Miracle-dz/UniFAR-FTUs huggingface dataset:
A Circadian Clock in the Olfactory Bulb Controls Olfactory Responsivity

Recently, it has been shown that multiple mammalian cell types express daily rhythms in vitro. Although the suprachiasmatic nucleus (SCN) of the hypothalamus is known to regulate a wide range of circadian behaviors, the role for intrinsic rhythmicity in other tissues is unknown. We tested whether the main olfactory bulb (OB) of mice mediates daily changes in olfaction. We found circadian rhythms in cedar oil-induced c-Fos, a protein marker of cellular excitation, in the mitral and granular layers of the OB and in the piriform cortex (PC). These oscillations persisted in constant darkness with a fourfold change in amplitude and a peak ∼4 h after the onset of daily locomotor activity. Electrolytic lesions of the SCN abolished circadian locomotor rhythms, but not odor-induced c-Fos rhythms in the OB or PC. Furthermore, removal of the OB abolished spontaneous circadian cycling of c-Fos in the PC, shortened the free-running period of locomotor rhythms, and accelerated re-entrainment after a 6 h advance and slowed re-entrainment after a 6 h delay in the light schedule. OB ablation or odorant altered the amplitude of c-Fos rhythms in the SCN and ablation of one OB abolished c-Fos rhythms in the ipsilateral PC, but not in the contralateral OB and PC. We conclude that the OB comprises a master circadian pacemaker, which enhances olfactory responsivity each night, drives rhythms in the PC, and interacts with the SCN to coordinate other daily behaviors.
Professional differences in interprofessional working

UK government policy is encouraging healthcare staff to blur traditional roles, in the drive to increase joint working between practitioners. However, there is currently a lack of clarity regarding the impact that changes to traditional working practice might have on staff delivering the services, or on patient care. In this article, we report findings from three qualitative case studies examining interprofessional practice in stroke care, in which the influence of professional differences emerged as a significant theme. We draw on findings from individual semi-structured interviews, as well as fieldwork observations, to describe the influence of professional knowledge and skills, role and identity, and power and status considerations in interprofessional working. The insights that were gained contribute to the understanding of how professional differences impact on healthcare staff joint working, and suggest that the elements identified need to be fully considered in drives towards changed working practice.
Lopinavir Dosing in HIV-infected Children in the United Kingdom and Ireland

Background: Uncertainty surrounds the correct dosing of lopinavir/r (LPV/r) in HIV-infected children not receiving non-nucleoside reverse transcriptase inhibitors. The licensed total daily dose is 460 mg/m2, whereas the original study, reporting excellent viral load (VL) suppression, used a higher 600 mg/m2 dose. Methods: We calculated LPV/r daily doses prescribed from 2000 to 2009 within the UK/Irish national Collaborative HIV Paediatric Study (CHIPS) cohort. Logistic and binomial mixed models were used to explore whether higher LPV/r doses affected VL suppression. Results: Four hundred forty-four of 1201 (37%) children on antiretroviral therapy in CHIPS had taken lopinavir/r without non-nucleoside reverse transcriptase inhibitors. Of 1065 recorded doses, 48% were syrup, 27% capsules and 25% tablets. Ten percent of doses were >10% below 460 mg/m2 per day, and 12% were >10% above 600 mg/m2. In multivariable models, predictors of lower doses were: once versus twice daily dosing (32 mg/m2 lower); syrup versus tablets/capsules (33 mg/m2 lower); higher weight-for-age and height-for-age (24 mg/m2 and 13 mg/m2 lower per unit higher, respectively); and older age (13 mg/m2 lower per year older for those aged >10 years, P < 0.05). Dosing varied widely by hospital (P = 0.0004), with some targeting higher and others lower doses. For those receiving lopinavir/r for ≥6 months, there was a greater chance of VL <400 copies/mL with higher doses (odds ratio = 1.15 [95% confidence interval: 1.06–1.25 per 50 mg/m2 higher], P = 0.001). Conclusions: Findings suggest substantial variation and large hospital-level effects in the LPV/r dose prescribed to HIV-infected children in the United Kingdom/Ireland. Higher doses appeared to improve long-term VL suppression, which may be critical in children who need life-long therapy. Results highlight the importance of optimizing dosing in HIV-infected children of all ages.
The evolution of human adiposity and obesity: where did it all go wrong?

