Miracle-dz/UniFAR-FTUs huggingface dataset:
C5a and Bradykinin Receptor Cross-Talk Regulates Innate and Adaptive Immunity in Trypanosoma cruzi Infection

Complement and the kallikrein–kinin cascade system are both activated in injured tissues. Little is known about their partnership in the immunopathogenesis of Chagas disease, the chronic infection caused by the intracellular protozoan Trypanosoma cruzi. In this study, we show that pharmacological targeting of the C5a receptor (C5aR) or the bradykinin B2 receptor (B2R) inhibited plasma leakage in hamster cheek pouch topically exposed to tissue culture trypomastigotes (TCTs). Further, angiotensin-converting enzyme inhibitors potentiated TCT-evoked paw edema in BALB/c, C57BL/6, and C5-deficient A/J mice through activation of joint pathways between C5aR/B2R or C3aR/B2R. In addition to generation of C5a and kinins via parasite-derived cruzipain, we demonstrate that macrophages internalize TCTs more efficiently through joint activation of C5aR/B2R. Furthermore, we found that C5aR targeting markedly reduces NO production and intracellular parasitism in macrophages. We then studied the impact of C5aR/B2R cross-talk in TCT infection on the development of adaptive immunity. We found that IL-12p40/70 expression was blunted in splenic dendritic cells by blocking either C5aR or B2R, suggesting that codominant signaling via C5aR and B2R fuels production of the Th1-polarizing cytokine. Finally, we assessed the impact of kinins and C5a liberated in parasite-laden tissues on Th cell differentiation. As predicted, BALB/c mice pretreated with angiotensin-converting enzyme inhibitors potentiated IFN-γ production by Ag-specific T cells via C5aR/B2R cross-talk. Interestingly, we found that B2R targeting upregulated IL-10 secretion, whereas C5aR blockade vigorously stimulated IL-4 production. In summary, we describe a novel pathway by which C5aR/B2R cross-talk couples transendothelial leakage of plasma proteins to the cytokine circuitry that coordinates antiparasite immunity.
Improving Image Segmentation Using Genetic Algorithm

This paper presents a new approach to the problem of semantic segmentation of digital images. We aim to improve the performance of some state-of-the-art approaches for the task. We exploit a new version of texton feature [28], which can encode image texture and object layout for learning a robust classifier. We propose to use a genetic algorithm for the learning parameters of weak classifiers in a boosting learning set up. We conducted extensive experiments on benchmark image datasets and compared the segmentation results with current proposed systems. The experimental results show that the performance of our system is comparable to, or even outperforms, those state-of-the-art algorithms. This is a promising approach as in this empirical study we used only texture-layout filter responses as feature and a basic setting of genetic algorithm. The framework is simple and can be extended and improved for many learning problems.
On the Power of Lasserre SDP Hierarchy

Author(s): Tan, Ning | Advisor(s): Raghavendra, Prasad | Abstract: Constraint Satisfaction Problems (CSPs) are a class of fundamental combinatorial optimization problems that have been extensively studied in the field of approximation algorithms and hardness of approximation. In a ground breaking result, Raghavendra showed that assuming Unique Games Conjecture, the best polynomial time approximation algorithm for all Max CSPs are given by a family of basic standard SDP relaxations. With Unique Games Conjecture remains as one of the most important open question in the field of Theoretical Computer Science, it is natural to ask whether hypothetically stronger SDP relaxations would be able to achieve better approximation ratio for Max CSPs and their variants.In this work, we study the power of Lasserre/Sum-of-Squares SDP Hierarchy. First part of this work focuses on using Lasserre/Sum-of-Squares SDP Hierarchy to achieve better approximation ratio for certain CSPs with global cardinality constraints. We present a general framework to obtain Sum-of-Squares SDP relaxation, round SDP solution and analyze the rounding algorithm for CSPs with global cardinality constraints. To demonstrate the approach, we show that one could use Sum-of-Squares SDP to achieve a 0.85-approximation algorithm for Max Bisection problem, improving on the previously best known 0.70 ratio. In the second part of this work, we study the computational power of general symmetric relaxations. Specifically, we show that Lasserre/Sum-of-Squares SDP solution achieves the best possible approximation ratio for all Max CSPs among all symmetric SDP relaxations of similar size. This result gives the first lower bounds for symmetric SDP relaxations of Max CSPs, andindicates that the Sum-of-Squares SDP is indeed the "right" SDP relaxation for this class of problems.
Diagnostic Imaging for Low Back Pain: Advice for High-Value Health Care From the American College of Physicians

