Miracle-dz/UniFAR-FTUs huggingface dataset:
Immune Recognition of Gene Transfer Vectors: Focus on Adenovirus as a Paradigm

Recombinant Adenovirus (Ad) based vectors have been utilized extensively as a gene transfer platform in multiple pre-clinical and clinical applications. These applications are numerous, and inclusive of both gene therapy and vaccine based approaches to human or animal diseases. The widespread utilization of these vectors in both animal models, as well as numerous human clinical trials (Ad-based vectors surpass all other gene transfer vectors relative to numbers of patients treated, as well as number of clinical trials overall), has shed light on how this virus vector interacts with both the innate and adaptive immune systems. The ability to generate and administer large amounts of this vector likely contributes not only to their ability to allow for highly efficient gene transfer, but also their elicitation of host immune responses to the vector and/or the transgene the vector expresses in vivo. These facts, coupled with utilization of several models that allow for full detection of these responses has predicted several observations made in human trials, an important point as lack of similar capabilities by other vector systems may prevent detection of such responses until only after human trials are initiated. Finally, induction of innate or adaptive immune responses by Ad vectors may be detrimental in one setting (i.e., gene therapy) and be entirely beneficial in another (i.e., prophylactic or therapeutic vaccine based applications). Herein, we review the current understanding of innate and adaptive immune responses to Ad vectors, as well some recent advances that attempt to capitalize on this understanding so as to further broaden the safe and efficient use of Ad-based gene transfer therapies in general.
Building Reliable and Fault Resilient Mobile Ad Hoc Networks

The nodes in a mobile ad hoc network (MANET) have limited processing power, memory and transmission range. The mobile nodes may dynamically enter or leave the ad hoc network. To improve the resilience of the ad-hoc networks to mobility, node and link failure, we propose an algorithm involving binary trees and a special form of cycles in the network graph subject to constraints in topology and use this information to re-route packets from source to destination when interconnecting links or nodes fail.
Protein Misfolding Detected Early in Pathogenesis of Transgenic Mouse Model of Huntington Disease Using Amyloid Seeding Assay*

Background: Huntington disease is associated with protein misfolding. Results: We developed an amyloid seeding assay for detecting misfolded huntingtin (HTT) protein and found early protein misfolding in a transgenic mouse model. Conclusion: The amyloid seeding assay allows for sensitive detection of misfolded HTT. Significance: The detection of misfolded HTT in young YAC128 mice suggests that protein misfolding may be an early event in pathogenesis. Huntington disease (HD) is one of several fatal neurodegenerative disorders associated with misfolded proteins. Here, we report a novel method for the sensitive detection of misfolded huntingtin (HTT) isolated from the brains of transgenic (Tg) mouse models of HD and humans with HD using an amyloid seeding assay (ASA), which is based on the propensity of misfolded proteins to act as a seed and shorten the nucleation-associated lag phase in the kinetics of amyloid formation in vitro. Using synthetic polyglutamine peptides as the substrate for amyloid formation, we found that partially purified misfolded HTT obtained from end-stage brain tissue of two Tg HD mouse models and brain tissue of post-mortem human HD patients was capable of specifically accelerating polyglutamine amyloid formation compared with unseeded reactions and controls. Alzheimer and prion disease brain tissues did not do so, demonstrating the specificity of the ASA. It is unclear whether early intermediates or later conformational species in the protein misfolding process act as seeds in the ASA for HD. However, we were able to detect misfolded protein in the brains of YAC128 mice early in disease pathogenesis (11 weeks of age), whereas large inclusion bodies have not been observed in the brains of these mice by histology until 78 weeks of age, much later in the pathogenic process. The sensitive detection of misfolded HTT protein early in the disease pathogenesis in the YAC128 Tg mouse model strengthens the argument for a causative role of protein misfolding in HD.
The internal mammary artery bypass--the principles of preoperative and postoperative diagnosis using colour-duplex ultrasound.

