bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Respiratory Syncytial Virus Nonstructural Protein 2 Residues Essential for Exploitation of the Host Ubiquitin System and Inhibition of Innate Immune Responses
Authors: Whelan Jillian N. , Tran Kim C. , van Rossum Damian B. , Teng Michael N.
Published: May 2016

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in young children worldwide. The RSV nonstructural protein 2 (NS2) is a multifunctional protein that primarily acts to antagonize the innate immune system by targeting STAT2 for proteasomal degradation. We investigated the structural determinants of NS2 important for interaction with the host ubiquitin system to degrade STAT2 during infection. We found that NS2 expression enhances ubiquitination of host proteins. Bioinformatics analysis provided a platform for identification of specific residues that limit NS2-induced ubiquitination. Combinations of multiple mutations displayed an additive effect on reducing NS2-induced ubiquitination. Using a reverse genetics system, we generated recombinant RSV (rRSV) containing NS2 ubiquitin mutations, which maintained their effect on ubiquitin expression during infection. Interestingly, STAT2 degradation activity was ablated in the NS2 ubiquitin mutant rRSV. In addition, NS2 ubiquitin mutations decreased rRSV replication, indicating a correlation between NS2's ubiquitin function and antagonism of innate immune signaling to enhance viral replication. Our approach of targeting NS2 residues required for NS2 inhibition of immune responses provides a mechanism for attenuating RSV for vaccine development.

IMPORTANCE
RSV has been circulating globally for more than 60 years, causing severe respiratory disease in pediatric, elderly, and immunocompromised populations. Production of a safe, effective vaccine against RSV is a public health priority. The NS2 protein is an effective target for prevention and treatment of RSV due to its antagonistic activity against the innate immune system. However, NS2-deleted RSV vaccine candidates rendered RSV overattenuated or poorly immunogenic. Alternatively, we can modify essential NS2 structural features to marginally limit viral growth while maintaining immune responses, providing the necessary balance between antigenicity and safety required for an effective vaccine. We coupled bioinformatics analysis with reverse genetics to introduce mutations into RSV's negative-sense genome. In this way we constructed rRSV NS2 ubiquitin mutants that limited NS2's ability to antagonize the innate immune system, thereby attenuating rRSV growth and increasing innate immune responses.
CD69 Deficiency Enhances the Host Response to Vaccinia Virus Infection through Altered NK Cell Homeostasis
Authors: Notario Laura , Alari-Pahissa Elisenda , de Molina Antonio , Lauzurica Pilar
Published: May 2016

During the host response to viral infection, the transmembrane CD69 protein is highly upregulated in all immune cells. We have studied the role of CD69 in the murine immune response to vaccinia virus (VACV) infection, and we report that the absence of CD69 enhances protection against VACV at both short and long times postinfection in immunocompetent and immunodeficient mice. Natural killer (NK) cells were implicated in the increased infection control, since the differences were greatly diminished when NK cells were depleted. This role of NK cells was not based on an altered NK cell reactivity, since CD69 did not affect the NK cell activation threshold in response to major histocompatibility complex class I NK cell targets or protein kinase C activation. Instead, NK cell numbers were increased in the spleen and peritoneum of CD69-deficient infected mice. That was not just secondary to better infection control in CD69-deficient mice, since NK cell numbers in the spleens and the blood of uninfected CD69−/−mice were already augmented. CD69-deficient NK cells from infected mice did not have an altered proliferation capacity. However, a lower spontaneous cell death rate was observed for CD69−/−lymphocytes. Thus, our results suggest that CD69 limits the innate immune response to VACV infection at least in part through cell homeostatic survival.

IMPORTANCEWe show that increased natural killer (NK) cell numbers augment the host response and survival after infection with vaccinia virus. This phenotype is found in the absence of CD69 in immunocompetent and immunodeficient hosts. As part of the innate immune system, NK lymphocytes are activated and participate in the defense against infection. Several studies have focused on the contribution of NK cells to protection against infection with vaccinia virus. In this study, it was demonstrated that the augmented early NK cell response in the absence of CD69 is responsible for the increased protection seen during infection with vaccinia virus even at late times of infection. This work indicates that the CD69 molecule may be a target of therapy to augment the response to poxvirus infection.
Four synchronous cancers in a patient with tongue pain as the only symptom
Authors: Heidemann Lene Nyhøj , Johansen Jørgen , Larsen Stine Rosenkilde , Sørensen Jens Ahm
Published: May 2016

Synchronous carcinomas may be present in up to 6% of patients with head and neck squamous cell carcinoma (HNSCC) and thus may represent a significant factor in the disease burden. This case report illustrates the importance of a thorough examination of these patients. This patient presented with three synchronous squamous cell carcinomas, two in the tongue and one in the aryepiglottic fold. Positron emission tomography CT (PET-CT) was required for the detection of the carcinomas as the initial MRI and CT scans were inconclusive due to artefacts. Furthermore, PET-CT also revealed increased metabolic activity in the lymph nodes of the neck, which subsequently led to detection of a low-grade follicular lymphoma in addition to the squamous cell carcinomas. These findings support a generous use of PET-CT in patients with HNSCC, at least in those with obvious risk factors.
Successful balloon mitral valvotomy in a rare coexistence of Ebstein's anomaly and rheumatic mitral stenosis
Authors: Sidhu Navdeep Singh , Kondethimmanahally Rangaiah Sunil Kumar , Ramesh Dwarikaprasad , Manjunath Cholenahally Nanjappa
Published: May 2016

