gebhart/patrepeval huggingface dataset:
Redirecting Migration of T Cells to Chemokine Secreted from Tumors by Genetic Modification with CXCR2 (2002)

T-cell-based immunotherapies provide a promising means of cancer treatment although durable antitumor responses are infrequent. A potential reason for these shortcomings may lie in the observed lack of trafficking of specific T cells to tumor. Our increasing knowledge of the process of trafficking involving adhesion molecules and chemokines affords us the opportunity to intervene and correct deficiencies in this process. Chemokines can be expressed by a range of tumors and may serve as suitable targets for directing specific T cells toward tumor. We initially sought to identify which chemokines were produced by a range of human tumor cell lines, and which chemokines and chemokine receptors were expressed by cultured T cells. We identified two chemokines: Growth-Regulated Oncogene-alpha (Gro-alpha; CXCL1) and Regulated on Activation Normal T Cell-Expressed and Secreted (RANTES; CCL5), to be secreted by several human tumor cell lines. Expression was also detected in fine-needle aspirates of melanoma from patients. In addition, we determined the expression of several chemokine receptors on cultured human T cells including CCR1, CCR2, CCR4, CCR5, CXCR3, and CXCR4. Cultured, activated human T cells expressed the chemokines lymphotactin (XCL1), RANTES, macrophage inflammatory protein-1 alpha (MIP-1 alpha; CCL3) and MIP-1 beta (CCL4), but no appreciable Gro-alpha. In a strategy to direct T cells toward chemokines expressed by tumors we chose Gro-alpha as the target chemokine because it was produced by tumor and not by T cells themselves. However, T cells did not express the receptor for Gro-alpha, CXCR2, and therefore, T cells were transduced with a retroviral vector encoding CXCR2. Calcium ion mobilization, an important first step in chemokine receptor signaling, was subsequently demonstrated in transduced T cells in response to Gro-alpha. In addition, Gro-alpha was chemotactic for T cells expressing CXCR2 in vitro toward both recombinant protein and tumor-derived chemokine. Interestingly we demonstrate, for the first time, that Gro-alpha was able to induce interferon-gamma (IFN-gamma) secretion from transduced T cells, thereby extending our knowledge of other potential functions of CXCR2. This study demonstrates the feasibility of redirecting the migration properties of T cells toward chemokines secreted by tumors.
Transcribing pancreas. (1998)

For approximately 30-35 years, our insight into some of the fundamental aspects of pancreas development has been based mainly on two independent studies performed in the 1960s by Golosow and Grobstein and Wessells and Cohen. By performing classical embryological experiments, these two reports described the morphogenesis of the pancreas and the epitheliomesenchymal interactions that are required for proper pancreas development. In the 1970s, the groups of LeDourain and associates and Rutter and associates showed, importantly, that despite their similarities with neurons, the pancreatic endocrine cells, like the exocrine and ductual cells, were of an endodermal origin. Then during the 1980s, studies pioneered by Rutter, but also performed by many other groups, were focused on the transcriptional regulation of endocrine and exocrine genes. This eventually lead to the cloning of various transcription factors. By using a genetic approach to study the function of these transcription factors, new insights into pancreas development have now emerged that, on a molecular level, are beginning to explain some of the earlier observations. This review discusses our current knowledge of the mechanisms by which the various pancreatic cell types are generated.
Visual Odometry [Tutorial] (2011)

Visual odometry (VO) is the process of estimating the egomotion of an agent (e.g., vehicle, human, and robot) using only the input of a single or multiple cameras attached to it. Application domains include robotics, wearable computing, augmented reality, and automotive. The term VO was coined in 2004 by Nister in his landmark paper [1]. The term was chosen for its similarity to wheel odometry, which incrementally estimates the motion of a vehicle by integrating the number of turns of its wheels over time. Likewise, VO operates by incrementally estimating the pose of the vehicle through examination of the changes that motion induces on the images of its onboard cameras. For VO to work effectively, there should be sufficient illumination in the environment and a static scene with enough texture to allow apparent motion to be extracted. Furthermore, consecutive frames should be captured by ensuring that they have sufficient scene overlap.
Isolated Cases of Plague — Inner Mongolia-Beijing, 2019 (2019)

