bluuebunny/crossref_metadata_2025_split huggingface dataset:
Degeneracy in the robust expression of spectral selectivity, subthreshold oscillations, and intrinsic excitability of entorhinal stellate cells
Authors: Mittal Divyansh , Narayanan Rishikesh 
Published: May 2018

Biological heterogeneities are ubiquitous and play critical roles in the emergence of physiology at multiple scales. Although neurons in layer II (LII) of the medial entorhinal cortex (MEC) express heterogeneities in channel properties, the impact of such heterogeneities on the robustness of their cellular-scale physiology has not been assessed. Here, we performed a 55-parameter stochastic search spanning nine voltage- or calcium-activated channels to assess the impact of channel heterogeneities on the concomitant emergence of 10 in vitro electrophysiological characteristics of LII stellate cells (SCs). We generated 150,000 models and found a heterogeneous subpopulation of 449 valid models to robustly match all electrophysiological signatures. We employed this heterogeneous population to demonstrate the emergence of cellular-scale degeneracy in SCs, whereby disparate parametric combinations expressing weak pairwise correlations resulted in similar models. We then assessed the impact of virtually knocking out each channel from all valid models and demonstrate that the mapping between channels and measurements was many-to-many, a critical requirement for the expression of degeneracy. Finally, we quantitatively predict that the spike-triggered average of SCs should be endowed with theta-frequency spectral selectivity and coincidence detection capabilities in the fast gamma-band. We postulate this fast gamma-band coincidence detection as an instance of cellular-scale-efficient coding, whereby SC response characteristics match the dominant oscillatory signals in LII MEC. The heterogeneous population of valid SC models built here unveils the robust emergence of cellular-scale physiology despite significant channel heterogeneities, and forms an efficacious substrate for evaluating the impact of biological heterogeneities on entorhinal network function. NEW & NOTEWORTHY We assessed the impact of heterogeneities in channel properties on the robustness of cellular-scale physiology of medial entorhinal cortical stellate neurons. We demonstrate that neuronal models with disparate channel combinations were endowed with similar physiological characteristics, as a consequence of the many-to-many mapping between channel properties and the physiological characteristics that they modulate. We predict that the spike-triggered average of stellate cells should be endowed with theta-frequency spectral selectivity and fast gamma-band coincidence detection capabilities.
Regulation of dynamic postural control to attend manual steadiness constraints
Authors: Teixeira Luis Augusto , Coutinho Joane de Figueiredo Serpa , Coelho Daniel Boari 
Published: May 2018

In daily living activities, performance of spatially accurate manual movements in upright stance depends on postural stability. In the present investigation, we aimed to evaluate the effect of the required manual steadiness (task constraint) on the regulation of dynamic postural control. A single group of young participants ( n = 20) were evaluated in the performance of a dual posturo-manual task of balancing on a platform oscillating in sinusoidal translations at 0.4-Hz (low) or 1-Hz (high) frequencies while stabilizing a cylinder on a handheld tray. Manual task constraint was manipulated by comparing the conditions of keeping the cylinder stationary on its flat or round side, corresponding to low and high manual task constraints, respectively. Results showed that in the low oscillation frequency the high manual task constraint led to lower oscillation amplitudes of the head, center of mass, and tray, in addition to higher relative phase values between ankle/hip-shoulder oscillatory rotations and between center of mass/center of pressure-feet oscillations as compared with values observed in the low manual task constraint. Further analyses showed that the high manual task constraint also affected variables related to both postural (increased amplitudes of center of pressure oscillation) and manual (increased amplitude of shoulder rotations) task components in the high oscillation frequency. These results suggest that control of a dynamic posturo-manual task is modulated in distinct parameters to attend the required manual steadiness in a complex and flexible way.NEW & NOTEWORTHY We evaluated dynamic postural control on a platform oscillating in sinusoidal translations at different frequencies while performing a manual task with low or high steadiness constraints. Results showed that high manual task constraint led to modulation of metric and coordination variables associated with greater postural stability. Our findings suggest that motor control is regulated in an integrative mode at the posturo-manual task level, with reciprocal interplay between the postural and manual components.
Induction of Neoantigen-Specific Cytotoxic T Cells and Construction of T-cell Receptor–Engineered T Cells for Ovarian Cancer
Authors: Matsuda Tatsuo , Leisegang Matthias , Park Jae-Hyun , Ren Lili , Kato Taigo , Ikeda Yuji , Harada Makiko , Kiyotani Kazuma , Lengyel Ernst , Fleming Gini F. , Nakamura Yusuke 
Published: May 2018

