Miracle-dz/UniFAR-FTUs huggingface dataset:
The Requirement of CD8+ T Cells To Initiate and Augment Acute Cardiac Inflammatory Response to High Blood Pressure

Macrophage infiltration and activation in myocardium are hallmarks of acute cardiac inflammatory response to high blood pressure. However, the underlying mechanisms remain elusive. In this article, we report that CD8+ T cells are required for cardiac recruitment and activation of macrophages. First, mice with CD8 gene-targeted (CD8 knockout) or CD8+ T cells depleted by Ab showed significantly reduced cardiac inflammatory response to the elevation of blood pressure after angiotensin II (Ang II) infusion, whereas CD8 knockout mice reconstituted with CD8+ T cells restored the sensitivity to Ang II. More importantly, CD8+ T cells were required for macrophage infiltration in myocardium and subsequent activation to express proinflammatory cytokines and chemokines. Furthermore, macrophage activation required direct contact with activated CD8+ T cells, but with TCR dispensable. TCR-independent activation of macrophages was further confirmed in MHC class I–restricted OVA-specific TCR transgenic mice, which showed a CD8+ T cell activation and cardiac proinflammatory response to Ang II similar to that of wild-type mice. Finally, only myocardium-infiltrated, but not peripheral, CD8+ T cells were specifically activated by Ang II, possibly by the cardiac IFN-γ that drove IFN-γR+ CD8+ T cell infiltration and activation. Thus, this work identified a TCR-independent innate nature of CD8+ T cells that was critical in initiating the sterile immune response to acute elevation of blood pressure.
Drivers and Outcomes of Business Model Innovation—Micro, Small and Medium-Sized Enterprises Perspective

Business model innovation (BMI) is one of the key activities, which has to be continuously undertaken in every enterprise to sustain competitiveness in today’s digital economy. Although the interest in business models (BM) has risen significantly since the late 1990s, little is known about BMI practices in small- and medium-sized enterprises (SMEs), representing a majority of enterprises in the European market. Our study addresses this research gap and focuses on the investigation of drivers and outcomes of BMI in SMEs. A partial least squares path modeling (PLS-PM) method was used to empirically test the model using data collected in 2017 from 71 SMEs in Slovenia. Results have shown that the innovativeness of enterprises and their business environment has a positive impact on the level of BMI activities in the enterprises. However, this is not the case of fast developing and rapidly changing information technology. In addition, the results show that the level of BMI has a positive impact on BMI outcomes and further on overall business performance. The results contribute to the body of knowledge in the field of BMI activities in SMEs and offer useful insights to SMEs that intend to innovate their business model(s) and government to create a supportive environment.
Meta-analysis of individual patient data from randomized trials: a review of methods used in practice

Background Meta-analyses based on individual patient data (IPD) are regarded as the gold standard for systematic reviews. However, the methods used for analysing and presenting results from IPD meta-analyses have received little discussion. Methods We review 44 IPD meta-analyses published during the years 1999–2001. We summarize whether they obtained all the data they sought, what types of approaches were used in the analysis, including assumptions of common or random effects, and how they examined the effects of covariates. Results Twenty-four out of 44 analyses focused on time-to-event outcomes, and most analyses (28) estimated treatment effects within each trial and then combined the results assuming a common treatment effect across trials. Three analyses failed to stratify by trial, analysing the data is if they came from a single mega-trial. Only nine analyses used random effects methods. Covariate-treatment interactions were generally investigated by subgrouping patients. Seven of the meta-analyses included data from less than 80% of the randomized patients sought, but did not address the resulting potential biases. Conclusions Although IPD meta-analyses have many advantages in assessing the effects of health care, there are several aspects that could be further developed to make fuller use of the potential of these time-consuming projects. In particular, IPD could be used to more fully investigate the influence of covariates on heterogeneity of treatment effects, both within and between trials. The impact of heterogeneity, or use of random effects, are seldom discussed. There is thus considerable scope for enhancing the methods of analysis and presentation of IPD meta-analysis.
Distributed Synchronization for Device-to-Device Communications in an LTE Network

