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ABSTRACTThis study investigates international research collaboration (IRC) dynamics between the United States and the United Kingdom, examining co-publication and co-patent indicators. While IRC is crucial for enhancing research competitiveness and economic development, the choice of indicators remains a challenge. The paper addresses this gap by examining the association between co-publications and co-patents on the measurement of IRC. Findings indicate a robust positive correlation between co-publications and co-patents, reflecting increased collaboration in academic and industrial domains. Despite distinct growth rates, their aligned trends suggest potential redundancy in using both indicators. Notably, co-patents have a lasting positive effect on co-publications, emphasising the role of industrial innovations in forecasting scientific collaboration. Acknowledging study limitations, particularly its focus on core countries, prompts future research avenues to broaden insights into IRC dynamics. This study connects theoretical understanding with practical implications, offering nuanced perspectives for policymakers to formulate strategic plans for global scientific collaboration. Researchers are encouraged to consider these insights when selecting indicators, aligning choices with data availability and analytical ease to enhance the relevance and impact of their studies.

Gillen, ZM, Burch, RF, Saucier, DN, Strawderman, L, Luczak, T, Piroli, A, Petway, AJ, and Rath, T. Effects of a strength and conditioning offseason program on countermovement jump ground reaction forces in Division I American football players. J Strength Cond Res38(3): e86–e95, 2024—The purpose of this study was to examine the effects of a 10-week strength and conditioning offseason program on the ground reaction forces (GRFs) of American football players during single-leg and double-leg countermovement jumps (SLJ and CMJ, respectively). Each subject visited the laboratory twice, once for preoffseason and once for postoffseason testing. During each visit, subjects performed CMJs and SLJs for each leg. Ground reaction forces were collected by force plates to quantify unweighting, braking, propulsive, and performance metrics for each jump. In addition, an efficiency index was calculated for each jump to examine changes in vertical jump efficiency. Dependent samples ttests compared all CMJ metrics. Two-way repeated measures analyses of variance (leg × time) compared all SLJ metrics. An alpha level of p≤ 0.05 was considered statistically significant. For the CMJ, propulsive phase duration decreased due to the program (p= 0.007), whereas peak braking power, peak propulsive power, mean propulsive force, and jump height increased (p≤ 0.012). For the SLJ, peak braking power, force at the low position, braking rate of force development, eccentric force, peak propulsive power, mean propulsive force, and jump height increased in both legs (p≤ 0.044). The efficiency index increased for the CMJ and the SLJ for both legs (p≤ 0.016). This study demonstrated that SLJ and CMJ vertical jump performance significantly increases in as few as 10 weeks of offseason strength and conditioning. Strength and conditioning programming may effectively increase vertical jump performance, as assessed by GRFs, which can be used as a simple indicator regarding changes in athletic performance.

ObjectiveThis pilot study sought to investigate the utility and acceptability of the KardiaMobile 6-lead ECG (KM6LECG) as a tool for remote monitoring in children with inherited cardiac conditions.DesignA single-centre prospective cohort study. Children underwent standard clinical evaluation including a 12-lead ECG and a KM6LECG in the clinic. Participants recorded KM6LECGs monthly at home for 3 months. Families completed a questionnaire on their experience.SettingGreat Ormond Street Hospital Centre for Inherited Cardiovascular Diseases.Participants64 children: 22 with hypertrophic cardiomyopathy (HCM); 22 with long QT syndrome and 20 unaffected siblings (controls).Main outcome measuresComparison of data extracted from the clinic 12-lead ECG and supervised KM6LECG, and the supervised and unsupervised KM6LECG recording.ResultsOf 64 children (35% female, mean age 12 years), 58 had a baseline 12-lead ECG and appropriate baseline KM6LECG. In children with HCM, abnormalities in ventricular depolarisation/repolarisation in the limb leads of the 12-lead ECG were reliably reproduced. From the whole cohort, there was a strong positive correlation between the corrected QT interval from the 12-lead ECG and baseline KM6LECG (intraclass correlation coefficient=0.839) and baseline KM6LECG with an unsupervised KM6LECG (intraclass correlation coefficient=0.736). Suspected ‘lead’ misplacement impacted 18% of unsupervised recordings. Overall, the acceptability of the KM6LECG to families was good.ConclusionsThe KM6LECG provides an accurate tool for assessing some ECG abnormalities associated with paediatric inherited cardiovascular disease and may provide a useful at-home adjunct to face-to-face clinical care of children requiring ECG assessment.

We develop an approach to estimate a blood alcohol signal from a transdermal alcohol signal using physics-informed neural networks (PINNs). Specifically, we use a generative adversarial network (GAN) with a residual-augmented loss function to estimate the distribution of unknown parameters in a diffusion equation model for transdermal transport of alcohol in the human body. We design another PINN for the deconvolution of the blood alcohol signal from the transdermal alcohol signal. Based on the distribution of the unknown parameters, this network is able to estimate the blood alcohol signal and quantify the uncertainty in the form of conservative error bands. Finally, we show how a posterior latent variable can be used to sharpen these conservative error bands. We apply the techniques to an extensive dataset of drinking episodes and demonstrate the advantages and shortcomings of this approach.

