Miracle-dz/UniFAR-FTUs huggingface dataset:
Multi‐round virus filter integrity test sensitivity

Virus filtration is becoming increasingly prominent in biopharmaceutical recovery processes as a robust method to remove a broad range of virus types. Increasing batch sizes will require large numbers of individual virus filter elements operating in parallel. Before adopting a more complex strategy for managing the integrity testing of large assemblies of virus filters, it is important to understand the sensitivity of the forward flow diffusion test for a single filter and for multiple filters in a single housing. An approach has been developed to estimate the largest hole that could consistently go undetected in a single filter within a larger assembly of virus filters. The integrity test limited minimum log reduction value (LRV) is determined based on the size of the hole as a function of the number of filters in the housing. This minimum LRV is shown to be largely insensitive to the number of filters within the housing. The likelihood of such damage occurring is expected to be very low. This analysis suggests there is minimal benefit to placing filters in individual housings or to adjusting the test specification to compensate for larger numbers of filters in a given housing. Biotechnol. Bioeng. 2009;103: 574–581. © 2009 Wiley Periodicals, Inc.
METHODS COMPARISON: ASSESSING AGREEMENT OF PHYSIOLOGICAL PARAMETERS OBTAINED FROM EXERCISE ON TWO DIFFERENT CYCLE ERGOMETERS.

The purpose of this study was to determine the agreement of physiological parameters measured during exercise testing on two devices at established power outputs (PO). Ten trained male cyclists were recruited. The devices used for comparison were the Lode stationary bicycle ergometer (SBE) (Lode Excalibur, Netherlands) and the PowerTap Pro+ (BPT) (Saris Cycling Group, Madison, WI) mobile ergometer. The physiological parameters recorded at established PO [50, 100, 150, 200, 250 Watts (W)] were: heart rate (HR), oxygen consumption (VO2), pulmonary ventilation (VE), blood lactate, and ratings of perceived exertion (RPE). Subjects were randomized once to the SBE and three times to a bicycle equipped with a BPT. Following 15-minutes of unloaded pedaling, the trial began with five minutes of cycling at 50W. Intensity increased by 50W every five minutes up to 250W. Physiological measures were recorded at each PO. Bland-Altman plots were constructed including computation of the ratio of half the range of limits of agreement (LOA) and the mean of the pairwise means (MPM) along with bivariate regression calculations for analysis of the linear association between device measurements. Moderate to good agreement was found for HR with agreement improving as PO increased. Comparisons of VO2 found agreement increased as the PO increased. VE, RPE, and lactate did not consistently provide similar measures across trials. The level of agreement between HR and VO2 when comparing the SBE and BPT, suggests that the PowerTap Pro+ is a sufficient tool for estimating PO and associated physiological parameters in the field.
Echoes analysis from spherical elastic shells by using iterative time reversal mirror

In the shallow water environment, detecting and classifying buried objects is a challenging problem with high operational importance. Acoustical wave becomes an important tool in the detection of objects in underwater systems due to its effectiveness of propagation in the water. Later on, the acoustic scattered field modal for fluid-loaded and thin spherical shell have been determined by the shell's physical properties and appropriate boundary conditions at the fluid interface. These spherical elastic shells produce lamb waves that contain energy within corresponding frequency bandwidth. The iterative time reversal process is then performed to enhance energy of responding lamb waves and makes it possible to distinguish target characteristics. In addition, target distance can be determined from wave propagation time. The study is developing a procedure to distinguish target characteristics such as material and size by observing convergence frequency through iterative time reversal process. The proposed procedure is verified from designed simulations and experiments by using spherical elastic shells as targets. In experiments, interrogating signals are transmitted from an unfocused broadband underwater transducer and recorded received by another same type transducer. Due to the enhancing effect of iterative time reversal, energy of iterative receiving signals converges to certain frequencies. After comparing these frequencies from varying target characteristics such as diameter of target sphere shell and thick of target sphere shell, the result proves that the proposed procedure is capable to distinguished properties of different targets.
A reassessment of whether cortical motor neurons die following spinal cord injury

