Miracle-dz/UniFAR-FTUs huggingface dataset:
Filovirus-induced endothelial leakage triggered by infected monocytes/macrophages

The pathogenetic mechanisms underlying hemorrhagic fevers are not fully understood, but hemorrhage, activation of coagulation, and shock suggest vascular instability. Here, we demonstrate that Marburg virus (MBG), a filovirus causing a severe form of hemorrhagic fever in humans, replicates in human monocytes/macrophages, resulting in cytolytic infection and release of infectious virus particles. Replication also led to intracellular budding and accumulation of viral particles in vacuoles, thus providing a mechanism by which the virus may escape immune surveillance. Monocytes/macrophages were activated by MBG infection as indicated by tumor necrosis factor alpha (TNF-alpha) release. Supernatants of monocyte/macrophage cultures infected with MBG increased the permeability of cultured human endothelial cell monolayers. The increase in endothelial permeability correlated with the time course of TNF-alpha release and was inhibited by a TNF-alpha specific monoclonal antibody. Furthermore, recombinant TNF-alpha added at concentrations present in supernatants of virus-infected macrophage cultures increased endothelial permeability in the presence of 10 micron H2O2. These results indicate that TNF-alpha plays a critical role in mediating increased permeability, which was identified as a paraendothelial route shown by formation of interendothelial gaps. The combination of viral replication in endothelial cells (H.-J. Schnittler, F. Mahner, D. Drenckhahn, H.-D. Klenk, and H. Feldmann, J. Clin. Invest. 19:1301-1309, 1993) and monocytes/macrophages and the permeability-increasing effect of virus-induced cytokine release provide the first experimental data for a novel concept in the pathogenesis of viral hemorrhagic fever.
Risk factors for severity and manifestations in systemic sclerosis and prediction of disease course

ABSTRACT Systemic sclerosis (SSc, or scleroderma) is a rheumatic disease with distinct features that encompass autoimmunity, vascular lesions (vasculopathy) and tissue fibrosis. The disease has a high morbidity and mortality compared with other rheumatic diseases. This review discusses risk factors and markers that predict the disease course and the occurrence of disease manifestations, with an emphasis on major organ involvement. In addition, risk factors will be described that are associated with mortality in SSc patients. The review addresses the impact of recent developments on screening, diagnosis and risk stratification as well as the need for further research where data are lacking.
Pediatric cardiac catheterization procedure with dexmedetomidine sedation: Radiographic airway patency assessment

Aims: The aim of the study was to measure airway patency objectively during dexmedetomidine sedation under radiographic guidance in spontaneously breathing pediatric patients scheduled for cardiac catheterization procedures. Subjects and Methods: Thirty-five patients in the age group 5–10 years scheduled for cardiac catheterization procedures were enrolled. All study patients were given loading dose of dexmedetomidine at 1 μg/kg/min for 10 min and then maintenance dose of 1.5 μg/kg/h. Radiographic airway patency was assessed at the start of infusion (0 min) and after 30 min. Antero-posterior (AP) diameters were measured manually at the nasopharyngeal and retroglossal levels. Dynamic change in airway between inspiration and expiration was considered a measure of airway collapsibility. Patients were monitored for hemodynamics, recovery time and complications. Statistical Analysis: Student paired t-test was used for data analysis. P < 0.05 was considered significant. Results: Minimum and maximum AP diameters were compared at 0 and 30 min. Nasopharyngeal level showed significant reduction in the minimum (6.27 ± 1.09 vs. 4.26 ± 1.03, P < 0.0001) and maximum (6.51 ± 1.14 vs. 5.99 ± 1.03, P < 0.0001) diameters. Similarly retroglossal level showed significant reduction in the minimum (6.98 ± 1.09 vs. 5.27 ± 1.15, P < 0.0001) and maximum (7.49 ± 1.22 vs. 6.92 ± 1.12, P < 0.0003) diameters. The degree of collapsibility was greater at 30 min than baseline (P < 0.0001). There was a significant decrease in heart rate (P < 0.0001), and the average recovery time was 39.86 ± 12.22 min. Conclusion: Even though airway patency was maintained in all children sedated with dexmedetomidine, there were significant reductions in the upper airway dimensions measured, so all precautions to manage the airway failure should be taken.
Evaluation of block turbo codes for long-haul optical networks