ABSTRACTWhile the essence of leadership communication is recognized as a linchpin in crisis management, the distinct characteristics that define successful communication are often unknown. Recent perspectives on the topic highlight the importance of incorporating political and value-based considerations to achieve a balanced communication style during a crisis. This article empirically tests these claims by examining whether an evidence-inclusive communication style of leadership tends to yield more successful outcomes in crisis management. We compare speeches by leaders from Portugal, Brazil, the United States, and New Zealand, to assess the main explicit knowledge and value bases of decision-making. Our findings suggest that success of a crisis response is associated with a leader’s ability to effectively communicate an evidence-based narrative, inclusive of different evidence sources, when tackling pressing and complex issues such as the COVID-19 pandemic.

Only recently have more specific circuit-probing techniques become available to inform previous reports implicating the rodent hippocampus in orexigenic appetitive processing1–4. This function has been reported to be mediated at least in part by lateral hypothalamic inputs, including those involving orexigenic lateral hypothalamic neuropeptides, such as melanin-concentrating hormone5,6. This circuit, however, remains elusive in humans. Here we combine tractography, intracranial electrophysiology, cortico-subcortical evoked potentials, and brain-clearing 3D histology to identify an orexigenic circuit involving the lateral hypothalamus and converging in a hippocampal subregion. We found that low-frequency power is modulated by sweet-fat food cues, and this modulation was specific to the dorsolateral hippocampus. Structural and functional analyses of this circuit in a human cohort exhibiting dysregulated eating behaviour revealed connectivity that was inversely related to body mass index. Collectively, this multimodal approach describes an orexigenic subnetwork within the human hippocampus implicated in obesity and related eating disorders.

Ultrasonic (US) cutting of cartilage in orthopaedic surgery has received little attention despite its potential to reduce chondrocyte death which could enhance cartilage repair. We aimed to investigate whether an ultrasonically-vibrating scalpel to cut human articular cartilage could reduce chondrocyte death, and to determine if hyper-osmolarity could provide chondroprotection during the procedure.

Garvin’s seminal work “What Does ‘Product Quality’ Really Mean?” defines product quality based on five approaches: transcendent, product-based, user-based, manufacturing-based, and value-based. In addition to presenting five definitions of product quality, Garvin presents eight dimensions of product quality: performance, features, reliability, conformance, durability, serviceability, aesthetics, and perceived quality. The purpose of this research is to present a taxonomy for establishing product quality metrics for basketball shoes based on Garvin’s eight dimensions and the user-based definition of product quality. There is no clear explanation for what constitutes a properly fitted and usable basketball shoe. Constructing a multi-dimensional basketball shoe quality taxonomy, as presented in this paper, captures relationships between features and user needs to improve the fitness for use in basketball shoes beyond commonly-used marketing jargon. Several contextual relationships of basketball are identified and associated with the requirements of basketball players, thereby resulting in a basketball shoe quality taxonomy that defines the relationships of shoe features to user preference. This taxonomy can be used to derive what product quality means to the basketball athlete and thus improve the decision-making process for the basketball shoe wearer and coaching staff.

Rodent models are commonly used in pre-clinical research of magnesium (Mg)-based and other types of biomaterials for fracture treatment. Most studies selected unstable fixation methods, and there is a lack of multimodal longitudinal in vivomonitoring of bone healing. The purpose of this study is to develop a rat femoral fracture model stabilized by external fixation with intra-medullary Mg implant, and to investigate the dynamic bone union process with several imaging techniques offering complementing insights into the process. Pure Mg pins were prepared, followed by an in vitrodegradation test. Male Sprague-Dawley rats in the experimental group underwent femoral osteotomy stabilized by external fixators with intra-medullary implantation of Mg pins, and the control group underwent external fixation without intra-medullary implants. Post-operative radiograph, micro-CT and B-mode ultrasonography were acquired directly after surgery, and re-examined at week 4, 8 and 12. Bone tissue volume, in vivoimplant degradation, histological staining and MRI images were analyzed using ex vivosamples. Both groups achieved fracture union at week 12, and the dynamic healing process was illustrated by in vivoradiograph, micro-CT and ultrasonography. Bilateral whole femur ex vivoanalysis further demonstrated increased ratio of bone tissue volume in the surgical femur with Mg implants, and in vivodegradation of Mg pins was slower than in vitroresults. Titanium screws rather than intra-medullary Mg pins were the source of artifact in MRI. This pilot study showed the rat fracture model with external fixation and intra-medullary Mg implantation to be an effective method for dynamic in vivomonitoring of the bone healing process. Future application of the animal model may facilitate pre-clinical translational research of biodegradable orthopaedic implant materials for fracture treatment.

ABSTRACTThe hypoxia-induced transcription factor HIF1 inhibits cell growth in normoxia through poorly understood mechanisms. A constitutive upregulation of hypoxia response is associated with increased malignancy, indicating a loss of antiproliferative effects of HIF1 in cancer cells. To understand these differences, we examined the control of cell cycle in primary human cells with activated hypoxia response in normoxia. Activated HIF1 caused a global slowdown of cell cycle progression through G1, S and G2 phases leading to the loss of mitotic cells. Cell cycle inhibition required a prolonged HIF1 activation and was not associated with upregulation of p53 or the CDK inhibitors p16, p21 or p27. Growth inhibition by HIF1 was independent of its Asn803 hydroxylation or the presence of HIF2. Antiproliferative effects of hypoxia response were alleviated by inhibition of lactate dehydrogenase and, more effectively, by boosting cellular production of NAD+, which was decreased by HIF1 activation. In comparison to normal cells, various cancer lines showed several fold-higher expressions of NAMPT, which is a rate-limiting enzyme in the main biosynthetic pathway for NAD+. Inhibition of NAMPT activity in overexpressor cancer cells sensitized them to antigrowth effects of HIF1. Thus, metabolic changes in cancer cells, such as enhanced NAD+production, create resistance to growth-inhibitory activity of HIF1 permitting manifestation of its tumor-promoting properties.Abbreviations: DMOG: dimethyloxalylglycine, DM-NOFD: dimethyl N-oxalyl-D-phenylalanine, NMN: β-nicotinamide mononucleotide

