Miracle-dz/UniFAR-FTUs huggingface dataset:
Review of eprodisate for the treatment of renal disease in AA amyloidosis

Secondary (AA) amyloidosis is a multisystem disorder complicating chronic infections or inflammatory diseases. It is characterized by extracellular deposit of fibrils composed of fragments of serum amyloid A (SAA), an acute phase reactant protein. The kidney is the most frequent organ involved, manifesting as progressive proteinuria and renal impairment. Attenuation of the level of circulating SAA protein by treating the underlying inflammatory condition remains the primary strategy in treating AA amyloidosis. However, at times, achieving adequate control of protein production can prove difficult. In addition, relapse of renal function often occurs rapidly following any subsequent inflammatory stimulus in patients with existing amyloidosis. Recently there has been an interest in finding other potential strategies targeting amyloid deposits themselves. Eprodisate is a sulfonated molecule with a structure similar to heparan sulfate. It competitively binds to the glycosaminoglycan-binding sites on SAA and inhibits fibril polymerization and amyloid deposition. Recent randomized clinical trial showed that it may slow down progressive renal failure in patients with AA amyloidosis. However confirmatory studies are needed and results of a second Phase III study are eagerly awaited to clarify whether or not eprodisate has a place in treating renal amyloid disease.
Use of Heterologous Complementary DNA Array Screening to Analyze Bovine Oocyte Transcriptome and Its Evolution During In Vitro Maturation1

Abstract We have analyzed gene expression in bovine oocytes before and after in vitro maturation (IVM) using heterologous hybridization onto cDNA array. Total RNA was purified from pools of over 200 oocytes either immediately after aspiration from follicles at the surface of slaughterhouse cow ovaries or following in vitro maturation. Radiolabeled cDNA probes were generated by reverse-transcription followed by linear PCR amplification and were hybridized to Atlas human cDNA arrays. To our knowledge, this is the first report of gene expression profiling by this technology in the mammalian female germ cell. Our results demonstrate that cDNA array screening is a suitable method for analyzing the transcription pattern in oocytes. About 300 identified genes were reproducibly shown to be expressed in the bovine oocyte, the largest profile available so far in this model. The relative abundance of most messenger RNAs appeared stable during IVM. However, 70 transcripts underwent a significant differential regulation (by a factor of at least two). Their potential role in the context of oocyte maturation is discussed. Together they constitute a molecular signature of the degree of oocyte cytoplasmic maturation achieved in vitro.
Occupational and environmental exposures and lung cancer in an industrialised area in Italy

Aims: To investigate the effects of occupational exposures and residence near to industrial sites on lung cancer mortality in an area in Italy. Methods: 234 cases of lung cancer and 729 controls matched by sex, age, and date of death were enrolled. Environmental exposure was evaluated using historical residence data. A geographical information system was used to compute distances from residence to pollution source (cement factory, power plants, harbour) and an average distance was computed for each subject. Odds ratios (OR) and 95% confidence intervals (CI) in a logistic regression model were used to estimate the relative risk of lung cancer associated with the risk factors (smoking habits and occupational exposure) collected by questionnaire; ORs for distances from pollution sources and from city centre were computed, adjusting for smoking habits, education, and occupation. Results: Smoking habits (⩽10 cigarettes/day, OR = 2.28; 11–20, OR = 4.64; >20, OR = 6.61) and occupational exposure to asbestos (OR = 3.50) were significantly associated with lung cancer risk. Reported traffic level of area of residence and residence near the four sources were not associated with increased risk of lung cancer. There was a significantly increased risk for those residing outside the city centre, in the southern outskirts (OR = 1.51). Conclusions: The increased lung cancer risk observed in the area can partly be explained by occupational exposures. The increased risk in the outskirts of the city is consistent with the results of dispersion models that indicate high levels of pollutant deposition in the same area.
False resistance to imipenem with a microdilution susceptibility testing system

Routine monitoring of antibiotic resistance at Children's Hospital, Boston, detected a dramatic increase in the prevalence of imipenem-resistant strains of Pseudomonas aeruginosa. Further studies documented that false resistance to imipenem was due, in part, to the loss of imipenem potency in customized MIC microdilution trays supplied by Sensititre Ltd. (West Sussex, United Kingdom). Recognition of the problem was delayed by use of the quality control standard recommended by the manufacturer, which were higher and broader than those suggested by the National Committee for Clinical Laboratory Standards.
A Survey of Malware Detection Techniques

