Miracle-dz/UniFAR-FTUs huggingface dataset:
MicroRNA-155 Deficiency Results in Decreased Macrophage Inflammation and Attenuated Atherogenesis in Apolipoprotein E–Deficient Mice

Objective—microRNA-155 (miR155) plays a critical role in immunity and macrophage inflammation. We aim to investigate the role of miR155 in atherogenesis. Approach and Results—Quantitative real-time polymerase chain reaction showed that miR155 was expressed in mouse and human atherosclerotic lesions. miR155 expression in macrophages was correlated positively with proinflammatory cytokine expression. Lentivirus-mediated overexpression of miR155 in macrophages enhanced their inflammatory response to lipopolysaccharide through targeting suppressor of cytokine signaling-1 and impaired cholesterol efflux from acetylated low-density lipoprotein–loaded macrophages, whereas deficiency of miR155 blunted macrophage inflammatory responses and enhanced cholesterol efflux possibly via enhancing lipid loading–induced macrophage autophagy. We next examined the atherogenesis in apolipoprotein E–deficient (apoE−/−) and miR155−/−/apoE−/− (double knockout) mice fed a Western diet. Compared with apoE−/− mice, the double knockout mice developed less atherosclerosis lesion in aortic root, with reduced neutral lipid content and macrophages. Flow cytometric analysis showed that there were increased number of regulatory T cells and reduced numbers of Th17 cells and CD11b+/Ly6Chigh cells in the spleen of double knockout mice. Peritoneal macrophages from the double knockout mice had significantly reduced proinflammatory cytokine expression and secretion both in the absence and presence of lipopolysaccharide stimulation. To determine whether miR155 in leukocytes contributes to atherosclerosis, we performed a bone marrow transplantation study. Deficiency of miR155 in bone marrow–derived cells suppressed atherogenesis in apoE−/− mice, demonstrating that hematopoietic cell–derived miR155 plays a critical role. Conclusions—miR155 deficiency attenuates atherogenesis in apoE−/− mice by reducing inflammatory responses of macrophages, enhancing macrophage cholesterol efflux and resulting in an antiatherogenic leukocyte profile. Targeting miR155 may be a promising strategy to halt atherogenesis.
Structural Tags, Annealing and Automatic Word Classification

This paper describes an automatic word classification system which uses a locally optimal annealing algorithm and average class mutual information. A new word-class representation, the structural tag is introduced and its advantages for use in statistical language modelling are presented. A summary of some results with the one million word LOB corpus is given; the algorithm is also shown to discover the vowel-consonant distinction and displays an ability to cluster words syntactically in a Latin corpus. Finally, a comparison is made between the current classification system and several leading alternative systems, which shows that the current system performs respectably well.
Rapid Molecular Detection of Rifampicin Resistance Facilitates Early Diagnosis and Treatment of Multi-Drug Resistant Tuberculosis: Case Control Study

Background Multi-drug resistant tuberculosis (MDR-TB) is a major public health concern since diagnosis is often delayed, increasing the risk of spread to the community and health care workers. Treatment is prolonged, and the total cost of treating a single case is high. Diagnosis has traditionally relied upon clinical suspicion, based on risk factors and culture with sensitivity testing, a process that can take weeks or months. Rapid diagnostic molecular techniques have the potential to shorten the time to commencing appropriate therapy, but have not been put to the test under field conditions. Methodology/Principal Findings This retrospective case-control study aimed to identify risk factors for MDR-TB, and analyse the impact of testing for rifampicin resistance using RNA polymerase B (rpoB) mutations as a surrogate for MDR-TB. Forty two MDR-TB cases and 84 fully sensitive TB controls were matched by date of diagnosis; and factors including demographics, clinical presentation, microbiology findings, management and outcome were analysed using their medical records. Conventionally recognised risk factors for MDR-TB were absent in almost half (43%) of the cases, and 15% of cases were asymptomatic. A significant number of MDR-TB cases were identified in new entrants to the country. Using rpoB mutation testing, the time to diagnosis of MDR-TB was dramatically shortened by a median of 6 weeks, allowing patients to be commenced on appropriate therapy a median of 51days earlier than those diagnosed by conventional culture and sensitivity testing. Conclusions/Significance MDR-TB is frequently an unexpected finding, may be asymptomatic, and is particularly prevalent among TB infected new entrants to the country. Molecular resistance testing of all acid fast bacilli positive specimens has the potential to rapidly identify MDR-TB patients and commence them on appropriate therapy significantly earlier than by conventional methods.
Differential testing: a new approach to change detection

Regression testing, as it's commonly practiced, is unsound due to inconsistent test repair and test addition. This paper presents a new technique, differential testing, that alleviates the test repair problem and detects more changes than regression testing alone. Differential testing works by creating test suites for both the original system and the modified system and contrasting both versions of the system with these two suites. Differential testing is made possible by recent advances in automated unit test generation. Furthermore, it makes automated test generators more useful because it abstracts away the interpretation and management of large volumes of tests by focusing on the changes between test suites. In our preliminary empirical study of 3 subjects, differential testing discovered 21%, 34%, and 21% more behavior changes than regression testing alone.
Eastern cooperative group trial of interferon gamma in metastatic melanoma: an innovative study design.

