Miracle-dz/UniFAR-FTUs huggingface dataset:
T cells specific for HPV16 E7 epitopes in patients with squamous cell carcinoma of the oropharynx

Squamous cell carcinomas of the oropharynx (SCCO) are often infected with oncogenic human papilloma virus (HPV) subtype 16. To determine the frequency of T cells specific for human leukocyte antigen (HLA)‐A2.1 restricted HPV16 E7 protein‐derived epitopes, tetramer analysis was performed using peripheral blood lymphocytes of 20 HLA‐A2.1+ patients and 20 HLA‐A2.1+ healthy individuals. Tetramers specific for 3 HPV16 peptides (E711–20, E782–90 and E786–93), an influenza matrix peptide (a model recall antigen) or an HIV reverse transcriptase peptide (a model novel antigen) were used in multicolor flow analysis. The HPV‐specific T‐cell frequencies were correlated with the HPV16 E7 and p16 status in tumor sections. In vitro stimulation (IVS) with autologous dendritic cells (DC) pulsed with HPV16 E7 epitopes was performed to demonstrate proliferation and antitumor activity of the HPV‐responsive T cells. Frequencies of CD8+ T cells specific for HPV16 E7 peptides were not significantly different in patients with SCCO relative to normal donors. However, patients with tumors expressing HPV16 E7 (60%) and p16 (50%) had an increased frequency (p < 0.05) of T cells specific for the E711–20 epitope compared to those with tumors negative for both markers. HPV16 E711–20 and HPV16 E786–93 specific T cells were expandable upon IVS with cognate peptide‐pulsed DC and were reactive against peptide‐pulsed targets or, in case of the E711–20 epitope‐specific T cells, against HPV16 E7 expressing CaSki cell line. Thus, in patients with HPV16+ SCCO, precursor T cells specific for E711–20 epitope are present (1/3,947) in the circulation, are responsive to stimulation with the cognate viral peptide and recognize in vitro HPV16 E7+ tumor cells. Further studies have to elucidate why those T cells are unable to eliminate the tumor in vivo and this might also allow for finding potential strategies that will increase the chances of developing a future HPV‐based vaccine in patients with SCCO. © 2005 Wiley‐Liss, Inc.
Enhancement of DNaseI Salt Tolerance by Mimicking the Domain Structure of DNase from an Extremely Halotolerant Bacterium Thioalkalivibrio sp. K90mix

In our previous work we showed that DNaseI-like protein from an extremely halotolerant bacterium Thioalkalivibrio sp. K90mix retained its activity at salt concentrations as high as 4 M NaCl and the key factor allowing this was the C-terminal DNA-binding domain, which comprised two HhH (helix-hairpin-helix) motifs. The further investigations revealed that this domain originated from proteins related to bacterial competence ComEA/ComE proteins. It is likely that in the course of evolution the DNA-binding domain from these proteins was fused to a metallo-β-lactamase superfamily domain. Very likely such domain organization having proteins subsequently “donated” the DNA-binding domain to bacterial DNases. In this study we have mimicked this evolutionary step by fusing bovine DNaseI and DNA-binding domains. We have created two fusions: one harboring the DNA-binding domain of DNaseI-like protein from Thioalkalivibrio sp. K90mix and the second one harboring the DNA-binding domain of bacterial competence protein ComEA from Bacillus subtilis. Both domains enhanced salt tolerance of DNaseI, albeit to different extent. Molecular modeling revealed the essential differences between their interaction with DNA shedding some light on the differences in salt tolerance. In this study we have enhanced salt tolerance of bovine DNaseI; thus, we successfully mimicked the Nature’s evolutionary engineering that created the extremely halotolerant bacterial DNase. We have demonstrated that the newly engineered DNaseI variants can be successfully used in applications where activity of the wild type bovine DNaseI is impeded by buffers used.
Presynaptic T-Type Ca2+ Channels Modulate Dendrodendritic Mitral–Mitral and Mitral–Periglomerular Connections in Mouse Olfactory Bulb