BACKGROUND The aim of the study was the assessment of functional characteristics of the left internal mammary artery (LIMA) bypass in patients after coronary artery bypass grafting (CABG) in comparison with the native LIMA using colour-duplex ultrasound as the non-invasive diagnostic method. METHODS We examined 303 patients after myocardial revascularization with the internal mammary artery bypass using the Hewllett Packard 2500, 5500 ultrasound units. Using the 7.5 MHz linear transducer we detected the LIMA from the left supraclavicular approach. We assessed the peak systolic velocity (PSV--cm/s), peak diastolic velocity (PDV--cm/s), end-diastolic velocity (EDV--cm/s) and we calculated the peak systolic/peak diastolic velocity ratio (SDVR) and resistance index RI (PSV-EDV/PSV). The obtained parameters were compared with the native LIMA flow characteristics of the 70 consecutive patients before CABG. RESULTS We observed the transformation of internal mammary artery flow from the predominantly systolic high resistance type of the native LIMA, to the low resistance biphasic waveform after its use as a coronary artery graft. We detected a significant increase of diastolic flow velocities and a significant decrease of resistance and of the SDVR ratio. In dysfunctional grafts we found a decrease of diastolic flow and an increase of LIMA resistance and SDVR. CONCLUSION The colour-duplex ultrasound is a perspective non-invasive method for the postoperative follow-up of patients with the LIMA graft. It allows the assessment of the bypass flow characteristics, functional status and patency and it could contribute to the early diagnosis of bypass failure. (Fig. 6, Tab. 4, Ref. 21.)
Different Regulation of Clonal Growth by Transforming Growth Factor-β 1 in Human Fetal Articular and Costal Chondrocytes

ABSTRACT: The variable affection of rib and limb growth in human skeletal dysplasias suggests the presence of sitespecific regulatory mechanisms for chondrocyte proliferation. We therefore studied the clonal growth of normal human costal and articular chondrocytes from the same four fetuses (15 to 30 wk of gestation) in a semisolid medium (0.8% methylcellulose) with a basal supplementation of 5% heat-inactivated FCS. IGF-I [0.3-12.5 ng/mL (0.04-1.6 nmol/L)], IGF-II [0.3-12.5 ng/mL (0.04-1.7 nmol/L)], and hGH [0.5-25 ng/mL (0.02-1.1 nmol/L)] stimulated clonal growth of articular and costal chondrocytes without site-specific difference. In contrast, a significant difference was found for transforming growth factorβ1, which proved to be a potent growth factor for fetal articular chondrocytes but did not stimulate or only minimally stimulated fetal costal chondrocytes [p < 0.05 for 0.3 ng/mL (0.01 nmol/L) TGF- β 1 andp < 0.01 for 1.25 ng/mL (0.05 nmol/L) TGF-β 1 using paired t test]. Preincubation with an IGF-I receptor antibody ( αIR-3) completely prevented the proliferative effect of IGF-I, IGF-II, and hGH, indicating that hGH acts via autocrine or paracrine induction of IGF. The antibody partly reduced TGF- β1 action on articular chondrocytes [p < 0.05 for 0.3 ng/mL (0.01 nmol/L) TGF- β1, NS for 1.25 ng/mL (0.05 nmol/L) TGF-β1 using paired t test]. These results indicate that TGF- β 1 is involved in the regulation of human fetal growth and has a different effect in ribs and limbs.
Mental symptoms in Parkinson's disease during chronic treatment with levodopa

Mental symptoms increased in frequency among 100 patients with parkinsonism treated with levodopa. Dementia was found in about one-third of patients throughout the 6-year treatment period. Thirteen patients became demented during the study, and dementia worsened severely in seven others. Agitated confusion became increasingly frequent and was observed in 60 percent of patients taking levodopa for 6 years. Withdrawal from levodopa decreased agitation, but not dementia. Ten patients received L-tryptophan along with levodopa, but no change in mentation was observed. In view of previous studies of mentation in Parkinson's disease and reports of widespread neuronal changes in the brain of autopsied patients with parkinsonism, our results suggest that the high incidence of dementia in patients with Parkinson's disease who take levodopa reflects prolongation of the course of the illness rather than a direct effect of the medication.
Theta lifting of unitary lowest weight modules and their associated cycles

