Miracle-dz/UniFAR-FTUs huggingface dataset:
Accelerated atherosclerosis in patients with Wegener’s granulomatosis

Background: Several autoimmune disorders are complicated by excess cardiovascular disease. In addition to traditional risk factors, non-traditional risk factors such as endothelial activation and excessive vascular remodelling might be determinants of the progression of atherosclerosis in patients with an autoimmune disease. Objective: To evaluate whether patients with Wegener’s granulomatosis (WG) have an increased prevalence of atherosclerosis and to determine predisposing factors. Methods: 29 WG patients (19 men; mean (SD) age, 53 (14) years) with inactive disease and 26 controls (16 men; age 53 (15) years) were studied. Common carotid intima–media thickness (IMT) was measured by ultrasound. In all individuals traditional risk factors for cardiovascular disease were determined. High sensitivity C reactive protein (hsCRP) was measured. Endothelial activation was assessed by measuring thrombomodulin, vascular cell adhesion molecule-1, and von Willebrand factor. As a marker of vascular remodelling matrix metalloproteinases (MMP-3 and MMP-9) and TIMP-1 were measured. Results: IMT was increased in WG patients compared with controls (p<0.05). No differences in traditional risk factors and endothelial activation markers between patients and controls were found. Levels of hsCRP, MMPs, and TIMP-1 were increased in WG patients (p<0.05). Conclusions: Increased IMT found in WG patients cannot be explained by an increased prevalence of traditional risk factors. Although endothelial activation markers in WG patients with inactive disease were not increased, the raised levels of hsCRP, MMPs, and TIMP-1 suggest that enhanced inflammation and excessive vascular remodelling are contributing factors in the development of accelerated atherosclerosis in WG.
Inhibiting macrophage proliferation suppresses atherosclerotic plaque inflammation

Nanoparticle-based delivery of simvastatin inhibits plaque macrophage proliferation in apolipoprotein E–deficient mice. Inflammation drives atherosclerotic plaque progression and rupture, and is a compelling therapeutic target. Consequently, attenuating inflammation by reducing local macrophage accumulation is an appealing approach. This can potentially be accomplished by either blocking blood monocyte recruitment to the plaque or increasing macrophage apoptosis and emigration. Because macrophage proliferation was recently shown to dominate macrophage accumulation in advanced plaques, locally inhibiting macrophage proliferation may reduce plaque inflammation and produce long-term therapeutic benefits. To test this hypothesis, we used nanoparticle-based delivery of simvastatin to inhibit plaque macrophage proliferation in apolipoprotein E–deficient mice (Apoe−/−) with advanced atherosclerotic plaques. This resulted in the rapid reduction of plaque inflammation and favorable phenotype remodeling. We then combined this short-term nanoparticle intervention with an 8-week oral statin treatment, and this regimen rapidly reduced and continuously suppressed plaque inflammation. Our results demonstrate that pharmacologically inhibiting local macrophage proliferation can effectively treat inflammation in atherosclerosis.
Genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2) and risk of non-Hodgkin lymphoma

Animal studies suggest that lymphomagenesis can be induced by exposure to carcinogenic aromatic and heterocyclic amines found in diet, cigarette smoke and the environment, but human epidemiologic investigations of these exogenous exposures have yielded conflicting results. As part of our evaluation of the role of aromatic and heterocyclic amines, which are metabolized by N-acetyltransferase (NAT) enzymes, in the etiology of non-Hodgkin lymphoma (NHL), we examined NHL risk in relation to genetic variation in NAT1 and NAT2 and exposure to cigarette smoke and dietary heterocyclic amines and mutagens. We genotyped 10 common single nucleotide polymorphisms (SNPs) in NAT1 and NAT2 among 1136 cases and 922 controls from a population-based case–control study in four geographical areas of the USA. Relative risk of NHL for NAT1 and NAT2 genotypes, NAT2 acetylation phenotype, and exposure to cigarette smoke and dietary heterocyclic amines and mutagens was estimated using odds ratios (ORs) and 95% confidence intervals (CIs) derived from unconditional logistic regression models. We observed increased risk of NHL among individuals with the NAT1*10/*10 genotype compared with individuals with other NAT1 genotypes (OR=1.60, 95% CI=1.04–2.46, P=0.03). We also observed increased NHL risk in a dose-dependent model among NAT2 intermediate- and rapid-acetylators compared with slow-acetylators, although only the trend was statistically significant (intermediate: OR=1.18, 95% CI=0.97–1.44, P=0.1; rapid: OR=1.43, 95% CI=0.97–2.14, P=0.07; P for linear trend =0.03). Compared with non-smokers, NHL risk estimates for current cigarette smoking were increased only among NAT2 intermediate/rapid-acetylators (OR=2.44, 95% CI=1.15–5.20, P=0.02). Our data provide evidence that NAT1 and NAT2 genotypes are associated with NHL risk and support a contributory role for carcinogenic aromatic and/or heterocyclic amines in the multi-factorial etiology of NHL.
Cooperative effects between two acyclovir resistance loci in herpes simplex virus

