Miracle-dz/UniFAR-FTUs huggingface dataset:
Rapamycin Augments Human DC IL‐12p70 and IL‐27 Secretion to Promote Allogeneic Type1 Polarization Modulated by NK Cells

Mammalian target of rapamycin kinase inhibitor (mTORi) rapamycin (RAPA) use in transplantation can lead to inflammatory complications in some patients. Our goal was to better understand how mTORi‐exposed human monocyte‐derived dendritic cells (DC) stimulated with pro‐inflammatory cytokines shape T cell allo‐immunity. RAPA‐conditioned‐DC (RAPA‐DC) displayed a more immature phenotype than untreated, control (CTRL)‐DC. However, subsequent exposure of RAPA‐DC to an inflammatory cytokine cocktail (ICC) plus IFN‐γ induced a mature Type‐1 promoting phenotype, consisting of elevated HLA‐DR and co‐stimulatory molecules, augmented IL‐12p70 and IL‐27 production, but decreased IL‐10 secretion compared to CTRL‐DC. Co‐culture of mature (m)RAPA‐DC with allogeneic peripheral blood mononuclear cells resulted in significantly increased Type‐1 (IFN‐γ) responses by T cells. Moreover, NK cells acted as innate modulators that conveyed activating cell‐to‐cell contact signals in addition to helper (IFN‐γ) and/or regulatory (IL‐10) soluble cytokines. We conclude that production of IL12‐p70, IL‐27 and low IL‐10 by RAPA‐DC allowed us to elucidate how these cytokines as well as NK‐DC interaction shapes T cell allo‐immunity. Thus, lack of inhibitory NK cell function during allo‐specific T cell activation by human ICC + IFN‐γ‐stimulated RAPA‐DC may represent an unwanted effector mechanism that may underlie RAPA‐induced inflammatory events in transplant patients undergoing microbial infection or allograft rejection.
Ethnic pride and self-control related to protective and risk factors: test of the theoretical model for the strong African American families program.

OBJECTIVE To test a theoretical model of how ethnic pride and self-control are related to risk and protective factors. DESIGN A community sample of 670 African American youth (mean age = 11.2 years) were interviewed in households. MAIN OUTCOME MEASURES Measures of cigarette smoking, alcohol use, and sexual behavior (lifetime to past month). RESULTS Structural modeling analyses indicated parenting was related to self-control and self-esteem, and racial socialization was related to ethnic pride. Self-control and self-esteem variables were related to levels of deviance-prone attitudes and to perceptions of engagers in, or abstainers from, substance use and sexual behavior. The proximal factors (behavioral willingness, resistance efficacy, and peer behavior) had substantial relations to the criterion variables. Participant gender and parental education also had several paths in the model. Results were generally similar for the 2 outcome behaviors. CONCLUSIONS In this population, self-esteem and self-control are related to parenting approaches and have pathways to attitudes and social perceptions that are significant factors for predisposing to, or protecting against, early involvement in substance use and sexual behavior.
Measuring extraordinary rendition and international cooperation: A response to Blakeley and Raphael

In my article, “Measuring extraordinary rendition and international cooperation” I present a model that can be used to measure extraordinary rendition and identify international cooperation in the Central Intelligence Agency’s Rendition, Detention and Interrogation program using public flight data and information on rendition flight characteristics. My analysis identifies 307 new likely rendition flights and 15 previously unidentified countries potentially involved. In response, Blakeley and Raphael argue that these results do not move beyond what they have already published, and also challenge the claim that these flights are “likely rendition flights” as they have not been triangulated by further evidence. However, it seems inconsistent to claim both that: (a) the findings are not new; and (b) the findings are wrong. I respond to their concerns by providing a detailed evaluation of my results in relation to their own findings. I demonstrate that there are important differences between the results in Blakeley and Raphael’s previous work and my own. I reinforce my earlier claim that triangulating these new results with reliable qualitative evidence is a crucial step.
Interlaboratory comparison of ultrasonic backscatter, attenuation, and speed measurements.