We study the problem of distributed time and frequency synchronization for device-to-device communication in LTE [1]. LTE is an OFDMA system that crucially uses tight time and frequency synchronization between UEs and the base station for intracell and intercell interference coordination. For consistency with the cyclic prefix length and tone spacing used in LTE, we target an accuracy of a few microseconds for time synchronization and 150 Hz for frequency synchronization. We examine the problem both from a link and a system-level perspective. Link-level challenges involve designing a synchronization signal for computationally and energy efficient receiver algorithms, and system-level challenges involve achieving consistent timing using a distributed algorithm while leveraging the multiuser aspect of the problem to improve performance.
A Novel Monoclonal Antibody to Secreted Frizzled-Related Protein 2 Inhibits Tumor Growth

Secreted frizzled-related protein 2 (SFRP2) is overexpressed in human angiosarcoma and breast cancer and stimulates angiogenesis via activation of the calcineurin/NFATc3 pathway. There are conflicting reports in the literature as to whether SFRP2 is an antagonist or agonist of β-catenin. The aims of these studies were to assess the effects of SFRP2 antagonism on tumor growth and Wnt-signaling and to evaluate whether SFRP2 is a viable therapeutic target. The antiangiogenic and antitumor properties of SFRP2 monoclonal antibody (mAb) were assessed using in vitro proliferation, migration, tube formation assays, and in vivo angiosarcoma and triple-negative breast cancer models. Wnt-signaling was assessed in endothelial and tumor cells treated with SFRP2 mAb using Western blotting. Pharmacokinetic and biodistribution data were generated in tumor-bearing and nontumor-bearing mice. SFRP2 mAb was shown to induce antitumor and antiangiogenic effects in vitro and inhibit activation of β-catenin and nuclear factor of activated T-cells c3 (NFATc3) in endothelial and tumor cells. Treatment of SVR angiosarcoma allografts in nude mice with the SFRP2 mAb decreased tumor volume by 58% compared with control (P = 0.004). Treatment of MDA-MB-231 breast carcinoma xenografts with SFRP2 mAb decreased tumor volume by 52% (P = 0.03) compared with control, whereas bevacizumab did not significantly reduce tumor volume. Pharmacokinetic studies show the antibody is long circulating in the blood and preferentially accumulates in SFRP2-positive tumors. In conclusion, antagonizing SFRP2 inhibits activation of β-catenin and NFATc3 in endothelial and tumor cells and is a novel therapeutic approach for inhibiting angiosarcoma and triple-negative breast cancer. Mol Cancer Ther; 12(5); 685–95. ©2013 AACR.
Assessment and comparison of thermal stability of phosphorothioate-DNA, DNA, RNA, 2′-F RNA, and LNA in the context of Phi29 pRNA 3WJ

The question of whether RNA is more stable or unstable compared to DNA or other nucleic acids has long been a subject of extensive scrutiny and public attention. Recently, thermodynamically stable and degradation-resistant RNA motifs have been utilized in RNA nanotechnology to build desired architectures and integrate multiple functional groups. Here we report the effects of phosphorothioate deoxyribonucleotides (PS-DNA), deoxyribonucleotides (DNA), ribonucleotides (RNA), 2′-F nucleotides (2′-F), and locked nucleic acids (LNA) on the thermal and in vivo stability of the three-way junction (3WJ) of bacteriophage phi29 motor packaging RNA. It was found that the thermal stability gradually increased following the order of PS-DNA/PS-DNA < DNA/DNA < DNA/RNA < RNA/RNA < RNA/2′-F RNA < 2’-F RNA/2′-F RNA < 2′-F RNA/LNA < LNA/LNA. This proposition is supported by studies on strand displacement and the melting of homogeneous and heterogeneous 3WJs. By simply mixing different chemically modified oligonucleotides, the thermal stability of phi29 pRNA 3WJ can be tuned to cover a wide range of melting temperatures from 21.2°C to over 95°C. The 3WJLNA was resistant to boiling temperature denaturation, urea denaturation, and 50% serum degradation. Intravenous injection of fluorescent LNA/2′-F hybrid 3WJs into mice revealed its exceptional in vivo stability and presence in urine. It is thus concluded that incorporation of LNA nucleotides, alone or in combination with 2′-F, into RNA nanoparticles derived from phi29 pRNA 3WJ can extend the half-life of the RNA nanoparticles in vivo and improve their pharmacokinetics profile.
SMG-2 Is a Phosphorylated Protein Required for mRNA Surveillance in Caenorhabditis elegans and Related to Upf1p of Yeast