Mitral cells express low-voltage activated Cav3.3 channels on their distal apical tuft dendrites (McKay et al., 2006; Johnston and Delaney, 2010). They also discharge Na+-dependent dendritic action potentials and release glutamate from these dendrites. Around resting membrane potentials, between −65 and −50 mV, Cav3.x channels are a primary determinant of cytoplasmic [Ca2+]. In this study using C57 mice, we present evidence that subthreshold Cav3.x-mediated Ca2+ influx modulates action potential evoked transmitter release and directly drives asynchronous release from distal tuft dendrites. Presynaptic hyperpolarization and selective block of Cav3.x channels with Z941 (Tringham et al., 2012) reduce mitral-to-mitral EPSP amplitude, increase the coefficient of variation of EPSPs, and increase paired-pulse ratios, consistent with a reduced probability of transmitter release. Both hyperpolarization and Cav3.x channel blockade reduce steady-state cytoplasmic [Ca2+] in the tuft dendrite without reducing action potential evoked Ca2+ influx, suggesting that background [Ca2+] modulates evoked release. We demonstrate that Cav3.x-mediated Ca2+ influx from even one mitral cell at membrane potentials between −65 and −50 mV is sufficient to produce feedback inhibition from periglomerular neurons. Deinactivation of Cav3.x channels by hyperpolarization increases T-type Ca2+ influx upon repolarization and increases feedback inhibition to produce subthreshold modulation of the mitral–periglomerular reciprocal circuit.
On the performance of cyclic moments-based parameter estimators of amplitude modulated polynomial phase signals

Parameter estimation of amplitude-modulated polynomial phase signals embedded in additive white Gaussian noise is considered. The amplitude modulation is modeled as the sum of a real-valued deterministic function and a zero mean correlated stationary random process. It is shown that cyclic moments-based estimators, previously proposed for parameter estimation of polynomial phase signals modulated by stationary random processes, can be adapted to the more general signal model considered here. The covariance matrices of the cyclic moments-based amplitude and phase parameter estimators are derived for large sample lengths. Using this result, it is shown how the lags can be chosen to minimize the large-sample variances of the cyclic moments-based phase parameter estimators. Comparisons with the Cramer-Rao bounds are performed under the assumption of a Gaussian modulating process. The theoretical derivations are confirmed by simulation results.
EZK: A Zero Knowledge Tool for Generating, Handling, and Securing Electronic Bills of Lading

EZK is a tool for generating, handling, and securing electronic bills of lading. EZK implements the cryptographic protocol suggested by Pagnoni and Visconti in (Pagnoni and Visconti, 2006), cryptographic protocol that is based on a shipper-carrier-holder model. This protocol makes use of (a) blind merchandise counts, or zero-knowledge counts, − that is, counts that do not reveal any information about the quantities actually counted, − (b) secure timestamps, and (c) digital signatures. We show how EZK generates and handles order e-BOLs and how the cryptographic techniques implemented in EZK make a number of common fraud schemes impossible.
of the Annual Meeting of the Cognitive Science Society Title Testing Descriptive or Prescriptive Conditionals and Differential Effects of Frequency Information Permalink

The author proposes and investigates different strategies for testing descriptive and prescriptive conditionals in Wason’s selection tasks. Two experiments examined the influence of frequency information on the postulated Bayesian and deontic test strategies. The rules in both the descriptive and the prescriptive case were social rules. The results of Experiment 1 showed only some of the predicted differences, and necessitated an extension of the advocated dichotomy. Based on this modification, Experiment 2 completely supported the predicted two types of test strategies. The discussion suggests a classification of different frequency effects that may be rational even for testing deontic rules.
Control architecture and operator interface for a free-flying robotic vehicle

Space and underwater vehicles with robotic arms can severely tax the capability of conventional control systems. Submersible vehicles used in neutral buoyancy simulation are subject to even greater demands since they must simulate the dynamics of spacecraft in orbit as well as function as a remotely-operated underwater vehicle. In this report, the onboard control architecture, human-machine interface, and vehicle/operator communications are described for one such vehicle in operation at the University of Maryland Neutral Buoyancy Research Facility (NBRF). The Ranger Neutral Buoyancy Vehicle (RNBV) exemplifies the high-dimensional, computationally intensive nature of the current fleet of autonomous underwater vehicles while its complement of four manipulators exceeds the capabilities of most remotely operated vehicles in service today. The sensor-based, embedded onboard control system is described, and its implementation using multiple control stations is discussed.
VIEWPOINT: COMMERCIAL SATELLITE IMAGERY AND THE CTBT VERIFICATION PROCESS

