Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel Latency Reversing Agents for HIV-1 Cure

Antiretroviral therapy (ART) has rendered HIV-1 infection a treatable illness, however ART is not curative due to the persistence of replication-competent, latent proviruses in long-lived resting T cells. Strategies that target these latently infected cells and allow for immune recognition and clearance of this reservoir will be necessary to eradicate HIV-1 in infected individuals. This review describes current pharmacologic approaches to reactivate the latent reservoir in a manner that infected cells can be recognized and targeted, with the ultimate goal of achieving an HIV-1 cure. of the host as resting memory cells. The HIV-1 provirus persists in a reversibly quiescent state within these long-lived cells, and can efficiently initiate viral replication upon spontaneous or antigen-driven cellular activation(1–3). ART must be administered indefinitely in order to block new cycles of replication arising from this P-TEFb TLR-8 agonist Ingenol has synergy with JQ1 in patient cells ex In separate work, ingenol-3-angelate showed similar synergistic behavior with JQ1 in patient cells ex vivo however this result was not observed in a study that made use of resting CD4 + T cells from rhesus macaques(86). Several other studies have examined the combinatorial effect of novel LRAs. An inhibitor of transcriptional activator Runx1 called R05-3335 synergy with vorinostat in patient PBMCs ex Panobinostat and romidepsin synergized with 5-azadC, a DNA demethylating agent A human lectin, galectin-9, synergized in patient cells ex vivo with vorinostat and JQ1 While it is difficult to directly compare results across these studies that make use of different in vitro and ex vivo systems and varying definitions of pharmacologic synergy, the overarching theme is that synergy appears to be achievable when combining different LRA classes. This is a promising observation that will hopefully translate into future LRA combination trials.
Probabilistic bridge weigh-in-motion

Conventional bridge weigh-in-motion (BWIM) uses a bridge influence line to find the axle weights of passing vehicles that minimize the sum of squares of differences between theoretical and measured responses. An alternative approach, probabilistic bridge weigh-in-motion (pBWIM), is proposed here. The pBWIM approach uses a probabilistic influence line and seeks to find the most probable axle weights, given the measurements. The inferred axle weights are those with the greatest probability amongst all possible combinations of values. The measurement sensors used in pBWIM are similar to BWIM, containing free-of-axle detector sensors to calculate axle spacings and vehicle speed and weighing sensors to record deformations of the bridge. The pBWIM concept is tested here using a numerical model and a bridge in Slovenia. In a simulation, 200 randomly generated 2-axle trucks pass over a 6 m long simply supported beam. The bending moment at mid-span is used to find the axle weights. In the field tests, 77 pre-weighed trucks traveled over an integral slab bridge and the strain response in the soffit at mid-span was recorded. Results show that pBWIM has good potential to improve the accuracy of BWIM.
Optical and Microcavity Modes Entanglement by means of Developed Opto-Mechanical System

To improve the performance of the traditional tripartite opto-mechanical system, we design a developed opto-mechanical tripartite system in which all subsystems such as an optical cavity, microresonator, and microcavity modes are coupled directly to each other. This system is analyzed quantum mechanically, and its dynamics of motion is studied by the Heisenberg-Langevin equations. Notably, the originality of this work contributes to embedding the spherical capacitor in the optical cavity where the plasmon-plasmon interaction between capacitor plates manipulates the internal electric field. Therefore, using plasmon-plasmon interaction inside the spherical capacitor, which leads to nonlinearity, causes the contributed polarization function of the plasmonic property. Actually, this plasmonic property manages the spherical capacitance. Although the spherical capacitor is fundamentally dependent on the plasmonic properties caused by the capacitor gap, the spherical capacitor for a design is required to be parallel to the microwave capacitor. The system developed in the present work proved that the stability of the entanglement between optical cavity and microcavity modes toward the temperature changing is dramatically increased; which is the original goal of this study. It is worth mentioning that the environment noise severely restricted the traditional tripartite system operated with a wide bandwidth, hence the present design can efficiently fix this issue.
Anatomy and Phylogenetic Position of Venaticosuchus rusconii Bonaparte, 1970 (Archosauria, Pseudosuchia), from the Ischigualasto Formation (Late Triassic), la Rioja, Argentina

