Miracle-dz/UniFAR-FTUs huggingface dataset:
Permeation of Biopolymers Across the Cell Membrane: A Computational Comparative Study on Polylactic Acid and Polyhydroxyalkanoate

Polymeric nanoparticles, which by virtue of their size (1–1000 nm) are able to penetrate even into cells, are attracting increasing interest in the emerging field of nanomedicine, as devices for, e.g., drugs or vaccines delivery. Because of the involved dimensional scale in the nanoparticle/cell membrane interactions, modeling approaches at molecular level are the natural choice in order to understand the impact of nanoparticle formulation on cellular uptake mechanisms. In this work, the passive permeation across cell membrane of oligomers made of two employed polymers in the biomedical field [poly-D,L-lactic acid (PDLA) and poly(3-hydroxydecanoate) (P3HD)] is investigated at fundamental atomic scale through molecular dynamics simulations. The free energy profile related to membrane crossing is computed adopting umbrella sampling. Passive permeation is also investigated using a coarse-grained model with MARTINI force field, adopting well-tempered metadynamics. Simulation results showed that P3HD permeation is favored with respect to PDLA by virtue of its higher hydrophobicity. The free energy profiles obtained at full atomistic and coarse-grained scale are in good agreement each for P3HD, while only a qualitative agreement was obtained for PDLA. Results suggest that a reparameterization of non-bonded interactions of the adopted MARTINI beads for the oligomer is needed in order to obtain a better agreement with more accurate simulations at atomic scale.
The immunohistochemical composition of corneal basement membrane in keratoconus.

PURPOSE Keratoconus is a gradually progressing disease of unknown cause, characterized by central thinning, increased curvature, and finally scarring of the cornea. This causes myopia and astigmatism and the ultimate treatment is keratoplasty. We studied the composition of basement membranes (BMs) in normal, scarred and keratoconus corneas to find out possible changes specific for keratoconus. METHODS Frozen sections of normal, scarred and keratoconus corneas were immunostained with various antibodies against basement membrane (BM) proteins and integrin beta 4. RESULTS In the keratoconus corneas, we found discontinuities or defects in Bowman's layer, sometimes distorted stroma beneath the defects, and also thinning of the stroma. The results show that within the defects in keratoconus corneas, there is an expression of proteins that are not normally present in the corneal BM, i.e. collagen alpha 1/2 (IV) chains, and on the contrary, absence of the expression of some proteins, i.e. collagen alpha 5-6 (IV) chains that normally are continuously expressed in the corneal epithelial BM. In addition, either increased or decreased expression of laminin-1 (alpha 1 beta 1 gamma 1), laminin-5 (alpha 3 beta 3 gamma 2) and collagen type VII, depending on the keratoconus defect, was seen and the expression of integrin beta 4 was decreased. These findings seem to be specific for keratoconus, as they were not found in scarred corneas. CONCLUSIONS The results show that the defects in BM and changes in the BM composition are involved in the pathogenesis of keratoconus. Furthermore, it seems that scarring alone does not explain the breaks in Bowman's layer and immunohistochemical changes seen in keratoconus. Therefore, we suggest that a process similar to wound healing, which is initiated by breaks in Bowman's layer, would largely contribute to the differences seen in keratoconus corneas.
Hepatitis C virus infection and genotypes among human immunodeficiency virus high‐risk groups in Cameroon