Several healthcare organizations across Minnesota have developed formal pharmacogenomic (PGx) clinical programs to increase drug safety and effectiveness. Healthcare professional and student education is strong and there are multiple opportunities in the state for learners to gain workforce skills and develop advanced competency in PGx. Implementation planning is occurring at several organizations and others have incorporated structured utilization of PGx into routine workflows. Laboratory-based and translational PGx research in Minnesota has driven important discoveries in several therapeutic areas. This article reviews the state of PGx activities in Minnesota including educational programs, research, national consortia involvement, technology, clinical implementation and utilization and reimbursement, and outlines the challenges and opportunities in equitable implementation of these advances.

A progressive loss of functional nephrons defines chronic kidney disease (CKD). Complications related to cardiovascular disease (CVD) are the principal causes of mortality in CKD; however, the acceleration of CVD in CKD remains unresolved. Our study used a complementary proteomic approach to assess mild and advanced CKD patients with different atherosclerosis stages and two groups of patients with different classical CVD progression but without renal dysfunction. We utilized a label-free approach based on LC-MS/MS and functional bioinformatic analyses to profile CKD and CVD leukocyte proteins. We revealed dysregulation of proteins involved in different phases of leukocytes’ diapedesis process that is very pronounced in CKD’s advanced stage. We also showed an upregulation of apoptosis-related proteins in CKD as compared to CVD. The differential abundance of selected proteins was validated by multiple reaction monitoring, ELISA, Western blotting, and at the mRNA level by ddPCR. An increased rate of apoptosis was then functionally confirmed on the cellular level. Hence, we suggest that the disturbances in leukocyte extravasation proteins may alter cell integrity and trigger cell death, as demonstrated by flow cytometry and microscopy analyses. Our proteomics data set has been deposited to the ProteomeXchange Consortium via the PRIDE repository with the data set identifier PXD018596.

Introduction:Pharmacogenetic (PGx) implementation has lagged behind the development of drug/gene pair guidelines. Materials & methods:This was a prospective study assessing the integration of PGx through medication therapy management in an outpatient clinic. Variables collected included patient diagnosis, current medications, failed or discontinued medications, PGx results/recommendations, turnaround time and pre/post clinical ratings. Results:A total of 91 participants completed study procedures with an average enrollment of approximately one consult per week. Participants were referred for testing primarily for guidance for current and future medications. The average number of recommendations per participant was 0.93. Conclusion:Integrating PGx testing into medication therapy management is feasible with PGx results available in under a week resulting in clinical recommendations in over half of patients tested.

Little is known about the relationships between alcohol consumption and cardiovascular disease (CVD) and related chronic conditions in Asian Americans and how such risk relationships vary among their subgroups. We examine these relationships in Asian Americans and their moderation by ethnic prevalence of a variant the aldehyde dehydrogenase gene: ALDH2*2. Multiple logistic regression modeling was performed using a nationally representative sample of Asian‐American adults aged 30 to 70 (n= 1,720) from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) Waves 2 (2004 to 2005) and 3 (2012 to 2013). Outcomes considered were diabetes, hypertension, high cholesterol, CVD, any of the 3 conditions (i.e., diabetes, high cholesterol, and CVD) documented to have a J‐shaped relationship with drinking (CVDRC3), and any of the CVD‐related conditions (ANYCVD). Demographic and socioeconomic characteristics, health insurance coverage, and other lifestyle risk factors (smoking and obesity/overweight) were adjusted. Analyses were stratified by gender. Alcohol consumption level was positively associated only with hypertension in Asian males, with consuming 7 to 14 drinks per week associated with more than double the risk of lifetime abstinence. For females, alcohol consumption had a dose–response relationship with high cholesterol and CVDRC3. Membership in the higher ALDH2*2ethnic group overall was associated with lower risk of CVD‐related conditions. However, compared to abstainers in lower ALDH2*2group, females in the higher ALDH2*2group who consumed more than 7 drinks per week had a higher risk of diabetes, hypertension, CVDRC3, and ANYCVD. Asian Americans may have increased risk of CVD‐related conditions at relatively low alcohol consumption levels. Among Asian‐American females, in particular, any amount of drinking may increase risk for high cholesterol or any of the CVD‐related conditions previously documented to have a curvilinear relationship with drinking. These risks may be particularly elevated for those in ethnic groups with a high prevalence of ALDH2*2. This is the first study conducted in the United States that examined alcohol‐related susceptibility to cardiovascular‐related conditions associated with a variant aldehyde dehydrogenase gene allele, ALDH2*2(commonly known as the ‘flushing gene’). Asian women in ethnic groups with higher prevalence of ALDH2*2who consumed more than 7 drinks weekly had higher risk for these conditions (including hypertension), compared with their counterparts in lower ALDH2*2groups. Study findings suggest elevated risks for alcohol‐related pathologies associated with ALDH2*2.