We consider a reductive dual pair (G,G′) in the stable range with G′ the smaller member and of Hermitian symmetric type. We study theta lifting of (holomorphic) nilpotent K ′ C -orbits in relation to theta lifting of unitary lowest weight modules of G′. We determine the associated cycles of all such representations. In particular, we prove that the multiplicity in the associated cycle is preserved under theta lifting.
Activity monitoring in daily life as an outcome measure for surgical pain relief intervention using smartphones

We investigate the potential of a smartphone to measure a patient's change in physical activity before and after a surgical pain relief intervention. We show feasibility for our smartphone system providing physical activity from acceleration, barometer and location data to measure the intervention's outcome. In a single-case study, we monitored a pain patient carrying the smartphone before and after a surgical intervention over 26 days. Results indicate significant changes before and after intervention, particularly in physical activity in the home environment.
Differential Desensitization, Receptor Phosphorylation, β-Arrestin Recruitment, and ERK1/2 Activation by the Two Endogenous Ligands for the CC Chemokine Receptor 7*

Many members of the chemokine receptor family of G protein-coupled receptors utilize multiple endogenous ligands. However, differences between the signaling properties of multiple chemokines through a single receptor have yet to be well characterized. In this study we investigated the early signaling events of CCR7 initiated by its two endogenous ligands, CCL19 and CCL21. Both CCL19 and CCL21 induce G protein activation and calcium mobilization with equal potency. However, only activation by CCL19, not CCL21, promotes robust desensitization of endogenous CCR7 in the human T cell lymphoma cell line H9. Desensitization occurs through the induction of receptor phosphorylation and β-arrestin recruitment (shown in HEK293 cells expressing CCR7-FLAG). The sites of CCL19-induced phosphorylation were mapped by mutating to alanines the serines and threonines found within kinase phosphorylation consensus sequences in the carboxyl terminus of CCR7. A cluster of sites, including Thr-373-376 and Ser-378 is important for CCL19-mediated phosphorylation of the receptor, whereas residues serine 356, 357, 364, and 365 are important for basal receptor phosphorylation by protein kinase C. Activation of CCR7 by both ligands leads to signaling to the ERK1/2 mitogen-activated protein kinase pathway. However, CCL19 promotes 4-fold more ERK1/2 phosphorylation than does CCL21. The mechanism by which CCL19 activates ERK1/2 was determined to be β-arrestin-dependent, because it is reduced both by depletion of β-arrestin-2 with small interfering RNA and by elimination of the phosphorylation sites in the tail of the receptor. Taken together, these findings demonstrate that CCL19 and CCL21 place CCR7 in functionally distinct conformations that are independent of their G protein-coupling potency: one that allows the efficient desensitization of the receptor and activation of ERK1/2, and another that is impaired in these functions.
Algorithms for syntax-aware statistical machine translation

All of the non-trivial algorithms that are necessary for building and applying a rudimentary syntax-aware statistical machine translation system are generalized parsers. This paper extends the “translation by parsing” architecture by adding two components that are invariably used by state-of-the-art statistical machine translation systems. First, the paper shows how a generic syntax-aware translation algorithm can accommodate independently estimated -gram language models. Second, the paper introduces an automatic MT evaluation method that accounts for meaning-preserving syntactic alternations. The core algorithms in both extensions are, again, generalized parsers.
Factores de riesgo asociados a trastornos de la conducta alimentaria en estudiantes que asisten al Centro Javeriano de Formación Deportiva

Now days,, the increase in the manifestation of disordered eating behavior (TCA ) in increasingly younger populations that are between adolescence and adulthood (15 to 29) , in addition to the few existing studies on these disorders in Latin America and 49 in Colombia in particular , made possible the exploration of these in the student population of the PUJ, especially those (as) attending the Javeriana Sports Training Center ( CJFD ), in order to investigate the existence of risk factors associated with TCA having a bearing on the type of physical activity, body image perception and possible compensatory behaviors related to eating behavior. The descriptive cross-sectional study was developed using a sample of 66 students , who were administered the survey of eating behavior (ECA). The results showed that 44 % (n = 29 RCTs scored positive ? 24) , which shows more risk factors associated with Nervous Bulimia . Risk factors found in that 44 % were: being female , age between 18 and 20 years, have body image distortion to the overestimation of body weight, the use of weight loss diets , self-induced vomiting , the use of diuretics or laxatives without a prescription, feel anxiety about food and feel guilty after eating, and all the above, despite having adequate nutritional status . Given these findings it is necessary to create strategies for prevention and timely treatment, to reduce the prevalence of eating disorders in college and improve their quality of life.
Partial activation precedes apoptotic death in T cells harboring an IAN gene mutation