Parenteral transmission of HCV is well established but other possible routes such as heterosexual transmission are still questioned. The Central African region is characterised by a high HCV endemicity without any evidence on the route of transmission. The information on HCV genotypes that circulate in this area is also limited and controversial. HIV infection is very frequent in this region and mostly acquired via the heterosexual route. The aim of this work was to investigate the trend of HCV infection and genotypes among HIV high‐risk groups from Cameroon. Four hundred eighty‐two patients including 229 tuberculosis clinic attendants, 184 sexually transmitted disease clinic attendants, and 69 HIV clinical suspects from another clinic were enrolled. All plasma samples were screened for antibodies to HCV and HCV RNA. Genotypes were assigned by sequencing a 5′UTR amplified fragment. The overall prevalence of HCV markers was 11.6% and a significant increasing trend with respect to age was observed. A proportion of 64.1% (34/53) of HCV antibody positive samples was viraemic. HCV RNA was found in 3 samples that were indeterminate in RIBA 3.0. One was negative in the antibody screening test and the two others were weakly positive. The data on HCV genotypes revealed that genotype 1 was involved in 57% of viraemias, genotype 2 in 24%, while genotypes 4 and 5a accounted for 16 and 3%, respectively. In contrary to the predominance of genotype 4 reported in some African countries and even the neighbouring countries, these data demonstrate clearly that HCV infection in Cameroon is dominated by genotypes 1 and 2. No association was found between the HCV markers and the presence of HIV infection. It is concluded, therefore, that the heterosexual route plays a minor role in HCV transmission in this country. J. Med. Virol. 66:179–186, 2002. © 2002 Wiley‐Liss, Inc.
[Uveitis and idiopathic juvenile arthritis in Spain. Epidemiological and therapeutic aspects].

PURPOSE The purpose of this paper is to describe the frequency and characteristics of uveitis associated with juvenile idiopathic arthritis at a tertiary referral centre in Spain. METHODS Review of clinical records. 205 children diagnosed with chronic juvenile arthritis over the last 15 years, of whom 26 presented anterior uveitis. Patients were classified according to their pattern of evolution, the time the uveitis was diagnosed with respect to the onset of arthritis, and the severity of uveitis at diagnosis. RESULTS The prevalence of uveitis was 12.7%. Of the patients affected with uveitis 71% were girls. The average age at which the arthritis was diagnosed was significantly earlier in the group of patients who developed uveitis (4.06 years). No differences were observed in the incidence of uveitis in girls and boys, nor in pauci/polyarticular affectation. ANA positivity was found in 84.6% of the uveitis-affected patients, this being significantly different to the ANA- group. The average age at which uveitis was diagnosed is 5.87 years. 48.1% of uveitis patients develop uveitis within 12 months of the onset of arthritis. This group presented more complications during the evolution of the condition. A total of 84.7% of the uveitis-affected patients presented with a final visual acuity of >0.5 during the observation period. CONCLUSIONS In our study, the development of uveitis was significantly associated with an earlier age of diagnosis of the arthritis and with the presence of ANA positivity. No differences were observed between boys and girls, or between pauci and polyarticular groups. A greater prevalence of complications was observed in cases presenting with a shorter time interval between the diagnosis of arthritis and uveitis and in those that presented with complications on diagnosis.
TNFα Potently Activates Osteoclasts, through a Direct Action Independent of and Strongly Synergistic with RANKL.

TNFalpha is pivotal to the pathogenesis of inflammatory and possibly postmenopausal osteolysis. Much recent work has clarified mechanisms by which TNFalpha promotes osteoclastogenesis, but the means by which it activates osteoclasts to resorb bone remain uncertain. We found that very low concentrations of TNFalpha promoted actin ring formation, which correlates with functional activation in osteoclasts, both in osteoclasts formed in vitro and extracted from newborn rats. TNFalpha was equipotent with RANKL for this action. Activation by TNFalpha was unaffected by blockade of RANKL by OPG, its soluble decoy receptor, suggesting that this was due to a direct action on osteoclasts. Bone resorption was similarly directly and potently stimulated, in a RANKL-independent manner in osteoclasts, whether these were formed in vitro or in vivo. Interestingly, TNFalpha promoted actin ring formation at concentrations an order of magnitude below those required for osteoclastic differentiation. Moreover, TNFalpha strongly synergized with RANKL, such that miniscule concentrations of TNFalpha were sufficient to substantially augment osteoclast activation. The extreme sensitivity of osteoclasts to activation by TNFalpha suggests that the most sensitive osteolytic response of bone to TNFalpha is through activation of existing osteoclasts; and the strong synergy with RANKL provides a mechanism whereby increased osteolysis can be achieved without disturbance to the underlying pattern of osteoclastic localization.
Which cues are credible? – The relative importance and interaction of expertise, likes, shares, pictures and involvement while assessing the credibility of politicians’ Facebook postings