Dr. Vipin Gupta and Mr. Frank Pabian are Remote Sensing and Nonproliferation Specialists with experience in the monitoring and analysis of nuclear weapons related sites. Gupta is a senior member of the technical staff at Sandia National Laboratories. Pabian is presently an inspector at the UNSC 687 (Iraq) Action Team within the International Atomic Energy Agency. This report was supported with exploratory and program development funds at Sandia National Laboratories. The research was done in consultation with scientists working on Sandia’s DOE-funded CTBT R & D program. The analysis, views, and opinions expressed in this report are the authors’ alone. Satellite imagery has a long history of monitoring nuclear test activity. During the 1960s, the U.S. CORONA satellites were used to track Soviet and Chinese nuclear test programs. 1 In the 1970s, U.S. and Soviet intelligence satellites were reportedly used to observe South Africa’s clandestine preparations for an underground nuclear test in the Kalahari Desert. 2 More recently, commercial imaging satellites were used to monitor underground nuclear testing at the U.S., Russian, and Chinese test sites. 3 These satellites were also used to investigate the December 1995 allegations of Indian nuclear test preparations in the Rajasthan Desert. 4
Model for the retino-tectal projection

A model for the retino-tectal projection is proposed which assumes that axonal growth proceeds predominantly in the direction of maximal slope of a guiding substance (or, more generally, of a system parameter subsuming the effect of several substances). The spatial distribution of this parameter, in turn, results from the interaction of components of retinal axons (which are graded with respect to position of origin in the retina) and tectal components. One or two gradients in each dimension of retina and tectum suffice. Conditions for the generation of a reliable projection on this basis are relatively simple and consistent with conventional enzyme and receptor kinetics. Adhesive forces could but need not be involed in the guiding mechanism. The slope of guiding substances that interfere with an intracellular pattern-forming mechanism within the growth cone may determine the polarity of activation and thus the direction of growth. Generation of primary projections and some features of regulation such as independence of projections on neural pathways, and observations on the innervation of rotated pieces of tectum, can be explained on the basis of the model. The model can be extended by introducing additional production of guiding substance depending on the density, and duration of presence, of fibre terminals in the course of innervation. This simple mechanism would suffice for observed effects of compression and expansion of the map following ablation of retinal and tectal tissue, respectively. It may but need not be involved in the primary projection, too.
COLONOSCOPY COMPLICATIONS IN THE ELDERLY: the impact of age and multimorbidity

ContextAge has been considered an independent risk factor for colonoscopy complications, especially when associated with multimorbidity.ObjectivesThe primary objective was to verify the relationships between age, multimorbidity and colonoscopy complications in the elderly.MethodsA retrospective cohort including patients of 60 years or older who had undergone a colonoscopy. Data relating to age, multimorbidities according to the cumulative illness scale for geriatrics and the Charlson index and complications related to bowel preparation and procedure (sedation and exam) were collected.ResultsOf the 207 patients (mean age 70.47 ± 7.04) with appropriate indication for colonoscopy according to the American Society for Gastrointestinal Endoscopy, 43 (20.77%) patients had some colonoscopy complications: 1 (0.48%) with the sedation (apnea), 4 (1.93%) with the procedure (abdominal pain and bacteremia) and 38 (18.35%) with the bowel preparation (acute renal failure, hypotension). Individuals ≥80 years had an RR = 3.4 (1.2-10.1),P = 0.025, and those with a Charlson index 3 had an RR = 5.2 (1.6-16.8), P = 0.006, for complications. The cumulative illness rating scale for geriatrics was not associated with complications (P = 0.45). ConclusionThere was a significant risk of complications in ≥80 years and in the group with a Charlson index 3. The cumulative illness rating scale for geriatrics was not a good predictor of risk in this sample.
Granulocyte‐macrophage colony stimulating factor blockade promotes ccr9+ lymphocyte expansion in Nod2 deficient mice

