bluuebunny/crossref_metadata_2025 huggingface dataset:
FABRICATION AND CHARACTERIZATIONS OF GELATIN/CHITOSAN WITH ALOE VERA AND ACHATINA FULICA SP MUCUS AS SCAFFOLD FOR SKIN TISSUE ENGINEERING
Authors: Nabilla Fathania , Widiyanti Prihartini , Hikmawati Dyah
Published: June 2019

Scaffold is a biomaterial widely used in tissue engineering. Scaffold is temporary porous structure which contain extracellular matrix. It serves as scaffolding which is required for cells infiltration and physical support to guide the cell proliferation and differentiation into the targeted functional tissues. Scaffold must be biocompatible, small pore size, flexible and support regenerative application. Aloe vera as natural resource, it has capability in accelerating wound healing, facilitating the inflammation, increasing wound contraction and epithelialization, and increasing organization of the regenerated tissue. Snail mucus (SM) has capability in inhibiting bacterial growth. This study aims to synthesize and characterize a scaffold made of gelatin-chitosan-Aloe vera (AV) - Achatina fulica sp mucus. The method is to synthesize scaffold with its compositions, gelatin-chitosan (1: 1 ratio) which is dissolved into 0.05 M acetic acid, then a variation of Aloe vera (AV) and snail mucus (SM) at 0% AV; 0% SM; 0.07 AV; 0.07 SM; 0.15 AV; 0.15 SM; 0.07 AV; 0.15 SM; 0.15 AV; 0.007 SM were mixed with the chitosan-gelatin solution, then used freeze dry method to obtain porous scaffold. Characterization which performed in this research including Fourier-transform infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM), porosity test, tensile strength test, swelling test, and degradation test. Based on FTIR test, Aloe vera and snail mucus interacted with free amino and hydroxyl groups of chitosan and gelatin, characterized by absorption bands at 2937.59 cm-1 wave numbers which are symmetrical and asymmetrical stretching of (-CH) .SEM test results obtained pore size of 70 - 235 μm. Porosity test results showed that five scaffolds have porosity value of 87-96%; thus, allowing the process of cell proliferation to occur well. The result of physical characteristic test yielded tensile strength of 1.425 MPa on gelatin-chitosan as control sample and 0.732 MPa for sample with 0.15% AV and 0.15% SM. Swelling test showed a variation of scaffold composition with Aloe vera with Achatina fulica sp’s mucus having a swelling percentage of 200-520%. The degradation test results showed that the whole sample was not depleted for 21 days; thus, giving time for cell regeneration. Sample with 0.15% Aloe vera and 0.07% snail mucus has some potentials as scaffolds for skin tissue in case of burns wound, due to its morfology, porosity, and degradation.
DURABILITY PROPERTIES OF TERNARY BLENDED FLOWABLE HIGH PERFORMANCE CONCRETE CONTAINING GROUND GRANULATED BLAST FURNACE SLAG AND PULVERIZED FUEL ASH
Authors: Chee Ban Cheah , Wee Kang Chow
Published: June 2019

The use of ordinary Portland cement as the primary binder in concrete production resulted in the high carbon footprint of the concrete material which cause a great deal of environmental impacts over the years. The consumption of OPC is especially significant for high strength concrete, which require a very high cement content (more than 450 kg/m3). Hence, supplementary cementitious materials such as ground granulated blast furnace slag (GGBS) and pulverized fuel ash (PFA) were chosen as partial replacement materials of OPC for concrete production in the research due to their ease of availability from the steelmaking manufacturing sectors and coal-fired electricity power stations in the country. As the sustainability of concrete is also our main concern, the durability performance of flowable high performance concrete containing high volume of GGBS and PFA (50-80% replacement of OPC) has been studied in this research. Therefore, the durability properties of flowable high performance concrete had been assessed in term of air permeability, porosity, water absorption and capillary action. From the results of assessment, all ternary blended concrete mixes exhibited better durability performances than control OPC concrete at later ages due to formation of denser microstructure by pozzolanic reaction of GGBS and PFA. It is concluded that the mix proportion of flowable high performance concrete production with 60% replacement of OPC by GGBS and PFA has the optimum durability performances than OPC concrete.
THE MECHANICAL STRENGTH AND DRYING SHRINKAGE BEHAVIOR OF HIGH PERFORMANCE CONCRETE WITH BLENDED MINERAL ADMIXTURE
Authors: Chee Ban Cheah , Sern Lim Jay , Jasme Nurshafarina
Published: June 2019

