Miracle-dz/UniFAR-FTUs huggingface dataset:
Adenocarcinoma of the uterine cervix: the presence of human papillomavirus and the method of detection

Background. Effective screening programs have contributed to a decrease in the incidence of cervical squamous cell carcinomas but have had a limited sensitivity in the detection of adenocarcinoma precursor lesions. The aim of our study was to analyze cervical adenocarcinoma in greater detail: symptoms preceding the detection, the method of detection and the prevalence of human papillomavirus (HPV) with respect to age at diagnosis.
Projections to the cochlear nuclei from principal cells in the medial nucleus of the trapezoid body in guinea pigs

Spherical and globular cells in the cochlear nucleus provide input to the cell groups in the superior olivary complex devoted to the analysis of binaural cues. Desending projections from the superior olivary complex appear to inhibit the spherical and globular cells. It is not known which of the numerous cell types in the superior olive provide this descending input, but recent studies have shown that some of the cells are located in the medial nucleus of the trapezoid body (MTB). The present experiments were designed to determine whether the MTB projections arise from principal cells, which are known to play a role sound localization, and to determine whether their projections terminate on spherical or globular cells.
Compact LP Relaxations for Allocation Problems

We consider the restricted versions of Scheduling on Unrelated Machines and the Santa Claus problem. In these problems we are given a set of jobs and a set of machines. Every job j has a size p_j and a set of allowed machines \Gamma(j), i.e., it can only be assigned to those machines. In the first problem, the objective is to minimize the maximum load among all machines; in the latter problem it is to maximize the minimum load. For these problems, the strongest LP relaxation known is the configuration LP. The configuration LP has an exponential number of variables and it cannot be solved exactly unless P = NP. Our main result is a new LP relaxation for these problems. This LP has only O(n^3) variables and constraints. It is a further relaxation of the configuration LP, but it obeys the best bounds known for its integrality gap (11/6 and 4). For the configuration LP these bounds were obtained using two local search algorithm. These algorithms, however, differ significantly in presentation. In this paper, we give a meta algorithm based on the local search ideas. With an instantiation for each objective function, we prove the bounds for the new compact LP relaxation (in particular, for the configuration LP). This way, we bring out many analogies between the two proofs, which were not apparent before.
Replication of interleukin 23 receptor and autophagy-related 16-like 1 association in adult- and pediatric-onset inflammatory bowel disease in Italy.

AIM To investigate gene variants in a large Italian inflammatory bowel disease (IBD) cohort, and to analyze the correlation of sub-phenotypes (including age at diagnosis) and epistatic interaction with other IBD genes. METHODS Total of 763 patients with Crohn's disease (CD, 189 diagnosed at age < 19 years), 843 with ulcerative colitis (UC, 179 diagnosed < 19 years), 749 healthy controls, and 546 healthy parents (273 trios) were included in the study. The rs2241880 [autophagy-related 16-like 1 (ATG16L1)], rs11209026 and rs7517847 [interleukin 23 receptor (IL23R)], rs2066844, rs2066845, rs2066847 (CARD15), rs1050152 (OCTN1), and rs2631367 (OCTN2) gene variants were genotyped. RESULTS The frequency of G allele of ATG16L1 SNP (Ala197Thr) was increased in patients with CD compared with controls (59% vs 54% respectively) (OR = 1.25, CI = 1.08-1.45, P = 0.003), but not in UC (55%). The frequency of A and G (minor) alleles of Arg381Gln, rs11209026 and rs7517847 variants of IL23R were reduced significantly in CD (4%, OR = 0.62, CI = 0.45-0.87, P = 0.005; 28%, OR = 0.64, CI = 0.55-0.75, P < 0.01), compared with controls (6% and 38%, respectively). The A allele (but not G) was also reduced significantly in UC (4%, OR = 0.69, CI = 0.5-0.94, P = 0.019). No association was demonstrated with sub-phenotypes and interaction with CARD15, and OCTN1/2 genes, although both gene variants were associated with pediatric-onset disease. CONCLUSION The present study confirms the association of IL23R polymorphisms with IBD, and ATG16L1 with CD, in both adult- and pediatric-onset subsets in our study population.
Catalysis of Strand Annealing by Replication Protein A Derives from Its Strand Melting Properties*