Various multiple-disciplinary terms and concepts (although most commonly “interdisciplinarity,” which is used herein) are used to frame education, scholarship, research, and interactions within and outside academia. In principle, the premise of interdisciplinarity may appear to have many strengths; yet, the extent to which interdisciplinarity is embraced by the current generation of academics, the benefits and risks for doing so, and the barriers and facilitators to achieving interdisciplinarity, represent inherent challenges. Much has been written on the topic of interdisciplinarity, but to our knowledge there have been few attempts to consider and present diverse perspectives from scholars, artists, and scientists in a cohesive manner. As a team of 57 members from the Canadian College of New Scholars, Artists, and Scientists of the Royal Society of Canada (the College) who self-identify as being engaged or interested in interdisciplinarity, we provide diverse intellectual, cultural, and social perspectives. The goal of this paper is to share our collective wisdom on this topic with the broader community and to stimulate discourse and debate on the merits and challenges associated with interdisciplinarity. Perhaps the clearest message emerging from this exercise is that working across established boundaries of scholarly communities is rewarding, necessary, and is more likely to result in impact. However, there are barriers that limit the ease with which this can occur (e.g., lack of institutional structures and funding to facilitate cross-disciplinary exploration). Occasionally, there can be significant risk associated with doing interdisciplinary work (e.g., lack of adequate measurement or recognition of work by disciplinary peers). Solving many of the world’s complex and pressing problems (e.g., climate change, sustainable agriculture, the burden of chronic disease, and aging populations) demands thinking and working across long-standing, but in some ways restrictive, academic boundaries. Academic institutions and key support structures, especially funding bodies, will play an important role in helping to realize what is readily apparent to all who contributed to this paper—that interdisciplinarity is essential for solving complex problems; it is the new norm. Failure to empower and encourage those doing this research will serve as a great impediment to training, knowledge, and addressing societal issues.

Histones and their posttranslational modifications (PTMs) are critical regulators of gene expression. Differentiation, environmental stressors, xenobiotics, and major human diseases cause significant changes in histone variants and PTMs. Western blotting is the mainstay methodology for detection of histones and their PTMs in the majority of studies. Surprisingly, despite their high abundance in cells, immunoblotting of histones typically involves loading of large protein amounts that are normally used for detection of sparse cellular proteins. We systematically examined technical factors in the Western-blotting-based detection of human histones with >30 antibodies. We found that under multiple protein transfer conditions, many histone epitopes on polyvinylidene fluoride (PVDF) membranes had a very low antibody accessibility, which was dramatically increased by the addition of a simple denaturation step. Denaturation of membrane-bound proteins also enhanced the specificity of some histone antibodies. In comparison to standard PVDF membranes, the sensitivity of histone detection on standard nitrocellulose membranes was typically much higher, which was further increased by the inclusion of the same denaturation step. Optimized protocols increased by >100-times detection sensitivity for the genotoxic marker γ-H2AX with two monoclonal antibodies. The impact of denaturation and nitrocellulose use varied for different histones, but for each histone, it was generally similar for antibodies targeting N-terminal and C-terminal regions. In summary, denaturation of membrane-bound histones strongly improves their detection by Westerns, resulting in more accurate measurements and permitting analyses with small biological samples.

Zur onkoplastischen Rekonstruktion der Brust stehen verschiedene Ansätze zur Verfügung. Ziel ist ein bestmögliches kosmetisches Ergebnis, ohne die onkologische Sicherheit aufs Spiel zu setzen. Planungsrelevante Kriterien sind z. B. die Brust-Tumor-Relation sowie die Brustform.

Macrobenthic secondary production is widely used to assess the trophic capacity, health, and functioning of marine and freshwater ecosystems. Annual production estimates are often calculated using empirical models and based on data collected during a single period of the year. Yet, many ecosystems show seasonal variations. Although ignoring seasonality may lead to biased and inaccurate estimates of annual secondary production, it has never been tested at the community level. Using time series of macrobenthic data collected seasonally at three temperate marine coastal soft‐bottom sites, we assessed seasonal variations in biomass of macrobenthic invertebrates at both population and community levels. We then investigated how these seasonal variations affect the accuracy of annual benthic production when assessed using an empirical model and data from a single sampling event. Significant and consistent seasonal variations in biomass at the three study sites were highlighted. Macrobenthic biomass was significantly lower in late winter and higher in summer/early fall for 18 of the 30 populations analyzed and for all three communities studied. Seasonality led to inaccurate and often biased estimates of annual secondary production at the community level when based on data from a single sampling event. Bias varied by site and sampling period, but reached ∼ 50% if biomass was sampled at its annual minimum or maximum. Since monthly sampling is rarely possible, we suggest that ecologists account for uncertainty in annual production estimates caused by seasonality.

Oscillatory activity is a ubiquitous property of brain signals, and yet relatively few studies have investigated how the phase of such ongoing oscillations affects our cognition. One of the main findings in this field is that the phase of electroencephalography (EEG) in the alpha band can affect perception of milliseconds-long stimuli. However, the importance of the phase of EEG for processing more naturalistic stimuli, which have a much longer duration, is still not clear. To address this question here, we presented word–nonword pairs, each of which was visible for 5 s and measured the effect of EEG phase during stimulus onset on later memory recall. The task consisted of an encoding (learning) phase in which 20 novel word–nonword pairs were presented, followed by a test phase in which participants were shown one of the seen words with four target nonwords to choose from. We found that memory recall performance was higher when the words during encoding were presented at a descending phase of the theta oscillation. This effect was the strongest in the frontal cortex. These results suggest that the phase of ongoing cortical activity can affect memorization of seconds-long stimuli that are an integral part of many daily tasks.