ABSTRACT mRNAs that contain premature stop codons are selectively degraded in all eukaryotes tested, a phenomenon termed “nonsense-mediated mRNA decay” (NMD) or “mRNA surveillance. ” NMD may function to eliminate aberrant mRNAs so that they are not translated, because such mRNAs might encode deleterious polypeptide fragments. In both yeasts and nematodes, NMD is a nonessential system. Mutations affecting three yeast UPF genes or seven nematode smg genes eliminate NMD. We report here the molecular analysis ofsmg-2 of Caenorhabditis elegans.smg-2 is homologous to UPF1 of yeast and to RENT1 (also called HUPF1), a human gene likely involved in NMD. The striking conservation of SMG-2, Upf1p, and RENT1/HUPF1 in both sequence and function suggests that NMD is an ancient system, predating the divergence of most eukaryotes. Despite similarities in the sequences of SMG-2 and Upf1p, expression of Upf1p in C. elegans does not rescue smg-2 mutants. We have prepared anti-SMG-2 polyclonal antibodies and identified SMG-2 on Western blots. SMG-2 is phosphorylated, and mutations of the six other smg genes influence the state of SMG-2 phosphorylation. In smg-1,smg-3, and smg-4 mutants, phosphorylation of SMG-2 was not detected. In smg-5, smg-6, andsmg-7 mutants, a phosphorylated isoform of SMG-2 accumulated to abnormally high levels. In smg-2(r866) andsmg-2(r895) mutants, which harbor single amino acid substitutions of the SMG-2 nucleotide binding site, phosphorylated SMG-2 accumulated to abnormally high levels, similar to those observed in smg-5, smg-6, and smg-7 mutants. We discuss these results with regard to the in vivo functions of SMG-2 and NMD.
Innovations and Revolutions in Indian Agriculture: A Review

: With a population of 1.35 billion to feed in 2018, innovations in Indian agriculture all along the value chains are critical to develop sustainable, productive and profitable agriculture. In this brief paper, focus is laid on innovations in various production technologies, farming practices, policies and institutional engineering that had significant impact in raising production and have been termed as revolutionary. For instance, Green Revolution is identified with significant changes in production of wheat and rice; White Revolution in milk; Blue Revolution in fisheries; Red Revolution in poultry meat and eggs; Golden Revolution in fruits and vegetables; Gene Revolution in cotton. The paper not only looks at these innovations and their impact in the past, but also peeps into innovations that are currently unfolding in other inputs in production processes such as in water use (irrigation), fertilizers usage, maintaining soil health, using farm machinery optimally in a small holder dominated agriculture. The key message of this paper is what can be achieved with small holders when innovations that are science based and are backed by right policies, are adopted.
Archivos y Derechos Humanos

En junio, el Tribunal Especial para el Líbano anunció que "cerrará después de julio debido a una crisis financiera". https://liberties.aljazeera. com/en/special-tribunal-for-lebanon-to-close-its-doors/ Pocos días después, el viceprimer ministro de Camboya "informó a los diplomáticos extranjeros que representan a 10 países donantes que las Cámaras Extraordinarias en los Tribunales de Camboya (ECCC por sus siglas en inglés), comúnmente conocidas como el Tribunal del Jemer Rojo, terminarán su último caso a finales de este año y se centrarán en el archivo a partir de entonces". https://www.phnompenhpost. com/national-kr-tribunal/eccc-closing-final-case-years-end
Design of UWB Planar Band-Notched Antenna Using Parasitic Elements

A method is described to reject certain bands within the passband of an ultrawideband (UWB) planar antenna using parasitic elements. In the presented design, the antenna is created by a planar monopole and a ground plane both of half circle shape, whereas parasitic elements are in the form of printed strips. Four examples of UWB antenna design are shown. The first design is without parasitic, while the remaining ones are with parasitics to reject a single narrow band, a wide band or three narrow bands. The results of simulation and measurements show that all these antenna designs exhibit a 10-dB return loss bandwidth from 3 GHz to 11 GHz excluding the rejected bands. More than 10 dB gain drop is recorded in the suppressed bands. The time domain transmission test between two identical antennas without the parasitic strips shows an almost distortionless pulse performance.
Cognitive function, gait, and gait variability in older people: a population-based study.

