Miracle-dz/UniFAR-FTUs huggingface dataset:
Toward a More Accurate Quantitation of the Activity of Recombinant Retroviruses: Alternatives to Titer and Multiplicity of Infection

ABSTRACT In this paper, we present a mathematical model with experimental support of how several key parameters govern the adsorption of active retrovirus particles onto the surface of adherent cells. These parameters, including time of adsorption, volume of virus, and the number, size, and type of target cells, as well as the intrinsic properties of the virus, diffusion coefficient, and half-life (t 1/2), have been incorporated into a mathematical expression that describes the rate at which active virus particles adsorb to the cell surface. From this expression, we have obtained estimates of C vo, the starting concentration of active retrovirus particles. In contrast to titer,C vo is independent of the specific conditions of the assay. The relatively slow diffusion (D = 2 × 10−8 cm2/s) and rapid decay (t 1/2 = 6 to 7 h) of retrovirus particles explain why C vo values are significantly higher than titer values. Values ofC vo also indicate that the number of defective particles in a retrovirus stock is much lower than previously thought, which has implications especially for the use of retroviruses for in vivo gene therapy. With this expression, we have also computed AVC (active viruses/cell), the number of active retrovirus particles that would adsorb per cell during a given adsorption time. In contrast to multiplicity of infection, which is based on titer and is subject to the same inaccuracies, AVC is based on the physicochemical parameters of the transduction assay and so is a more reliable alternative.
Sophisticated Denial of Service attacks aimed at application layer

Popularity of application services offered by Internet has grown a lot in recent years. Basically, Internet was built with the focus on its functionality and not with the focus on the security tasks. This has led to discovering embedded weaknesses in Internet architecture, which can be misused by attackers with malicious purposes. This paper focuses on application layer Denial of Service (DoS) and Distributed Denial of Service (DDoS) attacks detection, because these attacks present a continuous critical threat to the Internet services. DDoS attacks are typically carried out at the network layer. However, there is evidence to suggest that application layer DDoS attacks can be more effective than the traditional ones. Over some period of time, researchers proposed many solutions to prevent the DoS/DDoS attacks from different OSI layers, but there has been done only a very small research on application layer. In this paper, we consider sophisticated attacks that utilize legitimate application layer requests from legitimately connected network machines to overwhelm Web server. Since the attack signature of each application layer DDoS is represented in abnormal user behavior, we propose several mechanisms, which can be used for application DoS/DDoS attack detection.
Increased neuronal nitric oxide synthase interaction with soluble guanylate cyclase contributes to the splanchnic arterial vasodilation in portal hypertensive rats

Splanchnic arterial vasodilation represents the pathophysiological hallmark of the hemodynamic dysfunction observed in portal hypertensive states. The role of neuronal nitric oxide synthase (nNOS) in the splanchnic arterial vasodilation remains to be elucidated. We therefore investigated: (i) if nNOS is involved in the splanchnic arterial vasodilation; and (ii) the possible interaction of nNOS with soluble guanylate cyclase (sGC) in superior mesenteric arterial (SMA) beds in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation (PVL). To determine the role of nNOS, we removed endothelial layer and measured contractile response and nitric oxide (NO) release in the presence or absence of 7‐nitroindazole (7‐NI, 10 μM), an nNOS‐specific inhibitor. In endothelium‐removed vessels, nNOS inhibitor significantly increased the contractile response to methoxamine in SMA beds isolated from the portal hypertensive rats, compared to non‐treated SMA beds (106.8 ± 10.7 vs 86.8 ± 7.2 mmHg, P = 0.003). This effect of nNOS inhibitor was accompanied with decreased NO production in SMA of portal hypertensive rats (321.3 ± 18.6 vs 139.5 ± 16.9 pmol/mL/min, P = 0.0001). Unlike endothelial NOS that is located in endothelial cells, nNOS protein is highly expressed in smooth muscle layers of SMA. Furthermore, there was a significant increase in ~90 kDa nNOS protein in the portal hypertensive group, compared to the sham‐operated group (P < 0.01). Interestingly, this 90 kDa nNOS was coimmunoprecipitated with sGC. In conclusion, increased nNOS expression in smooth muscle layers of arteries in the splanchnic circulation may be an additional and more efficient pathway for the activation of sGC by NO, which sustains arterial vasodilation.
Deletion of the 19kDa antigen does not alter the protective efficacy of BCG.

