Miracle-dz/UniFAR-FTUs huggingface dataset:
Polypeptide Pattern of Apple Tissues Affected by Calcium-related Physiopathologies

Polypeptides from the apple pulp of Smoothee Golden Delicious and White Renete apples were resolved by 1-D denaturing sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). According to the electropherograms, there were lower concentrations of 88, 74, 70.6 and 47.5-42kDa proteins in bitter pit spots. Proteins weighing 30 and 26kDa were rare in sound pulp but frequently appeared in pits and adjacent tissue. Finally, a novel 18kDa protein was found in bitter pit spots in both varieties, and also in chemically induced corky lesions either by magnesium infiltration or ammonium oxalate cortical injections. The available data suggested that the novel protein might be an inhibitor of pectinmethylesterase, a small heat stress protein (smHSP) or a product of the Ypr-10 gene family identified with ‘Mal d 1’, the main allergen of apples. To elucidate the possible smHSP nature of the 18kDa, a set of apples were heated at 40°C for 20h, developing this protein in both the oxidised tissue and in the adjacent.
Staphylococcus aureus abscesses: methicillin-resistance or Panton-Valentine leukocidin presence?

Introduction Panton-Valentine leukocidin (PVL) is a toxin associated with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) worldwide and also occurs in community-associated methicillin-susceptible S aureus (CA-MSSA) strains. The aims of the study were to determine the prevalence of PVL in community-onset S aureus skin and soft-tissue infections (SSTIs) and to analyse the influence of methicillin resistance and PVL presence on the clinical characteristics of these infections. Patients and methods We prospectively enrolled all children with S aureus community-onset SSTIs attending the emergency department of a tertiary hospital between 2007 and 2009. Results A total of 142 S aureus SSTIs were identified, 46 (32%) were PVL positive. The proportion of subjects in each group was: 89 (63%) PVL-MSSA, 33 (23%) PVL+MSSA, 13 (9%) PVL+MRSA and 7 (5%) PVL-MRSA. PVL+infections were more frequently abscesses (63% vs 39%, p<0.01), and more often required incision and drainage (p<0.01) and hospital admission (46% vs 26%, p=0.02). MRSA infections were also more frequently associated with abscesses but in a multivariable analysis only PVL remained independently related (OR 2.33; 95% CI 1.10 to 4.90). Conclusions Our study found a high prevalence of PVL presence in community-onset S aureus SSTIs in children in Spain. This toxin is associated with more abscess formation, regardless of methicillin resistance.
The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem cell niche function

Mesenchymal stem cells (MSCs) and osteolineage cells contribute to the hematopoietic stem cell (HSC) niche in the bone marrow of long bones. However, their developmental relationships remain unclear. In this study, we demonstrate that different MSC populations in the developing marrow of long bones have distinct functions. Proliferative mesoderm-derived nestin− MSCs participate in fetal skeletogenesis and lose MSC activity soon after birth. In contrast, quiescent neural crest-derived nestin+ cells preserve MSC activity, but do not generate fetal chondrocytes. Instead, they differentiate into HSC niche-forming MSCs, helping to establish the HSC niche by secreting Cxcl12. Perineural migration of these cells to the bone marrow requires the ErbB3 receptor. The neonatal Nestin-GFP+ Pdgfrα− cell population also contains Schwann cell precursors, but does not comprise mature Schwann cells. Thus, in the developing bone marrow HSC niche-forming MSCs share a common origin with sympathetic peripheral neurons and glial cells, and ontogenically distinct MSCs have non-overlapping functions in endochondrogenesis and HSC niche formation. DOI: http://dx.doi. org/10.7554/eLife.03696. 001
Augmented Kernel Matrix vs Classifier Fusion for Object Recognition

