Miracle-dz/UniFAR-FTUs huggingface dataset:
Within the Enemy’s Camp: contribution of the granuloma to the dissemination, persistence and transmission of Mycobacterium tuberculosis

Pulmonary tuberculosis, caused by Mycobacterium tuberculosis (M.tb) represents a leading global health concern, with 8.7 million newly emerging cases, and 1.4 million reported deaths annually. Despite an estimated one third of the world’s population being infected, relatively few infected individuals ever develop active clinical disease. The ability of the host to remain latently infected while preventing disease is thought to be due to the generation of a robust type 1 immune response in the lung, capable of controlling, but not clearing, M.tb. A key feature of the type 1 immune response to M.tb is the formation of immune cellular aggregates termed granuloma. The granuloma structure has long been considered a hallmark of host’s protective response toward M.tb. Historically, a correlative relationship between granuloma formation/maintenance and bacterial control has been seen in models where disrupted granuloma formation or structure was found to be fatal. Despite this established relationship much about the granuloma’s role in M.tb immunity remains unknown. Recent publications suggest that the granuloma actually aids the persistence of M.tb and that the development of a necrotic granuloma is essential to person-to-person transmission. Our group and others have recently demonstrated that enclosed within the granuloma is a population of immunologically altered antigen-presenting cells and T lymphocyte populations. Of note, the ability of these populations to produce type 1 cytokines such as interferon-gamma, and bactericidal products including nitric oxide, are significantly reduced, while remaining competent to produce high levels immunosuppressive interleukin-10. These observations indicate that although the chronic granuloma represents a highly unique environment, it is more similar to that of a tumor than an active site of bacterial control. In this review we will explore what is known about this unique environment and its contribution to the persistence of M.tb.
Improving Performance of Heterogeneous MapReduce Clusters with Adaptive Task Tuning

Datacenter-scale clusters are evolving toward heterogeneous hardware architectures due to continuous server replacement. Meanwhile, datacenters are commonly shared by many users for quite different uses. It often exhibits significant performance heterogeneity due to multi-tenant interferences. The deployment of MapReduce on such heterogeneous clusters presents significant challenges in achieving good application performance compared to in-house dedicated clusters. As most MapReduce implementations are originally designed for homogeneous environments, heterogeneity can cause significant performance deterioration in job execution despite existing optimizations on task scheduling and load balancing. In this paper, we observe that the homogeneous configuration of tasks on heterogeneous nodes can be an important source of load imbalance and thus cause poor performance. Tasks should be customized with different configurations to match the capabilities of heterogeneous nodes. To this end, we propose a self-adaptive task tuning approach, Ant, that automatically searches the optimal configurations for individual tasks running on different nodes. In a heterogeneous cluster, Ant first divides nodes into a number of homogeneous subclusters based on their hardware configurations. It then treats each subcluster as a homogeneous cluster and independently applies the self-tuning algorithm to them. Ant finally configures tasks with randomly selected configurations and gradually improves tasks configurations by reproducing the configurations from best performing tasks and discarding poor performing configurations. To accelerate task tuning and avoid trapping in local optimum, Ant uses genetic algorithm during adaptive task configuration. Experimental results on a heterogeneous physical cluster with varying hardware capabilities show that Ant improves the average job completion time by 31, 20, and 14 percent compared to stock Hadoop (Stock), customized Hadoop with industry recommendations (Heuristic), and a profiling-based configuration approach (Starfish), respectively. Furthermore, we extend Ant to virtual MapReduce clusters in a multi-tenant private cloud. Specifically, Ant characterizes a virtual node based on two measured performance statistics: I/O rate and CPU steal time. It uses k-means clustering algorithm to classify virtual nodes into configuration groups based on the measured dynamic interference. Experimental results on virtual clusters with varying interferences show that Ant improves the average job completion time by 20, 15, and 11 percent compared to Stock, Heuristic and Starfish, respectively.
CRL4A-FBXW5–mediated degradation of DLC1 Rho GTPase-activating protein tumor suppressor promotes non-small cell lung cancer cell growth

