Miracle-dz/UniFAR-FTUs huggingface dataset:
Cell therapy: replacement.

Not long ago, the ability of the brain to restore function through regeneration of neural elements was thought to be nonexistent. It is now known that not only does some regenerative capacity exist, but implanted cells can integrate into the host brain, survive, and reverse neurological deficits. Neural stem cells, fetal transplants, immortalized cell lines, and bone marrow stromal cells show promise in experimental models of neurological disease including stroke. Although it is clear that transplanted cells function, the mechanism by which neurological deficits might improve is less certain. Transplanted cells may preserve existing host cells and connections through secretion of trophic factors; establish local connections that enhance synaptic activity; provide a bridge for host axonal regeneration; or actually replace cellular elements. Several observations from animal and human studies of cell therapy support the possibility that transplanted cells exert at least some of their effect through cellular replacement. In the early stages of brain development, implanting neural stem cells leads to replacement of multiple cellular elements including neurons and glia.1 Thus, the potential for cell replacement exists, but whether it persists into adulthood is uncertain. Models of Parkinson’s disease (PD) provide the most direct support for cell replacement as an important effect of cell therapy. Fetal ventral mesencephalic neurons grafted into the striatum in animal models of PD restore dopamine levels and improve function.2 Similar grafts outside the striatum fail to achieve clinical benefit. In humans, such fetal grafts produce clinical benefit 3 that accrues gradually rather than immediately, suggesting an accumulation of synaptic connections that eventually results in sufficient dopaminergic transmission to improve neurological deficits. Autopsy findings in patients receiving fetal grafts demonstrate implanted cell survival as well as axon growth and synaptic connections4. Additional support comes from
Dipeptidyl peptidase IV (CD26) on T cells cleaves the CXC chemokine CXCL11 (I‐TAC) and abolishes the stimulating but not the desensitizing potential of the chemokine

Dipeptidyl peptidase IV (DPP IV/CD26) is a costimulatory molecule as well as a protease highly expressed on T cells. Purified DPP IV has been recognized to inactivate peptide hormones, neuropeptides, and some chemokines by cleavage behind a proline residue at the penultimate N‐terminal amino acid position. Here, we identified another substrate for DPP IV among the chemokine family: the interferon‐inducible T cell α chemoattractant (I‐TAC/CXCL11). Using a specific DPP IV inhibitor, we demonstrate that DPP IV is responsible for the cleavage of the chemokine by PHA/IL‐2‐treated T cells. As PHA/IL‐2‐treated T cells also express the CXCL11 receptor (CXCR3), we investigated whether truncation of CXCL11 would modulate its biological activity for these cells. Truncated CXCL11 [CXCL11(3–73)] had an eightfold reduced potential to bind and to regulate CXCR3, but was completely inactive in calcium flux and chemotaxis assays. However, consistent with its reduced but still considerable ability to down‐regulate CXCR3, truncated CXCL11 desensitized T cell chemotaxis in response to the intact chemokine. Hence, CXCL11‐induced T cell recruitment may be regulated by DPP IV‐mediated proteolytic inactivation of CXCL11 and furthermore by desensitization of T cells via the degradation product CXCL11(3–73).
PLGA porous scaffolds by polydopamine-assisted immobilization of NGF for spinal cord injury repair

The degradable polymer biomaterials have great potential in the field of nerve regeneration, which have gradually been applied to spinal cord injury repair. In this study, a polylactic acid-glycolic acid copolymer (PLGA) porous scaffold was prepared by the process of phase inversion, then the surface of the scaffold was modified by polydopamine (PDA) as a substrate, followed by adsorption of nerve growth factor (NGF) to obtain a PDA-PLGA/NGF scaffold. The characterization and hydrophilicity of the scaffolds were evaluated by electron microscopy, EDX and contact angle measurement. The effect of PDA modification on the binding efficiency and release profile of NGF was observed by ELISA. The proliferation and differentiation of NSCs on the surface of biomaterials was evaluated by MTT, immunofluorescence staining and PCR. Subsequently, the rat T9 spinal cord transection model was established and the nerve scaffolds were implanted to injured site. Our results showed PDA modification could significantly improve the NGF adsorption capacity and provide sustained release of NGF. PDA-PLGA/NGF scaffolds could not only enhance NSCs proliferation and neuronal differentiation in vitro, but also promote recovery of spinal cord injury in vivo. Therefore, we believed that PDA-PLGA/NGF scaffolds could be a promising method to facilitate neurogenesis and repair spinal cord injury.
Tn and sialyl‐Tn antigens, aberrant O‐glycomics as human disease markers

