Tension Development Research Articles

Differential Mesenteric Venous and Arterial Vascular Reactivity to Adenosine between Rats, Dogs, Mini‐pigs, and Human

It is well established that adenosine induces arterial vasodilation in various vascular beds. However, its effect on the venous circulation is still largely unknown. The splanchnic system receives approximately 25% of cardiac output (CO) and contains approximately 20% of total blood volume. Mesenteric (part of splanchnic system, o. d. 150–250 μm) arteries (MA) and their adjacent veins (MV) from rats, dogs, mini‐pigs and humans were isolated and mounted on a myograph (DMT Technology, USA). Vessels were preconstricted with 1 μM phenylephrine (PE) for arteries and prostaglandin F2α (PGF2α) for veins. Cumulative concentrations of 5’‐N‐Ethylcarboxamidoadenosine (NECA, 10−11 – 10−5 M), a non‐specific adenosine agonist, were applied and evaluated. Tension development was normalized to the tension induced by PE/PGF2α as %. NECA induced a concentration dependent arterial vasodilation in all 3 animals and human MA (Fig. 1). The effects were very similar in all 3 animals (maximum of 91.09±10.94% to 93.88±1.93%), however human responses were less pronounced (maximum of 59.14±4.61%). Interestingly, veins from all species responded to NECA very differently (Fig. 2). MVs from rats were the only vessels that constricted strongly in response to NECA (182.94±17.52% of pre‐constriction), which has not been previously reported (Figs. 2– 3). NECA induced vasodilation in MV from the other species varied. NECA induced vasodilation in MV from dogs were similar to MA at high concentrations (Fig. 6, 10−8 M and above). However, MV from mini‐pig (Fig. 5) and human (Fig. 6) responses were minimal (Fig. 2, maximum of 24.56±14.67% in mini‐pig and 33.54±9.61% relaxation in human) compared to 92.93±2.26% relaxation in dogs. In conclusion, although mesenteric arterial vascular reactivity responds similarly to adenosine among species, mesenteric venous vascular reactivity responses varied greatly to adenosine among species. MVs from rats were the only vessel constricted strongly in response to NECA. Caution is advised when choosing animal models for studying vascular reactivity.Figure 1Figure 2Figure 3Figure 4Figure 5Figure 6

Military chaplaincy in Sweden: A contemporary perspective

Pastors serving as military chaplains have been an integral part of the Swedish Armed Forces for hundreds of years. This close relationship has continued even after the Church of Sweden was formally separated from the state in 2000. Yet contemporary research drawing from experiences of Swedish military chaplains during their pastoral and spiritual assignments within a military context is virtually non-existent. This research explores the contemporary situation for military chaplaincy in Sweden through the lenses of proportional accessibility for military personnel, availability to civilian congregations, increasing cultural and ethnic diversity, religious embeddedness in military culture, theological tension, and personal identity development among chaplains. It furthermore suggests that military chaplains navigate a complex situation: they are expected to serve professional service members, many of whom have war zone experiences, in addition to shepherding increasing volumes of conscripts now that conscription has been reinstated, all within a new interreligious paradigm.

Effectiveness of geosynthetic reinforcement for load transfer in column-supported embankments

Many column-supported embankment (CSE) design methods include geosynthetic reinforcement for vertical load transfer and/or settlement reduction regardless of project conditions. However, geosynthetic reinforcement may not be necessary for all applications, particularly if a sufficiently thick and strong soil layer overlies the compressible soil. A strong soil layer can transfer embankment loads to the columns without much differential settlement at the base of the embankment, limiting the development of tension in the reinforcement. If weak and compressible soil extends to the ground surface and the area replacement ratio is low, differential settlements may be so large that it may not be practically possible to provide enough reinforcement to avoid excessive strain or rupture. This paper describes parametric studies using the Load Displacement Compatibility method to investigate the influences of embankment height, geosynthetic stiffness, column diameter, and thickness of an upper sand layer on geosynthetic strain, differential settlement at the base of the embankment, and load distribution among the CSE components. Results of the parametric study show that site conditions, CSE system geometry, and performance requirements limit the range of circumstances for which geosynthetic reinforcement for settlement reduction is needed, effective, and practically possible.