ABSTRACT Ornithosuchidae is a group of Late Triassic pseudosuchian archosaurs of controversial phylogenetic affinities. This clade currently comprises three taxa: Venaticosuchus rusconii and Riojasuchus tenuisceps, both from Argentina, and Ornithosuchus longidens, from Scotland. V. rusconii was erected on the basis of an incomplete skull with articulated lower jaws and some elements of the postcranium that are currently lost. Venaticosuchus rusconii is redescribed here and included for the first time in a phylogenetic analysis to test its affinities with ornithosuchids. The bizarre morphology of V. rusconii has a unique combination of traits that distinguishes it from the other ornithosuchids, such as basipterygoid processes directed ventrally, dentary with the dorsal margin of the anterior end dorsally expanded, articular without a foramen on its medial side, and the absence of a surangular foramen, corroborating the validity of this taxon. V. rusconii is recovered as an ornithosuchid more closely related to R. tenuisceps than to O. longidens, based on the presence of a nearly pointed anterior margin of the antorbital fenestra, and a vertical bony strut of the jugal that separates the antorbital fenestra from the infratemporal fenestra.
Reliability of EMG activity versus bite-force from human masticatory muscles

The reproducibility of electromyographic (EMG) activity in relation to static bite-force from masticatory muscles for a given biting situation is largely unknown. Our aim was to evaluate the reliability of EMG activity in relation to static bite-force in humans. Eighty-four subjects produced 5 unilateral static bites of different forces at different biting positions on molars and incisors, at two separate sessions, while surface EMG activities were recorded from temporalis, masseter, and suprahyoid muscles bilaterally. Intraclass Correlation Coefficients (ICCs) were used, where an ICC of ≥ 0.60 indicated good reliability of these slopes. ICCs for jaw closing muscles during molar biting were: temporalis ipsilateral 0.58 to 0.93 and contralateral 0.88 to 0.91, masseter ipsilateral 0.75 to 0.86 and contralateral 0.69 to 0.88; while during incisor biting were: temporalis ipsilateral 0.56 to 0.81 and contralateral 0.34 to 0.86, masseter ipsilateral 0.65 to 0.78 and contralateral 0.59 to 0.80. For the suprahyoid muscles the confidence intervals were mostly wide and most included zero. Slopes of the EMG activity versus bite-force for a given biting situation were reliable for temporalis and masseter muscles. These results support the use of these outcome measurements for the estimation and validation of mechanical models of the masticatory system.
A probabilistic approach to remaining useful life prediction of rolling element bearings

In this article, we present a probabilistic approach for fault detection and prognosis of rolling element bearings based on a two-phase degradation model. One of the main issues in dealing with bearing degradation is that the degradation mechanism is unobservable and can only be inferred through appropriate surrogate measures obtained from indirect sensory measurements. Furthermore, the stochastic nature of the degradation path renders fault detection and estimating the end-of-life characteristics from such data extremely challenging. When such components are a part of a larger system, the exact degradation path depends on both the operating and loading conditions, which means that the most effective condition monitoring approach should estimate the degradation model parameters under operational conditions, and not solely from isolated component testing or historical information. Motivated by these challenges, a two-phase degradation model using surrogate measures of degradation from vibration measurements is proposed and a Bayesian approach is used to estimate the model parameters. The underlying methodology involves using priors from historical data, while the posterior calculations are undertaken using surrogate measures obtained from a monitored unit combined with the aforesaid priors. The problem of fault detection is posed as a change point location problem. This allows the prior knowledge obtained from the past failures to be integrated for maintenance planning of a currently working unit in a systematic way. The correlation between the degradation rate and the time of occurrence of the change point, an often overlooked aspect in prognosis, is also considered in here. A numerical example and a case study are presented to illustrate the overall methodology and the results obtained using this approach.
Feasibility of an evolutionary artificial intelligence (AI) scheme for modelling of load settlement response of concrete piles embedded in cohesionless soil

