Miracle-dz/UniFAR-FTUs huggingface dataset:
Real-Time PCR-Based Pathotyping of Newcastle Disease Virus by Use of TaqMan Minor Groove Binder Probes

ABSTRACT A real-time reverse-transcription PCR was developed to detect and pathotype Newcastle disease viruses (NDV) in clinical samples. Degenerate oligonucleotide primers and TaqMan probes with nonfluorescent minor groove binder (MGB) quencher amplified and hybridized to a region in the fusion protein (F) gene that corresponds to the cleavage site of the F0 precursor, which is a key determinant of NDV pathogenicity. The application of degenerate primers and TaqMan MGB probes provided high specificity to the assay, as was shown by the successful and rapid pathotype determination of 39 NDV strains representing all the known genotypes (I to VIII) and pathotypes (lentogens/mesogens/velogens). The PCR assays specific for lentogenic and velogenic/mesogenic strains had high analytical sensitivity, detecting approximately 10 and 20 copies of the target molecule per reaction, respectively. The detection limit was also determined in terms of 50% egg infective dose (EID50) by using dilution series of virus stock solutions to be approximately 101.0 and 10−1.3 EID50/ml for lentogens and velogens/mesogens, respectively. Organ, swab, and stool specimens from experimentally infected animals were tested to prove the clinical suitability of the method. The results of this study suggest that the described real-time PCR assay has the potential to be used for the rapid detection/pathotyping of NDV isolates and qualitative/quantitative measurement of the virus load.
MRI Discriminates Thrombus Composition and ST Resolution after Percutaneous Coronary Intervention in Patients with ST-Elevation Myocardial Infarction

Histological composition of material obtained by thrombus aspiration during percutaneous coronary intervention (PCI) in patients with ST-segment elevation acute myocardial infarction (STEMI) is highly variable. We aimed to characterize this material using magnetic resonance imaging (MRI) and to correlate MRI findings with the success of PCI in terms of ST-segment resolution. Thrombus aspiration during primary or rescue PCI was attempted in 100 consecutive STEMI patients, of whom enough material for MRI was obtained in 59. MR images were obtained at 9.4T and T1 and T2 values were measured. Patients with (n = 31) and without (n = 28) adequate ST resolution 120 min after PCI (≥70% of pre-PCI value) had similar baseline characteristics except for a higher prevalence of diabetes mellitus in the latter (10 vs. 43%, p = 0.003). T1 values were similar in both groups (1248±112 vs. 1307±85 ms, respectively, p = 0.7). T2 values averaged 31.2±10.3 and 36.6±12.2 ms; in thrombus from patients with and without adequate ST resolution (p = 0.09). After adjusting for diabetes and other baseline characteristics, lower T2 values were significantly associated with inadequate ST resolution (odds ratio for 1 ms increase 1.08, CI 95% 1.01–1.16, p = 0.027). Histology classified thrombus in 3 groups: coagulated blood (n = 38), fibrin rich (n = 9) and lipid-rich (n = 3). Thrombi composed mostly of coagulated blood were characterized as being of short (n = 10), intermediate (n = 15) or long evolution (n = 13), T2 values being 34.0±13.2, 31.9±8.3 and 31.5±7.9 ms respectively (p = NS). In this subgroup, T2 was significantly higher in specimens from patients with inadequate perfusion (35.9±10.3 versus 28.6±6.7 ms, p = 0.02). This can be of clinical interest as it provides information on the probability of adequate ST resolution, a surrogate for effective myocardial reperfusion.
OVOL2 antagonizes TGF-β signaling to regulate epithelial to mesenchymal transition during mammary tumor metastasis