Co-existence of Ebstein's anomaly of the tricuspid valve with rheumatic mitral stenosis is a very rare occurrence. We report the case of a young man who presented with progressive dyspnoea and was found to have rheumatic mitral stenosis with pulmonary hypertension and Ebstein's anomaly of the tricuspid valve. The patient underwent successful balloon mitral valvotomy resulting in marked improvement of symptoms.
‘For a quart of ale is a dish for a king’: not always
Authors: Zingone Fabiana , Russo Ilaria , Massari Angelo , Ciacci Carolina
Published: May 2016

We report the case of a man with a clear diagnosis of coeliac disease who nevertheless drank gluten-containing beer. We found that a 4-week period of drinking gluten-containing beer did not provoke significant changes in the intestinal mucosa of this patient with coeliac disease nor did it elicit any relevant symptoms. Serum antibody levels rose but did not reach a pathological threshold. However, a more prolonged gluten challenge may have led to clinically relevant changes in IgA antitransglutaminase titres. This case demonstrates how important individual sensitivity to gluten in a patient with coeliac disease is in determining symptoms, immunological response and intestinal mucosa damage.
Parkinsonism as a side effect of infliximab
Authors: Henriksen Jakob Nørgaard , Eriksson Bengt Oluf Mikael
Published: May 2016

We present a case of a 64-year-old man with Crohn's disease who developed parkinsonism after starting treatment with infliximab (Remicade). The patient had a 30-year history of Crohn's disease with previous surgical procedures and treatment with methotrexate. Treatment was augmented with infliximab, and 3 days after the first dose of 400 mg, a resting tremor began in the left leg. Over 4 months, symptoms progressed and now involved the right leg as well as both hands. There was no clinical effect of infliximab treatment, and the treatment was withdrawn 4 months later. The patient then experienced gradual, but continual, improvement of the resting tremor after withdrawal of infliximab. To the best of our knowledge, this is the first case report describing a patient developing parkinsonism after starting treatment with infliximab, with symptoms remitting on discontinuation.
Invasive lobular carcinoma: a rare presentation in the male breast
Authors: Melo Abreu Elisa , Pereira Pedro , Marques José Carlos , Esteves Gonçalo
Published: May 2016

Breast cancer in men is uncommon, accounting for <1% of all breast cancers. Even though lobular structures are quite infrequent in the male breast, rare cases of invasive lobular breast carcinoma have been described, representing 1–2% of all breast cancers in men. Risk factors include undescended testes, congenital inguinal hernia, orchiectomy, orchitis, testicular injury, infertility and Klinefelter's syndrome, previous thoracic radiotherapy, alterations of the oestrogen–testosterone ratio and familial history (BRCA 2 and 1). The authors present a case of a 52-year-old man with no relevant predisposing factors to breast cancer, who presented with a painless, firm nodule, fixed to the nipple on the left breast, associated with nipple retraction and ulceration, and fully characterised by mammogram and ultrasound. Histopathological and immunohistochemical analysis revealed the diagnosis of invasive lobular breast carcinoma and the patient underwent left radical mastectomy, followed by adjuvant chemotherapy, radiotherapy and hormonotherapy. A brief review of the literature is presented.
Screening for malnutrition in patients with gastro-entero-pancreatic neuroendocrine tumours: a cross-sectional study
Authors: Qureshi Sheharyar A , Burch Nicola , Druce Maralyn , Hattersley John G , Khan Saboor , Gopalakrishnan Kishore , Darby Catherine , Wong John L H , Davies Louise , Fletcher Simon , Shatwell William , Sothi Sharmila , Randeva Harpal S , Dimitriadis Georgios K , Weickert Martin O
Published: May 2016

Objectives

To investigate whether screening for malnutrition using the validated malnutrition universal screening tool (MUST) identifies specific characteristics of patients at risk, in patients with gastro-entero-pancreatic neuroendocrine tumours (GEP-NET).

Design

Cross-sectional study.

Setting

University Hospitals Coventry & Warwickshire NHS Trust; European Neuroendocrine Tumour Society Centre of Excellence.

Participants

Patients with confirmed GEP-NET (n=161) of varying primary tumour sites, functioning status, grading, staging and treatment modalities.

Main outcome measure

To identify disease and treatment-related characteristics of patients with GEP-NET who score using MUST, and should be directed to detailed nutritional assessment.

Results

MUST score was positive (≥1) in 14% of outpatients with GEP-NET. MUST-positive patients had lower faecal elastase concentrations compared to MUST-negative patients (244±37 vs 383±20 µg/g stool; p=0.018), and were more likely to be on treatment with long-acting somatostatin analogues (65 vs 38%, p=0.021). MUST-positive patients were also more likely to have rectal or unknown primary NET, whereas, frequencies of other GEP-NET including pancreatic NET were comparable between MUST-positive and MUST-negative patients.