Diagnostic imaging is indicated for patients with low back pain only if they have severe progressive neurologic deficits or signs or symptoms that suggest a serious or specific underlying condition. In other patients, evidence indicates that routine imaging is not associated with clinically meaningful benefits but can lead to harms. Addressing inefficiencies in diagnostic testing could minimize potential harms to patients and have a large effect on use of resources by reducing both direct and downstream costs. In this area, more testing does not equate to better care. Implementing a selective approach to low back imaging, as suggested by the American College of Physicians and American Pain Society guideline on low back pain, would provide better care to patients, improve outcomes, and reduce costs.
Design and optimization of Copper Indium Gallium Selenide solar cells for lightweight battlefield application

Abstract : The design and optimization of higher efficiency Copper Indium Gallium Selenide (CIGS) solar cells are investigated in this thesis. Optimizing the thickness layers of a cell for various band gaps was conducted in order to design a cell that exceeds the current industry efficiency record of 20.8%. Silvaco provides a modeling program called ATLAS that is specifically designed to model semiconductor devices. ATLAS was used to model a CIGS cell that is currently being produced to verify the validity of the model. Various thicknesses were then swept to determine the optimum thickness for a given band gap. Solar spectrum intensity varies by location around the Earth. Optimizing CIGS cells for various band gaps yields higher overall power output when dealing with drastic climate and location variations. Cells for five band gaps ranging from 1.14 eV to 1.69 eV were optimized in this thesis. The highest achieved efficiency was for a band gap of 1.69 eV with an overall theoretical efficiency of 22.4%.
Combining PCFG-LA Models with Dual Decomposition: A Case Study with Function Labels and Binarization

It has recently been shown that different NLP models can be effectively combined using dual decomposition. In this paper we demon-strate that PCFG-LA parsing models are suit-able for combination in this way. We exper-iment with the different models which result from alternative methods of extracting a gram-mar from a treebank (retaining or discarding function labels, left binarization versus right binarization) and achieve a labeled Parseval F-score of 92.4 on Wall Street Journal Sec-tion 23 – this represents an absolute improve-ment of 0.7 and an error reduction rate of 7% over a strong PCFG-LA product-model base-line. Although we experiment only with bina-rization and function labels in this study, there is much scope for applying this approach to other grammar extraction strategies.
Neuron-Derived Neurotrophic Factor Ameliorates Adverse Cardiac Remodeling After Experimental Myocardial Infarction

Background—Myocardial infarction (MI) is one of the major causes of death worldwide. Chronic heart failure is a serious complication of MI that leads to poor prognosis. We recently found that neuron-derived neurotrophic factor (NDNF) is a proangiogenic secretory protein that is upregulated in ischemic skeletal muscle. Here, we examined whether NDNF modulates cardiac remodeling in response to chronic ischemia. Methods and Results—C57BL/6J wild-type mice were subjected to the permanent ligation of the left anterior descending coronary artery to create MI. Adenoviral vectors expressing NDNF or &bgr;-galactosidase (control) were intramuscularly injected into mice 3 days before permanent left anterior descending coronary artery ligation. Intramuscular administration of adenoviral vectors expressing NDNF to mice resulted in increased levels of circulating NDNF. Adenoviral vectors expressing NDNF administration improved left ventricular systolic dysfunction and dilatation after MI surgery. Moreover, adenoviral vectors expressing NDNF enhanced capillary formation and reduced cardiomyocyte apoptosis and hypertrophy in the post-MI hearts. Treatment of cultured cardiomyocytes with recombinant NDNF protein led to reduced apoptosis under conditions of hypoxia. NDNF also promoted the phosphorylation of Akt and focal adhesion kinase in cardiomyocytes. Blockade of focal adhesion kinase activation blocked the stimulatory effects of NDNF on cardiomyocyte survival and Akt phosphorylation. Similarly, treatment of cultured endothelial cells with NDNF protein led to enhancement of network formation and Akt phosphorylation, which was diminished by focal adhesion kinase inhibition. Conclusions—These data suggest that NDNF ameliorates adverse myocardial remodeling after MI by its abilities to enhance myocyte survival and angiogenesis in the heart through focal adhesion kinase/Akt-dependent mechanisms.
On the Phase Reduction and Response Dynamics of Neural Oscillator Populations