Flux Of Glucose Through Pentose Phosphate Pathway And Glycolysis In Mouse Hearts Subjected To Low‐Flow Ischemia

IntroductionThe molecular events that lead to irreversible myocardial damage during severe ischemia remain poorly understood. Changes in cytosolic redox status and ability of mitochondria to oxidatively metabolize fatty acids and carbohydrates have been implicated in ischemic Injury. The pentose phosphate pathway (PPP) produces NADPH, which can be used to maintain glutathione in its reduced state, providing protection against oxidative damage. The rate of glycolysis during ischemia determines extent of ischemic injury. We investigated flux of glucose through PPP and glycolysis in mouse hearts subjected to low‐flow ischemia in this study.MethodsIsolated mouse hearts were perfused in Langendorff mode with 10mM [1,2‐13C2]‐glucose for 60min, followed by 90min low‐flow ischemia (perfused at 10% of baseline flow rate). The cardiac function was recorded with PowerLab Data Acquisition Systems. Lipid peroxidation was determined with Colorimetric/Fluorometric Assay Kit. The flux of glucose through the PPP and glycolysis was assessed by the contribution of the doublet (D23, [2,3‐13C2]‐lactate) and singlet (S3, [3‐13C]‐lactate) to the total 13C‐NMR signal of lactate C3 in effluent, respectively.Results90min low‐flow ischemia resulted in both systolic dysfunction (as indicated by decreased left ventricular systolic pressure, rate of tension development and developed pressure) and diastolic dysfunction (as indicated by increased end diastolic pressure and decreased rate of relaxation) accompanied with increased lipid peroxidation. Furthermore, the flux of glucose through PPP increased substantially and correlatively with that through glycolysis.Conclusion[1,2‐13C2]‐glucose can be used to simultaneously assess flux of glucose through PPP and glycolysis. The flux of glucose through both PPP and glycolysis increased during myocardial low‐flow ischemia.Support or Funding InformationThis study was supported by Department Fund.

Exercise Pressor Reflex in UC Davis Type‐2 Diabetes Mellitus (UCD‐T2DM) Rats Prior to the Onset of Diabetes

Both the exercise pressor reflex and mechanoreflex are exaggerated after the development of T2DM in UCD‐T2DM rats. Whether the pressor reflex is also exaggerated before UCD‐T2DM rats developed diabetes is not known. Therefore, the purpose of this study was to determine if both the exercise pressor reflex and mechanoreflex are exaggerated in the UCD‐T2DM rats before the onset of diabetes.MethodsFor this study, we used young (8–12 wk old), male (n=12) and female (n=10), non‐diabetic UCD‐T2DM rats and age‐matched, male (n=11) and female (n=7), healthy Sprague Dawley rats. The exercise pressor reflex was evoked by statically and intermittently contracting the hindlimb muscle for 30s, and the mechanoreflex was evoked by passively stretching the Achilles tendon for 30s. Changes in mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were continuously measured during both contraction and stretch.ResultsWe found that fasting blood glucose for both groups was below the threshold for diagnosis of diabetes (200mg/dl). Statically contracting the muscle did not significantly increase peak MAP (CTL: 11 ± 1 mmHg, n=12; UCD‐T2DM: 14 ± 2 mmHg, n=13, p>0.05), HR (CTL: 12 ± 4 bpm, n=12; UCD‐T2DM: 14 ± 5 bpm, n=13, p>0.05), or RSNA (CTL: 40 ± 20 %, n=4; UCD‐T2DM: 39 ± 23 %, n=3, p>0.05) in UCD‐T2DM rats compared to control rats with similar developed tensions. Likewise, intermittently contracting the muscle did not significantly increase peak MAP (CTL: 14 ± 2 mmHg, n=13; UCD‐T2DM: 14 ± 2 mmHg, n=6, p>0.05), HR (CTL: 16 ± 3 bpm, n=13; UCD‐T2DM: 14 ± 5 bpm, n=6, p>0.05), or RSNA (CTL: 73 ± 42 %, n=5; UCD‐T2DM: 34 ± 14 %, n=2, p>0.05) in UCD‐T2DM rats compared to control rats with similar developed tensions. Moreover, stretching the Achilles tendon did not significantly increase peak MAP (CTL: 15 ± 3 mmHg, n=11; UCD‐T2DM: 13 ± 1 mmHg, n=14, p>0.05), HR (CTL: 11 ± 4 bpm, n=11; UCD‐T2DM: 14 ± 2 bpm, n=14, p>0.05), or RSNA (CTL: 60 ± 12 %, n=3; UCD‐T2DM: 24 ± 19 %, n=4, p>0.05) in UCD‐T2DM rats compared to control rats with similar developed tensions.ConclusionWe conclude that both the exercise pressor reflex and the mechanoreflex are not exaggerated in UCD‐T2DM rats before the onset of diabetes. This study suggests that young UCD‐T2DM rats have similar MAP, HR, and RSNA responses to both muscle contraction and tendon stretch as seen in age‐matched Sprague Dawley rats prior to the onset of diabetes.Support or Funding InformationThis project was supported by NIH R01 HL144723.