With the fast in population development, there are a higher demand in housing and infrastructure such as high-rise buildings and long-span bridges. Therefore, high performance concrete (HPC) is used massively due to its technical and economical advantages to fulfil people demands towards the concrete usage. Optimum mineral blended admixture replacement ratio with the addition of superplasticizer are the main component which contributed to the formation of HPC in terms of high workability, high strength and high durability. Hence, the optimal cement to blended mineral admixture ratio with the optimum addition of PCE type superplasticizer to achieve the targeted mechanical strength performance of G60 and reduce the drying shrinkage behavior which will results in crack of the ternary blended concrete is highlighted in this report. The influence of the addition of two mineral blended admixture, ground granulated blast furnace slag (GGBS) and pulverized fly ash (PFA) with the ordinary Portland cement (OPC) in different ratio on engineering performance and its drying shrinkage behavior in the age of 7 days, 28 days and 90 days based on different mineral blended admixture replacement level in 50%, 60%, 70% and 80% which GGBS to PFA ratio are controlled in 4:1 and the water to cement ratio was kept in 0.35 is studied. There are two types of PCE type superplasticizer (SP) was added to enhance the workability of the fresh concrete and act as slump retainer. Ternary blended concrete results in low early age (7 days) strength but the performance at later age (28 days and beyond) was encouraging. Results revealed that 80% replacement level have the remarkable result in terms of mechanical strength and drying shrinkage behavior. The study showed that, presence of mineral additives with superplasticizer will produce a similar or enhance the concrete strength properties with the inclusion of GGBS and PFA at the ratio of 4:1 up to 80% as cement replacement.
OPTIMIZATION OF GLYCEROL MONOLAURATE (GML) SYNTHESIS FROM GLYCEROL AND LAURIC ACID USING DEALUMINATED ZEOLITE Y CATALYST
Authors: Anggoro Didi Dwi , Oktavianty Herawati , Kurniawan Bagas Prasetya , Daud Roynaldy
Published: June 2019

Glycerol Monolaurate (GML) is used as a surfactant, preservative and emulsifier in food, besides it can be used in cosmetics and medicines. This study obtained to optimize GML synthesis from glycerol and lauric acid. It consisted of two steps, dealumination of zeolite Y catalyst and optimization of GML synthesis. At dealumination process, zeolite Y will reacted with H2SO4 solution and aquadest with temperature at 60°C for 4 hours, then drying with temperature at 110°C for 1 hour, then furnace with temperature at 500°C for 3 hours. The synthesis of GML held by reacting glycerol and lauric acid using dealuminated zeolite Y. The synthesis of GML analyzed using GC-MS to determine the structure, molecular weight, and conversion of GML produced. This study obtained GML optimization to produce the greatest yield of GML. The best test results obtained is 90.75% of GML yield and the estimated value of optimization at temperature 130°C for 4 hours, and the mole ratio of lauric acid with glycerol 1: 7.5 (with the mass of lauric acid is 25 g, and the mass of glycerol is 87.654 g).
Autoriti Kerajaan Dalam Mewajibkan Vaksinasi Kanak-kanak: Kajian Menurut Perspektif Hukum Islam (Authority of the Government to Enforce Child Vaccination: A Study from the Islamic Ruling Perspective)
Authors: Ramli Mohd Anuar , Tengku Md Fauzi Tengku Fatimah Azzahra , Mohd Razif Noor Fahimah
Published: June 2019

Public health is the main priority of the government policy. In line with this, various efforts have been undertaken to improve the health of the community, including vaccination programs, explicitly the injection of vaccines, specifically immunization among children. This is due to the transmission of various types of diseases that risks the survival of children. However, there are parents who reject giving the vaccine to their children based on claims of non-halal vaccine sources and the adverse events following immunization. They deny the importance of vaccines by choosing alternative treatments that are said to be better and safer. Since the vaccine injection is not a mandatory requirement by the government, they feel entitled to reject the vaccine injection by choice. As a result of the vaccine rejection, some previously reduced vaccine-preventable diseases are on the increase in Malaysia. Therefore, this literature review, based on the qualitative approach, discusses the polemics of vaccines and governmental authorities in enforcing a policy from an Islamic ruling perspective. Findings of this study indicate that based on the principle of maslahah in Islam, it is permissible for the government to devise vaccination as a compulsory requirement for the citizens. Thus, the government can enforce mandatory vaccinations so that parents will allow their children to be vaccinated. The effects of not vaccinating children are not on the children only; they also pose risks to the community at large.
A novel form of glycolytic metabolism‐dependent cardioprotection revealed by PKCα and β inhibition
Authors: Brennan Sean , Chen Shen , Makwana Samir , Martin Christopher A. , Sims Mark W. , Alonazi Asma S.A. , Willets Jonathan M , Squire Iain B. , Rainbow Richard D.
Published: June 2019

Key points

Acute hyperglycaemia at the time of a heart attack worsens the outcome for the patient.

Acute hyperglycaemia is not limited to diabetic patients and can be due to a stress response in non‐diabetics.

This study suggests that the damaging cardiac effects of hyperglycaemia can be reversed by selective PKC inhibition.

If PKCα/β isoforms are inhibited, then high glucose itself becomes protective against ischaemic damage.

Selective PKC inhibition may therefore be a useful therapeutic tool to limit the damage that can occur during a heart attack by stress-induced hyperglycaemia.