Augmented Kernel Matrix (AKM) has recently been proposed to accommodate for the fact that a single training example may have different importance in different feature spaces, in contrast to Multiple Kernel Learning (MKL) that assigns the same weight to all examples in one feature space. However, the AKM approach is limited to small datasets due to its memory requirements. An alternative way to fuse information from different feature channels is classifier fusion (ensemble methods). There is a significant amount of work on linear programming formulations of classifier fusion (CF) in the case of binary classification. In this paper we derive primal and dual of AKM to draw its correspondence with CF. We propose a multiclass extension of binary n-LPBoost, which learns the contribution of each class in each feature channel. Existing approaches of CF promote sparse features combinations, due to regularization based on ‘1-norm, and lead to a selection of a subset of feature channels, which is not good in case of informative channels. We also generalize existing CF formulations to arbitrary ‘p-norm for binary and multiclass problems which results in more effective use of complementary information. We carry out an extensive comparison and show that the proposed nonlinear CF schemes outperform its sparse counterpart as well as state-of-the-art MKL approaches.
Drug Resistant Clinical Isolates of Mycobacterium tuberculosis from Different Genotypes Exhibit Differential Host Responses in THP-1 Cells

Mycobacterium tuberculosis (MTB) persistently infects and survives within the host macrophages. Substantial genotypic variation exists among MTB strains which correlate with their interactions with the host. The present study was designed to establish a correlation, if any, between infection and induction of innate immune response by genetically diverse drug resistant MTB isolates from India. For this purpose, three clinical isolates from ancient and modern lineages, along with H37Ra and H37Rv were evaluated for intracellular growth, phagocytic index, induction of proinflammatory cytokines and apoptosis following infection in THP-1 cell line. A wide variation in the induction of cytokines was revealed subsequent to infection with different strains. EAI-5 strain from ancient lineage 1, induced higher proinflammatory responses, higher apoptosis and moderate intracellular growth compared to other strains, in contrast, for Beijing strain of modern lineage 2, all three parameters were lowest among the clinical isolates. Further, the responses induced by LAM-6 from modern lineage 4 were at a moderate level, similar to the laboratory strain H37Rv which also belongs to lineage 4. Thus, these profiles were specific to their respective lineages and/or genotypes and independent of their drug resistance status. Further, a positive correlation, among TNF-α, IL-1β, IL-6 and IL-12 induced in infected THP-1 cells was demonstrated. In addition, induction of all pro-inflammatory cytokines correlated well with the host cell apoptosis. A positive correlation was observed between phagocytic index in the category of ‘>10 bacilli/cell’ and induction of apoptosis, only for virulent strains, indicating that initial accumulation of MTB strains inside the host cell may be an important determining factor for different innate responses.
Evaluation of Soil, Cement and Construction and Demolition Waste (CDW) Mixtures for Use in Road Pavement Base and Sub-Base Applications

Environmental harm caused by construction and demolition waste (CDW) can be minimized by using it as a raw material in other products used in civil construction. In Brazil, there are several studies on the use of CDW as an aggregate in asphalt paving mixtures. However, this application is limited by the excess of fine aggregates present in these waste materials. Therefore, a technical feasibility study was done to evaluate the use of soil, cement and CDW mixtures for road pavement base and sub-base applications by determining the Unconfined Compressive Strength of cylindrical specimens molded with mixtures of soil, cement and CDW, with cement in proportions of 2%, 4% and 6% by dry weight of the mixture of soil and CDW with variations of: 100% soil and 0% CDW; 75% soil and 25% CDW; and 50% soil and 50% CDW. Soils were sourced from the cities of Maringá and Mandaguaçu in the state of Parana with the following granulometric characteristics, respectively: high clay content and high fine sand distribution. The construction debris, derived from the grinding of ceramic bricks and mortar, was composed of the fraction that passed through a #10 sieve (2.0mm). The soils, the debris and their mixtures were classified by determining their physical properties, compaction properties and unconfined compressive strength. Results showed that the addition of CDW to soil and cement mixtures improves compaction characteristics and increases compressive strength.
FUS is Phosphorylated by DNA-PK and Accumulates in the Cytoplasm after DNA Damage