Significance The DLC1 tumor suppressor gene is commonly lost in cancer by genomic deletion or epigenetic silencing, leading to loss of gene transcription. DLC1 encodes a GTPase-activating protein for the RhoA small GTPase, and DLC1 loss of expression results in aberrant RhoA activation and signaling. Unexpectedly, we found that a subset of non-small cell lung cancer patient tumors and cell lines retained DLC1 mRNA but not protein expression. We determined that the CUL4A–DDB1–FBXW5 E3 ubiquitin ligase complex is responsible for loss of DLC1 protein expression. Suppression of FBXW5 function restored DLC1-dependent lung cancer cell growth suppression. Our observations identify a mechanism for posttranslational loss of DLC1 function in cancer and substrate for CRL4A-FBXW5–driven cancer growth. DLC1 encodes a RhoA GTPase-activating protein and tumor suppressor lost in cancer by genomic deletion or epigenetic silencing and loss of DLC1 gene transcription. We unexpectedly identified non-small cell lung cancer (NSCLC) cell lines and tumor tissue that expressed DLC1 mRNA yet lacked DLC1 protein expression. We determined that DLC1 was ubiquitinated and degraded by cullin 4A–RING ubiquitin ligase (CRL4A) complex interaction with DDB1 and the FBXW5 substrate receptor. siRNA-mediated suppression of cullin 4A, DDB1, or FBXW5 expression restored DLC1 protein expression in NSCLC cell lines. FBXW5 suppression-induced DLC1 reexpression was associated with a reduction in the levels of activated RhoA-GTP and in RhoA effector signaling. Finally, FBXW5 suppression caused a DLC1-dependent decrease in NSCLC anchorage-dependent and -independent proliferation. In summary, we identify a posttranslational mechanism for loss of DLC1 and a linkage between CRL4A-FBXW5–associated oncogenesis and regulation of RhoA signaling.
Structure, Seismicity, and Accretionary Processes at the Hot Spot‐Influenced Axial Seamount on the Juan de Fuca Ridge

Axial Seamount is the most volcanically active site of the northeast Pacific, and it has been monitored with a growing set of observations and sensors during the last two decades. Accurate imaging of the internal structure of volcanic systems is critical to better understand magma storage processes and to quantify mass and energy transport mechanisms in the crust. To improve the three‐dimensional velocity structure of Axial Seamount, we combined 469,891 new traveltime arrivals, from 12 downward extrapolated seismic profiles, with 3,962 existing ocean‐bottom‐seismometers traveltime arrivals, into a joint tomographic inversion. Our approach reveals two elongated magma reservoirs, with melt fraction up to 65%, representing an unusually large volume of melt (26–60 km3), which is likely the result of enhanced magma supply from the juxtaposition of the Cobb hot spot plume (0.26–0.53 m3/s) and the Axial spreading segment (0.79–1.06 m3/s). The tomographic model also resolves a subsided caldera floor that provides an effective trap for ponding lava flows, via a “trapdoor” mechanism. Our model also shows that Axial's extrusive section is thinnest beneath the elevated volcano, where anomalously thick (11 km) oceanic crust is present. We therefore suggest that focused and enhanced melt supply predominantly thickens the crust beneath Axial Seamount through diking accretion and gabbro crystallization. Lastly, we demonstrate that our three‐dimensional velocity model provides a more realistic starting point for relocating the local seismicity, better resolving a network of conjugate outward and inward dipping faults beneath the caldera walls. ©2018. The Authors.
Low‐pressure pneumoperitoneum during laparoscopic donor nephrectomy to optimize live donors’ comfort

Nowadays, laparoscopic donor nephrectomy (LDN) has become the gold standard to procure live donor kidneys. As the relationship between donor and recipient loosens, it becomes of even greater importance to optimize safety and comfort of the surgical procedure. Low‐pressure pneumoperitoneum has been shown to reduce pain scores after laparoscopic cholecystectomy. Live kidney donors may also benefit from the use of low pressure during LDN. To evaluate feasibility and efficacy to reduce post‐operative pain, we performed a randomized blinded study. Twenty donors were randomly assigned to standard (14 mmHg) or low (7 mmHg) pressure during LDN. One conversion from low to standard pressure was indicated by protocol due to lack of progression. Intention‐to‐treat analysis showed that low pressure resulted in a significantly longer skin‐to‐skin time (149 ± 86 vs. 111 ± 19 min), higher urine output during pneumoperitoneum (23 ± 35 vs. 11 ± 20 mL/h), lower cumulative overall pain score after 72 h (9.4 ± 3.2 vs. 13.5 ± 4.5), lower deep intra‐abdominal pain score (11 ± 3.3 vs. 7.5 ± 3.1), and a lower cumulative overall referred pain score (1.8 ± 1.9 vs. 4.2 ± 3). Donor serum creatinine levels, complications, and quality of life dimensions were not significantly different. Our data show that low‐pressure pneumoperitoneum during LDN is feasible and may contribute to increase live donors’ comfort during the early post‐operative phase.
The vanishing of intersection multiplicities of perfect complexes

Serre conjectured that these two statements hold for all regular local rings. In this paper we outline a proof that the first of these statements holds not only for arbitrary regular local rings, but for complete intersections and isolated singularities as well. This result has been proven independently in the case of complete intersections, using if-theoretic methods, by H. Gillet and C. Soulé [5]. Somewhat more generally, we prove a result on the vanishing of multiplicities for bounded complexes of finitely generated free modules; such complexes we call perfect. Let Y = Spec . R, and let E* and F* be perfect complexes. Let X = Supp(2? *) = the support of E+ = {P G Spec R\(E*)p is not exact}; let W = Supp(F„). Let p denote the closed point of Y. If G* is a complex with Supp(G.) = p, let X(G.) = E i e z ( l ) ' l eng th^(G, ) ) .
On the detection of pornographic digital images