In a study involving 10 different sites, independent results of measurements of ultrasonic properties on equivalent tissue‐mimicking samples are reported and compared. The properties measured were propagation speed, attenuation coefficients, and backscatter coefficients. Reasonably good agreement exists for attenuation coefficients, but less satisfactory results were found for propagation speeds. As anticipated, agreement was not impressive in the case of backscatter coefficients. Results for four sites agreed rather well in both absolute values and frequency dependence, and results from other sites were lower by as much as an order of magnitude. The study is valuable for laboratories doing quantitative studies.
Probing novel GPCR interactions using a combination of FRET and TIRF

Recent work on G-protein coupled receptors (GPCRs) has highlighted the importance of homo- and heterodimerization in all areas of GPCR function, including trafficking, signaling and desensitization. Novel GPCR dimers and even high-order oligomers are constantly being discovered. Advances in techniques such as fluorescent microscopy have improved our ability to detect these interactions. As GPCRs represent the largest class of transmembrane signaling molecules in biology, these new insights into their function could vastly improve our understanding of the complex physiological role GPCRs play in cellular signaling. Utilizing a combination of classic biochemical approaches and newer techniques such as fluorescence resonance energy transfer (FRET) and total internal reflection fluorescence microscopy (TIRF), we recently demonstrated a novel interaction between M2 muscarinic receptors and GABAB receptors. In this addendum, we address technical aspects of combining FRET and TIRF to study GPCR interactions and further discuss the physiological implications of the M2-GABAB heterodimer.
The Effects of Reviewer Expertise on Future Reputation, Popularity, and Financial Performance of Hotels: Insights from Data-Analytics

Although the impacts of reviews provided by reviewers with expertise are well documented, the literature lacks empirical research on how such reviews are longitudinally linked to performance indicators and whether management responses to such reviews lead to differential impacts on these indicators. This study investigates the effects of reviewer expertise on hotels’ online reputation, online popularity, and financial performance. Using a large data set of management responses and online reviews from 730 hotels over 26 quarters, matched with quarterly financial performance data, the authors found that the effects of average ratings and the number of reviews on hotels’ subsequent financial performance are attenuated when reviewer expertise increases. The study also demonstrates that business benefits are enhanced if hotels target reviewers of higher expertise when providing management responses to online reviews. Results suggest that when managing electronic word-of-mouth, practitioners should take strategic approaches that leverage the influence of reviewer expertise.
Calculation of Lightning-Induced Overvoltages on Overhead Lines Based on DEPACT Macromodel Using Circuit Simulation Software

One of the simple and accurate methods for calculating the lightning-induced overvoltages is based on the Agrawal et al. held-to-wire model, in which the coupling mechanisms are presented by distributed voltage sources along the lines. There is a difficulty in calculating the lightning-induced overvoltages with the built-in transmission line models or other circuit elements of various circuit simulation software such as the PSCAD/EMTDC, EMTP/ATP, PSpice, etc., as the distributed voltage sources due to the horizontal component of the electric held caused by the lightning channel are in series with the line and not in between two transmission-line segments. In this paper, a simple circuit approach for efficient calculation of the lightning-induced overvoltages using the circuit simulation software is proposed. The delay extraction passive compact circuit (DEPACT) macromodel is applied and the transmission line is divided into a cascade of DEPACT subnetworks which can be represented by a cascade of two lossless transmission lines and a lossy network. By assuming the incident held only couples with the lossless transmission line sections, the distributed equivalent voltage sources due to the horizontal component of the incident electric held can be lumped at the termination of the lines, which makes it convenient for the engineering technologist to calculate the lightning-induced overvoltages in various circuit simulation software. Furthermore, in order to treat the nonlinear element such as metal oxide arrester (MOA) directly, the DEPACT macromodel is improved and the macromodel of multiconductor transmission lines excited by the external electromagnetic held can be solved in the actual phase domain instead of in the modal domain. Compared with the existing method for calculating the lightning-induced overvoltages, the benefit of the proposed algorithm is that it can be used to calculate the transients of the transmission line more efficiently. Considering the PSCAD/EMTDC is a powerful simulation software which providing lots of equipment models in power system, such as transformer, generator, and protection modules et al., an implementation procedure in the PSCAD/EMTDC is provided in this paper, which makes it more convenient for the electrical engineering technologists to analyze the lightning-induced overvoltages problems in the power system. Several numerical calculations of the line transient responses are provided and the CPU time is compared, which indicate the validity and efficiency of the algorithm proposed in the paper. At last, this algorithm is applied to analyze the influence of the ground wire and the MOA on the lightning-induced overvoltages of the overhead lines.
Days With Pain and Substance Use Disorders: Is There an Association?