Eukaryotic DNA-binding protein replication protein A (RPA) has a strand melting property that assists polymerases and helicases in resolving DNA secondary structures. Curiously, previous results suggested that human RPA (hRPA) promotes undesirable recombination by facilitating annealing of flaps produced transiently during DNA replication; however, the mechanism was not understood. We designed a series of substrates, representing displaced DNA flaps generated during maturation of Okazaki fragments, to investigate the strand annealing properties of RPA. Until cleaved by FEN1 (flap endonuclease 1), such flaps can initiate homologous recombination. hRPA inhibited annealing of strands lacking secondary structure but promoted annealing of structured strands. Apparently, both processes primarily derive from the strand melting properties of hRPA. These properties slowed the spontaneous annealing of unstructured single strands, which occurred efficiently without hRPA. However, structured strands without hRPA displayed very slow spontaneous annealing because of stable intramolecular hydrogen bonding. hRPA appeared to transiently melt the single strands so that they could bind to form double strands. In this way, melting ironically promoted annealing. Time course measurements in the presence of hRPA suggest that structured single strands achieve an equilibrium with double strands, a consequence of RPA driving both annealing and melting. Promotion of annealing reached a maximum at a specific hRPA concentration, presumably when all structured single-stranded DNA was melted. Results suggest that displaced flaps with secondary structure formed during Okazaki fragment maturation can be melted by hRPA and subsequently annealed to a complementary ectopic DNA site, forming recombination intermediates that can lead to genomic instability.
1 DISTINCT ROLE OF PYK 2 IN MEDIATING THROMBOXANE GENERATION DOWNSTREAM OF BOTH G 12 / 13 AND INTEGRIN α IIb β IN PLATELETS *

DISTINCT ROLE OF PYK2 IN MEDIATING THROMBOXANE GENERATION DOWNSTREAM OF BOTH G12/13 AND INTEGRIN αIIbβ IN PLATELETS* Soochong Kim, Lina Cipolla, Gianni Guidetti, Mitsuhiko Okigaki, Jianguo Jin, Mauro Torti, and Satya P. Kunapuli From the Departments of Physiology and Pharmacology and Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA; Department of Biochemistry, University of Pavia, Italy; Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
An Individualized Risk Calculator for Research in Prodromal Psychosis.

OBJECTIVE Approximately 20%-35% of individuals 12-35 years old who meet criteria for a prodromal risk syndrome convert to psychosis within 2 years. However, this estimate ignores the fact that clinical high-risk cases vary considerably in risk. The authors sought to create a risk calculator, based on profiles of risk indicators, that can ascertain the probability of conversion to psychosis in individual patients. METHOD The study subjects were 596 clinical high-risk participants from the second phase of the North American Prodrome Longitudinal Study who were followed up to the time of conversion to psychosis or last contact (up to 2 years). The predictors examined were limited to those that are supported by previous studies and are readily obtainable in general clinical settings. Time-to-event regression was used to build a multivariate model predicting conversion, with internal validation using 1,000 bootstrap resamples. RESULTS The 2-year probability of conversion to psychosis was 16%. Higher levels of unusual thought content and suspiciousness, greater decline in social functioning, lower verbal learning and memory performance, slower speed of processing, and younger age at baseline each contributed to individual risk for psychosis. Stressful life events, trauma, and family history of schizophrenia were not significant predictors. The multivariate model achieved a concordance index of 0.71 and, as reported in an article by Carrión et al., published concurrently with this one, was validated in an independent external data set. The results are instantiated in a web-based risk prediction tool envisioned to be most useful in research protocols involving the psychosis prodrome. CONCLUSIONS A risk calculator comparable in accuracy to those for cardiovascular disease and cancer is available to predict individualized conversion risks in newly ascertained clinical high-risk cases. Given that the risk calculator can be validly applied only for patients who screen positive on the Structured Clinical Interview for Psychosis Risk Syndromes, which requires training to administer, its most immediate uses will be in research on psychosis risk factors and in research-driven clinical (prevention) trials.
A system for evaluating augmented reality user interfaces in wearable computers

