Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Mitochondria in Oxidative Stress and Aging

The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS), considered as the pathogenic agent of many diseases and of aging. We have investigated the role of Complex I in superoxide radical production and found by combined use of specific inhibitors of Complex I that the one‐electron donor in the Complex to oxygen is a redox center located prior to the sites where three different types of coenzyme Q (CoQ) competitors bind, to be identified with an Fe‐S cluster, most probably N2, or possibly an ubisemiquinone intermediate insensitive to all the above inhibitors. Short‐chain coenzyme Q analogues enhance superoxide formation, presumably by mediating electron transfer from N2 to oxygen. The clinically used CoQ analogue idebenone is particularly effective, raising doubts about its safety as a drug. The mitochondrial theory of aging considers somatic mutations of mitochondrial DNA induced by ROS as the primary cause of energy decline; in rat liver mitochondria, Complex I appears to be most affected by aging and to become strongly rate limiting for electron transfer. Mitochondrial energetics is also deranged in human platelets upon aging, as demonstrated by the decreased Pasteur effect (enhancement of lactate production by respiratory inhibitors). Cells counteract oxidative stress by antioxidants: CoQ is the only lipophilic antioxidant to be biosynthesized. Exogenous CoQ, however, protects cells from oxidative stress by conversion into its reduced antioxidant form by cellular reductases. The plasma membrane oxidoreductase and DT‐diaphorase are two such systems: likewise, they are overexpressed under oxidative stress conditions.
Exposure to pesticides or solvents and risk of Parkinson disease

Objective: To investigate the risk of Parkinson disease (PD) associated with exposure to pesticides and solvents using meta-analyses of data from cohort and case-control studies. Methods: Prospective cohort and case-control studies providing risk and precision estimates relating PD to exposure to pesticides or solvents or to proxies of exposure were considered eligible. The heterogeneity in risk estimates associated with objective study quality was also investigated. Results: A total of 104 studies/3,087 citations fulfilled inclusion criteria for meta-analysis. In prospective studies, study quality was not a source of heterogeneity. PD was associated with farming and the association with pesticides was highly significant in the studies in which PD diagnosis was self-reported. In case-control studies, study quality appeared to be a source of heterogeneity in risk estimates for some exposures. Higher study quality was frequently associated with a reduction in heterogeneity. In high-quality case-control studies, PD risk was increased by exposure to any-type pesticides, herbicides, and solvents. Exposure to paraquat or maneb/mancozeb was associated with about a 2-fold increase in risk. In high-quality case-control studies including an appreciable number of cases (>200), heterogeneity remained significantly high (>40%) only for insecticides, organochlorines, organophosphates, and farming; also, the risk associated with rural living was found to be significant. Conclusions: The literature supports the hypothesis that exposure to pesticides or solvents is a risk factor for PD. Further prospective and high-quality case-control studies are required to substantiate a cause-effect relationship. The studies should also focus on specific chemical agents.
Entamoeba histolytica Cysteine Proteinase 5 Binds Integrin on Colonic Cells and Stimulates NFκB-mediated Pro-inflammatory Responses*

Integrins are important mammalian receptors involved in normal cellular functions and the pathogenesis of inflammation and disease. Entamoeba histolytica is a protozoan parasite that colonizes the gut, and in 10% of infected individuals, causes amebic colitis and liver abscess resulting in 105 deaths/year. E. histolytica-induced host inflammatory responses are critical in the pathogenesis of the disease, yet the host and parasite factors involved in disease are poorly defined. Here we show that pro-mature cysteine proteinase 5 (PCP5), a major virulent factor that is abundantly secreted and/or present on the surface of ameba, binds via its RGD motif to αVβ3 integrin on Caco-2 colonic cells and stimulates NFκB-mediated pro-inflammatory responses. PCP5 RGD binding to αVβ3 integrin triggered integrin-linked kinase(ILK)-mediated phosphorylation of Akt-473 that bound and induced the ubiquitination of NF-κB essential modulator (NEMO). As NEMO is required for activation of the IKKα-IKKβ complex and NFκB signaling, these events markedly up-regulated pro-inflammatory mediator expressions in vitro in Caco-2 cells and in vivo in colonic loop studies in wild-type and Muc2−/− mice lacking an intact protective mucus barrier. These results have revealed that EhPCP5 RGD motif is a ligand for αVβ3 integrin-mediated adhesion on colonic cells and represents a novel mechanism that E. histolytica trophozoites use to trigger an inflammatory response in the pathogenesis of intestinal amebiasis.
Drug-Regulated Expression of Plasmodium falciparum P-Glycoprotein Homologue 1: a Putative Role for Nuclear Receptors

