Miracle-dz/UniFAR-FTUs huggingface dataset:
Breakthrough Virus Neutralization Resistance as a Correlate of Protection in a Nonhuman Primate Heterologous Simian Immunodeficiency Virus Vaccine Challenge Study

ABSTRACT Comprehensive assessments of immune correlates of protection in human immunodeficiency virus (HIV) vaccine trials are essential to vaccine design. Neutralization sieve analysis compares the neutralization sensitivity of the breakthrough transmitted/founder (TF) viruses from vaccinated and control animals to infer the molecular mechanisms of vaccine protection. Here, we report a robust neutralization sieve effect in a nonhuman primate simian immunodeficiency virus (SIV) vaccine trial (DNA prime/recombinant adenovirus type 5 [rAd5] boost) (VRC-10-332) that demonstrated substantial protective efficacy and revealed a genetic signature of neutralization resistance in the C1 region of env. We found significant enrichment for neutralization resistance in the vaccine compared to control breakthrough TF viruses when tested with plasma from vaccinated study animals, plasma from chronically SIV-infected animals, and a panel of SIV-specific monoclonal antibodies targeting six discrete Env epitopes (P < 0.008 for all comparisons). Neutralization resistance was significantly associated with the previously identified genetic signature of resistance (P < 0.0001), and together, the results identify virus neutralization as a correlate of protection. These findings further demonstrate the in vivo relevance of our previous in vitro analyses of the SIVsmE660 challenge stock, which revealed a broad range of neutralization sensitivities of its component viruses. In sum, this report demonstrates proof-of-concept that phenotypic sieve analyses can elucidate mechanistic correlates of immune protection following vaccination and raises a cautionary note for SIV and SHIV (simian-human immunodeficiency virus) vaccine studies that employ challenge strains with envelope glycoproteins that fail to exhibit neutralization resistance profiles typical of TF viruses. IMPORTANCE With more than 2 million new infections annually, the development of an effective vaccine against HIV-1 is a global health priority. Understanding immunologic correlates of protection generated in vaccine trials is critical to advance vaccine development. Here, we assessed the role of vaccine-elicited neutralizing antibodies in a recent nonhuman primate study of a vaccine that showed significant protection against simian immunodeficiency virus (SIV) challenge and suggested a genetic signature of neutralization sensitivity. We found that breakthrough viruses able to establish infection in vaccinated animals were substantially more resistant to antibody-mediated neutralization than were viruses from controls. These findings suggest that vaccine-elicited neutralizing antibodies selectively blocked the transmission of more sensitive challenge viruses. Sieve analysis also corroborated a genetic signature of neutralization sensitivity and highlighted the impact of challenge swarm diversity. Our findings suggest an important role for neutralization sieve analyses as an informative component of comprehensive immune-correlates analyses.
The effect of direct and indirect defenses in two wild brassicaceous plant species on a specialist herbivore and its gregarious endoparasitoid

Most studies on plant defenses against insect herbivores investigate direct and indirect plant defenses independently. However, these defenses are not necessarily mutually exclusive. Plant metabolites can be transmitted through the food chain and can also affect the herbivore's natural enemies. A conflict may arise when a natural enemy is attracted to a plant that is suboptimal in terms of its own fitness. In addition, plant defenses are often studied in cultivated plant species in which artificial selection may have resulted in reduced resistance against insect herbivores. In this study, we investigated both direct and indirect plant defenses in two closely related wild brassicaceous plant species, Brassica nigra L. and Sinapis arvensis L. The herbivore Pieris brassicae L. (Lepidoptera: Pieridae), which is specialized on brassicaceous plant species, developed faster and attained higher pupal mass when reared on B. nigra than on S. arvensis. In contrast, Cotesia glomerata L. (Hymenoptera: Braconidae), which is a gregarious endoparasitoid of P. brassicae caterpillars, developed equally well on P. brassicae irrespective of the food plant on which its host had been reared. The feeding strategy of the parasitoid larvae, that is, selectively feeding on hemolymph and fat body, is likely to allow for a much wider host‐size range without affecting the size or development time of the emerging parasitoids. In flight chamber experiments, C. glomerata, which had an oviposition experience in a host that fed on Brussels sprout, exhibited significant preference for host‐damaged B. nigra over host‐damaged S. arvensis plants. Headspace analysis revealed quantitative and qualitative differences in volatile emissions between the two plant species. This parasitoid species may use a range of cues associated with the host and the host's food plant in order to recognize the different plant species on which the host can feed. These results show that there is no conflict between direct and indirect plant defenses for this plant–host–parasitoid complex.
Rate of Statin Prescription in Younger Patients With Severe Dyslipidemia