Abstract 31 Introduction 42 What is Malware? 4 2.1 Who are the Users and Creators of Malware? 6 3 The Malware Detector 64 Malware Detection Techniques 7 4.1 Anomaly-based Detection . 94.1. 1 Dynamic Anomaly-based Detection . 104.1. 2 Static Anomaly-based Detection . 154.1. 3 Hybrid Anomaly-based Detection . 164.2 Speciﬁcation-based Detection . 184.2.1 Dynamic Speciﬁcation-based Detection . 184.2. 2 Static Speciﬁcation-based Detection . 264.2. 3 Hybrid Speciﬁcation-based Detection . 284.3 Signature-based detection . 314.3. 1 Dynamic Signature-based Detection . 334.3. 2 Static Signature-based Detection . 344.3. 3 Hybrid Signature-based Detection . 38
Involvement of the Glycogen Synthase Kinase-3 Signaling Pathway in TBI Pathology and Neurocognitive Outcome

Background Traumatic brain injury (TBI) sets in motion cascades of biochemical changes that result in delayed cell death and altered neuronal architecture. Studies have demonstrated that inhibition of glycogen synthase kinase-3 (GSK-3) effectively reduces apoptosis following a number of stimuli. The Wnt family of proteins, and growth factors are two major factors that regulate GSK-3 activity. In the absence of stimuli, GSK-3 is constitutively active and is complexed with Axin, adenomatous polyposis coli (APC), and casein kinase Iα (CK1α) and phosphorylates ß-Catenin leading to its degradation. Binding of Wnt to Frizzled receptors causes the translocation of GSK-3 to the plasma membrane, where it phosphorylates and inactivates the Frizzled co-receptor lipoprotein-related protein 6 (LRP6). Furthermore, the translocation of GSK-3 reduces ß-Catenin phosphorylation and degradation, leading to ß-Catenin accumulation and gene expression. Growth factors activate Akt, which in turn inhibits GSK-3 activity by direct phosphorylation, leading to a reduction in apoptosis. Methodology/Principal Findings Using a rodent model, we found that TBI caused a rapid, but transient, increase in LRP6 phosphorylation that is followed by a modest decrease in ß-Catenin phosphorylation. Phospho-GSK-3β immunoreactivity was found to increase three days post injury, a time point at which increased Akt activity following TBI has been observed. Lithium influences several neurochemical cascades, including inhibiting GSK-3. When the efficacy of daily lithium was assessed, reduced hippocampal neuronal cell loss and learning and memory improvements were observed. These influences were partially mimicked by administration of the GSK-3-selective inhibitor SB-216763, as this drug resulted in improved motor function, but only a modest improvement in memory retention and no overt neuroprotection. Conclusion/Significance Taken together, our findings suggest that selective inhibition of GSK-3 may offer partial cognitive improvement. As a broad spectrum inhibitor of GSK-3, lithium offers neuroprotection and robust cognitive improvement, supporting its clinical testing as a treatment for TBI.
Self-Care Dimensions of Complementary and Alternative Medicine Use among Older Adults

Background: There is a lack of understanding about the patterns and rates of CAM use among older adults owing to a lack of research on specific types of CAM. Objectives: This study examines several dimensions of self-care deemed to be associated with CAM. Unmet health care needs, self-care attitudes, and spirituality are interpreted as health belief structures underlying CAM. Methods: Logistic regression analysis was used to examine use of three groups of practitioner-based CAM: (a) chiropractic; (b) massage, and (c) acupuncture, homeopathy and/or naturopathy use. We analyze a subsample of 4,401 older adults drawn from the 1996/1997 and 1998/1999 waves of the Canadian National Population Health Survey. Results: The logistic regression analyses indicate that self-care attitude and spirituality represent important predictors of practitioner-based CAM use. The associations for unmet health care needs were not supported. The strongest factors associated with CAM use were the illness context variables, which suggest that measures of need are key factors in leading individuals to seek other forms of health care. Discussion: Practitioner-based CAM use among older adults is influenced by self-care attitude and spirituality, in addition to health status, but to varying degrees depending on the type of CAM. Support of these self-care facets suggests that there is a desire on the part of consumers to exercise choice and to participate in health care decisions when considering CAM.
RNA chaperone activity and RNA-binding properties of the E. coli protein StpA