The correlation between gadget usage and cervical muscle tension among the community of gamers

This study aimed to determine the correlation between gadget usage and the tension of cervical muscles in the gamers community. This study is an analytical study using a cross-sectional approach. This research was conducted at the Game Play Unknown Battleground (PUBG) Community in Makassar. Forty people (n=40) were included in the present study. Data including age, gender, and intensity (duration) of gadget usage, were collected using a questionnaire. Cervical muscle tension was assessed by palpation test and using goniometer. The relationship between the intensity of gadget usage in-game players and cervical muscle tension were found statistically significant (p<0.05). In addition, we assume that age plays a role in the development of cervical muscle tension (p<0.05). The intensity of gadget usage and age have a positive correlation with the development of cervical muscle tension in-game players.

Valuing Value in Innovation Ecosystems: How Cross-Sector Actors Overcome Tensions in Collaborative Sustainable Business Model Development

This article aims to uncover the processes of developing sustainable business models in innovation ecosystems. Innovation ecosystems with sustainability goals often consist of cross-sector partners and need to manage three tensions: the tension of value creation versus value capture, the tension of mutual value versus individual value, and the tension of gaining value versus losing value. The fact that these tensions affect all actors differently makes the process of developing a sustainable business model challenging. Based on a study of four sustainably innovative cross-sector collaborations, we propose that innovation ecosystems that develop a sustainable business model engage in a process of valuing value in which they search for a result that satisfies all actors. We find two different patterns of valuing value: collective orchestration and continuous search. We describe these patterns and the conditions that give rise to them. The identification of the two patterns opens up a research agenda that can shed further light on the conditions that need to be in place in order for an innovation ecosystem to develop effective sustainable business models. For practice, our findings show how cross-sector actors in innovation ecosystems may collaborate when developing a business model around emerging sustainability-oriented innovations.

Loss of smooth muscle α-actin effects on mechanosensing and cell-matrix adhesions.

