Miracle-dz/UniFAR-FTUs huggingface dataset:
Conservation Analysis of Dengue Virus T-cell Epitope-Based Vaccine Candidates Using Peptide Block Entropy

Broad coverage of the pathogen population is particularly important when designing CD8+ T-cell epitope vaccines against viral pathogens. Traditional approaches are based on combinations of highly conserved T-cell epitopes. Peptide block entropy analysis is a novel approach for assembling sets of broadly covering antigens. Since T-cell epitopes are recognized as peptides rather than individual residues, this method is based on calculating the information content of blocks of peptides from a multiple sequence alignment of homologous proteins rather than using the information content of individual residues. The block entropy analysis provides broad coverage of variant antigens. We applied the block entropy analysis method to the proteomes of the four serotypes of dengue virus (DENV) and found 1,551 blocks of 9-mer peptides, which cover 99% of available sequences with five or fewer unique peptides. In contrast, the benchmark study by Khan et al. (2008) resulted in 165 conserved 9-mer peptides. Many of the conserved blocks are located consecutively in the proteins. Connecting these blocks resulted in 78 conserved regions. Of the 1551 blocks of 9-mer peptides 110 comprised predicted HLA binder sets. In total, 457 subunit peptides that encompass the diversity of all sequenced DENV strains of which 333 are T-cell epitope candidates.
Two Cases of Hypophosphatemic Osteomalacia After Long-term Low Dose Adefovir Therapy in Chronic Hepatitis B and Literature Review

Adefovir dipivoxil (ADV) is a nucleotide used as long-term therapy of chronic hepatitis B. Many published reports have shown that long-term high-dose therapy with adefovir can be associated with proximal renal tubular dysfunction resulting in significant hypophosphatemia, renal insufficiency and osteomalacia. We have encountered two patients who developed evidence of hypophosphatemic osteomalacia while on long-term low-dose adefovir therapy for chronic hepatitis B. We report on its clinical features and its potential resolution with cessation of the drug and supplementation with phosphate. We also reviewed the other published cases associated with hypophosphatemic osteomalacia after low-dose adefovir therapy. The symptoms and the hypophosphatemia improved after cessation of the drug and supplementation with phosphate in most cases. Patients taking adefovir long-term should receive regular investigation of the phosphate level and renal function.
Estrone Sulfate Transport and Steroid Sulfatase Activity in Colorectal Cancer: Implications for Hormone Replacement Therapy

Hormone replacement therapy (HRT) affects the incidence and potential progression of colorectal cancer (CRC). As HRT primarily consists of estrone sulfate (E1S), understanding whether this conjugated estrogen is transported and metabolized in CRC will define its potential effect in this malignancy. Here, we show that a panel of CRC cell lines (Colo205, Caco2, HCT116, HT-29) have steroid sulfatase (STS) activity, and thus can hydrolyze E1S. STS activity is significantly higher in CRC cell lysate, suggesting the importance of E1S transport in intracellular STS substrate availability. As E1S transport is regulated by the expression pattern of certain solute carrier organic anion transporter polypeptides, we show that in CRC OATP4A1 is the most abundantly expressed transporter. All four CRC cell lines rapidly transported E1S into cells, with this effect significantly inhibited by the competitive OATP inhibitor BSP. Transient knockdown of OATP4A1 significantly disrupted E1S uptake. Examination of estrogen receptor status showed ERα was present in Colo205 and Caco2 cells. None of the cells expressed ERβ. Intriguingly, HCT116 and HT29 cells strongly expressed the G protein coupled estrogen receptor (GPER), and that stimulation of this receptor with estradiol (E2) and G1, a GPER agonist, significantly (p < 0.01) increased STS activity. Furthermore, tamoxifen and fulvestrant, known GPER agonist, also increased CRC STS activity, with this effect inhibited by the GPER antagonist G15. These results suggest that CRC can take up and hydrolyze E1S, and that subsequent GPER stimulation increases STS activity in a potentially novel positive feedback loop. As elevated STS expression is associated with poor prognosis in CRC, these results suggest HRT, tamoxifen and fulvestrant may negatively impact CRC patient outcomes.
Sensitivity of the TATB-based explosive PBX-9502 after thermal expansion