Because obesity is associated with diverse chronic diseases, little attention has been directed to the multiple beneficial functions of adipose tissue. Adipose tissue not only provides energy for growth, reproduction and immune function, but also secretes and receives diverse signaling molecules that coordinate energy allocation between these functions in response to ecological conditions. Importantly, many relevant ecological cues act on growth and physique, with adiposity responding as a counterbalancing risk management strategy. The large number of individual alleles associated with adipose tissue illustrates its integration with diverse metabolic pathways. However, phenotypic variation in age, sex, ethnicity and social status is further associated with different strategies for storing and using energy. Adiposity therefore represents a key means of phenotypic flexibility within and across generations, enabling a coherent life-history strategy in the face of ecological stochasticity. The sensitivity of numerous metabolic pathways to ecological cues makes our species vulnerable to manipulative globalized economic forces. The aim of this article is to understand how human adipose tissue biology interacts with modern environmental pressures to generate excess weight gain and obesity. The disease component of obesity might lie not in adipose tissue itself, but in its perturbation by our modern industrialized niche. Efforts to combat obesity could be more effective if they prioritized ‘external’ environmental change rather than attempting to manipulate ‘internal’ biology through pharmaceutical or behavioral means.
Assessment of Right Ventricular Function by Newer Imaging in Echocardiography in Idiopathic Pulmonary Arterial Hypertension

Background The aims of the study were to assess the right ventricular (RV) functions in patients with idiopathic pulmonary arterial hypertension (IPAH) with RV longitudinal strain (RVLS) in addition to conventional parameters, as well as its correlation with severity and prognosis in IPAH. Methods Twenty-two IPAH patients were followed up for 1 year. ANOVA and Gabriel’s pairwise comparison tests were used for comparison of RVLS with respect to WHO functional class status. Patients were divided into non-survival (group 1) and survival (group 2), and clinical and echocardiographic parameters of RV function were compared at baseline and at 6 months with t-test & Mann-Whitney test. Results At baseline, with respect to WHO functional class, mean RVLS showed no significant interclass difference (P = 0.0781). Among the other conventional echocardiographic parameters, RV E/A showed significant difference at baseline (P = 0.004), but not at 6 months (P = 0.366); whereas tricuspid annular plane systolic excursion (TAPSE) which had no significant difference initially (P = 0.174) revealed a significance level at 6 months (P = 0.029) between the two groups. Fractional area change (FAC), RV index of myocardial performance (RIMP), and right atrial (RA) area displayed significant difference neither at baseline nor at 6 months. RVLS exhibited significant difference neither at baseline (P = 0.912) nor at 6 months (P = 0.181). None of the echocardiographic parameters including RVLS showed a significant average change with change in severity of PAH both at 6 and 12 months. Conclusion RVLS was not proved to be a useful parameter for early detection of RV dysfunction and prognosis in patients with IPAH in comparison with the conventional echocardiographic parameters.
You are Known by the Directors You Keep: Reputable Directors as a Signaling Mechanism for Young Firms

In this paper, we develop an analytical model of outside directors' signaling role--a role that is especially important for entrepreneurial firms. We formally demonstrate that in the face of a market failure in which stakeholders refuse to align themselves with new firms, high-quality new ventures may be able to credibly signal their type by appointing reputable directors to their boards. However, this option is not universally feasible. Both directors' reputations and the quality of their information determine the effectiveness of this strategy. In contrast to earlier adverse selection models, we demonstrate that when the middlemen (directors) have incomplete information on firm quality, bad and good firms can coexist in equilibrium. In this equilibrium, the quality of the directors' information determines the mix of good and bad firms in the population of surviving firms. Avenues for future research and normative implications for practitioners are discussed.
Partial MHC/Neuroantigen Peptide Constructs: A Potential Neuroimmune-Based Treatment for Methamphetamine Addiction