Mutations in ACTA2, encoding smooth muscle α-actin, are a frequent cause of heritable thoracic aortic aneurysm and dissections. These mutations are associated with impaired vascular smooth muscle cell function, which leads to decreased ability of the cell to sense matrix-mediated mechanical stimuli. This study investigates how loss of smooth muscle α-actin affects cytoskeletal tension development and cell adhesion using smooth muscle cells explanted from aorta of mice lacking smooth muscle α-actin. We tested the hypothesis that reduced vascular smooth muscle contractility due to a loss of smooth muscle α-actin decreases cellular mechanosensing by dysregulating cell adhesion to the matrix. Assessment of functional mechanical properties of the aorta by stress relaxation measurements in thoracic aortic rings suggested two functional regimes for Acta2−/−mice. Lower stress relaxation was recorded in aortic rings from Acta2−/−mice at tensions below 10 mN compared with wild type, likely driven by cytoskeletal-dependent contractility. However, no differences were recorded between the two groups above the 10 mN threshold, since at higher tension the matrix-dependent contractility may be predominant. In addition, our results showed that at any given level of stretch, transmural pressure is lower in aortic rings from Acta2−/−mice than wild type mice. In addition, a three-dimensional collagen matrix contractility assay showed that collagen pellets containing Acta2−/−smooth muscle cells contracted less than the pellets containing the wild type cells. Moreover, second harmonic generation non-linear microscopy revealed that Acta2−/−cells locally remodeled the collagen matrix fibers to a lesser extent than wild type cells. Quantification of protein fluorescence measurements in cells also showed that in absence of smooth muscle α-actin, there is a compensatory increase in smooth muscle γ-actin. Moreover, specific integrin recruitment at cell–matrix adhesions was reduced in Acta2−/−cells. Thus, our findings suggest that Acta2−/−cells are unable to generate external forces to remodel the matrix due to reduced contractility and interaction with the matrix.Impact statementThoracic aneurysm formation is characterized by progressive enlargement of the ascending aorta, which predisposes the aorta to acute aortic dissection that can lead to sudden death. SMCs in the aorta play an integral role in regulating vessel wall contractility and matrix deposition in the medial layer. Recent studies show that mutations in genes associated with actomyosin apparatus reduce SMC contractility, increasing susceptibility to TAAD. Single-cell experiments enable discrete measurements of transient microscopic events that may be masked by a macroscopic average tissue behavior. Biophysical methods combined with microscopy techniques aid in understanding the specific roles of adhesion and cytoskeletal proteins in regulating SMC mechanosensing when SMα-actin is disrupted. Our findings suggest that Acta2−/−cells have increased SMγ-actin and decreased integrin recruitment at cell–matrix adhesion, hence a synthetic phenotype with reduced cellular mechanosensing.

Effect of supercritical CO2 treatment and kiln drying on collapse in Eucalyptus nitens wood

Collapse-prone timbers such as species of Eucalyptus are poorly utilised due to low conversion rates that necessitate long pre-drying times. A supercritical CO2 lumen water expulsion pre-treatment prior to kiln drying is proposed to bypass lengthy pre-drying. After drying (air, kiln or oven drying), shrinkage, collapse, washboard depression and checking of Eucalyptus nitens were determined using image analysis of 0.8 mm thick wafers and 5 mm thick biscuits. Lumen water expulsion-kiln drying reduced collapse by 75% and washboard depression by 71%, compared to drying from green. As water is removed from the water conductive tissue (vessels, rays, and fibre-tracheids) by lumen water expulsion, the water column is broken throughout the specimen, thereby disrupting the development of meniscus-induced water tension as subsequent drying occurs. Remaining water is proposed to reside in the non-water-conductive fibre tissue. If the process can be applied on large scale to Eucalyptus nitens, there is the opportunity for higher conversion rates to increase the commercial viability of solid wood products.

Preserved single muscle fiber specific force in facioscapulohumeral muscular dystrophy.

To investigate single muscle fiber contractile performance in muscle biopsies from patients with facioscapulohumeral muscular dystrophy (FSHD), one of the most common hereditary muscle disorders. We collected 50 muscle biopsies (26 vastus lateralis, 24 tibialis anterior) from 14 patients with genetically confirmed FSHD and 12 healthy controls. Single muscle fibers (n = 547) were isolated for contractile measurements. Titin content and titin phosphorylation were examined in vastus lateralis muscle biopsies. Single muscle fiber specific force was intact at saturating and physiologic calcium concentrations in all FSHD biopsies, with (FSHDFAT) and without (FSHDNORMAL) fatty infiltration, compared to healthy controls. Myofilament calcium sensitivity of force is increased in single muscle fibers obtained from FSHD muscle biopsies with increased fatty infiltration, but not in FSHD muscle biopsies without fatty infiltration (pCa50: 5.77-5.80 in healthy controls, 5.74-5.83 in FSHDNORMAL, and 5.86-5.90 in FSHDFAT single muscle fibers). Cross-bridge cycling kinetics at saturating calcium concentrations and myofilament cooperativity did not differ from healthy controls. Development of single muscle fiber passive tension was changed in all FSHD vastus lateralis and in FSHDFAT tibialis anterior, resulting in increased fiber stiffness. Titin content was increased in FSHD vastus lateralis biopsies; however, titin phosphorylation did not differ from healthy controls. Muscle weakness in patients with FSHD is not caused by reduced specific force of individual muscle fibers, even in severely affected tissue with marked fatty infiltration of muscle tissue.