Expression of the Mycobacterium tuberculosis 19kDa lipoprotein in saprophytic mycobacteria has been found to reduce their ability to prime a protective response to subsequent virulent challenge in the mouse model. The present study was designed to test whether 19kDa expression has an analogous detrimental effect on the efficacy of BCG vaccination. In contrast to the results in saprophytes, neither overexpression of the 19kDa antigen, nor deletion of the endogenous 19kDa gene altered the ability of BCG to protect against M. tuberculosis challenge in a mouse model.
Gastric cancer surgery: morbidity and mortality results from a prospective randomized controlled trial comparing D2 and extended para-aortic lymphadenectomy--Japan Clinical Oncology Group study 9501.

PURPOSE Radical gastrectomy with regional lymphadenectomy is the only curative treatment option for gastric cancer. The extent of lymphadenectomy, however, is controversial. The two European randomized trials only reported an increase in operative morbidity and mortality, but failed to show survival benefit, in the D2 lymphadenectomy group. We conducted a randomized controlled trial to compare the Japanese standard D2 and D2 + para-aortic nodal dissection. PATIENTS AND METHODS Only experienced surgeons in both procedures from 24 Japanese institutions participated in the study. Patients with potentially curable gastric adenocarcinoma (T2-subserosa, T3, or T4) who were surgically fit were intraoperatively randomized. Postoperative morbidity and hospital mortality were recorded prospectively in a fixed format and were compared between the two groups in this study. RESULTS A total of 523 patients were randomized between July 1995 and April 2001. Postoperative complications were reported in 24.5% of all patients. Although the morbidity for the extended surgery group (28.1%) was slightly higher than the standard group (20.9%), there was no difference in the incidence of four major complications (anastomotic leak, pancreatic fistula, abdominal abscess, pneumonia) between the two groups. Hospital mortality was reported at 0.80%: one patient in each group died of operative complications, while one from each group died of rapid progressive cancer while inpatient. CONCLUSION Specialized surgeons could safely perform gastrectomy with D2 lymphadenectomy in patients with low operative risks. Para-aortic lymphadenectomy could be added without increasing major surgical complications in this setting.
Time from HIV infection to virological suppression: dramatic fall from 2007 to 2016

Aim: Time from HIV infection to virological suppression: dramatic fall from 2007 to 2016. Objectives: We examined the time from HIV infection to virological suppression in MSM who were first diagnosed at Melbourne Sexual Health Centre between 2007 and 2016. Design: Retrospective cohort. Methods: Date of infection was imputed from the testing history or serological evidence of recent infection (negative or indeterminate western blot) or baseline CD4+ cell count. Date of virological suppression was determined using clinical viral load data. We analysed predictors of diagnosis with serological evidence of recent infection (logistic regression) and time from diagnosis to suppression and from infection to suppression (Cox regression) using demographic, clinical, and behavioral covariates. Results: Between 2007 and 2016, the median time from HIV infection to diagnosis fell from 6.8 to 4.3 months (P = 0.001), from diagnosis to suppression fell from 22.7 to 3.2 months (P < 0.0001), and from infection to suppression fell from 49.0 to 9.6 months (P < 0.0001). Serological evidence of recent infection increased from 15.6 to 34.3% (P < 0.0001) of diagnoses. In the multivariate analyses, age, being recently arrived from a non-English speaking country, history of IDU, other sexually transmitted infections, and sexual risk were not associated with any of these measures. Conclusion: The duration of infectiousness in MSM diagnosed with HIV infection at Melbourne Sexual Health Centre in Victoria has fallen dramatically between 2007 and 2016 and the proportion diagnosed with serological evidence of recent infection has increased. This effect is observed across all population subgroups and marks a positive milestone for the treatment as prevention paradigm.
Neurotrophic Roles of the Beta‐Thymosins in the Development and Regeneration of the Nervous System