Great progress has been achieved in the study of the role of TGF-β signaling in triggering epithelial-mesenchymal transition (EMT) in a variety of cancers; however, the regulation of TGF-β signaling during EMT in mammary tumor metastasis has not been completely defined. In the present study, we demonstrated that OVOL2, a zinc finger transcription factor, inhibits TGF-β signaling-induced EMT in mouse and human mammary tumor cells, as well as in mouse tumor models. Data from the Oncomine databases indicated a strong negative relationship between OVOL2 expression and breast cancer progression. Moreover, our experiments revealed that OVOL2 inhibits TGF-β signaling at multiple levels, including inhibiting Smad4 mRNA expression and inducing Smad7 mRNA expression, blocking the binding between Smad4 and target DNA, and interfering with complex formation between Smad4 and Smad2/3. These findings reveal a novel mechanism that controls the TGF-β signaling output level in vitro and in vivo. The modulation of these molecular processes may represent a strategy for inhibiting breast cancer invasion by restoring OVOL2 expression.
Loss of Extended Synaptotagmins ESyt2 and ESyt3 does not affect mouse development or viability, but in vitro cell migration and survival under stress are affected

The Extended Synaptotagmins (Esyts) are a family of multi-C2 domain membrane proteins with orthologs in organisms from yeast to human. Three Esyt genes exist in mouse and human and these have most recently been implicated in the formation of junctions between endoplasmic reticulum and plasma membrane, as well as the Ca2+ dependent replenishment of membrane phospholipids. The data are consistent with a function in extracellular signal transduction and cell adhesion, and indeed Esyt2 was previously implicated in both these functions in Xenopus. Despite this, little is known of the function of the Esyts in vivo. We have generated mouse lines carrying homozygous deletions in one or both of the genes encoding the highly homologous Esyt2 and Esyt3 proteins. Surprisingly, esyt2−/−/esyt3−/− mice develop normally and are both viable and fertile. In contrast, esyt2−/−/esyt3−/− mouse embryonic fibroblasts display a reduced ability to migrate in standard in vitro assays, and are less resistant to stringent culture conditions and to oxidative stress than equivalent wild type fibroblasts.
Genomic characterisation of a Fgf-regulated gradient-based neocortical protomap

Recent findings support a model for neocortical area formation in which neocortical progenitor cells become patterned by extracellular signals to generate a protomap of progenitor cell areas that in turn generate area-specific neurons. The protomap is thought to be underpinned by spatial differences in progenitor cell identity that are reflected at the transcriptional level. We systematically investigated the nature and composition of the protomap by genomic analyses of spatial and temporal neocortical progenitor cell gene expression. We did not find gene expression evidence for progenitor cell organisation into domains or compartments, instead finding rostrocaudal gradients of gene expression across the entire neocortex. Given the role of Fgf signalling in rostrocaudal neocortical patterning, we carried out an in vivo global analysis of cortical gene expression in Fgfr1 mutant mice, identifying consistent alterations in the expression of candidate protomap elements. One such gene, Mest, was predicted by those studies to be a direct target of Fgf8 signalling and to be involved in setting up, rather than implementing, the progenitor cell protomap. In support of this, we confirmed Mest as a direct transcriptional target of Fgf8-regulated signalling in vitro. Functional studies demonstrated that this gene has a role in establishing patterned gene expression in the developing neocortex, potentially by acting as a negative regulator of the Fgf8-controlled patterning system.
Dynamin 2 is required for the enhancement of HIV-1 infectivity by Nef

Nef is a virulence factor of HIV-1 and other primate lentiviruses that is crucial for rapid progression to AIDS. In cell culture, Nef increases the infectivity of HIV-1 progeny virions by an unknown mechanism. We now show that dynamin 2 (Dyn2), a key regulator of vesicular trafficking, is a binding partner of Nef that is required for its ability to increase viral infectivity. Dominant-negative Dyn2 or the depletion of Dyn2 by small interfering RNA potently inhibited the effect of Nef on HIV-1 infectivity. Furthermore, in Dyn2-depleted cells, this function of Nef could be rescued by ectopically expressed Dyn2 but not by Dyn1, a closely related isoform that does not bind Nef. The infectivity enhancement by Nef also depended on clathrin, because it was diminished in clathrin-depleted cells and profoundly inhibited in cells expressing the clathrin-binding domain of AP180, which blocks clathrin-coated pit formation but not clathrin-independent endocytosis. Together, these findings imply that the infectivity enhancement activity of Nef depends on Dyn2- and clathrin-mediated membrane invagination events.
Nonlinear flowering responses to climate: are species approaching their limits of phenological change?