BACKGROUND Gait impairments are associated with falls and loss of independence. The study of factors associated with poorer gait may assist in developing methods to preserve mobility in older people. The aim of this study was to examine the associations between a range of cognitive functions and gait and gait variability in a population-based sample of older people. METHODS Gait and intra-individual gait variability measures were obtained using the GAITRite walkway in a sample of older people, aged 60-85 years (N = 422), randomly selected from the Tasmanian electoral roll. Raw scores from a cognitive battery were subjected to principal component analyses deriving four summary domains: executive function/attention, processing speed, memory, and visuospatial ability. Multivariable linear regression was used to examine associations between cognitive domains and gait measures adjusting for age, sex, ambulatory activity, medication use, and mood. RESULTS The mean age of the sample was 72.0 years (SD = 7.0), with 238 men (56%). Poorer executive function was independently associated with poorer performance in most absolute gait measures and with greater variability in double support phase and step time. Processing speed was associated with absolute gait measures and double support phase variability. Visuospatial ability was only associated with greater double support phase variability, independently of executive function and processing speed. Memory was not independently associated with any gait measure. CONCLUSIONS In community-dwelling older people, executive function/attention and processing speed were associated with many aspects of gait, whereas visuospatial ability may only play a role in double support phase variability.
The role of CB1 receptors in sweet versus fat reinforcement: effect of CB1 receptor deletion, CB1 receptor antagonism (SR141716A) and CB1 receptor agonism (CP-55940)

It is well established that Cannabis sativa can increase appetite, particularly for sweet and palatable foods. In laboratory animals, cannabinoid CB1 receptor antagonism decreases motivation for palatable foods, and most recently, the CB1 receptor antagonist SR141716A, or rimonabant (Acomplia), was reported to produce weight loss in obese human subjects. Indeed, the endocannabinoid system plays a select role in the rewarding properties of palatable foods, and this is well characterized in laboratory animals with sweet sucrose solutions. In the present study, CB1 knockout mice (CB1 KO) and wild-type littermate mice (WT) were trained to respond for a complex sweet as well as a pure fat reinforcer under a progressive ratio (PR) schedule, to determine whether motivation to consume different palatable foods is tonically regulated by CB1 receptors. To assess sweet reinforcement, several concentrations of the liquid nutritional drink, Ensure, were presented under the PR schedule. For fat reinforcement, several concentrations of corn oil (emulsified in 3% xanthan gum) were made available. Additionally, to compare the result of genetic invalidation of the CB1 receptor to antagonism of the CB1 receptor system, the effect of SR141716A (3.0 mg/kg) on responding for Ensure and corn oil were also assessed using the PR schedule. We also assessed the effect of the CB1 agonist CP-55940 (30 μg/kg) on responding for Ensure and corn oil. CB1 KOs took significantly longer to acquire operant responding maintained by Ensure, and responding for Ensure under the PR schedule was significantly reduced in CB1 KOs as well as in WTs pretreated with SR141716A, as compared to WT controls. Additionally, pretreatment with the CB1 agonist CP-55940 increased responding for Ensure. In contrast, responding for corn oil during acquisition and under the PR schedule was not significantly different in CB1 KOs versus wild-type mice. However, SR141716A did reduce responding for corn oil in WTs, and CP-55940 significantly increased responding for corn oil. Taken together, these results suggest that CB1 receptors are preferentially involved in the reinforcing effects of a complex sweet, as compared to a pure fat, reinforcer. These data also suggest, however, that antagonism of CB1 receptors with SR141716A is sufficient to attenuate the reinforcing effect of Ensure and corn oil, while activation of the central CB1 system is sufficient to enhance Ensure and corn oil reinforcement.
Pro-Cyclicality of Traditional Risk Measurements: Quantifying and Highlighting Factors at its Source