Abstract: Beta‐thymosins (Tβs) are polypeptides abundant in the cytosol, nucleus, and extracellular space of many cell types. In the nervous system, the expression of Tβs is regulated during the development of the central nervous system and following neuronal insults in cell‐type and brain‐region dependent manners, which may be related to the function of Tβs in the growth and regeneration of the nervous system. Supporting such a proposition, overexpression of Tβs in neurons has been shown to modify the axonal branches in vivo and neurite branches in vitro. These neurite‐modifying functions have been suggested to be due to the activity of Tβs to bind actin. In addition, we recently observed that Tβs suppressed the apoptotic neuronal death in chick embryos, and these functions might be mediated by the extracellularly secreted form(s) of Tβs. These results suggest that Tβs play neurotrophic roles in the neuroprotection and neuronal growth/regeneration via their cytosolic actin‐remodeling activity and extracellular antiapoptotic activity. Even though further verification is required, we also observed that Tβ15 was translocated into the injured neuronal nuclei, and this event appeared to be an eliminatory process of the injured cells. Therefore, treatment with Tβs or their related peptides appear to be beneficial for neuronal diseases by preventing neuronal death or promoting neuronal regeneration.
A Comparison of 3 Hand‐Held Dynamometers Used to Measure Hip Abduction Strength

Quantification of strength with hand-held dynamometers is commonplace. Hand-held dynamometers offer ease of use; however, previous investigations have shown much variability between repeated measures using the same dynamometer. Even less is known regarding the degree of variability between various dynamometers. Therefore, the intent of this investigation was to compare measures of hip abduction strength recorded with 3 different but commonly used handheld dynamometers, specifically the Microfet 2 Load Cell, Jamar Hand-Held, and Dial Push-Pull Gauge. Maximal isometric hip abduction strength was recorded in 10 women (27.6 ± 6.2 years) over 3 consecutive days using a different device each day. A significant difference in recorded force was noted between the devices (p < 0.001) as the Microfet showed significantly less force than the others. This was supported by intraclass correlation coefficients (ICCs) ranging from 0.277 to 0.688. These data suggest that consideration must be given to using the same dynamometer when quantifying strength over repeated sessions.
Resuscitation with 21 or 100% Oxygen in Hypoxic Nicotine-Pretreated Newborn Piglets: Possible Neuroprotective Effects of Nicotine

Background: Perinatal asphyxia is a major concern in perinatal medicine. Resuscitation and ways to prevent and minimize adverse outcomes after perinatal asphyxia are subject to extensive research. Objectives: In this study we hypothesized that, prior to hypoxia, intravenously administered nicotine might have an effect on how newborn piglets tolerate hypoxia, with regard to the time and degree of damage inflicted, due to its suggested neuroprotective abilities, and further that resuscitation with 21 compared with 100% oxygen in nicotine-pretreated animals would cause less cerebral damage. Methods: Thirty anesthetized newborn piglets were randomized to either hypoxia or control groups, and pretreatment with either saline or nicotine. In addition, the nicotine/hypoxia group was randomized to resuscitation with either 21 or 100% oxygen for 15 min following hypoxia. Results: We found significantly more necrosis in the striatum and cortex combined (p = 0.036), and in the striatum alone (p = 0.026), in the animals pretreated with nicotine and resuscitated with 100% when compared to 21% oxygen. There was no significant difference in the cerebellum. We also found significantly increased tolerance to hypoxia as measured by the time interval that the animals endured hypoxia: 103.8 ± 28.2 min in the nicotine-pretreated animals vs. 66.5 ± 19.5 minin the saline-pretreated animals (p = 0.035). Conclusion: Nicotine enhances newborn piglets’ ability to endure hypoxia, and resuscitation with 21% oxygen inflicts less necrosis than 100% oxygen. The potential neuroprotective effects of nicotine in the newborn brain should be further investigated.
Circadian Blood Pressure Variability as a Function of Parity in Normotensive Pregnant Women