Abnormal cytoplasmic accumulation of Fused in Sarcoma (FUS) in neurons defines subtypes of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). FUS is a member of the FET protein family that includes Ewing's sarcoma (EWS) and TATA-binding protein-associated factor 2N (TAF15). FET proteins are predominantly localized to the nucleus, where they bind RNA and DNA to modulate transcription, mRNA splicing, and DNA repair. In ALS cases with FUS inclusions (ALS-FUS), mutations in the FUS gene cause disease, whereas FTLD cases with FUS inclusions (FTLD-FUS) do not harbor FUS mutations. Notably, in FTLD-FUS, all FET proteins accumulate with their nuclear import receptor Transportin 1 (TRN1), in contrast ALS-FUS inclusions are exclusively positive for FUS. In the present study, we show that induction of DNA damage replicates several pathologic hallmarks of FTLD-FUS in immortalized human cells and primary human neurons and astrocytes. Treatment with the antibiotic calicheamicin γ1, which causes DNA double-strand breaks, leads to the cytoplasmic accumulation of FUS, TAF15, EWS, and TRN1. Moreover, cytoplasmic translocation of FUS is mediated by phosphorylation of its N terminus by the DNA-dependent protein kinase. Finally, we observed elevated levels of phospho-H2AX in FTLD-FUS brains, indicating that DNA damage occurs in patients. Together, our data reveal a novel regulatory mechanism for FUS localization in cells and suggest that DNA damage may contribute to the accumulation of FET proteins observed in human FTLD-FUS cases, but not in ALS-FUS.
Cryopreserved Oocytes: Update on Clinical Applications and Success Rates

Importance Over the past 3 decades, oocyte cryopreservation procedures have improved rapidly. However, there is limited research reviewing the efficacy of different cooling protocols and inadequate data comparing in vitro fertilization (IVF) outcomes from fresh oocytes with cryopreserved oocytes. Objective The present review was performed to investigate advances in oocyte cryopreservation technologies and identify areas for further research, to determine whether results from IVF using cryopreserved oocytes are comparable to IVF using fresh oocytes, and to identify the patient populations requiring access to oocyte cryopreservation. Evidence Acquisition A literature review was conducted. OVID (MEDLINE) and PubMed databases were queried using phrases such as “oocyte or egg” and “cryopreservation,” “vitrification,” or “slow cooling or slow freezing. ” A total of 180 studies were selected for review. Results Current literature suggests that vitrified oocytes produce superior IVF results to slow-frozen oocytes and may yield comparable outcomes to IVF with fresh oocytes in certain patient populations. Patients at risk of infertility due to disease or age-related decline or oocyte donation programs, couples who fail to produce semen when required for IVF, and patients with legal or ethical reasons against embryo cryopreservation may access cryopreserved oocytes. Conclusions We suggest that women who comprise the previously mentioned patient populations should be offered oocyte vitrification technology. Further research is required to confirm IVF success across all patient populations and determine the best cryopreservation protocols. Relevance This review will be relevant to clinicians interested in fertility treatments using cryopreserved oocytes, fertility preservation, oncology and fertility, and immunology and fertility. Target Audience Obstetricians and gynaecologists, oncologists, immunologists, and rheumatologists Learning Objectives After completing this activity, physicians should be better able to discuss oocyte cryopreservation processes, select patients who may require access to oocyte cryopreservation technology, compare IVF using cryopreserved oocytes with IVF using fresh oocytes, counsel patients regarding the feasibility of oocyte cryopreservation and their chances of pregnancy with cryopreserved oocytes, and implement oocyte cryopreservation as a fertility preservation option in clinical practice.
The impact of geographic distribution and the nature of technical coupling on the quality of global software development projects

Geographically dispersed work is a fundamental trend that has shaped software development in the past few decades. Although researchers have shown that such a trend has its costs in terms of product quality, the past empirical work has neglected to consider the multidimensional nature of geographic dispersion and limited attention has been given to the nature of technical coupling in the context of distributed development. The work reported in this paper seeks to achieve a better understanding of how the quality of systems produced by distributed development projects is impacted by the various dimensions of geographic dispersion and by the forms of technical coupling. We examined 189 software projects from a multinational development organization and our results revealed the various dimensions of distribution that had an independent and complementary impact on the software quality. In particular, we found that projects with uneven distributions of developers across locations were more likely to exhibit higher levels of defects than projects with balanced distributions. Our results also showed that logical dependencies among architectural components are significantly more important for projects than syntactic dependencies. Moreover, considering technical coupling as conditional on project boundaries revealed that internal and external dependencies have a significant and independent impact on the software quality. Copyright © 2010 John Wiley & Sons, Ltd.
Functional subregions of the human entorhinal cortex