The patellofemoral joint is thought to be a common source for knee pain. Improper alignment and function of the patellofemoral joint can lead to abnormal contact pressures, which may explain patients' symptoms. In this review, the authors examine techniques for measuring patellofemoral joint contact pressures and summarize the relevant patellofemoral joint anatomy and contact pressures in normal knee kinematics. Finally, they discuss the results of studies investigating contact pressure changes in cases of patellar instability. This includes both reconstruction of the medial patellofemoral ligament and tibial tubercle osteotomy. [The patellofemoral joint is thought to be a common source for knee pain. Improper alignment and function of the patellofemoral joint can lead to abnormal contact pressures, which may explain patients' symptoms. In this review, the authors examine techniques for measuring patellofemoral joint contact pressures and summarize the relevant patellofemoral joint anatomy and contact pressures in normal knee kinematics. Finally, they discuss the results of studies investigating contact pressure changes in cases of patellar instability. This includes both reconstruction of the medial patellofemoral ligament and tibial tubercle osteotomy. [Orthopedics. 2019; 42(2):e172–e179.]

Surface modifications of dental implants play a crucial role for material stability, durability, and patient contentment; hence optimization of the commonly used techniques can have significant impact. Surface properties affect the osseointegration of implants; however, the surface for the optimal osseointegration is still being researched. Herein, the surface roughness and topography of dental implant screws after polishing, sandblasting, and laser treatment via tapping‐mode atomic force microscopy are investigated. The measurements are performed at the implants’ shank, crest, and root sites and evaluated for surface roughness, kurtosis, and skew values. Laser‐treated and sandblasted samples have a significantly higher roughness compared to the machined sample. The roughness at the root of the samples is higher in case of the laser‐treated and machined samples, while lower for the sandblasted implant. It is found that laser treatment leads to a roughness lower than that of sandblasted dental screws but significantly higher than that of mechanically polished implants. Differences in the roughness at different topological sites show the need for more precise treatment of implants in order to optimize the roughness. Herein, surface roughness parameters of dental implants are investigated with help of tapping‐mode atomic force microscopy. Screw dental implants after polishing, sandblasting, and laser treatment of surface are examined. Differences in roughness at different characteristic topological sites are described. Comparison of acquired results with available literature shows that improved osseointegration is expected for sandblasted and laser‐treated implants over other methods.

The poem "ABDUCTIONS," by Raymond Luczak is presented. First Line: Some summer nights I felt called to go outside. Last Line: I could touch the stars.

The study is focussing towards Metal Injection Moulding (MIM) of Mg-alloys for biomedical implant applications. Especially the influence of the sintering processing necessary for the consolidation of the finished part is in focus of this study. In doing so, the chosen high strength EZK400 Mg-alloy powder material was sintered using different sintering support bottom plate materials to evaluate the possibility of iron impurity pick up during sintering. It can be shown that iron pick up took place from the steel bottom plate into the specimen. Despite the fact that a separating boron nitrite (BN) barrier layer was used and the Mg-Fe phase diagram is not predicting any significant solubility to each other. As a result of this study a new bottom plate material not harming the sintering and the biodegradation performance of the as sintered material, namely a carbon plate material, was found.

Hybrid annotation techniques have emerged as a promising approach to carry out named entity recognition on noisy microposts. In this paper, we identify a set of content and crowdsourcing-related features (number and type of entities in a post, average length and sentiment of tweets, composition of skipped tweets, average time spent to complete the tasks, and interaction with the user interface) and analyse their impact on correct and incorrect human annotations. We then carried out further studies on the impact of extended annotation instructions and disambiguation guidelines on the factors listed above. This was all done using CrowdFlower and a simple, custom built gamified NER tool on three datasets from related literature and a fourth newly annotated corpus. Our findings show that crowd workers correctly annotate shorter tweets with fewer entities, while they skip (or wrongly annotate) longer tweets with more entities. Workers are also adept at recognising people and locations, while they have difficulties in identifying organisations and miscellaneous entities which they skip (or wrongly annotate). Finally, detailed guidelines do not necessarily lead to improved annotation quality. We expect these findings to lead to the design of more advanced NER pipelines, informing the way in which tweets are chosen to be outsourced to automatic tools, crowdsourced workers and nichesourced experts. Experimental results are published as JSON-LD for further use.

In this article we report about our efforts to develop and evaluate computational support tools for literary studies. We present a novel method and tool that allows interactive visual analytics of character occurrences in Victorian novels, and has been handed to humanities scholars and students for work with a number of novels from different authors. Our user study reveals insights about Victorian novels that are valuable for scholars in the digital humanities field, and informs UI as well as UX designers about how these domain experts interact with tools that leverage network science.

The reinforcement learning (RL) paradigm allows agents to solve tasks through trial-and-error learning. To be capable of efficient, long-term learning, RL agents should be able to apply knowledge gained in the past to new tasks they may encounter in the future. The ability to predict actions’ consequences may facilitate such knowledge transfer. We consider here domains where an RL agent has access to two kinds of information: agent-centric information with constant semantics across tasks, and environment-centric information, which is necessary to solve the task, but with semantics that differ between tasks. For example, in robot navigation, environment-centric information may include the robot’s geographic location, while agent-centric information may include sensor readings of various nearby obstacles. We propose that these situations provide an opportunity for a very natural style of knowledge transfer, in which the agent learns to predict actions’ environmental consequences using agent-centric information. These predictions contain important information about the affordances and dangers present in a novel environment, and can effectively transfer knowledge from agent-centric to environment-centric learning systems. Using several example problems including spatial navigation and network routing, we show that our knowledge transfer approach can allow faster and lower cost learning than existing alternatives.