Conclusions

Given the frequency of patients identified at malnutrition risk using MUST in our relatively large and diverse GEP-NET cohort and the clinical implications of detecting malnutrition early, we recommend routine use of malnutrition screening in all patients with GEP-NET, and particularly in patients who are treated with long-acting somatostatin analogues.
Occupational outcomes following mild traumatic brain injury in Canadian military personnel deployed in support of the mission in Afghanistan: a retrospective cohort study
Authors: Garber Bryan G , Rusu Corneliu , Zamorski Mark A , Boulos David
Published: May 2016

Objective

Deployment-related mild traumatic brain injury (MTBI) occurs in a significant number of military personnel but its long-term impacts are unclear. This study explores the impact of deployment-related MTBI on continued fitness-for-duty, with the ultimate intent of identifying potential targets for intervention to attenuate its effects.

Participants

Consisted of 16 193 Canadian Armed Forces (CAF) personnel who deployed in support of the mission in Afghanistan and completed an enhanced postdeployment screening (EPDS) questionnaire over the period January 2009–July 2012.

Primary outcome

The primary outcome was development of permanent medical unfitness defined as a ‘career-limiting medical condition’ (CL-MC). The secondary outcome was the diagnostic categories recorded for each individual at the time a CL-MC was established.

Design

This study used a retrospective cohort design. Linked administrative and health data provided the primary outcome and the diagnoses responsible for it. Survival analysis was used to estimate the risk of a CL-MC and Cox regression provided adjusted HRs (aHRs) for the association between a CL-MC and MTBI, accounting for key covariates and confounders. Diagnostic categories associated with CL-MCs were identified.

Results

Over a median follow-up period of 3.42 years, 6.57% of the study population developed a CL-MC. MTBI was independently associated with CL-MCs (aHR=1.65, 95% CI 1.35 to 2.03). Mental disorders and musculoskeletal conditions were the primary diagnoses associated with CL-MCs (identified as the primary diagnosis in 55.4% and 25.9%, respectively), and a neurological condition was only documented in 5.8% of those with MTBI who developed a CL-MC

Conclusions

Deployment-related MTBI was associated with adverse occupational outcome but mental disorders and musculoskeletal conditions primarily drove subsequent medical unfitness. These findings support a diagnostic and treatment approach focusing on these comorbidities as the most promising strategy to minimise the burden of disability in MTBI-exposed military personnel.
Longitudinal study of patients with chronic Chagas cardiomyopathy in Brazil (SaMi-Trop project): a cohort profile
Authors: Cardoso Clareci Silva , Sabino Ester Cerdeira , Oliveira Claudia Di Lorenzo , de Oliveira Lea Campos , Ferreira Ariela Mota , Cunha-Neto Edécio , Bierrenbach Ana Luiza , Ferreira João Eduardo , Haikal Desirée Sant'Ana , Reingold Arthur L , Ribeiro Antonio Luiz P
Published: May 2016

Purpose

We have established a prospective cohort of 1959 patients with chronic Chagas cardiomyopathy to evaluate if a clinical prediction rule based on ECG, brain natriuretic peptide (BNP) levels, and other biomarkers can be useful in clinical practice. This paper outlines the study and baseline characteristics of the participants.

Participants

The study is being conducted in 21 municipalities of the northern part of Minas Gerais State in Brazil, and includes a follow-up of 2 years. The baseline evaluation included collection of sociodemographic information, social determinants of health, health-related behaviours, comorbidities, medicines in use, history of previous treatment for Chagas disease, functional class, quality of life, blood sample collection, and ECG. Patients were mostly female, aged 50–74 years, with low family income and educational level, with known Chagas disease for >10 years; 46% presented with functional class >II. Previous use of benznidazole was reported by 25.2% and permanent use of pacemaker by 6.2%. Almost half of the patients presented with high blood cholesterol and hypertension, and one-third of them had diabetes mellitus. N-terminal of the prohormone BNP (NT-ProBNP) level was >300 pg/mL in 30% of the sample.

Findings to date

Clinical and laboratory markers predictive of severe and progressive Chagas disease were identified as high NT-ProBNP levels, as well as symptoms of advanced heart failure. These results confirm the important residual morbidity of Chagas disease in the remote areas, thus supporting political decisions that should prioritise in addition to epidemiological surveillance the medical treatment of chronic Chagas cardiomyopathy in the coming years. The São Paulo-Minas Gerais Tropical Medicine Research Center (SaMi-Trop) represents a major challenge for focused research in neglected diseases, with knowledge that can be applied in primary healthcare.

Future plans

We will continue following this patients’ cohort to provide relevant information about the development and progression of Chagas disease in remotes areas, with social and economic inequalities.

Trial registration number

NCT02646943; Pre-results.
Palliative care in small animal oncology
Authors: Mason Sarah
Published: May 2016

Cancer is a common diagnosis in companion animals and, increasingly, clients choose to pursue treatment for their pets. Veterinary oncology is a rapidly growing field and diagnostic and treatment options for animals with cancer are constantly improving and becoming more widely available. Treatment outcomes can be good, but in many cases definitive treatment is not an option and palliative treatment is necessary. This article explores the palliative care of dogs and cats that have been diagnosed with cancer and summarises the various treatment options, with a particular focus on quality of life and the role of communication in the decision‐making process.
Gender differences in risk factors and clinical outcomes in young patients with acute myocardial infarction
Authors: Cho Kyoung Im , Shin Eun-Seok , Ann Soe Hee , Garg Scot , Her Ae-Young , Kim Jeong Su , Han Jun Hee , Jeong Myung Ho
Published: May 2016

Background

There are limited data on the influence of gender on risk factors and clinical outcomes in young patients with acute myocardial infarction (AMI).