Relapse rates following current methamphetamine abuse treatments are very high (∼40–60%), and the neuropsychiatric impairments (e.g., cognitive deficits, mood disorders) that arise and persist during remission from methamphetamine addiction likely contribute to these high relapse rates. Pharmacotherapeutic development of medications to treat addiction has focused on neurotransmitter systems with only limited success, and there are no Food and Drug Administration approved pharmacotherapies for methamphetamine addiction. A growing literature shows that methamphetamine alters peripheral and central immune functions and that immune factors such as cytokines, chemokines, and adhesion molecules play a role in the development and persistence of methamphetamine induced neuronal injury and neuropsychiatric impairments. The objective of this study was to evaluate the efficacy of a new immunotherapy, partial MHC/neuroantigen peptide construct (RTL551; pI-Ab/mMOG-35-55), in treating learning and memory impairments induced by repeated methamphetamine exposure. C57BL/6J mice were exposed to two different methamphetamine treatment regimens (using repeated doses of 4 mg/kg or 10 mg/kg, s.c.). Cognitive performance was assessed using the Morris water maze and CNS cytokine levels were measured by multiplex assay. Immunotherapy with RTL551 improved the memory impairments induced by repeated methamphetamine exposure in both mouse models of chronic methamphetamine addiction. Treatment with RTL551 also attenuated the methamphetamine induced increases in hypothalamic interleukin-2 (IL-2) levels. Collectively, these initial results indicate that neuroimmune targeted therapies, and specifically RTL551, may have potential as treatments for methamphetamine-induced neuropsychiatric impairments.
Sparse Coding Quantization for Downlink MU-MIMO with Limited CSI Feedback

A novel quantization method, sparse coding quantization (SCQ), is proposed for downlink multiuser multiple-input multiple-output (MU-MIMO) systems. Compared to conventional vector quantization (VQ), SCQ utilizes a linear combination of several codewords rather than a single one to represent the channel matrix. Both analytical and simulation results reveal that the proposed technique can achieve the same sum rate performance as VQ at a reasonable cost in feedback overhead. Thus, SCQ is more practical because it significantly reduces the time and space complexity for generating, searching and storing the codebook. % The net capacity, which indicates the tradeoff between sum rate and overhead, is also studied.
miR-10a inhibits dendritic cell activation and Th1/Th17 cell immune responses in IBD

Objective Although both innate and adaptive responses to microbiota have been implicated in the pathogenesis of IBD, it is still largely unknown how they are regulated during intestinal inflammation. In this report, we investigated the role of microRNA (miR)-10a, a small, non-coding RNA, in the regulation of innate and adaptive responses to microbiota in IBD. Methods miR-10a expression was analysed in the inflamed mucosa of IBD patients treated with or without antitumour necrosis factor (anti-TNF) monoclonal antibodies (mAb) (infliximab) by qRT-PCR. Human monocyte-derived dendritic cells (DC) and IBD CD4+ T cells were transfected with miR-10a precursor to define their effect on the function of DC and CD4+ T cells. Results The expression of miR-10a was markedly decreased, while NOD2 and interleukin (IL)-12/IL-23p40 were significantly increased, in the inflamed mucosa of IBD patients compared with those in healthy controls. Commensal bacteria, TNF and interferon-γ inhibited human DC miR-10a expression in vitro. Anti-TNF mAb treatment significantly promoted miR-10a expression, whereas it markedly inhibited NOD2 and IL-12/IL-23p40 in the inflamed mucosa. We further identified NOD2, in addition to IL-12/IL-23p40, as a target of miR-10a. The ectopic expression of the miR-10a precursor inhibited IL-12/IL-23p40 and NOD2 in DC. Moreover, miR-10a was found to markedly suppress IBD T helper (Th)1 and Th17 cell responses. Conclusions Our data indicate that miR-10a is decreased in the inflamed mucosa of IBD and downregulates mucosal inflammatory response through inhibition of IL-12/IL-23p40 and NOD2 expression, and blockade of Th1/Th17 cell immune responses. Thus, miR-10a could play a role in the pathogenesis and progression of IBD.
Classical Planning with Simulators: Results on the Atari Video Games