Tensions as a Frame for Managing Work in Collaborative Workplaces: A Literature Review

Companies are increasingly implementing Collaborative Workplaces (CWs) to promote office collaboration and flexibility. Despite the rapid diffusion of CWs across industries and organizations, research findings suggest that their benefits often fail to materialize, due to the existence of tensions and contradictions that develop through the daily actions and interactions of workplace users. This literature review sheds some light on the development of tensions and contradictions in CWs by focusing on their implications for social relations at work. This review identifies the oppositional tensions that surface in CW research findings: flexibility vs. structure, fluidity vs. stability, and accessibility vs. privacy. In disclosing the underlying mechanisms, this study tied these tensions and their management to the autonomy-control paradox that emerges in CWs. It concludes by suggesting some approaches that are available to managers to deal with tensions and avoid inconsistencies.

Engineering political fluency: Identifying tensions in the political identity development of engineering majors

AbstractBackgroundEngineering can play a significant role in the public good. Changing political dynamics and a surge in activism among the broader science community have only heightened this reality. Yet little published research exists about how engineering students develop both their technical and political identities to affect the broader society.PurposeThis study sought to extend and complicate notions of engineering education that grapple with the political preparation of undergraduate students. The research question was the following: In what ways do students majoring in engineering navigate the process of acquiring an attitude of political fluency?DesignCase study methodology informed the research design with undergraduate engineering majors serving as the primary unit of analysis. Focus groups involving a total of 20 students and a review of electronic documents were conducted across three institutions in the Northeastern U.S. to produce data for this qualitative study.ResultsEngineering students described experiencing the following tensions that shaped their political involvement: (a) limited exposure to politically motivating events, (b) privileging private gains while noting aspirational contributions to the public good, and (c) politics positioned at the periphery of engineering.ConclusionsConsistent with increased attention to social justice and civic engagement outcomes, political engagement is a critical educational outcome for engineering educators to cultivate. However, if engineering programs are to contribute to the political identity formation of their students, structural changes in the preparation of engineering students will be necessary.

ИССЛЕДОВАНИЕ ГЕОДИНАМИКИ МАССИВА В ЗОНЕ СОПРЯЖЕНИЯ ОЧИСТНЫХ И ПОДГОТОВИТЕЛЬНЫХ ВЫРАБОТОК

Актуальность. При подземной разработке скальных металлических месторождений в зоне сопряжения очистных и подготовительных выработок динамика напряжений и деформаций осложняет процессы добычи руд и снижает эффективность производства. На участке сопряжения выработок деформации в породах служат источником локальных обрушений. Исследование механизма развития напряжений и деформаций в зоне вскрытия рудного тела горными выработками позволяет скорректировать параметры очистных работ, снижая результаты негативного проявления горного давления. Основными методами прогнозирования темпов развития горного давления являются натурные исследования с использованием геофизических и маркшейдерских методов. Полученные значения напряжений и деформаций являются основой для объективной оценки состояния массива в зоне сопряжения выработок. Результаты. По данным натурных исследований строили графики изменения деформации крепи во времени и пространстве вокруг выработки и оценивали механизм развития горного давления под влиянием горных работ. Определено, что массив характеризуется тремя участками действующих напряжений. Установлен незначительный рост напряжений в течение первых трех месяцев очистных работ, а также более медленные темпы нарастания напряжений в породе, чем в руде. Выявлено, что добыча руд в зоне сопряжения выработок по характеру развития деформаций подразделяется на три фазы, подчиняющиеся закономерностям. Выводы. Установленные закономерности развития напряжения в зоне ослабления массивом позволяют прогнозировать состояние массива с достаточной для управления детализацией, что дает возможность корректировать параметры разработки с получением экономического эффекта за счет уменьшения разубоживания руд и уменьшения опасности для горнорабочих.