Over the past century, the question of whether the cells of origin of the corticospinal tract (CST) die following spinal cord injury (SCI) has been debated. A recent study reported an approximately 20% loss of retrogradely labeled cortical motoneurons following damage to their axons resulting from SCI at T9 (Hains et al. [ 2003 ] J. Comp. Neurol. 462:328–341). In follow‐up studies, however, we failed to find any evidence of loss of CST axons in the medullary pyramid, which must occur if CST neurons die. Here, we seek to resolve the discrepancy by re‐evaluating possible loss of CST neurons using the same techniques as Hains et al. (quantitative analysis of retrograde labeling and staining for cell death markers including TUNEL and Hoechst labeling of the nuclei). Following either dorsal funiculus lesions at thoracic level 9 (T9) or lateral hemisection at cervical level 5 (C5), our results reveal no evidence for a loss of retrogradely labeled neurons and no evidence for TUNEL staining of axotomized cortical motoneurons. These results indicate that CST cell bodies do not undergo retrograde cell death following SCI, and therefore targeting such cell death is not a valid therapeutic target. J. Comp. Neurol. 519:2852–2869, 2011. © 2011 Wiley‐Liss, Inc.
Modified-prior PLDA and score calibration for duration mismatch compensation in speaker recognition system

To deal with the performance degradation of speaker recognition due to duration mismatch between enrollment and test utterances, a novel strategy to modify the standard normal prior distribution of the i-vector during probabilistic linear discriminant analysis (PLDA) modeling is employed. This new modified-prior PLDA model incorporates the covariance matrix scaled with duration of each utterance for each speaker, which achieves more discriminative characteristics by learning the duration variability as well as session variation in the i-vector space. Furthermore, an efficient Quality Measure Function (QMF) method which adopts duration variation as a compensation technique is employed to eliminate the linear shift in the score domain. To evaluate the robustness of the proposed approach, experiments were conducted on the NIST SRE10 core-core task in condition-5 with varying test utterance duration, in which the i-vectors of test utterances were extracted from full segment and randomly truncated segments of duration 10s and 20s. The results demonstrated the efficiency of modified-prior PLDA in different duration conditions, and the combined score calibration further improved the performance of speaker recognition.
Long-term auto-servoventilation or constant positive pressure in heart failure and coexisting central with obstructive sleep apnea.

BACKGROUND The coexistence of obstructive sleep apnea (OSA) and central sleep apnea (CSA) and Cheyne-Stokes respiration (CSR) is common in patients with heart failure (HF). While CPAP improves CSA/CSR by about 50%, maximal suppression is crucial in improving clinical outcomes. Auto-servoventilation (ASV) effectively suppresses CSA/CSR in HF, but few trials have been performed in patients with coexisting OSA and CSA/CSR. Our objective was to evaluate a randomized, controlled trial to compare the efficacy of ASV and CPAP in reducing breathing disturbances and improving cardiac parameters in patients with HF and coexisting sleep-disordered breathing. METHODS Both modes were delivered using the BiPAP autoSV (Philips Respironics) over a 12-month period. Seventy patients (63 men, 66.3 ± 9.1 y, BMI 31.3 ± 6.0 kg/m(2)) had coexisting OSA and CSA/CSR, arterial hypertension, coronary heart disease, or cardiomyopathy and clinical signs of heart failure New York Heart Association classes II-III. Polysomnography, brain natriuretic peptide (BNP), spiroergometry, and echocardiography were performed at baseline and after 3 and 12 months of treatment. RESULTS Both modes of therapy significantly improved respiratory disturbances, oxygen desaturations, and arousals over the study period. ASV reduced the central apnea hypopnea index (baseline CPAP, 21.8 ± 11.7; ASV, 23.1 ± 13.2; 12 months CPAP, 10.7 ± 8.7; ASV, 6.1 ± 7.8, P < .05) and BNP levels (baseline CPAP, 686.7 ± 978.7 ng/mL; ASV, 537.3 ± 891.8; 12 months CPAP, 847.3 ± 1848.1; ASV, 230.4 ± 297.4; P < .05) significantly more effectively as compared with CPAP. There were no relevant differences in exercise performance and echocardiographic parameters between the groups. CONCLUSIONS ASV improved CSA/CSR and BNP over a 12-month period more effectively than CPAP.
Cognitive dysfunction in multiple sclerosis: The effect of pharmacological interventions