In many different human disorders, the cellular glycome is altered. An interesting but poorly understood alteration occurs in the mucin‐type O‐glycome, in which there is aberrant expression of the truncated O‐glycans Tn (GalNAcα1‐Ser/Thr) and its sialylated version sialyl‐Tn (STn) (Neu5Acα2,6GalNAcα1‐Ser/Thr). Both Tn and STn are tumor‐associated carbohydrate antigens and tumor biomarkers, since they are not expressed normally and appear early in tumorigenesis. Moreover, their expression is strongly associated with poor prognosis and tumor metastasis. The Tn and STn antigens are also expressed in other human diseases and disorders, such as Tn syndrome and IgA nephropathy. The major pathological mechanism for expression of the Tn and STn antigens is compromised T‐synthase activity, resulting from alteration of the X‐linked gene that encodes for Cosmc, a molecular chaperone specifically required for the correct folding of T‐synthase to form active enzyme. This review will summarize our current understanding of the Tn and STn antigens in terms of their biochemistry and role in pathology.
On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection.

BACKGROUND Antiretroviral preexposure prophylaxis has been shown to reduce the risk of human immunodeficiency virus type 1 (HIV-1) infection in some studies, but conflicting results have been reported among studies, probably due to challenges of adherence to a daily regimen. METHODS We conducted a double-blind, randomized trial of antiretroviral therapy for preexposure HIV-1 prophylaxis among men who have unprotected anal sex with men. Participants were randomly assigned to take a combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) or placebo before and after sexual activity. All participants received risk-reduction counseling and condoms and were regularly tested for HIV-1 and HIV-2 and other sexually transmitted infections. RESULTS Of the 414 participants who underwent randomization, 400 who did not have HIV infection were enrolled (199 in the TDF-FTC group and 201 in the placebo group). All participants were followed for a median of 9.3 months (interquartile range, 4.9 to 20.6). A total of 16 HIV-1 infections occurred during follow-up, 2 in the TDF-FTC group (incidence, 0.91 per 100 person-years) and 14 in the placebo group (incidence, 6.60 per 100 person-years), a relative reduction in the TDF-FTC group of 86% (95% confidence interval, 40 to 98; P=0.002). Participants took a median of 15 pills of TDF-FTC or placebo per month (P=0.57). The rates of serious adverse events were similar in the two study groups. In the TDF-FTC group, as compared with the placebo group, there were higher rates of gastrointestinal adverse events (14% vs. 5%, P=0.002) and renal adverse events (18% vs. 10%, P=0.03). CONCLUSIONS The use of TDF-FTC before and after sexual activity provided protection against HIV-1 infection in men who have sex with men. The treatment was associated with increased rates of gastrointestinal and renal adverse events. (Funded by the National Agency of Research on AIDS and Viral Hepatitis [ANRS] and others; ClinicalTrials.gov number, NCT01473472.).
Comprehensive invasive and noninvasive approach to the right ventricle-pulmonary circulation unit: state of the art and clinical and research implications.