투해머 장력 측정 장치 개발

투해머의 투사거리는 투사속도와 가장 관련이 큰 것으로 알려져 있으며, 회전 시 장력의 유지여부가 투사속도 형성에 큰 영향을 미치는 것으로 보고되고 있다. 이에 본 연구에서는 현장에서의 실시간 측정 및 표시가 가능한 줄부착형 투해머 장력측정장치를 개발하고, 캘리브레이션 시험과 파일럿 시험을 통하여 그 유용성을 확인하고자 하였다. 공인 인장압축시험기를 이용한 캘리브레이션 시험 결과, 개발된 측정장치는 인장시험기의 인가 값과 0N∼2000N 범위에서 상대오차 평균 0.27%와 표준편차 0.26%를 기록하였으며, 투척거리 약 20m의 5회 파일럿 시험에서 회로의 동작과 무선전송이 정상적으로 이루어짐을 확인하였다. 제안된 장치는 투척훈련 시 실시간 장력 데이터 측정․표시와 훈련동영상 제공이 가능하도록 개발되어, 실제 투척연습에의 활용을 통해 경기력 향상에 기여할 것으로 판단된다.

Artificial oxygen carrier improves fatigue resistance in slow muscle but not in fast muscle in a rat in situ model.

The effects of liposome-encapsulated hemoglobin with high O2 affinity (h-LEH), an artificial O2 carrier in skeletal muscle, were studied by in situ fatigue resistance test in fast-type plantaris (PLT) and slow-type soleus (SOL) muscles with or without ischemia in the rat. The distal tendons of PLT and SOL muscles were isolated in situ and individually attached to the force transducers to record the developed tension in response to stimuli (80Hz tetanus train, 1.5minutes) to the ipsilateral sciatic nerve. The fatigue resistance test (five sets separated by 2-minute rests) was evaluated in terms of tension attenuation (fatigue) from the initial to the last tension (A) during each set, attenuation of the initial (B) or last tension (C) in each set, as compared to the first set in the presence or absence of ischemia or h-LEH (10mL/kg). While ischemia significantly enhanced fatigue only in PLT, h-LEH showed no effect regardless of the perfusion pattern (normal/ischemia) or muscle-type (PLT/SOL) during each set (A). In parameter (B), set-by-set fatigue development was observed in PLT, whereas h-LEH-SOL showed a trend of advanced fatigue resistance. Such trends became clear in the parameter C (last tension), because h-LEH-SOL exerted, rather than decreased, the tension enhancement regardless of the presence or absence of ischemia, whereas there were no h-LEH effects in PLT. In addition, faster recovery of the nicotinamide adenine dinucleotide content in the muscle after 10minutes of all fatigue tests was observed in h-LEH-SOL, while saline-SOL still showed a significantly higher value than that of control. These results suggested that additional O2 supply by h-LEH may accelerate the tricarboxylic acid cycle/electron transport chain in slow-type aerobic SOL muscle containing abundant mitochondria and contribute to the faster removal of muscle fatigue substances such as lactate.

P4428Physical exercise during uncontrolled systemic arterial hypertension

Abstract Introduction Physical exercise reduces systemic arterial blood pressure and improves cardiac remodeling. However, the effects of exercise during uncontrolled arterial hypertension remains poorly understood. This study evaluated the influence of physical training on cardiac remodeling in untreated spontaneously hypertensive rats (SHR). Methods Four experimental groups were used: sedentary (W-SED n=27) and trained (W-EX, n=31) normotensive Wistar rats, and sedentary (SHR-SED, n=27) and exercised (SHR-EX, n=32) hypertensive rats. At 13 months old, the exercise groups underwent treadmill exercise five days a week, for four months. Echocardiogram was performed to evaluate cardiac structures and function. In vitro myocardial function was analyzed in left ventricular (LV) papillary muscle preparations. Myocardial collagen was quantified by histology and hydroxyproline concentration and antioxidant enzyme activity was assessed by spectrophotometry. NADPH oxidase activity was analyzed by lucigenin reduction. Protein expression was quantified by Western blot. Matrix metalloproteinases (MMP) activity was evaluated by zymography. Statistical analyzes: two factor ANOVA and Bonferroni or Kruskal-Wallis and Dunn tests. Results Systolic blood pressure was higher in SHR groups. Exercised groups had greater physical capacity. Frequency of heart failure features was higher in hypertensive groups than controls; SHR-EX had a lower frequency of pleural effusion and tachypnea than SHR-SED. Echocardiogram showed lower LV wall thickness, LV relative wall thickness, left atrium diameter, and relaxation time in SHR-EX than SHR-SED. Myocardial function was better in SHR-EX (positive derivative of developed tension) than SHR-SED. SHR-EX had higher antioxidant enzyme activity than SHR-SED. Lipid hydroperoxide concentration, myocyte diameters, and phosphorylated JNK and total IkB protein expression were higher in hypertensive than control groups. Hydroxyproline, malondialdehyde, NADPH oxidase activity, and protein expression of collagen III, lysyl oxidase, TIMP-1, total JNK, phosphorylated p38, phosphorylated and total p65, and phosphorylated IkB did not differ between groups. Interstitial collagen fraction, MMP-2 activity, and protein expression of total p38, and total and phosphorylated ERK were higher in SHR-SED than W-SED. Exercise reduced MMP-2 activity and phosphorylated ERK in hypertensive rats. Conclusion Physical exercise improves physical capacity, reduces the frequency of heart failure features, and attenuates cardiac remodeling in spontaneously hypertensive rats. In addition, exercise increases antioxidant enzyme activity, decreases ERK phosphorylation and MMP-2 activity, and attenuates total ERK protein expression. Acknowledgement/Funding Fapesp, CNPq, Capes and UNESP

