Miracle-dz/UniFAR-FTUs huggingface dataset:
HIV Replication and Latency in a Humanized NSG Mouse Model during Suppressive Oral Combinational Antiretroviral Therapy

ABSTRACT Although current combinatorial antiretroviral therapy (cART) is therapeutically effective in the majority of HIV patients, interruption of therapy can cause a rapid rebound in viremia, demonstrating the existence of a stable reservoir of latently infected cells. HIV latency is therefore considered a primary barrier to HIV eradication. Identifying, quantifying, and purging the HIV reservoir is crucial to effectively curing patients and relieving them from the lifelong requirement for therapy. Latently infected transformed cell models have been used to investigate HIV latency; however, these models cannot accurately represent the quiescent cellular environment of primary latently infected cells in vivo. For this reason, in vivo humanized murine models have been developed for screening antiviral agents, identifying latently infected T cells, and establishing treatment approaches for HIV research. Such models include humanized bone marrow/liver/thymus mice and SCID-hu-thy/liv mice, which are repopulated with human immune cells and implanted human tissues through laborious surgical manipulation. However, no one has utilized the human hematopoietic stem cell-engrafted NOD/SCID/IL2rγnull (NSG) model (hu-NSG) for this purpose. Therefore, in the present study, we used the HIV-infected hu-NSG mouse to recapitulate the key aspects of HIV infection and pathogenesis in vivo. Moreover, we evaluated the ability of HIV-infected human cells isolated from HIV-infected hu-NSG mice on suppressive cART to act as a latent HIV reservoir. Our results demonstrate that the hu-NSG model is an effective surgery-free in vivo system in which to efficiently evaluate HIV replication, antiretroviral therapy, latency and persistence, and eradication interventions. IMPORTANCE HIV can establish a stably integrated, nonproductive state of infection at the level of individual cells, known as HIV latency, which is considered a primary barrier to curing HIV. A complete understanding of the establishment and role of HIV latency in vivo would greatly enhance attempts to develop novel HIV purging strategies. An ideal animal model for this purpose should be easy to work with, should have a shortened disease course so that efficacy testing can be completed in a reasonable time, and should have immune correlates that are easily translatable to humans. We therefore describe a novel application of the hematopoietic stem cell-transplanted humanized NSG model for dynamically testing antiretroviral treatment, supporting HIV infection, establishing HIV latency in vivo. The hu-NSG model could be a facile alternative to humanized bone marrow/liver/thymus or SCID-hu-thy/liv mice in which laborious surgical manipulation and time-consuming human cell reconstitution is required.
Spatial coding and physiological properties of hippocampal neurons in the Cornu Ammonis subregions

It is well‐established that the feed‐forward connected main hippocampal areas, CA3, CA2, and CA1 work cooperatively during spatial navigation and memory. These areas are similar in terms of the prevalent types of neurons; however, they display different spatial coding and oscillatory dynamics. Understanding the temporal dynamics of these operations requires simultaneous recordings from these regions. However, simultaneous recordings from multiple regions and subregions in behaving animals have become possible only recently. We performed large‐scale silicon probe recordings simultaneously spanning across all layers of CA1, CA2, and CA3 regions in rats during spatial navigation and sleep and compared their behavior‐dependent spiking, oscillatory dynamics and functional connectivity. The accuracy of place cell spatial coding increased progressively from distal to proximal CA1, suddenly dropped in CA2, and increased again from CA3a toward CA3c. These variations can be attributed in part to the different entorhinal inputs to each subregions, and the differences in theta modulation of CA1, CA2, and CA3 neurons. We also found that neurons in the subregions showed differences in theta modulation, phase precession, state‐dependent changes in firing rates and functional connectivity among neurons of these regions. Our results indicate that a combination of intrinsic properties together with distinct intra‐ and extra‐hippocampal inputs may account for the subregion‐specific modulation of spiking dynamics and spatial tuning of neurons during behavior. © 2016 Wiley Periodicals, Inc.
3D matrix‐embedding inhibits cycloheximide‐mediated sensitization to TNF‐alpha‐induced apoptosis of human endothelial cells