ABSTRACT Acquired resistance to therapeutic agents is a major clinical concern in the prevention/treatment of malaria. The parasite has developed resistance to specific drugs through two mechanisms: mutations in target proteins such as dihydrofolate reductase and the bc1 complex for antifolates and nathoquinones, respectively, and alterations in predicted parasite transporter molecules such as P-glycoprotein homologue 1 (Pgh1) and Plasmodium falciparum CRT (PfCRT). Alterations in the expression of Pgh1 have been associated with modified susceptibility to a range of unrelated drugs. The molecular mechanism(s) that is responsible for this phenotype is unknown. We have shown previously (A. M. Ndifor, R. E. Howells, P. G. Bray, J. L. Ngu, and S. A. Ward, Antimicrob. Agents Chemother. 37:1318-1323, 2003) that the anticonvulsant phenobarbitone (PB) can induce reduced susceptibility to chloroquine (CQ) in P. falciparum, and in the current study, we provide the first evidence for a molecular mechanism underlying this phenomenon. We demonstrate that pretreatment with PB can elicit decreased susceptibility to CQ in both CQ-resistant and CQ-sensitive parasite lines and that this is associated with the increased expression of the drug transporter Pgh1 but not PfCRT. Furthermore, we have investigated the proximal promoter regions from both pfmdr1 and pfcrt and identified a number of putative binding sites for nuclear receptors with sequence similarities to regions known to be activated by PB in mammals. Whole-genome analysis has revealed a putative nuclear receptor gene, providing the first evidence that nuclear receptor-mediated responses to drug exposure may be a mechanism of gene regulation in P. falciparum.
Less is More Probabilistic Models for Retrieving Fewer Relevant Documents

Traditionally, information retrieval systems aim to maximize the number of relevant documents returned to a user within some window of the top. For that goal, the probability ranking principle , which ranks documents in decreasing order of probability of relevance, is provably optimal. However, there are many scenarios in which that ranking does not optimize for the user’s information need. One example is when the user would be satisﬁed with some limited number of relevant documents, rather than needing all relevant documents. We show that in such a scenario, an attempt to return many relevant documents can actually reduce the chances of ﬁnding any relevant documents. We consider a number of information retrieval metrics from the literature, including the rank of the ﬁrst relevant result, the %no metric that penalizes a system only for retrieving no relevant re-sults near the top, and the diversity of retrieved results when queries have multiple interpretations. We observe that given a probabilistic model of relevance, it is appropriate to rank so as to directly optimize these metrics in expectation. While doing so may be computationally intractable, we show that a simple greedy optimization algorithm that approximately optimizes the given objectives produces rankings for TREC queries that outperform the standard approach based on the probability ranking principle.
Stock Prices, News and Economic Fluctuations

In this paper we show that the joint behavior of stock prices and TFP favors a view of business cycles driven largely by a shock that does not affect productivity in the short run -- and therefore does not look like a standard technology shock -- but affects productivity with substantial delay -- and therefore does not look like a monetary shock. One structural interpretation we suggest for this shock is that it represents news about future technological opportunities which is first captured in stock prices. We show that this shock causes a boom in consumption, investment and hours worked that precede productivity growth by a few years. Moreover, we show that this shock explains about 50\% of business cycle fluctuations.
On large deviation property of recurrence times