Hyperglycaemia has a powerful association with adverse prognosis for patients with acute coronary syndromes (ACS). Previous work shows that high glucose prevents ischaemic preconditioning and causes electrical and mechanical disruption via protein kinase C α/β (PKCα/β) activation. The present study aimed to: (i) determine whether the adverse clinical association of hyperglycaemia in ACS can be replicated in preclinical cellular models of ACS and (ii) determine the importance of PKCα/β activation to the deleterious effect of glucose. Freshly isolated rat, guinea pig or rabbit cardiomyocytes were exposed to simulated ischaemia after incubation in the presence of normal (5 mm) or high (20 mm) glucose in the absence or presence of small molecule or tat‐peptide‐linked PKCαβ inhibitors. In each of the four conditions, the following hallmarks of cardioprotection were recorded using electrophysiology or fluorescence imaging: cardiomyocyte contraction and survival, action potential stability and time to failure, intracellular calcium and ATP, mitochondrial depolarization, ischaemia‐sensitive leak current, and time to Kir6.2 opening. High glucose alone resulted in decreased cardiomyocyte contraction and survival; however, it also imparted cardioprotection in the presence of PKCα/β inhibitors. This cardioprotective phenotype displayed improvements in all of the measured parameters and decreased myocardium damage during whole heart coronary ligation experiments. High glucose is deleterious to cellular and whole‐heart models of simulated ischaemia, in keeping with the clinical association of hyperglycaemia with an adverse outcome in ACS. PKCαβ inhibition revealed high glucose to show a cardioprotective phenotype in this setting. The results of the present study suggest the potential for the therapeutic application of PKCαβ inhibition in ACS associated with hyperglycaemia.
Endogenous AT1 receptor–protein kinase C activity in the hypothalamus augments glutamatergic input and sympathetic outflow in hypertension
Authors: Ma Huijie , Chen Shao‐Rui , Chen Hong , Pan Hui‐Lin
Published: June 2019

Key points

The angiotensin AT1 receptor expression and protein kinase C (PKC)‐mediated NMDA receptor phosphorylation levels in the hypothalamus are increased in a rat genetic model of hypertension.

Blocking AT1 receptors or PKC activity normalizes the increased pre‐ and postsynaptic NMDA receptor activity of hypothalamic presympathetic neurons in hypertensive animals.

Inhibition of AT1 receptor–PKC activity in the hypothalamus reduces arterial blood pressure and sympathetic nerve discharges in hypertensive animals.

AT1 receptors in the hypothalamus are endogenously activated to sustain NMDA receptor hyperactivity and elevated sympathetic outflow via PKC in hypertension.

Increased synaptic N‐methyl‐d‐aspartate receptor (NMDAR) activity in the hypothalamic paraventricular nucleus (PVN) plays a major role in elevated sympathetic output in hypertension. Although exogenous angiotensin II (AngII) can increase NMDAR activity in the PVN, whether endogenous AT1 receptor–protein kinase C (PKC) activity mediates the augmented NMDAR activity of PVN presympathetic neurons in hypertension is unclear. Here we show that blocking AT1 receptors with losartan or inhibiting PKC with chelerythrine significantly decreased the frequency of NMDAR‐mediated miniature excitatory postsynaptic currents (mEPSCs) and the amplitude of puff NMDA currents of retrogradely labelled spinally projecting PVN neurons in spontaneously hypertensive rats (SHRs). Also, treatment with chelerythrine abrogated the potentiating effect of AngII on mEPSCs and puff NMDA currents of labelled PVN neurons in SHRs. In contrast, neither losartan nor chelerythrine had any effect on mEPSCs or puff NMDA currents in labelled PVN neurons in Wistar–Kyoto (WKY) rats. Furthermore, levels of AT1 receptor mRNA and PKC‐mediated NMDAR phosphorylation in the PVN were significantly higher in SHRs than in WKY rats. In addition, microinjection of losartan or chelerythrine into the PVN substantially reduced blood pressure and renal sympathetic nerve discharges in SHRs but not in WKY rats. Chelerythrine blocked sympathoexcitatory responses to AngII microinjected into the PVN. Our findings suggest that endogenous AT1 receptor–PKC activity is essential for presynaptic and postsynaptic NMDAR hyperactivity of PVN presympathetic neurons and for the augmented sympathetic outflow in hypertension. This information advances our mechanistic understanding of the interplay between angiotensinergic and glutamatergic excitatory inputs in hypertension.
Effect of Multiple Pulse Resistance Spot Welding Schedules on Liquid Metal Embrittlement Severity
Authors: Wintjes E. , DiGiovanni C. , He L. , Bag S. , Goodwin F. , Biro E. , Zhou Y.
Published: June 2019

Zinc-coated advanced high strength steels (AHSS) used in automotive applications are susceptible to liquid metal embrittlement (LME) during resistance spot welding (RSW). This study examines the impact of multiple pulse welding schedules on LME severity in welds of TRIP1100. Two different types of pulsing methodologies have been proposed to reduce LME severity: applying a pre-pulse before the welding current to remove the zinc coating and pulsing during the welding current to manage heat generation. However, the mechanisms by which these methods affect LME severity have not been fully explored. This work showed that a welding schedule consisting of two equal length pulses resulted in the least severe LME because it reduced the amount of free zinc available for LME without creating too much tensile stress. The majority of pre-pulse welding schedules caused an increase in LME cracking due to the additional heat introduced into the weld. However, a 4 kA (low current) pre-pulse applied for 3 cy (low time) reduced LME cracking by almost 30%. The pre-pulse allowed zinc to diffuse into the coating and stabilize the zinc, without introducing too much additional heat into the weld. These results indicate that multiple pulse welding schedules may be successfully used to reduce LME cracking, although the mechanisms by which they impact LME are more complicated than previously thought.
Nuclear DNA from two early Neandertals reveals 80,000 years of genetic continuity in Europe
Authors: Peyrégne Stéphane , Slon Viviane , Mafessoni Fabrizio , de Filippo Cesare , Hajdinjak Mateja , Nagel Sarah , Nickel Birgit , Essel Elena , Le Cabec Adeline , Wehrberger Kurt , Conard Nicholas J. , Kind Claus Joachim , Posth Cosimo , Krause Johannes , Abrams Grégory , Bonjean Dominique , Di Modica Kévin , Toussaint Michel , Kelso Janet , Meyer Matthias , Pääbo Svante , Prüfer Kay
Published: June 2019

