Miracle-dz/UniFAR-FTUs huggingface dataset:
Prions: Generation and Spread Versus Neurotoxicity

Neurodegenerative diseases are characterized by the aggregation of misfolded proteins in the brain. Among these disorders are the prion diseases, which are transmissible, and in which the misfolded proteins (“prions”) are also the infectious agent. Increasingly, it appears that misfolded proteins in Alzheimer and Parkinson diseases and the tauopathies also propagate in a “prion-like” manner. However, the association between prion formation, spread, and neurotoxicity is not clear. Recently, we showed that in prion disease, protein misfolding leads to neurodegeneration through dysregulation of generic proteostatic mechanisms, specifically, the unfolded protein response. Genetic and pharmacological manipulation of the unfolded protein response was neuroprotective despite continuing prion replication, hence dissociating this from neurotoxicity. The data have clear implications for treatment across the spectrum of these disorders, targeting pathogenic processes downstream of protein misfolding.
An atrial-fibrillation-linked connexin40 mutant is retained in the endoplasmic reticulum and impairs the function of atrial gap-junction channels

Connexin40 (Cx40)-containing gap-junction channels are expressed in the atrial myocardium and provide a low-resistance passage for rapid impulse propagation. A germline mutation in the GJA5 gene, which encodes Cx40, resulting in a truncated Cx40 (Q49X) was identified in a large Chinese family with lone (idiopathic) atrial fibrillation (AF). This mutation co-segregated with seven AF probands in an autosomal-dominant way over generations. To test the hypothesis that this Cx40 mutant affects the distribution and function of atrial gap junctions, we studied the Q49X mutant in gap-junction-deficient HeLa and N2A cells. The Q49X mutant, unlike wild-type Cx40, was typically localized in the cytoplasm and failed to form gap-junction plaques at cell-cell interfaces. When the Q49X mutant was co-expressed with Cx40 or Cx43, the mutant substantially reduced the gap-junction plaque formation of Cx40 and Cx43. Electrophysiological studies revealed no electrical coupling of cell pairs expressing the mutant alone and a significant decrease in the coupling conductance when the mutant was co-expressed with Cx40 or Cx43. Further colocalization experiments with the organelle residential proteins indicate that Q49X was retained in the endoplasmic reticulum. These findings provide evidence that the Q49X mutant is capable of impairing gap-junction distribution and function of key atrial connexins, which might play a role in the predisposition to and onset of AF.
Extensive in silico analysis of Mimivirus coded Rab GTPase homolog suggests a possible role in virion membrane biogenesis

Rab GTPases are the key regulators of intracellular membrane trafficking in eukaryotes. Many viruses and intracellular bacterial pathogens have evolved to hijack the host Rab GTPase functions, mainly through activators and effector proteins, for their benefit. Acanthamoeba polyphaga mimivirus (APMV) is one of the largest viruses and belongs to the monophyletic clade of nucleo-cytoplasmic large DNA viruses (NCLDV). The inner membrane lining is integral to the APMV virion structure. APMV assembly involves extensive host membrane modifications, like vesicle budding and fusion, leading to the formation of a membrane sheet that is incorporated into the virion. Intriguingly, APMV and all group I members of the Mimiviridae family code for a putative Rab GTPase protein. APMV is the first reported virus to code for a Rab GTPase (encoded by R214 gene). Our thorough in silico analysis of the subfamily specific (SF) region of Mimiviridae Rab GTPase sequences suggests that they are related to Rab5, a member of the group II Rab GTPases, of lower eukaryotes. Because of their high divergence from the existing three isoforms, A, B, and C of the Rab5-family, we suggest that Mimiviridae Rabs constitute a new isoform, Rab5D. Phylogenetic analysis indicated probable horizontal acquisition from a lower eukaryotic ancestor followed by selection and divergence. Furthermore, interaction network analysis suggests that vps34 (a Class III PI3K homolog, coded by APMV L615), Atg-8 and dynamin (host proteins) are recruited by APMV Rab GTPase during capsid assembly. Based on these observations, we hypothesize that APMV Rab plays a role in the acquisition of inner membrane during virion assembly.
Verbal versus physical victimization from other people's drinking: how do gender, age, and their interactions with drinking pattern affect vulnerability?