When epizootic plague is detected, local health-care providers and the public should be alerted about any possible risks. Public education efforts should focus on promoting personal protection measures.
High Performance Visual Tracking with Siamese Region Proposal Network (2018)

Visual object tracking has been a fundamental topic in recent years and many deep learning based trackers have achieved state-of-the-art performance on multiple benchmarks. However, most of these trackers can hardly get top performance with real-time speed. In this paper, we propose the Siamese region proposal network (Siamese-RPN) which is end-to-end trained off-line with large-scale image pairs. Specifically, it consists of Siamese subnetwork for feature extraction and region proposal subnetwork including the classification branch and regression branch. In the inference phase, the proposed framework is formulated as a local one-shot detection task. We can pre-compute the template branch of the Siamese subnetwork and formulate the correlation layers as trivial convolution layers to perform online tracking. Benefit from the proposal refinement, traditional multi-scale test and online fine-tuning can be discarded. The Siamese-RPN runs at 160 FPS while achieving leading performance in VOT2015, VOT2016 and VOT2017 real-time challenges.
Estado y globalización: las tareas pendientes (1996)

Este trabajo analiza los efectos de la globalizacion economica sobre el Estado mexicano, especificamente en la estructura y la estrategia de la administracion publica, planteado desde el punto de vista del redimensionamiento, que ha reducido al Estado a su expresion minima, con las pretensiones de que ello sea la clave para la eficiencia de la intervencion en el sistema economico nacional. Los autores analizan algunos resultados de la politica estatal de no intervencion. Aqui las politicas de privatizacion y desregulacion son el punto de referencia obligado para contextualizar debidamente el impacto de la globalizacion economica y de sus secuelas. Asi se concluye que no existe aun una cultura organizacional en la operatividad de la administracion publica.
Extracellular HMGB1, a signal of tissue damage, induces mesoangioblast migration and proliferation (2004)

High mobility group box 1 (HMGB1) is an abundant chromatin protein that acts as a cytokine when released in the extracellular milieu by necrotic and inflammatory cells. Here, we show that extracellular HMGB1 and its receptor for advanced glycation end products (RAGE) induce both migration and proliferation of vessel-associated stem cells (mesoangioblasts), and thus may play a role in muscle tissue regeneration. In vitro, HMGB1 induces migration and proliferation of both adult and embryonic mesoangioblasts, and disrupts the barrier function of endothelial monolayers. In living mice, mesoangioblasts injected into the femoral artery migrate close to HMGB1-loaded heparin-Sepharose beads implanted in healthy muscle, but are unresponsive to control beads. Interestingly, alpha-sarcoglycan null dystrophic muscle contains elevated levels of HMGB1; however, mesoangioblasts migrate into dystrophic muscle even if their RAGE receptor is disabled. This implies that the HMGB1-RAGE interaction is sufficient, but not necessary, for mesoangioblast homing; a different pathway might coexist. Although the role of endogenous HMGB1 in the reconstruction of dystrophic muscle remains to be clarified, injected HMGB1 may be used to promote tissue regeneration.
Modelling the effectiveness of counter-terrorism interventions (2014)

This paper models the connection between the rate of terrorist events and the occurrence of counter-terrorism interventions in order to examine the relative effectiveness of the interventions. Using data from the Global Terrorism Database and information on interventions collected by the authors, model results show that for Indonesia, the Philippines and Thailand, reactive types of interventions, such as arrests, indictments, imprisonments, assassinations and other operational activities show the strongest association with the rate of terrorism incidents over time. Maximum effectiveness—as measured by the number of days after an intervention exhibits its full inhibitory effect on the risk of subsequent terrorist attacks—was found to be greatest in Indonesia and the Philippines (11 days and 8 days respectively) and least effective in Thailand (impacting only on the day the intervention occurred). This paper also examines the number of days after an intervention that the response was able to maintain a high level of effectiveness—17 days in Indonesia, 13 days in the Philippines and one day in Thailand. There were significant differences across these three countries and these results highlight a new approach to conceptualising the interaction between terrorism and counter-terrorism efforts.
Hyphal Elongation of Glomus fasciculatus in Response to Root Exudates (1987)