ABSTRACT This investigation aimed to examine the load carrying capacity of piles embedded in sandy soil of various densities, and to develop a predictive model to determine pile settlement using a novel artificial intelligence (AI) method. Experimental pile load tests were conducted using three concrete piles, with aspect ratios of 12, 17 and 25. Evolutionary Levenberg–Marquardt MATLAB algorithms, enhanced by T-tests and F-tests, were used in this process. According to the statistical analysis and the relative importance study, pile length, applied load, pile flexural rigidity, pile aspect ratio and sand–pile friction angle were found to play a key role in pile settlement. Results revealed that the proposed optimum model algorithm precisely characterized pile settlement. There was close agreement between the experimental and predicted data (Pearson's R = 0.988, P = 6.28 × 10-31) with a relatively insignificant root mean square error of 0.002.
Feasibility and Utility of Online Dementia Care Training for Hospital Staff: The

The current project tested the feasibility and utility of the CARES ® Dementia-Friendly Hospital™ (CDFH) program, a 4-module, online training program for nursing assistants (NAs) and allied hospital workers (AHWs) who provide care to individuals with dementia. A single group pretest/ posttest design was used for 25 hospital NAs/AHWs, and quantitative and qualitative data were collected to determine whether NAs’/AHWs’ knowledge of hospital-based dementia care significantly increased, and if CDFH was perceived as useful and acceptable. Dementia care knowledge increased significantly (p < 0.001). Open- and closed-ended data suggested that the delivery of online training to NAs/AHWs to enhance dementia care is feasible, useful, and efficient. Ongoing gaps in care exist for individuals with dementia in hospitals, and delivering robust training for NAs/AHWs may serve as an effective modality to enhance quality of dementia care in such settings.
Urban Students' Perceptions of the School Environment's Influence on School Violence

This article provides information about the aspects of the school environment students perceive influence the occurrence of school violence. Concept mapping, a mixed methods methodology, was used with two groups of urban, primarily African American high school students (n=27) to create conceptual frameworks of their understanding of the school social and physical environment's influence on school violence. Each group of students identified over 50 different ways they perceived their school environment contributed to school violence. These ideas were categorized into six main topics: Student Behaviors, Norms of Behavior, Relationships with School Staff, Learning Environment, School Safety, and Neighborhood Environment. Students' perceptions supported the current conceptualization of the role of the school environment in school violence. However, this study supplements the current literature by identifying school level aspects of the social and physical environment that contribute to students perceptions of the safety of their school. At this level, differences were seen between the two school environments, indicating a need for intervention tailoring.
Connecting the genome: dynamics and stochasticity in a new hierarchy for chromosome conformation

Mammalian genomes encode genetic information in their linear sequence, but appropriate expression of their genes requires chromosomes to fold into complex three-dimensional structures. Transcriptional control involves the establishment of physical connections among genes and regulatory elements, both along and between chromosomes. Recent technological innovations in probing the folding of chromosomes are providing new insights into the spatial organization of genomes and its role in gene regulation. It is emerging that folding of large complex chromosomes involves a hierarchy of structures, from chromatin loops that connect genes and enhancers to larger chromosomal domains and nuclear compartments. The larger these structures are along this hierarchy, the more stable they are within cells, while becoming more stochastic between cells. Here, we review the experimental and theoretical data on this hierarchy of structures, and propose a key role for the recently discovered Topologically Associating domains.
Short Communication Expression of Lysosome-Associated Membrane Proteins in Human Colorectal Neoplasms and Inflammatory Diseases