•Troglitazone inhibits LTC4synthesis in asthma subjects and controls.•Troglitazone might be a potential element of therapy of bronchial asthma.•No effects of troglitazone on 15-HETE and eotaxin have been shown.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) hyperactivity causes cardiac arrhythmias, a major source of morbidity and mortality worldwide. Despite proven benefits of CaMKII inhibition in numerous preclinical models of heart disease, translation of CaMKII antagonists into humans has been stymied by low potency, toxicity, and an enduring concern for adverse effects on cognition due to an established role of CaMKII in learning and memory. To address these challenges, we asked whether any clinically approved drugs, developed for other purposes, were potent CaMKII inhibitors. For this, we engineered an improved fluorescent reporter, CaMKAR (CaMKII activity reporter), which features superior sensitivity, kinetics, and tractability for high-throughput screening. Using this tool, we carried out a drug repurposing screen (4475 compounds in clinical use) in human cells expressing constitutively active CaMKII. This yielded five previously unrecognized CaMKII inhibitors with clinically relevant potency: ruxolitinib, baricitinib, silmitasertib, crenolanib, and abemaciclib. We found that ruxolitinib, an orally bioavailable and U.S. Food and Drug Administration–approved medication, inhibited CaMKII in cultured cardiomyocytes and in mice. Ruxolitinib abolished arrhythmogenesis in mouse and patient-derived models of CaMKII-driven arrhythmias. A 10-min pretreatment in vivo was sufficient to prevent catecholaminergic polymorphic ventricular tachycardia, a congenital source of pediatric cardiac arrest, and rescue atrial fibrillation, the most common clinical arrhythmia. At cardioprotective doses, ruxolitinib-treated mice did not show any adverse effects in established cognitive assays. Our results support further clinical investigation of ruxolitinib as a potential treatment for cardiac indications.

Wikipedia represents a successful peer-produced knowledge-resource constructed via the endeav- ours of millions of volunteers. We examine the activity of Wikipedia by analysing WikiProjects, an community-driven feature which allows communities of Wikipedians to coordinate their efforts in order to improve or produce Wikipedia articles. We harvested the content of over 600 active Wikipedia projects, which comprised of over 100 million edits and 15 million Talk entries, associ- ated with over 1:5 million Wikipedia articles and Talk pages produced by 14 million unique users. Our analysis reveals findings related to the overall positive activity and growth of Wikipedia, as well as the connected community of Wikipedians within and between specific WikiProjects. We argue that the complexity of Wikipedia requires metrics which re ect the many aspects of the Wikipedia social machine, and by doing so, will offer insights into it's state of health.

Background: Asthma is an inflammatory disorder with multiple mediators involved in the inflammatory response. Despite several attempts, no new anti-inflammatory drugs have been registered for asthma treatment for several years. However, thiazolidinediones, peroxisome proliferator-activated receptor agonists, have demonstrated some anti-inflammatory properties in various experimental settings. The aim of this study was to assess the influence of troglitazone on LTC4and 15-HETE concentrations. It also evaluates TNF-induced eotaxin synthesis in peripheral blood mononuclear cells from 14 patients with mild asthma and 13 healthy controls. Methods: PBMCs were isolated from the whole blood of the asthmatics and healthy subjects and pretreated with 0.1, 1 or 10 µM of Troglitazone. The cells were then exposed to 10-6M calcium jonophore or 10 ng/ml TNF. The production and release of LTC4, 15-HETE and eotaxin were then assessed. Results: Troglitazone caused a dose-dependent inhibition in LTC4synthesis in both asthmatics and healthy subjects. Troglitazone did not influence 15-HETE or eotaxin production in either asthmatic patients or in healthy individuals. Conclusion: Due to its inhibition of LTC4synthesis, troglitazone therapy is an interesting potential therapeutic approach in asthma and other LTC4related inflammatory disorders.

An early age of drinking initiation (ADI) has been associated with increased risk for alcohol use disorders (AUDs), but the consistency of this risk across diverse samples has not been well studied. The purpose of this study was to examine whether the pathway from ADIto AUDsymptoms by early adulthood is moderated by ethnicity and possessing an alcohol‐metabolizing gene ALDH2*2variant allele. We used multigroup structural equation modeling, including 5 groups split by ethnicity and ALDH2*2, to examine the consistency of the path from ADIto AUDsymptoms in 604 Chinese‐, Korean‐, and White‐American college students. We further examined the effects of ALDH2*2,ethnicity, and their interaction in Asians to better understand their unique contributions to the moderation. The association between ADIand AUDsymptoms was moderated, with ADInegatively associated with AUDsymptoms among Koreans without ALDH2*2and Whites, but not among Koreans with ALDH2*2or Chinese regardless of ALDH2*2. Both ALDH2*2and ethnicity within Asians contributed unique variability in the effect. Ethnicity and ALDH2*2altered the relationship of ADIas a risk factor for AUDsymptoms. Being Chinese and possessing an ALDH2*2allele within Koreans both buffered against the risk for AUDsymptoms associated with earlier ADI, indicating that this relationship can be attenuated by protective factors. An early age of drinking initiation (ADI) has been associated with increased risk for alcohol use disorders (AUDs), but the consistency of this risk across diverse samples has not been well studied. We found both ethnicity (Chinese, Korean, White) and the alcohol metabolizing gene variant ALDH2*2moderated this relationship. Being Chinese and possessing an ALDH2*2allele within Koreans both buffered against the risk for AUDsymptoms associated with earlier ADI, indicating that this relationship can be attenuated by protective factors.

