bluuebunny/crossref_metadata_2025 huggingface dataset:
The KV7 channel activator retigabine suppresses mouse urinary bladder afferent nerve activity without affecting detrusor smooth muscle K+ channel currents
Authors: Tykocki Nathan R. , Heppner Thomas J. , Dalsgaard Thomas , Bonev Adrian D. , Nelson Mark T.
Published: December 2018

Key points

KV7 channels are a family of voltage‐dependent K+ channels expressed in many cell types, which open in response to membrane depolarization to regulate cell excitability.

Drugs that target KV7 channels are used clinically to treat epilepsy. Interestingly, these drugs also cause urinary retention, but it was unclear how.

In this study, we focused on two possible mechanisms by which retigabine could cause urinary retention: by decreasing smooth muscle excitability, or by decreasing sensory nerve outflow.

Urinary bladder smooth muscle had no measurable KV7 channel currents. However, the KV7 channel agonist retigabine nearly abolished sensory nerve outflow from the urinary bladder during bladder filling.

We conclude that KV7 channel activation likely affects urinary bladder function by blocking afferent nerve outflow to the brain, which is key to sensing bladder fullness.

KV7 channels are voltage‐dependent K+ channels that open in response to membrane depolarization to regulate cell excitability. KV7 activators, such as retigabine, were used to treat epilepsy but caused urinary retention. Using electrophysiological recordings from freshly isolated mouse urinary bladder smooth muscle (UBSM) cells, isometric contractility of bladder strips, and ex vivo measurements of bladder afferent activity, we explored the role of KV7 channels as regulators of murine urinary bladder function. The KV7 activator retigabine (10 μM) had no effect on voltage‐dependent K+ currents or resting membrane potential of UBSM cells, suggesting that these cells lacked retigabine‐sensitive KV7 channels. The KV7 inhibitor XE‐991 (10 μM) inhibited UBSM K+ currents; the properties of these currents, however, were typical of KV2 channels and not KV7 channels. Retigabine inhibited voltage‐dependent Ca2+ channel (VDCC) currents and reduced steady‐state contractions to 60 mM KCl in bladder strips, suggesting that reduction in VDCC current was sufficient to directly affect UBSM function. To determine if retigabine altered ex vivo bladder sensory outflow, we measured afferent activity during simulated transient contractions (TCs) of the bladder wall. Simulated TCs caused bursts of afferent activity that were nearly abolished by retigabine. The effects of retigabine were blocked by co‐incubation with XE‐991, suggesting specific activation of KV7 channels on afferent nerves. These results indicate that retigabine primarily affects urinary bladder function by inhibiting TC generation and afferent nerve activity, which are key to sensing bladder fullness. Any direct inhibition of UBSM contractility is likely to be from non‐specific effects on VDCCs and KV2 channels.
Effects of listener age and native language on perception of accented and unaccented sentences
Authors: Bieber Rebecca E. , Yeni-Komshian Grace H. , Freund Maya S. , Fitzgibbons Peter J. , Gordon-Salant Sandra
Published: December 2018

Degradations to auditory input have deleterious effects on speech recognition performance, especially by older listeners. Alterations to timing information in speech, such as occurs in rapid or foreign-accented speech, can be particularly difficult for older people to resolve. It is currently unclear how prior language experience modulates performance with temporally altered sentence-length speech utterances. The principal hypothesis is that prior experience with a foreign language affords an advantage for recognition of accented English when the talker and listener share the same native language, which may minimize age-related differences in performance with temporally altered speech. A secondary hypothesis is that native language experience with a syllable-timed language (Spanish) is advantageous for recognizing rapid English speech. Native speakers of English and Spanish completed speech recognition tasks with both accented and unaccented English sentences presented in various degrees of time compression (TC). Native English listeners showed higher or equivalent recognition of accented and unaccented English speech compared to native Spanish listeners in all TC conditions. Additionally, significant effects of aging were seen for native Spanish listeners on all tasks. Overall, the results did not support the hypotheses for a benefit of shared language experience for non-native speakers of English, particularly older native Spanish listeners.
Technology Feature | ChIP off the old block: Beyond chromatin immunoprecipitation
Authors: Schubert Charlotte
Published: December 2018

Chromatin immunoprecipitation, now over 30 years old, modernizes to include emerging techniques such as gene editing and single-cell platforms.
Endothelial cell adaptation in regeneration
Authors: Gomez-Salinero Jesus M. , Rafii Shahin
Published: December 2018

Tissue-specific endothelial cells maintain organ homeostasis and instruct regeneration
Bad metallic transport in a cold atom Fermi-Hubbard system
Authors: Brown Peter T. , Mitra Debayan , Guardado-Sanchez Elmer , Nourafkan Reza , Reymbaut Alexis , Hébert Charles-David , Bergeron Simon , Tremblay A.-M. S. , Kokalj Jure , Huse David A. , Schauß Peter , Bakr Waseem S.
Published: December 2018

Simulating transport with cold atoms

Much can be learned about the nature of a solid from how charge and spin propagate through it. Transport experiments can also be performed in quantum simulators such as cold atom systems, in which individual atoms can be imaged using quantum microscopes. Now, two groups have investigated transport in the so-called Fermi-Hubbard model using a two-dimensional optical lattice filled with one fermionic atom per site (see the Perspective by Brantut). Moving away from half-filling to enable charge transport, Brown
et al.
found that the resistivity had a linear temperature dependence, not unlike that seen in the strange metal phase of cuprate superconductors. In a complementary study on spin transport, Nichols
et al.
observed spin diffusion driven by superexchange coupling.

