Miracle-dz/UniFAR-FTUs huggingface dataset:
Partially Phosphorylated T Cell Receptor ζ Molecules Can Inhibit T Cell Activation

The T cell receptor complex (TCR) ζ chain is constitutively tyrosine phosphorylated specifically at two of the six ζ immunoreceptor tyrosine-based activation motif (ITAM) tyrosine residues in resting peripheral T cells. Further phosphorylation of ζ is induced by both agonist and antagonist ligands of the TCR, with agonists inducing complete phosphorylation of the ζ ITAM tyrosines. After antagonist stimulation, ζ phosphorylation is incomplete and generates discrete forms of partially phosphorylated ITAMs. Here, we mutate specific tyrosines in chimeric human CD8-ζ molecules to reflect phosphorylation in resting T cells as well as phosphorylation induced by agonist and antagonist ligands. We demonstrate that such partially phosphorylated TCR-ζ species can inhibit IL-2 production in T cell hybridomas and proliferation in T cell clones. This reveals a previously unrecognized, inhibitory function of partially phosphorylated ITAMs. These findings support the concept that TCR antagonism can arise through the generation of an inhibitory signal within the TCR complex and that constitutive ζ phosphorylation in resting T cells is an inhibitory signaling environment.
Contractile Dysfunction Irrespective of the Mutant Protein in Human Hypertrophic Cardiomyopathy With Normal Systolic Function

Background— Hypertrophic cardiomyopathy (HCM), typically characterized by asymmetrical left ventricular hypertrophy, frequently is caused by mutations in sarcomeric proteins. We studied if changes in sarcomeric properties in HCM depend on the underlying protein mutation. Methods and Results— Comparisons were made between cardiac samples from patients carrying a MYBPC3 mutation (MYBPC3mut; n=17), mutation negative HCM patients without an identified sarcomere mutation (HCMmn; n=11), and nonfailing donors (n=12). All patients had normal systolic function, but impaired diastolic function. Protein expression of myosin binding protein C (cMyBP-C) was significantly lower in MYBPC3mut by 33±5%, and similar in HCMmn compared with donor. cMyBP-C phosphorylation in MYBPC3mut was similar to donor, whereas it was significantly lower in HCMmn. Troponin I phosphorylation was lower in both patient groups compared with donor. Force measurements in single permeabilized cardiomyocytes demonstrated comparable sarcomeric dysfunction in both patient groups characterized by lower maximal force generating capacity in MYBPC3mut and HCMmn, compared with donor (26.4±2.9, 28.0±3.7, and 37.2±2.3 kN/m2, respectively), and higher myofilament Ca2+-sensitivity (EC50=2.5±0.2, 2.4±0.2, and 3.0±0.2 &mgr;mol/L, respectively). The sarcomere length-dependent increase in Ca2+-sensitivity was significantly smaller in both patient groups compared with donor (&Dgr;EC50: 0.46±0.04, 0.37±0.05, and 0.75±0.07 &mgr;mol/L, respectively). Protein kinase A treatment restored myofilament Ca2+-sensitivity and length-dependent activation in both patient groups to donor values. Conclusions— Changes in sarcomere function reflect the clinical HCM phenotype rather than the specific MYBPC3 mutation. Hypocontractile sarcomeres are a common deficit in human HCM with normal systolic left ventricular function and may contribute to HCM disease progression.
Health-Related Quality of Life in Children With Autoimmune Liver Disease