Optical network traffic has been increasing significantly over the last decade, and strong forward error correction (FEC) is essential to deal with the traffic. While hard-decision codes have been used for the first and the second generation FECs, soft-decision codes are being actively studied as candidates for the third generation codes. The requirements for the third generation codes are over 10 dB net coding gain (NCG) with about 20 % overhead. According to Tzimpragos et al. [1], block turbo codes (BTCs) with 15 % and 20 % overhead obtained the NCGs of over 11 dB. In this paper, we study the BTC pool that targets the long-haul optical networks and evaluate the BTC candidates. In order to achieve the target bit error rate (BER) of 10-15, a large minimum distance is essential for the BTCs. Thus, we estimate the BER performances of the BTCs with the minimum distances of 24 and 36. Since the target BER requires extensive simulations, we estimate the NCGs by observing the BER down to 10-9 and conjecturing about the rest of the BER. We also compare the candidate BTCs in terms of the decoding-complexity.
A Co-Integration Analysis of the Interdependencies between Crude Oil and Distillate Fuel Prices

The co-evolution and co-movement of financial time series is of utmost importance in contemporary finance, especially when considering the joint behaviour of asset price realizations. The ability to model interdependencies and volatility spill-over effects introduces interesting dimensions in finance. This paper explores co-integrating relationships between crude oil and distillate fuel prices. Existence of multivariate co-integrating relations and bidirectional Granger-Causality is established among the series. It is also established that even after fitting a full VECM, the residuals are not necessarily multivariate normal suggesting the noise could as well be multivariate GARCH.
A new gene locus of Bordetella pertussis defines a novel family of prokaryotic transcriptional accessory proteins

Recently, a novel type of regulatory mutation causing differential effects on the expression of virulence genes due to a slight overexpression of the RNA polymerase alpha subunit (RpoA) was found in Bordetella pertussis (N. H. Carbonetti, T. M. Fuchs, A. A. Patamawenu, T. J. Irish, H. Deppisch, and R. Gross, J. Bacteriol. 176:7267-7273, 1994). To gather information on the molecular events behind this phenomenon, we isolated suppressor mutants of the RpoA-overexpressing strains after random mutagenesis. Genetic characterization of these suppressor strains revealed the existence of at least three distinct groups of dominant alleles. Mutations occurred either in the rpoA locus itself, in the bvg locus, or in unknown gene loci. One mutant of the latter group was further characterized. By the introduction of a cosmid library containing genomic B. pertussis DNA into this suppressor strain, we isolated a cosmid which suppressed the phenotype of the suppressor strain, thus restoring the negative effect on transcription of the ptx and cya toxin genes. Mutagenesis of the cosmid with Tn5 led to the identification of the gene locus responsible for this phenomenon. Its DNA sequence revealed the presence of an open reading frame (ORF) consisting of 2,373 bp coding for a hypothetical 86-kDa protein with extensive sequence similarities to ORFs with not yet identified functions of Escherichia coli, Haemophilus influenzae, and Neisseria meningitidis. The new gene, termed tex, for toxin expression, seems to be an essential factor for B. pertussis, as it cannot be deleted from the bacterial chromosome. All members of this new protein family show significant sequence similarities with the mannitol repressor protein MtlR and with the presumptive RNA-binding domains of the Pnp and ribosomal S1 proteins of E. coli in their N- and C-terminal parts, respectively. These sequence similarities and the fact that the tex gene was isolated by virtue of its effects on gene expression in B. pertussis indicate that the members of this new protein family may play an important role in the transcription machinery of prokaryotic organisms.
Ultrastructural quantification of pulmonary intravascular macrophages in newborn and 2‐week‐old lambs

