bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computer‐Assisted Recombination (CompassR) Teaches us How to Recombine Beneficial Substitutions from Directed Evolution Campaigns
Authors: Cui Haiyang , Cao Hao , Cai Haiying , Jaeger Karl‐Erich , Davari Mehdi D. , Schwaneberg Ulrich 
Published: September 2019

AbstractA main remaining challenge in protein engineering is how to recombine beneficial substitutions. Systematic recombination studies show that poorly performing variants are usually obtained after recombination of 3 to 4 beneficial substitutions. This limits researchers in exploiting nature's potential in generating better enzymes. The Computer‐assisted Recombination (CompassR) strategy provides a selection guide for beneficial substitutions that can be recombined to gradually improve enzyme performance by analysis of the relative free energy of folding (ΔΔGfold). The performance of CompassR was evaluated by analysis of 84 recombinants located on 13 positions of Bacillus subtilis lipase A. The finally obtained variant F17S/V54K/D64N/D91E had a 2.7‐fold improved specific activity in 18.3 % (v/v) 1‐butyl‐3‐methylimidazolium chloride ([BMIM][Cl]). In essence, the deducted CompassR rule allows recombination of beneficial substitutions in an iterative manner and empowers researchers to generate better enzymes in a time‐efficient manner.
Behavioral changes and nutritional consequences to elk (Cervus canadensis) avoiding perceived risk from human hunters
Authors: Spitz Derek B. , Rowland Mary M. , Clark Darren A. , Wisdom Michael J. , Smith Joshua B. , Brown Casey L. , Levi Taal 
Published: September 2019

AbstractThe life‐and‐death stakes of predator–prey encounters justify the high price of many anti‐predator behaviors. In adopting these behaviors, prey incur substantial non‐consumptive costs that can have population‐level consequences. Because prey knowledge of risk is imperfect, individuals may even adopt these costly behaviors in the absence of a real threat. For example, rather than only avoid hunters, many species categorically avoid all anthropogenic activity. Although hunting seasons only increase risk for specific individuals (e.g., males), non‐target individuals may still perceive human hunters as a source of risk and respond accordingly. Here, we used a large‐scale experiment including 89 animal‐years of location data from 62 unique individuals over 6 yr to quantify the duration, magnitude, and energetic consequences of changes to movement and resource selection behavior adopted by non‐target female elk (Cervus canadensis) in response to human hunters during three separate experimental 5‐d hunts (elk archery, deer rifle (Odocoileus hemionus or Odocoileus virginianus), and elk rifle). We predicted that elk response to hunters would be brief, but that strong behavioral responses to hunters (e.g., strengthened avoidance of roads and trails) would carry nutritional costs. We measured the duration of hunt‐related changes in elk speed using quantile regression, further quantified the strength of elk behavioral responses to hunters using population‐level resource selection functions, and evaluated whether anti‐predator resource selection behavior translated to measurable metabolic costs in the form of reduced body fat heading into winter. Elk responses to human hunters were stronger in the day than at night and were generally more pronounced during the elk hunts than during deer hunts. During hunts, elk shifted their diurnal behavior to avoid forage and intensified their avoidance of roads and trails. The combination of these changes in behavior led to a predicted pattern of distribution during the hunt that differed substantially from the distribution prior to the hunt. Lactating females that more strongly avoided roads entered winter in poorer nutritional condition, suggesting that the changes in resource selection we describe carry corresponding nutritional costs that have the potential to impact subsequent population performance.
The intestinal expansion of TCRγδ+ and disappearance of IL4+ T cells suggest their involvement in the evolution from potential to overt celiac disease
Authors: Vitale Serena , Santarlasci Veronica , Camarca Alessandra , Picascia Stefania , Pasquale Angela Di , Maglio Mariantonia , Maggi Enrico , Cosmi Lorenzo , Annunziato Francesco , Troncone Riccardo , Auricchio Renata , Gianfrani Carmen 
Published: September 2019

AbstractCeliac disease (CD) is characterized by a spectrum of intestinal inflammatory lesions. Most patients have villous atrophy (overt‐CD), while others have a morphologically normal mucosa, despite the presence of CD‐specific autoantibodies (potential‐CD). As the mechanism responsible for villous atrophy is not completely elucidated, we investigated biomarkers specific for the different celiac lesions. Phenotype and cytokine production of intestinal mucosa cells were analyzed by flow cytometry in gut biopsies of children with overt‐ or potential‐CD and in healthy controls. Density of TCRγδ+ T cells was found markedly enhanced in intestinal mucosa of children with overt‐CD compared to potential‐CD or controls. By contrast, very few IL4+ T cells infiltrated the mucosa with villous atrophy compared to morphologically normal mucosa. IL4+ T cells were classical CD4+ T‐helper cells (CD161−), producing or not IFN‐γ, and negative for IL17A. Our study demonstrated that the transition to villous atrophy in CD patients is characterized by increased density of TCRγδ+ T cells, and concomitant disappearance of IL4+ cells. These findings suggest that immunomodulatory mechanisms are active in potential‐CD to counteract the inflammatory cascade responsible of villous atrophy. Further studies are required to validate the use of IL4+ and TCRγδ+ T cells as biomarkers of the different CD forms.
HOXC10 promotes cell migration, invasion, and tumor growth in gastric carcinoma cells through upregulating proinflammatory cytokines
Authors: Li Jingzhang , Tong Gangling , Huang Cheng , Luo Yunsheng , Wang Shubin , Zhang Ying , Cheng Boran , Zhang Zhihong , Wu Xuan , Liu Qiumei , Li Min , Li Laiqing , Ni Bingqiang 
Published: September 2019