Methods

This prospective study stratified outcomes according to gender in patients of age ≤50 years with a diagnosis of AMI, and who were enrolled in the nationwide registry of the Korea Working Group of Myocardial Infarction. The end point was the incidence of major adverse cardiovascular events (MACEs) defined as the composite of cardiac death, recurrent myocardial infarction (MI), and repeat revascularisation at 30 days and 1 year after admission.

Results

The registry enrolled 30 001 patients with AMI, of whom 5200 met the study inclusion criteria; 4805 patients were male and 395 were female. Current smoking was significantly higher in men, while hypertension and diabetes mellitus were significantly more common in women. Women underwent less coronary revascularisation, and were less likely to be on optimal medical therapy compared with men despite having a higher Killip class at presentation and higher risk angiographic findings. Although women had higher rates of MACEs (3.8% vs 1.8%, p=0.018 at 30 days and 7.8% vs 4.7%, p=0.004 at 1-year follow-up) compared with men, female gender was not an independent predictor of MACEs after adjusting for propensity score.

Conclusions

There were significant gender differences in the risk factors for coronary artery disease and the short-term and long-term clinical outcomes of young patients with AMI. Continued preventive strategies should be focused on gender-different risk factor reduction in these young patients.
Taphocoenoses and diversification patterns of calcimicrobes and calcareous algae, Ordovician, Tarim Basin, China
Authors: Shen Yuefeng , Neuweiler Fritz
Published: May 2016

Despite the crucial role of epibenthic primary producers (cyanobacteria, green and red algae), no diversity curves for calcimicrobes and calcareous algae are available to assess the pyramiding paleoecology characterizing the Ordovician biodiversification episode. A total of 24 taxa of calcimicrobes and calcareous algae are identified from a Dapingian to lower Katian succession of carbonate sedimentary rocks exposed at the Leyayilitag ridge, Bachu Uplift, Tarim Basin, northwest China. Calcimicrobes (14 taxa), Dasycladales (seven taxa), Bryopsidales (one taxon), and Cyclocrinales (two taxa) contribute to five distinct taphocoenoses characterizing a suite of carbonate mounds. In stratigraphic order, these are calathid sponge mounds, algal calcimicrobial mounds, algal mounds, algal reefs, and calcimicrobial mounds. Within the lower Katian Belodina confluens Zone, the diversity increases substantially from around 5 to more than 20 taxa per 2 Ma. This increase in diversity is based on new calcimicrobes (Bija, Ortonella, Garwoodia, Hedstroemia, Rothpletzella, Phacelophyton, Rauserina) and the diversification of Dasycladales and Cyclocrinales. By comparison, the global diversity of calcimicrobes and calcareous algae (derived from literature data) started to increase earlier, namely within the late Darriwilian Pygodus serra Zone (offset of about 4 Ma). This offset might be due to the peculiar lithology of the Sandbian Tumuxiuke Formation (condensed section of red nodular limestones bounded by disconformities). However, a similar temporal offset is recorded for calathid sponge mounds; therefore, the Tarim tectonic microplate (Tarim Block) might display an endemic–anachronistic character. The diversity curves of Ordovician benthic primary producers (calcimicrobes, calcareous algae) are similar to those recorded by some fossil groups, in particular eleutherozoan echinoderms.
Chua Corsage Memristor Oscillator via Hopf Bifurcation
Authors: Mannan Zubaer Ibna , Choi Hyuncheol , Kim Hyongsuk
Published: May 2016

This paper demonstrates that the Chua Corsage Memristor, when connected in series with an inductor and a battery, oscillates about a locally-active operating point located on the memristor’s DC [Formula: see text]–[Formula: see text] curve. On the operating point, a small-signal equivalent circuit is derived via a Taylor series expansion. The small-signal admittance [Formula: see text] is derived from the small-signal equivalent circuit and the value of inductance is determined at a frequency where the real part of the admittance [Formula: see text] of the small-signal equivalent circuit of Chua Corsage Memristor is zero. Oscillation of the circuit is analyzed via an in-depth application of the theory of Local Activity, Edge of Chaos and the Hopf-bifurcation.
Stochastic Sensitivity Analysis and Noise-Induced Chaos in 2D Logistic-Type Model
Authors: Bashkirtseva Irina , Ekaterinchuk Ekaterina , Ryashko Lev
Published: May 2016

We study the dynamics of stochastically forced 2D logistic-type discrete model. Under random disturbances, stochastic trajectories leaving deterministic attractors can form complex dynamic regimes that have no analogue in the deterministic case. In this paper, we analyze an impact of the random noise on 2D logistic-type model in the bistability zones with coexisting attractors (equilibria, closed invariant curves, discrete cycles). For the constructive probabilistic analysis of the random states distribution around such attractors, a stochastic sensitivity functions technique and method of confidence domains are used. For the considered model, on the base of the suggested approach, a phenomenon of noise-induced transitions between attractors and the generation of chaos are analyzed.
The Analysis of Eigenstates of a Few Generalized Quantum Baker’s Maps Using Hadamard and Related Transforms
Authors: Meenakshisundaram N.
Published: May 2016