… And I ask, as the lungs are so close at hand, and in continual motion, and the vessel that supplies them is of such dimensions, what is the use or meaning of this pulse of the right ventricle? And why was nature reduced to the necessity of adding another ventricle for the sole purpose of nourishing the lungs? — —William Harvey, Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus, 1628 There is still no answer to William Harvey’s rhetorical question. He included the right ventricle (RV), its “pulse,” the large pulmonary arteries (PAs), and the lungs in the same sentence, emphasizing the concept of a “unit. ” Although Harvey realized the importance of the RV and its interactions with the pulmonary circulation, 4 centuries later, the RV is largely understudied. At the same time, there has been significant progress in our understanding of the pathology of pulmonary vascular disease and, over the past few years, an explosion of clinical therapeutic trials for PA hypertension (PAH). 1 This unbalanced approach has generated a number of problems and controversies. For example, it is now becoming apparent that even if experimental therapies improve or reverse PAH pathology, this does not necessarily lead to clinical improvement and prolonged survival unless accompanied by a parallel improvement in RV function. The degree of pulmonary hypertension (ie, PA pressure [PAP]) does not strongly correlate with symptoms or survival, whereas RV mass and size and right atrial pressure reflect functional status and are strong predictors of survival.2 The 6-minute walk test, used as the primary end point in most PAH clinical trials, correlates better with RV function (ie, cardiac output) than with the degree of pulmonary pressure elevation. However, this test is being heavily criticized because of multiple inherent problems and the fact that it does …
Combined vascular endothelial growth factor and TP53 status predicts poor response to tamoxifen therapy in estrogen receptor-positive advanced breast cancer.

PURPOSE In recent studies, we showed that TP53 gene mutation or high levels of cytosolic vascular endothelial growth factor (VEGF) in estrogen receptor (ER)-alpha-positive primary breast tumors predict a poor disease outcome for patients treated with first-line tamoxifen for advanced disease. Mutant TP53 may up-regulate VEGF, whereas, on the other hand, wild-type TP53 may decrease VEGF production. EXPERIMENTAL DESIGN In the present study, we aimed to assess the combined predictive value of TP53 gene mutation and VEGF status of 160 advanced breast cancer patients with ER-positive tumors who were treated with tamoxifen (median follow-up from start of tamoxifen treatment, 64 months). To assess TP53 gene mutation status, the entire open reading frame was sequenced; for VEGF status, an ELISA was used. RESULTS In univariate analysis, both TP53 gene mutation (28% of the tumors) and a VEGF level above the median value were significantly associated with a short progression-free survival, post-relapse overall survival, and a poor rate of response to tamoxifen. In Cox multivariate regression analysis including the traditional predictive factors, the addition of TP53 gene mutation and VEGF status, alone or in combination, significantly predicted a poor efficacy of tamoxifen treatment. When the two factors were combined, a significantly decreased odds ratio was seen for the rate of response (odds ratio, 0.27). Similarly, an increased hazard ratio (HR) was seen for progression-free survival (HR, 2.32) and post-relapse overall survival (HR, 1.68) in the group with mutant TP53 and high VEGF compared with the group with both risk factors absent. CONCLUSIONS Combined TP53 gene mutation status and high VEGF levels of ER-positive primary breast tumors independently predict a poor course of the disease of patients with advanced breast cancer treated with tamoxifen. These patients, having unfavorable tumor characteristics, might benefit more from other types of (individualized) treatment protocols.
Dynamic contrast‐enhanced MRI in the diagnosis and management of breast cancer

Dynamic contrast‐enhanced MRI (DCE‐MRI) is an evolving tool for determining breast disease, which benefits from the move to imaging at 3 T. It has major capabilities for the diagnosis, detection and monitoring of malignancy. It benefits from being non‐invasive and three‐dimensional, allowing visualisation of the extent of disease and its angiogenic properties, visualisation of lesion heterogeneity, detection of changes in angiogenic properties before morphological alterations, and the potential to predict the overall response either before the start of therapy or early during treatment. In addition, DCE‐MRI is emerging as a powerful tool for screening high‐risk patients and for detecting high‐grade ductal carcinoma in situ. However, there are also a number of limitations, including the overlap in enhancement patterns between malignant and benign disease, the failure to resolve microscopic disease particularly in the neoadjuvant setting, and the inconsistent predictive value of the enhancement pattern for clinical outcome. Careful consideration should be given to the technical requirements of individual examinations and the need for automation of post‐processing techniques to appropriately handle the growing volume of data acquired. Research continues, focusing on the use of higher field strengths with improved spatial and temporal resolution data, improving understanding of the mechanism of contrast enhancement at the cellular level, and developing macromolecular and targeted contrast agents. Copyright © 2008 John Wiley & Sons, Ltd.
Performance Analysis of Sequence Alignment Applications