Pulmonary intravascular macrophages are resident cells in the pulmonary circulation of sheep. Sheep, unlike species without pulmonary intravascular macrophages, exhibit pulmonary hypertension in response to intravenously injected particles. We reported in lambs that pulmonary vascular reactivity to intravenous particles increases with age as the population of intravascular macrophages develops. Preliminary quantitative histologic data showed that newborn lambs are born with few intravascular macrophages, but a large population develops over 2 weeks after birth. In this study, we present a complete quantitative analysis at the ultrastructural level.
Workplace Democracy : Representation and Participation Gaps in the Norwegian Labour Market Model

Employee participation and cooperation are core elements institutionalized in the Nordic model of labour relations as well as in the Nordic notion of a democratic working life. We term this participation/cooperation the ‘one leg’ in the model. The right to participate has been morally justified on the basis of two different but interrelated arguments: it is democratic, and it is efficient. In a European setting, where loss of trade union power and influence is part of an ongoing discussion, the Norwegian case might be seen as a robust one when studying important institutional features such as participation and cooperation at the company level. Nevertheless, taking a deeper look into the presence of institutional arrangements and the activity of employees’ representatives we find variation across industries. In this chapter we discuss whether this variation could be understood as a process of drift or a failed institutionalization of the Norwegian model of labour relations in part of the labour market.
Caspase‐6 gene disruption reveals a requirement for lamin A cleavage in apoptotic chromatin condensation

To study the role of caspase‐6 during nuclear disassembly, we generated a chicken DT40 cell line in which both alleles of the caspase‐6 gene were disrupted. No obvious morphological differences were observed in the apoptotic process in caspase‐6‐ deficient cells compared with the wild type. However, examination of apoptosis in a cell‐free system revealed a block in chromatin condensation and apoptotic body formation when nuclei from HeLa cells expressing lamin A or lamin A‐transfected Jurkat cells were incubated in caspase‐6‐deficient apoptotic extracts. Transfection of exogenous caspase‐6 into the clone reversed this phenotype. Lamins A and C, which are caspase‐6‐only substrates, were cleaved by the wild‐type and heterozygous apoptotic extracts but not by the extracts lacking caspase‐6. Furthermore, the caspase‐6 inhibitor z‐VEID‐fmk mimicked the effects of caspase‐6 deficiency and prevented the cleavage of lamin A. Taken together, these observations indicate that caspase‐6 activity is essential for lamin A cleavage and that when lamin A is present it must be cleaved in order for the chromosomal DNA to undergo complete condensation during apoptotic execution.
Intratumoral but not peritumoral lymphatic vessel density measured by D2-40 expression predicts poor outcome in gastric cancer--ROC curve analysis to find cut-off point.

BACKGROUND Neolymphangiogenesis, a process of lymphatic vessel development in neoplastic tissue, may be a key event in the transmission of cancer cells into lymph nodes. The current study examined the relationship between lymphatic vessel density (LVD) measured by podoplanin (D2-40) expression, clinicopathological parameters and patient survival in gastric cancer. MATERIALS AND METHODS D2-40 expression was examined by immunohistochemistry in formalin-fixed paraffin-embedded tissue specimens obtained from 60 patients with gastric cancer. D2-40 immunoreactivity was analyzed in intratumoral and peritumoral compartments of tumors and correlated with tumor grade, type in Lauren's classification, lymph node status, distant metastasis, presence of ulceration, inflammatory infiltration, angio-invasion, lymphangio-invasion and patient survival using a Receiver Operating Characteristic (ROC) curve analysis to find cut-off points that enabled fair decision making in survival analysis. RESULTS The mean values of intratumoral and peritumoral LVD were 6.63 and 11.25, respectively. Enhanced intratumoral LVD measured by D2-40 immunoexpression was correlated with the presence of lymph node metastases (p=0.04). Our study revealed a statistically significant correlation between intratumoral LVD measured by D2-40 expression and survival of patients with gastric cancer: an intratumoral LVD higher than 4.68 is significantly correlated with unfavorable prognosis, with a probability of death of approximately 80%. No significant relationship was identified between peritumoral LVD, lymph node status and survival in patients with gastric cancer. CONCLUSION A high intratumoral LVD measured by D2-40 expression in specimens from primary tumors is strongly associated with lymph node metastasis and predicts worse clinical outcome. Increased intratumoral D2-40 immunoreactivity is a putative predictor of aggressive gastric cancer behavior.
Paroxetine: a review.