The Biobreeding diabetes‐prone rat suffers from a profound peripheral lymphopenia and yet succumbs to a T cell‐dependent autoimmune disease. Lymphopenia segregates with a mutated chromosomal locus, termed lyp, recently identified as a frameshift mutation in IAN4. Others have correlated loss of IAN4 function with decreased mitochondrial integrity resulting in T cell apoptosis. Here we report that IAN4–/– T cells enter a state similar to that of partial activation wherein they down‐regulate CD62L and undergo incomplete blasting yet do not progress through mitosis. When given a strong stimulus, this partial activation phenotype can be overcome. This phenotype can be recapitulated in wild‐type T cells through suboptimal stimulation. The phenotype is not simply a reaction to the lymphopenic environment, as spontaneous CD62L down‐regulation occurs in mature single‐positive medullary thymocytes that develop within a non‐lymphopenic environment, and normal T cells do not undergo similar blasting when parked in a lymphopenic environment. Finally, we show that IAN4–/– T cells are more readily triggered via TCR stimulation. Thus, in addition to their role in apoptosis, IAN family members may also play a role in regulating the T cell activation state through modulation of TCR signaling strength.
Comment on "Fitting of viscosity: Distinguishing the temperature dependences predicted by various models of supercooled liquids"

In a recent paper, Kivelson et al. [Phys. Rev. E 53, 751 (1996)] presented fits to viscosity and relaxation time data for a variety of glass-forming liquids and concluded that the success of their model in fitting the data provides support for the existence of a high-temperature avoided critical point ${\mathit{T}}^{\mathrm{*}}$. We compare fits obtained with the theory of Kivelson et al. with those of the free-volume theory and conclude that the analysis of Kivelson et al. does not provide convincing evidence for the applicability of their theory to supercooled liquids. \textcopyright{} 1996 The American Physical Society.
Assessing Regional Climate and Local Landcover Impacts on Vegetation with Remote Sensing

Landcover change alters not only the surface landscape but also regional carbon and water cycling. The objective of this study was to assess the potential impacts of landcover change across the Kansas River Basin (KRB) by comparing local microclimatic impacts and regional scale climate influences. This was done using a 25-year time series of Normalized Difference Vegetation Index (NDVI) and precipitation (PPT) data analyzed using multi-resolution information theory metrics. Results showed both entropy of PPT and NDVI varied along a pronounced PPT gradient. The scalewise relative entropy of NDVI was the most informative at the annual scale, while for PPT the scalewise relative entropy varied temporally and by landcover type. The relative entropy of NDVI and PPT as a function of landcover showed the most information at the 512-day scale for all landcover types, implying different landcover types had the same response across the entire KRB. This implies that land use decisions may dramatically alter the local time scales of responses to global climate change. Additionally, altering land cover (e.g., for biofuel production) may impact ecosystem functioning at local to regional scales and these impacts must be considered for accurately assessing future implications of climate change.
Studies on YKL-40 in knee joints of patients with rheumatoid arthritis and osteoarthritis. Involvement of YKL-40 in the joint pathology.