The acyclovir-resistant mutant SC16 R9C2 (H.J. Field, G. Darby, and P. Wildy , J. Gen. Virol. 49:115-124, 1980) has been shown to contain two resistance loci which segregate independently on recombination with wild-type virus. One locus is in thymidine kinase, and the other is in DNA polymerase. Both induced enzymes have altered properties, thymidine kinase showing a low affinity for acyclovir and low activity, and DNA polymerase showing a low affinity for acyclovir triphosphate. Other properties of both enzymes are described which distinguish them from their wild-type counterparts. Recombinants containing either mutant thymidine kinase ( RSC -11) or mutant DNA polymerase ( RSC -26), but not both, have been used to investigate the relative contribution of each lesion to resistance and pathogenicity. Although SC16 R9C2 and both recombinants grow as well as does wild-type virus in tissue culture, they are considerably attenuated in vivo, the greatest attenuation of virulence being seen with SC16 R9C2 and RSC -26. With respect to both acyclovir resistance and in vivo growth, the lesions appear to behave synergistically. Cross resistance studies have shown the recombinant RSC -26, which contains mutant DNA polymerase but which evidently expresses wild-type thymidine kinase, to be cross resistant to both 5-iodo-2'-deoxyuridine and 5-trifluoromethyl-2'-deoxyuridine but not to (E)-5-(2-bromovinyl)-2'-deoxyuridine or 9-beta-D-arabinofuranosyladenine.
Atp6v1c1 May Regulate Filament Actin Arrangement in Breast Cancer Cells

Previous studies have shown that the rate of breast cancer metastasis correlates with the expression of vacuolar H+-ATPases (V-ATPases). However, how V-ATPase is involved in breast cancer metastasis remains unknown. Our previous study showed that Atp6v1c1-depleted osteoclasts did not form organized actin rings and that Atp6v1c1 co-localizes with F-actin. In this study, we found that the normal arrangement of filamentous actin is disrupted in Atp6v1c1-depleted 4T1 mouse breast cancer cells and in the ATP6V1C1-depleted human breast cancer cell lines MDA-MB-231 and MDA-MB-435s. We further found that Atp6v1c1 co-localizes with F-actin in 4T1 cells. The results of our study suggest that high expression of Atp6v1c1 affects the actin structure of cancer cells such that it facilitates breast cancer metastasis. The findings also indicate that Atp6v1c1 could be a novel target for breast cancer metastasis therapy.
Association of telomere length of peripheral blood leukocytes with hematopoietic relapse, malignant transformation, and survival in severe aplastic anemia.