Paroxetine is a potent and selective serotonin reuptake inhibitor (SSRI) with currently approved indications for the treatment of depression, obsessive-compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post traumatic stress disorder, premenstrual dysphoric disorder and chronic headache. Paroxetine, a phenylpiperidine derivative, is the most potent inhibitor of the reuptake of serotonin (5-hydroxytryptamine, 5-HT) of all the currently available antidepressants including the class of SSRIs. It is a very weak inhibitor of norepinephrine (NE) uptake but it is still more potent at this site than the other SSRIs. The selectivity of paroxetine, i.e., the ratio of inhibition of uptake of norepinephrine to serotonin (NE/5-HT) is amongst the highest of the SSRIs. Paroxetine has little affinity for catecholaminergic, dopaminergic or histaminergic systems and by comparison with tricyclic antidepressants (TCAs) has, therefore, a reduced propensity to cause central and autonomic side effects. Paroxetine exhibits some affinity for the muscarinic cholinergic receptor but much less than the TCAs. In addition, the adaptive changes of somatodendritic (5-HT(1A)) and terminal (5-HT(1B/1D)) autoreceptors observed with paroxetine are different to those observed with TCAs; it also inhibits nitric oxide synthase. It is both a substrate and an inhibitor of cytochrome isoenzyme P450 2D6. Paroxetine is well absorbed orally and undergoes extensive first pass metabolism that is partially saturable. Its metabolites are pharmacologically inactive in vivo. Steady state levels are achieved after 4-14 days and an elimination half-life of 21 h is consistent with once-daily dosing. There is wide inter-individual variation in the pharmacokinetics of paroxetine in adults as well as in the young and the elderly with higher plasma concentrations and slower elimination noted in the latter. Elimination is also reduced in severe renal and hepatic impairment. Serious adverse events are, however, extremely rare even in overdose. In summary, paroxetine is well tolerated and effective in the treatment of both depressive and anxiety disorders across the age range.
Stabilization of a Turbulent Premixed Flame Using a Nanosecond Repetitively Pulsed Plasma

A nanosecond repetitively pulsed plasma (NRPP) produced by electric pulses of 10 kV during 10 ns at a frequency of up to 30 kHz has been used to stabilize and improve the efficiency of a 25-kW lean turbulent premixed propane/air flame (ReD=30000) at atmospheric pressure. We show that, when placed in the recirculation zone of the flow, the plasma significantly increases the heat release and the combustion efficiency, thus allowing to stabilize the flame under lean conditions where it would not exist without plasma. Stabilization is obtained with a very low level of plasma power of about 75 W, or 0.3% of the maximum power of the flame. In addition, they find that at high flow rates, where the flame should normally blow out, the NRPP allows the existence of an intermittent V-shaped flame with significant heat release, and at even higher flow rates the existence of a small dome-shaped flame confined near the electrodes that can serve as a pilot flame to reignite the combustor. Optical emission spectroscopy measurements are presented to determine the temperature of the plasma-enhanced flame, the electron number density, and to identify the active species produced by the plasma, namely O, H, and OH
Face Recognition for Intelligent Robot Safety Verification System

The current intelligent robots lack a certain degree of security, can not accurately identify the user. Embedded devices exist in the existing face recognition is not accurate enough, the depth of learning resources and other issues is not enough. We presented a new type of ResNet face recognition model for transplanting in embedded devices. We used the machine to learn to face the face detection, and extracted 68 face key points, the use of depth residual network algorithm for further identification, and ultimately compared the European distance to determine and identify the user. Experiments show that the scheme has the advantages of good precision and good accuracy, and can be used in the intelligent robot system.
Pancreatic cancer: Update on immunotherapies and algenpantucel-L