OBJECTIVE The main objectives of this study were to determine (1) the extent of differential association of gender and age with being the victim of aggression by someone who has been drinking (i.e., alcohol-related victimization) for both verbal and physical forms of victimization and (2) whether drinking status/pattern interacts with gender and age in predicting verbal and physical victimization. METHOD A general population survey of Canadian adults ages 18-76 was conducted using random digit dialing and computer-assisted telephone interviewing. Respondents who reported verbal victimization only, physical victimization only, and any combination of verbal and physical victimization were compared with those who reported no victimization. RESULTS Verbal victimization was significantly more likely for women than for men, whereas physical victimization was more likely for men than for women. Younger age was more strongly associated with physical than with verbal victimization. In terms of significant interaction effects, the relationship between heavy episodic drinking (HED) and experiencing verbal victimization alone and combined verbal and physical victimization (but not for physical victimization alone) was significant for women but not for men. HED was significantly associated with experiencing combined verbal and physical victimization for younger people but not for older people. CONCLUSIONS Future research on alcohol-related victimization needs to take into consideration the nature of alcohol-related victimization (e.g., verbal vs physical) and potential interactions involving gender and age. The significant relationship between HED and combined verbal and physical victimization for younger persons suggests that prevention efforts aimed at decreasing heavy drinking among young people may reduce their risk of victimization.
A randomized trial of atropine vs patching for treatment of moderate amblyopia: follow-up at age 10 years.

OBJECTIVE To determine the visual acuity outcome at age 10 years for children younger than 7 years when enrolled in a treatment trial for moderate amblyopia. METHODS In a multicenter clinical trial, 419 children with amblyopia (visual acuity, 20/40-20/100) were randomized to patching or atropine eyedrops for 6 months. Two years after enrollment, a subgroup of 188 children entered long-term follow-up. Treatment after 6 months was at the discretion of the investigator; 89% of children were treated. MAIN OUTCOME MEASURE Visual acuity at age 10 years with the electronic Early Treatment Diabetic Retinopathy Study test. APPLICATION TO CLINICAL PRACTICE Patching and atropine eyedrops produce comparable improvement in visual acuity that is maintained through age 10 years. RESULTS The mean amblyopic eye acuity, measured in 169 patients, at age 10 years was 0.17 logMAR (logarithm of the minimum angle of resolution) (approximately 20/32), and 46% of amblyopic eyes had an acuity of 20/25 or better. Age younger than 5 years at entry into the randomized trial was associated with a better visual acuity outcome (P < .001). Mean amblyopic and sound eye visual acuities at age 10 years were similar in the original treatment groups (P = .56 and P = .80, respectively). CONCLUSIONS At age 10 years, the improvement of the amblyopic eye is maintained, although residual amblyopia is common after treatment initiated at age 3 years to younger than 7 years. The outcome is similar regardless of initial treatment with atropine or patching.
Toolkit for Modifying Evidence-Based Practices to Increase Cultural Competence

Acknowledgements The authors of this Toolkit have benefited greatly and drawn from the work of many others in the fields of mental health services and cultural competence. has generously lent the Toolkit project team her expertise in mental health services and cultural competence and has provided invaluable input on the design and focus of the Toolkit. Early work on the Toolkit also involved collaborators at the NYU School of Medicine, Drs. The Toolkit has also benefited from extensive review and consideration by the following experts in the field who generously gave their time to this endeavor:
Detection and Validation of Unscalable Item Score Patterns Using Item Response Theory: An Illustration with Harter's Self-Perception Profile for Children