CONTEXT Critically short telomeres produce apoptosis, cell senescence, and chromosomal instability in tissue culture and animal models. Variations in telomere length have been reported in severe aplastic anemia but their clinical significance is unknown. OBJECTIVE To investigate the relationship between telomere length and clinical outcomes in severe aplastic anemia. DESIGN, SETTING, AND PATIENTS Single institution analysis of 183 patients with severe aplastic anemia who were treated in sequential prospective protocols at the National Institutes of Health from 2000 to 2008. The pretreatment leukocyte age-adjusted telomere length of patients with severe aplastic anemia consecutively enrolled in immunosuppression protocols with antithymocyte globulin plus cyclosporine for correlation with clinical outcomes were analyzed. MAIN OUTCOME MEASURES Hematologic response, relapse, clonal evolution, and survival. RESULTS There was no relationship between hematologic response and telomere length with response rates of 56.5% of 46 patients in the first, 54.3% of 46 in the second, 60% of 45 in the third, and 56.5% of 46 in the fourth quartiles. Multivariate analysis demonstrated that telomere length was associated with relapse, clonal evolution, and mortality. Evaluated as a continuous variable, telomere length inversely correlated with the probability of hematologic relapse (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.03-0.69; P = .01). The probability of clonal evolution was higher in patients in the first quartile (24.5%; 95% CI, 8.7%-37.5%) than in quartiles 2 through 4 (8.4%; 95% CI, 3.2%-13.3%; P = .009), and evolution to monosomy 7 or complex cytogenetics was more common in the first quartile (18.8%; 95% CI, 3.5%-31.6%) [corrected] than in quartiles 2 through 4 (4.5%; 95% CI, 0.5%-8.2%; P = .002) [corrected]. Survival between these 2 groups differed, with 66% (95% CI, 52.9%-82.5%) surviving 6 years in the first quartile compared with 83.8% (95% CI, 77.3%-90.9%) in quartiles 2 through 4 (P = .008). CONCLUSION In a cohort of patients with severe aplastic anemia receiving immunosuppressive therapy, telomere length was unrelated to response but was associated with risk of relapse, clonal evolution, and overall survival.
Studies on delayed hypersensitivity to hepatitis B antigen in chimpanzees.

SUMMARY Twenty-eight chimpanzees weredivided into sixgroups according totheir history of previous immunization orexposure tohepatitis Bantigen (HBAg) andstudied for delayed hypersensitivity (DH)toHBAg.Purified HBAgderived fromanormal humancarrier wasusedforinvivoskintesting andinvitro leucocyte migration inhibition tests. Ofseventeen chimpanzees immunized withHBAginFreund's complete adjuvant (FCA), nineexhibited positive DH reactions toHBAgwith goodcorrelation between theinvivo andinvitro responses. Oftheseventeen chimpanzees, fourteen also exhibited positive DH reactions topurified protein derivative oftuberculin (PPD) withmarked erythema andinduration; theother three exhibitedonlyerythema withnoinduration. Noneoftheseventeen animals exhibited anyimmediate reactivity toeither HBAgorPPD.Intradermal injection ofHBAgnegative humanserumfailed toelicit DH reactions infour animals whoshowed positive skin test withpurified HBAg;theDH response wasthus probably HBAgspecific. Nineteen chimpanzees, including sixunimmunized animals, three chronic carriers ofHBAgandtwowhichhadbeeninjected withHBAgwithout FCA, failed toshowDH response toHBAg.Thus, DH toHBAgwasobserved onlyin animals hyperimmunized withHBAginFCA.
Big Data is the Future of Healthcare

Big data is already changing the way business decisions are made — and it’s still early in the game. However, because big data exceeds the capacity and capabilities of conventional storage, reporting and analytics systems, it demands new problem-solving approaches. With the convergence of powerful computing, advanced database technologies, wireless data, mobility and social networking, it is now possible to bring together and process big data in many profitable ways.
Memory-Based Acquisition of Argument Structures and its Application to Implicit Role Detection

We propose a generic, memory-based approach for the detection of implicit semantic roles. While state-of-the-art methods for this task combine hand-crafted rules with specialized and costly lexical resources, our models use large corpora with automated annotations for explicit semantic roles only to capture the distribution of predicates and their associated roles. We show that memory-based learning can increase the recognition rate of implicit roles beyond the state-of-the-art.
Offload (only) the right jobs: Robust offloading using the Markov decision processes

We consider a dynamic offloading problem arising in the context of mobile cloud computing (MCC). In MCC, three types of tasks can be identified: (i) those which can be processed only locally in a mobile device, (ii) those which are processed in the cloud, and (iii) those which can be processed either in the mobile or in the cloud. For type (iii) tasks, it is of interest to consider when they should be processed locally and when in the cloud. Furthermore, for both type (ii) and (iii) tasks, there is typically two ways to access the cloud: via a (costly) cellular connection or via intermittently available WLAN hotspots. The optimal strategy involves multi-dimensional considerations such as the availability of WLAN hotspots, energy consumption, communication costs and the expected delays. We approach this challenging problem in the framework of Markov decision processes and derive a near-optimal offloading policy.
Real-time continuous gesture recognition for natural multimodal interaction