Usability tests with wearable computers are difficult to conduct due to the nature of wearable computers. Wearable computers are intended for personal use and the test supervisor does not know exactly what the test subject is currently seeing in augmented reality through the head-worn display of the wearable computer. Due to this personal nature, the concepts of traditional usability testing need some rethinking. This paper presents a combination of techniques that connects the computers of the test subject and the supervisor. Both of the computers share the same view of augmented reality and the supervisor knows exactly what the user is doing and what state the computer is in. All actions and sensor data are also recorded for later analysis. Complete usability tests have been made with this system and the system fulfilled its goals.
Structural and Functional Studies on the Interaction of Adenovirus Fiber Knobs and Desmoglein 2

ABSTRACT Human adenovirus (Ad) serotypes Ad3, Ad7, Ad11, and Ad14, as well as a recently emerged strain of Ad14 (Ad14p1), use the epithelial junction protein desmoglein 2 (DSG2) as a receptor for infection. Unlike Ad interaction with CAR and CD46, structural details for Ad binding to DSG2 are still elusive. Using an approach based on Escherichia coli expression libraries of random Ad3 and Ad14p1 fiber knob mutants, we identified amino acid residues that, when mutated individually, ablated or reduced Ad knob binding to DSG2. These residues formed three clusters inside one groove at the extreme distal end of the fiber knob. The Ad3 fiber knob mutant library was also used to identify variants with increased affinity to DSG2. We found a number of mutations within or near the EF loop of the Ad3 knob that resulted in affinities to DSG2 that were several orders of magnitude higher than those to the wild-type Ad3 knob. Crystal structure analysis of one of the mutants showed that the introduced mutations make the EF loop more flexible, which might facilitate the interaction with DSG2. Our findings have practical relevance for cancer therapy. We have recently reported that an Ad3 fiber knob-containing recombinant protein (JO-1) is able to trigger opening of junctions between epithelial cancer cells which, in turn, greatly improved the intratumoral penetration and efficacy of therapeutic agents (I. Beyer, et al., Clin. Cancer Res. 18:3340–3351, 2012; I. Beyer, et al., Cancer Res. 71:7080–7090, 2011). Here, we show that affinity-enhanced versions of JO-1 are therapeutically more potent than the parental protein in a series of cancer models.
Update on idiopathic colitides

Purpose of reviewThis article summarizes the latest developments for three types of idiopathic colitis: ulcerative colitis, Crohn's disease, and microscopic colitis. Recent findingsCrohn's disease and ulcerative colitis are highly related genetically. Colonoscopy remains the gold standard for making a diagnosis. The addition of chromoendoscopy can aid in identification and removal of colonic dysplasia in both disorders. The therapy for ulcerative colitis and Crohn's disease has been transformed with the introduction of anti-TNF treatment. For ulcerative colitis, recent data show that prolonged use of infliximab is effective, well tolerated and that early mucosal healing is associated with decreased risk of colectomy. There is no evidence of a significant increased risk for anti-TNF-induced malignancies. Combination therapy with azathioprine and infliximab for ulcerative colitis has now been shown to be superior to monotherapy. Natalizumab is effective in anti-TNF failures and patients can be risk stratified for progressive multifocal leukoencephalopathy by testing for John Cunningham virus antibodies. Microscopic colitis can often be related to medications, and symptoms may be worsened by coexisting celiac disease. SummaryCombination therapy with an anti-TNF and a thiopurine is currently the most effective treatment for moderate-to-severe Crohn's disease or ulcerative colitis. Stem cell therapy for perianal fistulas in patients with Crohn's disease is a promising new therapy approach.
Swimming into prominence: the zebrafish as a valuable tool for studying human myopathies and muscular dystrophies

A new and exciting phase of muscle disease research has recently been entered. The application of next generation sequencing technology has spurred an unprecedented era of gene discovery for both myopathies and muscular dystrophies. Gene‐based therapies for Duchenne muscular dystrophy have entered clinical trial, and several pathway‐based therapies are doing so as well for a handful of muscle diseases. While many factors have aided the extraordinary developments in gene discovery and therapy development, the zebrafish model system has emerged as a vital tool in these advancements. In this review, we will highlight how the zebrafish has greatly aided in the identification of new muscle disease genes and in the recognition of novel therapeutic strategies. We will start with a general introduction to the zebrafish as a model, discuss the ways in which muscle disease can be modeled and analyzed in the fish, and conclude with observations from recent studies that highlight the power of the fish as a research tool for muscle disease.
Associations Between Hepatitis B Virus Genotype and Mutants and the Risk of Hepatocellular Carcinoma