The Atari 2600 games supported in the Arcade Learning Environment [Bellemare et al., 2013] all feature a known initial (RAM) state and actions that have deterministic effects. Classical planners, however, cannot be used off-the-shelf as there is no compact PDDL-model of the games, and action effects and goals are not known a priori. Indeed, there are no explicit goals, and the planner must select actions on-line while interacting with a simulator that returns successor states and rewards. None of this precludes the use of blind lookahead algorithms for action selection like breadth-first search or Dijkstra's yet such methods are not effective over large state spaces. We thus turn to a different class of planning methods introduced recently that have been shown to be effective for solving large planning problems but which do not require prior knowledge of state transitions, costs (rewards) or goals. The empirical results over 54 Atari games show that the simplest such algorithm performs at the level of UCT, the state-of-the-art planning method in this domain, and suggest the potential of width-based methods for planning with simulators when factored, compact action models are not available.
Two New Computational Methods for Universal DNA Barcoding: A Benchmark Using Barcode Sequences of Bacteria, Archaea, Animals, Fungi, and Land Plants

Taxonomic identification of biological specimens based on DNA sequence information (a.k.a. DNA barcoding) is becoming increasingly common in biodiversity science. Although several methods have been proposed, many of them are not universally applicable due to the need for prerequisite phylogenetic/machine-learning analyses, the need for huge computational resources, or the lack of a firm theoretical background. Here, we propose two new computational methods of DNA barcoding and show a benchmark for bacterial/archeal 16S, animal COX1, fungal internal transcribed spacer, and three plant chloroplast (rbcL, matK, and trnH-psbA) barcode loci that can be used to compare the performance of existing and new methods. The benchmark was performed under two alternative situations: query sequences were available in the corresponding reference sequence databases in one, but were not available in the other. In the former situation, the commonly used “1-nearest-neighbor” (1-NN) method, which assigns the taxonomic information of the most similar sequences in a reference database (i.e., BLAST-top-hit reference sequence) to a query, displays the highest rate and highest precision of successful taxonomic identification. However, in the latter situation, the 1-NN method produced extremely high rates of misidentification for all the barcode loci examined. In contrast, one of our new methods, the query-centric auto-k-nearest-neighbor (QCauto) method, consistently produced low rates of misidentification for all the loci examined in both situations. These results indicate that the 1-NN method is most suitable if the reference sequences of all potentially observable species are available in databases; otherwise, the QCauto method returns the most reliable identification results. The benchmark results also indicated that the taxon coverage of reference sequences is far from complete for genus or species level identification in all the barcode loci examined. Therefore, we need to accelerate the registration of reference barcode sequences to apply high-throughput DNA barcoding to genus or species level identification in biodiversity research.
High-Dose Naltrexone Treatment and Gender in Alcohol Dependence

ObjectivesLittle is known about whether safety and effectiveness of high-dose naltrexone (150 mg/d) are different in alcohol-dependent women and men. This study investigated sex differences in safety and treatment outcomes in alcohol-dependent women and men on high-dose naltrexone (150 mg/d). MethodsIn this exploratory study, safety and effectiveness of high-dose naltrexone (150 mg/d) were examined in men and women with alcohol dependence (n = 24; 11 men and 13 women) treated in an 8-week outpatient setting. ResultsWomen and men had similar dropout rates, adverse effects, tolerability, and hepatic function during high-dose naltrexone treatment (150 mg/d). Drinking outcomes were significantly improved in both women and men, but no sex differences were found. ConclusionsHigh-dose naltrexone seems to be well tolerated, safe, and effective in both men and women with alcohol dependence in this small study. Given the small sample size of the current study, our results cannot be considered definitive, and larger trials with longer durations are needed to confirm these findings.
Complex Elliptically Symmetric Distributions: Survey, New Results and Applications