The sensitivity of TATB-based explosive PBX-9502 is affected by non-reversible thermal expansion, or “ratchet growth. ” PBX-9502 is a plastic-bonded explosive consisting of 95 wt % TATB (2,4,6-trinitro-1,3,5-benzenetriamine) and 5 wt % Kel-F 800 binder (chlorotrifluoroethylene/vinylidine 3:1 copolymer). The magnitude of the increase in size and the corresponding increase in sensitivity is reported here for a particular pressing of PBX-9502, after repeated thermal cycling. The physical morphology of the expanded material is examined using scanning electron microscopy, in an effort to determine the increase in intergranular holes, intragranular cracks and fissures in the TATB crystals, and the change in the distribution of the Kel-F, all of which are suspected to affect the sensitivity of the material. These images support the proposed mechanism for ratchet growth. Sensitivity, growth of the reactive wave behind the shock front, and Hugoniot data are obtained from in-material particle velocity gauge records .
Multilocus Sequence Typing Methods for the Emerging Campylobacter Species C. hyointestinalis, C. lanienae, C. sputorum, C. concisus, and C. curvus

Multilocus sequence typing (MLST) systems have been reported previously for multiple food- and food animal-associated Campylobacter species (e.g., C. jejuni, C. coli, C. lari, and C. fetus) to both differentiate strains and identify clonal lineages. These MLST methods focused primarily on campylobacters of human clinical (e.g., C. jejuni) or veterinary (e.g., C. fetus) relevance. However, other, emerging, Campylobacter species have been isolated increasingly from environmental, food animal, or human clinical samples. We describe herein four MLST methods for five emerging Campylobacter species: C. hyointestinalis, C. lanienae, C. sputorum, C. concisus, and C. curvus. The concisus/curvus method uses the loci aspA, atpA, glnA, gltA, glyA, ilvD, and pgm, whereas the other methods use the seven loci defined for C. jejuni (i.e., aspA, atpA, glnA, gltA, glyA, pgm, and tkt). Multiple food animal and human clinical C. hyointestinalis (n = 48), C. lanienae (n = 34), and C. sputorum (n = 24) isolates were typed, along with 86 human clinical C. concisus and C. curvus isolates. A large number of sequence types were identified using all four MLST methods. Additionally, these methods speciated unequivocally isolates that had been typed ambiguously using other molecular-based speciation methods, such as 16S rDNA sequencing. Finally, the design of degenerate primer pairs for some methods permitted the typing of related species; for example, the C. hyointestinalis primer pairs could be used to type C. fetus strains. Therefore, these novel Campylobacter MLST methods will prove useful in differentiating strains of multiple, emerging Campylobacter species.
Importance of guided fine needle aspiration cytology (FNAC) for the diagnostics of thyroid nodules - own experience.

UNLABELLED The aim of our study was to assess the accuracy and limitations of ultrasound guided fine-needle aspiration cytology (FNAC) of thyroid nodules. METHODS The usg-FNAC results of 245 patients with thyroid nodules, who afterwards underwent thyroid surgery or who died, and autopsies were carried out, and compared retrospectively with cytologic results. Patients with malignant cytologic conclusion without histological confirmation after surgery or autopsy were excluded from the study (9 persons). The usg-FNAC results were divided as follows: group 1: diagnosis of malignancy (n = 30), group 2: suspicion of malignancy (n = 28), group 3: benign (n = 126), group 4: inconclusive (n = 29). RESULTS Assuming the cytologic results of group 1 and group 2 were interpreted as being malignant and those of group 3 as being benign, the sensitivity, specificity and accuracy of usg-FNAC were 90 %, 85 % and 86 % respectively. Comparing the cytologic conclusions between a group of patients with follicular lesions and a subgroup of other lesions a statistically significant difference (p < 0,01) between both subgroups using Fisher's test was found. Sensitivity, specificity and diagnostic accuracy in subgroup of follicular lesions were low (71 %, 63 %, 67 %), while in the subgroup of other lesions were high (94 %, 86 %, 88 %). FNAC can specify the nature of focal lesion with high sensitivity, specificity and diagnostic accuracy in the cases of non-follicular lesions. Histological evaluation is required to specification of the nature in cases in which cytology is indicative of follicular proliferation.
An Island of Stability: Art Images and Natural Scenes – but Not Natural Faces – Show Consistent Esthetic Response in Alzheimer’s-Related Dementia