Background and Aim: Health-related quality of life (HRQOL), a pivotal outcome indicator of health care interventions, has not been evaluated in children with autoimmune liver disease (AILD). The aim of this study was to determine HRQOL in children with AILD and the factors affecting it. Methods: The Pediatric Quality Of Life Inventory, generic core scale, was used to collect HRQOL data on children with AILD. Specific liver disease–related questions were added. Results: Survey responses were received from 30 of 40 patients. Patients’ mean age at diagnosis was 11.6 ± 4.5 years, with M:F ratio of 1:1.3, and AILD for average of 4.6 ± 4.3 years. Seventy-three percent of patients had advanced liver disease. Mean overall health summary scores for the group per child and parent reports were 71.6 ± 19.0 and 71.3 ± 17.1, respectively, which were lower than healthy controls: 83.9 ± 12.5 and 82.3 ± 15.6 (P = 0.002). Frequent liver-related symptoms were associated with impaired physical and school functioning by child (P = 0.034 and 0.047) and parent reports (P = 0.051 and P = 0.018). Abdominal pain, fatigue, and psychological symptoms were found to adversely affect the HRQOL. Although it was difficult to estimate the effect of individual features of advanced liver disease such as cirrhosis, history of upper gastrointestinal bleed, and portal hypertension on the HRQOL, because of a relatively small sample size, the presence of ascites revealed lower social functioning score per parent report (P = 0.036). In an analysis of patients with any of the above complications versus those without, however, children reported lower social functioning scores (P = 0.018). There were no differences in HRQOL scores in children with autoimmune hepatitis versus primary sclerosing cholangitis versus autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome. Conclusions: First study to date shows that AILD in children significantly affects HRQOL, especially with frequent liver disease–related symptoms, even in early stages of disease. Findings need to be validated in larger, multicenter studies and will help practitioners understand their patients better and optimize care.
Context-Aware Gaussian Fields for Non-rigid Point Set Registration

Point set registration (PSR) is a fundamental problem in computer vision and pattern recognition, and it has been successfully applied to many applications. Although widely used, existing PSR methods cannot align point sets robustly under degradations, such as deformation, noise, occlusion, outlier, rotation, and multi-view changes. This paper proposes context-aware Gaussian fields (CA-LapGF) for nonrigid PSR subject to global rigid and local non-rigid geometric constraints, where a laplacian regularized term is added to preserve the intrinsic geometry of the transformed set. CA-LapGF uses a robust objective function and the quasi-Newton algorithm to estimate the likely correspondences, and the non-rigid transformation parameters between two point sets iteratively. The CA-LapGF can estimate non-rigid transformations, which are mapped to reproducing kernel Hilbert spaces, accurately and robustly in the presence of degradations. Experimental results on synthetic and real images reveal that how CA-LapGF outperforms state-of-the-art algorithms for non-rigid PSR.
Precise Sequential DNA Ligation on A Solid Substrate: Solid-Based Rapid Sequential Ligation of Multiple DNA Molecules

Ligation, the joining of DNA fragments, is a fundamental procedure in molecular cloning and is indispensable to the production of genetically modified organisms that can be used for basic research, the applied biosciences, or both. Given that many genes cooperate in various pathways, incorporating multiple gene cassettes in tandem in a transgenic DNA construct for the purpose of genetic modification is often necessary when generating organisms that produce multiple foreign gene products. Here, we describe a novel method, designated PRESSO (precise sequential DNA ligation on a solid substrate), for the tandem ligation of multiple DNA fragments. We amplified donor DNA fragments with non-palindromic ends, and ligated the fragment to acceptor DNA fragments on solid beads. After the final donor DNA fragments, which included vector sequences, were joined to the construct that contained the array of fragments, the ligation product (the construct) was thereby released from the beads via digestion with a rare-cut meganuclease; the freed linear construct was circularized via an intra-molecular ligation. PRESSO allowed us to rapidly and efficiently join multiple genes in an optimized order and orientation. This method can overcome many technical challenges in functional genomics during the post-sequencing generation.
PRESBURGER ARITHMETIC, RATIONAL GENERATING FUNCTIONS, AND QUASI-POLYNOMIALS

Abstract Presburger arithmetic is the first-order theory of the natural numbers with addition (but no multiplication). We characterize sets that can be defined by a Presburger formula as exactly the sets whose characteristic functions can be represented by rational generating functions; a geometric characterization of such sets is also given. In addition, if p = (p1, . . . , pn) are a subset of the free variables in a Presburger formula, we can define a counting function g(p) to be the number of solutions to the formula, for a given p. We show that every counting function obtained in this way may be represented as, equivalently, either a piecewise quasi-polynomial or a rational generating function. Finally, we translate known computational complexity results into this setting and discuss open directions.
Impulse conduction in multiple sclerosis: a theoretical basis for modification by temperature and pharmacological agents

The simplest model for explaining conduction defects in multiple sclerosis (MS) and other demyelinating diseases assumes that the only abnormality present is loss of myelin. The consequences of such an assumption have been investigated by numerical solution of a well-known set of differential equations describing conduction in a model demyelinated axon. In agreement with clinical findings, we show that this model predicts that the temperature at which conduction block occurs is a steep function of the extent of demyelination, so that small temperature increases may block large numbers of conducting fibres. Decreasing calcium concentration (or increasing pH) is calculated markedly to improve the conduction velocity of conducting demyelinated fibres and will, in addition, restore conduction in blocked fibres. The effects of other pharmacological agents have also been computed. The presence of a demyelinating lesion in a nerve fibre is shown greatly to impair the ability of the fibre to conduct repetitive impulses, conduction failing at much lower frequencies than in normal fibres. These calculations provide some insight into the nature of conduction defects in demyelinated nerve, demonstrate that many clinical features of MS are the expected consequence of loss of myelin and do not require the presence of other defects for their explanation, and provide a useful approach to the search for a symptomatic therapy.
Endometrial cancer patients have a significant risk of harboring isolated tumor cells in histologically negative lymph nodes

In this study, we examine the prevalence of finding isolated tumor cells (ITCs) in negative lymph nodes of endometrial cancer patients using immunohistochemistry. Seventy-six endometrial cancer patients with lymph nodes histologically negative for metastatic disease were examined. Nodal tissue sections were stained with anticytokeratin antibodies AE-1 and CAM 5.2. Nodes with single or groups of cells (two to four cells) ≤0.2 mm and showing cytokeratin reactivity were positive for ITCs. Findings were compared to features of the primary tumor and patient outcome. ITCs were present in 31 of 1712 lymph nodes. Fifteen (19.7%) patients had ITC-positive nodes. ITCs involved only pelvic nodes in nine cases, only para-aortic nodes in five cases, and pelvic and para-aortic in one case. Tumor in adnexa was the only pathologic feature associated with nodal ITCs (P = 0.0485). All 15 patients with nodal ITCs were alive at follow-up. One (6.7%) patient suffered recurrent disease but was alive at last encounter. Disease recurred in 5 (8.8%) of 57 patients without nodal ITCs. Two are alive without disease, two alive with disease, and one died from her cancer. In summary, a significant proportion of endometrial cancer patients have ITCs detected by immunohistochemistry in histologically negative regional lymph nodes.
Mechanical Behavior of Nanocrystalline Materials and Application of Shear Punch Test

Guduru, Ramesh Kumar. Mechanical Behavior of Nanocrystalline Materials and Application of Shear Punch Test. (Under the direction of Prof. Ronald O. Scattergood) Nanocrystalline (nc) materials show superior strength compared to conventional grain size materials. Synthesizing bulk nc materials often results in small quantities, which limits making large scale specimens for conventional testing such as tensile, compression etc. In such instances, miniaturized specimen test techniques are very useful. The intent of the present work was to study the mechanical behavior of nc materials and also to develop a miniaturized specimen testing procedure -“shear punch test (SPT)” for nc material testing. A new setup for SPT was built and the testing procedure was standardized using different conventional metals. A linear correlation between SPT measurements and tensile data was established. The effect of test setup parameters such as specimen thickness and the die-punch clearance was studied in order to rationalize the technique. Using Finite Element Analysis, SPT was modeled and the physical basis of through-thickness plastic zone development at shear yield measurements was examined. The deformation behavior and the state of stress at different stages of the punching operation during an SPT test were studied. In order to understand the mechanical behavior of various materials from conventional to amorphous through nano regime, studies were done on investigating the mechanical properties of a Zr – based amorphous alloy (BMG – 11 alloy) using SPT. Strain rate dependent deformation behavior was studied and at high strain rates reduced strength was attributed to thermal softening. In order to examine the applicability of SPT for testing of nc materials, initial experiments were carried out on electrodeposited nc Cu. The SPT and mini tensile experiments were conducted and compared. An attempt was made to examine the strain rate effect. The SPT technique was extended to measure the strain rate sensitivity and the activation volumes and compared with the isostrain rate tensile test measurements. The nc materials pure Fe, Fe-Pb alloys and Fe-Al2O3 composites were processed using high energy ball milling technique and were characterized by means of X-ray diffraction, transmission electron microscopy, scanning electron microscopy and differential scanning calorimetry. The mechanical properties were evaluated using the nanoindentation technique. Solid solution strengthening of Fe-Pb system was studied. Enhanced strengthening of Fe-Al2O3 composites was attributed to the refined Fe grain size. Mechanical Behavior of Nanocrystalline Materials and Application of Shear Punch Test by RAMESH KUMAR GUDURU A dissertation submitted to the Graduate Faculty of North Carolina State University in partial fulfillment of the requirements for the Degree of Doctor of Philosophy MATERIALS SCIENCE AND ENGINEERING Raleigh, NC, USA. 2006
The Slow Axonal Transport of the Microtubule-Associated Protein Tau and the Transport Rates of Different Isoforms and Mutants in Cultured Neurons

We demonstrate that the microtubule-associated protein tau, in the form of enhanced green fluorescent protein (EGFP) tau, is transported along axons of neurons in culture in the slow component of axonal transport with a speed comparable with that previously measuredin vivo. It was demonstrated that the EGFP tag has no effect on transport characteristics, and the methodology enables slow transport rates of individual tau isoforms and tau mutants to be measured. We also expressed EGFP-tagged tau isoforms containing either three or four C-terminal repeats and zero or two N-terminal inserts in cultured neurons. No significant differences were found in the average rate of slow transport of the wild-type tau isoforms, suggesting that the exon 10 C-terminal repeat or the N-terminal inserts do not contain regions that play a significant regulatory role in axonal transport. Similarly, we found that missense mutations in tau have no noticeable effect on the rate of transport; hence their ability to cause neurodegeneration is by another mechanism other than that affecting the overall slow axonal transport of tau.
Associated factors of overweight in adolescents from public schools in Northern Minas Gerais State, Brazil

OBJECTIVE: In order to support plans and actions that combat the local increasing overweight and obesity prevalence in adolescents, the factors associated to weight excess in public school students from Montes Claros, MG, Southeast Brazil, were studied. METHODS: Cross-sectional study with a sample of adolescents from the public schools of the city. The nutritional status was evaluated and an inquiry was carried out in the schools to determine food consumption and practice of physical activities. Factors associated to weight excess were assessed by bivariate analysis followed by logistic regression. RESULTS: Weight excess prevalence was detected in 18.5% of the 535 adolescents evaluated. The factors associated to weight excess were: per capita income above half minimum wage (OR 1.99; 95%CI 1.01-3.93), candy consumption above two daily portions (OR 1.94; 95%CI 1.13-3.32) and absence of sport activity during leisure time (OR 2.54; 95%CI 1.15-5.59). CONCLUSIONS: The proportion of weight excess in adolescents from public schools is relevant and associated with socioeconomic condition of the family, bad eating habits and sedentary life.
Teaching basic skills to children with Down syndrome and developmental delays: the relative efficacy of interactive modeling with social rewards for benchmark achievements and passive observation.

In interventions attempting to remediate deficiencies in the skills repertoire of developmentally delayed children, no less than in medical interventions, it may be fairly said that less is more. That is, the instructor should intervene as little as possible both from the perspective of efficient instructional practice and from time allotment concerns which modern classrooms face. Evidence from this laboratory has indicated that in skills training for children with severe developmental delays the passive observation of a model demonstrating the target skill is more effective than interactive modeling involving hand-over-hand instruction with verbal prompting. We have considered the role of verbal prompting in interactive modeling and have found that prompts intended to provide typical social reinforcers are counterproductive (e.g., Biederman, Davey, Ryder, & Franchi, 1994). The present study examines the efficacy of hand-over-hand modeling with response-contingent verbal prompts. In such instruction, tasks are divided into identifiable sequential components, and the achievement of each component is marked by the delivery of some form of verbal prompt. In a within-subjects design, children were trained in one skill with response-contingent verbal prompts and in a second skill with simple passive observation. A separate group of children were trained with less rigorous verbal prompting in one skill and with passive observation in a second. Consistent with previous research, we found that passive modeling was overall significantly more effective than hand-over-hand modeling and moreover that passive modeling was significantly more effective than hand-over-hand modeling with response-contingent prompting. Our evidence therefore indicates that current classroom practice in training basic skills to children with severe developmental delays may require reassessment in that simple observation of modeled skills appears to be more effective than more labor-intensive instruction.
Repetitive Immunization Breaks Tolerance to Type XVII Collagen and Leads to Bullous Pemphigoid in Mice