We extend the study by Ornstein and Weiss on the asymptotic behavior of the normalized version of recurrence times and establish the large deviation property for a certain class of mixing processes. Further, an estimator for entropy based on recurrence times is proposed for which large deviation behavior is proved for stationary and ergodic sources satisfying similar mixing conditions.
Survey and analysis on the mental health of 231 postgraduates

Objective:To investigate the mental health status present among postgraduates.Methods:Symptom checklist 90(SCL-90)was employed to appraise the mental health status in 231 postgraduates.Results:43.70% of the postgraduates were in abnormal psychological state.Compared with the national Chinese adult norm,the subjects scored over on the essential factors such as somatization disorder,depressed mood,anxiety,hostile feeling,feeling of fear,paranoid idea and even mental illness.Also,the mental condition varied significantly in terms of different ages,grades,marital status and work experience.Conclusion:Poor mental health is nowadays popular in a considerable number of postgraduates.
Experimental manipulation shows that the white wing patch in collared flycatchers is a male sexual ornament

Descriptive analysis suggests that a conspicuous white wing patch in dichromatic (black and white) pied and collared flycatchers is under sexual selection. Here, we use an experimental approach to test whether this trait is indeed the target of selection. We caught 100 collared flycatcher Ficedula albicollis males soon after their arrival on the breeding site. We reduced (blackened) part of the white wing patch in half of these males and recorded their mating success and within and extra-pair offspring production. Reduction of the size of the white wing patch lowered a male's probability to attract a secondary social female, but not a primary female. However, primary females paired to males with a reduced wing patch were smaller (in tarsus), suggesting that male choice of partner or female–female competition over mates occurs in this species. The probability of pairing with a primary female (but not other components of male reproductive success) declined with arrival time (proxied by the date of capture). Males with a reduced wing patch size tended to sire less extra-pair offspring, although this relationship was reversed in one of the three study plots, suggesting that mating dynamics are context dependent. While our findings show that wing patch size is the target of sexual selection, the pathways and the strength of selection on this ornament differed markedly from a previous descriptive study. Nonexperimental studies of sexual selection in the wild may overestimate its importance because male fitness and ornamentation both depend positively on environmental conditions.
Fast imaging of an atmospheric pressure glow discharge in He with a polymer film

To visualize the development of an atmospheric pressure glow discharge in He and the influence of polymer film on the discharge, short exposure time images were recorded using a gated intensified charge coupled detector. If the polymer film is stretched in the middle of the gap, a discharge region on each side of the polymer is created with the characteristic structure of a glow discharge. In this case, strongly asymmetric discharge current pulses can be generated depending on the frequency and the applied voltage.
Annotation of Sentence Structure; Capturing the Relationship among Clauses in Czech Sentences

The goal of the presented project is to assign a structure of clauses to Czech sentences from the Prague Dependency Treebank (PDT) as a new layer of syntactic annotation, a layer of clause structure. The annotation is based on the concept of segments, linguistically motivated and easily automatically detectable units. The task of the annotators is to identify relations among segments, especially relations of super/subordination, coordination, apposition and parenthesis. Then they identify individual clauses forming complex sentences. In the pilot phase of the annotation, 2,699 sentences from PDT were annotated with respect to their sentence structure.
prk, a Cytokine-inducible Human Protein Serine/Threonine Kinase Whose Expression Appears to be Down-regulated in Lung Carcinomas*