The entorhinal cortex (EC) is the primary site of interactions between the neocortex and hippocampus. Studies in rodents and nonhuman primates suggest that EC can be divided into subregions that connect differentially with perirhinal cortex (PRC) vs parahippocampal cortex (PHC) and with hippocampal subfields along the proximo-distal axis. Here, we used high-resolution functional magnetic resonance imaging at 7 Tesla to identify functional subdivisions of the human EC. In two independent datasets, PRC showed preferential intrinsic functional connectivity with anterior-lateral EC and PHC with posterior-medial EC. These EC subregions, in turn, exhibited differential connectivity with proximal and distal subiculum. In contrast, connectivity of PRC and PHC with subiculum followed not only a proximal-distal but also an anterior-posterior gradient. Our data provide the first evidence that the human EC can be divided into functional subdivisions whose functional connectivity closely parallels the known anatomical connectivity patterns of the rodent and nonhuman primate EC. DOI: http://dx.doi. org/10.7554/eLife.06426. 001
Expression and Characterization of GSK-3 Mutants and Their Effect on β-Catenin Phosphorylation in Intact Cells*

Glycogen synthase kinase-3 (GSK-3) is a serine-threonine kinase that is involved in multiple cellular signaling pathways, including the Wnt signaling cascade where it phosphorylates β-catenin, thus targeting it for proteasome-mediated degradation. Unlike phosphorylation of glycogen synthase, phosphorylation of β-catenin by GSK-3 does not require primingin vitro, i.e. it is not dependent on the presence of a phosphoserine, four residues C-terminal to the GSK-3 phosphorylation site. Recently, a means of dissecting GSK-3 activity toward primed and non-primed substrates has been made possible by identification of the R96A mutant of GSK-3β. This mutant is unable to phosphorylate primed but can still phosphorylate unprimed substrates (Frame, S., Cohen, P., and Biondi R. M. (2001) Mol. Cell 7, 1321–1327). Here we have investigated whether phosphorylation of Ser33, Ser37, and Thr41 in β-catenin requires priming through prior phosphorylation at Ser45 in intact cells. We have shown that the Arg96 mutant does not induce β-catenin degradation but instead stabilizes β-catenin, indicating that it is unable to phosphorylate β-catenin in intact cells. Furthermore, if Ser45 in β-catenin is mutated to Ala, β-catenin is markedly stabilized, and phosphorylation of Ser33, Ser37, and Thr41 in β-catenin by wild type GSK-3β is prevented in intact cells. In addition, we have shown that the L128A mutant, which is deficient in phosphorylating Axin in vitro, is still able to phosphorylate β-catenin in intact cells although it has reduced activity. Mutation of Tyr216 to Phe markedly reduces the ability of GSK-3β to phosphorylate and down-regulate β-catenin. In conclusion, we have found that the Arg96 mutant has a dominant-negative effect on GSK-3β-dependent phosphorylation of β-catenin and that targeting of β-catenin for degradation requires prior priming through phosphorylation of Ser45.
Prophage association of mef(A) elements encoding efflux-mediated erythromycin resistance in Streptococcus pyogenes.

OBJECTIVES To compare different mef(A) elements of Streptococcus pyogenes for a possible chimeric genetic nature, i.e. a transposon inserted into a prophage. METHODS Eleven S. pyogenes isolates with efflux-mediated erythromycin resistance were used. The isolates were typed using several genotypic approaches. Gene detection was performed by PCR using specific primer pairs. The mef(A) elements of the test strains were induced with mitomycin C and phage DNA was extracted. Induction was monitored by PCR using primers targeting mef(A). RESULTS Six tetracycline-susceptible isolates had PCR evidence of all of the eight open reading frames (ORFs) of the Tn1207.1 element; their mef(A) element was consistent with the Tn1207.3 element in four isolates and with the 58.8 kb chimeric element in two. Five tetracycline-resistant isolates had no PCR evidence of orf1 and orf2 and showed variable patterns as to orf3, orf7, and orf8. Three ORFs placed along the conserved region downstream of Tn1207.1 in the 58.8 kb mef(A) chimeric element were detected in the six tetracycline-susceptible, but not in the five tetracycline-resistant isolates. Induction assays with mitomycin C demonstrated that the mef(A) elements of all strains tested were present in culture supernatants in a DNAse-resistant form, such as a phage capsid. CONCLUSIONS All recognized mef(A) elements of S. pyogenes appear to be prophage-associated. Whereas the two elements detected in tetracycline-susceptible isolates (Tn1207.3 and the 58.8 kb one) were apparently inserted into the same prophage, the tet(O)-mef(A) element was inserted into a different prophage. Phage transfer is likely to play a critical role in the dissemination of erythromycin resistance in S. pyogenes populations.
Short-term clinical disease progression in HIV-1-positive patients taking combination antiretroviral therapy: the EuroSIDA risk-score