In recent years social media channels have become increasingly powerful tools for any kind of communication. Nowadays even political information and news are often solely consumed on social media. Besides the promising opportunities of direct interaction and real-time updates, the lack of gate keepers raises credibility concerns. Therefore, it is crucial to better understand how recipients assess if a message is believable or not. Approaches like the MAIN Model [26] and the Rule Concept [12] claim that source, message or meta-informational cues are able to serve as anchors for evaluations. Aiming to comprehensively investigate the role and interplay of cues available in social media communication, an online experiment (N = 341; 1366 postings) tested the impact of source expertise, likes, shares, pictures and topic involvement on evaluations of politicians’ Facebook postings. Results revealed source cues to lead to higher credibility judgments, whereas higher likes and shares unexpectedly decreased credibility. Against expectations, recipients’ involvement and message agreement did not moderate the effects.
Do Financial Remittancces Build Household-Level Adaptive Capacity? A Case Study of Flood-Affected Households in India

This paper examines the role of financial remittances on the adaptive capacity of households in floodaffected rural communities of Upper Assam in India. Findings reveal that remittances-receiving households are likely to have better access to formal financial institutions, insurance and communication devices than nonrecipient households. This study indicates that the duration for which remittances are received by a household has a significant and positive association with structural changes made by the household to address flood impacts, farm mechanization, the household’s access to borrowing, and participation in collective action on flood relief, recovery and preparedness. The adaptation potential of remittances of remittances can be realized if policy attention is given to attempts to enable gains in financial capital to be translated to gains in other types of capital and how the social element of remittances can be used to boost social capital. For example, by facilitating an increase in financial literacy and skills training, particularly among the poorer households in areas likely to be affected by the impacts of climate change and variability.
Resolution in PET hypoxia imaging: Voxel size matters

Introduction. Tumor hypoxia adversely affects treatment outcome, especially in squamous cell carcinomas (SCCs). Image guided radiotherapy (IGRT) based on PET-generated tumor hypoxia maps allows dose boosting to hypoxic sub-volumes and has received considerable interest. However, the combination of slow oxygenation-dependent tracer retention, slow clearance of unbound tracer from non-hypoxic tissue and the necessity to average signal over large non-homogenous tissue areas due to the low PET resolution remains problematic. Materials and Methods. To assess pitfalls inherent to low-resolution imaging we have analyzed the fine-scale distribution of a PET hypoxia tracer (autoradiograms) and tissue architecture (immunofluorecence microscopy) in sectioned experimental SCCs, and compared the results to those obtained when applying macroscopic averaging mimicking the resolution in clinical PET scanners. Results and Discussion. We show that tumor areas that would be classified as non-hypoxic based on simple PET threshold identification, often contains foci of hypoxic cells, in particular in tumors where necrosis and severely hypoxic cells are intermixed. In contrast, in a non-necrotic tumor model we found that the risk of missing hypoxic cells was greatly reduced, however, its patchy hypoxic pattern made a clear delineation of a target to boost unfeasible. We discuss the implications of these and other complicating factors in PET hypoxia-imaging and outline future strategies to overcome or circumvent them.
Evaluation of serum squamous cell carcinoma antigen as a novel biomarker for diagnosis of hepatocellular carcinoma in Egyptian patients.

BACKGROUND Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world. In Egypt, HCC was reported to account for about 4.7% of chronic liver disease (CLD) patients. Squamous cell carcinoma antigen (SCCA) has been reported to be strongly expressed in HCC tissue hampering its extensive use in clinical practice. AIM To evaluate the clinical usefulness of serum SCCA levels as a serological marker for early detection of HCC among high-risk patients compared to AFP. MATERIALS AND METHODS The study comprised of three groups. Group A included 30 patients with CLD diagnosed based on clinical, laboratory, and ultrasonographical investigations; group B included 49 patients with HCC diagnostically confirmed by spiral CT, elevated alfafetoprotein (AFP), and/or liver biopsy; and group C, the control group, included 15 healthy subjects matched for age and sex. All groups were subjected to thorough history taking, full clinical examination, and laboratory investigations including liver functions, viral markers, and AFP and SCCA estimation using ELISA technique. RESULTS This study revealed a highly significant difference between patients with HCC, CLD, and controls regarding serum SCCA levels (5.138 +/- 7.689, 1.133 +/- 0.516, and 0.787 +/- 0.432 ng/ml, respectively). SCCA level was persistently elevated in patients with HCC with normal AFP levels representing its useful role in early detection and follow-up of patients treated for HCC. The area under the curve (AUC) of SCCA was 0.869 (95% CI 0.783-0.929), the cut-off value was established at 1.5 ng/ml with sensitivity of 77.6% and specificity of 84.4%). The difference between AUC of SCCA and that of AFP was 0.09 which mounted statistical significance. CONCLUSIONS SCCA could represent a useful tool as a marker for detection of HCC.
Strategic Corporate Layoffs