Cardiovascular disease affects 1 in 3 patients and remains the leading cause of death in the United States.1 Severe elevation of low-density lipoprotein cholesterol (LDL-C) levels is a modifiable risk factor for developing premature cardiovascular disease, and elevation levels of 190 mg/dL or greater (to convert LDL-C values to millimoles per liter, multiply by 0.0259) may indicate a monogenic etiology such as familial hypercholesterolemia.2 Treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors or statins is recommended (class IA) for all adults 21 years or older with an LDL-C of 190 mg/dL or greater. Statin treatment appears to reduce mortality and result in cost savings for health systems.3,4 Therefore, we sought to examine rates of statin prescription in patients screened for dyslipidemia to identify treatment gaps in a real-world contemporary setting.
An approach for feature extraction using spline approximation for Indian characters (SAIC) in recognition engines

Optical character recognition for printed Indian text is a classical problem because of round nature of these characters and presence of ldquomaatrasrdquo. Recognition accuracy of optical character recognition engines depends heavily upon correct representation of characters obtained by feature extraction method. Thus feature extraction is heart of recognition engines. We propose a novel spline approximation based method for feature extraction in recognition engines. The spline approximation is implemented for Indian characters and the results obtained are very encouraging as compared to existing feature extraction methods.
Cell‐free DNA in healthy individuals, noncancerous disease and strong prognostic value in colorectal cancer

The purpose was to investigate total cell‐free DNA (cfDNA) in colorectal cancer (CRC) patients during treatment with second‐line chemotherapy and in healthy controls and patients with different comorbidities. Patient treated with second‐line irinotecan for metastatic CRC (n = 100), a cohort of healthy controls with and without comorbidity (n = 70 and 100, respectively) were included. cfDNA was quantified by an in‐house developed quantitative polymerase chain reaction from plasma samples drawn prior to the first cycle of chemotherapy and at time of progression. cfDNA levels were significantly higher in CRC compared to controls, with a clear capability for discriminating between the groups (receiver operation curve analysis; area under the curve 0.82, p < 0.0001). Patients with high levels had a shorter survival from irinotecan compared to those with lover levels. The cohort independent upper normal limit divided patients into high and low risk groups. The progression‐free survival (PFS) was 2.1 months [95% confidence interval (CI) 2.0–3.4] and 6.5 (95% CI 4.2–7.2) months [hazard ratio (HR) 2.53; 95% CI 1.57–4.06, p < 0.0001] and overall survival (OS) 7.4 months (95% CI 4.3–8.7) and 13.8 months (95% CI 11.9–18.9; HR 2.52; 95% CI 1.54–4.13, p < 0.0000), respectively. Cox regression multivariate analysis showed a PFS HR of 1.4 (95% CI 1.1–1.7) for each increase in cfDNA quartile, p = 0.03 and 1.6 (1.3–2.0) for OS, p < 0.0001, respectively. A combined marker analysis with plasma KRAS mutations added further prognostic impact, which was consistent when performed on the samples drawn at time of progression. In conclusion, cfDNA measurement holds important clinical information and could become a useful tool for prediction of outcome from chemotherapy in mCRC.
Open-label study of donepezil in chronic poststroke aphasia