Science
, this issue p.
379
, p.
383
; see also p.
344
Semiconducting polymer blends that exhibit stable charge transport at high temperatures
Authors: Gumyusenge Aristide , Tran Dung T. , Luo Xuyi , Pitch Gregory M. , Zhao Yan , Jenkins Kaelon A. , Dunn Tim J. , Ayzner Alexander L. , Savoie Brett M. , Mei Jianguo
Published: December 2018

Beating the heat by blending

Charge carriers move through semiconductor polymers by hopping transport. In principle, these polymers should be more conductive at higher temperatures. In practice, conductivity drops at high temperatures because interchain contacts are disrupted, which limits potential applications. Gumyusenge
et al.
now show that appropriate blending of a semicrystalline conjugated polymer with an insulating polymer that has a high glass-transition temperature creates a morphology that stabilizes a network of semiconductor channels. High charge conductivity was maintained in these materials up to 220°C.

Science
, this issue p.
1131
Building two-dimensional materials one row at a time: Avoiding the nucleation barrier
Authors: Chen Jiajun , Zhu Enbo , Liu Juan , Zhang Shuai , Lin Zhaoyang , Duan Xiangfeng , Heinz Hendrik , Huang Yu , De Yoreo James J.
Published: December 2018

No barriers to growing a row

Classical nucleation theory predicts that two-dimensional islands on a surface must reach a critical size before they continue to grow; below that size, they dissolve. Chen
et al.
used phage display to select for short peptides that would bind to molybdenum disulfide (MoS
2
) (see the Perspective by Kahr and Ward). Hexagonal arrays of these peptides grew epitaxially as dimers but without a size barrier—the critical nuclei size was zero. Although two-dimensional arrays formed, growth occurred one row at time. Classical nucleation theory indeed predicts the absence of a barrier for such one-dimensional growth.

Science
, this issue p.
1135
; see also p.
1111
Novel Modified Vaccinia Virus Ankara Vector Expressing Anti-apoptotic Gene
B13R
Delays Apoptosis and Enhances Humoral Responses
Authors: Chea Lynette S. , Wyatt Linda S. , Gangadhara Sailaja , Moss Bernard , Amara Rama R.
Published: December 2018

MVA is an attractive viral vector for vaccine development due to its safety and immunogenicity in multiple species and humans even under conditions of immunodeficiency. Here, to further improve the immunogenicity of MVA, we developed a novel vector, MVA-
B13R
, by replacing the fragmented anti-apoptotic genes
181R
/
182R
with a functional version derived from vaccinia virus,
B13R
. Our results show that MVA-
B13R
significantly delays apoptosis in antigen-presenting cells and muscle cells
in vitro
and augments vaccine-induced humoral immunity in mice, leading to the development of a novel vector for vaccine development against infectious diseases and cancer.
Development of Stable Rotavirus Reporter Expression Systems
Authors: Kanai Yuta , Kawagishi Takahiro , Nouda Ryotaro , Onishi Misa , Pannacha Pimfhun , Nurdin Jeffery A. , Nomura Keiichiro , Matsuura Yoshiharu , Kobayashi Takeshi
Published: December 2018

Development of reporter RVs has been hampered by the lack of comprehensive reverse genetics systems. Recently, we developed a plasmid-based reverse genetics system that enables generation of reporter RVs expressing NLuc luciferase. The prototype reporter RV had some disadvantages (i.e., the transgene was unstable and was expressed as a fusion protein with a partial NSP1 peptide); however, the improved reporter RV overcomes these problems through modification of the untranslated region of the reporter-NSP1 chimeric gene. This strategy for generating stable reporter RVs could be expanded to diverse transgenes and be used to develop RV transduction vectors. Also, the data improve our understanding of the importance of 5′- and 3′-terminal sequences in terms of genome replication, assembly, and packaging.
Achieving high-quality universal health coverage: a perspective from the National Health Service in England
Authors: Friebel Rocco , Molloy Aoife , Leatherman Sheila , Dixon Jennifer , Bauhoff Sebastian , Chalkidou Kalipso
Published: December 2018

Governments across low-income and middle-income countries have pledged to achieve universal health coverage by 2030, which comes at a time where healthcare systems are subjected to multiple and persistent pressures, such as poor access to care services and insufficient medical supplies. While the political willingness to provide universal health coverage is a step into the right direction, the benefits of it will depend on the quality of healthcare services provided. In thisanalysis paper, we ask whether there are any lessons that could be learnt from the English National Health Service, a healthcare system that has been providing comprehensive and high-quality universal health coverage for over 70 years. The key areas identified relate to the development of a coherent strategy to improve quality, to boost public health as a measure to reduce disease burden, to adopt evidence-based priority setting methods that ensure efficient spending of financial resources, to introduce an independent way of inspecting and regulating providers, and to allow for task-shifting, specifically in regions where staff retention is low.
Ethical rationales for past and present military medical practices
Authors: Howe Edmund
Published: December 2018

This paper reviews changes in the ethical challenges that have arisen in military medicine over the past four decades. This includes the degree, if any, to which providers during the Vietnam conflict have carried out what we now refer to as harsh interrogation measures in an attempt to extract information from captured enemy soldiers, the extent, if any, to which the USA used medicine as a means to try to win over the hearts and minds of civilians in occupied territory and how providers should treat service members who return from the front with combat fatigue. An issue that arose during the first Gulf War in 1991 is discussed, namely US service persons being required to take botulism vaccine without their consent. Finally, present challenges are discussed including interrogation measures such as waterboarding and the ethical issues posed in the recent past by the exclusion of gay service members and those posed presently by the inclusion of transgender members. Two ethical values are suggested that have remained constant, namely giving priority to the individual needs of service personnel over those of the unit when there are no urgent combat needs and the reliance on individual virtue when what they should do is morally unclear.
Pulmonary actinomycosis and hypertrophic osteopathy in a red kangaroo (Macropus rufus)
Authors: Kunze Patricia Edith , Sanchez Carlos R , Pich Ashley , Aronson Stuart , Dennison Sophie
Published: December 2018

A five‐year‐old red kangaroo (Macropus rufus) presented with bilateral, firm thickening of the radius, ulna and metatarsal bones with local tissue hyperthermia. Radiographs revealed a soft tissue opacity left intrathoracic mass lying cranial to the heart, and extensive areas of smooth to palisading periosteal reaction along radius, ulna and metatarsus bilaterally. Culture of an aspirate from the mass yielded Actinomyces species. Treatment consisting of injectable penicillin and oral amoxicillin/clavulanic acid, meloxicam and tramadol was implemented for nine months. While receiving antibiotic therapy, the animal’s clinical condition improved, however, clinical signs returned after antibiotics were discontinued. Keeping it on daily medications indefinitely was considered neither practical nor safe for the staff and highly stressful for the animal. The kangaroo was euthanased one year and two months after initial diagnosis. Gross necropsy and histological findings confirmed the clinical diagnosis of pulmonary actinomycotic abscessation with hypertrophic osteopathy.
A Common Set of Weights for Ranking Decision-Making Units with Undesirable Outputs: A Double Frontiers Data Envelopment Analysis Approach
Authors: Chen Lei , Wu Fei-Mei , Feng Feng , Lai Fujun , Wang Ying-Ming
Published: December 2018

Major drawbacks of the traditional data envelopment analysis (DEA) method include selecting optimal weights in a flexible manner, lacking adequate discrimination power for efficient decision-making units, and considering only desirable outputs. By introducing the concept of global efficiency optimization, this study proposed a double frontiers DEA approach with undesirable outputs to generate a common set of weights for evaluating all decision-making units from both the optimistic and pessimistic perspectives. For a unique optimal solution, compromise models for individual efficiency optimization were developed as a secondary goal. Finally, as an illustration, the models were applied to evaluate the energy efficiency of the Chinese regional economy. The results showed that the proposed approach could improve discrimination power and obtain a fair result in a case where both desirable and undesirable outputs exist.
Two semi-quantum secure direct communication protocols based on Bell states
Authors: Sun Yuhua , Yan Lili , Chang Yan , Zhang Shibin , Shao Tingting , Zhang Yan
Published: December 2018

Quantum secure direct communication allows one participant to transmit secret messages to another directly without generating a shared secret key first. In most of the existing schemes, quantum secure direct communication can be achieved only when the two participants have full quantum ability. In this paper, we propose two semi-quantum secure direct communication protocols to allow restricted semi-quantum or “classical” users to participate in quantum communication. A semi-quantum user is restricted to measure, prepare, reorder and reflect quantum qubits only in the classical basis [Formula: see text]. Both protocols rely on quantum Alice to randomly prepare Bell states, perform Bell basis measurements and publish the initial Bell states, but the semi-quantum Bob only needs to measure the qubits in classical basis to obtain secret information without quantum memory. Security and qubit efficiency analysis have been given in this paper. The analysis results show that the two protocols can avoid some eavesdropping attacks and their qubit efficiency is higher than some current related quantum or semi-quantum protocols.
Quantum-based automated short answer scoring system
Authors: Walia Tarandeep Singh , Josan Gurpreet Singh , Singh Amarpal
Published: December 2018

Answer Scoring is defined as an act of assigning a score to an answer by a human grader. This scoring technique is costly and requires deep logical efforts and it depends on less-than-perfect human assessment. However, the Automated Scoring (AS) System has its importance in providing the student with a score as well as feedback within seconds. This paper describes an AS system in which scores are assigned to essays automatically based upon predefined algorithms. Most of the educational sectors carry out an important examination process, i.e. to examine and assess the capabilities of the student based on his/her given answers. To accomplish this process, the human graders can apply this Automated Answer Scoring system. The paper goes through the existing techniques for automated answer scoring systems and then goes on to explain the newly developed system in which scoring is done by the statistical method adopting and integrating rule-based semantic quantum-based features analysis resulting in more accuracy. It is in a way a hybrid system suitable for short answer type scoring. It also presents the methodology and architecture of AS.
Quantum-inspired minimum distance classification in a biomedical context
Authors: Sergioli Giuseppe , Russo Giorgio , Santucci Enrica , Stefano Alessandro , Torrisi Sebastiano Emanuele , Palmucci Stefano , Vancheri Carlo , Giuntini Roberto
Published: December 2018

We propose an application of a quantum-inspired version of the Nearest Mean Classifier (NMC) (G. Sergioli, E. Santucci, L. Didaci, J. A. Miszczak and R. Giuntini, A quantum inspired version of the NMC classifier, Soft Comput. 22(3) (2018) 691. G. Sergioli, G. M. Bosyk, E. Santucci and R. Giuntini, A quantum-inspired version of the classification problem, Int. J. Theo. Phys. 56(12) (2017) 3880. E. Santucci and G. Sergioli, Classification problem in a quantum framework, in quantum foundations, probability and information, Proc. Quantum and Beyond Conf., 13–16 June 2016, Vaxjo, Sweden, A. Khrennikov and T. Bourama, Springer-Berlin, Germany, 2018 (in press, 2018). E. Santucci, Quantum minimum distance classifier, Entropy 19(12) (2017) 659.) to a biomedical context. In particular, we benchmark the performances of such a quantum-variant of NMC against NMC and other (nonlinear) classifiers with respect to the problem of classifying the probability of survival for patients affected by idiopathic pulmonary fibrosis (IPF).
Numerical Simulation of Wave Breaking Over a Submerged Step with SPH Method
Authors: Wen Hongjie , Ren Bing , Wang Guoyu , Zhao Yumeng
Published: December 2018

Wave breaking over a submerged step with a steep front slope and a wide horizontal platform is studied by smoothed particle hydrodynamic (SPH) method. By adding a momentum source term and a velocity attenuation term into the governing equation, a nonreflective wave maker system is introduced in the numerical model. A suitable circuit channel is specifically designed for the present SPH model to avoid the nonphysical rise of the mean water level on the horizontal platform of the submerged step. The predicted free surface elevations and the spatial distributions of wave height and wave setup over the submerged step are validated using the corresponding experimental data. In addition, the vertical distributions of wave-induced current over the submerged step are also investigated at both low and high tides.
Beating Approximation Factor Two for Weighted Tree Augmentation with Bounded Costs
Authors: Adjiashvili David
Published: December 2018

The Weighted Tree Augmentation Problem (WTAP) is a fundamental well-studied problem in the field of network design. Given an undirected tree
G
=(
V
,
E
), an additional set of edges
L
⊑
V
×
V
disjoint from
E
called
links
and a cost vector
c
∈ R
≥ 0

L

, WTAP asks to find a minimum-cost set
F
⊑
L
with the property that (
V
,
E
∪
F
) is 2-edge connected. The special case where
c
ℓ
= 1 for all ℓ ∈
L
is called the Tree Augmentation Problem (TAP).

For the class of bounded cost vectors, we present the first improved approximation algorithm for WTAP in more than three decades. Concretely, for any
M
∈ R
≥ 1
and ε > 0, we present an LP based (μ +ϵ)-approximation for WTAP restricted to cost vectors
c
in [1,
M
]

L

for μ ≈ 1.96417. More generally, our result is a (μ +ϵ)-approximation algorithm with running time
n

r

O
(1)

, where
r
=
c
max
/
c
min
is the ratio between the largest and the smallest cost of any link. For the special case of TAP, we improve this factor to 5/3+ϵ.

Our results rely on several new ideas, including a new LP relaxation of WTAP and a two-phase rounding algorithm. In the first phase, the algorithm uses the fractional LP solution to guide a simple decomposition method that breaks the tree into well-structured trees and equips each with a part of the fraction LP solution. In the second phase, the fractional solution in each part of the decomposition is rounded to an integral solution with two rounding procedures and the best outcome is included in the solution. One rounding procedure exploits the constraints in the new LP, while the other one exploits a connection to the Edge Cover Problem. We show that both procedures cannot have a bad approximation guarantee simultaneously to obtain the claimed approximation factor.
Sympathetic responses induced by radiofrequency catheter ablation of atrial fibrillation
Authors: Cui Jian , Gonzalez Mario D. , Blaha Cheryl , Hill Ashley , Sinoway Lawrence I.
Published: December 2018

Radiofrequency catheter ablation (RFCA) is a frequently performed procedure in patients with atrial fibrillation. Prior studies have shown that the RFCA may directly stimulate vagal afferents during the procedure, whereas the vagal tone assessed by heart rate variability (HRV) is lowered weeks after the RFCA procedure. The effects of RFCA performed in the left atrium on sympathetic nerve activity have not been assessed. In the present study, we hypothesized that RFCA would lower muscle sympathetic nerve activity (MSNA) during ablation and would raise MSNA 1 day postablation. A total of 18 patients were studied. In protocol 1 ( n = 10), electrocardiogram, blood pressure, and MSNA in the peroneal nerve were recorded through the RFCA procedure performed in the electrophysiology laboratory. In protocol 2, eight patients were studied before the procedure and 1 day postablation. RFCA led to a decrease in MSNA immediately after the procedure (25.4 ± 3.2 to 17.2 ± 3.8 bursts/min, P < 0.05). Cardiac parasympathetic activity was determined using indexes of HRV and increased during the procedure. One day postablation, MSNA was above baseline values (21.3 ± 3.7 to 35.7 ± 2.6 bursts/min, P < 0.05). HRV indexes of cardiac parasympathetic activity fell, and the HRV index of sympathovagal balance was not significantly altered. The results show that RFCA raised cardiac parasympathetic activity and decreased MSNA during the procedure. One day postablation, MSNA rose and cardiac parasympathetic activity fell. In addition, RFCA evokes differentiated sympathetic responses directed to the heart and skeletal muscles.

NEW & NOTEWORTHY The effects of radiofrequency catheter ablation performed in the left atrium on muscle sympathetic nerve activity (MSNA) have not been assessed. The results of this study show that radiofrequency catheter ablation raised cardiac parasympathetic activity and decreased MSNA during the procedure. One day postablation, MSNA rose and cardiac parasympathetic activity fell. We speculate that the partial autonomic afferent denervation induces these effects on autonomic activity.
miR-494 Sensitizes Gastric Cancer Cells to TRAIL Treatment Through Downregulation of Survivin
Authors: Xu Shuning , Li Danyang , Li Tianyuan , Qiao Lei , Li Ke , Guo Leiming , Liu Ying
Published: December 2018

Background/Aims: TNF-related apoptosis-inducing ligand (TRAIL) is a novel and low-toxic anti-tumor drug used for various cancers. However, cancer cells usually develop mechanisms to acquire the resistance against TRAIL. Among these changes, dysregulation of microRNAs (miRNAs) usually occurs in cancer cells and is responsible for induction of drug resistance. Methods: Expression of miR-494 in gastric cancer tissues and cell lines was detected by quantitative reverse transcriptase real time PCR (qRT-PCR) analysis. Effect of miR-494 on regulating the TRAIL sensitivity to gastric cancer cell lines was evaluated by MTT assays. Bioinformatics and luciferase reporter assays were used to confirm the regulation of miR-494 on survivin. Mitochondrial apoptosis pathway in gastric cancer cells was tested by western blot and flow cytometry analysis. Results: Obvious downregulation of miR-494 was observed in gastric cancer cells. Furthermore, we found that expression profile of miR-494 was associated with TRAIL-sensitivity in gastric cancer. Enforced expression of miR-494 was found to sensitize the gastric cancer cells to TRAIL-induced cytotoxicity. Mechanically, Luciferase reporter assays proved that survivin was the target of miR-494 in gastric cancer cells. Enforced expression of miR-494 decreased the expression of survivin, and thus promoted the TRAIL-induced mitochondria collapse and apoptosis pathway. Conclusion: MiR-494/survivin axis represents a potential mechanism which is responsible for TRAIL resistance in gastric cancer cells. Increasing the miR-494 expression may serve as a novel therapeutic strategy to sensitize gastric cancer cells to TRAIL treatment.
Establishment of a Mouse Model of Premature Ovarian Failure Using Consecutive Superovulation
Authors: Nie Xiaowei , Dai Youjin , Zheng Yuan , Bao Dan , Chen Qin , Yin Yuan , Fu Heling , Hou Daorong
Published: December 2018

Background/Aims: This study investigated the effect of consecutive superovulation on the ovaries and established a premature ovarian failure (POF) model in mice. Methods: The mouse POF model was induced by 5-15 consecutive superovulation treatments with pregnant mare serum gonadotropin (PMSG), human chorionic gonadotropin (HCG) and prostaglandin F2α (PGF2α). Normal adult mice were compared with mice displaying natural ovarian aging. The following serum biochemical parameters were measured: including follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), estradiol (E2), inhibin B (INH B), malondialdehyde (MDA), total superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels. Follicles were counted using H&E staining. Levels of 8-hydroxyguanosine (8-OhdG), 4-hydroxynonenal (4-HNE), nitrotyrosine (NTY), anti-Mullerian hormone (AMH) and CDKN2A/ p16 (p16) were detected using immunohistochemical staining. Reactive oxygen species (ROS) levels were measured using dihydroethidium (DHE) staining. Cell apoptosis was detected using an in situ TUNEL fluorescence staining assay. Levels of proteins involved in ROS-related pathways and the p16 protein were detected using Western blotting. Sod1, Sod2 and Sod3 mRNA levels were detected using quantitative polymerase chain reaction (Q-PCR). Oocyte quality was evaluated using in vitro fertilization (IVF) and zygote culture. Results: Consecutive superovulation groups presented lower P, E2, SOD, GSH-Px and INH B levels, significantly higher FSH, LH, MDA and ROS levels, and significantly fewer primordial follicles compared with the control group. Consecutive superovulation groups presented significantly increased levels of Sod2, 8-OhdG, 4-HNE, NTY, significantly increased levels of the SIRT1 and FOXO1 proteins, significantly increased levels of the senescence-associated protein p16, as well as decreased AMH, Sod1 and Sod3 levels and increased granulosa cell apoptosis compared with the control group. Conclusion: Consecutive superovulation significantly decreased ovarian function and oocyte quality and increased oxidative stress and apoptosis in the ovary via a mechanism involving the p16 and SIRT1/FOXO1 signaling pathways. These findings suggest that consecutive superovulation may be used to establish a mouse model of ovarian aging.
Ezetimibe in Combination With Simvastatin Reduces Remnant Cholesterol Without Affecting Biliary Lipid Concentrations in Gallstone Patients
Authors: Ahmed Osman , Littmann Karin , Gustafsson Ulf , Pramfalk Camilla , Öörni Katariina , Larsson Lilian , Minniti Mirko E. , Sahlin Staffan , Camejo German , Parini Paolo , Eriksson Mats
Published: December 2018

Background

In randomized trials (SHARP [Study of Heart and Renal Protection],
IMPROVE
‐IT [Improved Reduction of Outcomes: Vytorin Efficacy International Trial]), combination of statin and ezetimibe resulted in additional reduction of cardiovascular events. The reduction was greater in patients with type 2 diabetes mellitus (T2
DM
), where elevated remnant cholesterol and high cardiovascular disease risk is characteristic. To evaluate possible causes behind these results, 40 patients eligible for cholecystectomy, randomized to simvastatin, ezetimibe, combined treatment (simvastatin+ezetimibe), or placebo treatment during 4 weeks before surgery, were studied.

Methods and Results

Fasting blood samples were taken before treatment start and at the end (just before surgery). Bile samples and liver biopsies were collected during surgery. Hepatic gene expression levels were assessed with
qPCR
. Lipoprotein, apolipoprotein levels, and content of cholesterol, cholesteryl ester, and triglycerides were measured after lipoprotein fractionation. Lipoprotein subclasses were analyzed by nuclear magnetic resonance. Apolipoprotein affinity for human arterial proteoglycans (
PG
) was measured. Biomarkers of cholesterol biosynthesis and intestinal absorption and bile lipid composition were analyzed using mass spectrometry. Combined treatment caused a statistically significant decrease in plasma remnant particles and apolipoprotein B (ApoB)/lipoprotein content of cholesterol, cholesteryl esters, and triglycerides. All treatments reduced ApoB‐lipoprotein
PG
binding. Simvastatin and combined treatment modified the composition of lipoproteins. Changes in biomarkers of cholesterol synthesis and absorption and bile acid synthesis were as expected. No adverse events were found.

Conclusions

Combined treatment caused atheroprotective changes on ApoB‐lipoproteins, remnant particles, bile components, and in ApoB‐lipoprotein affinity for arterial
PG
. These effects might explain the decrease of cardiovascular events seen in the
SHARP
and
IMPROVE
‐
IT
trials.

Clinical Trial Registration

URL
:
www.clinicaltrialsregister.eu
. Unique identifier: 2006‐004839‐30).
Religion in a Democratic and Pluralistic Society (The Experience of Indonesia)
Authors: Sunarko Adrianus
Published: December 2018

In order that religions in a multicultural modern democratic society like Indonesia do not become a source of conflict, the adherents of religions must develop a certain rationality of faith. That rationality is related to the attitude towards other religions and beliefs, to the autonomy of science, and to the procedures inherent in the democratic system. Hopefully, religious communities can develop a positive attitude towards those three things, without denying their religious identity. The learning process associated with them cannot be imposed from outside, but must be born of the dynamics within the community of the faith/ religious community itself. If the learning process is successfully pursued, the adherents of the religions can give an important contribution to the development of democracy in Indonesia.
The larvae of two species of Bokermannohyla (Anura, Hylidae, Cophomantini) endemic to the highlands of central Brazil
Authors: LINS ANNA CAROLINA RAMALHO , DE MAGALHÃES RAFAEL FÉLIX , COSTA RENAN NUNES , BRANDÃO REUBER ALBUQUERQUE , PY-DANIEL TAINÃ RAPP , DE OLIVEIRA MIRANDA NÚBIA ESTHER , MACIEL NATAN MEDEIROS , NOMURA FAUSTO , PEZZUTI TIAGO LEITE
Published: December 2018

Bokermannohyla (tribe Cophomantini) is an endemic genus of Brazilian treefrogs containing 32 species arranged into four phenetic groups. The B. pseudopseudis group includes nine species, which are typically found in rupestrian ecosystems of disjunct Brazilian mountain ranges. Tadpoles have been shown to be important sources of information for the taxonomy of this genus, although careful analyses of character variation and descriptions of internal anatomy remain scarce. Since the first description of B. pseudopseudis tadpoles was based on a mixed series containing specimens of B. pseudopseudis and B. sapiranga, we describe the larvae of these two species from their type localities, including their external morphology, oral cavity, and skeletal system. Tadpoles of B. pseudopseudis are easily distinguished from those of B. sapiranga by aspects of their coloration and characters of their oral disc (more labial tooth rows, more numerous submarginal papillae and flaps with labial teeth). These morphological differences may be diagnostic for these two similar species, whereas their chondrocranium, hyobranchial apparatus, and oral cavity are alike, suggesting less variability in these character systems between closely related species. Finally, we provide the first comparison of data on the skeletal system of Bokermannohyla and other Cophomantini, highlighting characters of potential relevance to the systematics of the tribe.
Reexamination of the Late Pliocene Climate over China Using a 25-km Resolution General Circulation Model
Authors: Yan Qing , Wei Ting , Zhang Zhongshi
Published: December 2018

Simulations of past warm climate provide an opportunity to better understand how the climate system may respond to increased greenhouse gas emissions. Using the ~25-km-resolution Community Atmosphere Model, version 4 (CAM4), we examine climate change over China in the Late Pliocene warm period (3.264–3.025 Ma) and further explore the influences of different sea surface temperature (SST) forcings and model horizontal resolutions. Initial evaluation shows that the high-resolution CAM4 performs well in capturing the climatological distribution of present-day temperature, precipitation, and low-level monsoon circulations over China. Based on the standard Pliocene Research, Interpretation and Synoptic Mapping (version 4; PRISM4) boundary conditions, CAM4 predicts an increase of annual mean temperature by ~0.5°C over China in the Late Pliocene relative to the preindustrial era, with the greatest warming in northwest China but cooling in southwest China. Enhanced annual mean precipitation is observed in the Late Pliocene over most of China except for northwest China where precipitation is decreased. The East Asian summer (winter) monsoon is intensified (weakened) in the Late Pliocene as suggested by geological evidence, which is attributed to the enhanced (reduced) land–sea thermal contrast. The East Asian monsoon domain exhibits a northwestward expansion in the Late Pliocene, especially over the Tibetan Plateau. Additionally, our results indicate that the modeled climate change is sensitive to the Late Pliocene SST forcings and model resolution. Particularly, different SST forcings [PRISM4-based vs Pliocene Model Intercomparison Project (PlioMIP)-based SSTs] affect the modeled phase change of summer monsoon and the associated precipitation change, while model resolution (~25 vs 400 km) mainly impacts precipitation change.
Spatial Coherence of Water Vapor and Rainfall over the Indian Subcontinent during Different Monsoon Seasons
Authors: Radhakrishna Basivi , Rao T. Narayana , Saikranthi K.
Published: December 2018

Spatial coherency in atmospheric water vapor and rainfall and their association have been studied over the Indian subcontinent utilizing high spatiotemporal resolution data. Total column water vapor (TCWV) values derived from the Indian National Satellite (INSAT) system series (INSAT-3D) are first evaluated against data from an International GNSS Service (IGS) GPS receiver at Bangalore and the Global Precipitation Measurement Microwave Imager (GMI). The bias, correlation coefficient, and RMSE of TCWV between INSAT-3D and GMI show that, except for the south Bay of Bengal, the datasets compare well. The seasonal mean TCWV shows large values with lower standard deviation during the southwest monsoon (SWM) than in the northeast monsoon (NEM). Different temporal scales that contribute to the TCWV variance at a given point are quantified, and the variability due to 30–60-day oscillations is found to be dominant during both the monsoon seasons. TCWV and rainfall show good correspondence over the whole Indian subcontinent during both monsoon seasons except over the Arabian Sea and southern Myanmar regions, where large TCWV values show less rainfall during the SWM. On the whole, the spatial homogeneity and intergrid correlations in TCWV and rainfall are higher in NEM than in SWM. The decorrelation distance d0 for TCWV is found to be 10 times larger than that for rainfall, indicating that the rainfall homogeneity is generally limited to smaller areas. The large d0 values of TCWV are mainly due to the occurrence of source and sink processes at large spatial scales over those regions.
Capacity Constraints and Horizontal Merger Effects
Authors: Ezrielev Jay
Published: December 2018

This article examines how capacity constraints affect horizontal mergers. Binding capacity constraints for merging firms may mitigate merger price effects, but capacity constraints for nonmerging firms may either amplify or mitigate such effects. The presence of capacity constraints for both the merging and nonmerging firms in a market further complicates the analysis of merger price effects. Capacity constraints may also confound the relationship between market concentration and merger price effects. In addition, capacity constraints affect market definition analysis and analytical tools such as merger simulation and upward pricing pressure indexes. Analyzing the effects of capacity constraints on mergers continues to be a challenge for merger reviews.
Consumer Welfare Theory as an Ethical Consideration:: An Essay on Hipsters, Invisible Feet, and the “Science” of Economics
Authors: Bush Darren
Published: December 2018

This article outlines the principle of efficiency as taken from physics and misapplied into the realm of economics. The result of the misapplication has been a narrow view of antitrust policy, culminating in an extremely conservative application of the consumer welfare standard. The result of such policy has been increasing concentration in many industries, abdication of any examination of monopoly power in the context of Section 2 of the Sherman Act, and dogmatic defense of “consumer welfare” as the only scientific approach to antitrust law. Part II reviews of the original goals of antitrust, as viewed without the lens of present-day economic efficiency. These are policy goals as described in legislative history and judicial development of common law. As such, they are ethical considerations distinct from consumer welfare. In part III, the article discusses the central tenets of economics in antitrust policy. These central notions are policy considerations that are misapplications of physics. Part IV discusses the physics definition of efficiency, with some insights as to the issues arising from adopting such a standard in terms of antitrust markets. Part V addresses the failures of antitrust using the lens of physics, explaining that consumer welfare is an ethical argument, not a scientific one. Part VI addresses other potential ethical standards for antitrust enforcement, as well as empirical evidence that support such norms. Part VII offers concluding thoughts where the article argues that there are superior ethical norms that would boost antitrust enforcement and that are consistent with the goals of antitrust.
Profane cooks and minor condiments: Chutnification and “cooking the world” in Salman Rushdie’s Midnight’s Children
Authors: Ray Shakuntala
Published: December 2018

The exploration of food in Salman Rushdie’s canonical novel Midnight’s Children (1981) is neither provincial nor an act of strategic essentialism. Food as a central artistic device has been understudied in the contexts of this novel, its ambitious scope and transnational implications left unexplored through a contextual lens. This article uncovers the hidden significance of “pure” or sacred cooks in the subcontinental imagination and the ramifications of such comparison for the consideration of abject embodiment as a site of creativity and transcendence in the text. It also reveals the ways in which Rushdie both reinstates and reworks a South Asian understanding of food in his use of pickles as portable magic.
Self-control, sleep disturbance, and the mediating role of occupational burnout in married couples
Authors: Seibert Gregory S. , Jaurequi Matthew E. , May Ross W. , Cooper Ashley N. , Ledermann Thomas , Kimmes Jonathan G. , Fincham Frank D.
Published: December 2018

Although the importance of occupational burnout for sleep has long been recognized, it is largely examined as an individual phenomenon. Because a majority of adults in the U.S. share the bedroom with their partner, the current study examines the role of occupational burnout in understanding the link between self-control and sleep disturbance in close relationships. Data from 96 married couples were analyzed using the actor–partner interdependence mediation model. Both husbands’ and wives’ self-control (predictor) were linked to their levels of occupational burnout (mediator), and to husbands’ sleep disturbance (outcome) through husbands’ occupational burnout. Neither husbands’ or wives’ self-control nor occupational burnout scores related to wives’ sleep disturbance. Findings from the current study identify burnout management in husbands as a potential nonpharmacological alternative approach to treating sleep disorders and emphasizes the need to examine predictors of sleep in a relational context.
Privacy rules for revealing one’s undocumented status to nonfamily members: Exploring the perspectives of undocumented youth of Mexican origin
Authors: Kam Jennifer A. , Steuber Fazio Keli , Mendez Murillo Roselia
Published: December 2018

Based on the theory of communication privacy management, we explored: (a) undocumented immigrant youth’s privacy rules for managing their undocumented status disclosures to nonfamily members, and (b) responses to disclosures by recipients and undocumented youth. Semi-structured interviews were conducted with 30 undocumented youth (10th–12th grades) who immigrated to the U.S. from Mexico. Youth managed their undocumented status with nonfamily members using criteria related to support activation, protection, acceptance, and a sense of empowerment. When disclosed, most recipients responded by providing emotional support and advice. Youth felt positively toward recipient reactions that were nonjudgmental. Lastly, most participating youth felt better after revealing their undocumented status because the youth learned that the recipient was in a similar situation or because the youth experienced catharsis. Our results show the extent to which preexisting privacy management research applies to an understudied, marginalized group and provides new insights on privacy management.
Jomini versus Clausewitz: Hamley’s Operations of War and Military Thought in the British Army, 1866–1933
Authors: Dighton Adam
Published: December 2018

Although Edward Hamley’s Operations of War was first published in 1866, it still occupied a dominant position in the British Army’s military thought in 1914. Despite this, historians have failed to explain why it was influential for so long. By considering how the volume was revised, this article demonstrates that it provided the army with a standard way to conceptualize war between 1870 and 1895, before being amended to reflect subsequent advances in military thought. Therefore, Hamley’s book provides an insight into how British military thought developed, particularly the way it transitioned from a Jominian to a Clausewitzian understanding of war.
Looking Through Dementia: What Do Commercial Stock Images Tell Us About Aging and Cognitive Decline?
Authors: Harvey Kevin , Brookes Gavin
Published: December 2018

Commercial stock images are existing, artificially constructed visuals used by businesses and media outlets to articulate certain values, assumptions and beliefs. Despite their pervasiveness and accessibility, little is known about the ways in which stock images communicate meanings relating to health and illness. This study examines a broad range of common stock images that depict dementia and aging, revealing the tendency for older people with dementia to be represented in objectifying and de-humanizing terms—emphasizing disease and deficit at the expense of the whole person, whereas precluding any possibility of enduring personhood. As well as introducing a multimodal critical discourse approach that can be adopted by other researchers examining the ideological underpinnings of health and illness imagery, this study underscores the importance of critically interrogating stock photography—a much neglected, yet profoundly influential, cultural resource that can shape the ways we think about and respond to illness and disease.
Ribociclib in HR+/HER2− Advanced or Metastatic Breast Cancer Patients
Authors: Rascon Kaitlin , Flajc Goran , De Angelis Carmine , Liu Xinli , Trivedi Meghana V. , Ekinci Ekim
Published: December 2018

Objective: To review the chemistry, pharmacology, pharmacokinetics, safety, and efficacy of ribociclib (LEE011, Kisqali) in hormone receptor–positive/human epidermal growth factor receptor-2–negative (HR+/HER2−) metastatic breast cancer. Data Sources: A PubMed search was performed using the terms ‘Ribociclib’, ‘Kisqali’, and ‘LEE011’ between May 2018 and November 2018. References of published articles and reviews were also assessed for additional information. Study Selection and Data Extraction: English-language preclinical and clinical studies on the chemistry, pharmacology, pharmacokinetics, safety, and efficacy of ribociclib were evaluated. Data Synthesis: Ribociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, is Food and Drug Administration (FDA) approved in combination with endocrine therapy for treatment of HR+/HER2− advanced or metastatic breast cancer in premenopausal/perimenopausal and postmenopausal women. Three phase III trials have evaluated ribociclib in combination with endocrine therapy, including letrozole, anastrozole, tamoxifen, and fulvestrant. These studies found that ribociclib 600 mg/d, 21 days on, 7 days off, leads to a significantly greater median progression-free survival (PFS), ranging from 8 to 13 months. Ribociclib is well tolerated in elderly patients, maintains health-related quality of life, and significantly reduces pain scores. The dose-limiting toxicities found in phase I studies were neutropenia, thrombocytopenia, and QTc prolongation. Common adverse effects seen in phase III trials include neutropenia, leukopenia, nausea, diarrhea, vomiting, and fatigue. Relevance to Patient Care and Clinical Practice: Literature on the safety and efficacy of ribociclib as well as its place in therapy in comparison to other FDA-approved CDK4/6 inhibitors for breast cancer is discussed. Conclusions: Ribociclib, when added to endocrine therapy, significantly improves PFS and has manageable toxicity in premenopausal/perimenopausal and postmenopausal women with HR+/HER2− advanced breast cancer.