The lysosome-associated membrane proteins (LAMPs)-1 and -2 are major constituents of the lysosomal membrane. These molecules are known to be among the most glycosylated proteins of several types of cells and cancer cells, and their expression in cancer cells is marked by a distinct difference in the structures of the oligosaccharides as compared to nonmalignant cells. We analyzed by immunohistochemistry the intensity and distribution of LAMP-1 and LAMP-2 in 9 human colorectal cancer cases and in 16 control cases, including inflammatory diseases (diverticulitis, ulcerative colitis, and Crohn’s disease). LAMP proteins were expressed more intensely in the epithelium of colorectal neoplasms than in normal mucosa ( P < 0.05), and no significant differences were found between adenoma and cancer cells ( P > 0.05) in the same tissue section. Further, in sites of inactive inflammatory diseases and nonneoplastic areas in cancer specimens, no significant
Tracking macrophage infiltration in a mouse model of pancreas cancer with the PET tracer [11C]PBR28

Background: The tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) contains abundant immunosuppressive tumor associated macrophages (TAM). High level of infiltration is associated with poor outcome and is thought to represent a major roadblock to lymphocyte based immunotherapy. Efforts to block macrophage infiltration has been met with some success but non-invasive means to track TAMs in PDAC are lacking. Translocator protein (TSPO) is a mitochondrial membrane receptor which is upregulated in activated macrophages. We sought to identify if a radiotracer labeled cognate ligand could track macrophages in PDAC. Materials and Methods: A murine PDAC cell line was established from a transgenic mouse with pancreas specific mutations in KRAS and the p53. After confirming lack of endogenous TSPO expression, tumors were established in syngeneic mice. A radiolabeled TSPO specific ligand ([11C]PBR28) was delivered intravenously and tumor uptake assessed by autoradiography, ex vivo, or micro-PET imaging. Results: Resected tumors contained abundant macrophages as determined by immunohistochemistry and flow cytometry. Immunoblotting revealed murine macrophages expressed TSPO with increasing concentration on activation and polarization. Autoradiography of resected tumors confirmed [11C]PBR28 uptake and whole mount sections demonstrated the ability to localize tumors. To confirm the findings were macrophage specific, experiments were repeated in CD11b deficient mice and the radiotracer uptake was diminished. Micro-PET imaging validated radiotracer uptake and tumor localization in a clinically applicable manner. Conclusion: As new immunotherapeutics reshape the PDAC microenvironment, tools are needed to better measure and track immune cell subsets. We have demonstrated the potential to measure changes in macrophage infiltration in PDAC using [11C]PBR28. for Positron Emission Tomography (PET) of subtle brain inflammation seen in conditions such as Parkinson’s Disease(12), Alzheimer’s and stroke(14). Biodistribution studies identified high levels of [11C]PBR28 binding in heart, lung and kidney tissues and relatively low levels in brain, intestine and pancreas(13). Previously, our group determined that [11C]PBR28 could also be used to identify extra-neuroaxial sites of inflammation related to experimentally induced aortic aneurysms and arthritis 16). Here, the [11C]PBR28 uptake was directly proportional to macrophage infiltration and in vitro studies confirmed rapid uptake of radiotracer by macrophages on activation. We sought to determine if macrophage recruitment to pancreas cancer could be identified using [11C]PBR28 small animal PET.
Calculation of muscle forces and joint reaction loads in the shoulder area via an OpenSim based computer model

Abstract Using the OpenSim software and verified anatomical data, a computer model for the calculation of biomechanical parameters is developed and used to determine the effect of a reattachment of the Supraspinatus muscle with a medial displacement of the muscle attachment point, which may be necessary for a rupture of the supraspinatus tendon. The results include the influence of the operation on basic biomechanical parameters such as the lever arm, as well as the calculated the muscle activations for the supraspinatus and deltoid. In addition, the influence on joint stability is examined by an analysis of the joint reaction force. The study provides a detailed description of the used model, as well as medical findings to a reattachment of the supraspinatus.
Influence of Ligament Properties on Knee Mechanics in Walking