IFN-gamma is a potent immunomodulator, which has activity against melanoma in vitro and in murine models. However, preclinical data suggests that the optimal therapeutic and immunomodulatory dose may not be the maximally tolerated clinical dose. We conducted a Phase II/III trial in good prognosis patients with metastatic melanoma to determine whether a therapeutic and immunomodulatory dose-response curve of IFN-gamma could be identified, and whether the two could be correlated. Ninety-eight patients with metastatic melanoma were randomized to one of seven dose levels of IFN-gamma ranging from 0.01 to 0.90 mg/m2. All patients were required to have s.c. , skin, soft tissue, or nodal disease, although visceral disease was also allowed, and no more than one prior chemotherapy regimen. Patients received IFN-gamma as a 1-h i.v. infusion three times per week for at least 8 weeks or until progressive disease. Ninety-five patients were eligible for toxicity evaluation; 81 were eligible for tumor response. Four patients responded to therapy (response rate, 5%) at three dose levels: two patients at 0.01 mg/m2 and one each at 0.5 and 0.9 mg/m2. The duration of response ranged from 5 to 58 weeks. Toxicities were typical of IFNs and included flu-like constitutional symptoms. No dose-response relationship was identified for efficacy. A dose-response relationship for toxicity was observed only for fever and chills (p = 0.035) and hepatic toxicity (p = 0.034). IFN-gamma has minimal activity in metastatic melanoma, and a therapeutic dose-response curve could not be identified. Although potent dose-dependent effects on immunomodulation were identified (J. M. Kirkwood, J. Bryant, J. H. Schiller, M. M. Oken, E. C. Borden, and T. L. Whiteside. Immunomodulatory function of interferon gamma in patients with metastatic melanoma: results of a phase IIB trial in subjects with metastatic melanoma: ECOG Study E4987, submitted for publication), this biological activity does not translate into therapeutic activity in the metastatic disease setting in this trial.
Convex Optimization-based Beamforming : From Receive to Transmit and Network Designs

n this article, an overview of advanced convex optimization approaches to multisensor beamforming is presented, and connections are drawn between different types of optimization-based beamformers that apply to a broad class of receive, transmit, and network beamformer design problems. It is demonstrated that convex optimization provides an indispensable set of tools for beamforming, enabling rigorous formulation and effective solution of both long-standing and emerging design problems.
Bacterioplankton distribution and production in the bathypelagic ocean: Directly coupled to particulate organic carbon export?,

A recently published evaluation of bacterioplankton abundance and productivity in the bathypelagic North Pacific suggests that these properties are generally coupled with particulate organic carbon (POC) fluxes. In that analysis, bacterial biomass and productivity were several–fold greater in subarctic than subtropical waters, consistent with the basin–scale distribution of POC flux and suggestive of a sinking POC > DOC > bacteria transformation of the carbon. To test this hypothesis, we sought to determine whether the very strong spatial and temporal gradients in POC flux in the Arabian Sea would force similar deep–ocean gradients in bacterial variables. On both a within and between–cruise basis, there was variability in bacterial abundance and thymidine incorporation in the deep Arabian Sea, but correspondence was equivocal between these variables and several correlates to export: flux of biogenic carbon from the euphotic zone, state of the monsoon, and proximity to productive coastal upwelling zones. However, when annual mean bacterial abundance at 2,000 m was compared with annual POC flux at that depth, a strong correspondence emerged: high annual flux supported high bacterial abundance (such a correspondence was not found for bacterial productivity). This finding suggests that bathypelagic bacterial abundance responds to the long–term mean input of organic matter and less to episodic inputs. A comparative evaluation of the North Pacific revealed that although the bathypelagic bacteria there showed correspondence to deep POC flux, that variable alone would not account for the wide meridional variations in bacterial abundance that have been reported.
Time-to-digital converter with vernier delay mismatch compensation for high resolution on-die clock jitter measurement

A time-to-digital converter (TDC) utilizing a vernier delay line (VDL) technique has relatively large timing errors when the mismatch of the vernier delay is large. In order to overcome this problem, we propose a technique for compensating the vernier delay mismatch using multiple ring oscillation measurements of VDL. We verified it using an on-die jitter measurement circuit implemented in 90 nm CMOS technology and 0.880 ps timing resolution was obtained experimentally.
VSA-CubeBot: A modular variable stiffness platform for multiple degrees of freedom robots