The spore germination rates on water agar of the vesicular-arbuscular mycorrhizal fungus Glomus fasciculatus were highest at water potentials of −4 to −6 bars. Root exudates from plants grown in a sterile nutrient solution, with or without phosphorus, did not affect germination. Root exudates collected from 2-, 4-, and 6-week-old Trifolium repens cv. `Ladino' seedlings that were deprived of P enabled hyphal growth from germinated Glomus fasciculatus spores of 21.4, 14.7, and 7.6 mm, respectively. Hyphal elongation in the presence of exudates from plants grown with P, or in the absence of exudates, was negligible (&lt;1 mm). Root P at 2 weeks was not significantly different between plants grown with and without P. There were no significant differences between the quantities of exudates from plants grown with or without P at 2, 4, and 6 weeks. The data suggest that it is the quality of exudates from plants experiencing P deprivation that is important in stimulating vesicular-arbuscular mycorrhizal hyphal elongation.
The RNA-Binding Protein SYNCRIP Is a Component of the Hepatocyte Exosomal Machinery Controlling MicroRNA Sorting (2016)

Despite clear evidence that exosomal microRNAs (miRNAs) are able to modulate the cellular microenvironment and that exosomal RNA cargo selection is deregulated in pathological conditions, the mechanisms controlling specific RNA sorting into extracellular vesicles are still poorly understood. Here, we identified the RNA binding protein SYNCRIP (synaptotagmin-binding cytoplasmic RNA-interacting protein; also known as hnRNP-Q or NSAP1) as a component of the hepatocyte exosomal miRNA sorting machinery. SYNCRIP knockdown impairs sorting of miRNAs in exosomes. Furthermore, SYNCRIP directly binds to specific miRNAs enriched in exosomes sharing a common extra-seed sequence (hEXO motif). The hEXO motif has a role in the regulation of miRNA localization, since embedment of this motif into a poorly exported miRNA enhances its loading into exosomes. This evidence provides insights into the mechanisms of miRNA exosomal sorting process. Moreover, these findings open the way for the possible selective modification of the miRNAs exosomal cargo.
Statins: Beneficial or Adverse for Glucose Metabolism (2006)

Large-scale clinical trials have established that statin use for lowering blood cholesterol is beneficial in reducing atherosclerotic cardiovascular diseases in different populations. However, the general reputation of statins seems to be clouded by a potential adverse effect of a class of statins on glucose metabolism. This paper reviewed clinical data of statins regarding the effects on diabetes mellitus and glucose metabolism. At least five randomized controlled studies, primarily investigating the protective effect of statins on the risk of cardiovascular diseases, have addressed the effect of statins on glucose metabolism in Western countries. One study showed that pravastatin (40 mg/day) was protective against the development of diabetes mellitus. Two studies of atorvastatin (10 mg/day) and one study of simvastatin (40 mg/day) showed no measurable effect of these regimens on the risk of diabetes mellitus or the clinical course of diabetes mellitus. One study of atorvastatin (80 mg/day) versus pravastatin (40 mg/day) suggested a deterioration of glucose metabolism associated with a high dose of atorvastatin. In Japan, a few case reports have noted a potential adverse effect of atorvastatin on glycemic control in patients with diabetes mellitus; however, seven clinical trials have showed no such effect of atorvastatin although these studies were relatively small in size and short in follow-up. Only one of the two observational studies suggested a possible adverse effect of atorvastatin on glycemic control. Evidence is extremely limited regarding atorvastatin use and deterioration in glycemic control, and further studies are needed to draw a conclusion on this issue.
RNA secondary structure regulates the translation of sxy and competence development in Haemophilus influenzae (2007)