Background The risk of hepatocellular carcinoma (HCC) increases with increasing level of hepatitis B virus (HBV) in serum (viral load). However, it is unclear whether genetic characteristics of HBV, including HBV genotype and specific genetic mutations, contribute to the risk of HCC. We examined the HCC risk associated with HBV genotypes and common variants in the precore and basal core promoter (BCP) regions. Methods From January 5, 1991, to December 21, 1992, baseline blood samples were collected from 2762 Taiwanese men and women who were seropositive for HBV surface antigen but had not been diagnosed with HCC; the samples were tested for HBV viral load by real-time polymerase chain reaction and genotyped by melting curve analysis. Participants who had a baseline serum HBV DNA level greater than 104 copies/mL (n = 1526) were tested for the precore G1896A and BCP A1762T/G1764A mutants by direct sequencing. Incident cases of HCC were ascertained through follow-up examinations and computerized linkage to the National Cancer Registry and death certification profiles. A Cox proportional hazards model was used to estimate the risk of HCC associated with HBV genotype and precore and BCP mutants after adjustment for other risk factors. All statistical tests were two-sided. Results A total of 153 HCC cases occurred during 33 847 person-years of follow-up. The HCC incidence rates per 100 000 person-years for participants infected with HBV genotype B or C were 305.6 (95% confidence interval [CI] = 236.9 to 388.1) and 785.8 (95% CI = 626.8 to 972.9), respectively. Among participants with a baseline HBV DNA level of at least 104 copies/mL, HCC incidence per 100 000 person-years was higher for those with the precore G1896 (wild-type) variant than for those with the G1896A variant (955.5 [95% CI = 749.0 to 1201.4] vs 269.4 [95% CI = 172.6 to 400.9]) and for those with the BCP A1762T/G1764A double mutant than for those with BCP A1762/G1764 (wild-type) variant (1149.2 [95% CI = 872.6 to 1485.6] vs 358.7 [95% CI = 255.1 to 490.4]). The multivariable-adjusted hazard ratio of developing HCC was 1.76 (95% CI = 1.19 to 2.61) for genotype C vs genotype B, 0.34 (95% CI = 0.21 to 0.57) for precore G1896A vs wild type, and 1.73 (95% CI = 1.13 to 2.67) for BCP A1762T/G1764A vs wild type. Risk was highest among participants infected with genotype C HBV and wild type for the precore 1896 variant and mutant for the BCP 1762/1764 variant (adjusted hazard ratio = 2.99, 95% CI = 1.57 to 5.70, P < .001). Conclusions HBV genotype C and specific alleles of BCP and precore were associated with risk of HCC. These associations were independent of serum HBV DNA level.
Efficiency of a machine translation system

In the field of machine translation ample amount of work has been done to improve the essence of translation systems. It all started in 1949 when Warren Weaver proposed the first idea of using computer for translation. Since then several approaches have been followed out to ameliorate the quality of translation. But even after continuing development in this field, we haven't reached the level where we could get the exact translation of the source text. The aim of this paper is to brief about different approaches of machine translation and introduce a mechanism for the evaluation of the efficiency of translation systems based on the lexical, syntactical and semantics differences between source text and translated text. This mechanism provides a statistical analysis of translation systems, the results of this analysis can be used as a rating mechanism on the translation systems used worldwide. In this paper, we have emphasized on translation between English and Hindi.
Examining Family Firm Succession From a Social Exchange Perspective

We use a social exchange perspective to review family firm succession literature owing to its fit with the multiphase, multistakeholder nature of the process. We searched the history of 34 journals, finding 88 published or forthcoming articles that quantitatively examined succession. We consider the primary phases of the management succession process (ground rules, successor development, and transition) and the relevant stakeholder exchanges occurring during each phase, including exchanges between incumbents and successors, within family boundaries, and across family boundaries. We contribute to the family firm succession literature by identifying how a social exchange perspective can help guide future research.
Occupational exposure to chemical agents in the plywood industry.