The E. coli protein StpA has RNA annealing and strand displacement activities and it promotes folding of RNAs by loosening their structures. To understand the mode of action of StpA, we analysed the relationship of its RNA chaperone activity to its RNA-binding properties. For acceleration of annealing of two short RNAs, StpA binds both molecules simultaneously, showing that annealing is promoted by crowding. StpA binds weakly to RNA with a preference for unstructured molecules. Binding of StpA to RNA is strongly dependent on the ionic strength, suggesting that the interactions are mainly electrostatic. A mutant variant of the protein, with a glycine to valine change in the nucleic-acid-binding domain, displays weaker RNA binding but higher RNA chaperone activity. This suggests that the RNA chaperone activity of StpA results from weak and transient interactions rather than from tight binding to RNA. We further discuss the role that structural disorder in proteins may play in chaperoning RNA folding, using bioinformatic sequence analysis tools, and provide evidence for the importance of conformational disorder and local structural preformation of chaperone nucleic-acid-binding sites.
Isolation and typing of Clostridium spp . 16 S rRNA from soil samples obtained in areas with sudden mortality history in Colombia

A Longitudinal epidemiologic study was developed for the isolation, biochemical characterization and molecular typing the bacterial pathogen Clostridium spp found in soil from areas affected by bovine sudden mortality. Weincluded 10 herds, located in three localities. The genetic variability of Clostridium genus was analyzed by DNA sequence of a 1500 bp fragment from the 16S rRNA gene. Twenty four Clostridium isolates were biochemically classified as Clostridium sordellii (41,7%), Clostridium glycolicum (12,5%), Clostridium hastiforme (12,5%); Clostridium botulinum (8,3%), Clostridium butyricum (8,3%); Clostridium chauvoei (4,3%),Clostridium limosum (4,3%), Clostridium septicum (4,3%) and Clostridium tertium (4,3%). The bacteria that showed pathogenic activity were studied further by 16S rRNA gene sequencing at, which 55.5% was classified as C. botulinum, where the native strain isolated from areas with outbreaks wasfound in a different group from Clostridium spp. used by commercial laboratories for vaccine production. Additionally, the native strain identified here differs from others reported in Gen Bank, indicating that the native pathogenic Clostridium spp. is genetically different to other Clostridium spp. used to prepare immunogens affecting vaccine efficiency. Our results indicate that the use of native strains could improve commercial vaccine preparations, increasing bovine immune response.
Passive Immunization with a Multicomponent Vaccine against Conserved Domains of Apical Membrane Antigen 1 and 235-Kilodalton Rhoptry Proteins Protects Mice against Plasmodium yoelii Blood-Stage Challenge Infection

ABSTRACT During malaria parasite invasion of red blood cells, merozoite proteins bind receptors on the surface of the erythrocyte. Two candidate Plasmodium yoelii adhesion proteins are apical membrane antigen 1 (AMA1) and the 235-kDa rhoptry proteins (P235). Previously, we have demonstrated that passive immunization with monoclonal antibodies (MAbs) 45B1 and 25.77 against AMA1 and P235, respectively, protects against a lethal challenge infection with P. yoelii YM. We show that MAb 45B1 recognizes an epitope located on a conserved surface of PyAMA1, as determined by phage display and analysis of the three-dimensional structure of AMA1, in a region similar to that bound by the P. falciparum AMA1-specific inhibitory antibody 4G2. The epitope recognized by 25.77 could not be assigned. We report here that MAbs 45B1 and 25.77 also protect against challenge with the nonlethal parasite line 17X, in which PyAMA1 has a significantly different amino acid sequence from that in YM. When administered together, the two MAbs acted at least additively in providing protection against challenge with the virulent YM parasite. These results support the concept of developing a multicomponent blood-stage vaccine and the inclusion of polymorphic targets such as AMA1, which these results suggest contain conserved domains recognized by inhibitory antibodies.
Stability of microtubuie attachment to metaphase kinetochores in PtICi cells