Advances in molecular biology have led to a continued growth in the biological information generated by the scientific community. Additionally, this area has become a multi-disciplinary field, including components of mathematics, biology, chemistry, and computer science, generating several challenges in the scientific community from different points of view. For this reason, bioinformatic applications represent an increasingly important workload. However, even though the importance of this field is clear, common bioinformatic applications and their implications on micro-architectural design have not received enough attention from the computer architecture community. This paper presents a micro-architecture performance analysis of recognized bioinformatic applications for the comparison and alignment of biological sequences, including BLAST, FASTA and some recognized parallel implementations of the Smith-Waterman algorithm that use the Altivec SIMD extension to speed-up the performance. We adopt a simulation-based methodology to perform a detailed workload characterization. We analyze architectural and micro-architectural aspects like pipeline configurations, issue widths, functional unit mixes, memory hierarchy and their implications on the performance behavior. We have found that the memory subsystem is the component with more impact in the performance of the BLAST heuristic, the branch predictor is responsible for the major performance loss for FASTA and SSEARCH34, and long dependency chains are the limiting factor in the SIMD implementations of Smith-Waterman
Finite Sections of Random Jacobi Operators

This article is about a problem in the numerical analysis of random operators. We study a version of the finite section method for the approximate solution of equations $Ax=b$ in infinitely many variables, where $A$ is a random Jacobi (i.e., tridiagonal) operator. In other words, we approximately solve infinite second order difference equations with stochastic coefficients by reducing the infinite volume case to the (large) finite volume case via a particular truncation technique. For most of the paper we consider non-self-adjoint operators $A$, but we also comment on the self-adjoint case when simplifications occur.
The dopamine transporter role in psychiatric phenotypes

The dopamine transporter (DAT) is one of the most relevant and investigated neurotransmitter transporters. DAT is a plasma membrane protein which plays a homeostatic role, controlling both extracellular and intracellular concentrations of dopamine (DA). Since unbalanced DA levels are known to be involved in numerous mental disorders, a wealth of investigations has provided valuable insights concerning DAT role into normal brain functioning and pathological processes. Briefly, this extensive but non‐systematic review discusses what is recently known about the role of SLC6A3 gene which encodes the dopamine transporter in psychiatric phenotypes. DAT protein, SLC6A3 gene, animal models, neuropsychology, and neuroimaging investigations are also concisely discussed. To conclude, current challenges are reviewed in order to provide perspectives for future studies.
Human Amniotic Fluid Stem Cells Can Integrate and Differentiate into Epithelial Lung Lineages

A new source of stem cells has recently been isolated from amniotic fluid; these amniotic fluid stem cells have significant potential for regenerative medicine. These cells are multipotent, showing the ability to differentiate into cell types from each embryonic germ layer. We investigated the ability of human amniotic fluid stem cells (hAFSC) to integrate into murine lung and to differentiate into pulmonary lineages after injury. Using microinjection into cultured mouse embryonic lungs, hAFSC can integrate into the epithelium and express the early human differentiation marker thyroid transcription factor 1 (TTF1). In adult nude mice, following hyperoxia injury, tail vein‐injected hAFSC localized in the distal lung and expressed both TTF1 and the type II pneumocyte marker surfactant protein C. Specific damage of Clara cells through naphthalene injury produced integration and differentiation of hAFSC at the bronchioalveolar and bronchial positions with expression of the specific Clara cell 10‐kDa protein. These results illustrate the plasticity of hAFSC to respond in different ways to different types of lung damage by expressing specific alveolar versus bronchiolar epithelial cell lineage markers, depending on the type of injury to recipient lung.
Multicast in deflection networks

Multicasting in deflection networks is more difficult than in store-and-forward networks, because of the difficulties in sending multiple copies of the same packet on several output ports. On the other hand, deflected packets stray from their optimal paths and may visit the multicast recipients "accidentally", not necessary in the order envisioned by the sender. We compare a number of simple multicast strategies for deflection networks based on a few simple rules and assumptions. In particular, we never buffer packets that cannot be relayed immediately.
Enhanced Lipid Production under High Light Intensity High to Low Nitrogen Concentration