We have cloned and characterized a putative protein serine/threonine kinase termed prk through a combination of polymerase chain reaction and conventional cDNA library screening approaches. There are apparently two distinct domains within prk protein deduced from its nucleotide sequences. The amino-terminal portion has the feature of the catalytic domain of a serine/threonine kinase and shows strong homology to mouse fnk and other polo family kinases including mouse snk, human and murine plk, Drosophila polo, and yeast Cdc5. The carboxyl-terminal portion, presumably the regulatory domain, shares extensive homology to mouse fnk. Northern blotting analyses reveal that prk expression is restricted to a very limited number of tissues with placenta, ovaries, and lung containing detectable amounts of prk mRNA. prk mRNA expression is also detected at a low level in the megakaryocytic cell line Dami, MO7e, and three brain glioma cell lines. In addition, refeeding of serum-deprived MO7e, Dami, and K562 cells of hematopoietic origin and GMOO637D of lung fibroblasts rapidly activates prk mRNA expression with its peak induction around 2 h after serum addition. prk gene activation by the serum requires no new protein synthesis. The recombinant cytokines such as interleukin-3 and thrombopoietin also activate prk mRNA expression in MO7e cells. Furthermore, a survey of RNAs isolated from the tumor and the uninvolved tissues from 18 lung cancer patients reveals that prk mRNA expression is significantly down-regulated in tumor tissues. Southern blotting analysis indicates that the prk gene is present in a single copy in the genome of tumors and normal cells. Taken together, these results suggest that prk expression may be restricted to proliferating cells and involved in the regulation of cell cycle progression. The molecular cloning of prk cDNA will facilitate the study of its biological role as well as its potential role in tumorigenesis.
Reliability of sternal instability scale (SIS) for transverse sternotomy in lung transplantation (LTX)

ABSTRACT A surgical incision for bilateral sequential lung transplantation (BSLTX) is the “clam shell” (CSI) approach via bilateral anterior thoracotomies and a transverse sternotomy to allow for sequential replacement of the lungs. This can be associated with significant post-operative pain, bony overriding or sternal instability. The sternal instability scale (SIS) is a non-invasive manual assessment tool that can be used to detect early bony non-union or instability following CSI; however, its reliability is unknown. Objective: This prospective blinded reliability study aimed to assess intra-rater and inter-rater reliability of the SIS following lung transplantation. Method: Participants post BSLTX aged older than 18 years underwent sternal assessment utilizing the SIS. Two assessors examined the sternum using a standardized protocol at two separate time points with a test–re-test time of 48 hours. The outcome measure was SIS tool using four categories from 0 (clinically stable) to 3 (separated sternum with overriding). Results: In total, 20 participants (75% female) with a mean age of 48 years (SD 17) and mean pain score of 3 out of 10 were included, 60% having well healed wounds and 25% reporting symptoms of sternal clicking. The most painful self-reported painful activity was coughing. The SIS demonstrated excellent reliability with a kappa = 0.91 by different assessors on the same day, and kappa = 0.83 for assessments by the same assessor on different days. Conclusion: The SIS is a reliable manual assessment tool for evaluation of sternal instability after CSI following BSLTX and may facilitate the timely detection and management of sternal instability.
Multicenter Clinical Trial of Bortezomib in Relapsed/Refractory Waldenstrom's Macroglobulinemia: Results of WMCTG Trial 03-248

Purpose: Waldenstrom's macroglobulinemia (WM) is a B-cell disorder. Despite advances in the therapy, WM remains incurable. As such, novel therapeutic agents are needed for the treatment of WM. Experimental Design: In this multicenter study, 27 patients with WM received up to eight cycles of bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11. All but one patient had relapsed/or refractory disease. Results: Following therapy, median serum IgM levels declined from 4,660 to 2,092 mg/dL (P < 0.0001). The overall response rate was 85%, with 10 and 13 patients achieving minor and major responses, respectively. Responses were prompt and occurred at median of 1.4 months. The median time to progression for all responding patients was 7.9 (range, 3-21.4+) months. The most common grade III/IV toxicities occurring in ≥5% of patients were sensory neuropathies (22.2%), leukopenia (18.5%), neutropenia (14.8%), dizziness (11.1%), and thrombocytopenia (7.4%). Sensory neuropathies resolved or improved in nearly all patients following cessation of therapy. Conclusions: The results of these studies show that bortezomib is an active agent in relapsed and refractory WM.
Mannan-coated gelatin nanoparticles for sustained and targeted delivery of didanosine: In vitro and in vivo evaluation