Sequences from two ~120,000-year-old individuals reveal the deep population history of European Neandertals.
Identification of Potential Cerebrospinal Fluid Biomarkers To Discriminate between Infection and Sterile Inflammation in a Rat Model of Staphylococcus epidermidis Catheter Infection
Authors: Skar Gwenn L. , Beaver Matthew , Aldrich Amy , Lagundzin Dragana , Thapa Ishwor , Woods Nicholas , Ali Hesham , Snowden Jessica , Kielian Tammy
Published: June 2019

Staphylococcus epidermidiscerebrospinal fluid (CSF) shunt infection is a common complication of hydrocephalus treatment, creating grave neurological consequences for patients, especially when diagnosis is delayed. The current method of diagnosis relies on microbiological culture; however, awaiting culture results may cause treatment delays, or culture may fail to identify infection altogether, so newer methods are needed.
Complete Genome Sequence of
Lily Symptomless Virus
, Isolated from
Alstroemeria
Plants in Ecuador
Authors: Flores Francisco , Garrido Patricia , Guevara Fiama , Granda Roberto
Published: June 2019

In this work, we present the complete genome sequence of
Lily symptomless virus
isolated from
Alstroemeria
plants. The genome is 8,391-bp long, arranged into six open reading frames (ORFs), with a 5′-untranslated region (5′-UTR) of 55 nucleotides (nt) and a 3′-UTR of 48 nt.
Smokers’ strategies across social grades to minimise the cost of smoking in a period with annual tax increases: evidence from a national survey in England
Authors: Kuipers Mirte AG , Partos Timea , McNeill Ann , Beard Emma , Gilmore Anna B , West Robert , Brown Jamie
Published: June 2019

Objectives

To assess associations between smokers’ strategies to minimise how much their smoking costs and cost of smoking among smokers across three social grades during a period of annual tax increases in England.

Design

Repeat cross-sectional.

Setting

England, May 2012–December 2016.

Participants

16 967 adult smokers in 56 monthly surveys with nationally representative samples.

Measures and analysis

Weighted generalised additive models assessed associations between four cost-minimising strategies (factory-made and roll-your-own (RYO) cigarette consumption levels, illicit and cross-border purchases) and cost of smoking (£/week). We adjusted for inflation rate, age, gender and secular and seasonal trends.

Results

Cost of smoking did not increase above the rate of inflation. Factory-made cigarette consumption decreased, while proportion of RYO and, to a much lesser extent, illicit and cross-border purchases increased. These trends were only evident in lowest social grade. Cost of smoking was 12.99% lower with consumption of 10 fewer factory-made cigarettes (95% CI −13.18 to −12.80) and 5.86% lower with consumption of 10 fewer RYO cigarettes (95% CI −5.66 to −6.06). Consumption levels accounted for 60% of variance in cost. Cross-border and illicit tobacco purchases were associated with 9.64% (95% CI −12.94 to −6.33) and 9.47% (95% CI −12.74 to −6.20) lower costs, respectively, but due to low prevalence, accounted for only 0.2% of variation. Associations were similar across social grades, although weaker for illicit and cross-border purchases and stronger for consumption in higher social grades compared with lower social grades.

Conclusion

During a period of annual tax increases, the weekly cost of smoking did not increase above inflation. Cost-minimising strategies increased, especially among more disadvantaged smokers. Reducing cigarette consumption and switching to RYO tobacco explained a large part of cost variation, while use of illicit and cross-border purchasing played only a minor role.
Healthcare provision, functional ability and quality of life after proximal femoral fracture - ’ProFem': Study protocol of a population-based, prospective study based on individually linked survey and statutory health insurance data
Authors: Andrich Silke , Ritschel Michaela , Meyer Gabriele , Hoffmann Falk , Stephan Astrid , Baltes Marion , Blessin Juliane , Jobski Kathrin , Fassmer Alexander M , Haastert Burkhard , Gontscharuk Veronika , Arend Werner , Theunissen Lena , Colley Denise , Hinze Raoul , Thelen Simon , Fuhrmann Petra , Sorg Christian G G , Windolf Joachim , Rupprecht Christoph J , Icks Andrea
Published: June 2019

Introduction

Proximal femoral fractures (PFF) are among the most frequent fractures in older people. However, the situation of people with a PFF after hospital discharge is poorly understood. Our aim is to (1) analyse healthcare provision, (2) examine clinical and patient-reported outcomes (PROs), (3) describe clinical and sociodemographic predictors of these and (4) develop an algorithm to identify subgroups with poor outcomes and a potential need for more intensive healthcare.

Methods and analysis

This is a population-based prospective study based on individually linked survey and statutory health insurance (SHI) data. All people aged minimum 60 years who have been continuously insured with the AOK Rheinland/Hamburg and experience a PFF within 1 year will be consecutively included (SHI data analysis). Additionally, 700 people selected randomly from the study population will be consecutively invited to participate in the survey. Questionnaire data will be collected in the participants’ private surroundings at 3, 6 and 12 months after hospital discharge. If the insured person considers themselves to be only partially or not at all able to take part in the survey, a proxy person will be interviewed where possible. SHI variables include healthcare provision, healthcare costs and clinical outcomes. Questionnaire variables include information on PROs, lifestyle characteristics and socioeconomic status. We will use multiple regression models to estimate healthcare processes and outcomes including mortality and cost, investigate predictors, perform non-responder analysis and develop an algorithm to identify vulnerable subgroups.