Complex elliptically symmetric (CES) distributions have been widely used in various engineering applications for which non-Gaussian models are needed. In this overview, circular CES distributions are surveyed, some new results are derived and their applications e.g., in radar and array signal processing are discussed and illustrated with theoretical examples, simulations and analysis of real radar data. The maximum likelihood (ML) estimator of the scatter matrix parameter is derived and general conditions for its existence and uniqueness, and for convergence of the iterative fixed point algorithm are established. Specific ML-estimators for several CES distributions that are widely used in the signal processing literature are discussed in depth, including the complex t -distribution, K-distribution, the generalized Gaussian distribution and the closely related angular central Gaussian distribution. A generalization of ML-estimators, the M-estimators of the scatter matrix, are also discussed and asymptotic analysis is provided. Applications of CES distributions and the adaptive signal processors based on ML- and M-estimators of the scatter matrix are illustrated in radar detection problems and in array signal processing applications for Direction-of-Arrival (DOA) estimation and beamforming. Furthermore, experimental validation of the usefulness of CES distributions for modelling real radar data is given.
Control of variable-speed wind turbines: standard and adaptive techniques for maximizing energy capture

This article considers an adaptive control scheme previously developed for region 2 control of a variable speed wind turbine. In this paper, the question of theoretical stability of the torque controller is addressed, showing that the rotor speed is asymptotically stable under the torque control law in the constant wind speed input case and L/sub 2/ stable with respect to time-varying wind input. Further, a method is derived for selecting /spl gamma//sub /spl Delta/M/ in the gain adaptation law to guarantee convergence of the adaptive gain M to its optimal value M*.
Anonymizing Social Networks

Advances in technology have made it possible to collect data about individuals and the connections between them, such as email correspondence and friendships. Agencies and researchers who have collected such social network data often have a compelling interest in allowing others to analyze the data. However, in many cases the data describes relationships that are private (e.g., email correspondence) and sharing the data in full can result in unacceptable disclosures. In this paper, we present a framework for assessing the privacy risk of sharing anonymized network data. This includes a model of adversary knowledge, for which we consider several variants and make connections to known graph theoretical results. On several real-world social networks, we show that simple anonymization techniques are inadequate, resulting in substantial breaches of privacy for even modestly informed adversaries. We propose a novel anonymization technique based on perturbing the network and demonstrate empirically that it leads to substantial reduction of the privacy threat. We also analyze the eect that anonymizing the network has on the utility of the data for social network analysis.
Unconscious relational encoding depends on hippocampus

See Mayes (doi:10.1093/brain/awu284) for a scientific commentary on this article. The hippocampus is thought to support only conscious memory, while neocortex supports both conscious and unconscious memory. Duss et al. show that amnesic patients with damage to the hippocampal–anterior thalamic axis exhibit a diminished form of unconscious encoding and retrieval, suggesting that certain forms of unconscious memory are hippocampus-dependent.
Metabolomic profile in pancreatic cancer patients: a consensus-based approach to identify highly discriminating metabolites

Purpose pancreatic adenocarcinoma is the fourth leading cause of cancer related deaths due to its aggressive behavior and poor clinical outcome. There is a considerable variability in the frequency of serum tumor markers in cancer' patients. We performed a metabolomics screening in patients diagnosed with pancreatic cancer. Experimental Design Two targeted metabolomic assays were conducted on 40 serum samples of patients diagnosed with pancreatic cancer and 40 healthy controls. Multivariate methods and classification trees were performed. Materials and Methods Sparse partial least squares discriminant analysis (SPLS-DA) was used to reduce the high dimensionality of a pancreatic cancer metabolomic dataset, differentiating between pancreatic cancer (PC) patients and healthy subjects. Using Random Forest analysis palmitic acid, 1,2-dioleoyl-sn-glycero-3-phospho-rac-glycerol, lanosterol, lignoceric acid, 1-monooleoyl-rac-glycerol, cholesterol 5α,6α epoxide, erucic acid and taurolithocholic acid (T-LCA), oleoyl-L-carnitine, oleanolic acid were identified among 206 metabolites as highly discriminating between disease states. Comparison between Receiver Operating Characteristic (ROC) curves for palmitic acid and CA 19-9 showed that the area under the ROC curve (AUC) of palmitic acid (AUC=1.000; 95% confidence interval) is significantly higher than CA 19-9 (AUC=0.963; 95% confidence interval: 0.896-1.000). Conclusion Mass spectrometry-based metabolomic profiling of sera from pancreatic cancer patients and normal subjects showed significant alterations in the profiles of the metabolome of PC patients as compared to controls. These findings offer an information-rich matrix for discovering novel candidate biomarkers with diagnostic or prognostic potentials.