Objectives:We investigated possible associations between pain frequency and the 5 most common substance use disorders: alcohol abuse/dependence, cocaine abuse/dependence, methamphetamine abuse/dependence, opioid abuse/dependence, and marijuana abuse/dependence. Methods:We used data from the Rural Stimulant Study, a longitudinal (7 waves), observational study of at-risk stimulant users (cocaine and methamphetamine) in Arkansas and Kentucky (n=462). In fixed-effects logistic regression models, we regressed our measures of substance use disorders on the number of days with pain in the past 30 days and depression severity. Results:Time periods when individuals had 1 to 15 days [odds ratio (OR)=1.85, P<0.001] or 16+ days (OR=2.18, P<0.001) with pain in the past 30 days were more likely to have a diagnosis of alcohol abuse/dependence, compared with time periods when individuals had no days with pain. Compared with time periods when individuals had no pain days in the past 30 days, time periods when individuals had 16+ pain days were more likely to have a diagnosis of opioid abuse/dependence (OR=3.32, P=0.02). Number of days with pain was not significantly associated with other substance use disorders. Discussion:Pain frequency seems to be associated with an increased risk for alcohol abuse/dependence and opioid abuse/dependence in this population, and the magnitude of the association is medium to large. Further research is needed to investigate this in more representative populations and to determine causal relationships.
Spinal cord injury and neural repair: focus on neuroregenerative approaches for spinal cord injury.

BACKGROUND This review discusses the urgent need for improved therapeutic approaches aimed at restoring function following traumatic spinal cord injury (SCI). The focus of this paper is neuroregenerative approaches for SCI, with a highlighted comparison of recent advances in the field and comparisons to that made by Cethrin (Alseres Pharmaceuticals, Inc.), the leading nerve repair product. OBJECTIVE This review first provides the reader with an understanding of SCI. The market for promising therapeutics that can either intervene in secondary etiological mechanisms or ameliorate symptoms associated with SCI are then discussed. The reader will also learn about Cethrin and its current status in clinical evaluation. METHODS Review of the preclinical literature and clinical SCI trials relevant to the discovery and current development of Cethrin. RESULTS/CONCLUSION In a recently concluded Phase I/IIa clinical trial involving 37 patients with either cervical or thoracic SCIs, the evidence for Cethrin indicates that topical administration of either 0.3, 1, 3 or 6 mg of the recombinant rho inhibitor following surgical decompression is safe. Alseres has announced that planning is underway for a Phase IIB trial of Cethrin to include a placebo arm to assess better the drugs' clinical efficacy.
Variants of the rat basophilic leukemia cell line for the study of histamine release.

Cloning of the rat basophilic leukemia (RBL) cell lines demonstrates variability in cell chromosome number (approximately 44-70) and in their capacity to release histamine following an IgE- or Ca2+-ionophore stimulus. After IgE activation there is increased phospholipid methylation, Ca2+ influx, arachidonic acid, and histamine release. On Ca2+ ionophore A23187 stimulation, phospholipid methylation is not increased, but Ca2+ influx, arachidonic acid, and histamine release occur. Variants of the RBL-cloned sublines defective at different stages in the release process were obtained and used to sequence the different events in the release process: IgE activation is followed by methylation, Ca2+ influx, arachidonic acid, and histamine release. However, there are other variants with defects in intermediate steps in the pathway, e.g., increased phospholipid methylation that is not followed by Ca2+ influx or arachidonic acid release not followed by histamine release. Isolating variants carrying drug-resistance markers made hybridization (reconstitution) experiments possible. Two variants were recognized, each of which was deficient in one of the two phospholipid methyltransferase enzymes. Neither of these two variants released histamine; hybrids formed by fusion of these two cell lines have both phospholipid methyltransferase enzymes and release histamine. By other complementation experiments, groups of variants with defects at different steps in the histamine release sequence were recognized. Clearly, these basophilic leukemia cell lines provide a unique system for the study of the mechanism of histamine release.
Explanatory factors in the renewal of contracts for the privatisation of public services