Studies based on office blood pressure measurements concluded that parity has significant effects on blood pressure during pregnancy. The authors evaluated possible differences in the circadian pattern of blood pressure as a function of parity in normotensive women systematically studied by ambulatory blood pressure monitoring. They analyzed 1400 blood pressure series sampled for 48 consecutive hours every 4 weeks from the first obstetric visit (usually within the first trimester of pregnancy) until delivery in 234 women. The circadian pattern of blood pressure variation for each group (nulliparous vs. multiparous) and trimester of gestation was established by population multiple‐component analysis. A highly statistically significant circadian pattern, described by a model that includes components with periods of 24 and 12 hours, was demonstrated for systolic and diastolic blood pressure for both groups of pregnant women in all trimesters (p<0.001). There was no significant difference in 24‐hour mean among groups divided by parity at any stage of pregnancy (p>0.315). Data obtained from systematic ambulatory monitoring in normotensive pregnant women indicate the lack of differences in blood pressure according to parity. Reference thresholds for blood pressure in pregnancy could thus be developed as a function of rest‐activity cycle and gestational age only, independent of parity.
VLSI Implementation of a Low-Cost High-Quality Image Scaling Processor

In this brief, a low-complexity, low-memory-requirement, and high-quality algorithm is proposed for VLSI implementation of an image scaling processor. The proposed image scaling algorithm consists of a sharpening spatial filter, a clamp filter, and a bilinear interpolation. To reduce the blurring and aliasing artifacts produced by the bilinear interpolation, the sharpening spatial and clamp filters are added as prefilters. To minimize the memory buffers and computing resources for the proposed image processor design, a T-model and inversed T-model convolution kernels are created for realizing the sharpening spatial and clamp filters. Furthermore, two T-model or inversed T-model filters are combined into a combined filter which requires only a one-line-buffer memory. Moreover, a reconfigurable calculation unit is invented for decreasing the hardware cost of the combined filter. Moreover, the computing resource and hardware cost of the bilinear interpolator can be efficiently reduced by an algebraic manipulation and hardware sharing techniques. The VLSI architecture in this work can achieve 280 MHz with 6.08-K gate counts, and its core area is 30378 μm2 synthesized by a 0.13-μm CMOS process. Compared with previous low-complexity techniques, this work reduces gate counts by more than 34.4% and requires only a one-line-buffer memory.
Risk Factors for Peak Dose Dyskinesia in 100 Levodopa-treated Parkinsonian Patients

Abstract Background : No clinical parameter other than “sufficient” dopamine denervation and exposure to exogenous levodopa has been unquestionably linked to dyskinesia in levodopa-treated Parkinson’s disease patients. Methods : We retrospectively analyzed data on 100 consecutive patients treated with levodopa for 1 to 18 years to identify clinical risk factors for dyskinesia. The cumulative dyskinesia-free survival probability in relation to levodopa therapy was assessed using the Kaplan-Meier method. Results : Overall, 56% of patients developed dyskinesia after a mean of 2.9 years, a figure similar to the average duration of levodopa treatment in the non-dyskinetic group. Dyskinetic patients were significantly younger at disease onset, but their mean latency to dyskinesia induction after levodopa initiation was not different from older dyskinetic individuals and the overall dyskinesia-free survival of younger subjects was not worse either. Dyskinetic patients were on a higher daily levodopa dose than non-dyskinetic subjects when dyskinesia emerged, but the cumulative levodopa dose used prior to dyskinesia did not discriminate dyskinetic from non-dyskinetic patients. A delay in initiating levodopa therapy of more than three years after disease onset and levodopa treatment initiation in Hoehn-Yahr stage II compared to stage I patients did not increase the probability of developing dyskinesia over time. Conclusions : Since withholding levodopa therapy did not increase the risk for dyskinesia in our patients and can delay the emergence of dyskinesia after onset of parkinsonian symptom, a trial with a dopaminomimetic agonist as initial treatment appears logical.
Optimizing detector placement and mapping using imaging techniques

This paper presents a proposed method with implementation of imaging techniques aiming to aid the current oil and gas industries for detector mapping in refineries and petrochemical plants. The proposed method is developed using MATLAB and the Image Processing Toolbox. Various type of imaging techniques are reviewed and chosen to be used in certain modules of this method. Currently the method is still in early stage of development and the testing is done to validate it.
Persistent changes in the intrinsic excitability of rat deep cerebellar nuclear neurones induced by EPSP or IPSP bursts