Research has recently focused on cognitive dysfunction in multiple sclerosis (MS). Cognitive deficits are frequently encountered in patients and account for important impairment in quality of life, therefore posing a major therapeutic challenge for the disease. We presently review studies on cognitive effects of pharmacological treatments in MS. There is evidence for a possible beneficial effect of immunomodulatory treatments, particularly of interferons, and also of acetylcholinesterase inhibitors on cognition in MS, which, however, requires evaluation in larger, multi-centre, longitudinal studies. Methodological issues and future prospects regarding the investigation of this issue are also discussed.
Mutations logistiques de la cyber-épicerie française : quand les groupements d’associés défient la distribution intégrée

Au cours de cet article, nous montrons que l’épicerie en ligne connaît désormais un développement significatif en France. Nous y rappellons que le back-office constitue, au sein du canal de distribution, une condition de réussite tout aussi essentielle que le front-office en affirmant précisément que la logistique paraît enfin « trouver ses marques » en France. D’ailleurs, il ne semble plus, contrairement à un passé récent, qu’un modèle unique domine. Différentes alternatives paraissent co-exister, s’appuyant tantôt sur des infrastructures logistiques dédiées et tantôt sur des points de vente. Il semble encore que ces différents modèles soient liés au statut des détaillants en ligne : des différences significatives sont en effet observées entre le grand commerce intégré (Carrefour et Auchan en particulier) et les groupements de commerçants indépendants.
Video Delivery Performance of a Large-Scale VoD System and the Implications on Content Delivery

Video delivery performance is the main factor that affects Internet video quality. Characterizing the video delivery performance, especially the delivery throughput, can help content providers as well as Internet service providers (ISPs) in system optimization and network planning. Based on a unique dataset consisting of 20 million video download speed measurements , this paper comprehensively studies the video delivery throughput of a large-scale commercial video-on- demand (VoD) system. We observe that user speed exhibits a large variation over time of day as well as across provincial locations. In particular, the worst performance of day is 30% lower than the peak performance . The analysis also reveals that video download speed has a notable impact on Internet video quality, which in turn influences user engagement . The impact, however, becomes limited when the speed increases beyond a certain threshold, which is mostly dependent on the video encoded bitrates. We further examine the interaction between Internet infrastructure and video delivery throughput using the linear regression model and find that crossing the ISP or regional network border yields 15-20% speed loss. Based on these observations , we finally evaluate the potential of edge caching and hybrid CDN-P2P in the improvement of video download performance and video quality.
Biomarkers distinguish apoptotic and necrotic cell death during hepatic ischemia/reperfusion injury in mice

Hepatic ischemia/reperfusion (IRP) injury is a significant clinical problem during tumor‐resection surgery (Pringle maneuver) and liver transplantation. However, the relative contribution of necrotic and apoptotic cell death to the overall liver injury is still controversial. To address this important issue with a standard murine model of hepatic IRP injury, plasma biomarkers of necrotic cell death such as micro‐RNA 122, full‐length cytokeratin 18 (FK18), and high‐mobility group box 1 (HMGB1) protein and plasma biomarkers of apoptosis such as plasma caspase‐3 activity and caspase‐cleaved fragment of cytokeratin 18 (CK18) coupled with markers of inflammation (hyperacetylated HMGB1) were compared by histological features in hematoxylin and eosin–stained and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick‐end labeling (TUNEL)–stained liver sections. After 45 minutes of hepatic ischemia and 1 to 24 hours of reperfusion, all necrosis markers increased dramatically in plasma by 40‐ to >10,000‐fold over the baseline with a time course similar to that of alanine aminotransferase. These data correlated well with histological characteristics of necrosis. Within the area of necrosis, most cells were TUNEL positive; initially (≤3 hours of reperfusion), the staining was restricted to nuclei, but it later spread to the cytosol, and this is characteristic of karyorrhexis during necrotic cell death. In contrast, the lack of morphological evidence of apoptotic cell death and relevant caspase‐3 activity in the postischemic liver correlated well with the absence of caspase‐3 activity and CK18 (except for a minor increase at 3 hours of reperfusion) in plasma. A quantitative comparison of FK18 (necrosis) and CK18 (apoptosis) release indicated dominant cell death by necrosis during IRP and only a temporary and very minor degree of apoptosis. These data suggest that the focus of future research should be the elucidation of necrotic signaling mechanisms to identify relevant targets, which may be used to attenuate hepatic IRP injury. Liver Transpl 20:1372‐1382, 2014. © 2014 AASLD.
Up‐regulation of the peroxiredoxin‐6 related metabolism of reactive oxygen species in skeletal muscle of mice lacking neuronal nitric oxide synthase