We undertake a probabilistic analysis of the response of repetitively firing neural populations to simple pulselike stimuli. Recalling and extending results from the literature, we compute phase response curves (PRCs) valid near bifurcations to periodic firing for Hindmarsh-Rose, Hodgkin-Huxley, Fitz Hugh-Nagumo, and Morris-Lecar models, encompassing the four generic (codimension one) bifurcations. Phase density equations are then used to analyze the role of the bifurcation, and the resulting PRC, in responses to stimuli. In particular, we explore the interplay among stimulus duration, baseline firing frequency, and population-level response patterns. We interpret the results in terms of the signal processing measure of gain and discuss further applications and experimentally testable predictions.
High-dimensional graphs and variable selection with the Lasso

The pattern of zero entries in the inverse covariance matrix of a multivariate normal distribution corresponds to conditional independence restrictions between variables. Covariance selection aims at estimating those structural zeros from data. We show that neighborhood selection with the Lasso is a computationally attractive alternative to standard covariance selection for sparse high-dimensional graphs. Neighborhood selection estimates the conditional independence restrictions separately for each node in the graph and is hence equivalent to variable selection for Gaussian linear models. We show that the proposed neighborhood selection scheme is consistent for sparse high-dimensional graphs. Consistency hinges on the choice of the penalty parameter. The oracle value for optimal prediction does not lead to a consistent neighborhood estimate. Controlling instead the probability of falsely joining some distinct connectivity components of the graph, consistent estimation for sparse graphs is achieved (with exponential rates), even when the number of variables grows as the number of observations raised to an arbitrary power.
Search for NTRK1 proto-oncogene rearrangements in human thyroid tumours originated after therapeutic radiation

Rearrangements of NTRK1 proto-oncogene were detected in ‘spontaneous’ papillary thyroid carcinomas with a frequency varying from 5 to 25% in different studies. These rearrangements result in the formation of chimaeric genes composed of the tyrosine kinase domain of NTRK1 fused to 5′ sequences of different genes. To investigate if the NTRK1 gene plays a role in radiation-induced thyroid carcinogenesis, we looked for the presence of NTRK1 -activating rearrangements in 32 human thyroid tumours (16 follicular adenomas, 14 papillary carcinomas and two lymph-node metastases of papillary thyroid carcinomas) from patients who had received external radiation, using the reverse transcription polymerase chain reaction, Southern blot and direct sequencing techniques. These data were compared with those obtained in a series of 28 ‘spontaneous’ benign and malignant thyroid tumours, collected from patients without a history of radiation exposure and four in vitro culture cell lines derived from lsquo;spontaneous’ thyroid cancers. Our results concerning the radiation-associated tumours showed that only rearrangements between NTRK1 and TPM3 genes (TRK oncogene) were detected in 2/14 papillary carcinomas and in one lymph-node metastasis of one of these papillary thyroid carcinomas. All the radiation-associated adenomas were negative. In the ‘spontaneous’ tumours, only one of the 14 papillary carcinomas and one of the four in vitro culture cell lines, derived from a papillary carcinoma, presented a NTRK1 rearrangement also with the TPM3 gene. Twenty-five of this series of radiation-associated tumours were previously studied for the ras and RET/PTC oncogenes. In conclusion, our data: (a) show that the overall frequency of NTRK1 rearrangements is similar between radiation-associated (2/31: 6%) and ‘spontaneous’ epithelial thyroid tumours (2/32: 6%). The frequency, if we consider exclusively the papillary carcinomas, is in both cases 12%; (b) show that the TRK oncogene plays a role in the development of a minority of radiation-associated papillary thyroid carcinomas but not in adenomas; and (c) confirm that RET/PTC rearrangements are the major genetic alteration associated with ionizing radiation-induced thyroid tumorigenesis. © 2000 Cancer Research Campaign
Pharmacological Inhibition of Cochlear Mitochondrial Respiratory Chain Induces Secondary Inflammation in the Lateral Wall: A Potential Therapeutic Target for Sensorineural Hearing Loss