The programmed form of cell death (apoptosis) is essential for normal development of multicellular organisms. Dysregulation of apoptosis has been linked with embryonal death and is involved in the pathophysiology of various diseases. Others and we previously demonstrated endothelial biology being intertwined with biochemical and structural composition of the subendothelial basement membrane. We now demonstrate that a three‐dimensional growing environment significantly shields endothelial cells from cytokine‐induced apoptosis. Detailed analysis reveals differences in intracellular signaling pathways in naive endothelial cells and cytokine‐stimulated endothelial cells when cells are grown within a three‐dimensional collagen‐based matrix compared to cells grown on two‐dimensional tissue culture plates. Main findings are significantly reduced p53 expression and level of p38‐phosphorylation in three‐dimensional grown endothelial cells. Despite similar concentrations of focal adhesion kinase, three‐dimensional matrix‐embedded endothelial cells express significantly less tyrosine‐phosphorylated focal adhesion kinase. Pretreatment with antibodies against integrin αvβ3 partially reversed the protective effect of three‐dimensional matrix‐embedding on endothelial apoptosis. Our findings provide detailed insights into the mechanisms of endothelial apoptosis with respect to the spatial matrix environment. These results enhance our understanding of endothelial biology and may otherwise help in the design of tissue‐engineered materials. Furthermore, findings on focal adhesion kinase phosphorylation might enhance our understanding of clinical studies with tyrosine kinase inhibitors.
Sparse-as-possible SVBRDF acquisition

We present a novel method for capturing real-world, spatially-varying surface reflectance from a small number of object views (k). Our key observation is that a specific target's reflectance can be represented by a small number of custom basis materials (N) convexly blended by an even smaller number of non-zero weights at each point (n). Based on this sparse basis/sparser blend model, we develop an SVBRDF reconstruction algorithm that jointly solves for n, N, the basis BRDFs, and their spatial blend weights with an alternating iterative optimization, each step of which solves a linearly-constrained quadratic programming problem. We develop a numerical tool that lets us estimate the number of views required and analyze the effect of lighting and geometry on reconstruction quality. We validate our method with images rendered from synthetic BRDFs, and demonstrate convincing results on real objects of pre-scanned shape and lit by uncontrolled natural illumination, from very few or even a single input image.
Decision Making Among Persons Living With Heart Failure

Background:Persons with heart failure (HF) are required to make decisions on a daily basis related to their declining health and make urgent decisions during acute illness exacerbations. However, little is known about the types of decisions patients make. Objective:The aims of this study were to critically evaluate the current quantitative literature related to decision making among persons with HF and identify research gaps in HF decision-making research. Methods:A systematic search of literature about decisions persons with HF make was conducted using PubMed, CINAHL, and PsychINFO databases. The following inclusion criteria were used: sample composed of at least 50% HF participants, concrete decisions were made, and a quantitative study design was used. Two authors performed title, abstract, and full-text reviews independently to identify eligible articles. Results:Twelve quantitative articles were included. Study samples were predominately older, white, male, and married. Two-thirds of the articles focused on decisions related to the end-of-life topics (ie, resuscitation decisions, advanced care planning). The other one-third focused on decisions about care seeking, participant’s involvement in treatment decisions during their last clinic visit, and self-care behaviors. Conclusions:Within the HF literature, the term decision is often ill-defined or not defined. Limitations in methodological rigor limit definitive conclusions about HF decision making. Future studies should consider strengthening study rigor and examining other decision topics such as inclusion of family in making decisions as HF progresses. Research rigorously examining HF decision making is needed to develop interventions to support persons with HF.
DeepToF

Time-of-flight (ToF) imaging has become a widespread technique for depth estimation, allowing affordable off-the-shelf cameras to provide depth maps in real time. However, multipath interference (MPI) resulting from indirect illumination significantly degrades the captured depth. Most previous works have tried to solve this problem by means of complex hardware modifications or costly computations. In this work, we avoid these approaches and propose a new technique to correct errors in depth caused by MPI, which requires no camera modifications and takes just 10 milliseconds per frame. Our observations about the nature of MPI suggest that most of its information is available in image space; this allows us to formulate the depth imaging process as a spatially-varying convolution and use a convolutional neural network to correct MPI errors. Since the input and output data present similar structure, we base our network on an autoencoder, which we train in two stages. First, we use the encoder (convolution filters) to learn a suitable basis to represent MPI-corrupted depth images; then, we train the decoder (deconvolution filters) to correct depth from synthetic scenes, generated by using a physically-based, time-resolved renderer. This approach allows us to tackle a key problem in ToF, the lack of ground-truth data, by using a large-scale captured training set with MPI-corrupted depth to train the encoder, and a smaller synthetic training set with ground truth depth to train the decoder stage of the network. We demonstrate and validate our method on both synthetic and real complex scenarios, using an off-the-shelf ToF camera, and with only the captured, incorrect depth as input.
Do antipsychotic drugs affect brain structure? A systematic and critical review of MRI findings