AbstractHOXC10 plays a critical role in many cellular processes, such as proliferation, migration, and invasion, but the function of HOXC10 in gastric carcinoma is not clear. In this study, we aimed to investigate the expression profile of HOXC10 and its role in gastric carcinoma cells and in vivo experiments. HOXC10 expression patterns were detected in clinical samples and gastric cancer cells lines by reverse transcriptase polymerase chain reaction assays, and then, we focused on its role in regulating cell proliferation, cell cycle, migration, and invasion after transfection of silencing and overexpression plasmids in vitro and in vivo. Finally, we confirmed the correlation between HOXC10 and nuclear factor‐κB (NF‐κB), tumor necrosis factor‐α (TNF‐α), transforming growth factor‐β (TGF‐β), and epidermal growth factor receptor expression. We found that HOXC10 expression increased in clinical samples, especially in poorly differentiated (PD) gastric cancer cells. Silencing HOXC10 suppressed proliferation, migration, and invasion in vitro, and inhibited tumor growth and induced apoptosis in vivo. Overexpression of HOXC10 showed the opposite effect on PD gastric cancer cells. In addition, silencing HOXC10 inhibited the expression of interleukin‐6, TNF‐α, TGF‐β, and epidermal growth factor, and overexpressing HOXC10 induced their expression both in vitro and in vivo. Luciferase reporter assays and chromatin immunoprecipitation indicated that HOXC10 may activate the NF‐κB signaling pathway through regulation of P65 transcriptional activity by binding to the P65 promoter. HOXC10 may play an important role in PD gastric carcinoma cell proliferation, cell cycle, migration, invasion, and metastasis through upregulating proinflammatory cytokines via NF‐κB pathway, suggesting HOXC10 may serve as a novel therapeutic target for PD gastric cancer.
Patients' willingness to reconsider cancer genetic testing after initially declining: Mention it again
Authors: Halverson Colin M. E. , Wessinger Bronson C. , Clayton Ellen W. , Wiesner Georgia L. 
Published: September 2019

AbstractPatients at risk for hereditary cancer syndromes sometimes decline clinically appropriate genetic testing. The purpose of the current study was to understand what preferences, concerns, and desires informed their refusal as well as their current level of interest in being tested. We interviewed patients who had been seen in a hereditary cancer clinic at Vanderbilt University Medical Center and had declined genetic testing. In all, 21 in‐depth, semi‐structured qualitative interviews were conducted. Although patients provided many reasons for declining testing, they most often cited their psychosocial state at the time of the initial invitation to participate in genetic testing as their reason for refusal. The majority (67%) said that they either would or had changed their mind about testing if/when their clinicians ‘mentioned it again'. Patients at risk for hereditary cancer who refuse testing at the time of genetic counseling may later change their mind. In particular, if a patient declines testing around the time of a major medical diagnosis or intervention, clinicians who are providing ongoing care may want to raise the topic afresh after the patient has had time to recover from initial distress related to diagnosis or treatment. Strategies to prompt clinicians to have these conversations are suggested.
Testing the Canyon Hypothesis: Evaluating light and nutrient controls of phytoplankton growth in penguin foraging hotspots along the West Antarctic Peninsula
Authors: Carvalho Filipa , Fitzsimmons Jessica N. , Couto Nicole , Waite Nicole , Gorbunov Maxim , Kohut Josh , Oliver Matthew J. , Sherrell Robert M. , Schofield Oscar 
Published: September 2019