The paper addresses the problem of distinguishing between pornographic and non-pornographic photographs, for the design of semantic filters for the web. Both, decision forests of trees built according to CART (Classification And Regression Trees) methodology and Support Vectors Machines (SVM), have been used to perform the classification. The photographs are described by a set of low-level features, features that can be automatically computed simply on gray-level and color representation of the image. The database used in our experiments contained 1500 photographs, 750 of which labeled as pornographic on the basis of the independent judgement of several viewers.
Performance Comparisons, Design, and Implementation of RC5 Symmetric Encryption Core using Reconfigurable Hardware

With the wireless communications coming to homes and offices, the need to have secure data transmission is of utmost importance. Today, it is important that information is sent confidentially over the network without fear of hackers or unauthorized access to it. This makes security implementation in networks a crucial demand. Symmetric Encryption Cores provide data protection via the use of secret key only known to the encryption and decryption ends of the communication path. In this paper, first, an overview of two well known symmetric encryption cores is presented, namely the 3DES and RC5. Then a performance evaluation of their computer based implementation is compared to demonstrate the RC5 superior performance. The conventional hardware architecture of the RC5 core is presented and investigated. A hardware system design is proposed to improve its performance. The proposed architecture achieved with three stage pipeline technique an increased encryption throughput as compared to related work. By exploiting modern features in Field Programmable Gate Arrays (FPGA), which allow the modeling of a System-on- Programmable-Chip (SoPC), this paper proposes a model for symmetric encryption algorithms ( e.g., RC5). Structural System analysis of the proposed model shows that it offers extra security against single-site physical access attack that other implementations are vulnerable to. By evaluating the performance of this proposed SoPC model, one finds that it raises the encryption throughput to 300 Mbps. Hence, we report over 80% increase in the encryption throughput as compared to related work. Moreover, our work lowers the implementation cost due to the integration of all system parts into one chip.
A comprehensive solution to the XML-to-relational mapping problem

The use of relational database management systems (RDBMSs) to store and query XML data has attracted considerable interest with a view to leveraging their powerful and reliable data management services. Due to the mismatch between the relational and XML data models, it is necessary to first shred and load the XML data into relational tables, and then btranslate XML queries over the original data into equivalent SQL queries over the mapped tables. Although there is a rich literature on XML-relational storage, none of the existing solutions addresses all the storage problems in a single framework. Works on mapping strategies often have little or no details about query translation, and proposals for query translation often target a specific mapping strategy. XML-storage solutions provided by RDBMS also have limitations. Notably, they are tied to a specific backend and use proprietary mapping languages, which not only may require a steep learning curve, but often are unable to express certain desirable mappings. In order to address these limitations, we developed ShreX, a XML-to-relational mapping framework and system that provides the first comprehensive and end-to-end solution to the relational storage of XML data. Mappings in ShreX are defined through annotations to an XML Schema. The use of XML Schema simplifies the mapping process, since it does not require users to master a new specialized mapping language. The use of annotations allows mapping choices to be combined in many different ways. As a result, ShreX not only supports all the mapping strategies proposed in the literature, but also new useful strategies that had not been considered previously. ShreX provides generic (and automatic) document shredding and query translation capabilities; and it is portable --- its mapping specifications are independent of the database backend.
The association between serum cortisol and cognitive decline in older persons.

OBJECTIVE To investigate whether serum cortisol levels are associated with cognitive performance and cognitive decline in elderly persons and whether this association differs by age, sex, and depression status. DESIGN Data from the Longitudinal Aging Study Amsterdam, with repeated measurements of cognitive performance after 3 and 6 years. PARTICIPANTS A total of 1,154 persons, aged 65-88 years. MEASUREMENTS Serum concentrations of total cortisol (CRT) and corticosteroid binding globulin (CBG) were measured at baseline, and from these free cortisol index (CRT/CBG) was computed. At baseline and 3 and 6 years of follow-up, global cognitive functioning, verbal memory performance, and speed of information processing were assessed. RESULTS After adjustment for demographics, health, and life style variables, a significant association between high levels of free cortisol and poorer performance on verbal learning (B = -0.32; 95% confidence interval: -0.64 to -0.01) was found in both women and men. Additional adjustment for depression did not change this association. In women, but not in men, high levels of free cortisol (B = -0.85; 95% confidence interval: -1.40 to -0.31) were associated with slower speed of information processing. The associations between cortisol and cognitive performance were the same for the younger and the older old and for depressed and nondepressed persons. Higher levels of cortisol were not associated with cognitive decline over a period of 6 years. CONCLUSION Our study provides further evidence that high levels of cortisol measured during the day are associated with lower memory function and speed of information processing but not with decline in cognitive functioning over 6 years of time.
Adrenaline during mental stress in relation to fitness, metabolic risk factors and cardiovascular responses in young men