Application of the Hadamard and related transforms on a few generalized quantum baker’s maps have been studied. Effectiveness of the Hadamard transform and a new transform which combines the Fourier and the Hadamard transforms, for simplifying the eigenstates or resonances of the quantization of a few generalized baker’s map namely tetradic baker and lazy baker’s map when the Hilbert space dimension is power of [Formula: see text] has been done by comparing the participation ratios in the transformed basis with respect to the position basis. Several special family of states based on their maximal compression in either Hadamard transform or the new transform are identified and they are related to the ubiquitous Thue–Morse and allied sequences. Evidence is provided that these special family of states as well as average over all eigenstates exhibits multifractal nature.
Stability and Bifurcation in a State-Dependent Delayed Predator–Prey System
Authors: Hou Aiyu , Guo Shangjiang
Published: May 2016

In this paper, we consider a class of predator–prey equations with state-dependent delayed feedback. Firstly, we investigate the local stability of the positive equilibrium and the existence of the Hopf bifurcation. Then we use perturbation methods to determine the sub/supercriticality of Hopf bifurcation and hence the stability of Hopf bifurcating periodic solutions. Finally, numerical simulations supporting our theoretical results are also provided.
Bifurcations and Chaos in the Dynamics of Two Point Vortices in an Acoustic Wave
Authors: Vetchanin E. V. , Kazakov A. O.
Published: May 2016

In this paper, we consider a system governing the motion of two point vortices in a flow excited by an external acoustic forcing. It is known that the system of two vortices is integrable in the absence of acoustic forcing. However, the addition of the acoustic forcing makes the system much more complex, and the system becomes nonintegrable and loses the phase volume preservation property. The objective of our research is to study chaotic dynamics and typical bifurcations. Numerical analysis has shown that the reversible pitchfork bifurcation is typical. Also, we show that the existence of strange attractors is not characteristic for the system under consideration.
Automatic Reassembly of Three-Dimensional Jigsaw Puzzles
Authors: Grim Anna , O’Connor Timothy , Olver Peter J. , Shakiban Chehrzad , Slechta Ryan , Thompson Robert
Published: May 2016

In this paper, we present an effective algorithm for reassembling three-dimensional apictorial jigsaw puzzles obtained by dividing a curved surface into a finite number of interlocking pieces. As such, our algorithm does not make use of any picture or design that may be painted on the surface; nor does it require a priori knowledge of the overall shape of the original surface. A motivating example is the problem of virtually reconstructing a broken ostrich egg shell. In order to develop and test the algorithm, we also devise a method for constructing synthetic three-dimensional puzzles by randomly distributing points on a compact surface with respect to surface area measure, then determining the induced Voronoi tessellation, and finally curving the Voronoi edges by using Bezier curves with selected control points. Our edge-matching algorithm relies on the method of Euclidean signature curves. The edges of the puzzle pieces are divided into bivertex arcs, whose signatures are directly compared. The algorithm has been programmed in Matlab and is able to successfully reassemble a broad range of artificial puzzles, including those subjected to a reasonable amount of noise. Moreover, significant progress has been made on reassembly of the real-world ostrich egg data.
Media Resources Availability and Utilisation for Effective Publication Output by Agricultural Researchers in Southwestern Nigeria
Authors: Ogunjobi T. E. , Oyewusi F. O.
Published: May 2016

The study examines media resource utilisation and effective publication output by agricultural researchers in Southwestern Nigeria. The respondents consisted of agricultural researchers in agricultural research institutes in Southwest Nigeria. The descriptive survey of correlational type was used. Four hundred and sixty two copies of the questionnaire were distributed using total enumeration technique, 334 were returned representing 72.3 return rate. The data collected were analysed using descriptive statistic of frequency counts, percentages, mean and standard deviation while Pearson product moment correlation and multiple regressions were used to test the hypothesis. The result of the finding showed that the internet ([Formula: see text]), Email ([Formula: see text]), and laptops ([Formula: see text]) were the frequently used media resources. Agricultural databases were scantly used. The result also revealed that Email and the internet were the most available media resources while AGORA, LanTEEAL and FAO publications were the most available agricultural databases. Also, some researchers (0.6%) and others (62.3%) had below four local publications while on international publications, 3% researchers had above 16 international publications and 50.6% researchers had below 6 international publications. The study further revealed that there was a positive and significant relationship between media resources utilisation and publication output of researchers ([Formula: see text], [Formula: see text], [Formula: see text]). A significant relationship also exists between media resource availability and publication output and a joint relationship existed among media resource availability, media resource utilisation and publication output. The study identified poor funding, irregular electricity and inadequate electronic media resources as constraint to electronic media usage in Nigeria. Finally, the study recommends constant electricity, more funding for purchase of media and training for researchers.
Perovskite solid solutions with multiferroic morphotropic phase boundaries and property enhancement
Authors: Algueró M. , Amorín H. , Fernández-Posada C. M. , Peña O. , Ramos P. , Vila E. , Castro A.
Published: May 2016