Although neuronal nitric oxide synthase (nNOS) plays a substantial role in skeletal muscle physiology, nNOS‐knockout mice manifest an only mild phenotypic malfunction in this tissue. To identify proteins that might be involved in adaptive responses in skeletal muscle of knockout mice lacking nNOS, 2D‐PAGE with silver‐staining and subsequent tandem mass spectrometry (LC‐MS/MS) was performed using extracts of extensor digitorum longus muscle (EDL) derived from nNOS‐knockout mice in comparison to C57Bl/6 control mice. Six proteins were significantly (P≤ 0.05) more highly expressed in EDL of nNOS‐knockout mice than in that of C57 control mice, all of which are involved in the metabolism of reactive oxygen species (ROS). These included prohibitin (2.0‐fold increase), peroxiredoxin‐3 (1.9‐fold increase), Cu2+/Zn2+‐dependent superoxide dismutase (SOD; 1.9‐fold increase), heat shock protein β‐1 (HSP25; 1.7‐fold increase) and nucleoside diphosphate kinase B (2.6‐fold increase). A significantly higher expression (4.1‐fold increase) and a pI shift from 6.5 to 5.9 of peroxiredoxin‐6 in the EDL of nNOS‐knockout mice were confirmed by quantitative immunoblotting. The concentrations of the mRNA encoding five of these proteins (the exception being prohibitin) were likewise significantly (P≤ 0.05) higher in the EDL of nNOS‐knockout mice. A higher intrinsic hydrogen peroxidase activity (P≤ 0.05) was demonstrated in EDL of nNOS‐knockout mice than C57 control mice, which was related to the presence of peroxiredoxin‐6. The treatment of mice with the chemical NOS inhibitor l‐NAME for3 days induced a significant 3.4‐fold up‐regulation of peroxiredoxin‐6 in the EDL of C57 control mice (P≤ 0.05), but did not alter its expression in EDL of nNOS‐knockout mice. ESR spectrometry demonstrated the levels of superoxide to be 2.5‐times higher (P≤ 0.05) in EDL of nNOS‐knockout mice than in C57 control mice while an in vitro assay based on the emission of 2,7‐dichlorofluorescein fluorescence disclosed the concentration of ROS to be similar in both strains of mice. We suggest that the up‐regulation of proteins that are implicated in the metabolism of ROS, particularly of peroxiredoxin‐6, within skeletal muscles of nNOS‐knockout mice functionally compensates for the absence of nNOS in scavenging of superoxide.
Cancer Stage‐to‐Age Relationship: Implications for Cancer Screening in the Elderly *

In a study specifically addressing the age‐stage relationship, the authors examined the distribution of 30,991 cancers by disease‐stage versus patient‐age at the time of diagnosis. For cancer of the bladder, breast, cervix, ovary and uterus (endometrium), a highly significant positive relationship was found between advancing stage and advancing age (P < 0.001). For cancer of the kidney and stomach, the relationship held but was less significant (P < 0.05). For colorectal cancer, no relationship was evident. For bronchial cancer there was a highly significant inverse relationship (P < 0.001). After the site of origin of the cancer, the stage at the time of diagnosis was the next most important determinant for treatment and survival. These data emphasize the importance of periodic pelvic examination as a means of screening for asymptomatic cervical, ovarian, or other uterine (endometrial) cancer in elderly women. Also, the data support the importance of breast self‐examination and mammography in screening for breast cancer in older women. The inverse relationship of age to stage in bronchial cancer suggests that screening by periodic chest roentgenograms and cytologic sputum examinations may be more appropriate for elderly than for younger populations in whom these screening methods have proved disappointing.
Mechanism of Ligand Binding to E- and P-selectin Analyzed Using Selectin/Mannose-binding Protein Chimeras*