Alzheimer’s disease (AD) causes severe impairments in cognitive function but there is evidence that aspects of esthetic perception are somewhat spared, at least in early stages of the disease. People with early Alzheimer’s-related dementia have been found to show similar degrees of stability over time in esthetic judgment of paintings compared to controls, despite poor explicit memory for the images. Here we expand on this line of inquiry to investigate the types of perceptual judgments involved, and to test whether people in later stages of the disease also show evidence of preserved esthetic judgment. Our results confirm that, compared to healthy controls, there is similar esthetic stability in early stage AD in the absence of explicit memory, and we report here that people with later stages of the disease also show similar stability compared to controls. However, while we find that stability for portrait paintings, landscape paintings, and landscape photographs is not different compared to control group performance, stability for face photographs – which were matched for identity with the portrait paintings – was significantly impaired in the AD group. We suggest that partially spared face-processing systems interfere with esthetic processing of natural faces in ways that are not found for artistic images and landscape photographs. Thus, our work provides a novel form of evidence regarding face-processing in healthy and diseased aging. Our work also gives insights into general theories of esthetics, since people with AD are not encumbered by many of the semantic and emotional factors that otherwise color esthetic judgment. We conclude that, for people with AD, basic esthetic judgment of artistic images represents an “island of stability” in a condition that in most other respects causes profound cognitive disruption. As such, esthetic response could be a promising route to future therapies.
Detection of viral DNA sequences in the cerebrospinal fluid of patients with multiple sclerosis

The role of viruses in the pathogenesis of multiple sclerosis (MS) is a subject of heated debate. The presence of six different neurotropic viruses was sought, including JC virus (JCV), varicella zoster virus (VZV), human herpesvirus 6 (HHV‐6), and Epstein‐Barr virus (EBV), in cerebrospinal fluid (CSF) samples collected from 51 patients with MS and 30 patients with other neurological diseases. Cell‐free or cell‐associated viral DNA in CSF samples was detected by real‐time PCR, and viral loads were determined. Magnetic resonance imaging (MRI) examinations were also performed to look for active lesions. Cell‐associated JCV DNA was detected in 3 of the 51 patients with MS and in 2 of the 30 patients with other neurological disease. Cell‐free JCV DNA was detected in one additional patient with MS. Cell‐free VZV DNA was detected in one patient without MS, cell‐free HHV‐6 was detected in one patient with MS, and cell‐free EBV was detected in one patient with MS. All other study patients had no detectable viral DNA in CSF samples and no double infections were found. The small percentage of patients with detectable viral DNA in CSF samples was comparable between patients with MS and those with other neurological disease, and presence of viral DNA was not a predictor of brain lesions. Additional observations suggest that cell trafficking from the periphery, rather than leakage through the blood–brain barrier, results in the transport of viruses to the CNS, where local immunosurveillance can control viral replication in immunocompetent individuals. J. Med. Virol. 82:1051–1057, 2010. © 2010 Wiley‐Liss, Inc.
Learning to Ask: Neural Question Generation for Reading Comprehension

We study automatic question generation for sentences from text passages in reading comprehension. We introduce an attention-based sequence learning model for the task and investigate the effect of encoding sentence- vs. paragraph-level information. In contrast to all previous work, our model does not rely on hand-crafted rules or a sophisticated NLP pipeline; it is instead trainable end-to-end via sequence-to-sequence learning. Automatic evaluation results show that our system significantly outperforms the state-of-the-art rule-based system. In human evaluations, questions generated by our system are also rated as being more natural (i.e.,, grammaticality, fluency) and as more difficult to answer (in terms of syntactic and lexical divergence from the original text and reasoning needed to answer).
Safety and Adherence to Intermittent Pre-Exposure Prophylaxis (PrEP) for HIV-1 in African Men Who Have Sex with Men and Female Sex Workers