Background: Ileal involvement in Crohn's disease (CD) is associated with NOD2 mutations and granulocyte‐macrophage colony stimulating factor autoantibodies (GM‐CSF Ab), and GM‐CSF blockade promotes ileitis in Nod2/Card15‐deficient (C15KO) mice. RALDH2‐expressing dendritic cells (DC) and IL‐4 promote CCR9 imprinting and small bowel homing of T lymphocytes, in conjunction with CCL25 expression by ileal epithelial cells (IEC). We hypothesized that GM‐CSF neutralization promotes ileal disease by modulating expression of CCL25 by IEC and CCR9 by T lymphocytes via Nod2‐dependent and independent pathways. Methods: CCL25 and CCR9 expression were determined in pediatric CD patients stratified by GM‐CSF Ab. Ileitis was induced in C15KO mice via GM‐CSF Ab administration followed by nonsteroidal antiinflammatory drug (NSAID) exposure, and expression of CCL25, CCR9, FOXP3, intracellular cytokines, and RALDH2 was determined in IEC and immune cell populations. Results: The frequency of CCL25+ IEC and CCR9+ T lymphocytes was increased in CD patients with elevated GM‐CSF Ab. In the murine model, GM‐CSF blockade alone induced IEC CCL25 expression, and reduced the frequency of mesenteric lymph node (MLN) CD4+FOXP3+ cells, while Card15 deficiency alone enhanced MLN DC RALDH2 expression. Both GM‐CSF neutralization and Card15 deficiency were required for downregulation of MLN DC IL‐10 expression; under these conditions NSAID exposure led to an expansion of IL‐4+ and IL‐17+ CCR9+ lymphocytes in the ileum. Conclusions: GM‐CSF prevents ileal expansion of CCR9+ lymphocytes via Nod2‐dependent and independent pathways. CCR9 blockade may be beneficial in CD patients with elevated GM‐CSF Ab.
Surfel Set Simplification With Optimized Feature Preservation

In this paper, we propose a novel scheme for simplifying a surfel set with the resultant surfels computed and distributed to preserve prominent geometric and textural features. It works by iteratively collapsing local neighborhoods around surfels until a given data reduction ratio is reached. For optimized feature preservation, novel techniques are proposed in various steps of the scheme. The local neighborhood collapses are prioritized according to a cost metric that takes into account the local complexities of both the geometric and the textural information. Methods for surfel attribute computation are proposed for faithful representation of geometric and textural features in the simplified model. The proposed algorithm is further extended to support out-of-core simplification for large models by optimally determining the reduction ratios for different parts of the model in consideration of the surface features. Experimental results demonstrate the outstanding performance of the proposed scheme.
2,3,7,8-Tetrachlorodibenzo-P-Dioxin (TCDD) or Diethylstilbestrol (DES) Cause Similar Hematopoietic Hypocellularity and Hepatocellular Changes in Murine Fetal Liver, but Differentially Affect Gene Expression

TCDD and DES have immunotoxic effects, including selective diminution of T lymphocyte progenitors in the fetal liver. The histologic presentation of fetal liver after exposure to either chemical has not been described. Similarly, limited information exists regarding mechanisms by which TCDD or DES may alter fetal hematopoiesis. Treatment of pregnant C57BL/6 mice with either 10 μg/kg/day TCDD or 48 μg/kg/day DES on gestation days (gd) 14 and 16 led to increased fetal liver weight on gd 18. Moderate anisocytosis and anisokaryosis with increased cytoplasmic and nuclear sizes, and increased cytoplasmic basophilia were present within hepatocytes after TCDD or DES. Both chemicals also decreased the presence of hematopoietic cells, however megakaryocyte numbers were unaffected. In contrast to these similar outcomes, real time quantitative PCR using a preliminary panel of 4 genes suggested that the chemicals act through different gene targets. TCDD increased c-jun gene expression in fetal liver, and decreased p53 without alteration in bcl-2 expression, indicating possible pro-proliferative and antiapoptotic effects. DES decreased c-jun and bcl-2, without altering p53, suggesting a shift away from proliferation. Both agents decreased PKCα expression, which may suggest shared decreased phosphorylation of substrates required for normal cell cycle progression.
A step in the right direction: Assessing exercise tolerance in cystic fibrosis