I have developed a real-time continuous gesture recognition system capable of dealing with two important problems that have previously been neglected: (a) smoothly handling two different kinds of gestures: those characterized by distinct paths and those characterized by distinct hand poses; and (b) determining how and when the system should respond to gestures. The novel approaches in this thesis include: a probabilistic recognition framework based on a flattened hierarchical hidden Markov model (HHMM) that unifies the recognition of path and pose gestures; and a method of using information from the hidden states in the HMM to identify different gesture phases (the pre-stroke, the nucleus and the post-stroke phases), allowing the system to respond appropriately to both gestures that require a discrete response and those needing a continuous response. The system is extensible: new gestures can be added by recording 3-6 repetitions of the gesture; the system will train an HMM model for the gesture and integrate it into the existing HMM, in a process that takes only a few minutes. Our evaluation shows that even using only a small number of training examples (e.g. 6), the system can achieve an average F1 score of 0.805 for two forms of gestures. To evaluate the performance of my system I collected a new dataset (YANG dataset) that includes both path and pose gestures, offering a combination currently lacking in the community and providing the challenge of recognizing different types of gestures mixed together. I also developed a novel hybrid evaluation metric that is more relevant to realtime interaction with different gesture flows. Thesis Supervisor: Randall Davis Title: Professor
Alteration of methotrexate uptake in human leukemia cells by other agents.

The uptake of methotrexate (MTX) and the effect of drugs known to either inhibit or enhance MTX transport in L1210 murine leukemia were studied in man using blast cells from patients with acute myelogenous leukemia in vitro. MTX uptake was found to proceed slowly, requiring at least 160 min for cells to reach a "steady state" when extracellular MTX concentrations were 1 muM. Efflux of MTX from preloaded cells required 80 to 120 min and the nonexchangeable or tightly bound fraction was 40% of the total intracellular drug. Utilizing doses that are estimates of achievable peak blood levels following single i.v. injection, cephalothin (21 mug/ml) and hydrocortisone (20 mug/ml) inhibited net MTX accumulation by 20 and 28%, respectively. Vincristine sulfate at 8.3 and 0.083 mug/ml enhanced MTX uptake by 54 and 33%, respectively, by inhibiting MTX efflux, thus increasing the level of intracellular drug in excess of the tightly bound fraction. The potential clinical implications of using MTX in combination with the aforementioned drugs for cancer chemotherapy are discussed.
Evidence for complement activation in the amniotic fluid of women with spontaneous preterm labor and intra-amniotic infection

Objective. The complement system plays an important role in host defense against infection. Concentrations of complement split products or anaphylatoxins (C3a, C4a, and C5a) in biological fluids are considered to reflect complement activation. The purpose of this study was to determine if term and preterm parturition are associated with evidence of complement activation in the amniotic fluid. Study design. Amniotic fluid (AF) samples were collected from 270 women in the following groups: (1) normal pregnant women in midtrimester (n = 70), (2) term not in labor (n = 23), (3) term in labor (n = 48), and (4) preterm labor (PTL) (n = 129). PTL was categorized into: (a) PTL without microbial invasion of the amniotic cavity (MIAC) who delivered at term (n = 42), (b) PTL who delivered preterm without MIAC (n = 57), and (c) PTL with MIAC (n = 30). C5a, C4a, and C3a concentrations in amniotic fluid were determined by ELISA. Nonparametric tests were used for statistical analysis. Results. (1) The median AF C5a concentration was higher in women at term than that of those in the midtrimester (p = 0.02); (2) Spontaneous labor at term was not associated with changes in AF concentrations of anaphylatoxins C3a, C4a, and C5a (all p > 0.05); (3) Among patients with PTL who delivered preterm, those with MIAC had higher AF C4a and C5a concentrations than those without infection (p < 0.01); and (4) AF C3a, C4a, and C5a concentrations were higher in patients with PTL with MIAC than in those with PTL without MIAC who delivered at term. Conclusion. Patients with spontaneous preterm labor and intact membranes with microbial invasion of the amniotic cavity had higher median amniotic fluid concentration of complement split products C3a, C4a, and C5a than patients without intra-amniotic infection. These findings suggest that preterm labor in the context of infection is associated with activation of the complement system.
The impact of "non-evaluative" and "evaluative" friends on cardiovascular reactivity during a stressful math task