We studied plasma adrenaline (A) in relation to physical fitness, metabolic cardiovascular risk factors and cardiovascular responses. Men (age 21–24 years) with high and normal (both n = 19) screening blood pressure (BP) were studied cross‐sectionally. We measured peak oxygen uptake (VO2peak) (treadmill exercise), and plasma catecholamines, heart rate (HR), finger systolic (SBP) and diastolic (DBP) BP, and insulin‐adjusted glucose disposal rate (GDR/I) during a hyperinsulinaemic glucose clamp (rest) and mental arithmetic stress test (MST). By multiple regression, A at rest (Arest) (β = 0.37, p<0.05) and during MST (Amst) (β = 0.40, p<0.01) were associated with high screening BP. In the respective models, Arest was negatively related to body mass index (BMI) (β = −0.56, p<0.001) and Amst positively to VO2peak (β = 0.54, p<0.001). BP and HR responses correlated positively with VO2peak, but were determined by Amst in multiple regression models. Independently of BMI and VO2peak, serum high‐density lipoprotein cholesterol was positively related to A levels, whereas GDR/I was independently related only to VO2peak. Increased adrenaline secretion may be related to high BP, but may at the same time be associated with a beneficial metabolic profile.
Effect of computerised evidence based guidelines on management of asthma and angina in adults in primary care: cluster randomised controlled trial

Abstract Objective: To evaluate the use of a computerised support system for decision making for implementing evidence based clinical guidelines for the management of asthma and angina in adults in primary care. Design: A before and after pragmatic cluster randomised controlled trial utilising a two by two incomplete block design. Setting: 60 general practices in north east England. Participants: General practitioners and practice nurses in the study practices and their patients aged 18 or over with angina or asthma. Main outcome measures: Adherence to the guidelines, based on review of case notes and patient reported generic and condition specific outcome measures. Results: The computerised decision support system had no significant effect on consultation rates, process of care measures (including prescribing), or any patient reported outcomes for either condition. Levels of use of the software were low. Conclusions: No effect was found of computerised evidence based guidelines on the management of asthma or angina in adults in primary care. This was probably due to low levels of use of the software, despite the system being optimised as far as was technically possible. Even if the technical problems of producing a system that fully supports the management of chronic disease were solved, there remains the challenge of integrating the systems into clinical encounters where busy practitioners manage patients with complex, multiple conditions.
Metabolomics-Based Discovery of Small Molecule Biomarkers in Serum Associated with Dengue Virus Infections and Disease Outcomes

Background Epidemic dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) are overwhelming public health capacity for diagnosis and clinical care of dengue patients throughout the tropical and subtropical world. The ability to predict severe dengue disease outcomes (DHF/DSS) using acute phase clinical specimens would be of enormous value to physicians and health care workers for appropriate triaging of patients for clinical management. Advances in the field of metabolomics and analytic software provide new opportunities to identify host small molecule biomarkers (SMBs) in acute phase clinical specimens that differentiate dengue disease outcomes. Methodology/Principal Findings Exploratory metabolomic studies were conducted to characterize the serum metabolome of patients who experienced different dengue disease outcomes. Serum samples from dengue patients from Nicaragua and Mexico were retrospectively obtained, and hydrophilic interaction liquid chromatography (HILIC)-mass spectrometry (MS) identified small molecule metabolites that were associated with and statistically differentiated DHF/DSS, DF, and non-dengue (ND) diagnosis groups. In the Nicaraguan samples, 191 metabolites differentiated DF from ND outcomes and 83 differentiated DHF/DSS and DF outcomes. In the Mexican samples, 306 metabolites differentiated DF from ND and 37 differentiated DHF/DSS and DF outcomes. The structural identities of 13 metabolites were confirmed using tandem mass spectrometry (MS/MS). Metabolomic analysis of serum samples from patients diagnosed as DF who progressed to DHF/DSS identified 65 metabolites that predicted dengue disease outcomes. Differential perturbation of the serum metabolome was demonstrated following infection with different DENV serotypes and following primary and secondary DENV infections. Conclusions/Significance These results provide proof-of-concept that a metabolomics approach can be used to identify metabolites or SMBs in serum specimens that are associated with distinct DENV infections and disease outcomes. The differentiating metabolites also provide insights into metabolic pathways and pathogenic and immunologic mechanisms associated with dengue disease severity.