We illustrate the usefulness of person-fit methodology for personality assessment. For this purpose, we use person-fit methods from item response theory. First, we give a nontechnical introduction to existing person-fit statistics. Second, we analyze data from Harter's (1985) Self-Perception Profile for Children (Harter, 1985) in a sample of children ranging from 8 to 12 years of age (N = 611) and argue that for some children, the scale scores should be interpreted with care and caution. Combined information from person-fit indexes and from observation, interviews, and self-concept theory showed that similar score profiles may have a different interpretation. For some children in the sample, item scores did not adequately reflect their trait level. Based on teacher interviews, this was found to be due most likely to a less developed self-concept and/or problems understanding the meaning of the questions. We recommend investigating the scalability of score patterns when using self-report inventories to help the researcher interpret respondents' behavior correctly.
First isolation of Mycobacterium avium subsp Paratuberculosis from commercial pasteurized milk in Argentina

Mycobacterium avium subsp paratuberculosis was isolated from two out of seventy samples (2.86 %) of pasteurized and ultra-pasteurized milk. The isolates were positives to IS900 PCR and showed a C17 RFLP pattern, the most prevalent in Argentina. The present study is the first report of Mycobacterium avium subsp paratuberculosis culture from pasteurized milk in Argentina.
High-Speed Magnetohydrodynamic Flow Control Analyses With 3-D Simulations

Abstract : Magnetohydrodynamic studies of high-speed flow control are described with emphasis on understanding fluid response to specific plasma-based perturbations. Detailed analysis is presented of the effect of magnitudes and gradients of magnetic and electric fields, their orientation relative to the velocity vector, ionized region location and extent, and various nondimensional parameters. The balance between ponderomotive force and heating is a major determinant of the effectiveness through competition between work and ohmic dissipation, while viscous/inviscid interactions play a crucial role by distorting the velocity field. The interaction with an external circuit through electrodes is relatively efficient when fluid is slowed and energy is extracted, but yields high boundary layer heating and loss of control performance when fluid is accelerated. These observations are employed to unify results focused on a broad range of objectives including heat transfer reduction, 3-D separation suppression through momentum transfer, inviscid instability growth rate modulation and energy management in multiple simulated tip-to-tail scramjet designs
Production of Biogenic Mn Oxides by Leptothrix discophora SS-1 in a Chemically Defined Growth Medium and Evaluation of Their Pb Adsorption Characteristics

ABSTRACT Biogenic Mn oxides were produced by the bacterium Leptothrix discophora SS-1 (= ATCC 3182) in a chemically defined mineral salts medium, and the Pb binding and specific surface area of these oxides were characterized. Growth of SS-1 in the defined medium with pyruvate as a carbon and energy source required the addition of vitamin B12. Complete oxidation of Mn(II) within 60 h required the addition of ≥0.1 μM FeSO4. Pb adsorption isotherms were determined for the biogenic Mn oxides (and associated cells with their extracellular polymer) and compared to the Pb adsorption isotherms of cells and exopolymer alone, as well as to abiotic Mn oxides. The Pb adsorption to cells and exopolymer with biogenic Mn oxides (0.8 mmol of Mn per g) at pH 6.0 and 25°C was 2 orders of magnitude greater than the Pb adsorption to cells and exopolymer alone (on a dry weight basis). The Pb adsorption to the biogenic Mn oxide was two to five times greater than the Pb adsorption to a chemically precipitated abiotic Mn oxide and several orders of magnitude greater than the Pb adsorption to two commercially available crystalline MnO2 minerals. The N2Brunauer-Emmet-Teller specific surface areas of the biogenic Mn oxide and fresh Mn oxide precipitate (224 and 58 m2/g, respectively) were significantly greater than those of the commercial Mn oxide minerals (0.048 and 4.7 m2/g). The Pb adsorption capacity of the biogenic Mn oxide also exceeded that of a chemically precipitated colloidal hydrous Fe oxide under similar solution conditions. These results show that amorphous biogenic Mn oxides similar to those produced by SS-1 may play a significant role in the control of trace metal phase distribution in aquatic systems.
Characterization and Cloning of CelR, a Transcriptional Regulator of Cellulase Genes from Thermomonospora fusca *