Background Little is known about safety of and adherence to intermittent HIV PrEP regimens, which may be more feasible than daily dosing in some settings. We present safety and adherence data from the first trial of an intermittent PrEP regimen among Kenyan men who have sex with men (MSM) and female sex workers (FSW). Methods/Principal Findings MSM and FSW were randomized to daily oral FTC/TDF or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral FTC/TDF or placebo in a 2∶1∶2∶1 ratio; volunteers were followed monthly for 4 months. Adherence was assessed with the medication event monitoring system (MEMS). Sexual activity data were collected via daily text message (SMS) queries and timeline followback interviews with a one-month recall period. Sixty-seven men and 5 women were randomized into the study. Safety was similar among all groups. Median MEMS adherence rates were 83% [IQR: 63–92] for daily dosing and 55% [IQR:28–78] for fixed intermittent dosing (p = 0.003), while adherence to any post-coital doses was 26% [IQR:14–50]. SMS response rates were low, which may have impaired measurement of post-coital dosing adherence. Acceptability of PrEP was high, regardless of dosing regimen. Conclusions/Significance Adherence to intermittent dosing regimens, fixed doses, and in particular coitally-dependent doses, may be more difficult than adherence to daily dosing. However, intermittent dosing may still be appropriate for PrEP if intracellular drug levels, which correlate with prevention of HIV acquisition, can be attained with less than daily dosing and if barriers to adherence can be addressed. Additional drug level data, qualitative data on adherence barriers, and better methods to measure sexual activity are necessary to determine whether adherence to post-coital PrEP could be comparable to more standard regimens. Trial Registration ClinicalTrials.gov NCT00971230
Threshold effect of growth rate on population variability of Escherichia coli cell lengths

A long-standing question in biology is the effect of growth on cell size. Here, we estimate the effect of Escherichia coli growth rate (r) on population cell size distributions by estimating the coefficient of variation of cell lengths (CVL) from image analysis of fixed cells in DIC microscopy. We find that the CVL is constant at growth rates less than one division per hour, whereas above this threshold, CVL increases with an increase in the growth rate. We hypothesize that stochastic inhibition of cell division owing to replication stalling by a RecA-dependent mechanism, combined with the growth rate threshold of multi-fork replication (according to Cooper and Helmstetter), could form the basis of such a threshold effect. We proceed to test our hypothesis by increasing the frequency of stochastic stalling of replication forks with hydroxyurea (HU) treatment and find that cell length variability increases only when the growth rate exceeds this threshold. The population effect is also reproduced in single-cell studies using agar-pad cultures and ‘mother machine’-based experiments to achieve synchrony. To test the role of RecA, critical for the repair of stalled replication forks, we examine the CVL of E. coli ΔrecA cells. We find cell length variability in the mutant to be greater than wild-type, a phenotype that is rescued by plasmid-based RecA expression. Additionally, we find that RecA-GFP protein recruitment to nucleoids is more frequent at growth rates exceeding the growth rate threshold and is further enhanced on HU treatment. Thus, we find growth rates greater than a threshold result in increased E. coli cell lengths in the population, and this effect is, at least in part, mediated by RecA recruitment to the nucleoid and stochastic inhibition of division.
Human Myt1 Is a Cell Cycle-regulated Kinase That Inhibits Cdc2 but Not Cdk2 Activity*

Activation of the Cdc2·cyclin B kinase is a pivotal step of mitotic initiation. This step is mediated principally by the dephosphorylation of residues threonine 14 (Thr14) and tyrosine 15 (Tyr15) on the Cdc2 catalytic subunit. In several organisms homologs of the Wee1 kinase have been shown to be the major activity responsible for phosphorylating the Tyr15 inhibitory site. A membrane-bound kinase capable of phosphorylating residue Thr14, the Myt1 kinase, has been identified in the frog Xenopus laevis and more recently in human. In this study, we have examined the substrate specificity and cell cycle regulation of the human Myt1 kinase. We find that human Myt1 phosphorylates and inactivates Cdc2-containing cyclin complexes but not complexes containing Cdk2 or Cdk4. Analysis of endogenous Myt1 demonstrates that it remains membrane-bound throughout the cell cycle, but its kinase activity decreased during M phase arrest, when Myt1 became hyperphosphorylated. Further, Cdc2·cyclin B1 was capable of phosphorylating Myt1 in vitro, but this phosphorylation did not affect Myt1 kinase activity. These findings suggest that human Myt1 is negatively regulated by an M phase-activated kinase and that Myt1 inhibits mitosis due to its specificity for Cdc2·cyclin complexes.
Performance and Repeatability of the NEI-VFQ-25 in Patients With Dry Eye