Kinetochore microtubules are known to be differentially stable to a variety of microtubuie depolymerization agents compared to the non-kinetochore polar microtubules, but the dynamics of microtubuie attachment to the kinetochore is currently controversial. We have examined the stability of kinetochore microtubules in metaphase PtKx spindles at 23 °C when microtubuie assembly is abruptly blocked with the drug nocodazole. Metaphase cells were incubated in medium containing 34/iM nocodazole for various times before fixation and processing either for immunofluorescence light microscopy or serial-section electron microscopy. Microtubules not associated with kinetochore fibers disappeared completely in less than 1 min. Kinetochore fibers persisted and shortened, as the spindle poles moved close to the chromosomes over a 10—20 min interval. During this shortening process, the number of kinetochore microtubules decreased slowly. The mean number of kinetochore microtubules was 24 ±5 in control cells and zero in cells incubated with nocodazole for 20 min. The half-time of microtubuie attachment to the kinetochore was ~7.5 min. These results show that when microtubuie assembly is blocked, kinetochore microtubules shorten more slowly and persist about 10 times longer than the labile polar microtubules. If kinetochore microtubules shorten by tubulin dissociation at their plus-ends like the non-kinetochore polar microtubules, then the microtubuie surface lattice must be able to translocate through the kinetochore attachment site without frequent detachment occurring.
Unsupervised All-words Word Sense Disambiguation with Grammatical Dependencies

We present experiments that analyze the necessity of using a highly interconnected word/sense graph for unsupervised allwords word sense disambiguation. We show that allowing only grammatically related words to influence each other’s senses leads to disambiguation results on a par with the best graph-based systems, while greatly reducing the computation load. We also compare two methods for computing selectional preferences between the senses of every two grammatically related words: one using a Lesk-based measure on WordNet, the other using dependency relations from the British National Corpus. The best configuration uses the syntactically-constrained graph, selectional preferences computed from the corpus and a PageRank tie-breaking algorithm. We especially note good performance when disambiguating verbs with grammatically constrained links.
Accumulation of c-Cbl and Cbl-b Immunological Synapses with Enhanced T Cells Form Mature + Anergic CD4

CD4 + T cell recognition of MHC:peptide complexes in the context of a costimulatory signal results in the large-scale redistribution of molecules at the T cell–APC interface to form the immunological synapse. The immunological synapse is the location of sustained TCR signaling and delivery of a subset of effector functions. T cells activated in the absence of costimulation are rendered anergic and are hyporesponsive when presented with Ag in the presence of optimal costimulation. Several previous studies have looked at aspects of immunological synapses formed by anergic T cells, but it remains unclear whether there are differences in the formation or composition of anergic immunological synapses. In this study, we anergized primary murine CD4 + T cells by incubation of costimulation-deﬁcient, transfected ﬁbroblast APCs. Using a combination of TCR, MHC:peptide, and ICAM-1 staining, we found that anergic T cells make mature immunological synapses with characteristic central and peripheral supramolecular activation cluster domains that were indistinguishable from control synapses. There were small increases in total phosphotyrosine at the anergic synapse along with signiﬁcant decreases in phosphorylated ERK 1/2 accumulation. Most striking, there was speciﬁc accumulation of c-Cbl and Cbl-b to the anergic synapses. Cbl-b, previously shown to be essential in anergy induction, was found in both the central and the peripheral supramolecular activation clusters of the anergic synapse. This Cbl-b (and c-Cbl) accumulation at the anergic synapse may play an important role in anergy maintenance, induction, or both. The Journal of Immunology , 2010, 184: 3598–3608.
Long‐term risk of cardiovascular disease in Hodgkin lymphoma survivors—Retrospective cohort analyses and a concept for prospective intervention