Ethics and dissemination

The study was approved by the ethics committee of the Faculty of Medicine, Heinrich-Heine-University Düsseldorf (approval reference 6128R). All participants including proxies providing written and informed consent can withdraw from the study at any time. The study findings will be disseminated through scientific journals and public information.

Trial registration number

DRKS00012554.
Better Use of Data to improve parent Satisfaction (BUDS): protocol for a prospective before-and-after pilot study employing mixed methods to improve parent experience of neonatal care
Authors: Sakonidou Susanna , Andrzejewska Izabela , Kotzamanis Sophia , Carnegie Wendy , Nakubulwa Mable , Woodcock Thomas , Modi Neena , Bell Derek , Gale Chris
Published: June 2019

Introduction

Having a baby that requires neonatal care is stressful and traumatic. Parents often report dissatisfaction with communication of clinical information. In the UK neonatal care data are recorded daily using electronic patient record systems (EPR), from which deidentified data form the National Neonatal Research Database (NNRD). We aim to evaluate the impact of sharing neonatal EPR data with parents, on parent-reported satisfaction, parent–staff interactions, staff workload and data completeness.

Methods

A prospective, before-and-after, mixed-method study. Participants are parents of inpatient babies (maximum 90) and staff in a tertiary neonatal intensive care unit, London, UK. The intervention was developed by former neonatal parents, neonatologists and neonatal nurses: a communication tool for parents comprising individualised, written, daily infant updates for parents, derived from EPR data. The intervention will be provided to parents over 6 weeks. Plan-Do-Study-Act cycles will inform the tool’s iterative development and improvement. The tool’s impact will be measured using a validated parent survey, staff survey, data completeness measures and interviews.

Analysis

Primary outcome: parent satisfaction ‘with communication of clinical information and involvement in care’. Secondary outcomes: parent–staff interactions, staff workload, data completeness. Baseline survey data will be obtained from clinical service evaluation preceding the intervention. Baseline data completeness will be derived from the NNRD. During the intervention, surveys will be administered biweekly and data completeness assessed daily. We will analyse outcomes using run charts and partially paired statistical tests. Parent and staff interviews will explore information exchange and the communication tool’s impact.

Discussion

This study will evaluate the impact of a parent co-designed intervention on communication with parents in neonatal care and the completeness of routinely recorded electronic clinical data. Better use of routinely recorded clinical data provides the opportunity to improve parent satisfaction and increase the research utility of such data, benefiting clinical care.

Ethics and dissemination

Reviewed and approved by the West Midlands—South Birmingham REC (18/WM/0175).

Registration number

ISRCTN62718241.
Family carer support in home and hospital: a cross-sectional survey of specialised palliative care
Authors: Vermorgen Maarten , De Vleminck Aline , Leemans Kathleen , Van den Block Lieve , Van Audenhove Chantal , Deliens Luc , Cohen Joachim
Published: June 2019

Objectives

To evaluate: (1) to what extent family carers of people supported by specialised palliative care services felt they had been provided with information, support and aftercare and (2) how this varied by type of palliative care service, length of enrolment and characteristics of deceased.

Methods

A cross-sectional postal survey was conducted using a structured questionnaire with nine items on information, support and aftercare provided by specialised palliative care services to family carers. Flemish family carers of people who had made use of specialised palliative care services at home or in hospital were contacted.

Results

Of all primary family carers (response rate of 53.5% resulting in n=1504), 77.7% indicated they were asked frequently by professionals how they were feeling. Around 75% indicated they had been informed about specific end-of-life topics and around 90% felt sufficiently supported before and immediately after the death. Family carers of people who had died in a palliative care unit, compared with other types of specialised palliative care services, indicated having received more information, support and aftercare.

Conclusions

Family carers evaluate the professional assistance provided more positively when death occurred in a palliative care unit. Policy changes might be needed to reach the same level of care across all specialised palliative care services.
Failsafe Mechanism Design for Autonomous Aerial Refueling using State Tree Structures
Authors: Dong Ke , Quan Quan , Wonham W. Murray
Published: June 2019

Autonomous Aerial Refueling (AAR) is vulnerable to various failures and involves cooperation among autonomous receivers, tankers and remote pilots. Dangerous flight maneuvers may be executed when unexpected failures or command conflicts happen. To solve this problem, a failsafe mechanism based on State Tree Structures (STS) is proposed. The failsafe mechanism is a control logic that guides what subsequent actions the autonomous receiver should take, by observing real-time information of internal low-level subsystems such as guidance and drogue&probe and external instructions from tankers and pilots. To generate such a controller using STS, the AAR procedure is decomposed into several modes, and safety issues related with seven low-level subsystems are summarized. Then common functional demands and safety requirements are textually described. On this basis, the AAR plants and specifications are modeled by STS, and a supervisor is synthesized to control the AAR model. To prove its feasibility and correctness, a simulation environment incorporating such a logic supervisor is built and tested. The design procedures presented in this paper can be used in decision-making strategies for similar flight tasks. Supporting materials can be downloaded in Github, [ https://github.com/KevinDong0810/Failsafe-Design-for-AAR-using-STS ] including related software, input documents and output files.
Identifying and de-risking near-field opportunities through reliable pre-stack broadband attributes: examples from the Paleocene North Sea (UK–Norway) injectites play
Authors: Pernin Noémie , Feuilleaubois Laurent , Bird Tim , Reiser Cyrille
Published: June 2019