Abstract
Purpose: Current evolution of cancer immunotherapies, such as immune checkpoint blockade, has implicated neoantigens as major targets of anticancer cytotoxic T cells. Adoptive T-cell therapy with neoantigen-specific T-cell receptor (TCR)–engineered T cells would be an attractive therapeutic option for advanced cancers where the host antitumor immune function is strongly inhibited. We previously developed a rapid and efficient pipeline for production of neoantigen-specific TCR-engineered T cells using peripheral blood from an HLA-matched healthy donor. Our protocol required only 2 weeks from stimulation of T cells with neoantigen-loaded dendritic cells to the identification of neoantigen-specific TCRs. We conducted the pilot study to validate our protocol.
Experimental Design: We used tumors from 7 ovarian cancer patients to validate our protocol.
Results: We chose 14 candidate neoantigens from 7 ovarian tumors (1–3 candidates for each patient) and then successfully induced three neoantigen-specific T cells from 1 healthy donor and identified their TCR sequences. Moreover, we validated functional activity of the three identified TCRs by generating TCR-engineered T cells that recognized the corresponding neoantigens and showed cytotoxic activity in an antigen dose–dependent manner. However, one case of neoantigen-specific TCR-engineered T cells showed cross-reactivity against the corresponding wild-type peptide.
Conclusions: This pilot study demonstrated the feasibility of our efficient process from identification of neoantigen to production of the neoantigen-targeting cytotoxic TCR-engineered T cells for ovarian cancer and revealed the importance of careful validation of neoantigen-specific TCR-engineered T cells to avoid severe immune-related adverse events. Clin Cancer Res; 24(21); 5357–67. ©2018 AACR.
See related commentary by Anczurowski and Hirano, p. 5195
Contamination by parasites of zoonotic importance in fecal samples from Florianópolis Beaches, Santa Catarina State, Brazil
Authors: Bricarello Patrizia Ana , Magagnin Ellen Antunes , Oliveira Thailini de , Silva Alice da , Lima Lenilza Mattos 
Published: May 2018

Helminths and protozoa are examples of endoparasites that, during their biological cycles, can alternate between free-life stages and parasitic stages in the environment. Pets, such as dogs and cats, live together with men and play an important role in the society; however, these animals may carry a large number of parasites which, besides showing direct pathogenicity to the host, represent risks to the human health, as is the case of parasitic zoonoses. Public areas like parks, gardens, squares and beaches may offer risks to human users since these environments may contain feces deposited by parasitized dogs. The present study verified the occurrence of helminth eggs and/or protozoan cysts or oocysts in fecal samples collected from sand strips at the beaches Armação do Pântano do Sul, Campeche and Morro das Pedras, in the south of Florianópolis Island, Santa Catarina State (SC), during the summer period. Pet feces were collected in the 2016/2017 summer season, from December 2016 to February 2017. In the Laboratory of Animal Parasitology (CCA-UFSC), fecal samples were processed based on Willis-Mollay flotation technique and Hoffman sedimentation technique. Samples from all three analyzed beaches were positive for the presence of parasites and fecal material was found along the seashore, sites where people walk freely and barefoot. Of 104 fecal samples collected, 45 (43.27%) were positive for one or more parasites. The greatest prevalence was found in Campeche Beach, which had 72.22% positive samples. Ancylostomids were most prevalent, indicating that cutaneous larva migrans is likely to occur in humans. Other parasites such as Trichuris vulpis, Toxocara spp. and Giardia spp. were also detected in coproparasitological analyses. Based on the results, it was concluded that contamination of the beaches in Florianópolis Island, SC, constitutes a public health problem due to the possibility of zoonosis transmission. These results reinforce the importance of establishing health programs for parasite control and educational programs for elucidating the risks of transmission of these zoonoses to the population, as an attempt to reduce environmental contamination risks at beaches of seaside resorts.
Bilirubin Is Inversely Associated With Cardiovascular Disease Among HIV‐Positive and HIV‐Negative Individuals in VACS (Veterans Aging Cohort Study)
Authors: Marconi Vincent C. , Duncan Meredith S. , So‐Armah Kaku , Re Vincent Lo , Lim Joseph K. , Butt Adeel A. , Goetz Matthew Bidwell , Rodriguez‐Barradas Maria C. , Alcorn Charles W. , Lennox Jeffrey , Beckman Joshua A. , Justice Amy , Freiberg Matthew 
Published: May 2018