Background The potential effects of antipsychotic drugs on brain structure represent a key factor in understanding neuroanatomical changes in psychosis. This review addresses two issues: (1) do antipsychotic medications induce changes in total or regional human brain volumes and (2) do such effects depend on antipsychotic type? Method A systematic review of studies reporting structural brain magnetic resonance imaging (MRI) measures: (1) directly in association with antipsychotic use; and (2) in patients receiving lifetime treatment with antipsychotics in comparison with drug-naive patients or healthy controls. We searched Medline and EMBASE databases using the medical subject heading terms: ‘antipsychotics’ AND ‘brain’ AND (MRI NOT functional). The search included studies published up to 31 January 2007. Wherever possible, we reported the effect size of the difference observed. Results Thirty-three studies met our inclusion criteria. The results suggest that antipsychotics act regionally rather than globally on the brain. These volumetric changes are of a greater magnitude in association with typical than with atypical antipsychotic use. Indeed, there is evidence of a specific effect of antipsychotic type on the basal ganglia, with typicals specifically increasing the volume of these structures. Differential effects of antipsychotic type may also be present on the thalamus and the cortex, but data on these and other brain areas are more equivocal. Conclusions Antipsychotic treatment potentially contributes to the brain structural changes observed in psychosis. Future research should take into account these potential effects, and use adequate sample sizes, to allow improved interpretation of neuroimaging findings in these disorders.
A new method of forced vibration problem of deep beams under distributed harmonic load

In this paper, the control equation is first set up by using the reciprocal theory method when considering the section rotation of deep beam, shear deformation of adjacent cross section and the transverse stress. Then the control equation of deep beams under three kinds of boundary conditions is established. According to the comparison between the numerical value and finite element simulation value, we can know that the control equation and the deflection equation of the forced vibration of deep beams are correct. This is a new computing method of the forced vibration problem of deep beams under distributed harmonic load.
Activation of Sphingosine Kinase-1 Reverses the Increase in Lung Vascular Permeability Through Sphingosine-1-Phosphate Receptor Signaling in Endothelial Cells

The lipid mediator sphingosine-1-phosphate (S1P), the product of sphingosine kinase (SPHK)-induced phosphorylation of sphingosine, is known to stabilize interendothelial junctions and prevent microvessel leakiness. Here, we investigated the role of SPHK1 activation in regulating the increase in pulmonary microvessel permeability induced by challenge of mice with lipopolysaccharide or thrombin ligation of protease-activating receptor (PAR)-1. Both lipopolysaccharide and thrombin increased mouse lung microvascular permeability and resulted in a delayed activation of SPHK1 that was coupled to the onset of restoration of permeability. In contrast to wild-type mice, Sphk1−/− mice showed markedly enhanced pulmonary edema formation in response to lipopolysaccharide and PAR-1 activation. Using endothelial cells challenged with thrombin concentration (50 nmol/L) that elicited a transient but reversible increase in endothelial permeability, we observed that increased SPHK1 activity and decreased intracellular S1P concentration preceded the onset of barrier recovery. Thus, we tested the hypothesis that released S1P in a paracrine manner activates its receptor S1P1 to restore the endothelial barrier. Knockdown of SPHK1 decreased basal S1P production and Rac1 activity but increased basal endothelial permeability. In SPHK1-depleted cells, PAR-1 activation failed to induce Rac1 activation but augmented RhoA activation and endothelial hyperpermeability response. Knockdown of S1P1 receptor in endothelial cells also enhanced the increase in endothelial permeability following PAR-1 activation. S1P treatment of Sphk1−/− lungs or SPHK1-deficient endothelial cells restored endothelial barrier function. Our results suggest the crucial role of activation of the SPHK1→S1P→S1P1 signaling pathway in response to inflammatory mediators in endothelial cells in regulating endothelial barrier homeostasis.
An Optical-Fiber-Based Smart Textile (Smart Socks) to Manage Biomechanical Risk Factors Associated With Diabetic Foot Amputation

Objective: This study aimed to validate a smart-textile based on fiber-optics for simultaneous measurement of plantar temperature, pressure, and joint angles in patients with diabetic peripheral neuropathy (DPN). Methods: After in-vitro validation in the laboratory, 33 eligible subjects with DPN were recruited (age: 58 ± 8 years, BMI: 31.5 ± 8 kg/m2) for assessing plantar pressure and temperature during habitual gait-speed in a clinical-setting. All participants were asked to walk at their habitual speed while wearing a pair of sensorized socks made from highly flexible fiber optics (SmartSox). An algorithm was designed to estimate temperature, pressure, and toe range of motion from optical wavelength generated from SmartSox. To validate the device, results from thermal stress response (TSR) using thermography and peak pressure measured by computerized pressure insoles (F-Scan) were used as gold standards. Results: In laboratory and under controlled conditions, the agreements for parameters of interest were excellent (r > .98, P = .000), and no noticeable cross-talks between measurements of temperature, angle, and pressure were observed. During clinical data acquisition, a significant correlation was found for pressure profile under different anatomical regions of interest between SmartSox and F-Scan (r = .67, P < .050) as well as between thermography and SmartSox (r = .55, P < .050). Conclusion: This study demonstrates the validity of an innovative smart textile for assessing simultaneously the key parameters associated with risk of foot ulcers in patients with DPN. It may empower clinicians to objectively stratify foot risk and provide timely care. Another study is warranted to validate its clinical application in preventing limb threating problems in patients with DPN.
Atomistic Origins of Temperature-Dependent Shear Strength in 2D Materials