Donepezil hydrochloride (HCl), a reversible acetylcholinesterase inhibitor with a selective central action, is effective in ameliorating language and cognitive deficits in dementia of Alzheimer type.1 Preliminary clinical experience in single-case studies and small numbers of patients suggests that donepezil HCl may also stabilize cognitive deficits associated with subcortical vascular dementia2 and may improve language deficits in patients with post-stroke aphasia.3,4⇓ We studied donepezil HCl in chronic poststroke aphasia. ### Subjects and study design. This was a 20-week open-label pilot study evaluating the effects of donepezil HCl in chronic poststroke aphasia. The patients were recruited from a language therapy center, where they received two weekly sessions of conventional speech–language therapy. All patients and their responsible family member signed an informed consent agreement. The study was approved by the ethical committees of the centers. The primary outcome measure was the mean score change from baseline to endpoints at weeks 4 and …
Identification of Upper Limb Movements through EMG Signals with Fuzzy Logic Algorithm

Electromyography consists on recording the electrical potential generated by the activation of muscle fibers when performing voluntary or involuntary movements. Thus, EMG signals (EMGs) are directly linked to the human intention of motion. However, due to the random nature of EMGs; the correct prediction of the intention of motion is considered the most difficult part of the myoelectric control. A movement identification algorithm to distinguish among nine different movements of the upper limb is presented. Three fuzzy stages were developed. The if-then rules at each stage reflect the behavior of muscle fibers when performing a particular movement. This algorithm was evaluated using surface EMG recordings measured over the Deltoid, Bicep and Pronator Teres muscles. Three main features were extracted from each channel, the root mean square, the contractility characteristic and the onset value. Results have shown a high percentage of accuracy.
Histopathologic Evaluation of Hepatocellular Carcinoma with Special Reference to Small Early Stage Tumors

Over the past decade extensive studies on small early stage hepatocellular carcinomas (HCCs) have defined their pathomorphologic features. Most early HCCs are well differentiated, with an ill-defined nodular appearance. Proliferation of well-differentiated small HCCs is closely related to tumor dedifferentiation. When a well-differentiated HCC reaches a size of about 1.0-1.5 cm in diameter, less-differentiated cancerous tissues with greater proliferative activity evolve within it. Such a phenomenon is often appreciated grossly and/or histologically as a "nodule-in-nodule" appearance. Subsequently, moderately to poorly differentiated HCC tissues gradually replace the initial surrounding HCC. This replacement of well-differentiated HCC tissue is completed when the tumor reaches a size of about 2-3 cm. Hyperplastic nodular lesions in cirrhotic livers may have a premalignant potency. HCC frequently occurs multicentrically whether synchronously or metachronously, defying complete cure by conventional therapies other than liver transplantation.
Cognitive function in young adults following intrauterine growth restriction with abnormal fetal aortic blood flow

Intrauterine growth restriction (IUGR) is a recognized risk factor for neurological deficits later in life. Abnormal fetal blood flow in the presence of IUGR helps to distinguish fetuses with true growth impairment from those that are small but normally grown. This study aimed to evaluate the influence of IUGR with abnormal fetal blood flow on cognitive function and psychological development in young adults.
Ciclo cafetero y comportamiento macroeconómico en Colombia, 1940-1987

“Las interrelaciones que existen entre los precios de las materias primas y el comportamiento macroeconomico en los paises en desarrollo han sido ampliamente analizadas en la literatura economica. La relacion entre el precio internacional del cafe y la actividad economica agregada ha sido objeto de atencion cuidadosa por parte de los analistas colombianos. La mayoria de los estudios existentes, tanto a nivel internacional como en el pais, se concentran en el analisis de casos aislados de alzas o de reducciones de las cotizaciones internacionales de productos basicos y se encuentran pocos intentos por analizar los ciclos de precios en su conjunto. La extensa literatura sobre la llamada "enfermedad holandesa" se ha centrado fundamentalmente en los efectos macroeconomicos de alzas en los precios de las materias primas. En el otro extremo, la literatura sobre estabilizacion macroeconomica en paises en desarrollo y los analisis sobre el proceso de ajuste ante una crisis externa en el caso colombiano han servido de marco para el analisis del impacto domestico de una caida brusca de los terminos de intercambio. El trabajo que aqui se presenta utiliza esta literatura y diversos estudios existentes en el pais para analizar la relacion que ha existido entre los ciclos de los precios externos del cafe y el comportamiento macroeconomico en Colombia durante el periodo 1921-0-1987. El trabajo se divide en tres partes, dos de las cuales se presentan en esta entrega de Coyuntura Economica. En la primera se analiza la mencionada relacion desde un punto de vista conceptual. En la segunda se estudia el comportamiento historico de un aspecto particular de dicha relacion. Finalmente, en la proxima edicion de Coyuntura Economica, se presentara la tercera parte, en donde se desarrolla en detalle el tema central de este estudio. ”
Option pricing using TR-BDF 2 time stepping method