Objectives:To derive and validate a clinically applicable prognostic score for predicting short-term disease progression in HIV-infected patients taking combination antiretroviral therapy (cART). Design and methods:Poisson regression was used to identify prognostic markers for new AIDS/death in patients taking cART. A score was derived for 4169 patients from EuroSIDA and validated on 5150 patients from the Swiss HIV Cohort Study (SHCS). Results:In EuroSIDA, 658 events occurred during 22 321 person-years of follow-up: an incidence rate of 3.0/100 person-years of follow-up [95% confidence interval (CI), 2.7–3.3]. Current levels of viral load, CD4 cell count, CD4 cell slope, anaemia, and body mass index all independently predicted new AIDS/death, as did age, exposure group, a prior AIDS diagnosis, prior antiretroviral treatment and stopping all antiretroviral drugs. The EuroSIDA risk-score was divided into four strata; a patient in the lowest strata would have predicted chance of new AIDS/death of 1 in 801, 1 in 401 and 1 in 201 within the next 3, 6 or 12 months, respectively. The corresponding figures for the highest strata were 1 in 17, 1 in 9 and 1 in 5, respectively. A single-unit increase in the risk-score was associated with a 2.70 times higher incidence of clinical progression (95% CI, 2.56–2.84) in EuroSIDA and 2.88 (95% CI, 2.75–3.02) in SHCS. Conclusions:A clinically relevant prognostic score was derived in EuroSIDA and validated within the SHCS, with good agreement. The EuroSIDA risk-score will be made available publicly via an interface that will perform all calculations for the individual.
Sybil defenses via social networks: a tutorial and survey

The sybil attack in distributed systems refers to individual malicious users joining the system multiple times under multiple fake identities. Sybil attacks can easily invalidate the overarching prerequisite of many fault-tolerant designs which assume that the fraction of malicious nodes is not too large. This article presents a tutorial and survey on effective sybil defenses leveraging social networks. Since this approach of sybil defenses via social networks was introduced 5 years ago, it has attracted much more attention from the research community than many other alternatives. We will first explain the intuitions and insights behind this approach, and then survey a number of specific sybil defense mechanisms based on this approach, including SybilGuard, SybilLimit, SybilInfer, Gatekeeper, SumUp, Whanau, and Ostra. We will also discuss some practical implications and deployment considerations of this approach.
Activation of Neuronal Caspase-3 by Intracellular Accumulation of Wild-Type Alzheimer Amyloid Precursor Protein

Forced overexpression of wild-type Alzheimer amyloid precursor protein (APP) causes postmitotic neurons to degenerate. Caspase-3 (CPP32) is a principal cell death protease involved in neuronal apoptosis during physiological development and under pathological conditions. Here, we investigated whether APP overexpression activates caspase-3 in human postmitotic neurons using adenovirus-mediated gene transfer. When a recombinant adenovirus vector expressing human wild-type APP695 was infected in vitro into neurally differentiated embryonal carcinoma NT2 cells, only postmitotic neurons underwent severe degeneration. Before neurodegeneration, full-length APP- and Aβ-immunoreactive peptides were accumulated in infected neurons, and caspase-3-like protease activity was markedly elevated. Western blot analysis revealed that activated caspase-3 subunits were generated in APP-accumulating neurons. Such neuronal caspase-3 activation was undetectable in NT2 neurons infected with β-galactosidase-expressing adenovirus. Addition of the caspase-3 inhibitor acetyl-Asp-Glu-Val-Asp-aldehyde to the culture medium significantly reduced the severity of degeneration exhibited by APP-overexpressing neurons. Immunocytochemical analyses revealed that some APP-accumulating neurons contained activated caspase-3 subunits and exhibited the characteristics of apoptosis, such as chromatin condensation and DNA fragmentation. Activation of caspase-3 was also observed in vivo in rat hippocampal neurons infected with the APP-expressing adenovirus. These results suggest that wild-type APP is an intrinsic activator of caspase-3-mediated death machinery in postmitotic neurons.