CelR, a protein that regulates transcription of cellulase genes in Thermomonospora fusca(Actinomycetaceae) was purified to homogeneity. A 6-kilobase NotI-SacI fragment of T. fuscaDNA containing the celR gene was cloned intoEsherichia coli and sequenced. The celR gene encodes a 340-residue polypeptide that is highly homologous to members of the GalR-LacI family of bacterial transcriptional regulators. CelR specifically binds to a 14-base pair inverted repeat, which has sequence similarity to the binding sites of other family members. This site is present in regions upstream of all six cellulase genes inT. fusca. The binding of CelR to the celEpromoter is inhibited specifically by low concentrations of cellobiose (0.2–0.5 mm), the major end product of cellulases. The other sugars tested did not affect binding at equivalent or 50-fold higher concentrations. The results suggest that CelR may act as a repressor, and that the mechanism of induction involves a direct interaction of CelR with cellobiose.
Patterns of Local and Nodal Failure in Malignant Pleural Mesothelioma After Extrapleural Pneumonectomy and Photon-Electron Radiotherapy

Introduction: Multimodality therapy including extrapleural pneumonectomy (EPP), chemotherapy, and radiotherapy (RT) is often recommended for fit patients with early stage malignant pleural mesothelioma. Planning RT after an EPP is difficult due to the large target area, the high doses required to prevent recurrence, and the proximity of critical structures. We studied patterns of local and nodal recurrence in patients treated at our institution with EPP and RT, and whether advanced treatment planning techniques, such as intensity modulated radiotherapy (IMRT), could have been of potential benefit. Methods: From 1993 to 2008, 86 patients with malignant pleural mesothelioma underwent EPP followed by hemithoracic RT (median dose: 54 Gy). The RT technique included a combination of photons and electrons to maximize dose to the target, whereas minimizing dose to normal tissues. After treatment, patients were followed with serial imaging and patterns of local and nodal failure were studied. Results: Median follow-up time for 78 analyzed patients was 17 months. Eight percent were in stage I, 35% stage II, 55% stage III, and 2% stage IV. Ten percent of all patients developed late grade 3 pulmonary toxicity and no patient died of RT. Fifteen patients failed in local and/or nodal sites and did not have a distant component to their failure pattern. Of these 15 patients, 10 failed in regions of dose inhomogeneity and could have possibly benefited from IMRT. Conclusions: The photon-electron technique was tolerable, but IMRT may provide better target coverage in some patients. IMRT’s advantages must be balanced against the increased risk of fatal pulmonary toxicity.
What is the fate of erosions in early rheumatoid arthritis? Tracking individual lesions using x rays and magnetic resonance imaging over the first two years of disease.

OBJECTIVES To investigate the progression of erosions at sites within the carpus, in patients with early rheumatoid arthritis (RA), using magnetic resonance imaging (MRI) and plain radiology over a two year period. METHODS Gadolinium enhanced MRI scans of the dominant wrist were performed in 42 patients with RA at baseline (within six months of symptom onset) and one year. Plain wrist radiographs (x rays) and clinical data were obtained at baseline, one year, and two years. Erosions were scored by two musculoskeletal radiologists on MRI and x ray at 15 sites in the wrist. A patient centred analysis was used to evaluate the prognostic value of a baseline MRI scan. A lesion centred analysis was used to track the progression of individual erosions over two years. RESULTS The baseline MRI erosion score was predictive of x ray erosion score at two years (p=0.004). Patients with a "total MRI score" (erosion, bone oedema, synovitis, and tendonitis) > or =13 at baseline were significantly more likely to develop erosions on x ray at two years (odds ratio 13.4, 95% CI 2.65 to 60.5, p=0.002). Baseline wrist MRI has a sensitivity of 80%, a specificity of 76%, a positive predictive value of 67%, and a high negative predictive value of 86% for the prediction of wrist x ray erosions at two years. A lesion centred analysis, which included erosions scored by one or both radiologists, showed that 84% of baseline MRI erosions were still present at one year. When a more stringent analysis was used which required complete concordance between radiologists, all baseline lesions persisted at one year. The number of MRI erosion sites in each patient increased from 2.1 (SD 2.7) to 5.0 (4.6) (p<0.0001) over the first year of disease. When MRI erosion sites were tracked, 21% and 26% were observed on x ray, one and two years later. A high baseline MRI synovitis score, Ritchie score, and erythrocyte sedimentation rate were predictive of progression of MRI erosions to x ray erosions over one year (p=0.005, 0.01, and 0.03 respectively), but there was no association with the shared epitope. Progression of MRI erosions to x ray erosions was not seen in those with transient polyarthritis. CONCLUSIONS MRI scans of the wrist, taken when patients first present with RA, can predict radiographic erosions at two years. MRI may have a role in the assessment of disease prognosis and selection of patients for more or less aggressive treatment. However, only one in four MRI erosions progresses to an x ray erosion over one year, possibly owing to healing, observer error, or technical limitations of radiography at the carpus. Progression of MRI erosions to x ray erosions is greatest in those with high baseline disease activity.
Cotransplantation of MSCs and HSCs.