We propose a prototype of a Variable Stiffness Actuator (VSA) conceived with low cost as its first goal. This approach was scarcely covered in past literature. Many recent works introduced a large number of actuators with adjustable stiffness, optimized for a wide set of applications. They cover a broad range of design possibilities, but their availability is still limited to small quantities. This work presents the design and implementation of a modular servo-VSA multi-unit system, called VSA-CubeBot. It offers a customizable platform for the realization and test of variable stiffness robotic structures with many degrees of freedom. We present solutions relative to the variable stiffness mechanism, embedded electronics, mechanical and electrical interconnections. Characteristics, both theoretic and experimental, of the single actuator are reported and, finally, five units are interconnected to form a single arm, to give an example of the many possible applications of this modular VSA actuation unit.
Scattering and Imaging of Nonlinearly Loaded Antenna Structures in Half-Space Environments

The electromagnetic scattering responses of nonlinearly loaded antenna structures excited by single-tone or multi-tone incident fields are considered in the frequency domain by employing a combination of the method-of-moments and a harmonic balance technique. Subsequently, standoff detection and localization of the scatterers in the presence of a half space is demonstrated with a subspace imaging procedure by exploiting the steady-state, multistatic harmonic scattering responses collected over an aspect-limited aperture. The attenuation rates of the harmonic scattered fields as a function of sensing range are investigated. The Green's function vector in the imaging functional is derived efficiently with the application of second-order-accurate asymptotic propagation techniques, and near-field imaging performance for single and multiple targets is also examined in the presence of noise and linear clutter. This study is intended to provide an analysis and simulation framework needed to facilitate the development of a complementary nonlinear detection capability for an existing near-ground, forward-looking linear imaging radar system.
Comparative effectiveness of second-line targeted therapies for metastatic renal cell carcinoma: synthesis of findings from two multi-practice chart reviews in the United States

Abstract Background: Second-line targeted therapies for metastatic renal cell carcinoma (mRCC) include mammalian target of rapamycin (mTOR) inhibitors and tyrosine kinase inhibitors (TKIs). This study compares the effectiveness of these therapies in a multi-practice chart review and synthesizes the findings with those of a similarly designed study. Methods: Medical oncologists/hematologists (N = 36) were recruited to review charts for patients aged ≥18 years, received a first-line TKI and initiated second-line targeted therapy in 2010 or later. The primary outcome was time from second-line initiation to treatment failure (TTF; discontinuation, physician-assessed progression, or death, whichever occurred first). TTF was compared among patients receiving second-line everolimus (EVE), temsirolimus (TEM), or TKI as a class, using a Cox proportional hazards model adjusting for type of initial TKI and response, histological subtype, performance status, and sites of metastasis. Hazard ratios (HRs) for TTF were pooled, in a meta-analysis, with previously reported HRs for progression-free survival from a chart review with a similar design. Results: A total of 138, 64 and 79 patients received second-line therapy with EVE, TEM or a TKI, respectively. Adjusting for baseline characteristics, EVE was associated with numerical, but not statistically significant, reductions of 28% (HR = 0.72; 95% CI [0.45–1.16]) and 26% (HR = 0.74; 95% CI [0.48–1.15]) in the hazard of TTF compared to TEM and TKI, respectively. After pooling the HRs from both studies, EVE was associated with significantly reduced hazards of TTF compared to TEM and TKI (HR = 0.73; 95% CI [0.57–0.93]; and HR = 0.75; 95% CI [0.57–0.98], respectively). Limitations: Limitations include retrospective analyses with possible missing or erroneous chart data, confounding of unobserved factors due to non-randomization, and limited data for axitinib during the study period. Conclusions: In pooled results from two independent multi-practice chart reviews of second-line mRCC treatment, EVE was associated with significantly reduced hazards of treatment failure compared to TEM and to TKIs as a class.
Neurophysiological Influence of Musical Training on Speech Perception

Does musical training affect our perception of speech? For example, does learning to play a musical instrument modify the neural circuitry for auditory processing in a way that improves one's ability to perceive speech more clearly in noisy environments? If so, can speech perception in individuals with hearing loss (HL), who struggle in noisy situations, benefit from musical training? While music and speech exhibit some specialization in neural processing, there is evidence suggesting that skills acquired through musical training for specific acoustical processes may transfer to, and thereby improve, speech perception. The neurophysiological mechanisms underlying the influence of musical training on speech processing and the extent of this influence remains a rich area to be explored. A prerequisite for such transfer is the facilitation of greater neurophysiological overlap between speech and music processing following musical training. This review first establishes a neurophysiological link between musical training and speech perception, and subsequently provides further hypotheses on the neurophysiological implications of musical training on speech perception in adverse acoustical environments and in individuals with HL.
Region-specific RNA m6A methylation represents a new layer of control in the gene regulatory network in the mouse brain