The sxy (tfoX) gene product is the central regulator of DNA uptake by naturally competent gamma-proteobacteria such as Haemophilus influenzae, Vibrio cholerae and probably Escherichia coli. However, the mechanisms regulating sxy gene expression are not understood despite being key to understanding the physiological role of DNA uptake. We have isolated mutations in H. influenzae sxy that greatly elevate translation and thus cause competence to develop in otherwise non-inducing conditions (hypercompetence). In vitro nuclease analysis confirmed the existence of an extensive secondary structure at the 5' end of sxy mRNA that sequesters the ribosome-binding site and start codon in a stem-loop. All of the hypercompetence mutations reduced mRNA base pairing, and one was shown to cause a global destabilization that increased translational efficiency. Conversely, mutations engineered to add mRNA base pairs strengthened the secondary structure, resulting in reduced translational efficiency and greatly reduced competence for genetic transformation. Transfer of wild-type cells to starvation medium improved translational efficiency of sxy while independently triggering the sugar starvation regulator (CRP) to stimulate transcription at the sxy promoter. Thus, mRNA secondary structure is responsive to conditions where DNA uptake will be favorable, and transcription of sxy is simultaneously enhanced if CRP activation signals that energy supplies are limited.
Tracking the Total CD8 T Cell Response to Infection Reveals Substantial Discordance in Magnitude and Kinetics between Inbred and Outbred Hosts (2009)

Determining the magnitude and kinetics, together with the phenotypic and functional characteristics of responding CD8 T cells, is critical for understanding the regulation of adaptive immunity as well as in evaluating vaccine candidates. Recent technical advances have allowed tracking of some CD8 T cells responding to infection, and a body of information now exists describing phenotypic changes that occur in CD8 T cells of known Ag-specificity during their activation, expansion, and memory generation in inbred mice. In this study, we demonstrate that Ag but not inflammation-driven changes in expression of CD11a and CD8alpha can be used to distinguish naive from Ag-experienced (effector and memory) CD8 T cells after infection or vaccination. Interestingly and in contrast to inbred mice, tracking polyclonal CD8 T cell responses with this approach after bacterial and viral infections revealed substantial discordance in the magnitude and kinetics of CD8 T cell responses in outbred hosts. These data reveal limitations to the use of inbred mouse strains as preclinical models at vaccine development and suggest the same dose of infection or vaccination can lead to substantial differences in the magnitude and timing of Ag-specific CD8 expansion as well in differences in protective memory CD8 T cell numbers in outbred individuals. This concept has direct relevance to development of vaccines in outbred humans.
IL-11 Receptor α in the Pathogenesis of IL-13-Induced Inflammation and Remodeling (2005)

IL-13 is a major stimulator of inflammation and tissue remodeling at sites of Th2 inflammation. In Th2-dominant inflammatory disorders such as asthma, IL-11 is simultaneously induced. However, the relationship(s) between IL-11 and IL-13 in these responses has not been defined, and the role(s) of IL-11 in the genesis of the tissue effects of IL-13 has not been evaluated. We hypothesized that IL-11, signaling via the IL-11Ralpha-gp130 receptor complex, plays a key role in IL-13-induced tissue responses. To test this hypothesis we compared the expression of IL-11, IL-11Ralpha, and gp130 in lungs from wild-type mice and transgenic mice in which IL-13 was overexpressed in a lung-specific fashion. We simultaneously characterized the effects of a null mutation of IL-11Ralpha on the tissue effects of transgenic IL-13. These studies demonstrate that IL-13 is a potent stimulator of IL-11 and IL-11Ralpha. They also demonstrate that IL-13 is a potent stimulator of inflammation, fibrosis, hyaluronic acid accumulation, myofibroblast accumulation, alveolar remodeling, mucus metaplasia, and respiratory failure and death in mice with wild-type IL-11Ralpha loci and that these alterations are ameliorated in the absence of IL-11Ralpha. Lastly, they provide insight into the mechanisms of these processes by demonstrating that IL-13 stimulates CC chemokines, matrix metalloproteinases, mucin genes, and gob-5 and stimulates and activates TGF-beta1 via IL-11Ralpha-dependent pathways. When viewed in combination, these studies demonstrate that IL-11Ralpha plays a key role in the pathogenesis of IL-13-induced inflammation and remodeling.
Thermodynamic Analysis of mRNA Cap Binding by the Human Initiation Factor eIF4E via Free Energy Perturbations (2009)