Recently, large phase-change magnetoelectric response has been anticipated by a first-principles investigation of phases in the BiFeO3–BiCoO3 perovskite binary system, associated with the existence of a discontinuous morphotropic phase boundary (MPB) between multiferroic polymorphs of rhombohedral and tetragonal symmetries. This might be a general property of multiferroic phase instabilities, and a novel promising approach for room temperature magnetoelectricity. We review here our current investigations on the identification and study of additional material systems, alternative to BiFeO3–BiCoO3 that has only been obtained by high pressure synthesis. Three systems, whose phase diagrams were, in principle, liable to show multiferroic MPBs have been addressed: the BiMnO3–PbTiO3 and BiFeO3–PbTiO3 binary systems, and the BiFeO3–BiMnO3–PbTiO3 ternary one. A comprehensive study of multiferroism across different solid solutions was carried out based on electrical and magnetic characterizations, complemented with mechanical and electromechanical measurements. An in-depth structural analysis was also accomplished when necessary.
A Combinatorial, Primal-Dual Approach to Semidefinite Programs
Authors: Arora Sanjeev , Kale Satyen
Published: May 2016

Semidefinite programs (SDPs) have been used in many recent approximation algorithms. We develop a general primal-dual approach to solve SDPs using a generalization of the well-known multiplicative weights update rule to symmetric matrices. For a number of problems, such as S
parsest
C
ut
and B
alanced
S
eparator
in undirected and directed weighted graphs, M
in
U
n
C
ut
and M
in
2CNF D
eletion
, this yields combinatorial approximation algorithms that are significantly more efficient than interior point methods. The design of our primal-dual algorithms is guided by a robust analysis of rounding algorithms used to obtain integer solutions from fractional ones. Our ideas have proved useful in quantum computing, especially the recent result of Jain et al. [2011] that QIP = PSPACE.
Computational Complexity of Quantum Satisfiability
Authors: Herrmann Christian , Ziegler Martin
Published: May 2016

We connect both discrete and algebraic complexity theory with the satisfiability problem in certain non-Boolean lattices.

Specifically, quantum logic was introduced in 1936 by Garrett Birkhoff and John von Neumann as a framework for capturing the logical peculiarities of quantum observables: in the 1D case it coincides with Boolean propositional logic but, starting with dimension two, violates the distributive law.

We introduce the weak and strong satisfiability problem for quantum logic propositional formulae. It turns out that in dimension two, both are also
NP
--complete.

For higher-dimensional spaces ℝ

d

and ℂ

d

with
d
≥ 3 fixed, on the other hand, we show both problems to be complete for the nondeterministic Blum-Shub-Smale (BSS) model of real computation. This provides a unified view on both Turing and real BSS complexity theory, and extends the (still relatively scarce) list of problems established
NP
ℝ
--complete with one, perhaps, closest in spirit to the classical Cook-Levin Theorem. More precisely, strong satisfiability of ∧ ∨ ∧ --terms is complete, while that of ∧ ∨--terms (i.e., those in conjunctive form) can be decided in polynomial time in dimensions
d
≥ 2.

The decidability of the infinite-dimensional case being still open, we proceed to investigate the case of indefinite finite dimensions. Here, weak satisfiability still belongs to
NP
R
and strong satisfiability is still hard; the latter, in fact, turns out as polynomial-time equivalent to the feasibility of noncommutative integer polynomial equations over matrix rings.
Enjoy the Trip: Calcium in Mitochondria Back and Forth
Authors: De Stefani Diego , Rizzuto Rosario , Pozzan Tullio
Published: May 2016

In the last 5 years, most of the molecules that control mitochondrial Ca2+ homeostasis have been finally identified. Mitochondrial Ca2+ uptake is mediated by the Mitochondrial Calcium Uniporter (MCU) complex, a macromolecular structure that guarantees Ca2+ accumulation inside mitochondrial matrix upon increases in cytosolic Ca2+. Conversely, Ca2+ release is under the control of the Na+/Ca2+ exchanger, encoded by the NCLX gene, and of a H+/Ca2+ antiporter, whose identity is still debated. The low affinity of the MCU complex, coupled to the activity of the efflux systems, protects cells from continuous futile cycles of Ca2+ across the inner mitochondrial membrane and consequent massive energy dissipation. In this review, we discuss the basic principles that govern mitochondrial Ca2+ homeostasis and the methods used to investigate the dynamics of Ca2+ concentration within the organelles. We discuss the functional and structural role of the different molecules involved in mitochondrial Ca2+ handling and their pathophysiological role.
Transcription Dynamics in Living Cells
Authors: Lenstra Tineke L. , Rodriguez Joseph , Chen Huimin , Larson Daniel R.
Published: May 2016

The transcription cycle can be roughly divided into three stages: initiation, elongation, and termination. Understanding the molecular events that regulate all these stages requires a dynamic view of the underlying processes. The development of techniques to visualize and quantify transcription in single living cells has been essential in revealing the transcription kinetics. They have revealed that (a) transcription is heterogeneous between cells and (b) transcription can be discontinuous within a cell. In this review, we discuss the progress in our quantitative understanding of transcription dynamics in living cells, focusing on all parts of the transcription cycle. We present the techniques allowing for single-cell transcription measurements, review evidence from different organisms, and discuss how these experiments have broadened our mechanistic understanding of transcription regulation.
Protein Folding—How and Why: By Hydrogen Exchange, Fragment Separation, and Mass Spectrometry
Authors: Englander S. Walter , Mayne Leland , Kan Zhong-Yuan , Hu Wenbing
Published: May 2016