After analysing the explanatory factors underlying the renewal of privatisation contracts, this paper examines the likelihood of local authorities renewing their contracts with private entities for the provision of public services, by studying a sample of 623 Spanish municipalities for the period 2002–2013, using a logit model. The type of service, the duration of the contract and certain political and economic factors were all found to influence the renewal or otherwise of this type of contract. Moreover, this effect differed between initial privatisation and subsequent contract renewal.
The Unintended Impact of Pretrial Detention on Case Outcomes: Evidence from New York City Arraignments

In the United States, over 400,000 individuals are in jail daily waiting for their criminal cases to be resolved. The majority of detainees are held because they cannot post bail. We estimate the impact of being detained pretrial on the likelihood of being convicted and sentence length using data on nearly a million criminal cases in New York City. Causal effects are identified using variation across arraignment judges in their propensities to detain defendants. We find that being detained increases the probability of conviction by 13 percentage points for felony defendants. Although pretrial detention lowers the probability of rearrest while cases are being adjudicated, this reduction in criminal activity is mostly offset by an increase in recidivism within 2 years after disposition. Higher pretrial detention rates among minority defendants explain 40 percent of the black-white gap in rates of being sentenced to prison and 28 percent of the Hispanic-white gap. Excessive bail shall not be required, nor excessive fines imposed, nor cruel and unusual punishments inflicted. (US Constitution, Eighth Amendment) Excessive bail shall not be required, nor excessive fines imposed, nor cruel and unusual punishments inflicted. (US Constitution, Eighth Amendment)
Appearance of Phosphatidylserine on Apoptotic Cells Requires Calcium-mediated Nonspecific Flip-Flop and Is Enhanced by Loss of the Aminophospholipid Translocase*

Phosphatidylserine (PS), ordinarily sequestered in the plasma membrane inner leaflet, appears in the outer leaflet during apoptosis, where it triggers non-inflammatory phagocytic recognition of the apoptotic cell. The mechanism of PS appearance during apoptosis is not well understood but has been associated with loss of aminophospholipid translocase activity and nonspecific flip-flop of phospholipids of various classes. The human leukemic cell line HL-60, the T cell line Jurkat, and peripheral blood neutrophils, undergoing apoptosis induced either with UV irradiation or anti-Fas antibody, were probed in the cytofluorograph for (i) surface PS using fluorescein isothiocyanate-labeled annexin V, (ii) PS uptake by the aminophospholipid translocase using [6-[(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino] caproyl] (NBD)-labeled PS, (iii) nonspecific uptake of phospholipids (as a measure of transbilayer flip-flop) using NBD-labeled phosphatidylcholine, and (iv) the appearance of hypodiploid DNA. In all three types of cells undergoing apoptosis, the appearance of PS followed loss of aminophospholipid translocase and was accompanied by nonspecific phospholipid flip-flop. Importantly, however, in the absence of extracellular calcium, the appearance of PS was completely inhibited despite DNA fragmentation and loss of aminophospholipid translocase activity, the latter demonstrating that loss of the translocase is insufficient for PS appearance during apoptosis. Furthermore, while both the appearance of PS and nonspecific phospholipid uptake demonstrated identical extracellular calcium requirements with an ED50 of nearly 100 μm, the magnitude of PS appearance depended on the level of aminophospholipid translocase activity. Taken together, the data strongly suggest that while nonspecific flip-flop is the driving event for PS appearance in the plasma membrane outer leaflet, aminophospholipid translocase activity ultimately modulates its appearance.
Escherichia coli RNA Polymerase Recognition of a σ70-Dependent Promoter Requiring a −35 DNA Element and an Extended −10 TGn Motif