Eukaryotic mRNAs are appended at the 5' end, with the 7-methylguanosine cap linked by a 5'-5'-triphosphate bridge to the first transcribed nucleoside (m7GpppX). Initiation of cap-dependent translation of mRNA requires direct interaction between the cap structure and the eukaryotic translation initiation factor eIF4E. Biophysical studies of the association between eIF4E and various cap analogs have demonstrated that m(7)GTP binds to the protein ca. -5.0 kcal/mol more favorably than unmethylated GTP. In this work, a thermodynamic analysis of the binding process between eIF4E and several cap analogs has been conducted using Monte Carlo (MC) simulations in conjunction with free energy perturbation (FEP) calculations. To address the role of the 7-methyl group in the eIF4E/m7GpppX cap interaction, binding free energies have been computed for m(7)GTP, GTP, protonated GTP at N(7), the 7-methyldeazaguanosine 5'-triphosphate (m(7)DTP), and 7-deazaguanosine 5'-triphosphate (DTP) cap analogs. The MC/FEP simulations for the GTP-->m(7)DTP transformation demonstrate that half of the binding free energy gain of m(7)GTP with respect to GTP can be attributed to favorable van der Waals interactions with Trp166 and reduced desolvation penalty due to the N(7) methyl group. The methyl group both eliminates the desolvation penalty of the N(7) atom upon binding and creates a larger cavity within the solvent that further facilitates the desolvation step. Analysis of the pair m(7)GTP-m(7)DTP suggests that the remaining gain in affinity is related to the positive charge created on the guanine moiety due to the N(7) methylation. The charge provides favorable cation-pi interactions with Trp56 and Trp102 and decreases the negative molecular charge, which helps the transfer from the solvent, a more polar environment, to the protein.
What was lost in translation in the DHA trial is whom you should intend to treat (2011)

The results of a randomized double-blind placebocontrolled trial with docosahexaenoic acid (DHA) supplementation in mild to moderate Alzheimer's disease (AD) published by Quinn and colleagues in JAMA argues against overall efficacy of DHA in slowing progression. However, certain caveats in the results caution against discarding DHA altogether, raising questions about oxidation, dosage, pharmacogenomics and stage of intervention.One potential misconception is that what works for prevention will slow progression in AD subjects.Preclinical studies with DHA supported the rationale for early stage intervention; and three epidemiological studies indicated DHA intake was associated with reduced risk in non-apolipoprotein E4 (ApoE4) carriers. Putative drugs are initially tested for impact on progression because prevention approaches are problematic. However, should a drug be discarded for prevention if it fails to modify progression? Consistent with epidemiology, DHA significantly benefited two measures of cognition in mild to moderate non-ApoE4 carriers. Although the results of this trial were overall negative, failing to modify other outcomes, this commentary discusses important questions raised by them. Should future trials pursue DHA in non-ApoE4 carriers for slowing progression? Since in vivo oxidation of DHA may have adverse effects, particularly in ApoE4 patients, should preclinical and clinical studies be performed to optimize dose and mitigate oxidation before pursuing intervention or prevention trials with DHA? And finally, should DHA be tested now for mild cognitive impairment or prevention?
Photoacoustic Detection of Melanoma Micrometastasis in Sentinel Lymph Nodes (2009)

Melanoma is the deadliest form of skin cancer and has the fastest growth rate of all cancer types. Proper staging of melanoma is required for clinical management. One method of staging melanoma is performed by taking a sentinel node biopsy, in which the first node in the lymphatic drainage path of the primary lesion is removed and tested for the presence of melanoma cells. Current standard of care typically involves taking fewer than ten histologic sections of the node out of the hundreds of possible sections available in the tissue. We have developed a photoacoustic method that probes the entire intact node. We acquired a lymph node from a healthy canine subject. We cultured a malignant human melanoma cell line HS 936. Approximately 1 x 10(6) cells were separated and injected into the lymph node. We also had a healthy lymph node in which no melanoma cells were implanted. We used a tunable laser system set at 532 nm to irradiate the lymph nodes. Three piezoelectric acoustic detectors were positioned near the lymph node to detect photoacoustic pulses generated within the lymph nodes. We also acquired lymph nodes from pigs and repeated the experiments with increased amplification and improved sensors. We detected photoacoustic responses from a lymph node with as few as 500 melanoma cells injected into the tissue, while normal lymph nodes showed no response. Photoacoustic generation can be used to detect melanoma micrometastasis in sentinel lymph nodes. This detection can be used to guide further histologic study of the node, increasing the accuracy of the sentinel lymph node biopsy.