Background

Bilirubin may protect against cardiovascular disease (
CVD
) by reducing oxidative stress. Whether elevated bilirubin reduces the risk of
CVD
events among
HIV
+
individuals and if this differs from uninfected individuals remain unclear. We assessed whether bilirubin independently predicted the risk of
CVD
events among
HIV
+
and uninfected participants in
VACS
(Veterans Aging Cohort Study).

Methods and Results

We conducted a prospective cohort study using
VACS
participants free of baseline
CVD
. Total bilirubin was categorized by quartiles.
CVD
as well as acute myocardial infarction, heart failure, and ischemic stroke events were assessed. Cox regression was used to evaluate hazard ratios of outcomes associated with quartiles of total bilirubin in
HIV
+
and uninfected people after adjusting for multiple risk factors. There were 96 381 participants (30 427
HIV
+
); mean age was 48 years, 48% were black, and 97% were men. There were 6603 total incident
CVD
events over a mean of 5.7 years. In adjusted models, increasing quartiles of baseline total bilirubin were associated with decreased hazards of all outcomes (hazard ratio, 0.86; 95% confidence interval, 0.80–0.91). Among
HIV
+
participants, results persisted for heart failure, ischemic stroke, and total
CVD
, but nonsignificant associations were observed for acute myocardial infarction.

Conclusions

VACS
participants (regardless of
HIV
status) with elevated bilirubin levels had a lower risk of incident total
CVD
, acute myocardial infarction, heart failure, and ischemic stroke events after adjusting for known risk factors. Future studies should investigate how this apparently protective effect of elevated bilirubin could be harnessed to reduce
CVD
risk or improve risk estimation among
HIV
+
individuals.
Xanthine Oxidase Inhibitor Allopurinol Prevents Oxidative Stress‐Mediated Atrial Remodeling in Alloxan‐Induced Diabetes Mellitus Rabbits
Authors: Yang Yajuan , Zhao Jianping , Qiu Jiuchun , Li Jian , Liang Xue , Zhang Zhiwei , Zhang Xiaowei , Fu Huaying , Korantzopoulos Panagiotis , Letsas Konstantinos P. , Tse Gary , Li Guangping , Liu Tong 
Published: May 2018

Background

There are several mechanisms, including inflammation, oxidative stress and abnormal calcium homeostasis, involved in the pathogenesis of atrial fibrillation. In diabetes mellitus (
DM
), increased oxidative stress may be attributable to higher xanthine oxidase activity. In this study, we examined the relationship between oxidative stress and atrial electrical and structural remodeling, and calcium handling abnormalities, and the potential beneficial effects of the xanthine oxidase inhibitor allopurinol upon these pathological changes.

Methods and Results

Ninety rabbits were randomly and equally divided into 3 groups: control, DM, and allopurinol‐treated DM group. Echocardiographic and hemodynamic assessments were performed in vivo. Serum and tissue markers of oxidative stress and atrial fibrosis, including the protein expression were examined. Atrial interstitial fibrosis was evaluated by Masson trichrome staining. I
CaL
was measured from isolated left atrial cardiomyocytes using voltage‐clamp techniques. Confocal microscopy was used to detect intracellular calcium transients. The Ca
2+
handling protein expression was analyzed by Western blotting. Mitochondrial‐related proteins were analyzed as markers of mitochondrial function. Compared with the control group, rabbits with DM showed left ventricular hypertrophy, increased atrial interstitial fibrosis, oxidative stress and fibrosis markers, I
CaL
and intracellular calcium transient, and atrial fibrillation inducibility. These abnormalities were alleviated by allopurinol treatment.