Metabolic production of acetyl coenzyme A (acetyl-CoA) is linked to histone acetylation and gene regulation, but the precise mechanisms of this process are largely unknown. Here we show that the metabolic enzyme acetyl-CoA synthetase 2 (ACSS2) directly regulates histone acetylation in neurons and spatial memory in mammals. In a neuronal cell culture model, ACSS2 increases in the nuclei of differentiating neurons and localizes to upregulated neuronal genes near sites of elevated histone acetylation. A decrease in ACSS2 lowers nuclear acetyl-CoA levels, histone acetylation, and responsive expression of the cohort of neuronal genes. In adult mice, attenuation of hippocampal ACSS2 expression impairs long-term spatial memory, a cognitive process that relies on histone acetylation. A decrease in ACSS2 in the hippocampus also leads to defective upregulation of memory-related neuronal genes that are pre-bound by ACSS2. These results reveal a connection between cellular metabolism, gene regulation, and neural plasticity and establish a link between acetyl-CoA generation ‘on-site’ at chromatin for histone acetylation and the transcription of key neuronal genes.

Ambipolar organic field-effect transistors (OFETs) based on heterojunction active films still suffer from an imbalance in the transport of electrons and holes. This problem is related to an uncontrolled phase separation between the donor and acceptor organic semiconductors in the thin films. In this work, we have developed a concept to improve the phase separation in heterojunction transistors to enhance their ambipolar performance. This concept is based on preaggregation of the donor polymer, in this case poly(3-hexylthiophene) (P3HT), before solution mixing with the small-molecular-weight acceptor, phenyl-C61-butyric acid methyl ester (PCBM). The resulting heterojunction transistor morphology consists of self-assembled P3HT fibers embedded in a PCBM matrix, ensuring balanced mobilities reaching 0.01 cm2/V s for both holes and electrons. These are the highest mobility values reported so far for ambipolar OFETs based on P3HT/PCBM blends. Preaggregation of the conjugated polymer before fabricating binary blends can be regarded as a general concept for a wider range of semiconducting systems applicable in organic electronic devices.

Continuous electroencephalography (cEEG) improves monitoring of the brain in unconscious patients, but implementation at ICU is difficult. The present investigation shows a way to introduce cEEG at an anesthesiological ICU and discusses the first experiences.

CFTR,the cystic fibrosis (CF) gene, encodes for the CFTR protein that plays an essential role in anion regulation and tissue homeostasis of various epithelia. In the gastrointestinal (GI) tract CFTR promotes chloride and bicarbonate secretion, playing an essential role in ion and acid–base homeostasis. Cftrhas been identified as a candidate driver gene for colorectal cancer (CRC) in several Sleeping BeautyDNA transposon-based forward genetic screens in mice. Further, recent epidemiological and clinical studies indicate that CF patients are at high risk for developing tumors in the colon. To investigate the effects of CFTR dysregulation on GI cancer, we generated ApcMinmice that carried an intestinal-specific knockout of Cftr. Our results indicate that Cftris a tumor suppressor gene in the intestinal tract as Cftrmutant mice developed significantly more tumors in the colon and the entire small intestine. In Apc+/+mice aged to ~1 year, Cftrdeficiency alone caused the development of intestinal tumors in >60% of mice. Colon organoid formation was significantly increased in organoids created from Cftrmutant mice compared with wild-type controls, suggesting a potential role of Cftrin regulating the intestinal stem cell compartment. Microarray data from the Cftr-deficient colon and the small intestine identified dysregulated genes that belong to groups of immune response, ion channel, intestinal stem cell and other growth signaling regulators. These associated clusters of genes were confirmed by pathway analysis using Ingenuity Pathway Analysis and gene set enrichment analysis (GSEA). We also conducted RNA Seq analysis of tumors from Apc+/+Cftrknockout mice and identified sets of genes dysregulated in tumors including altered Wnt ß-catenin target genes. Finally we analyzed expression of CFTR in early stage human CRC patients stratified by risk of recurrence and found that loss of expression of CFTR was significantly associated with poor disease-free survival.

Supplemental Digital Content is available in the text.

Our article discusses the research results aimed at finding relations between Internet usage styles and attitudes toward globalization. The research included 597 people, aged 15 to 39 years, from Poland by using two methods: 1) The World-I Questionnaire (by A. Senejko, Z. Los) to diagnose attitudes toward globalization (accepting, critical, fearful); 2) The Internet-Interpersonal Relations Questionnaire (by D. Chmielewska-Luczak) – diagnoses four categories of Internet usage styles (distanced, frustrated, omnipotent, ambivalent).

In this article the authors evaluate the adoption and applicability of established ontology engineering results by the Linked Data providers' community. The evaluation relies on a combination of qualitative and quantitative methods; in particular, the authors conducted an analytical survey containing structured interviews with data publishers in order to give an account of the current ontology engineering practice in Linked Data provisioning, and compared and expanded our findings with statistics on ontology development and usage provided by the Billion Triple Challenges datasets from 2012 (using the vocab.cc platform) and from 2014 and other related tools. The findings of the evaluation allow data practitioners and ontologists to yield a better understanding of the conceptual part of the LOD Cloud; and form the basis for the definition of purposeful, empirically grounded guidelines and best practices for developing, managing and using ontologies in the new application scenarios that arise in the context of Linked Data.