The Trapezoidal Rule with second order Backward Difference Formula (TR-BDF2) time stepping method was applied to the Black-Scholes PDE for option pricing. It is proved that TR-BDF2 time stepping method is unconditionally stable, and compared to the usual Crank-Nicolson time stepping method, the TR-BDF2 shows fewer oscillations when computing the derivatives of the solution, which are important hedging parameters.
Using Eulerian and Lagrangian Approaches to Investigate Wind-Driven Changes in the Southern Ocean Abyssal Circulation

This study uses a global ocean eddy-permitting climate model to explore the export of abyssal water from the Southern Ocean and its sensitivity to projected twenty-first-century poleward-intensifying Southern Oceanwind stress. The abyssalflow pathways and transportareinvestigated usinga combinationofLagrangian and Eulerian techniques. In an Eulerian format, the equator- and poleward flows within similar abyssal density classes are increased by the wind stress changes, making it difficult to explicitly diagnose changes in the abyssal export in a meridional overturning circulation framework. Lagrangian particle analyses are used to identify the major export pathways of Southern Ocean abyssal waters and reveal an increase in the number of particles exported to the subtropics from source regions around Antarctica in response to the wind forcing. Both the Lagrangian particleand Eulerian analyses identify transients asplaying a key rolein the abyssal export ofwater from the Southern Ocean. Wind-driven modifications to the potential energy component of the vorticity balance in the abyss are also found to impact the Southern Ocean barotropic circulation.
Long-term and Short-term Effects of Insomnia in Cancer and Effective Interventions

AbstractSleep disorders and insomnia are more prevalent in patients with cancer than in the normal population. Sleep disorders consist of delayed sleep latency, waking episodes after sleep onset, unrefreshing sleep, reduced quality of sleep, and reduced sleep efficiency. Sleep disorders cluster with pain, fatigue, depression, anxiety, and vasomotor symptoms, depending on stage of disease, treatment, and comorbidities. Premorbid sleep problems and shift work have been associated with a higher prevalence of cancer; in fact, shift work has been labeled a carcinogen. Treatment for insomnia includes cognitive behavioral therapy with sleep hygiene, bright-light therapy, exercise, yoga, melatonin, and hypnotic medications. Unfortunately, there are few randomized trials in cancer-related sleep disorders such that most recommendations particularly for hypnotics are based on treatment for primary insomnia. In this article, insomnia is reviewed as a predisposing factor to cancer, prior to and during treatment, in cancer survivorship and in advanced cancer. Recommendations for treatment are based on low-quality evidence but are also reviewed.
Viral Load of Human Herpesvirus 8 in Peripheral Blood of Human Immunodeficiency Virus-Infected Patients with Kaposi's Sarcoma