Many alpine and subalpine plant species exhibit phenological advancements in association with earlier snowmelt. While the phenology of some plant species does not advance beyond a threshold snowmelt date, the prevalence of such threshold phenological responses within plant communities is largely unknown. We therefore examined the shape of flowering phenology responses (linear versus nonlinear) to climate using two long-term datasets from plant communities in snow-dominated environments: Gothic, CO, USA (1974–2011) and Zackenberg, Greenland (1996–2011). For a total of 64 species, we determined whether a linear or nonlinear regression model best explained interannual variation in flowering phenology in response to increasing temperatures and advancing snowmelt dates. The most common nonlinear trend was for species to flower earlier as snowmelt advanced, with either no change or a slower rate of change when snowmelt was early (average 20% of cases). By contrast, some species advanced their flowering at a faster rate over the warmest temperatures relative to cooler temperatures (average 5% of cases). Thus, some species seem to be approaching their limits of phenological change in response to snowmelt but not temperature. Such phenological thresholds could either be a result of minimum springtime photoperiod cues for flowering or a slower rate of adaptive change in flowering time relative to changing climatic conditions.
FAT1 is a novel upstream regulator of HIF1α and invasion of high grade glioma

The hypoxic microenvironment is an important contributor of glioblastoma (GBM) aggressiveness via HIF1α, while tumour inflammation is profoundly influenced by FAT Atypical Cadherin (FAT1). This study was designed to explore the functional interaction and significance of FAT1 and HIF1α under severe hypoxia‐mimicking tumour microenvironment in primary human tumours. We first identified a positive correlation of FAT1 with HIF1α and its target genes in GBM tumour specimens, revealing the significance of the FAT1‐HIF1α axis in glioma cells. We found that severe hypoxia leads to an increased expression of FAT1 and HIF1α in U87MG and U373MG cells. To reveal the relevance of FAT1 under hypoxic conditions, we depleted endogenous FAT1 under hypoxia and found a substantial reduction in the expression of HIF1α and its downstream target genes like CA9, GLUT1, VEGFA, MCT4, HK2, BNIP3 and REDD1, as well as a significant reduction in the invasiveness in GBM cells. At the molecular level, under hypoxia the FAT1 depletion‐associated reduction in HIF1α was due to compromised EGFR‐Akt signaling as well as increased VHL‐dependent proteasomal degradation of HIF1α. In brief, for the first time, these results reveal an upstream master regulatory role of FAT1 in the expression and role of HIF1α under hypoxic conditions and that FAT1‐HIF1α axis controls the invasiveness of GBM. Hence, FAT1 represents a novel potential therapeutic target for GBM.
The clinical assessment of aggressive periodontitis patients

Purpose Few epidemiologic studies have investigated aggressive periodontitis in Koreans, but such studies of disease prevalence and other clinical characteristics would be invaluable in providing proper treatment. The aim of this study was to assess the prevalence of aggressive periodontitis and to measure the extent of associated periodontal breakdown. Methods The study population consisted of 1,692 patients who visited the Department of Periodontology, Wonkwang Daejeon Dental Hospital from January to December, 2010. Clinical parameters (probing depth, gingival recession, periodontal attachment loss) were measured by a single examiner, and radiographic examination was performed at the baseline. Results Twenty-eight (1.65%) patients showed clinical features of aggressive periodontitis, of which 27 patients exhibited the generalized form, and 1 exhibited the localized form. There was no significant difference between the percentage of male and female patients. The probing pocket depth of the maxillary first molar was deeper than that of the other teeth and gingival recession was also the most serious at the maxillary first molar. The periodontal attachment loss was the highest at the maxillary first molar. The average number of missing teeth was 1.29 per subject. Loss of the second molar was prominent. Conclusions Within the limitations of this study, the periodontal breakdown evaluated by attachment loss was found to be most severe at the first molars of aggressive periodontitis patients. However, further large scale multicenter studies are necessary to access more precise data, including prevalence.
Coded caching with partial adaptive matching