Exercise tolerance may be reduced in patients with cystic fibrosis, but it is not always possible to predict this from standard lung function measurements. Formal exercise testing may, therefore, be necessary, and the test should be simple and readily available. We have developed a “3‐minute step test” and compared it with the standard 6‐minute walking test. Subjects stepped up and down a 15‐cm‐high single step at a rate of 30 steps per minute for 3 minutes. The effect of the step test on spirometry was tested first in 31 children with CF (mean age, 12.0 years), who had a mean (range) baseline forced expired volume in 1 second (FEV1) of 64% (18–94%) of predicted values. The step test was then compared with the standard 6‐minute walk in a further 54 patients with cystic fibrosis (mean age, 12.5 years), with mean (range) baseline FEV1 of 61% (14–103%) of predicted values. Outcome measures were minimum arterial oxygen saturation (SaO2), maximum pulse rate, and the modified Borg dyspnea score.
Policy, Systems, and Environmental Change in the Mississippi Delta

Community-level policy, systems, and environmental (PSE) change strategies may offer an economical and sustainable approach to chronic disease prevention. The rapidly growing number of untested but promising PSE strategies currently underway offers an exciting opportunity to establish practice-based evidence for this approach. This article presents lessons learned from an evaluation of a community-based PSE initiative targeting stroke and cardiovascular disease prevention in the Mississippi Delta. Its purpose is to describe one approach to evaluating this type of PSE initiative, to stimulate discussion about best practices for evaluating PSE strategies, and to inform future evaluation and research efforts to expand practice-based evidence. The evaluation used a descriptive mixed-methods design and focused on the second year of a multisectoral, multiyear initiative. Cross-sectional data were collected in the summer and fall of 2010 using four data collection instruments: a grantee interview guide (n = 32), a health council member survey (n = 256), an organizational survey (n = 60), and a grantee progress report (n = 26). Fifty-eight PSE changes were assessed across five sectors: health, faith, education, worksite, and community/city government. PSE strategies aligned with increased access to physical activity opportunities, healthy food and beverage options, quality health care, and reduced exposure to tobacco. Results showed that grantees were successful in completing a series of steps toward PSE change and that sector-specific initiatives resulted in a range of PSE changes that were completed or in progress. Considerations for designing evaluations of community-based PSE initiatives are discussed.
Selection of Glutamate-Rich Protein Long Synthetic Peptides for Vaccine Development: Antigenicity and Relationship with Clinical Protection and Immunogenicity

ABSTRACT Antibodies against three long synthetic peptides (LSPs) derived from the glutamate-rich protein (GLURP) of Plasmodium falciparum were analyzed in three cohorts from Liberia, Ghana, and Senegal. Two overlapping LSPs, LR67 and LR68, are derived from the relatively conserved N-terminal nonrepeat region (R0), and the third, LR70, is derived from the R2 repeat region. A high prevalence of antibody responses to each LSP was observed in all three areas of endemic infection. Levels of cytophilic immunoglobulin G (IgG) antibodies against both GLURP regions were significantly correlated with protection from clinical P. falciparum malaria. Protected children from the Ghana cohort possessed predominantly IgG1 antibodies against the nonrepeat epitope and IgG3 antibodies against the repeat epitope. T-cell proliferation responses, studied in the cohort from Senegal, revealed that T-helper-cell epitopes were confined to the nonrepeat region. When used as immunogens, the LR67 and LR68 peptides elicited strong IgG responses in outbred mice and LR67 also induced antibodies in mice of different H-2haplotypes, confirming the presence of T-helper-cell epitopes in these constructs. Mouse antipeptide antisera recognized parasite proteins as determined by immunofluorescence and immunoblotting. This indicates that synthetic peptides derived from relatively conserved epitopes of GLURP might serve as useful immunogens for vaccination against P. falciparum malaria.