Dunaliella salina (D. salina) is a potential source of lipids and subsequent bi odiesel production. However lipid production from dependent on biomass production rate and lipid cont ent. To get more lipid, production efficiency need to be improved. The aim was to application of twostage culture strategy for improved microalgal grow th and lipid Production. In this study the culture was grown under four different nitrogen concentrations (2 mM) to low nitrogen (2 mM) concentration under high (800 to get the high lipid yield. The result showed that maximum lipid contents (46%) and lipid per cell (3 7 culture grown under low nitrogen concentration wher eas high nitrogen culture showed maximum lipid conc entration 0.73 g L productivity 56.32 mg L day when grown under high light intensity. The culture grown increased the overall lipid productivity due to inc rease the biomass dry weight (2.13 g L However the culture shifted from high nitrogen to l ow nitrogen concent of lipids (56.47%), concentration of lipid (1.169 g L shifting of D. salina culture from high to low nit overall lipid production in D. salina. This strategy can be used for outdoor cultivation for efficient algal biofuels production.
Rescalable solid-state nanopores

Nanopores in 10–30 nm thickness Si4N3 membranes were milled using Ga+ ions. Dose dependence of the hole diameter and shape was established and explained as resulting from the intensity distribution of the focused ion beam. The initial diameter of the milled pore is dependent on the full-width half-maximum of the axial portion of the beam, whereas shape variations with dose are related to characteristics of the beam periphery. Membrane milling can thereby yield information on the FIB system itself, since obfuscating re-deposition is effectively eliminated. Gradual closure of the nanopore can be realized through raster scan exposure to an electron beam. This simple method provides shape control of the milled nano-pores as well as of more complex patterns milled in membranes.
Measurement and Modeling of Video Watching Time in a Large-Scale Internet Video-on-Demand System

Video watching time is a crucial measure for studying user watching behavior in online Internet video-on-demand (VoD) systems. It is important for system planning, user engagement understanding, and system quality evaluation. However, due to the limited access of user data in large-scale streaming systems, a systematic measurement, analysis, and modeling of video watching time is still missing. In this paper, we measure PPLive, one of the most popular commercial Internet VoD systems in China, over a three week period. We collect accurate user watching data of more than 100 million streaming sessions of more than 100 thousand distinct videos. Based on the measurement data, we characterize the distribution of watching time of different types of videos and reveal a number of interesting characteristics regarding the relation between video watching time and various video-related features (including video type, duration, and popularity). We further build a suite of mathematical models for characterizing these relationships. Extensive performance evaluation shows the high accuracy of these models as compared with commonly used data-mining based models. Our measurement and modeling results bring forth important insights for simulation, design, deployment, and evaluation of Internet VoD systems.
Inhibition of placental growth factor activity reduces the severity of fibrosis, inflammation, and portal hypertension in cirrhotic mice

Placental growth factor (PlGF) is associated selectively with pathological angiogenesis, and PlGF blockade does not affect the healthy vasculature. Anti‐PlGF is therefore currently being clinically evaluated for the treatment of cancer patients. In cirrhosis, hepatic fibrogenesis is accompanied by extensive angiogenesis. In this paper, we evaluated the pathophysiological role of PlGF and the therapeutic potential of anti‐PlGF in liver cirrhosis. PlGF was significantly up‐regulated in the CCl4‐induced rodent model of liver cirrhosis as well as in cirrhotic patients. Compared with wild‐type animals, cirrhotic PlGF−/− mice showed a significant reduction in angiogenesis, arteriogenesis, inflammation, fibrosis, and portal hypertension. Importantly, pharmacological inhibition with anti‐PlGF antibodies yielded similar results as genetic loss of PlGF. Notably, PlGF treatment of activated hepatic stellate cells induced sustained extracellular signal‐regulated kinase 1/2 phosphorylation, as well as chemotaxis and proliferation, indicating a previously unrecognized profibrogenic role of PlGF. Conclusion: PlGF is a disease‐candidate gene in liver cirrhosis, and inhibition of PlGF offers a therapeutic alternative with an attractive safety profile. (HEPATOLOGY 2011;)