Cochlear lateral wall has recently been reported as a common site of inflammation, yet precise molecular mechanisms of the inflammatory responses remain elucidated. The present study examined the inflammatory responses in the lateral wall following acute mitochondrial dysfunction induced by a mitochondrial toxin, 3-nitropropionic acid (3-NP). Reverse-transcription (RT)-PCR revealed increases in the expression of the proinflammatory cytokines interleukin (IL)-1β and IL-6. Immunohistochemistry showed an increase in the number of activated cochlear macrophages in the lateral wall, which were in close proximity to IL-6-expressing cells. A genome-wide DNA microarray analysis of the lateral wall revealed that 35% and 60% of the genes showing >2-fold upregulation at 1 d and 3 d post-3-NP administration, respectively, were inflammatory genes, including CC- and CXC-type chemokine genes. High expression of CCL-1, 2, and 3 at 1 d, and of CCL-1, 2, 3, 4, and 5, CCR-2 and 5, and CX3CR1 at 3 d post-3-NP administration, coupled with no change in the level of CX3CL1 expression suggested that macrophages and monocytes may be involved in the inflammatory response to 3-NP-mediated injury. Quantitative (q)RT-PCR showed a transient induction of IL-1β and IL-6 expression within 24 h of 3-NP-mediated injury, followed by sustained expression of the chemoattractants, CCL-2, 4 and 5, up until 7 d after injury. The expression of CCL-2 and IL-6 was higher in animals showing permanent hearing impairment than in those showing temporary hearing impairment, suggesting that these inflammatory responses may be detrimental to hearing recovery. The present findings suggest that acute mitochondrial dysfunction induces secondary inflammatory responses in the lateral wall of the cochlear and that the IL-6/CCL-2 inflammatory pathway is involved in monocyte activation. Therefore, these secondary inflammatory responses may be a potential post-insult therapeutic target for treatments aimed at preventing the damage caused by acute mitochondrial dysfunction in the cochlear lateral wall.
Genotyping markers used for multi locus VNTR analysis with ompA (MLVA-ompA) and multi sequence typing (MST) retain stability in Chlamydia trachomatis

We aimed to evaluate the stability of the Chlamydia trachomatis multi locus VNTR analysis (MLVA-ompA) and multi sequence typing (MST) systems through multiple passages in tissue culture. Firstly, we analyzed the stability of these markers through adaptation of C. trachomatis to tissue culture and secondly, we examined the stability of a four-locus MLVA-ompA and a five-locus MST system after multiple passages in tissue culture. Marker sequences were monitored through successive chlamydial developmental cycles to evaluate the stability of the individual DNA markers through many bacterial divisions and this, in turn, informed us of the usefulness of using such typing systems for short and long-term molecular epidemiology. Southampton genitourinary medicine (GUM) clinic isolates from endocervical swabs collected from C. trachomatis positive women were passaged through tissue culture. MLVA-ompA typing was applied to primary swab samples and to the same samples after C. trachomatis had been passaged through cell culture (eight passages). Sequence data from time-zero and passage-eight isolates were aligned with reference sequences to determine the stability of the markers. The Swedish new variant (nvCT) underwent 72 passages in cell culture and the markers of the two schemes were similarly analyzed. Analysis of genetic markers of the MLVA-ompA typing system before and after the isolates were introduced to tissue culture showed no change in the dominant sequence. The nvCT that had been passaged 72 times over the duration of a year also showed no variation in the dominant sequence for both the genotyping schemes. MLVA-ompA and MST markers are stable upon adaptation of C. trachomatis to tissue culture following isolation of strains from primary endocervical swab samples. These markers remain stable throughout multiple rounds of cell-division in tissue culture, concomitant with the incubation period and appearance of symptoms normally associated with host-infection. Both genotyping schemes are, therefore, suitable for epidemiology of C. trachomatis.
Reproductive Biology and Endocrinology Open Access a Link between High Serum Levels of Human Chorionic Gonadotrophin and Chorionic Expression of Its Mature Functional Receptor (lhcgr) in Down's Syndrome Pregnancies