ABSTRACT Escherichia coli σ70-dependent promoters have typically been characterized as either −10/−35 promoters, which have good matches to both the canonical −10 and the −35 sequences or as extended −10 promoters (TGn/−10 promoters), which have the TGn motif and an excellent match to the −10 consensus sequence. We report here an investigation of a promoter, Pminor, that has a nearly perfect match to the −35 sequence and has the TGn motif. However, Pminor contains an extremely poor σ70 −10 element. We demonstrate that Pminor is active both in vivo and in vitro and that mutations in either the −35 or the TGn motif eliminate its activity. Mutation of the TGn motif can be compensated for by mutations that make the −10 element more canonical, thus converting the −35/TGn promoter to a −35/−10 promoter. Potassium permanganate footprinting on the nontemplate and template strands indicates that when polymerase is in a stable (open) complex with Pminor, the DNA is single stranded from positions −11 to +4. We also demonstrate that transcription from Pminor incorporates nontemplated ribonucleoside triphosphates at the 5′ end of the Pminor transcript, which results in an anomalous assignment for the start site when primer extension analysis is used. Pminor represents one of the few −35/TGn promoters that have been characterized and serves as a model for investigating functional differences between these promoters and the better-characterized −10/−35 and extended −10 promoters used by E. coli RNA polymerase.
Cinaciguat, a soluble guanylate cyclase activator, unloads the heart but also causes hypotension in acute decompensated heart failure.

AIMS Cinaciguat (BAY 58-2667) is a novel soluble guanylate cyclase activator. This study evaluated the haemodynamic effect and safety of cinaciguat added to standard therapy in patients with acute decompensated heart failure (ADHF). METHODS AND RESULTS In this placebo-controlled, phase IIb study (NCT00559650), 139 patients admitted with ADHF, pulmonary capillary wedge pressure (PCWP) ≥18 mmHg, left ventricular ejection fraction <40%, and a pre-existing need for invasive haemodynamic monitoring were randomized 2:1 to cinaciguat:placebo (continuous i.v. infusion). The dose was titrated for 8 h and maintained for 16-40 h (starting dose: 100 μg/h). At 8 h, mean PCWP changed from 25.7 ± 5.0 mmHg by -7.7 mmHg with cinaciguat and from 25.0 ± 5.3 mmHg by -3.7 mmHg with placebo (P < 0.0001). The mean right atrial pressure changed from 12.4 ± 5.3 mmHg by -2.7 mmHg with cinaciguat and from 11.8 ± 4.9 mmHg by -0.6 mmHg with placebo (P= 0.0019). Cinaciguat also decreased the pulmonary and systemic vascular resistance and the mean arterial pressure, and increased the cardiac index (all P < 0.0001 vs. placebo). Systolic blood pressure changed by -21.6 ± 17.0 mmHg with cinaciguat and -5.0 ± 14.5 mmHg with placebo. Adverse events were experienced by 71 and 45% of patients receiving cinaciguat and placebo, respectively. No adverse effects on the 30-day mortality were seen; however, the trial was stopped prematurely due to an increased occurrence of hypotension at cinaciguat doses ≥200 µg/h. CONCLUSION Cinaciguat unloaded the heart in patients with ADHF. However, high doses were associated with hypotension.
EDITORIAL: Pacific media advocacy

IN SAMOA during July 2015, a new Pacific journalism education and training advocacy era was born with the establishment of the Media Educators Pacific (MEP) after a talkfest had gone on for years about the need for such a body. A draft constitution had even been floated at a journalism education conference hosted at the University of the South Pacific in 2012. The initiative created unity of sorts between the Technical, Vocational and Educational Training (TVET) media institutes from Fiji, Samoa, Solomon Islands and Vanuatu, and the regional University of the South Pacific journalism programme. Founding president Misa Vicky Lepou of the National University of Samoa pledged at the time to produce a vision with a difference: