bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex with a transgender or gender diverse person among patients attending a sexual health centre in Melbourne, Australia
Authors: Cleere Eoin F , Fairley Christopher K , McGrath Launcelot , Bradshaw Catriona S , Chen Marcus Y , Chow Eric P F
Published: June 2018

Objectives

All males and females attending the Melbourne Sexual Health Centre (MSHC) from August 2017 were asked whether they had had sex with a transgender or gender diverse (TGD) person using computer-assisted self-interviewing (CASI). We aimed to verify the self-reported responses via chart review. The secondary aim of this study was to identify whether having sex with a TGD person was associated with STI risk.

Methods

This was a retrospective chart analysis of patients visiting MSHC between August and December 2017. Chart review was performed to verify the self-reported responses. Multivariable logistic regression was performed to examine the association between having sex with a TGD person and patients’ characteristics and STI risk.

Results

Of the 10 100 male and female consultations, the proportion who reported having sex with a TGD person was 111 (1.0%) and was higher among males (1.3%) than females (0.6%) (p=0.001). After chart review, we could verify 66.9% of the responses, more for males (75.2%) than females (45.2%) (p<0.001). Of the 6822 males, men aged ≥35 years (adjusted OR=2.2; 95% CI 1.1 to 4.1) were more likely to have sex with a TGD person compared with men aged ≤24 years, after adjusting for confounding factors. Sex with a TGD person was not associated with sexual orientation in males. Of the 3278 females, gay and bisexual females had 13.7-fold (95% CI 5.1 to 37.0) higher odds of having sex with a TGD person than heterosexual females. There was no association between chlamydia positivity and sex with a TGD person in both males and females.

Conclusion

When a question on TGD partners is asked as part of routine sexual history using CASI, the majority of responses could be verified. TGD partners were most commonly reported among males. These findings underscore the value of asking patients about sex with TGD partners.
Corwin–Greenleaf multiplicity function for compact extensions of the Heisenberg group
Authors: Halima Majdi Ben , Messaoud Anis
Published: June 2018

Let [Formula: see text] be the [Formula: see text]-dimensional Heisenberg group and [Formula: see text] a closed subgroup of [Formula: see text] acting on [Formula: see text] by automorphisms such that [Formula: see text] is a Gelfand pair. Let [Formula: see text] be the semidirect product of [Formula: see text] and [Formula: see text]. Let [Formula: see text] be the respective Lie algebras of [Formula: see text] and [Formula: see text], and [Formula: see text] the natural projection. For coadjoint orbits [Formula: see text] and [Formula: see text], we denote by [Formula: see text] the number of [Formula: see text]-orbits in [Formula: see text], which is called the Corwin–Greenleaf multiplicity function. In this paper, we give two sufficient conditions on [Formula: see text] in order that [Formula: see text] For [Formula: see text], assuming furthermore that [Formula: see text] and [Formula: see text] are admissible and denoting respectively by [Formula: see text] and [Formula: see text] their corresponding irreducible unitary representations, we also discuss the relationship between [Formula: see text] and the multiplicity [Formula: see text] of [Formula: see text] in the restriction of [Formula: see text] to [Formula: see text]. Especially, we study in Theorem 4 the case where [Formula: see text]. This inequality is interesting because we expect the equality as the naming of the Corwin–Greenleaf multiplicity function suggests.
A groove engineered ultralow frequency piezomems energy harvester with ultrahigh output voltage
Authors: Kordrostami Zoheir , Roohizadegan Sajjad
Published: June 2018

In this paper, for the first time, a new design for a MEMS cantilever-based energy harvester (EH) has been proposed which takes advantage of two engineered piezoelectric layers. The output voltage of the EH has been increased by the aid of making grooves in the piezoelectric layers. By application of the grooves in the piezoelectric layers, the sensitivity of the cantilever as the vibration sensor or the EH has been improved. Results have shown that these grooves can increase the output voltage and decrease the resonance frequency which are desired changes in designing EHs. The single and double groove bimorph cantilevers have been compared and discussed. The position, length and depth of the grooves have been used as optimization parameters and consequently an optimal design has been proposed at the end of the paper. In the optimal design the top and the bottom piezoelectric layers have not covered the entire beam and have different lengths to produce maximum voltage. By means of groove engineering, we could rise the voltage from 5.395 V to 28.35 V which is considered a great improvement compared to other structures reported previously.
A novel metal-matrix phononic crystal with a low-frequency, broad and complete, locally-resonant band gap
Authors: Li Suobin , Dou Yihua , Chen Tianning , Wan Zhiguo , Guan Zhengrong
Published: June 2018

In this paper, a novel metal-matrix phononic crystal with a low-frequency, broad and complete, locally-resonant band gap, which includes the in-plane and out-of-plane band gaps, is investigated numerically. The proposed structure consists of double-sided single “hard” cylinder stubs, which are deposited on a two-dimensional locally-resonant phononic-crystal plate that consists of an array of rubber fillers embedded in a steel plate. Our results indicate that both the out-of-plane band gap and the in-plane band gap increase after introducing single “hard” cylinder stubs. More specifically, the out-of-plane band gap is increased by the out-of-plane analogous-rigid mode, while the in-plane band gap is increased by the in-plane analogous-rigid mode. The out-of-plane and the in-plane analogous-rigid mode are formed after introduction of the single “hard” cylinder stub. As a result, a broad, complete locally-resonant band gap in the low frequency is obtained due to the broad in-plane and out-of-plane band gaps overlapping. Compared to the classical double-sided stubbed metal-matrix phononic-crystal plate, the absolute bandwidth of the complete band gap is increased by a factor of 4.76 in the proposed structure. Furthermore, the effect of simple “hard” stubs on complete band gaps is investigated. The results show that the location of the complete band gaps can be modulated using a low frequency, and the bandwidth can be extended to a larger frequency range using different “hard” stubs. The new structure provides an effective way for metal-matrix phononic crystals to obtain broad and complete locally-resonant band gaps in the low-frequency range, which has many applications for low-frequency vibration reduction.
Almost valuation property in bi-amalgamations and pairs of rings
Authors: Azaiez Najib Ouled , Moutui Moutu Abdou Salam
Published: June 2018

This paper examines the transfer of the almost valuation property to various constructions of ring extensions such as bi-amalgamations and pairs of rings. Namely, Sec. 2 studies the transfer of this property to bi-amalgamation rings. Our results cover previous known results on duplications and amalgamations, and provide the construction of various new and original examples satisfying this property. Section 3 investigates pairs of integral domains where all intermediate rings are almost valuation rings. As a consequence of our results, we provide necessary and sufficient conditions for a pair (R, T), where R arises from a (T, M, D) construction, to be an almost valuation pair. Furthermore, we study the class of maximal non-almost valuation subrings of their quotient field.
Dirac–Bergmann constraints in physics: Singular Lagrangians, Hamiltonian constraints and the second Noether theorem
Authors: Lusanna Luca
Published: June 2018

There is a review of the main mathematical properties of system described by singular Lagrangians and requiring Dirac–Bergmann theory of constraints at the Hamiltonian level. The following aspects are discussed:

(i)the connection of the rank and eigenvalues of the Hessian matrix in the Euler–Lagrange equations with the chains of first- and second-class constraints;(ii)the connection of the Noether identities of the second Noether theorem with the Hamiltonian constraints;(iii)the Shanmugadhasan canonical transformation for the identification of the gauge variables and for the search of the Dirac observables, i.e. the quantities invariant under Hamiltonian gauge transformations.
China’s New Guiding Ideology: The Unfolding of the Xi Jinping Era
Authors: GORE Lance L P
Published: June 2018

Unveiled at the 19th Party Congress, China’s new guiding ideology of “Xi Jinping Thought of Socialism with Chinese Characteristics for a New Era” offers a blueprint for development to mid-21st century. Xi is in a position to demand loyalty, enforce strict discipline and fight the centrifugal forces within the Party. Domestically Xi faces the challenge of motivating the cadre corps demoralised by anti-corruption campaigns. Internationally a more assertive foreign policy is expected.
Non-Traditional Security Issues across Vietnam and China Land Borders
Authors: CUONG Nguyen Xuan , HOA Nguyen Thi Phuong
Published: June 2018

Cultural and social similarities and the sharing of thousands of kilometres of a borderline with many international and national border gates, among others, have boosted Vietnam-China and non-traditional security problems. These problems, arising and accumulating in the development process, are worsening and require increasingly urgent solutions. These issues have become complicated and uncontrollable, posing threats to the socioeconomic security of border regions of the two countries, especially Vietnam.
Data Structures for Weighted Matching and Extensions to
b
-matching and
f
-factors
Authors: Gabow Harold N.
Published: June 2018

This article shows the weighted matching problem on general graphs can be solved in time
O
(
n
(
m
+
n
log
n
)) for
n
and
m
the number of vertices and edges, respectively. This was previously known only for bipartite graphs. The crux is a data structure for blossom creation. It uses a dynamic nearest-common-ancestor algorithm to simplify blossom steps, so they involve only back edges rather than arbitrary nontree edges.

The rest of the article presents direct extensions of Edmonds’ blossom algorithm to weighted
b
-matching and
f
-factors. Again, the time bound is the one previously known for bipartite graphs: for
b
-matching the time is
O
(min {
b
(
V
),
n
log
n
}(
m
+
n
log
n
)), and for
f
-factors the time is
O
(min {
f
(
V
),
m
log
n
}(
m
+
n
log
n
)), where
b
(
V
) and
f
(
V
) both denote the sum of all degree constraints. Several immediate applications of the
f
-factor algorithm are given: The generalized shortest path structure of Reference [19], i.e., the analog of the shortest-paths tree for conservative undirected graphs, is shown to be a version of the blossom structure for
f
-factors. This structure is found in time
O
(|
N
|(
m
+
n
log
n
)) for
N
, the set of negative edges (0 < |
N
| <
n
). A shortest
T
-join is found in time
O
(
n
(
m
+
n
log
n
)) or
O
(|
T
|(
m
+
n
log
n
)) when all costs are nonnegative. These bounds are all slight improvements of previously known ones, and are simply achieved by proper initialization of the
f
-factor algorithm.
A Systematic Mapping Study on Intrusion Alert Analysis in Intrusion Detection Systems
Authors: Ramaki Ali Ahmadian , Rasoolzadegan Abbas , Bafghi Abbas Ghaemi
Published: June 2018

Intrusion alert analysis is an attractive and active topic in the area of intrusion detection systems. In recent decades, many research communities have been working in this field. The main objective of this article is to achieve a taxonomy of research fields in intrusion alert analysis by using a systematic mapping study of 468 high-quality papers. The results show that there are 10 different research topics in the field, which can be classified into three broad groups: pre-processing, processing, and post-processing. The processing group contains most of the research works, and the post-processing group is newer than others.
Neural Vector Spaces for Unsupervised Information Retrieval
Authors: Gysel Christophe Van , de Rijke Maarten , Kanoulas Evangelos
Published: June 2018

We propose the Neural Vector Space Model (NVSM), a method that learns representations of documents in an unsupervised manner for news article retrieval. In the NVSM paradigm, we learn low-dimensional representations of words and documents from scratch using gradient descent and rank documents according to their similarity with query representations that are composed from word representations. We show that NVSM performs better at document ranking than existing latent semantic vector space methods. The addition of NVSM to a mixture of lexical language models and a state-of-the-art baseline vector space model yields a statistically significant increase in retrieval effectiveness. Consequently, NVSM adds a complementary relevance signal. Next to semantic matching, we find that NVSM performs well in cases where lexical matching is needed. NVSM learns a notion of term specificity directly from the document collection without feature engineering. We also show that NVSM learns regularities related to Luhn significance. Finally, we give advice on how to deploy NVSM in situations where model selection (e.g., cross-validation) is infeasible. We find that an unsupervised ensemble of multiple models trained with different hyperparameter values performs better than a single cross-validated model. Therefore, NVSM can safely be used for ranking documents without supervised relevance judgments.
Near-Optimal Light Spanners
Authors: Chechik Shiri , Wulff-Nilsen Christian
Published: June 2018

A spanner
H
of a weighted undirected graph
G
is a “sparse” subgraph that approximately preserves distances between every pair of vertices in
G
. We refer to
H
as a δ-spanner of
G
for some parameter δ ≥ 1 if the distance in
H
between every vertex pair is at most a factor δ bigger than in
G
. In this case, we say that
H
has stretch δ. Two main measures of the sparseness of a spanner are the size (number of edges) and the total weight (the sum of weights of the edges in the spanner).

It is well-known that for any positive integer
k
, one can efficiently construct a (2
k
− 1)-spanner of
G
with
O
(
n

1+1/
k

) edges where
n
is the number of vertices [2]. This size-stretch tradeoff is conjectured to be optimal based on a girth conjecture of Erdős [17]. However, the current state of the art for the second measure is not yet optimal.

Recently Elkin, Neiman and Solomon [ICALP 14] presented an improved analysis of the greedy algorithm, proving that the greedy algorithm admits (2
k
− 1) · (1 + ϵ) stretch and total edge weight of
O
ϵ
((
k
/ log
k
) · ω (
MST
(
G
)) ·
n

1/
k

), where ω(
MST
(
G
)) is the weight of a MST of
G
. The previous analysis by Chandra et al. [SOCG 92] admitted (2
k
− 1) · (1 + ϵ) stretch and total edge weight of
O
ϵ
(
k
ω(
MST
(
G
))
n

1/
k

). Hence, Elkin et al. improved the weight of the spanner by a log
k
factor.

In this article, we completely remove the
k
factor from the weight, presenting a spanner with (2
k
− 1) · (1 + ϵ) stretch,
O
ϵ
(ω(
MST
(
G
))
n

1/
k

) total weight, and
O
(
n

1+1/
k

) edges. Up to a (1 + ϵ) factor in the stretch this matches the girth conjecture of Erdős [17].
SemRe-Rank
Authors: Zhang Ziqi , Gao Jie , Ciravegna Fabio
Published: June 2018

Automatic Term Extraction (ATE) deals with the extraction of terminology from a domain specific corpus, and has long been an established research area in data and knowledge acquisition. ATE remains a challenging task as it is known that there is no existing ATE methods that can consistently outperform others in any domain. This work adopts a refreshed perspective to this problem: instead of searching for such a ‘one-size-fit-all’ solution that may never exist, we propose to develop generic methods to ‘enhance’ existing ATE methods. We introduce SemRe-Rank, the first method based on this principle, to incorporate semantic relatedness—an often overlooked venue—into an existing ATE method to further improve its performance. SemRe-Rank incorporates word embeddings into a personalised PageRank process to compute ‘semantic importance’ scores for candidate terms from a graph of semantically related words (nodes), which are then used to revise the scores of candidate terms computed by a base ATE algorithm. Extensively evaluated with 13 state-of-the-art base ATE methods on four datasets of diverse nature, it is shown to have achieved widespread improvement over all base methods and across all datasets, with up to 15 percentage points when measured by the Precision in the top ranked
K
candidate terms (the average for a set of
K
’s), or up to 28 percentage points in F1 measured at a
K
that equals to the expected real terms in the candidates (F1 in short). Compared to an alternative approach built on the well-known TextRank algorithm, SemRe-Rank can potentially outperform by up to 8 points in Precision at top
K
, or up to 17 points in F1.
Spatio-Temporal Routine Mining on Mobile Phone Data
Authors: Qin Tian , Shangguan Wufan , Song Guojie , Tang Jie
Published: June 2018

Mining human behaviors has always been an important subarea of Data Mining. While it provides empirical evidences to psychological/behavioral studies, it also builds the foundation of various big-data systems, which rely heavily on the prediction of human behaviors. In recent years, the ubiquitous spreading of mobile phones and the massive amount of spatio-temporal data collected from them make it possible to keep track of the daily commute behaviors of mobile subscribers and further conduct routine mining on them. In this article, we propose to model mobile subscribers’ daily commute behaviors by three levels: location trajectory, one-day pattern, and routine pattern. We develop the model Spatio-Temporal Routine Mining Model (STRMM) to characterize the generative process between these three levels. From daily trajectories, the STRMM model unsupervisedly extracts spatio-temporal routine patterns that contain two aspects of information: (1) How people’s typical commute patterns are. (2) How much their commute behaviors vary from day to day. Compared to traditional methods, STRMM takes into account the different degrees of behavioral uncertainty in different timespans of a day, yielding more realistic and intuitive results. To learn model parameters, we adopt Stochastic Expectation Maximization algorithm. Experiments are conducted on two real world datasets, and the empirical results show that the STRMM model can effectively discover hidden routine patterns of human commute behaviors and yields higher accuracy results in trajectory prediction task.
Path Categories and Propositional Identity Types
Authors: Berg Benno Van Den
Published: June 2018

Connections between homotopy theory and type theory have recently attracted a lot of attention, with Voevodsky’s univalent foundations and the interpretation of Martin-Löf’s identity types in Quillen model categories as some of the highlights. In this article, we establish a connection between a natural weakening of Martin-Löf’s rules for the identity types that has been considered by Cohen, Coquand, Huber and Mörtberg in their work on a constructive interpretation of the univalence axiom on the one hand and the notion of a path category, a slight variation on the classic notion of a category of fibrant objects due to Brown, on the other. This involves showing that the syntactic category associated to a type theory with weak identity types carries the structure of a path category, strengthening earlier results by Avigad, Lumsdaine, and Kapulkin. In this way, we not only relate a well-known concept in homotopy theory with a natural concept in logic but also provide a framework for further developments.
A new perspective on computational thinking
Authors: Yaşar Osman
Published: June 2018

Addressing its cognitive essence, universal value, and curricular practices.
MFPR
Authors: Shi Chuan , Liu Jian , Zhang Yiding , Hu Binbin , Liu Shenghua , Yu Philip S.
Published: June 2018

Recently, recommender systems have played an important role in improving web user experiences and increasing profits. Recommender systems exploit users’ behavioral history (i.e., feedback on items) to build models. The feedback usually includes explicit feedback (e.g., ratings) and implicit feedback (e.g., browsing history, click logs), which are both useful for improving recommendations. However, as far as we are concerned, no existing works have integrated both explicit and multiple implicit feedback simultaneously. Therefore, we propose a unified and flexible model, named Multiple Feedback-based Personalized Ranking (MFPR), to make full use of multiple feedback, which uses a personalized ranking framework. To train model MFPR, we design an algorithm to generate ordered item pairs as labeled data, with consideration of both rating scores and multiple implicit feedback. Extensive experiments on two real-world datasets validate the effectiveness of the MFPR model. With the integration of multiple feedback, MFPR significantly improves recommendation performance.
Blockchain revolution without the blockchain?
Authors: Halaburda Hanna
Published: June 2018

Most of the suggested benefits of blockchain technologies do not come from elements unique to the blockchain.
Beyond diversity
Authors: Ahmed Alex
Published: June 2018

Considering the confluence of research questions and sociopolitical dynamics.
Successful Memory Aging
Authors: Nyberg Lars , Pudas Sara
Published: June 2018

For more than 50 years, psychologists, gerontologists, and, more recently, neuroscientists have considered the possibility of successful aging. How to define successful aging remains debated, but well-preserved age-sensitive cognitive functions, like episodic memory, is an often-suggested criterion. Evidence for successful memory aging comes from cross-sectional and longitudinal studies showing that some older individuals display high and stable levels of performance. Successful memory aging may be accomplished via multiple paths. One path is through brain maintenance, or relative lack of age-related brain pathology. Through another path, successful memory aging can be accomplished despite brain pathology by means of efficient compensatory and strategic processes. Genetic, epigenetic, and lifestyle factors influence memory aging via both paths. Some of these factors can be promoted throughout the life course, which, at the individual as well as the societal level, can positively impact successful memory aging.
Elementary Motion Detection inDrosophila: Algorithms and Mechanisms
Authors: Yang Helen H. , Clandinin Thomas R.
Published: June 2018

Motion in the visual world provides critical information to guide the behavior of sighted animals. Furthermore, as visual motion estimation requires comparisons of signals across inputs and over time, it represents a paradigmatic and generalizable neural computation. Focusing on the Drosophila visual system, where an explosion of technological advances has recently accelerated experimental progress, we review our understanding of how, algorithmically and mechanistically, motion signals are first computed.
Blood-brain barrier dysfunction in ischemic stroke: targeting tight junctions and transporters for vascular protection
Authors: Abdullahi Wazir , Tripathi Dinesh , Ronaldson Patrick T.
Published: June 2018

The blood-brain barrier (BBB) is a physical and biochemical barrier that precisely controls cerebral homeostasis. It also plays a central role in the regulation of blood-to-brain flux of endogenous and exogenous xenobiotics and associated metabolites. This is accomplished by molecular characteristics of brain microvessel endothelial cells such as tight junction protein complexes and functional expression of influx and efflux transporters. One of the pathophysiological features of ischemic stroke is disruption of the BBB, which significantly contributes to development of brain injury and subsequent neurological impairment. Biochemical characteristics of BBB damage include decreased expression and altered organization of tight junction constituent proteins as well as modulation of functional expression of endogenous BBB transporters. Therefore, there is a critical need for development of novel therapeutic strategies that can protect against BBB dysfunction (i.e., vascular protection) in the setting of ischemic stroke. Such strategies include targeting tight junctions to ensure that they maintain their correct structure or targeting transporters to control flux of physiological substrates for protection of endothelial homeostasis. In this review, we will describe the pathophysiological mechanisms in cerebral microvascular endothelial cells that lead to BBB dysfunction following onset of stroke. Additionally, we will utilize this state-of-the-art knowledge to provide insights on novel pharmacological strategies that can be developed to confer BBB protection in the setting of ischemic stroke.
A novel fibroblast activation inhibitor attenuates left ventricular remodeling and preserves cardiac function in heart failure
Authors: Bradley Jessica M. , Spaletra Pablo , Li Zhen , Sharp Thomas E. , Goodchild Traci T. , Corral Laura G. , Fung Leah , Chan Kyle W. H. , Sullivan Robert W. , Swindlehurst Cathy A. , Lefer David J.
Published: June 2018

Cardiac fibroblasts are critical mediators of fibrotic remodeling in the failing heart and transform into myofibroblasts in the presence of profibrotic factors such as transforming growth factor-β. Myocardial fibrosis worsens cardiac function, accelerating the progression to decompensated heart failure (HF). We investigated the effects of a novel inhibitor (NM922; NovoMedix, San Diego, CA) of the conversion of normal fibroblasts to the myofibroblast phenotype in the setting of pressure overload-induced HF. NM922 inhibited fibroblast-to-myofibroblast transformation in vitro via a reduction of activation of the focal adhesion kinase-Akt-p70S6 kinase and STAT3/4E-binding protein 1 pathways as well as via induction of cyclooxygenase-2. NM922 preserved left ventricular ejection fraction ( P < 0.05 vs. vehicle) and significantly attenuated transverse aortic constriction-induced LV dilation and hypertrophy ( P < 0.05 compared with vehicle). NM922 significantly ( P < 0.05) inhibited fibroblast activation, as evidenced by reduced myofibroblast counts per square millimeter of tissue area. Picrosirius red staining demonstrated that NM922 reduced ( P < 0.05) interstitial fibrosis compared with mice that received vehicle. Similarly, NM922 hearts had lower mRNA levels ( P < 0.05) of collagen types I and III, lysyl oxidase, and TNF-α at 16 wk after transverse aortic constriction. Treatment with NM922 after the onset of cardiac hypertrophy and HF resulted in attenuated myocardial collagen formation and adverse remodeling with preservation of left ventricular ejection fraction. Future studies are aimed at further elucidation of the molecular and cellular mechanisms by which this novel antifibrotic agent protects the failing heart.

NEW & NOTEWORTHY Our data demonstrated that a novel antifibrotic agent, NM922, blocks the activation of fibroblasts, reduces the formation of cardiac fibrosis, and preserves cardiac function in a murine model of heart failure with reduced ejection fraction.
Purinergic plasticity within petrosal neurons in hypertension
Authors: Moraes Davi J. A. , da Silva Melina P. , Spiller Pedro F. , Machado Benedito H. , Paton Julian F. R.
Published: June 2018

The carotid bodies are peripheral chemoreceptors and contribute to the homeostatic maintenance of arterial levels of O2, CO2, and [H+]. They have attracted much clinical interest recently because of the realization that aberrant signaling in these organs is associated with several pathologies including hypertension. Herein, we describe data suggesting that sympathetic overactivity in neurogenic hypertension is, at least in part, dependent on carotid body tonicity and hyperreflexia that is related to changes in the electrophysiological properties of chemoreceptive petrosal neurons. We present results showing critical roles for both ATP levels in the carotid bodies and expression of P2X3 receptors in petrosal chemoreceptive, but not baroreceptive, terminals in the etiology of carotid body tonicity and hyperreflexia. We discuss mechanisms that may underlie the changes in electrophysiological properties and P2X3 receptor expression in chemoreceptive petrosal neurons, as well as factors affecting ATP release by cells within the carotid bodies. Our findings support the notion of targeting the carotid bodies to reduce sympathetic outflow and arterial pressure, emphasizing the potential clinical importance of modulating purinergic transmission to treat pathologies associated with carotid body dysfunction but, importantly, sparing physiological chemoreflex function.
Increased megalin expression in early type 2 diabetes: role of insulin-signaling pathways
Authors: Bryniarski Mark A. , Yee Benjamin M. , Jaffri Irum , Chaves Lee D. , Yu Jin Ah , Guan Xiaowen , Ghavam Nazanin , Yacoub Rabi , Morris Marilyn E.
Published: June 2018

The megalin/cubilin complex is responsible for the majority of serum protein reclamation in the proximal tubules. The current study examined if decreases in their renal expression, along with the albumin recycling protein neonatal Fc receptor (FcRn) could account for proteinuria/albuminuria in the Zucker diabetic fatty rat model of type 2 diabetes. Immunoblots of renal cortex samples obtained at worsening disease stages demonstrated no loss in megalin, cubilin, or FcRn, even when proteinuria was measured. Additionally, early diabetic rats exhibited significantly increased renal megalin expression when compared with controls (adjusted P < 0.01). Based on these results, the ability of insulin to increase megalin was examined in a clonal subpopulation of the opossum kidney proximal tubule cell line. Insulin treatments (24 h, 100 nM) under high glucose conditions significantly increased megalin protein ( P < 0.0001), mRNA ( P < 0.0001), and albumin endocytosis. The effect on megalin expression was prevented with inhibitors against key effectors of insulin intracellular signaling, phosphatidylinositide 3-kinase and Akt. Studies using rapamycin to inhibit the mechanistic target of rapamycin complex 1 (mTORC1) resulted in a loss of insulin-induced megalin expression. However, subsequent evaluation demonstrated these effects were independent of initial mTORC1 suppression. The presented results provide insight into the expression of megalin, cubilin, and FcRn in type 2 diabetes, which may be impacted by elevated insulin and glucose. Furthermore, proximal tubule endocytic activity in early diabetics may be enhanced, a process that could have a significant role in proteinuria-induced renal damage.
Tune it in: mechanisms and computational significance of neuron-autonomous plasticity
Authors: Reuveni Iris , Barkai Edi
Published: June 2018

The activity of a neural network is a result of synaptic signals that convey the communication between neurons and neuron-based intrinsic currents that determine the neuron’s input-output transfer function. Ample studies have demonstrated that cell-based excitability, and in particular intrinsic excitability, is modulated by learning and that these modifications play a key role in learning-related behavioral changes. The field of cell-based plasticity is largely growing, and it entails numerous experimental findings that demonstrate a large diversity of currents that are affected by learning. The diverse effect of learning on the neuron’s excitability emphasizes the need for a framework under which cell-based plasticity can be categorized to enable the assessment of the computational roles of the intrinsic modifications. We divide the domain of cell-based plasticity into three main categories, where the first category entails the currents that mediate the passive properties and single-spike generation, the second category entails the currents that mediate spike frequency adaptation, and the third category entails a novel learning-induced mechanism where all excitatory and inhibitory synapses double their strength. Curiously, this elementary division enables a natural categorization of the computational roles of these learning-induced plasticities. The computational roles are diverse and include modification of the neuronal mode of action, such as bursting, prolonged, and fast responsive; attention-like effect where the signal detection is improved; transfer of the network into an active state; biasing the competition for memory allocation; and transforming an environmental cue into a dominant cue and enabling a quicker formation of new memories.
Simultaneous and opposing horizontal VOR adaptation in humans suggests functionally independent neural circuits
Authors: Gimmon Yoav , Migliaccio Americo A. , Todd Christopher J. , Figtree William V. C. , Schubert Michael C.
Published: June 2018

The healthy vestibulo-ocular reflex (VOR) ensures that images remain on the fovea of the retina during head rotation to maintain stable vision. VOR behavior can be measured as a summation of linear and nonlinear properties although it is unknown whether asymmetric VOR adaptation can be performed synchronously in humans. The purpose of the present study is twofold. First, examine whether the right and left VOR gains can be synchronously adapted in opposing directions. Second, to investigate whether the adaptation context transfers between both sides. Three separate VOR adaptation sessions were randomized such that the VOR was adapted Up-bilaterally, Down-bilaterally, or Mixed (one side up, opposite side down). Ten healthy subjects completed the study. Subjects were tested while seated upright, 1 meter in front of a wall in complete dark. Each subject made active (self-generated) head impulse rotations for 15 min while viewing a gradually increasing amount of retinal slip. VOR training demand changed by 10% every 90 s. The VOR changed significantly for all training conditions. No significant differences in the magnitude of VOR gain changes between training conditions were found. The human VOR can be simultaneously driven in opposite directions. The similar magnitude of VOR gain changes across training conditions suggests functionally independent VOR circuits for each side of head rotation that mediate simultaneous and opposing VOR adaptations.

NEW & NOTEWORTHY Our results indicate that humans have the adaptive capacity for concurrent and opposing directions of vestibulo-ocular reflex (VOR) motor learning. Context specificity of VOR adaptation is dependent on the error signal being unilateral or bilateral, which we illustrate via a lack of VOR gain transfer using unique adaptive demands.
Hyperexcitability of brain stem pathways in cerebral palsy
Authors: Smith A. T. , Gorassini M. A.
Published: June 2018

Individuals with cerebral palsy (CP) experience impairments in the control of head and neck movements, suggesting dysfunction in brain stem circuitry. To examine if brain stem circuitry is altered in CP, we compared reflexes evoked in the sternocleidomastoid (SCM) muscle by trigeminal nerve stimulation in adults with CP and in age/sex-matched controls. Increasing the intensity of trigeminal nerve stimulation produced progressive increases in the long-latency suppression of ongoing SCM electromyography in controls. In contrast, participants with CP showed progressively increased facilitation around the same reflex window, suggesting heightened excitability of brain stem pathways. We also examined if there was altered activation of cortico-brain stem pathways in response to prenatal injury of the brain. Motor-evoked potentials (MEPs) in the SCM that were conditioned by a prior trigeminal afferent stimulation were more facilitated in CP compared with controls, especially in ipsilateral MEPs that are likely mediated by corticoreticulospinal pathways. In some participants with CP, but not in controls, a combined trigeminal nerve and cortical stimulation near threshold intensities produced large, long-lasting responses in both the SCM and biceps brachii muscles. We propose that the enhanced excitatory responses evoked from trigeminal and cortical inputs in CP are produced by heightened excitability of brain stem circuits, resulting in the augmented activation of reticulospinal pathways. Enhanced activation of reticulospinal pathways in response to early injury of the corticospinal tract may provide a compensated activation of the spinal cord or, alternatively, contribute to impairments in the precise control of head and neck functions.

NEW & NOTEWORTHY This is the first study to show that in adults with spastic cerebral palsy, activation of brain stem circuits by cortical and/or trigeminal afferents produces excitatory responses in anterior neck muscles compared with inhibitory responses in age/sex-matched controls. This may reflect a more excitable reticulospinal tract in response to early brain injury to provide a compensated activation of postural muscles. On the other hand, a hyperexcitable brain stem may contribute to impairments in the precise control of head and neck functions.
Effects of pruritogens and algogens on rostral ventromedial medullary ON and OFF cells
Authors: Follansbee T. , Akiyama T. , Fujii M. , Davoodi A. , Nagamine M. , Iodi Carstens M. , Carstens E.
Published: June 2018

Rostroventromedial medulla (RVM) ON and OFF cells are thought to facilitate and inhibit spinal nociceptive transmission, respectively. However, it is unknown how ON and OFF cells respond to pruritic stimuli or how they contribute to descending modulation of spinal itch signaling. In pentobarbital sodium-anesthetized mice, single-unit recordings were made in RVM from ON and OFF cells identified by their respective increase or decrease in firing that occurred just before nocifensive hindlimb withdrawal elicited by paw pinch. Of RVM ON cells, 75% (21/28) were excited by intradermal histamine, 50% (10/20) by intradermal chloroquine, and 75% (27/36) by intradermal capsaicin. Most chemically responsive units also responded to a scratch stimulus applied to the injected hindpaw. Few ON cells responded to intradermal injection of vehicle (saline: 5/32; Tween 2/17) but still responded to scratching. For OFF cells, intradermal histamine and scratching inhibited 32% (6/19) with no effect of histamine in the remainder. Intradermal chloroquine inhibited 44% (4/9) and intradermal capsaicin inhibited 61% (11/18) of OFF cells. Few OFF cells were affected by vehicles (Tween: 1 inhibited, 7 unaffected; saline: 3 excited, 1 inhibited, 8 unaffected). Both ON and OFF cells that responded to one chemical usually also responded to others, whereas units unresponsive to the first-tested chemical tended not to respond to others. These results indicate that ascending pruriceptive signals activate RVM ON cells and inhibit RVM OFF cells. These effects are considered to facilitate and disinhibit spinal pain transmission, respectively. It is currently not clear if spinal itch transmission is similarly modulated.

NEW & NOTEWORTHY The rostroventromedial medulla (RVM) contains ON and OFF cells that are, respectively, excited and inhibited by noxious stimuli and have descending projections that facilitate and inhibit spinal nociceptive transmission. Most RVM ON cells were excited, and OFF cells inhibited, by intradermal injection of the pruritogens histamine and chloroquine, as well as the algogen capsaicin. These results indicate that itchy stimuli activate RVM neurons that presumably give rise to descending modulation of spinal itch transmission.
Blunted cardiovascular responses to exercise in Parkinson’s disease patients: role of the muscle metaboreflex
Authors: Sabino-Carvalho Jeann L. , Teixeira André L. , Samora Milena , Daher Maurício , Vianna Lauro C.
Published: June 2018

Patients with Parkinson’s disease (PD) exhibit attenuated cardiovascular responses to exercise. The underlying mechanisms that are potentially contributing to these impairments are not fully understood. Therefore, we sought to test the hypothesis that patients with PD exhibit blunted cardiovascular responses to isolated muscle metaboreflex activation following exercise. For this, mean blood pressure, cardiac output, and total peripheral resistance were measured using finger photoplethysmography and the Modelflow method in 11 patients with PD [66 ± 2 yr; Hoehn and Yahr score: 2 ± 1 a.u.; time since diagnosis: 7 ± 1 yr; means ± SD) and 9 age-matched controls (66 ± 3 yr). Measurements were obtained at rest, during isometric handgrip exercise performed at 40% maximal voluntary contraction, and during postexercise ischemia. Also, a cold pressor test was assessed to confirm that blunted cardiovascular responses were specific to exercise and not representative of generalized sympathetic responsiveness. Changes in mean blood pressure were attenuated in patients with PD during handgrip (PD: ∆25 ± 2 mmHg vs. controls: ∆31 ± 3 mmHg; P < 0.05), and these group differences remained during postexercise ischemia (∆17 ± 1 mmHg vs. ∆26 ± 1 mmHg, respectively; P < 0.01). Additionally, changes in total peripheral resistance were attenuated during exercise and postexercise ischemia, indicating blunted reflex vasoconstriction in patients with PD. Responses to cold pressor test did not differ between groups, suggesting no group differences in generalized sympathetic responsiveness. Our results support the concept that attenuated cardiovascular responses to exercise observed in patients with PD are, at least in part, explained by an altered skeletal muscle metaboreflex.

NEW & NOTEWORTHY Patients with Parkinson’s disease (PD) presented blunted cardiovascular responses to exercise. We showed that cardiovascular response evoked by the metabolic component of the exercise pressor reflex is blunted in patients with PD. Furthermore, patients with PD presented similar pressor response during the cold pressor test compared with age-matched controls. Altogether, our results support the hypothesis that attenuated cardiovascular responses to exercise observed in patients with PD are mediate by an altered skeletal muscle metaboreflex.
Hyperoxia enhances slow-wave forebrain states in urethane-anesthetized and naturally sleeping rats
Authors: Hauer Brandon E. , Negash Biruk , Chan Kingsley , Vuong Wesley , Colbourne Frederick , Pagliardini Silvia , Dickson Clayton T.
Published: June 2018

Oxygen (O2) is a crucial element for physiological functioning in mammals. In particular, brain function is critically dependent on a minimum amount of circulating blood levels of O2 and both immediate and lasting neural dysfunction can result following anoxic or hypoxic episodes. Although the effects of deficiencies in O2 levels on the brain have been reasonably well studied, less is known about the influence of elevated levels of O2 (hyperoxia) in inspired gas under atmospheric pressure. This is of importance due to its typical use in surgical anesthesia, in the treatment of stroke and traumatic brain injury, and even in its recreational or alternative therapeutic use. Using local field potential (EEG) recordings in spontaneously breathing urethane-anesthetized and naturally sleeping rats, we characterized the influence of different levels of O2 in inspired gases on brain states. While rats were under urethane anesthesia, administration of 100% O2 elicited a significant and reversible increase in time spent in the deactivated (i.e., slow-wave) state, with concomitant decreases in both heartbeat and respiration rates. Increasing the concentration of carbon dioxide (to 5%) in inspired gas produced the opposite result on EEG states, mainly a decrease in the time spent in the deactivated state. Consistent with this, decreasing concentrations of O2 (to 15%) in inspired gases decreased time spent in the deactivated state. Further confirmation of the hyperoxic effect was found in naturally sleeping animals where it similarly increased time spent in slow-wave (nonrapid eye movement) states. Thus alterations of O2 in inspired air appear to directly affect forebrain EEG states, which has implications for brain function, as well as for the regulation of brain states and levels of forebrain arousal during sleep in both normal and pathological conditions.

NEW & NOTEWORTHY We show that alterations of oxygen concentration in inspired air biases forebrain EEG state. Hyperoxia increases the prevalence of slow-wave states. Hypoxia and hypercapnia appear to do the opposite. This suggests that oxidative metabolism is an important stimulant for brain state.
Detecting multivariate cross-correlation between brain regions
Authors: Rodu Jordan , Klein Natalie , Brincat Scott L. , Miller Earl K. , Kass Robert E.
Published: June 2018

The problem of identifying functional connectivity from multiple time series data recorded in each of two or more brain areas arises in many neuroscientific investigations. For a single stationary time series in each of two brain areas statistical tools such as cross-correlation and Granger causality may be applied. On the other hand, to examine multivariate interactions at a single time point, canonical correlation, which finds the linear combinations of signals that maximize the correlation, may be used. We report here a new method that produces interpretations much like these standard techniques and, in addition, 1) extends the idea of canonical correlation to 3-way arrays (with dimensionality number of signals by number of time points by number of trials), 2) allows for nonstationarity, 3) also allows for nonlinearity, 4) scales well as the number of signals increases, and 5) captures predictive relationships, as is done with Granger causality. We demonstrate the effectiveness of the method through simulation studies and illustrate by analyzing local field potentials recorded from a behaving primate.

NEW & NOTEWORTHY Multiple signals recorded from each of multiple brain regions may contain information about cross-region interactions. This article provides a method for visualizing the complicated interdependencies contained in these signals and assessing them statistically. The method combines signals optimally but allows the resulting measure of dependence to change, both within and between regions, as the responses evolve dynamically across time. We demonstrate the effectiveness of the method through numerical simulations and by uncovering a novel connectivity pattern between hippocampus and prefrontal cortex during a declarative memory task.
Metformin Improves Epithelial-to-Mesenchymal Transition Induced by TGF-β1 in Renal Tubular Epithelial NRK-52E Cells via Inhibiting Egr-1
Authors: Guan Meiping , Li Wenqi , Xu Lingling , Zeng Yanmei , Wang Dan , Zheng Zongji , Lyv Fuping , Xue Yaoming
Published: June 2018

The early growth response- (Egr-) 1 has been found to play a key role in organ fibrosis. Metformin has been shown to be effective in attenuating renal tubular epithelial-to-mesenchymal transition (EMT), which is involved in renal fibrosis. However, it is unknown whether metformin improves EMT via inhibiting Egr-1. In this study, rat renal tubular epithelial (NRK-52 E) cells, treated by transforming growth factor- (TGF-)β1 of 10 ng/ml with or without metformin of 1 mmol/l, were transfected by siEgr-1 or M61-Egr-1 plasmids to knock down or overexpress Egr-1, respectively. The gene and protein expressions of E-cadherin,α-SMA, fibronectin (FN), and Egr-1 were determined by real-time quantitative PCR and Western blotting, respectively. We observed that TGF-β1 significantly reduced E-cadherin expression and upregulated the expressions of FN,α-SMA, and Egr-1, which can be reversed by metformin. M61-Egr-1 transfection could exacerbate EMT, which can be reversed by metformin. Taken together, our data show that Egr-1 plays an important role in TGF-β1-induced EMT of renal tubular epithelial cells and metformin improves EMT while inhibiting Egr-1, which provides a potential novel target to combat renal fibrosis.