The mechanism of oligosaccharide binding to the selectin cell adhesion molecules has been analyzed by transferring regions of the carbohydrate-recognition domains of E- and P-selectin into corresponding sites in the homologous rat serum mannose-binding protein. Insertion of two basic regions and an adjacent glutamic acid residue leads to efficient binding of HL-60 cells and sialyl-Lewisx-conjugated serum albumin. Substitution of glycine for a histidine residue known to stabilize mannose in the binding site of wild type mannose-binding protein results in dramatic loss of affinity for mannose without decreasing binding to sialyl-Lewisx. The accumulated effect of these changes is to alter the ligand binding selectivity of the domain so that it resembles E- or P-selectin more closely than it resembles the parental mannose-binding domain. Affinity labeling using sialyl-Lewisx in which the sialic acid has been mildly oxidized has been used to verify this switch in specificity and to show that the sialic acid-containing portion of the ligand interacts near the sequence Lys-Lys-Lys corresponding to residues 111–113 of E-selectin. The binding of sialyl-Lewisx-serum albumin is inhibited dramatically at physiological and higher salt concentrations, consistent with a significant electrostatic component to the binding interaction. The binding characteristics of these gain-of-function chimeras suggest that they contain many of the selectin residues responsible for selective ligand binding.
Evaluation of the ATB 32 A system for identification of anaerobic bacteria isolated from clinical specimens

A new miniaturized 4-h method for the identification of anaerobic bacteria, ATB 32 A (API System SA, Montalieu Vercieu, France), was evaluated against conventional methods of identification. The evaluation was done by using 260 recent clinical isolates and 21 reference strains of anaerobic bacteria. All reference strains were correctly identified and did not figure in the detailed analysis. Of the 140 gram-negative bacilli, 90.6% of Bacteroides spp. and 95.5% of Fusobacterium spp. were correctly identified to the species level, with an additional 8.4% of the Bacteroides spp. being identified to the genus level. Clostridia were correctly identified in 85.9% of cases, with an additional 9.9% being identified to the genus level. Peptostreptococci were correctly identified in 91.6% of cases. The 4 strains of Actinomyces spp. were all identified correctly, as were 10 of the 11 strains of Propionibacterium spp. A total of 3.1% of strains were not identified by ATB 32 A, while for 1.9% of strains, completely false identifications were obtained. Estimation of the individual preformed enzyme results may pose problems, although these decrease with familiarity with the system. With certain enzyme profiles, additional testing was necessary to arrive at an identification; however, there was no requirement for gas-liquid chromatography. If certain additions are made to the data base and the difficulties of determination of organisms to the species level among the non-Bacteroides fragilis (sensu stricto) members of the B. fragilis group can be reduced, this system holds promise as a reliable standardized alternative for the identification of anaerobic bacteria in clinical laboratories.
Structural Basis for Ca2+-mediated Interaction of the Perforin C2 Domain with Lipid Membranes*

Background: Perforin is a critical component of immune homeostasis, responsible for clearing virally infected cells. Results: The molecular details of calcium binding by the perforin C2 domain are revealed. Conclusion: Calcium-mediated structural rearrangement activates perforin for membrane binding. Significance: The C2 domain regulates membrane binding by calcium-dependent events, which have now been defined for a mammalian perforin C2. Natural killer cells and cytotoxic T-lymphocytes deploy perforin and granzymes to kill infected host cells. Perforin, secreted by immune cells, binds target membranes to form pores that deliver pro-apoptotic granzymes into the target cell. A crucial first step in this process is interaction of its C2 domain with target cell membranes, which is a calcium-dependent event. Some aspects of this process are understood, but many molecular details remain unclear. To address this, we investigated the mechanism of Ca2+ and lipid binding to the C2 domain by NMR spectroscopy and x-ray crystallography. Calcium titrations, together with dodecylphosphocholine micelle experiments, confirmed that multiple Ca2+ ions bind within the calcium-binding regions, activating perforin with respect to membrane binding. We have also determined the affinities of several of these binding sites and have shown that this interaction causes a significant structural rearrangement in CBR1. Thus, it is proposed that Ca2+ binding at the weakest affinity site triggers changes in the C2 domain that facilitate its interaction with lipid membranes.