Previous studies have shown increased cardiovascular mortality as late side effects in Hodgkin lymphoma (HL) patients. This study identifies stratifying risk factors for surveillance and defines concepts for a clinical feasible and noninvasive prospective protocol for intervention of cardiovascular side effects. HL patients diagnosed between 1965 and 1995 (n = 6.946) and their first‐degree relatives (FDR) were identified through the Swedish Cancer Registry and the Swedish Multigeneration Registry. For the HL and FDR cohort, in‐patient care for cardiovascular disease (CVD) was registered through the Hospital Discharge Registry, Sweden. Standard incidence ratios of developing CVD for the HL cohort were calculated. A markedly increased risk for in‐patient care of CVD was observed in HL patients with HL diagnosed at age 40 years or younger and with more than 10 years follow‐up. In the HL survivors, a family history of congestive heart failure (CHF) and coronary artery disease (CAD) increased the risk for these diseases. The Swedish Hodgkin Intervention and Prevention study started in 2007. In the pilot feasibility study for prospective intervention (47 patients), about 25% of the cases had side effects and laboratory abnormalities. These patients were referred to a cardiologist or general practitioner. In the prospective cohort, a positive family history for CHF or CAD could be a stratifying risk factor when setting up a surveillance model. The prospective on‐going study presents an intervention model that screens and treats for comorbidity factors. This article also presents an overview of the study concept. © 2008 Wiley‐Liss, Inc.
Association between obstructive sleep apnea severity and glucose control in patients with untreated versus treated diabetes

The purpose of this study was to determine whether the association between obstructive sleep apnea severity and glucose control differs between patients with newly diagnosed and untreated type 2 diabetes, and patients with known and treated type 2 diabetes. This multicentre cross‐sectional study included 762 patients investigated by sleep recording for suspected obstructive sleep apnea, 497 of whom were previously diagnosed and treated for type 2 diabetes (treated diabetic patients), while 265 had no medical history of diabetes but had fasting blood glucose ≥126 mg dL−1 and/or glycated haemoglobin (HbA1c) ≥6.5% consistent with newly diagnosed type 2 diabetes (untreated diabetic patients). Multivariate regression analyses were performed to evaluate the independent association between HbA1c and obstructive sleep apnea severity in treated and untreated patients with diabetes. In untreated diabetic patients, HbA1c was positively associated with apnea–hypopnea index (P = 0.0007) and 3% oxygen desaturation index (P = 0.0016) after adjustment for age, gender, body mass index, alcohol habits, metabolic dyslipidaemia, hypertension, statin use and study site. The adjusted mean value of HbA1c increased from 6.68% in the lowest quartile of the apnea–hypopnea index (<17) to 7.20% in the highest quartile of the apnea–hypopnea index (>61; P = 0.033 for linear trend). In treated patients with diabetes, HbA1c was associated with non‐sleep variables, including age, metabolic dyslipidaemia and insulin use, but not with obstructive sleep apnea severity. Obstructive sleep apnea may adversely affect glucose control in patients with newly diagnosed and untreated type 2 diabetes, but may have a limited impact in patients with overt type 2 diabetes receiving anti‐diabetic medications.
Retracted: Mathematical relationships and their consequences between rat pulse waveform parameters and blood pressure during decreasing NO bioavailability

What is the central question of this study? We wanted to find out whether the relationship between rat arterial pulse waveform (APW) parameters and blood pressure could be described by known mathematical functions and find mathematical parameters for conditions of hypertension resulting from decreased NO bioavailability. What is the main finding and its importance? We found mathematical functions and their parameters that approximate the relationships of 12 APW parameters to systolic and diastolic blood pressure in conditions of decreased NO bioavailability. The results may assign APW parameters to decreased NO bioavailability, which may have predictive or diagnostic value.
On the selection of optimum diversity and code rate for FFH/8FSK under partial band interference for multimedia data transmission

The built-in diversity of the fast frequency hopped spread spectrum communication system can provide inherent protection against interference for the multimedia data transmission for tactical use. Additionally, FEC coding can greatly enhance the system performance. However, care must be taken toward optimum performance in a power limited system. In this paper, effect of diversity L is observed with/without convolutional coding for the performance of the FFH/8FSK modem under additive white Gaussian noise (AWGN) and partial band noise interference using different nonlinear diversity combiners. Simulation results show that proper combination of diversity/nonlinear combiners, M-ary modulation and FEC coding is very effective. However, for the modems using coding, use of high diversity L does not necessarily improve the BER performance, thus resulting in an optimum value of diversity for each particular modem under consideration.