Mannan-coated gelatin nanoparticles for sustained and targeted delivery of didanosine: In vitro and in vivo evaluation Macrophages of the reticuloendothelial system and brain act as major reservoir for HIV because of their long term survival after HIV infection and ability to spread virus particles to bystander CD4 positive lymphocyte cells. The objective of the present study was to investigate mannan-coated nanoparticles for macrophage targeting of didanosine. Different didanosine loaded nanoparticles were prepared using the double desolvation technique and were characterized in vitro, ex vivo and in vivo. Results of the ex vivo cellular uptake study indicated 5--fold higher uptake of didanosine from the mannan-coated nanoparticles formulation (62.5 ± 5.4%) by the macrophages in comparison with didanosine solution in phosphate buffer saline (PBS, pH 7.4) (12.1 ± 2.3%). The better cellular uptake from the nanoparticles formulation was further confirmed by fluorescence microscopy using hydrophilic 6-carboxyfluorescein as a marker. Results of the quantitative biodistribution study showed 1.7, 12.6 and 12.4 times higher localization of didanosine in the spleen, lymph nodes and brain, respectively, after administration of mannan-coated nanoparticles compared to that after injection of didanosine solution in PBS (pH 7.4). Results of the present study showed that the mannan-coated nanoparticles targeted didanosine to the macrophage by mannosyl receptor mediated endocytosis. Želatinske nanočestice obložene mananom za polaganu i ciljanu isporuku didanozina: In vitro i in vivo vrednovanje Makrofagi retikuloendotelnog sustava i mozak djeluju kao glavni rezervoari za HIV zbog njihovog dugoročnog preživljavanja nakon infekcije HIV-om i sposobnosti da usmjere virusne čestice u CD4 pozitivne limfocite. Cilj rada bio je ispitati nanočestice obložene mananom za ciljanu isporuku didanozina u makrofage. Koristeći metodu dvostruke desolvatacije pripravljene su različite nanočestice s didanozinom te su zatim karakterizirane in vitro, ex vivo i in vivo. Rezultati ex vivo ispitivanja ukazuju da je unos didanozina u makrofage 5 puta veći iz nanočestica obloženih mananom (62,5 ± 5,4%) u usporedbi s otopinom didanozina u fosfatnom puferu (PBS, pH 7,4) (12,1 ± 2,3%). Bolji celularni unos iz nanočestica potvrđen je fluorescentnom mikroskopijom koristeći hidrofilni 6-karboksifluorescein kao marker. Rezultati kvantitativne biodistribucije pokazuju da je lokalizacija didanozina u slezeni, limfnim čvorovima i mozgu 1,7, 12,6, odnosno 12,4 puta veća nakon primjene nanočestica obloženih mananom nego nakon primjene otopine didanozina u PBS-u (pH 7,4). Nanočestice s mananom usmjeravaju didanozin u makrofage procesom endocitoze u kojoj posreduju receptori za manozu.
"Broken Arabic" and Ideologies of Completeness: Contextualizing the Category of Native and Heritage Speaker in the University Arabic Classroom

A traves de la observacion semanal de los participantes y once entrevistas semiestructuradas realizadas con estudiantes bilingues de la segunda generacion en una clase del arabe por hablantes nativos / hablantes de la lengua de origen (heritage language speakers) en City University de Nueva York (CUNY), hago investigacion en las conexiones interdiscursivas entre la nocion, por parte de los estudiantes, sobre 'el arabe roto' y el concepto de 'la adquisicion incompleto' y / o 'la atricion' (Montrul, 2013). En este trabajo se aleja del concepto de dominio de la lengua hacia su performatividad para reconocer y apoyar diversos repertorios en movimiento.
Psychological Status at Time of Diagnosis and Patients' Ratings of Cosmesis Following Radiation Therapy for Breast Cancer

Abstract This retrospective pilot study examined the relationship between psychological status at the time of breast cancer diagnosis and ratings of cosmetic outcome later. Sixty-three patients completed measures of depression, anxiety, and quality of life at the time of diagnosis. Following lumpectomy and radiation therapy, these patients and their radiation oncologists completed ratings of the quality of the cosmetic outcome (Cosmesis). The results indicated that both psychological distress and quality of life were related to patients' ratings of Cosmesis, while only patients' quality of life was related to physicians' ratings of Cosmesis. We conclude that Cosmesis is a multifaceted construct that incorporates both physical and psychological factors.