As part of an International Agency for Research on Cancer (IARC) international epidemiological study of workers in the pulp and paper industry, previously unpublished exposure measurements were assembled in a database. This article summarizes the results of 3,873 measurements carried out in the production departments of paper and paperboard mills and recycling plants in 12 countries. In the paper and paperboard mills, most of the agents were measured in the pulping and refining departments and in on-machine coating and winding of paper/paperboard. Exposures to asbestos, carbon monoxide, formaldehyde, fungal spores, bacteria, nitrogen dioxide, minerals dusts, paper dust, sulphuric acid and different solvents sometimes exceeded exposure limit values. In the re-pulping and de-inking departments of recycling plants high exposures to formaldehyde, fungal spores, bacteria and paper dust were observed. High exposures to asbestos, bioaerosols, carbon monoxide and paper dust were found in many departments; ammonia, formaldehyde, mineral and paper dust and solvents were found in coating machines; and diphenyl and polychlorobiphenyls (PCBs) were found in some special circumstances. Measurements in the newsprint and uncoated paper machine departments revealed only a few elevated exposures. In nearly all departments, measurements of epichlorohydrin, PCBs, sulphur dioxide, hydrogen sulphide and mercaptans tended to be low, often even below their detection limits. In spite of some uncertainties in the measurement data, the study provides new insights into the level and variation of occupational exposures of production workers in the paper and paperboard industry.
Mutational analysis of adeno-associated virus Rep protein-mediated inhibition of heterologous and homologous promoters

The four Rep proteins encoded by adeno-associated virus type 2 (AAV-2) inhibit transcription of their own promoters and of several heterologous promoters. To gain insight into the molecular mechanism of Rep-mediated transcription repression, we studied the effects of the four Rep proteins on the accumulation of mRNA transcribed from the human papillomavirus type 18 upstream regulatory region HPV18 URR, the human immunodeficiency virus long terminal repeat, and the AAV-2 p5 and p19 promoters by transient transfection experiments in HeLa cells. We observed a distinct contribution of the C- and N-terminal sequences in which the four Rep proteins (Rep78, Rep68, Rep52, and Rep40) differ from each other. While Rep78 showed a more than 10-fold inhibition of the four promoters studied, transcriptional repression mediated by Rep68 and Rep52 was reduced and nearly completely abolished for Rep40. The contribution of the C terminus of Rep78 was reduced with respect to the inhibition of the AAV-2 p5 and p19 promoters. Point mutations and deletions showed that a C-terminal zinc binding motif is required for zinc binding in vitro but plays no obvious role in the inhibition of homologous and heterologous promoters. Overall, inhibition of the four different promoters was dependent on the identical Rep protein domains with the exception of the AAV-2 p5 promoter. Expression of the AAV-2 p5 promoter was inhibited by a Rep78 protein with a mutation in the nucleotide binding motif, whereas expression of the AAV-2 p19 promoter, the human immunodeficiency virus long terminal repeat, and the HPV18 URR was not. Mutational analysis of the HPV18 URR showed that several, but not a single, cis regulatory elements are involved in the inhibition process. This finding suggests that transcriptional repression is mediated by protein-protein interactions of the Rep proteins either with multiple transcription factors or with target proteins of sequence-specific transcription factors of the basal transcription machinery.
Carnosine: A Possible Drug for Vascular Dementia

Carnosine (β–alanyl histidine) is a small dipeptide with numerous beneficial effects, including the maintenance of the acid–base balance, antioxidant, chelating, anti–crosslinking, and anti–glycation activities in the living organism. High levels of carnosine are found in the skeletal muscles and in the brain. We have found that carnosine inhibits Zn2+–induced neuronal death, which plays acrucial role in the pathogenesis of vascular dementia. Our previous research demonstrated that carnosine participates in the Endoplasmic Reticulum (ER)–stress pathway in Zn– induced neurotoxicity and we have applied for a patent related to drugs for Vascular Dementia (VD). Here, we review the roles of carnosine in VD and otherneuro degenerative diseases and discuss perspectives about the future therapeutic use ofthis dipeptide.