We study the coded caching problem when we are allowed to match users to caches based on their requested files. We focus on the case where caches are divided into clusters and each user can be assigned to a unique cache from a specific cluster. We show that neither the coded delivery strategy (approximately optimal when the user-cache assignment is pre-fixed) nor the uncoded replication strategy (approximately optimal when all caches belong to a single cluster) is sufficient for all memory regimes. We propose a hybrid solution that combines ideas from both schemes and that performs at least as well as either strategy in most memory regimes. Finally, we show that this hybrid strategy is approximately optimal in most memory regimes.
Brucellosis in children in Bosnia and Herzegovina in the period 2000 - 2013.

AIM To analyse clinical, laboratory and epidemiological characteristics of brucellosis in children in Bosnia and Herzegovina. METHODS The study included 246 children aged 0-18 years, who were hospitalized in Clinics and Departments for Infectious Diseases in Tuzla, Sarajevo, Banja Luka, Zenica and Bihać in the period 2000-2013, in whom the diagnosis of brucellosis was established based on anamnestic data, clinical features and positive results from blood culture and/or positive results from one of the serological tests. RESULTS In this period, a total of 2630 patients, 246 (9.35%) of whom were children, were treated from brucellosis at the Clinics and Departments in Bosnia and Herzegovina. In the majority of cases, the children were from rural parts of the country, 226 (91.87%);214 (87.04%) cases had direct contact with sick animals, sick family member or consumption of unpasteurized dairy products from farms where brucellosis had been already established. Male children predominated, 157 (63.82%). The most frequent clinical features in affected children were fever, 194 (78.86%) and joint pain, 158 (64.22%). The average duration of antimicrobial treatment was 42.85 ± 10.67 days. A total of 228 (92.68%) children were completely cured, while relapses occurred in 18 (7.32%) children. CONCLUSION Since brucellosis is an endemic disease in Bosnia and Herzegovina, it is important that physicians in their daily practice consider brucellosis and establish proper diagnosis and therapy in children with prolonged fever, arthralgia, leukopenia and positive epidemiological data, especially in rural parts of the country.
Workload Dependent Performance Evaluation of the Linux 2 . 6 I / O Schedulers

The 2.6 release introduced the option to select a particular I/O scheduler at boot time. The 2.4 Linus elevator was retired, incorporated are now the anticipatory (AS), the deadline, the noop, as well as the completely fair queuing (CFQ) I/O schedulers. Each scheduler has its strengths and weaknesses. The question is under what workload scenarios does a particular I/O scheduler excel, as well as what is the performance gain that is possible by utilizing the available tuning options. This study quantifies the performance of the 4 I/O schedulers under various workload scenarios (such as mail, web, and file server based conditions). The hardware is being varied from a single-CPU single-disk setup to machines with many CPUs that are utilizing large RAID arrays. In addition to characterizing the performance behavior and making actual recommendations on which scheduler to utilize under certain workload scenarios, the study looks into ways to actually improve the performance through either the existing tuning options or any potential code changes/enhancements.
Renal histology in Chinese patients with anti-myeloperoxidase autoantibody-positive Wegener's granulomatosis.