ABSTRACT Pancreatic adenocarcinoma is notoriously lethal, and despite improvements in systemic chemotherapy approaches bringing survival rates for metastatic disease to almost 1 year, by 2030 it is expected to become the second leading cause of cancer death. Pancreatic cancer (PC) prognosis has been associated with both the presence of intratumoral helper and cytotoxic T lymphocytes, as well as humoral immune responses to tumor associated antigens like mesothelin. It is well described that the PC microenvironment is characterized by a fibroinflammatory and immunosuppressive stroma. On these premises several immune-targeted strategies have been developed to harness the adaptable immune system with a goal of improving survival with little toxicity. Cancer vaccines involve the administration of tumor-associated antigens with the goal of inducing an endogenous anti-tumor response. Among several strategies discussed, we will focus on the algenpantucel-L (HyperAcute™ Pancreas) immunotherapy. Algenpantucel-L is a whole cell immunotherapy consisting of irradiated allogeneic PC cells genetically engineered to express the murine enzyme α(1,3)-galactosyltransferase (αGT), which ultimately leads to hyperacute rejection with complement- and antibody-dependent cytotoxicity. While phase III data in the adjuvant treatment of pancreatic cancer are pending, phase II results have been encouraging, particularly for patients who demonstrated humoral immunologic responses. Novel strategies using immune checkpoint inhibitors, costimulatory antibodies, and combinations with cancer vaccines may overcome immunotolerance and improve treatment success.
Proliferation and Differentiation of Adult Endogenous Neural Stem Cells in Response to Neurodegenerative Process within the Striatum

The ongoing process of neurogenesis in the adult mammalian forebrain suggests the possible capacity for limited self-repair after brain injury. Previously, we have demonstrated that in an animal model of Huntington’s disease the neurodegenerative process initiates immediate intensive cell proliferation and differentiation resulting in characteristic enlargement of the subependymal zone (SEZ) of lateral brain ventricles. Now, our interest is focused on the architecture of the neurogenic niche of the SEZ in the identical model, particularly on characteristic features of astrocyte-like cells which are considered to be not only niche cells but also neural stem cells. Our findings prove higher activation of the lateral part of the SEZ (L-SEZ) adjacent to the degenerated striatum compared with the rostral part of the SEZ (R-SEZ). In the activated L-SEZ, niche cells which ensheathe clusters of neural progenitors are of immature astrocytic phenotype because of nestin and vimentin expression (except the expression of glial fibrillary acidic protein). However, the coexpression of all three filaments is not always found. Intermediate filaments also enable us to distinguish the basic shape of astrocytic cells within the SEZ, majority of which resemble protoplasmic rather than fibrillary astrocytes. Furthermore, our results show a wide plasticity of these astrocyte-like cells in immediate response to an extensive pathological process in the brain. These observations are consistent with the fact that adult stem cells undergo different processes in an already mature environment, and therefore can exhibit some specific characteristics unlike the embryonic or fetal neural stem cells.
Fusidic acid and heparin lock solution for the prevention of catheter-related bloodstream infections in critically ill neonates: A retrospective study and a prospective, randomized trial*

Objective: Catheter-related bloodstream infections (CRBSIs) are one of the main morbidities in critically ill neonates. The objective of the present study was to assess the efficacy of a fusidic acid-heparin lock in the prevention of CRBSIs. Design: A preliminary retrospective study showed that staphylococcal infections were largely prevalent. We planned a prospective, randomized trial to ascertain whether fusidic acid and heparin lock of central venous catheters would reduce the incidence of CRBSIs. Setting: Level III neonatal intensive care unit. Patients: One hundred three neonates were enrolled and randomly assigned to a treatment group (n = 50) or control group (n = 53). Interventions: Fusidic acid (4 mg/mL) and heparin (10 IU/mL) lock in the treatment group. Measurements and Main Results: The treatment group showed significantly lower incidence of CRBSIs (6.6 vs. 24.9 per 1000 catheter days; p < .01; relative risk 0.28; 95% confidence interval 0.13–0.60). No staphylococcal infections occurred in the treatment group, while in the control group Staphylococcus remained the main agent of CRBSI. Cost analysis comparing the present study and for the treatment of CRBSIs proved that antibiotic lock is financially favorable. Conclusions: Fusidic acid-heparin lock solution reduced the incidence of CRBSIs in our neonatal intensive care unit. However, we recommend basing antibiotic lock on local CRBSI epidemiology. With regard to fusidic acid, further and broader studies could be useful to confirm our results.