We present a model that predicts the macroscale temperature-dependent interfacial shear strength of 2D materials like MoS2 based on atomistic mechanisms and energetic barriers to sliding. Atomistic simulations were used to systematically determine the lamellar size-dependent rotation and translation energy barriers, that were used to accurately predict a broad range of experimental data. This framework provides insight about the origins of characteristic shear strengths of 2D materials.
Focused Ultrasound Immunotherapy for Central Nervous System Pathologies: Challenges and Opportunities

Immunotherapy is rapidly emerging as the cornerstone for the treatment of several forms of metastatic cancer, as well as for a host of other pathologies. Meanwhile, several new high-profile studies have uncovered remarkable linkages between the central nervous and immune systems. With these recent developments, harnessing the immune system for the treatment of brain pathologies is a promising strategy. Here, we contend that MR image-guided focused ultrasound (FUS) represents a noninvasive approach that will allow for favorable therapeutic immunomodulation in the setting of the central nervous system. One obstacle to effective immunotherapeutic drug delivery to the brain is the blood brain barrier (BBB), which refers to the specialized structure of brain capillaries that prevents transport of most therapeutics from the blood into brain tissue. When applied in the presence of circulating microbubbles, FUS can safely and transiently open the BBB to facilitate the delivery of immunotherapeutic agents into the brain parenchyma. Furthermore, it has been demonstrated that physical perturbations of the tissue microenvironment via FUS can modulate immune response in both normal and diseased tissue. In this review article, we provide an overview of FUS energy regimens and corresponding tissue bioeffects, followed by a review of the literature pertaining to FUS for therapeutic antibody delivery in normal brain and preclinical models of brain disease. We provide an overview of studies that demonstrate FUS-mediated immune modulation in both the brain and peripheral settings. Finally, we provide remarks on challenges facing FUS immunotherapy and opportunities for future expansion in this area.
Are Prophylactic Systemic Antibiotics Necessary with Nasal Packing? A Systematic Review

Background The use of prophylactic systemic antibiotics with nasal packing has been a controversial topic. There are few evidence-based studies to determine the need for prophylactic systemic antibiotics. We performed a systematic literature review to determine the role of prophylactic systemic antibiotics with nasal packing in the prevention of toxic shock syndrome and local nasal infections. Objective The purpose of this study was to perform a systematic literature review to determine the role of prophylactic systemic antibiotics with nasal packing in the prevention of toxic shock syndrome and local nasal infections. Methods A search for studies that reviewed the efficacy of prophylactic systemic antibiotics in the prevention of toxic shock or nasal infections and/or sinusitis for patients with nasal packing for epistaxis and postoperative septoplasties was performed. This was conducted in a number of medical literature data bases by following the methods of the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Only English publications and human studies that were randomized control trials, quasi-randomized control trials, controlled clinical trials, retrospective studies, and case series were included. Results Six studies, with a total of 990 patients, met the inclusion criteria for the review and were included. Primary outcomes were signs and symptoms of nasal or sinus infections in patients who underwent nasal packing for epistaxis or septoplasty. There were no reports of toxic shock syndrome in any patients, and there was no statistical difference in purulent drainage in patients who had septoplasty (9.9 versus 11.2%) treated with or without antibiotics. Conclusion There is a paucity of literature that reviewed the need for prophylactic systemic antibiotics with nasal packing. The available literature does not show a significant benefit to the use of antibiotics with nasal packing, but the studies were underpowered to detect such a difference. One must consider the associated risks of prophylactic antibiotics to the patient as well when deciding to prescribe prophylactic antibiotics.
Poster: On the effects of cooperative platooning on traffic shock waves

Cooperative platooning has been proposed as a promising solution to traffic congestion, safety, and pollution. A platooning application forms road trains of vehicles that autonomously follow a common leader, separated by a small inter-vehicle gap. In terms of traffic efficiency, platooning should improve the vehicular flow and reduce shock waves. The latter are the cause of start-and-stop dynamics which, besides disrupting traffic flow, can lead to accidents. The aim of this poster is to analyze, by means of simulations, the impact of platoons on both the traffic flow and the formation of shock waves.