BACKGROUND Proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA) was the serological marker for Wegener's granulomatosis (WG), while myeloperoxidase (MPO)-ANCA was the serological marker for microscopic polyangiitis (MPA). However, our previous study suggested that patients with MPO-ANCA positive WG were common in Chinese. This study aimed to analyse the renal histology of patients with MPO-ANCA positive WG. METHODS Patients in our centre with WG were selected according to both the Chapel Hill Consensus Conference (CHCC) definition and American College of Rheumatology classification criteria. Patients with MPA were selected according to the CHCC definition. The renal histology was compared between patients with MPO-ANCA positive WG and with PR3-ANCA positive WG as well as patients with MPO-ANCA positive MPA. RESULTS Sixty-one patients with WG had complete renal histological data, 39/61 with positive MPO-ANCA and 22/61 with positive PR3-ANCA. Among patients with crescents in glomeruli, those with MPO-ANCA had fewer cellular crescents and more fibrous crescents than those with PR3-ANCA (P < 0.01 and P < 0.05, respectively). Interstitial fibrosis and tubular atrophy were more prevalent and severe in patients with MPO-ANCA than in those with PR3-ANCA (P < 0.01 and P < 0.05, respectively). Compared with 44 patients with MPO-ANCA positive MPA, patients with MPO-ANCA positive WG had fewer glomeruli with crescents and more normal glomeruli (P < 0.01 and P < 0.01, respectively). CONCLUSION Patients with MPO-ANCA positive WG are common in Chinese. In renal histology, chronic lesions were more severe and prevalent in patients with MPO-ANCA positive WG than in patients with PR3-ANCA positive WG. Glomerular lesions were less severe and less prevalent in patients with MPO-ANCA positive WG than in those with MPO-ANCA positive MPA.
Exponential Stability Analysis for Delayed Neural Networks With Switching Parameters: Average Dwell Time Approach

This paper is concerned with the problem of exponential stability analysis of continuous-time switched delayed neural networks. By using the average dwell time approach together with the piecewise Lyapunov function technique and by combining a novel Lyapunov-Krasovskii functional, which benefits from the delay partitioning method, with the free-weighting matrix technique, sufficient conditions are proposed to guarantee the exponential stability for the switched neural networks with constant and time-varying delays, respectively. Moreover, the decay estimates are explicitly given. The results reported in this paper not only depend upon the delay but also depend upon the partitioning, which aims at reducing the conservatism. Numerical examples are presented to demonstrate the usefulness of the derived theoretical results.
Improving web availability for clients with MONET

Despite the increasing degree of multi-homing, path and data redundancy, and capacity available in the Internet, today's clients experience outage rates of a few percent when accessing Web sites. MONET ("Multi-homed Overlay NETwork), is a new system that improves client availability to Web sites using a combination of link multi-homing and a cooperative overlay network of peer proxies to obtain a diverse collection of paths between clients and Web sites. This approach creates many potential paths between clients and Web sites, requiring a scalable way to selecting a good path. MONET solves this problem using a waypoint selection algorithm, which picks a good small subset of all available paths to actively probe. MONET runs on FreeBSD, Linux, and Mac OS X, and is deployed at six different sites. These installations have been running MONET for over one year, serving about fifty users on a daily basis. Our analysis of proxy traces shows that the proxy network avoids between 60% and 94% of observed failures, including access link failures, Internet routing problems, persistent path congestion, and DNS failures. The proxy avoids nearly 100% of failures due to client and wide-area network failures, with negligible overhead.
Adiponectin promotes endothelial cell differentiation from human peripheral CD14+ monocytes in vitro

Adiponectin was revealed to have anti‐atherogenic and anti‐inflammatory properties and has been recently found to stimulate angiogenesis in vivo and in vitro. However, the role of adiponectin in endothelial differentiation remains unclear. The objective of this study was to investigate whether adiponectin can promote peripheral CD14+ monocytes differentiation into endothelial cells (ECs). Human peripheral blood CD14+ monocytes were cultured with or without adiponectin (10 μg/ml) for 10 days. Adiponectin significantly promoted EC morphology formation from CD14+ monocytes. By flow cytometery analysis, cells treated with adiponection substantially increased mean fluorescence intensity of vascular endothelial growth factor receptor‐2 (VEGFR‐2) and endothelial nitric oxide synthase (eNOS), two specific endothelial markers, by 49.2% and 53.9%, respectively, as compared to control cells. By real time PCR analysis, the mRNA level of eNOS in adiponectin‐treated cells was also increased by 31.9% of that of the control cells. However, the mRNA levels of calponin and SMMHC, two specific SMC markers, in adiponectin‐treated cells were decreased by 81.1% and 79.7% of that of the control cells, respectively. These data demonstrated that adiponectin could promote endothelial differentiation from peripheral blood CD14+ monocytes by morphology change, upregulation of EC markers and downregulation of SMC markers. Adiponectin‐promoted EC differentiation may contribute to vascular healing and angiogenesis.