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A recent increase in sea temperature has established a new ecosystem dynamic regime in the North Sea. Climate-induced changes in decapods have played an important role. Here, we reveal a coincident increase in the abundance of swimming crabs and lesser black-backed gull colonies in the North Sea, both in time and in space. Swimming crabs are an important food source for lesser black-backed gulls during the breeding season. Inhabiting the land, but feeding mainly at sea, lesser black-backed gulls provide a link between marine and terrestrial ecosystems, since the bottom-up influence of allochthonous nutrient input from seabirds to coastal soils can structure the terrestrial food web. We, therefore, suggest that climate-driven changes in trophic interactions in the marine food web may also have ensuing ramifications for the coastal ecology of the North Sea.

Selective attention involves the exclusion of irrelevant information in order to optimize perception of a single source of sensory input; failure to do so often results in the familiar phenomenon of distraction. The term ‘distraction’ broadly refers to a perceptual phenomenon. In the present study we attempted to find the electrophysiological correlates of distraction using an auditory discrimination task. EEG and event-related potential responses to identical stimuli were compared under two levels of distraction (continuous broad-band noise or continuous speech). Relative to broad-band noise, the presence of a continuous speech signal in the unattended ear impaired task performance and also attenuated the N1 peak evoked by nontarget stimuli in the attended ear. As the magnitude of a peak in the event-related potential waveform can be modulated by differences in intertrial power but also by differences in the stability of EEG phase across trials, we sought to characterize the effect of distraction on intertrial power and intertrial phase locking around the latency of the N1. The presence of continuous speech resulted in a prominent reduction of theta EEG band intertrial phase locking around the latency of the N1. This suggests that distraction may act not only to disrupt a sensory gain mechanism but also to disrupt the temporal fidelity with which the brain responds to stimulus events.

Background: A mechanistic model has been proposed for how alcohol‐metabolizing gene variants protect individuals from the development of alcohol use disorders, with heightened sensitivity to alcohol being an early step (endophenotype) in this model. This study was designed to determine whether possession of 2 alcohol‐metabolizing genes variations, the aldehyde dehydrogenase ALDH2*2allele and the alcohol dehydrogenase ADH1B*2allele, was associated with self‐reported sensitivity to alcohol at low doses and at initial use.

The fate of ionic liquids in soils and sediments is significant for the sustainable application of ILs in industry. We are obliged to understand how these compounds are transformed in (bio-) chemical processes and how long they will persist in the environment. In addition, we must understand how ionic liquids interact in complex systems. This review analyzes and summarizes the results obtained to date by a significant number of research groups on solution and surface interactions of ionic liquids. Due to the structural similarity of ionic liquids with surfactants, it is possible to determine the interaction mechanism of the ionic liquids, with soils and sediments. It was found that highly lipophilic ILs possessing long alkyl substituents or large organic anions are expected to interact with soils/sediments organic matter thus being rather immobile. Conversely, the weak lipophilic ILs probably be the most mobile in the soil and water, due to their high water solubility as well as their lower affinity to organic matter. For this reason they are thought to present the greatest threat for ground water contamination.

Catecholamines increase heart rate by augmenting the cAMP-responsive hyperpolarization-activated cyclic nucleotide-gated channel 4 pacemaker current (If) and by promoting inward NaCa2exchanger current (INCX) by a “Ca2clock” mechanism in sinoatrial nodal cells (SANCs). The importance, identity, and function of signals that connect Ifand Ca2clock mechanisms are uncertain and controversial, but the multifunctional Ca2calmodulin-dependent protein kinase II (CaMKII) is required for physiological heart rate responses to -adrenergic receptor (-AR) stimulation. The aim of this study was to measure the contribution of the Ca2clock and CaMKII to cardiac pacing independent of -AR agonist stimulation.

In this paper we study the size of the largest clique ?(G(n, a)) in a random graph G(n, a) on nvertices which has power-law degree distribution with exponent a. We show that, for ‘flat’ degree sequences with a > 2, with high probability, the largest clique in G(n, a) is of a constant size, while, for the heavy tail distribution, when 0 < a < 2, ?(G(n, a)) grows as a power of n. Moreover, we show that a natural simple algorithm with high probability finds in G(n, a) a large clique of size (1 - o(1))?(G(n, a)) in polynomial time.

Methane fermentation of poultry slaughterhouse wasteOne of the alternative methods for the treatment of animal by-products is their utilization in biological processes with a simultaneous production of energy-rich biogas. The results of the investigations of methane fermentation of animal waste are discussed in the study. The methane fermentation was carried out at 35°C. The substrates used in the experiments included poultry heads and muscle tissue. Furthermore, the fermentation residues subjected previously to hydrothermal processing were used as a substrate. The suspension of those substrates in the initial concentration range from 1 g TOC/dm3to 11 g TOC/dm3was used in the process. Additionally, the effect of the preliminary stage of hydrothermal substrate processing on methane fermentation efficiency was assessed. Poultry waste was subjected to thermohydrolysis at the temperature from 100°C to 300°C and pressure up to 9.0 MPa. The efficiency of the methane fermentation was estimated on the basis of biogas generated in the process. The biogas production was between 0.17 Ndm3/g TOC and 1.53 Ndm3/g TOC. In the case of poultry heads, a beneficial impact of hydrothermal processing at the temperatures from 100°C to 175°C was confirmed. For poultry meat the preliminary thermohydrolysis brought about a decrease of methane fraction in the biogas evolved. The preliminary hydrothermal processing made it possible to meet the requirements of legal regulations for the hygienization of by-products of animal origin. The obtained results allowed us to identify conditions under which the methane fermentation was carried out and which ensured a high level of methanization.