Tertiary injectites, which are re-mobilized sandstones, represent commercially attractive targets for near-field, long-reach tie-backs to existing field infrastructure above and adjacent to producing reservoirs. Injectites exhibit exceptional porosity–permeability and productivity, such that discoveries can add incremental reserves and lift production decline in mature fields. Abundant injectites are visible on seismic data in the Tertiary of the Viking Graben, but, as some disappointing wells have established, not all are hydrocarbon-charged. The challenge is to reliably distinguish hydrocarbon-filled high porosity–permeability features from tight or dry reservoirs in a cost-effective way. Regional rock physics analysis of injectite reservoirs, using well data from fields in Norway and the UK, reveals that a combination of elastic attributes can effectively discriminate lithology and hydrocarbon presences in these reservoirs. After pre-stack conditioning, broadband seismic data correlate reliably with wells, giving confidence that pre-stack seismic is faithfully imaging the elastic properties of the subsurface in lower Tertiary target intervals. Informed by rock physics analysis, a combination of broadband seismic elastic attributes is used to predict sand presence and de-risk hydrocarbon presence in reservoirs v. water-wet targets. Hydrocarbon sand distribution predicted from relative acoustic impedance and
V
P
/
V
S
matches to known accumulations and identifies remaining near-field opportunities.
One North Sea fairway analysis: revealing opportunities through data integration across scales
Authors: Roberts Paul , Jordan Oliver , Steen Øyvind , Leppard Christopher , Janssen Jose Salvadores , Baudia Emmanuelle , Ramm Alice , Helgesen Geir
Published: June 2019

While the North Sea has many well-established prolific plays, the downwards trend of annual discovered resources has cast doubt on the continued ability of the stratigraphy to provide world-class future discoveries. However, despite this downwards trend, significant discoveries can still be made, such as Johan Sverdrup (Norwegian North Sea in 2010). Furthermore, new sub-plays within this petroleum system and new unproven plays with alternative source rocks are still being tested, although often with associated higher perceived pre-drill subsurface risk (Pg) and/or lower volume potential. There is room for new optimism, however, as new approaches and technologies are deployed, which could lead to future success. The analysis of regionally extensive integrated datasets allows for the interpretation of ‘One North Sea’ fairway maps that honour detailed observations from the prospect scale through to the play scale and beyond. By integrating source-rock maturity, hydrocarbon expulsion and migration, well shows, seismically defined gas chimneys, and direct hydrocarbon indications onto regional fairway maps, hydrocarbons can be traced from the source kitchens to the traps. By utilizing a zoom-in/zoom-out methodology, models can be developed, tested and applied across the basin, allowing new ideas to emerge, de-risk established prospects and reveal under-appreciated hydrocarbon volumetric upsides.
Are Truthful Bidders Paying too Much? Efficiency and Revenue in Display Ad Auctions
Authors: Sutterer Paul , Waldherr Stefan , Bichler Martin
Published: June 2019

Display ad auctions have become the predominant means to allocate user impressions on a website to advertisers. These auctions are conducted in milliseconds online, whenever a user visits a website. The impressions are typically priced via a simple second-price rule. For single-item auctions, this Vickrey payment rule is known to be incentive-compatible. However, it is unclear whether bidders should still bid truthful in an online auction where impressions (or items) arrive dynamically over time and their valuations are not separable, as is the case with campaign targets or budgets. The allocation process might not maximize welfare and the payments can differ substantially from those paid in an offline auction with a Vickrey-Clarke-Groves (VCG) payment rule or also competitive equilibrium prices. We study the properties of the offline problem and model it as a mathematical program. In numerical experiments, we find that the welfare achieved in the online auction process with truthful bidders is high compared to the theoretical worst-case efficiency, but that the bidders pay significantly more on average compared to what they would need to pay in a corresponding offline auction in thin markets with up to four bidders. However, incentives for bid shading in these second-price auctions decrease quickly with additional competition and bidders risk losing.
Distribution and activation of matrix metalloproteinase-2 in skeletal muscle fibers
Authors: Ren Xiaoyu , Lamb Graham D. , Murphy Robyn M.
Published: June 2019