This study was conducted to further examine the role of social support in moderating cardiovascular reactivity to behavioral stress. Specifically, evaluation potential was manipulated in order to determine if absence of evaluation is a critical ingredient for the beneficial effects of support on cardiovascular reactivity. Forty-eight female university students performed a stressful math task while alone or in the presence of a close female friend. The friend condition was designed to be either high or low in evaluation potential. This was achieved by manipulating whether the friend could view the subject’s questions and answers to the math task. Findings indicate that subjects who were assigned to the “non-evaluative” friend condition showed a trend for reduced systolic blood pressure reactivity compared to subjects who were alone during the task. Significant differences only emerged during the last minute of the task. Subjects in the “evaluative” friend condition did not show differences from the other groups on any cardiovascular measure, thereby suggesting that a social support manipulation can fail if evaluative situational elements are not carefully controlled for. The validity of the evaluation vs. non-evaluation distinction was supported by the observation that the friends’ cardiovascular activity level during the task showed significant differences in systolic and diastolic blood pressure. Specifically, the “non-evaluative” friends showed habituation on these measures during the task, whereas the “evaluative” friends did not habituate, remaining at pre-task levels of response.
Degradable Hollow Mesoporous Silicon/Carbon Nanoparticles for Photoacoustic Imaging-Guided Highly Effective Chemo-Thermal Tumor Therapy in Vitro and in Vivo

The development of nanoscaled theranostic agents for cancer combination therapies has received intensive attention in recent years. In this report, a degradable hollow mesoporous PEG-Si/C-DOX NP is designed and fabricated for pH-responsive, photoacoustic imaging-guided highly effective chemo-thermal combination therapy. The intrinsic hollow mesoporous structure endows the as-synthesized nanoparticles (NPs) with a high drug loading capacity (31.1%). Under NIR (808 nm) irradiation, the photothermal conversion efficiency of the Si/C NPs is as high as 40.7%. Preferential accumulation of the PEG-Si/C-DOX NPs around tumor tissue was demonstrated with photoacoustic images. Cellular internalization of the NPs and release of the DOX in nuclei are shown with fluorescent images. With efficient NIR photothermal conversion and high DOX loading capacity, the PEG-Si/C-DOX NPs are demonstrated to have remarkable cancer-cell-killing ability and to achieve complete in vivo tumor elimination via combinational chemo-thermal therapy. Last but not least, the NPs show good biodegradability and biosafety, making them a promising candidate for multifunctional drug delivery and cancer theranostic.
Solving dynamic economic dispatch problems using cellular differential evolution

This paper proposes cellular differential evolution (cDE) algorithm for solving dynamic economic dispatch (DED) problems with valve-point effects. DEDs are high dimensional optimization problems with many equality and inequality constraints. The problem of premature convergence in solving high dimensional optimization problems using evolutionary algorithms (EAs) could be fought using population structuring. This work investigates the suitability a structured DE algorithm, called cDE, in solving these large dimensional optimization tasks. The suitability and effectiveness of the proposed algorithm is validated using two test systems consisting of 10 and 13 thermal units respectively. Numerical results clearly show that the proposed method outperforms existing methods in terms of solution quality and robustness.
Identification and sequence analysis of a new member of the mouse HSP70 gene family and characterization of its unique cellular and developmental pattern of expression in the male germ line

A unique member of the mouse HSP70 gene family has been isolated and characterized with respect to its DNA sequence organization and expression. The gene contains extensive similarity to a heat shock-inducible HSP70 gene within the coding region but diverges in both 3' and 5' nontranslated regions. The gene does not yield transcripts in response to heat shock in mouse L cells. Rather, the gene appears to be activated uniquely in the male germ line. Analysis of RNA from different developmental stages and from enriched populations of spermatogenic cells revealed that this gene is expressed during the prophase stage of meiosis. A transcript different in size from the major heat-inducible mouse transcripts is most abundant in meiotic prophase spermatocytes and decreases in abundance in postmeiotic stages of spermatogenesis. This pattern of expression is distinct from that observed for another member of this gene family, which was previously shown to be expressed abundantly in postmeiotic germ cells. These observations suggest that specific HSP70 gene family members play distinct roles in the differentiation of the germ cell lineage in mammals.