Firms in the S&P 500 often announce layoffs within days of one another, despite the fact that the average S&P 500 constituent announces layoffs once every 5 years. By contrast, similarsized privately-held firms do not behave in this way. This paper provides empirical evidence that such clustering behavior is largely due to CEOs managing their reputation in financial markets. To interpret these results we develop a theoretical framework in which managers delay layoffs during good economic states to avoid damaging the markets perception of their ability. The model predicts clustering in the timing of layoff announcements, and illustrates a mechanism through which the cyclicality of firms layoff policies is amplified. Our findings suggest that reputation management is an important driver of layoff policies both at daily frequencies and over the business cycle, and can have significant macroeconomic consequences.
Study of Spectral-Domain Optical Coherence Tomography in Children: Normal Values and Influence of Age, Sex, and Refractive Status

Purpose To establish normal values for retinal nerve fiber layer (RNFL), macular thickness, and macular volume in children using spectral-domain optical coherence tomography (OCT). Methods A descriptive cross-sectional study was performed in healthy children between 3 and 14 years of age. Each child underwent a comprehensive ophthalmic examination that included 3 OCT scans with Spectralis (Heidelberg Engineering, Heidelberg, Germany). All measurements were performed by the same operator, and one eye was randomly selected. The influence of age, sex, and refraction on OCT measurements was analyzed. Results The sample consisted of 162 Caucasian subjects, mean age 8.1 ± 3.03 years. The spherical equivalent was 0.03 ± 0.19 D (range ±4 D, astigmatism <1 D). The average values were 263.69 ± 4.54 µm for central macular thickness, 0.21 ± 0.01 mm3 for central macular volume, and 100.45 ± 1.98 µm for RNFL. A significant correlation between RNFL and spherical equivalent was found for the nasal (p = 0.001), inferior (p = 0.009), and inferior nasal (p = 0.005) sectors. No differences were found with regard to sex (p>0.05). However, central macular thickness and central macular volume were correlated with age (p = 0.027, p = 0.02). Conclusions This study provides reference values for macular thickness, macular volume, and RNFL in healthy children.
Transmitter Glutamate Release from Isolated Nerve Terminals: Evidence for Biphasic Release and Triggering by Localized Ca2+

Abstract: The kinetics of Ca2+‐dependent release of glutamate from guinea‐pig cerebrocortical synaptosomes evoked by KCl or 4‐aminopyridine are investigated using a continuous flu‐orimetric assay. Release by both agents is biphasic, with a rapid phase complete within 2 s followed by a more extensive slow phase with a half‐maximal release in 52 s for KCl‐evoked release and > 120 s for 4‐aminopyridine‐evoked release. The two phases ofglutamate release may reflect a dual localization of releasable vesicles at the active zone and in the bulk cytoplasm. Decreasing depolarization depresses the extent rather than increasing the time for half‐maximal Ca2+‐dependent release. Both the fast and the slow phases of glutamate release require external Ca2+ and cytoplasmic ATP. KCl depolarization produces a transient “spike”of cytoplasmic free Ca2+ ([Ca2+]c), which recovers to a plateau; the major component of glutamate release occurs during this plateau. Predepolarization in the absence of added external Ca2+, to inhibit transient Ca2+ channels, does not affect the subsequent glutamate release evoked by Ca2+ readdition. Thus, release involves primarily noninactivating Ca2+ channels. For a given increase in [Ca2+]c, KCl and 4‐aminopyridine cause equal release of glutamate, while ionomycin releases much less glutamate. This lowered efficiency is not due to ATP depletion. It is concluded that glutamate exocytosis is evoked by localized Ca2+ entering through noninactivating voltage‐dependent Ca2+ channels and that nonlocalized Ca2+ entry with ionomycin is inefficient.
Global link arrangement for practical Dragonfly