P5373Mechanical heterogeneity across the left ventricular wall - a study using intact multicellular preparations

Abstract Introduction The importance of transmural heterogeneity for left ventricular (LV) function is well recognised. Mid-wall systolic shortening is a better predictor of cardiovascular morbidity than ejection fraction. While variation in electrical properties is well-documented, transmural mechanical differences remain poorly characterised. Most studies are based on isolated cells or permeabilised preparations, with limited data acquired in living multicellular myocardial preparations. Purpose Here, we test the hypothesis that heterogeneity in intrinsic mechanical properties exists across the LV wall. We use a novel intact organotypic preparation, myocardial slices, from different layers of the ventricular wall. Methods 300μm-thick living tangential myocardial slices with preserved structure and function were sequentially obtained from LVs of adult male Sprague-Dawley rats using a high precision vibrating microtome. Each slice corresponded to a different layer of the LV wall. Slices from endo-, mid- and epicardium were used (Fig 1C). To rule out transmural differences in Ca2+ -response, force-Ca2+ experiments were first performed on slices at 2.1μm sarcomere length (SL) with a half-log [Ca2+] (10–3.5 to 10–2.0 M) in the supernatant. SL-tension experiments were then conducted by measuring steady state force of isometrically twitching slices at 2.00-, 2.10-, 2.20-, 2.25-, 2.35-, &amp; 2.40μm SL in Tyrode solution containing the EC50 [Ca2+], determined from the force-Ca2+ experiments. Analysis of co-variance and two-way ANOVA with Turkey post-hoc were used for statistical comparisons. Results Force-Ca2+ data were fit with a variable hill-slope. As no differences in the EC50 of endo-, mid-, and epi- slices (n=6, 5, 4) were found, length-tension experiments were performed at a common EC50 [Ca2+] (10–2.54 M). Increasing SL increased developed tension in all slices. However, mid- generated significantly greater tension than endo- at 2.25-, 2.35-, &amp; 2.40μm SL but not epi- slices (p=0.006, 0.045, 0.048 respectively) (Fig 1A). A linear regression was fit to the SL-active tension data of the different layers. Epi- had significantly steeper slope than endo- (p=0.0137) suggesting greater ability to respond to stretch (n=6, 5, 6) (Fig 1B). Increasing SL increased passive tension in all slices. Epi- was significantly stiffer than endo- at 2.35- &amp; 2.40μm SL (p=0.023, 0.0002 respectively). Mid- was also significantly stiffer than endo- at 2.40μm SL (p=0.0007) (n=6, 5, 6) (Fig 1A). Figure 1. A: SL-Tension; B: Slopes; C: Schematic Conclusions Here, we demonstrate for the first time the use of myocardial slices for investigation of transmural mechanics in intact adult cardiac tissue. We show that both active and passive mechanical properties differ across the LV wall. Coupled with transmural electrical differences, mechanical heterogeneity may act to orchestrate the normal operation of the whole heart. In disease, loss of heterogeneity may contribute to impaired LV function and accelerate clinical deterioration. Acknowledgement/Funding British Heart Foundation (MBBS PhD Studentship FS/18/37/33642)