Bullous pemphigoid (BP) is a subepidermal autoimmune blistering disease of the elderly associated with considerable morbidity and mortality. As unspecific immunosuppressants are still the mainstay of BP therapy, several animal models, based on the passive transfer of autoantibodies or immune cells, have been developed to obtain a better understanding of the pathogenesis of BP and evaluate novel therapeutic interventions. We describe in this study an experimental model inducing BP by immunization of immunocompetent mice with a recombinant form of the immunodominant 15th noncollagenous domain of murine BP180 (type XVII collagen). The homologous noncollagenous 16A domain of human BP180 has previously been identified as an immunodominant region in human BP. Immunization of female SJL/J mice with the murine peptide led to clinical disease within 14 wk in 56% of mice. In contrast, none of the other strains developed blisters despite the presence of autoantibodies. The clinical disease manifested for at least 8 wk without further manipulation. This novel immunization-induced model reflects key immunopathological characteristics of human BP, including binding of complement-fixing autoantibodies along the dermal–epidermal junction, elevated total IgE serum levels, and infiltration of skin lesions with eosinophilic granulocytes. The use of immunocompetent mice and the induction of sustained clinical disease not requiring additional interventions make this immunization-induced mouse model most suitable to further explore the pathogenesis of BP and novel therapeutic interventions for this and other autoantibody-mediated diseases.
A non-local formulation of rotational water waves

Abstract The classical equations of irrotational water waves have recently been reformulated as a system of two equations, one of which is an explicit non-local equation for the wave height and for the velocity potential evaluated on the free surface. Here, in the two-dimensional case: (a) we generalize the relevant formulation to the case of constant vorticity, as well as to the case where the free surface is described by a multivalued function; (b) in the case of travelling waves we derive an upper bound for the free surface; (c) in the case of constant vorticity we construct a sequence of nearly Hamiltonian systems which provide an approximation in the asymptotic limit of certain physical small parameters. In particular, the explicit dependence of the vorticity on the coefficients of the Korteweg–de Vries equation is clarified.
Quality of breast cancer care: perception versus practice.

PURPOSE Because insurers use performance and quality metrics to inform reimbursement, identifying remediable causes of poor-quality cancer care is imperative. We undertook this descriptive cohort study to assess key predictors of women's perceived quality of their breast cancer care and actual guideline-concordant quality of care received. PATIENTS AND METHODS We surveyed inner-city women with newly diagnosed and surgically treated early-stage breast cancer requiring adjuvant treatment who were enrolled onto a randomized controlled trial (RCT) of patient assistance to reduce disparities in care. We assessed women's perceived quality of care and perceived quality of the process of getting care, such as getting referrals, test results, and treatments; we abstracted records to determine the actual quality of care. RESULTS Of the 374 new patients with early-stage breast cancer enrolled onto the RCT, only a slight majority of women (55%) perceived their quality of care as excellent; 88% actually received good-quality, guideline-concordant care. Excellent perceived quality (P < .001) was significantly associated with patients' perception of the quality of the process of getting care (adjusted relative risk [RR], 1.78; 95% CI, 1.65 to 1.87). Also associated with perceived quality-and mediated by race-were trust in one's physician (adjusted RR, 1.43; 95% CI, 1.16 to 1.64) and perceived racism, which affected black women more than women of other races/ethnicities (black race-adjusted RR for perceived racism, 0.33 [95% CI, 0.10 to 0.87]; black race-adjusted RR for trust, 1.61 [95% CI, 0.97 to 1.90]; c = 0.82 for the model; P < .001). Actual quality of care provided did not affect perceived quality of care received. CONCLUSION Patients' perceived quality of care differs from their receipt of high-quality care. Mutable targets to improve perceived quality of care include the processes of getting care and trusting their physician.