The deep cerebellar nuclei (DCN) are the major output of the cerebellum, and have been proposed as a site of memory storage for certain forms of motor learning. Microelectrode and whole‐cell patch recordings were performed on DCN neurones in acute slices of juvenile rat cerebellum. DCN neurones display tonic and bursting basal firing patterns. In tonically firing neurones, a stimulus consisting of EPSP bursts produced a brief increase in dendritic Ca2+ concentration and a persistent increase in the number of spikes elicited by a depolarizing test pulse, along with a decrease in spike threshold. In intrinsically bursting DCN neurones, EPSP bursts induced an increase in the number of depolarization‐evoked spikes in some neurones, but in others produced a change to a more tonic firing pattern. Application of IPSP bursts evoked a large number of rebound spikes and an associated dendritic Ca2+ transient, which also produced a persistent increase in the number of spikes elicited by a test pulse. Intracellular perfusion of the Ca2+ chelator BAPTA prevented the increase in intrinsic excitability. Thus, rapid changes in intrinsic excitability in the DCN may be driven by bursts of both EPSPs and IPSPs, and may result in persistent changes to both firing frequency and pattern.
Competition and Coexistence between Streptococcus mutans and Streptococcus sanguinis in the Dental Biofilm

ABSTRACT The human mucosal surface is colonized by the indigenous microflora, which normally maintains an ecological balance among different species. Certain environmental or biological factors, however, may trigger disruption of this balance, leading to microbial diseases. In this study, we used two oral bacterial species, Streptococcus mutans and Streptococcus sanguinis (formerly S. sanguis), as a model to probe the possible mechanisms of competition/coexistence between different species which occupy the same ecological niche. We show that the two species engage in a multitude of antagonistic interactions temporally and spatially; occupation of a niche by one species precludes colonization by the other, while simultaneous colonization by both species results in coexistence. Environmental conditions, such as cell density, nutritional availability, and pH, play important roles in determining the outcome of these interactions. Genetic and biochemical analyses reveal that these interspecies interactions are possibly mediated through a well-regulated production of chemicals, such as bacteriocins (produced by S. mutans) and hydrogen peroxide (produced by S. sanguinis). Consistent with the phenotypic characteristics, production of bacteriocins and H2O2 are regulated by environmental conditions, as well as by juxtaposition of the two species. These sophisticated interspecies interactions could play an essential part in balancing competition/coexistence within multispecies microbial communities.
Dietary management of peanut and tree nut allergy: what exactly should patients avoid?

Peanut and tree nut allergies are the commonest cause of life‐threatening food‐allergic reactions and significantly affect quality of life in children and their families. Dietary nut avoidance and provision of emergency medication is currently the mainstay of treatment. Nut avoidance has consequences on both quality of life and nutrition. We review the terminology that may cause confusion and lead to unnecessary dietary restrictions. In peanut or tree nut‐allergic children, introduction of specific nuts to which the child is not allergic may improve quality of life and should be considered in patients with multiple foods allergies, vegan or ethnic‐specific diets, in whom nuts are an important source of protein. Nut‐allergic consumers do not just need to avoid foods containing nuts as an ingredient, but also contend with pre‐packed foods which frequently have precautionary allergen labelling (PAL) referring to possible nut contamination. Although the published rate of peanut contamination in ‘snack’ foods with PAL (see Box ) ranges from 0.9–32.4%, peanut contamination in non‐snack items with PAL is far less common. We propose that in some peanut‐allergic patients (depending on history of reactivity to trace levels of peanut, reaction severity, other medical conditions, willingness to always carry adrenaline, etc.), consideration may be given to allow the consumption of non‐snack foods containing PAL following discussion with the patient's (and their family's) specialist. More work is needed to provide consumers with clearer information on the risk of potential nut contamination in pre‐packed food. We also draw attention to the change in legislation in December 2014 that require mandatory disclosure of allergens in non‐pre‐packed foods.