Purpose. The use of the National Eye Institute Visual Function Questionnaire (NEI-VFQ) has increased as a method of assessing patients' impressions of their vision-specific quality of life. The purpose of this study was to assess the performance and test-retest repeatability of the 25-question format of the NEI-VFQ in patients with dry eye. Methods. The self-administered NEI-VFQ-25 was administered to 75 patients with dry eye on two occasions in a university-based optometry practice. Dry eye severity was assessed with use of the European criteria for dry eye. The weighted kappa statistic (&kgr;w) was used to evaluate test-retest repeatability of the NEI-VFQ-25 individual test questions, and the 95% limits of agreement and the intraclass correlation coefficients were calculated for the overall VFQ and subscale scores. Results. With use of the European dry eye criteria, 21.9% of participants were classified with moderate to severe dry eye. For the sample, the ocular pain subscale score was lower (indicating more ocular pain) than published normative values. Repeatability of individual NEI-VFQ-25 questions ranged from moderate to substantial (&kgr;wvalues: 0.42 [pain and discomfort] to 0.90 [stay home because of vision]). The intervisit mean (± standard deviation) difference in the overall VFQ score was −0.66 ± 4.26 (95% limits of agreement: −9.02, 7.69), and the intraclass correlation coefficient for the ocular pain subscale was 0.57. Conclusion. Patients with dry eye have lower ocular pain subscale scores. The repeatability of the overall NEI-VFQ score and the subscale scores was moderate to high, and it may be influenced by the number of questions in each subscale.
Histological, morphometric, protein and gene expression analyses of rat retinas with ischaemia–reperfusion injury model treated with sildenafil citrate

The aim of this study was to better understand the role of apoptosis in a retinal ischaemia–reperfusion injury model and to determine whether sildenafil citrate treatment can prevent retinal cell apoptosis. Thirty‐six rats were divided into a control group (n = 6) and two experimentally induced ischaemia–reperfusion groups (7 and 21 days; n = 15 per group). The induced ischaemia–reperfusion groups were treated with sildenafil for 7 and 21 days (n = 10 per group), and 10 animals were treated with a placebo for the same period (n = 5 per group). Paracentesis of the anterior chamber was performed with a 30‐G needle attached to a saline solution (0.9%) bag positioned at a height of 150 cm above the eye for 60 min. Intraocular pressure was measured by rebound tonometer (TonoVet®). The eyes were analysed by histology and morphometry, and by immunohistochemistry and qRT‐PCR for expression of Caspase‐7, Caspase‐6, Caspase‐9, Tnf‐r2, Fas‐l, Bcl‐2 and Bax. Sildenafil‐treated animals showed lower levels of histopathological changes (inflammatory, cellular and tissue) than their placebo‐treated counterparts at both 7 and 21 days. The retinal ganglion cell layer (RGC) was preserved in the sildenafil groups (SG), with a cell count closer to control than in the placebo groups (PG). Caspase‐7 expression was significantly higher in both treated groups at 7 days compared to controls. Gene expression levels in both treatment groups differed from the controls, but in SG Bax and Caspase‐6 expression levels were similar to control animals. These results suggest that the main mechanism of retinal cell death in this model is apoptosis, as there is an increase in pro‐apoptotic factors and decrease in the anti‐apoptotic ones. Also, sildenafil seems to protect the retinal ganglion cell layer from apoptosis. Cell survival was evident in the histological and morphometric analyses, and sildenafil treatment had a protective effect in the apoptosis pathways, with gene expression levels in SG similar to the controls.
Optimal Agreement in a Scale-Free Network Environment

Generally, the task in a distributed system must achieve an agreement. It requires a set of processors to agree on a common value even if some components are corrupted. There are significant studies on this agreement problem in a regularized network environment, such as the Fully Connected, BroadCast and MultiCast Networks. Recently, many large complex networks have emerged and displayed a scale-free feature, which influences the system to reach a common value differently. Unfortunately, existing agreement protocols and results cannot cope with the new network environment and the agreement problem thus needs to be revisited. In this paper, we propose a new agreement protocol to adapt to the scale-free network environment and derive its bound of allowable faulty TMs with two rounds of message exchange. We have proved the correctness of this protocol and analyzed its complexity. It is observed that the scale-free network with the proposed agreement protocol can tolerate more faulty TMs than the networks based on previous studies.