A substantial intracellular localization of matrix metalloproteinase 2 (MMP2) has been reported in cardiomyocytes, where it plays a role in the degradation of the contractile apparatus following ischemia-reperfusion injury. Whether MMP2 may have a similar function in skeletal muscle is unknown. This study determined that the absolute amount of MMP2 is similar in rat skeletal and cardiac muscle and human muscle (~10–18 nmol/kg muscle wet wt) but is ~50- to 100-fold less than the amount of calpain-1. We compared mechanically skinned muscle fibers, where the extracellular matrix (ECM) is completely removed, with intact fiber segments and found that ~30% of total MMP2 was associated with the ECM, whereas ~70% was inside the muscle fibers. Concordant with whole muscle fractionation, further separation of skinned fiber segments into cytosolic, membranous, and cytoskeletal and nuclear compartments indicated that ~57% of the intracellular MMP2 was freely diffusible, ~6% was associated with the membrane, and ~37% was bound within the fiber. Under native zymography conditions, only 10% of MMP2 became active upon prolonged (17 h) exposure to 20 μM Ca2+, a concentration that would fully activate calpain-1 in seconds to minutes; full activation of MMP2 would require ~1 mM Ca2+. Given the prevalence of intracellular MMP2 in skeletal muscle, it is necessary to investigate its function using physiological conditions, including isolation of any potential functional relevance of MMP2 from that of the abundant protease calpain-1.
Deletion of organic cation transporter Oct3 promotes hepatic fibrosis via upregulation of TGFβ
Authors: Vollmar Johanna , Kim Yong Ook , Marquardt Jens U. , Becker Diana , Galle Peter R. , Schuppan Detlef , Zimmermann Tim
Published: June 2019

Organic cation transporters (OCT) are responsible for the intracellular uptake and detoxification of a broad spectrum of endogenous and exogenous substrates. OCTs are downregulated in cholestasis, fibrosis, and hepatocellular carcinoma, but the underlying molecular mechanisms and downstream effects of OCT deletion are unknown. Oct3-knockout ( Oct3−/−; FVB.Slc22a3tm10pb) and wild-type (WT; FVB) mice were subject to escalating doses of carbon tetrachloride (CCl4) or thioacetamide (TAA) for 6 wk to induce advanced parenchymal liver fibrosis. Secondary biliary fibrosis was generated by bile duct ligation. Liver fibrosis was assessed by hydroxyproline determination, quantitative Sirius red morphometry, and quantitative real-time PCR for fibrosis and inflammation-related genes. Ductular reaction was assessed by bile duct count per field of view in hematoxylin and eosin staining. General gene expression analyses were performed in liver tissue from untreated Oct3−/− and WT mice. Finally, primary murine hepatocytes were treated with the nonselective OCT inhibitor quinine, and transforming growth factor-β1 ( Tgfβ1) protein expression was quantified by quantitative real-time PCR and Western blot. Oct3−/− mice developed significantly more fibrosis after bile duct ligation and CCl4 treatment compared with WT mice. Ductular reaction was enhanced in the long-term model. Concomitantly, Oct1 mRNA expression was downregulated during cholestatic and chemically (TAA and CCl4) induced fibrogenesis. The downregulation of Oct1 mRNA in fibrotic liver tissue reversed within 4 wk after TAA cessation. Gene expression analysis by next-generation sequencing revealed an enrichment of Tgfβ1 target genes in Oct3−/− mice. Tgfβ1 mRNA expression was significantly upregulated after chemically induced fibrosis ( P < 0.001) in Oct3−/− compared with WT mice. Accordingly, in primary murine hepatocytes functional inhibition of OCT led to an upregulation of Tgfβ1 mRNA expression. Loss of Oct3 promotes fibrogenesis by affecting Tgfβ-mediated homeostasis in mice with chronic biliary and parenchymal liver damage and fibrosis.

NEW & NOTEWORTHY We show for the first time that organic cation transporter 3 (Oct3) is not only downregulated in fibrosis but loss of Oct3 also leads to an upregulation of transforming growth factor-β contributing to fibrosis progression.
Role of estrogen and stress on the brain-gut axis
Authors: Jiang Yanyan , Greenwood-Van Meerveld Beverley , Johnson Anthony C. , Travagli R. Alberto
Published: June 2019

Symptoms of functional gastrointestinal disorders (FGIDs), including fullness, bloating, abdominal pain, and altered gastrointestinal (GI) motility, present a significant clinical problem, with a reported prevalence of 25%–40% within the general population. More than 60% of those affected seek and require healthcare, and affected individuals report a significantly decreased quality of life. FGIDs are highly correlated with episodes of acute and chronic stress and are increased in prevalence and reported severity in women compared with men. Although there is evidence that sex and stress interact to exacerbate FGID symptoms, the physiological mechanisms that mediate these sex-dependent disparities are incompletely understood, although hormonal-related differences in GI motility and visceral sensitivity have been purported to play a significant role in the etiology. In this mini review, we will discuss brain-gut axis control of GI motility and sensitivity, the influence of estrogen on GI motility and sensitivity, and stress modulation of the brain-gut axis.
Interactions of mild hypothermia and hypoxia on finger vasoreactivity to local cold stress
Authors: Keramidas Michail E. , Kölegård Roger , Mekjavic Igor B. , Eiken Ola
Published: June 2019