Computational knee models provide a powerful platform to investigate the effects of injury and surgery on functional knee behavior. The objective of this study was to use a multibody knee model to investigate the influence of ligament properties on tibiofemoral kinematics and cartilage contact pressures in the stance phase of walking. The knee model included 14 ligament bundles and articular cartilage contact acting across the tibiofemoral and patellofemoral joints. The knee was incorporated into a lower extremity musculoskeletal model and used to simulate knee mechanics during the stance phase of normal walking. A Monte Carlo approach was employed to assess the influence ligament stiffness and reference strains on knee mechanics. The ACL, MCL and posterior capsule properties exhibited significant influence on anterior tibial translation at heel strike, with the ACL acting as the primary restraint to anterior translation in mid-stance. The MCL and LCL exhibited the greatest influence on tibial rotation from heel strike through mid-stance. Simulated tibial plateau contact location was dependent on the ACL, MCL and LCL properties, while pressure magnitudes were most dependent on the ACL. A decrease in ACL stiffness or reference strain significantly increased average contact pressure in mid-stance, with the pressure migrating posteriorly on the medial tibial plateau. These ligament-dependent shifts in tibiofemoral cartilage contact during walking are potentially relevant to consider when investigating the causes of early onset osteoarthritis following knee ligament injury and surgical treatment.
THE IMPACT OF HIV INFECTION ON COLONIZATION AND SEROEPIDEMIOLOGY OF STREPTOCOCCUS PNEUMONIAE AMONG ZAMBIAN WOMEN

Nasopharyngeal colonization precedes invasive pneumococcal disease. HIV infection increases rates of invasive disease; its effect on colonization is unknown. In a longitudinal cohort of HIV-positive/negative Zambian mothers, HIV increased the risk of colonization (RR 1.9, 95% CI 1.3– 2.8) and repeated colonizations (RR 2.4, 95% CI 1.1–5.3), and reduced time to new colonization (p=0.01). Repeated colonizations with homologous sero/factor-types occurred only among HIV-positive mothers. Pediatric serotypes 6, 19 and 23 accounted for the excess colonization in the HIV-positive mothers. HIV significantly increases the risk of pneumococcal colonization. Increased colonization by pediatric serotypes suggests a potential role for the 7-valent pneumococcal vaccine.
Comparison of Nonparametric Statistics for Detection of Linkage in Nuclear Families: Single-Marker Evaluation

We have evaluated 23 different statistics, from a total of 10 popular software packages for model-free linkage analysis of nuclear-family data, by applying them to single-marker data simulated under several two-locus disease models. The statistics that we examined fall into two broad categories: (1) those that test directly for increased identity-by-state or identity-by-descent sharing (by use of the programs APM, Genetic Analysis System [GAS] SIBSTATE and SIBDES, SAGE SIBPAL, ERPA, SimIBD, and Genehunter NPL) and (2) those that are based on likelihood-ratio tests and that report LOD scores (by use of the programs Splink, SIBPAIR, Mapmaker/Sibs, ASPEX, and GAS SIBMLS). For each of eight two-locus disease models, we analyzed six data sets; the first three data sets consisted of two-child families with both sibs affected and zero, one, or both parents typed, whereas the other three data sets consisted of four-child families with at least two affected sibs and zero, one, or both parents typed. We report false-positive rates, overall rank by power, and the power for each statistic. We give rough recommendations regarding which programs provide the most powerful tests for linkage, as well as the programs to be avoided under certain conditions. For the likelihood-ratio-based statistics, we examined the effects of various treatments of sibships with multiple affected individuals. Finally, we explored the use of some simple two-of-three composite statistics and found that such tests are of only marginal benefit over the most powerful single statistic.