ABSTRACT Viral load is an important marker of activity of viral diseases for a number of viruses. We wished to evaluate whether the viral load of human herpesvirus 8 (HHV-8) in peripheral blood was a consistent feature of Kaposi's sarcoma (KS) patients and whether the viral load correlated with human immunodeficiency virus (HIV) RNA levels, CD4 counts, and/or the HHV-8 seroreactivity. Fifty-four consecutive plasma samples from 14 patients with KS were evaluated for HHV-8 viral load by quantitative real-time PCR. Samples were analyzed at the start of highly active antiretroviral therapy (HAART) and at different intervals during treatments. The median HHV-8 DNA load before HAART treatment was 8,998 (ranging from 170 to 40,100) copies/ml and 12,270 (ranging from 40 to 142,575) copies/ml during HAART. There were both increasing and decreasing trends. There was an association between HHV-8 DNA and HIV RNA viral loads (odds ratio [OR] = 5.40; 95% confidence interval [95% CI], 1.54 to 18.98) and between HHV-8 viral load and CD4 cell counts (OR = 7.24; 95% CI, 1.30 to 40.35). High HHV-8 viral load was also correlated with the titers of antibodies to the lytic HHV-8 antigen detected with immunofluorescence (P < 0.01), but not with antibodies to the latent HHV-8 antigen. In conclusion, we found that HHV-8 viremia in KS is associated with HIV viral load, CD4 cell counts, and lytic HHV-8 serological reactivity. HHV-8 viral load monitored by real time PCR might be useful for determination HHV-8 viral load during the follow-up of KS patients.
Onset of Lymphocyte Function in the Developing Human Fetus

Extract: Lymphocytes capable of responding to phytohemagglutinin (PHA) were present in human fetal thymus tissue by 12-week gestational age and in spleens 2–4 weeks later. In spleens, establishment of the PHA response was associated with the appearance of small lymphocytes in cuffs surrounding central arterioles.Speculation: Onset of PHA responsiveness in lymphocytes obtained from the embryonic thymus precedes that of the spleen. It would be of particular interest to know when bone marrow cells and lymph node lymphocytes start to show this function.
Reliability, maintainability, availability and failure rate analysis of IGBT triggering system designed for marine environment

The High voltage static converter systems are deployed at different military and DoD assets in which power electronics is used for the isolated and stabilized AC or DC voltage/frequency conversion process and the Insulated Gate Bipolar Transistor (IGBT) triggering system plays crucial role in such systems. Such type of systems and equipments are being operated by the combat deployed personnel and they rely upon in order to complete their critical missions. Therefore, it is evident that reliability and availability during the mission and maintainability of the system before and after the mission is paramount. The objective of this paper is to present the predicted Reliability, Maintainability, Availability and Failure rate analysis of the IGBT triggering system. The analysis is made in the marine environment by defining specific parameters. The method used to calculate the reliability prediction of the IGBT triggering system is based on the calculation of Mean Time Between Failure (MTBF), which is obtained from the calculation of Failure rate of individual components used in the system. The maintainability analysis is done based on the length of the time required by the repairable components, repair through replaceable components or replacing the whole system. Therefore, this analysis will use the Mean Time To Repair (MTTR). MTBF and MTTR are used as key elements in the availability analysis of the system. Pareto analysis is presented in order to show the individual components failure rate contribution used in the system. The presented analysis shows the relationship between reliability, maintainability and availability of a system and also shows how the reliability and maintainability analysis improves the availability of the designed system. The presented analysis can be viewed with reference to system lifetime calculation as it will help in investment plan of designed system in marine environment.
Estimate of the Fermi Large Area Telescope sensitivity to gamma-ray polarization

Although not designed primarily as a polarimeter, the \textit{Fermi}-Large Area Telescope (LAT) has the potential to detect high degrees of linear polarization from some of the brightest gamma-ray sources. To achieve the needed accuracy in the reconstruction of the event geometry, low-energy ($\leq200$ MeV) events converting in the silicon detector layers of the LAT tracker have to be used. We present preliminary results of the ongoing effort within the LAT collaboration to measure gamma-ray polarization. We discuss the statistical and systematic uncertainties affecting such a measurement. We show that a $5\sigma$ minimum detectable polarization (MDP) of $\approx30-50\%$ could be within reach for the brightest gamma-ray sources as the Vela and Crab pulsars and the blazar 3C 454.3, after 10 years of observation. To estimate the systematic uncertainties, we stack bright AGN, and use this stack as a test source. LAT sensitivity to polarization is estimated comparing the data to a simulation of the expected unpolarized emission of the stack. We measure a 5$\sigma$ sensitivity limit corresponding to a polarization degree of $\approx37\%$. This is in agreement with a purely statistical estimate, suggesting that the systematic errors are likely to be small compared to the statistical ones.