We examined the interactive effects of mild hypothermia and hypoxia on finger vasoreactivity to local cold stress. Eight male lowlanders performed, in a counterbalanced order, a normoxic and a hypoxic (partial pressure of oxygen: ~12 kPa) hand cold provocation (consisting of a 30-min immersion in 8°C water), while immersed to the chest either in 21°C [cold trials; 0.5°C fall in rectal temperature (Trec) from individual preimmersion values], or in 35.5°C water, or while exposed to 27°C air. The duration of the trials was kept constant in each breathing condition. Physiological (Trec, skin temperature, cutaneous vascular conductance, oxygen uptake) and perceptual (thermal sensation and comfort, local pain, affective valence) reactions were monitored continually. Hypoxia accelerated the drop in Trec by ~14 min ( P = 0.06, d = 0.67). In the air-exposure trials, hypoxia did not alter finger perfusion during the local cooling, whereas it impaired the finger rewarming response following the cooling ( P < 0.01). During the 35.5°C immersion, the finger vasomotor tone was enhanced, especially in hypoxia ( P = 0.01). Mild hypothermia aggravated finger vasoconstriction instigated by local cooling ( P < 0.01), but the response did not differ between the two breathing conditions ( P > 0.05). Hypoxia tended to attenuate the sensation of coldness ( P = 0.10, r = 0.40) and thermal discomfort ( P = 0.09, r = 0.46) in the immersed hand. Both in normoxia and hypoxia, the whole body thermal state dictates the cutaneous vasomotor reactivity to localized cold stimulus.
Different vasodilator mechanisms in intermediate- and small-sized arteries from the hindlimb vasculature of the toadRhinella marina
Authors: Cameron Melissa S. , Donald John A.
Published: June 2019

In this study, myography was used to determine the effect of arterial size on nitric oxide (NO) vasodilatory mechanisms in the hindlimb vasculature of the toad Rhinella marina. Immunohistochemical analysis showed NO synthase (NOS) 1 immunoreactivity in perivascular nitrergic nerves in the iliac and sciatic arteries. Furthermore, NOS3 immunoreactivity was observed in the vascular smooth muscle of the sciatic artery, but not the endothelium. Acetylcholine (ACh) was used to facilitate intracellular Ca2+signaling to activate vasodilatory pathways in the arteries. In the iliac artery, ACh-mediated vasodilation was abolished by blockade of the soluble guanylate cyclase pathway with the soluble guanylate cyclase inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, 10−5M) and blockade of the prostaglandin signaling pathway with indomethacin (10−5M). Furthermore, disruption of the endothelium had no effect on the ACh-mediated vasodilation in the iliac artery, and generic inhibition of NOS with Nω-nitro-l-arginine (3 × 10−4M) significantly inhibited the vasodilation, indicating NO signaling. In contrast to the iliac artery, ACh-mediated vasodilation of the sciatic artery had a significant endothelium-dependent component. Interestingly, the vasodilation was not significantly affected by Nω-nitro-l-arginine, but it was significantly inhibited by the specific NOS1 inhibitor N5-(1-imino-3-butenyl)-l-ornithine (vinyl-l-NIO, 10−4M). ODQ mostly inhibited the ACh-mediated vasodilation. In addition, indomethacin also significantly inhibited the ACh-mediated vasodilation, indicating a role for prostaglandins in the sciatic artery. This study found that the mechanisms of vasodilation in the hindlimb vasculature of R. marina vary with vessel size and that the endothelium is involved in vasodilation in the smaller sciatic artery.
Sex differences in diabetes and kidney disease: mechanisms and consequences
Authors: Shepard Blythe D.
Published: June 2019

Type 1 and type 2 diabetes, along with their accompanying hyperglycemia, are associated with a multitude of comorbidities including the development of diabetic kidney disease. Although the hallmarks of these metabolic disorders have been well characterized in population and animal studies, it is becoming increasingly apparent that diabetes manifests itself differently in men and women. This review summarizes the recent diabetic literature with a focus on known sex differences in clinical and preclinical studies. It explores the physiological differences of glucose handling and the development of diabetes between men and women. This review also uncovers potential mechanisms for these differences, honing in on the vital role that sex hormone signaling plays in the progression of diabetes and renal complications.
Spike-field Granger causality for hybrid neural data analysis
Authors: Gong Xiajing , Li Wu , Liang Hualou
Published: June 2019

Neurotechnological innovations allow for simultaneous recording at various scales, ranging from spiking activity of individual neurons to large neural populations’ local field potentials (LFPs). This capability necessitates developing multiscale analysis of spike-field activity. A joint analysis of the hybrid neural data is crucial for bridging the scales between single neurons and local networks. Granger causality is a fundamental measure to evaluate directional influences among neural signals. However, it is mainly limited to inferring causal influence between the same type of signals—either LFPs or spike trains—and not well developed between two different signal types. Here we propose a model-free, nonparametric spike-field Granger causality measure for hybrid data analysis. Our measure is distinct from existing methods in that we use “binless” spikes (precise spike timing) rather than “binned” spikes (spike counts within small consecutive time windows). The latter clearly distort the information in the mixed analysis of spikes and LFP. Therefore, our spectral estimate of spike trains is directly applied to the neural point process itself, i.e., sequences of spike times rather than spike counts. Our measure is validated by an extensive set of simulated data. When the measure is applied to LFPs and spiking activity simultaneously recorded from visual areas V1 and V4 of monkeys performing a contour detection task, we are able to confirm computationally the long-standing experimental finding of the input-output relationship between LFPs and spikes. Importantly, we demonstrate that spike-field Granger causality can be used to reveal the modulatory effects that are inaccessible by traditional methods, such that spike→LFP Granger causality is modulated by the behavioral task, whereas LFP→spike Granger causality is mainly related to the average synaptic input.

NEW & NOTEWORTHY It is a pressing question to study the directional interactions between local field potential (LFP) and spiking activity. In this report, we propose a model-free, nonparametric spike-field Granger causality measure that can be used to reveal directional influences between spikes and LFPs. This new measure is crucial for bridging the scales between single neurons and neural networks; hence it represents an important step to explicate how the brain orchestrates information processing.