Apilot study by Wu et al. (1) suggests that umbilical cordYderived mesenchymal stem cells (UCMSCs) promote hematopoietic engraftment when cotransplanted with cord blood (CB) cells (Fig. 1A). The authors make good use of two somatic stem cells, both derived from umbilical cord. Together with the establishment of their UCMSC bank, their trial appears to be potentially meaningful for future development of UCMSC cotransplantation. A recent article by de Lima et al. (2) demonstrates that hematopoietic engraftment is improved by transplantation of CB cells that are expanded ex vivo with allogeneic bone marrowYderived MSCs (BMMSCs). In this study (2), two CB units were transplanted: one was an expanded CB unit and the other was an unmanipulated CB unit (Fig. 1B). Although BMMSCs were used ex vivo only (2), expanded CB in combination with unmanipulated CB significantly improved engraftment compared with unmanipulated CB only. Based on these findings, it would be interesting to investigate whether addition of ex vivo expanded CB to the pilot study setting by Wu et al. (1) would further improve engraftment (Fig. 1C). The study by de Lima et al. (2) appears to be safe and effective, because ex vivo expanded CB unit would contribute to rapid recovery of hematopoiesis. However, this study raises some concerns. (i) CB was expanded under culture condition with cytokines including granulocyte colony-stimulating factor, which would expand myeloid progenitor cells at the expense of longterm hematopoietic stem cells (LT-HSCs) (Fig. 1B). Because long-term repopulation has been shown to be dependent on unmanipulated CB, there might be a longterm risk of cytopenia. (ii) Due to reduced percentage of lymphocytes in expanded CB described by de Lima et al. (2), there might be an increased risk of viral infection. Regarding (i), recent evidence suggests that in vitro maintenance of LT-HSCs is possible by dual inhibition (2i) of both glycogen synthase kinase-3 and mammalian target of rapamycin, without use of cytokines that promote differentiation of LT-HSCs (3). Although LT-HSCs were shown to be preserved
Blind speech separation employing directional statistics in an Expectation Maximization framework

In this paper we propose to employ directional statistics in a complex vector space to approach the problem of blind speech separation in the presence of spatially correlated noise. We interpret the values of the short time Fourier transform of the microphone signals to be draws from a mixture of complexWatson distributions, a probabilistic model which naturally accounts for spatial aliasing. The parameters of the density are related to the a priori source probabilities, the power of the sources and the transfer function ratios from sources to sensors. Estimation formulas are derived for these parameters by employing the Expectation Maximization (EM) algorithm. The E-step corresponds to the estimation of the source presence probabilities for each time-frequency bin, while the M-step leads to a maximum signal-to-noise ratio (MaxSNR) beamformer in the presence of uncertainty about the source activity. Experimental results are reported for an implementation in a generalized sidelobe canceller (GSC) like spatial beamforming configuration for 3 speech sources with significant coherent noise in reverberant environments, demonstrating the usefulness of the novel modeling framework.