Advanced hydrogen exchange (HX) methodology can now determine the structure of protein folding intermediates and their progression in folding pathways. Key developments over time include the HX pulse labeling method with nuclear magnetic resonance analysis, the fragment separation method, the addition to it of mass spectrometric (MS) analysis, and recent improvements in the HX MS technique and data analysis. Also, the discovery of protein foldons and their role supplies an essential interpretive link. Recent work using HX pulse labeling with MS analysis finds that a number of proteins fold by stepping through a reproducible sequence of native-like intermediates in an ordered pathway. The stepwise nature of the pathway is dictated by the cooperative foldon unit construction of the protein. The pathway order is determined by a sequential stabilization principle; prior native-like structure guides the formation of adjacent native-like structure. This view does not match the funneled energy landscape paradigm of a very large number of folding tracks, which was framed before foldons were known and is more appropriate for the unguided residue-level search to surmount an initial kinetic barrier rather than for the overall unfolded-state to native-state folding pathway.
How Bacteria Subvert Animal Cell Structure and Function
Authors: Jimenez Alyssa , Chen Didi , Alto Neal M.
Published: May 2016

Bacterial pathogens encode a wide variety of effectors and toxins that hijack host cell structure and function. Of particular importance are virulence factors that target actin cytoskeleton dynamics critical for cell shape, stability, motility, phagocytosis, and division. In addition, many bacteria target organelles of the general secretory pathway (e.g., the endoplasmic reticulum and the Golgi complex) and recycling pathways (e.g., the endolysosomal system) to establish and maintain an intracellular replicative niche. Recent research on the biochemistry and structural biology of bacterial effector proteins and toxins has begun to shed light on the molecular underpinnings of these host-pathogen interactions. This exciting work is revealing how pathogens gain control of the complex and dynamic host cellular environments, which impacts our understanding of microbial infectious disease, immunology, and human cell biology.
The Role of Adipocytes in Tissue Regeneration and Stem Cell Niches
Authors: Shook Brett , Rivera Gonzalez Guillermo , Ebmeier Sarah , Grisotti Gabriella , Zwick Rachel , Horsley Valerie
Published: May 2016

Classically, white adipose tissue (WAT) was considered an inert component of connective tissue but is now appreciated as a major regulator of metabolic physiology and endocrine homeostasis. Recent work defining how WAT develops and expands in vivo emphasizes the importance of specific locations of WAT or depots in metabolic regulation. Interestingly, mature white adipocytes are integrated into several tissues. A new perspective regarding the in vivo regulation and function of WAT in these tissues has highlighted an essential role of adipocytes in tissue homeostasis and regeneration. Finally, there has been significant progress in understanding how mature adipocytes regulate the pathology of several diseases. In this review, we discuss these novel roles of WAT in the homeostasis and regeneration of epithelial, muscle, and immune tissues and how they contribute to the pathology of several disorders.
Nanoparticle-Based Modulation of the Immune System
Authors: Fang Ronnie H. , Zhang Liangfang
Published: May 2016

The immune system is an incredibly complex biological network that plays a significant role in almost all disease pathogenesis. With an increased understanding of how this vital system operates, there has been a great emphasis on leveraging, manipulating, and/or supplementing endogenous immunity to better prevent or treat different disease states. More recently, the advent of nanotechnology has ushered in a plethora of new nanoparticle-based platforms that can be used to improve existing immunomodulation modalities. As the ability to engineer at the nanoscale becomes increasingly sophisticated, nanoparticles can be finely tuned to effect the desired immune responses, leading to exciting new avenues for addressing pressing issues in public health. In this review, we give an overview of the different areas in which nanoparticle technology has been applied toward modulating the immune system and highlight the recent advances within each.
Ocean Basin Evolution and Global-Scale Plate Reorganization Events Since Pangea Breakup
Authors: Müller R. Dietmar , Seton Maria , Zahirovic Sabin , Williams Simon E. , Matthews Kara J. , Wright Nicky M. , Shephard Grace E. , Maloney Kayla T. , Barnett-Moore Nicholas , Hosseinpour Maral , Bower Dan J. , Cannon John
Published: May 2016

We present a revised global plate motion model with continuously closing plate boundaries ranging from the Triassic at 230 Ma to the present day, assess differences among alternative absolute plate motion models, and review global tectonic events. Relatively high mean absolute plate motion rates of approximately 9–10 cm yr−1 between 140 and 120 Ma may be related to transient plate motion accelerations driven by the successive emplacement of a sequence of large igneous provinces during that time. An event at ∼100 Ma is most clearly expressed in the Indian Ocean and may reflect the initiation of Andean-style subduction along southern continental Eurasia, whereas an acceleration at ∼80 Ma of mean rates from 6 to 8 cm yr−1 reflects the initial northward acceleration of India and simultaneous speedups of plates in the Pacific. An event at ∼50 Ma expressed in relative, and some absolute, plate motion changes around the globe and in a reduction of global mean plate speeds from about 6 to 4–5 cm yr−1 indicates that an increase in collisional forces (such as the India–Eurasia collision) and ridge subduction events in the Pacific (such as the Izanagi–Pacific Ridge) play a significant role in modulating plate velocities.
Reconstructing Ocean pH with Boron Isotopes in Foraminifera
Authors: Foster Gavin L. , Rae James W.B.
Published: May 2016