Human chorionic gonadotrophin (hCG) is released from placental trophoblasts and is involved in establishing pregnancy by maintaining progesterone secretion from the corpus luteum. Serum hCG is detected in the maternal circulation within the first 2–3 wks of gestation and peaks at the end of the first trimester before declining. In Down's syndrome (DS) pregnancies, serum hCG remains significantly high compared to gestation age-matched uncompromised pregnancies. It has been proposed that increased serum hCG levels could be due to transcriptional hyper-activation of the CGB (hCG beta) gene, or an increased half life of glycosylated hCG hormone, or both. Another possibility is that serum hCG levels remain high due to reduced availability of the hormone's cognate receptor, LHCGR, leading to lack of hormone utilization. We have tested this hypothesis by quantifying the expression of the hCG beta (CGB) RNA, LHCGR RNA and LHCGR proteins in chorionic villous samples. We demonstrate that chorionic expression of hCG beta (CGB) mRNA directly correlates with high serum hCG levels. The steady-state synthesis of LHCGR mRNA (exons 1–5) in DS pregnancies was significantly higher than that of controls, but the expression of full-length LHCGR mRNA (exons 1–11) in DS was comparable to that of uncompromised pregnancies. However, the synthesis of high molecular weight mature LHCGR proteins was significantly reduced in DS compared to uncompromised pregnancies, suggesting a lack of utilization of circulating hCG in DS pregnancies. which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cholera Outbreaks in Urban Bangladesh In 2011.

BACKGROUND In 2011, a multidisciplinary team investigated two diarrhoea outbreaks affecting urban Bangladeshi communities from the districts of Bogra and Kishorganj to identify etiology, pathways of transmission, and factors contributing to these outbreaks. METHODS We defined case-patients with severe diarrhoea as residents from affected communities admitted with ≥3 loose stools per day. We listed case-patients, interviewed and examined them, and collected rectal swabs. We visited the affected communities to explore the water and sanitation infrastructure. We tested the microbial load of water samples from selected case household taps, tube wells, and pump stations. We conducted anthropological investigations to understand community perceptions regarding the outbreaks. RESULTS We identified 21 case-patients from Bogra and 84 from Kishorganj. The median age in Bogra was 23 years, and 21 years in Kishorganj. There were no reported deaths. We isolated Vibrio in 29% (5/17) of rectal swabs from Bogra and in 40% (8/20) from Kishorganj. We found Vibrio in 1/8 tap water samples from Bogra and in both of the samples from Kishorganj. We did not find Vibrio in water samples from pumps or tube wells in either outbreak. Ground water extracted through deep tube wells was supplied intermittently through interconnected pipes without treatment in both areas. We found leakages in the water pipes in Bogra, and in Kishorganj water pipes passed through open sewers. CONCLUSION The rapid onset of severe diarrhoea predominantly affecting adults and the isolation of cholera in rectal swabs confirmed that these outbreaks were caused by Vibrio cholerae. The detection of Vibrio in water samples organisms from taps but not from pumps or tube wells, suggested contamination within the pipes. Safe water provision is difficult in municipalities where supply is intermittent, and where pipes commonly leak. Research to develop and evaluate water purification strategies could identify appropriate approaches for ensuring safe drinking water in resource-poor cities.