Since the introduction of risk-based solvency regulation, pro-cyclicality has been a subject of concerns from all market participants. Here, we lay down a methodology to evaluate the amount of pro-cyclicality in the way financial institutions measure risk, and identify factors explaining this pro-cyclical behavior. We introduce a new indicator based on the Sample Quantile Process (SQP, a dynamic generalization of Value-at-Risk), conditioned on realized volatility to quantify the pro-cyclicality, and evaluate its amount in the markets, considering 11 stock indices as realizations of the SQP. Then we determine two main factors explaining the pro-cyclicality: the clustering and return-to-the-mean of volatility, as it could have been anticipated but not quantified before, and, more surprisingly, the very way risk is measured, independently of this return-to-the-mean effect.
Vibrio vulnificus RTX toxin kills host cells only after contact of the bacteria with host cells

Vibrio vulnificus causes acute cell death and a fatal septicaemia. In this study, we show that contact with host cells is a prerequisite to the acute cytotoxicity. We screened transposon mutants defective in the contact‐dependent cytotoxicity. Two mutants had insertions within two open reading frames in a putative RTX toxin operon, the rtxA1 or rtxD encoding an RTX toxin (4701 amino acids) or an ABC type transporter (467 amino acids). An rtxA1 mutation resulted in a cytotoxicity defect, which was fully restored by in trans complementation. The expression of RtxA1 toxin increased after host cell contact in a time‐dependent manner. The RtxA1 toxin induced cytoskeletal rearrangements and plasma membrane blebs, which culminated in a necrotic cell death. RtxA1 colocalized with actin and caused actin aggregation coinciding with a significant decrease in the F/G actin ratio. The RtxA1 toxin caused haemolysis through pore formation (radius 1.63 nm). The rtxA1 deletion mutant was defective in invading the blood stream from ligated ileal loops of CD1 mice. The rtxA1 null mutation resulted in over 100‐fold increase in both intragastric and intraperitoneal LD50s against mice. Overall, these results show that the RtxA1 toxin is a multifunctional cytotoxin and plays an essential role in the pathogenesis of V. vulnificus infections.
Police personality classification using principle component analysis-artificial neural network

Personality is the defining essence of an individual as it guides the way we think, act and interpret external stimuli. Classification of personality is important as it can serves as a framework in the job assignment task, particularly, in the high risk job including the Police Force. There are many attributes of individual traits but not all of them can be used to indicate individual personality. In this paper, two classification models were developed to predict individual personality for the Royal Malaysian police (RMP) based on Type A and Type B personality theory. Both classification models are based on Artificial Neural Network (ANN). But, the second model applied Principle Component Analysis or called as PCA-ANN model. The second classification model successfully reduces the number of personality features to six features compared to initial 10 features. Furthermore, PCA-ANN improves the classification accuracy to 98.6% compared to 94.4% classification accuracy found in the first ANN model.
New Dates on Northern Yukon Artifacts: Holocene Not Upper Pleistocene

New radiocarbon dates on four artifacts that were thought to provide evidence for human occupation of the Yukon Territory during the upper Pleistocene indicate that all four are of late Holocene age. The original radiocarbon age obtained for one artifact (the so-called "Old Crow flesher") was in error by almost 26,000 years.
Looking at Allergens Increases Symptom Report in Patients with Allergic Asthma

Objective. Accurate symptom perception is highly important for self-management and clinical treatment of asthma. Recent findings suggest that psychological factors can greatly impact asthma symptom perception. This study examined whether looking at allergens would lead to changes in perceived asthma symptoms. Methods. Allergic asthma patients and healthy controls viewed picture series containing either allergens or neutral material. Symptom reports and respiratory parameters were measured. Results. The present results demonstrate that looking at pictures with allergens increases subjective symptom reports in patients with allergic asthma in the absence of changes in objective respiratory parameters, but not in healthy controls. Conclusions. The results are suggestive of preceding learning processes during which patients have learned the association between visual representations of allergens and symptom-inducing effects of real contact with these allergens. This impacts asthma symptom perception without changes in respiratory status and might influence treatment decisions.