OBJECTIVE The presence of YKL-40 (human cartilage glycoprotein 39) in synovium, cartilage and synovial fluid (SF) from knee joints of patients with rheumatoid arthritis and osteoarthritis (OA) were related to histopathological changes in synovium and cartilage and to serum YKL-40 and other biochemical markers. METHODS The localization of YKL-40 in synovium and cartilage was determined by immunohistochemistry. Synovial inflammation was estimated histologically and by magnetic resonance imaging (MRI). Biochemical markers of inflammation, neutrophil activation and cartilage metabolism were analysed. YKL-40 concentrations in serum and SF were determined by RIA and ELISA. RESULTS In the synovium YKL-40 positive cells were found in lining and stromal cells (macrophages) and the number of YKL-40 positive cells was related to the degree of synovitis. In arthritic cartilage, YKL-40 was located to chondrocytes. YKL-40 levels in SF were higher in RA patients with moderate/severe or none/slight synovitis of the knee joint compared to OA patients with moderate/severe or none/slight synovitis. SF YKL-40 correlated with the synovial membrane and the joint effusion volumes determined by magnetic resonance imaging (MRI) and with other biochemical markers of intercellular matrix metabolism. SF YKL-40 was higher than serum YKL-40, and a relationship existed between the YKL-40 levels in SF and serum. Intraarticular glucocorticoid injection was followed by clinical remission and a decrease in serum YKL-40, which increased again at clinical relapse. CONCLUSIONS YKL-40 in SF is derived from cells in the inflamed synovium, chondrocytes and SF neutrophils. Joint derived YKL-40 influences serum YKL-40. YKL-40 may be involved in the pathophysiology of the arthritic processes and reflect local disease activity.
Strategic Behavior of Moralists and Altruists

Does altruism and morality lead to socially better outcomes in strategic interactions than selfishness? We shed some light on this complex and non-trivial issue by examining a few canonical strategic interactions played by egoists, altruists and moralists. By altruists, we mean people who do not only care about their own material payoffs but also about those to others, and, by a moralist, we mean someone who cares about own material payoff and also about what would be his or her material payoff if others were to act like himself or herself. It turns out that both altruism and morality may improve or worsen equilibrium outcomes, depending on the nature of the game. Not surprisingly, both altruism and morality improve the outcomes in standard public goods games. In infinitely repeated games, however, both altruism and morality may diminish the prospects of cooperation, and to different degrees. In coordination games, morality can eliminate socially inefficient equilibria while altruism cannot.
Understanding phase maps in MRI: a new cutline phase unwrapping method

This paper describes phase maps. A review of the phase unwrapping problem is given. Different structures, in particular fringelines, cutlines, and poles, contained within a phase map are described and their origin and behavior investigated. The problem of phase unwrapping can then be addressed with a better understanding of the source of poles or inconsistencies. This understanding, along with some assumptions about what is being encoded in the phase of a magnetic resonance image, are used to derive a new method for phase unwrapping which relies only on the phase map. The method detects cutlines and distinguishes between noise-induced poles and signal undersampling poles based on the length of the fringelines. The method was shown to be robust to noise and successful in unwrapping challenging clinical cases.
Chronic insulin administration elevates blood pressure in rats.

To examine the relative contribution of dietary glucose and infused insulin on blood pressure, we administered a 4% glucose supplement (in drinking water) with and without insulin infusion (15.8 nmol [2.2 U]/d via osmotic minipump) to male Sprague-Dawley rats (n = 6). We also tested the effect of the sympatholytic agent clonidine on rats receiving glucose and insulin. Blood pressure and heart rate were recorded via a novel radio telemetry system. Experiments were performed using a crossover design with three animals receiving treatment and three receiving vehicle for 10 days. After a 10-day washout period, the groups were reversed, and the experiment was repeated. Blood samples for insulin and glucose were drawn throughout the study. Systolic and diastolic blood pressures increased (by 6.0 +/- 1.2 and 2.2 +/- 1.3 mm Hg, respectively) in the animals given glucose alone in association with an increase in plasma insulin. However, blood pressure increased more rapidly and to a greater extent, systolic by 8.6 +/- 0.7 mm Hg and diastolic by 2.9 +/- 1.1 mm Hg, during the insulin treatment that raised plasma insulin above the levels observed during glucose feeding alone. Heart rate increased equally during both treatments. The average change in blood pressure and average plasma insulin during the infusion were correlated (r = .72, P = .009). Blood pressure dropped during the week following discontinuation of the insulin infusion. On rechallenge with insulin and glucose, blood pressure again rose and then decreased after termination of the insulin and glucose administration. Clonidine prevented the rise in blood pressure and heart rate. (ABSTRACT TRUNCATED AT 250 WORDS)