What Empirically Based Research Tells Us About Game Development

This paper reviews empirically grounded research on practices in game development with the intent to give a comprehensive overview of contemporary development practices used in the video game industry. While there are many intangible elements that inform game development processes, this review specifically covers the more immediate practical challenges. The review covers a total of 48 papers published between 2006 and 2016, which were all subjected to thematic analysis by three reviewers. The results of the review show that an almost universal characteristic of game development is that it is almost impossible to accurately plan a development project in detail, largely due to the soft requirements inherent in game production which emerge mid-process during development projects, during when testing is coupled with continuous ideation and refinement. Practicing game developers have created their own frameworks that accommodate for this lack of planning. They include flat hierarchies, democratic decision-making, creative autonomy, and informal communication, which are designed to create an environment that maintains creativity and openness to product changes long into the production process. These frameworks vary significantly between studios and often between individual projects. This review also shows that the term ‘Agile’, while often used by both researchers and developers to characterize the process of game development, is not an apt descriptor of how game developers actually work. Agile is used as shorthand for unstructured and flexible development, rather than serving as a descriptor of a definable or unified work method. Finally, as companies develop more complicated hierarchies of stakeholders and staff, the desired flexibility and autonomy of game development becomes increasingly complicated to maintain, and often necessitates more formalized management processes and company structures. In these cases, inherent tensions of game development become more pronounced, and continuous creativity is hard to maintain due to a growing need to formalize processes.

Stress generation during anisotropic lithiation in silicon nanopillar electrodes: A reactive force field study

Models that are developed to investigate lithiation-induced stress in high-volume-change electrodes are often based on continuum approaches with simplifying assumptions. In this work, we investigate stress generation during the first lithiation of crystalline silicon electrodes solely using atomistic simulations with chemo-mechanical fidelity. We use a 〈100〉-oriented silicon nanopillar as a model system and perform molecular statics simulations with a reactive force field. The simulation approach incorporates the key physical feature of the lithiation – anisotropic formation and migration of an atomistically-sharp phase boundary. The resulting stress fields show the development of hoop tension near the nanopillar surface, which drives surface fracture at angular sites between two adjacent {110} facets. This work links the atomic-level physics of the lithiation directly with the stress generation and accounts for the geometric effect of the sharp phase boundary.

Chronic Alcohol Consumption, but not Acute Intoxication, Decreases In Vitro Skeletal Muscle Contractile Function.

Skeletal muscle myopathy accompanying chronic alcohol misuse results in part from a decrease in protein synthesis typically observed in type II-rich muscles that leads to muscle weakness. However, there is a paucity of studies investigating whether the alcohol-induced weakness is intrinsic to the muscle or results primarily from the loss of muscle mass. The present study determines whether acute alcohol (ethanol) intoxication or chronic alcohol consumption decreases the intrinsic contractile function of muscle. Adult male mice were randomly assigned to the chronic alcohol group or given a binge dose of alcohol, and contractile characteristics of the extensor digitorum longus (EDL) were determined in vitro. The weight and physiological cross-sectional area (PCSA) of the EDL were decreased in alcohol-fed mice. Maximum twitch and tetanic tension were also reduced, and there was a downward shift of the absolute force-frequency curve in alcohol-fed mice. However, no alcohol-induced changes were noted when these contractile parameters were normalized for the lower PCSA. Alcohol-fed mice demonstrated greater fatigability, and alcohol-induced decreases in postfatigue specific twitch and tetanic force were independent of a decreased PCSA. Furthermore, postfatigue recovery of muscle force over time was reduced. While alcohol did not alter the content of high-energy phosphates or oxidative phosphorylation complexes I-V, it did reduce myosin heavy chain and troponin-T content. In contrast, contractile properties were not altered when examined 2hours after binge alcohol. These data demonstrate chronic alcohol consumption decreases isometric and tetanic tension development due to a reduction in muscle CSA, whereas the increased fatigability observed was independent of muscle mass. As none of the functional changes were produced by acute alcohol, which produced higher blood alcohol levels than chronic ingestion, our data suggest defects in intrinsic muscle contractility require sustained intake and appear independent of defects in basal energy production.