The Dragonfly network organizes routers into groups, with connectivity within each group provided by local links and connectivity between groups provided by global links. The specification of Dragonfly leaves many options for arranging global links. In this work, we study global link arrangement for practical Dragonfly topologies where (1) there are multiple global links connecting each pair of groups, and (2) the global link bandwidth is similar to the local link bandwidth. We found that existing global link arrangement schemes such as the absolute, relative and circulant-based arrangements do not specify an important component in global connectivity for practical Dragonfly, which we call per-router arrangement. Per-router arrangement determines how the global links from each individual router are connected. We integrate per-router arrangement into existing schemes, develop a unified algorithm to compute a large class of global link arrangements for practical Dragonfly, and carry out an extensive simulation study to evaluate different global link arrangement schemes. Our results indicate that the existing understanding of the global link arrangement does not apply to practical Dragonfly: contradict to the existing understanding that global link arrangement does not make significant difference in performance when global links have similar bandwidth as local links, per-router arrangement significantly impacts the network performance of practical Dragonfly. We identify the schemes that yield high performance for practical Dragonfly.
Functional Near-Infrared Spectroscopy Indicates That Asymmetric Right Hemispheric Activation in Mental Rotation of a Jigsaw Puzzle Decreases With Task Difficulty

Mental rotation (MR) is a cognitive skill whose neural dynamics are still a matter of debate as previous neuroimaging studies have produced controversial results. In order to investigate the underlying neurophysiology of MR, hemodynamic responses from the prefrontal cortex of 14 healthy subjects were recorded with functional near-infrared spectroscopy (fNIRS) during a novel MR task that had three categorical difficulty levels. Hemodynamic activity strength (HAS) parameter, which reflects the ratio of brain activation during the task to the baseline activation level, was used to assess the prefrontal cortex activation localization and strength. Behavioral data indicated that the MR requiring conditions are more difficult than the condition that did not require MR. The right dorsolateral prefrontal cortex (DLPFC) was found to be active in all conditions and to be the dominant region in the easiest task while more complex tasks showed widespread bilateral prefrontal activation. A significant increase in left DLPFC activation was observed with increasing task difficulty. Significantly higher right DLPFC activation was observed when the incongruent trials were contrasted against the congruent trials, which implied the possibility of a robust error or conflict-monitoring process during the incongruent trials. Our results showed that the right DLPFC is a core region for the processing of MR tasks regardless of the task complexity and that the left DLPFC is involved to a greater extent with increasing task complexity, which is consistent with the previous neuroimaging literature.
On the elicitation of indirect preferences in interactive evolutionary multiple objective optimization

We consider essential challenges related to the elicitation of indirect preference information in interactive evolutionary algorithms for multiple objective optimization. The methods in this stream use holistic judgments provided by the Decision Maker (DM) to progressively bias the evolutionary search toward his/her most preferred region in the Pareto front. We enhance such an interactive process using three targeted developments and illustrate their efficiency in the context of a decomposition-based evolutionary framework. Firstly, we present some active learning strategies for selecting solutions from the current population that should be critically compared by the DM. These strategies implement the paradigm of maximizing the potential information gain derived from the DM's answer. Secondly, we discuss the procedures for deciding when the DM should be questioned for preference information. In this way, we refer to a more general problem of distributing the DM's interactions with the method in a way that ensures sufficient evolutionary pressure. Thirdly, we couple the evolutionary schemes with different types of indirect preferences, including pairwise comparisons, preference intensities, best-of-k judgments, and complete orders of a small subset of solutions. A thorough experimental analysis indicates that the three introduced advancements have a positive impact on the DM-perceived quality of constructed solutions.