Conclusions
Allopurinol, via its antioxidant effects, reduces atrial mechanical, structural, ion channel remodeling and mitochondrial synthesis abnormalities induced by DM‐related increases in oxidative stress.
Applications of an Updated Atmospheric Energetics Formulation
Authors: Trenberth Kevin E. , Fasullo John T. 
Published: May 2018

AbstractAs observations and atmospheric reanalyses have improved, the diagnostics that can be computed with confidence also increase. Accordingly, a new formulation of the energetics of the atmosphere is laid out, with a view to advancing diagnostic studies of Earth’s energy budget and flows. It is utilized to produce assessments of the vertically integrated divergences in both the atmosphere and ocean. Careful conservation of mass is required, with special attention given to the hydrological cycle and redistribution of mass associated with precipitation and evaporation, and a new method for ensuring this is developed. It guarantees that the atmospheric divergence is associated with moisture and precipitation, unlike previous methods. A new term, identified as associated with the enthalpy of precipitation, is included in a preliminary way. It is sensitive to the formulation, and the use of temperature in degrees Celsius instead of Kelvin greatly reduces errors and produces the extra term with values up to about ±5 W m−2. New results for 2000 to 2016 are presented for the vertical-mean and annual-mean diabatic atmospheric heating, atmospheric moistening, and total atmospheric energy divergence. Results for the atmospheric divergence are combined with top-of-atmosphere radiation observations to deduce total surface energy fluxes. Along with estimates of changes in ocean heat content, the Atlantic Ocean meridional heat transports are recomputed for March 2000 through 2013. The new results are compared with previous estimates and an assessment is made of the effects of the new mass balance, change in temperature scale, and the extra precipitation enthalpy term.
On the Detection of Statistical Heterogeneity in Rain Measurements
Authors: Jameson A. R. , Larsen M. L. , Kostinski A. B. 
Published: May 2018

AbstractThe application of the Wiener–Khintchine theorem for translating a readily measured correlation function into the variance spectrum, important for scale analyses and for scaling transformations of data, requires that the data be wide-sense homogeneous (stationary), that is, that the first and second moments of the probability distribution of the variable are the same at all times (stationarity) or at all locations (homogeneity) over the entire observed domain. This work provides a heuristic method independent of statistical models for evaluating whether a set of data in rain is wide-sense stationary (WSS). The alternative, statistical heterogeneity, requires 1) that there be no single global mean value and/or 2) that the variance of the variable changes in the domain. Here, the number of global mean values is estimated using a Bayesian inversion approach, while changes in the variance are determined using record counting techniques. An index of statistical heterogeneity (IXH) is proposed for rain such that as its value approaches zero, the more likely the data are wide-sense stationary and the more acceptable is the use of the Wiener–Khintchine theorem. Numerical experiments as well as several examples in real rain demonstrate the potential of IXH to identify statistical homogeneity, heterogeneity, and statistical mixtures. In particular, the examples demonstrate that visual inspections of data alone are insufficient for determining whether they are wide-sense stationary. Furthermore, in this small data collection, statistical heterogeneity was associated with convective rain, while statistical homogeneity appeared in more stratiform or mixed rain events. These tentative associations, however, need further substantiation.
Quo vadis? The local government in Turkey after public management reforms
Authors: Tan Evrim 
Published: May 2018

In the 2000s, Turkey has reformed its public administration system in line with New Public Management (NPM) principles towards a more decentralized system. Although the initial aim of the reform process is set to achieve a decentralized and more efficient public management system, the empirical data and official statistics cast doubt on whether this outcome will ever be achieved. Analyzing local government legislation, the discretion of central government in local governance, and the changes in the status of local government in public governance, the article presents the evolution of the local government system in Turkey during the Justice and Development Party government. Points for practitioners The public management reform experience of Turkey resembles the NPM reform patterns in countries with Napoleonic state tradition. Similar to these countries, the emphasis on managerial practices over participatory elements has been prevalent in improving the efficiency and effectiveness of public services. Yet, the findings in the Turkish case challenge the proposition that managerial reforms alone, without improving local democratic governance, can enhance the efficiency and effectiveness of public services.
Characterization of Pharmacy Resident Interventions on an Academic Inpatient Internal Medicine Rotation
Authors: Petite Sarah E. 
Published: May 2018