N6-methyladenosine (m6A) is the most abundant epitranscriptomic mark found on mRNA and has important roles in various physiological processes. Despite the relatively high m6A levels in the brain, its potential functions in the brain remain largely unexplored. We performed a transcriptome-wide methylation analysis using the mouse brain to depict its region-specific methylation profile. RNA methylation levels in mouse cerebellum are generally higher than those in the cerebral cortex. Heterogeneity of RNA methylation exists across different brain regions and different types of neural cells including the mRNAs to be methylated, their methylation levels and methylation site selection. Common and region-specific methylation have different preferences for methylation site selection and thereby different impacts on their biological functions. In addition, high methylation levels of fragile X mental retardation protein (FMRP) target mRNAs suggest that m6A methylation is likely to be used for selective recognition of target mRNAs by FMRP in the synapse. Overall, we provide a region-specific map of RNA m6A methylation and characterize the distinct features of specific and common methylation in mouse cerebellum and cerebral cortex. Our results imply that RNA m6A methylation is a newly identified element in the region-specific gene regulatory network in the mouse brain.
Nitric Oxide Synthesis Enhances Human Immunodeficiency Virus Replication in Primary Human Macrophages

ABSTRACT Macrophages are suspected to play a major role in human immunodeficiency virus (HIV) infection pathogenesis, not only by their contribution to virus dissemination and persistence in the host but also through the dysregulation of immune functions. The production of NO, a highly reactive free radical, is thought to act as an important component of the host immune response in several viral infections. The aim of this study was to evaluate the effects of HIV type 1 (HIV-1) Ba-L replication on inducible nitric oxide synthase (iNOS) mRNA expression in primary cultures of human monocyte-derived macrophages (MDM) and then examine the effects of NO production on the level of HIV-1 replication. Significant induction of the iNOS gene was observed in cultured MDM concomitantly with the peak of virus replication. However, this induction was not accompanied by a measurable production of NO, suggesting a weak synthesis of NO. Surprisingly, exposure to low concentrations of a NO-generating compound (sodium nitroprusside) andl-arginine, the natural substrate of iNOS, results in a significant increase in HIV replication. Accordingly, reduction ofl-arginine bioavailability after addition of arginase to the medium significantly reduced HIV replication. The specific involvement of NO was further demonstrated by a dose-dependent inhibition of viral replication that was observed in infected macrophages exposed to N G-monomethyll-arginine andN G-nitro-l-arginine methyl ester (l-NAME), two inhibitors of the iNOS. Moreover, an excess of l-arginine reversed the addition of L-NAME, confirming that an arginine-dependent mechanism is involved. Finally, inhibitory effects of hemoglobin which can trap free NO in culture supernatants and in biological fluids in vivo confirmed that endogenously produced NO could interfere with HIV replication in human macrophages.
Modelling Irrigation and Salinity Management Strategies in the Ord Irrigation Area

The Ord River Irrigation Area (ORIA) is located within northern Western Australia near the Northern Territory border. Since the beginning of irrigated agriculture in the ORIA the groundwater levels have been continuously rising and are now close to the soil surface in some parts of ORIA in northern Western Australia. The groundwater is now saline throughout most of the ORIA and soil salinity risks are high where the watertables are shallow. This research evaluated irrigation and salinity management strategies for sugarcane and maize crops grown over deep and shallow, non-saline and saline watertables in the ORIA. The LEACHC model, calibrated using field data, was used to predict the impacts of various irrigation management strategies on water use and salt accumulation in the root zone. This study concluded that irrigation application equal to 100% of total fortnightly pan evaporation applied at 14 day intervals was a good irrigation strategy for the maize grown over a deep watertable area. This strategy would require around 11 ML/ha of irrigation water per growing season. Irrigation application equal to 75% of total fortnightly pan evaporation, applied every fortnight during first half of the growing season, and 75% of total weekly pan evaporation, applied on a weekly basis during second half of the growing season, would be the best irrigation strategy if it is feasible to change the irrigation interval from 14 to seven days. This irrigation strategy is predicted to have minimal salinity risks and save around 40% irrigation water. The best irrigation strategy for sugarcane grown on Cununurra clay over a deep watertable area would be irrigation application equal to 50% of the total fortnightly pan evaporation, applied every fortnight during first quarter of the growing season, and irrigation application amounts equal to 100% of total weekly pan evaporation, applied every week during rest of the season. The model predicted no soil salinity risks from this irrigation strategy. The best irrigation strategy for sugarcane over a non-saline, shallow watertable of one or two m depth would be irrigation application amounts equal to 50% of total fortnightly pan evaporation applied every fortnight. In the case of a saline watertable the same irrigation strategy was predicted to the best with respect to water use efficiency but will have high salinity risks without any drainage management.