCTR yaw bandwidth shows the current Level 1 boundary needs to be relaxed to help account for a large pilot off-set from the c.g. Future efforts should continue to investigate the applicability/refinement of the current ADS-33 requirements to large vehicles, like an LCTR.
Alterations in melatonin and 5‐HT signalling in the colonic mucosa of mice with dextran‐sodium sulfate‐induced colitis

Inflammatory bowel disease (IBD) is characterized by pain, bleeding, cramping and altered gastrointestinal (GI) function. Changes in mucosal 5‐HT (serotonin) signalling occur in animal models of colitis and in humans suffering from IBD. Melatonin is co‐released with 5‐HT from the mucosa and has a wide variety of actions in the GI tract. Here, we examined how melatonin signalling is affected by colitis and determined how this relates to 5‐HT signalling.