Purpose: To characterize the clinical interventions of postgraduate year 1 (PGY-1) pharmacy residents on a required, 1-month, inpatient adult internal medicine service at an academic medical center. Methods: The interventions completed by PGY-1 pharmacy residents on a required, adult internal medicine rotation were analyzed. Documentation of clinical interventions was performed by the PGY-1 residents, and the significance of the intervention was subsequently determined. Acceptance rates of clinical interventions were also documented and reviewed. Results: A total of 2161 interventions were documented by 14 PGY-1 pharmacy residents between January 2016 and May 2017. Of these interventions, 2016 (93.3%) had a positive, or accepted, outcome. The significance of the majority of interventions was moderate (93.5%), indicating that either an improvement in drug therapy effectiveness, decreased hospital length of stay, reduction in cost, or prevention in harm had occurred. The most common intervention types were recommendations to add, change, or discontinue a medication therapy, completion of a pharmacy dosing consult or conducting an admission medication reconciliation. Conclusion: PGY-1 pharmacy residents have a positive impact on patient care in the inpatient adult internal medicine setting.
Comparison of Postoperative Bleeding in Total Hip and Knee Arthroplasty Patients Receiving Rivaroxaban, Enoxaparin, or Aspirin for Thromboprophylaxis
Authors: Lindquist Desirae E. , Stewart David W. , Brewster Aaryn , Waldroup Caitlin , Odle Brian L. , Burchette Jessica E. , El-Bazouni Hadi 
Published: May 2018

Background: Guidelines recommend the use of multiple pharmacologic agents and/or mechanical compressive devices for prevention of venous thromboembolism, but preference for any specific agent is no longer given in regard to safety or efficacy. Objective: To compare postoperative bleeding rates in patients receiving enoxaparin, rivaroxaban, or aspirin for thromboprophylaxis after undergoing elective total hip arthroplasty or total knee arthroplasty. Methods: This retrospective cohort analysis evaluated patients who received thromboprophylaxis with either enoxaparin, rivaroxaban, or aspirin. All data were collected from the electronic medical record. The primary outcome was any postoperative bleeding. Results: A total of 1244 patients were included with 366 in the aspirin, 438 in the enoxaparin, and 440 in the rivaroxaban arms. Those who received aspirin or enoxaparin were less likely to experience any bleeding compared to those patients who received rivaroxaban ( P < .05). There was also a lower rate of major bleeding in these groups, but the differences were not significant. Conclusions: Aspirin and enoxaparin conferred similar bleeding risks, and both exhibited less bleeding than patients who received rivaroxaban.
Power, Mechanisms, and Denunciations: Understanding Compliance with Human Rights in International Relations
Authors: Rousseau Elise 
Published: May 2018

The four volumes on human rights norms reviewed here investigate a puzzle introduced by quantitative studies, which shows that the expansion of commitments with human rights does not guarantee compliance with these rights in practice. Going beyond the classical opposition between constructivism and rationalism, the volumes explore the conditions and mechanisms that are likely to close this ‘compliance gap’. This essay starts by reviewing the arguments of the books before focusing on two major themes: compliance mechanisms and international denunciations. It argues that the introduction of ‘reintegrative shaming’ and ‘stigma’ to compliance research may help refine current knowledge on normative change and resistance to change. Betts A and Orchard P (eds) (2014) Implementation and World Politics: How International Norms Change Practice. Oxford: Oxford University Press. Friman HR (2015) The Politics of Leverage in International Relations: Name, Shame, and Sanctions. Basingstoke; New York: Palgrave Macmillan. Hafner-Burton E (2013) Making Human Rights a Reality. Princeton, NJ; Oxford: Princeton University Press. Risse T, Ropp SC, and Sikkink K (eds) (2013) The Persistent Power of Human Rights: From Commitment to Compliance. Cambridge: Cambridge University Press.