In order to better understand the effect of CO2 on the Earth system in the future, geologists may look to CO2-induced environmental change in Earth's past. Here we describe how CO2 can be reconstructed using the boron isotopic composition (δ11B) of marine calcium carbonate. We review the chemical principles that underlie the proxy, summarize the available calibration data, and detail how boron isotopes can be used to estimate ocean pH and ultimately atmospheric CO2 in the past. δ11B in a variety of marine carbonates shows a coherent relationship with seawater pH, in broad agreement with simple models for this proxy. Offsets between measured and predicted δ11B may in part be explained by physiological influences, though the exact mechanisms of boron incorporation into carbonate remain unknown. Despite these uncertainties, we demonstrate that δ11B may provide crucial constraints on past ocean acidification and atmospheric CO2.
New Perspectives on Genomic Imprinting, an Essential and Multifaceted Mode of Epigenetic Control in the Developing and Adult Brain
Authors: Perez Julio D. , Rubinstein Nimrod D. , Dulac Catherine
Published: May 2016

Mammalian evolution entailed multiple innovations in gene regulation, including the emergence of genomic imprinting, an epigenetic regulation leading to the preferential expression of a gene from its maternal or paternal allele. Genomic imprinting is highly prevalent in the brain, yet, until recently, its central roles in neural processes have not been fully appreciated. Here, we provide a comprehensive survey of adult and developmental brain functions influenced by imprinted genes, from neural development and wiring to synaptic function and plasticity, energy balance, social behaviors, emotions, and cognition. We further review the widespread identification of parental biases alongside monoallelic expression in brain tissues, discuss their potential roles in dosage regulation of key neural pathways, and suggest possible mechanisms underlying the dynamic regulation of imprinting in the brain. This review should help provide a better understanding of the significance of genomic imprinting in the normal and pathological brain of mammals including humans.
Correlations and Neuronal Population Information
Authors: Kohn Adam , Coen-Cagli Ruben , Kanitscheider Ingmar , Pouget Alexandre
Published: May 2016

Brain function involves the activity of neuronal populations. Much recent effort has been devoted to measuring the activity of neuronal populations in different parts of the brain under various experimental conditions. Population activity patterns contain rich structure, yet many studies have focused on measuring pairwise relationships between members of a larger population—termed noise correlations. Here we review recent progress in understanding how these correlations affect population information, how information should be quantified, and what mechanisms may give rise to correlations. As population coding theory has improved, it has made clear that some forms of correlation are more important for information than others. We argue that this is a critical lesson for those interested in neuronal population responses more generally: Descriptions of population responses should be motivated by and linked to well-specified function. Within this context, we offer suggestions of where current theoretical frameworks fall short.
The Genetic Basis of Hydrocephalus
Authors: Kousi Maria , Katsanis Nicholas
Published: May 2016

Studies of syndromic hydrocephalus have led to the identification of >100 causative genes. Even though this work has illuminated numerous pathways associated with hydrocephalus, it has also highlighted the fact that the genetics underlying this phenotype are more complex than anticipated originally. Mendelian forms of hydrocephalus account for a small fraction of the genetic burden, with clear evidence of background-dependent effects of alleles on penetrance and expressivity of driver mutations in key developmental and homeostatic pathways. Here, we synthesize the currently implicated genes and inheritance paradigms underlying hydrocephalus, grouping causal loci into functional modules that affect discrete, albeit partially overlapping, cellular processes. These in turn have the potential to both inform pathomechanism and assist in the rational molecular classification of a clinically heterogeneous phenotype. Finally, we discuss conceptual methods that can lead to enhanced gene identification and dissection of disease basis, knowledge that will potentially form a foundation for the design of future therapeutics.
Alterations of Mitochondrial Function and Insulin Sensitivity in Human Obesity and Diabetes Mellitus
Authors: Koliaki Chrysi , Roden Michael
Published: May 2016

Mitochondrial function refers to a broad spectrum of features such as resting mitochondrial activity, (sub)maximal oxidative phosphorylation capacity (OXPHOS), and mitochondrial dynamics, turnover, and plasticity. The interaction between mitochondria and insulin sensitivity is bidirectional and varies depending on tissue, experimental model, methodological approach, and features of mitochondrial function tested. In human skeletal muscle, mitochondrial abnormalities may be inherited (e.g., lower mitochondrial content) or acquired (e.g., impaired OXPHOS capacity and plasticity). Abnormalities ultimately lead to lower mitochondrial functionality due to or resulting in insulin resistance and type 2 diabetes mellitus. Similar mechanisms can also operate in adipose tissue and heart muscle. In contrast, mitochondrial oxidative capacity is transiently upregulated in the liver of obese insulin-resistant humans with or without fatty liver, giving rise to oxidative stress and declines in advanced fatty liver disease. These data suggest a highly tissue-specific interaction between insulin sensitivity and oxidative metabolism during the course of metabolic diseases in humans.