AbstractBiological hotspots along the West Antarctic Peninsula (WAP) are characterized by high phytoplankton productivity and biomass as well as spatially focused penguin foraging activity. While unique physical concentrating processes were identified in one of these hotspots, understanding the mechanisms driving the blooms at these locations is of high importance. Factors posited to explain the blooms include the upwelling of macronutrient‐ and micronutrient‐enriched modified Upper Circumpolar Deep Water (mUCDW) and the depth of the mixed layer influencing overall light availability for phytoplankton. Using shipboard trace‐metal clean incubation experiments in three different coastal biological hotspots spanning a north‐south gradient along the WAP, we tested the Canyon Hypothesis (upwelling) for enhanced phytoplankton growth. Diatoms dominated the Southern region, while the Northern region was characterized by a combination of diatoms and cryptophytes. There was ample concentration of macronutrients at the surface and no phytoplankton growth response was detected with the addition of nutrient‐enriched mUCDW water or iron solution to surface waters. For all treatments, addition of mUCDW showed no enhancement in phytoplankton growth, suggesting that local upwelling of nutrient‐enriched deep water in these hotspots was not the main driver of high phytoplankton biomass. Furthermore, the dynamics in the photoprotective pigments were consistent with the light levels used during these incubations showing that phytoplankton are able to photoacclimate rapidly to higher irradiances and that in situ cells are low light adapted. Light availability appears to be the critical variable for the development of hotspot phytoplankton blooms, which in turn supports the highly productive regional food web.
Vertical stratification and stability of biogeochemical processes in the deep saline waters of Lake Vanda, Antarctica
Authors: Schutte Charles A. , Samarkin Vladimir A. , Peters Brian , Madigan Michael T. , Bowles Marshall , Morgan‐Kiss Rachael , Casciotti Karen , Joye Samantha 
Published: September 2019

AbstractLake Vanda is a permanently ice‐covered lake in the McMurdo Dry Valleys of Antarctica. Its bottom waters remain stratified year‐round because of a strong salinity‐driven density gradient. We have assessed spatial patterns in and relationships between major biogeochemical processes in the water column of Lake Vanda. Samples were collected in the austral summers of 2008 and 2011 to measure concentrations of metabolites associated with a suite of biogeochemical processes across the deep salinity gradient. The shapes of the resulting geochemical profiles were consistent between 2008 and 2011. Metabolite production and consumption rates were estimated using a reactive transport model based on the assumption that vertical diffusion was the only active physical transport process. We validated this model for nitrification by using stable isotope incubations to show that this process was only active at depths predicted by the model. No nitrification activity was observed at 68 m depth in spite of overlapping oxygen and ammonium gradients. We attribute this lack of activity to the competitive inhibition of ammonia monooxygenase by methane. Net nitrous oxide and nitrate consumption were observed in the oxic water column, providing evidence of aerobic denitrification. The depth of maximum net oxygen production did not coincide with the deep chlorophyll maxima (at 59.3, 63, and 68.2 m) measured in the same profile. Finally, the integrated sulfide oxidation rate was high compared with other oxidation processes, indicating that sulfide was an important electron donor for the water column microbial community.
Patient Perspectives of High‐Quality Care on the Liver Transplant Waiting List: A Qualitative Study
Authors: Shen Nicole T. , Wu Ashley , Farrell Karen , Ivatorov Amanda , Dawod Enad , Raver Michael , Russo Nicholas , Robbins Laura , Safford Monika , Brown Robert S. 
Published: September 2019

The prevalence of advanced liver disease and listing for liver transplantation is increasing. Prior assessments of quality of care neither incorporate nor emphasize the patient perspective on quality of care, which may impact clinical outcomes. Our aim was to identify patients’ perceptions on what constitutes high quality of care, comparing the findings to existing frameworks and assessments to determine if a patient‐derived tool assessing quality of care could facilitate efforts to improve health care. We conducted semistructured interviews of patients wait‐listed for liver transplantation, asking patients to describe the quality of their health care with a specific focus on how coordination, communication, office visits, hospitalizations, and cost affect their perceptions of the quality of their care. Data collection conducted concurrently with analyses determined emerging themes and saturation. Themes were mapped to an existing quality‐of‐care conceptual framework. Qualitative analysis revealed thematic saturation after 15 interviews, and an additional 15 interviews were analyzed that confirmed thematic saturation, maximizing the strength of the results. The 30 patients had a median age of 56 years (range, 32‐72 years) and included 15 (50%) men. Although patients believed they received a high quality of care, which was substantiated on current existing measures, a qualitative analysis suggested that patient priorities emphasized 5 themes not currently assessed: managing expectations, providing education, responding to patient needs, executing the care plan efficiently, and utilizing interdisciplinary communication and coordination of care. In conclusion, transplant candidates perceived 5 themes that constitute quality of care, and existing quality‐of‐care measures do not assess these domains, suggesting a role for creating a patient‐derived quality‐of‐care tool to improve health care and clinical outcomes.
Extreme Value Statistics
Authors: Jacob Maria , Neves Cláudia , Vukadinović Greetham Danica 
Published: September 2019

AbstractWhen studying peaks in electricity demand, we may be interested in understanding the risk of a certain large level for demand being exceeded. For example, there is potential interest in finding the probability that the electricity demand of a business or household exceeds the contractual limit. An alternative, yet in principle equivalent way, involves assessment of maximal needs for electricity over a certain period of time, like a day, a week or a season within a year. This would stem from the potential interested in quantifying the largest electricity consumption for a substation, household or business.
Assembling a prehistory for formal methods: a personal view
Authors: Haigh Thomas 
Published: September 2019

Abstract
The history of formal methods has barely been written. Haigh recapitulates his own exposure to relevant material during three phases of his development as a scholar: as a student of computer science, as a graduate student in history, and as a professor researching the history of computing. Triangulating these perspectives suggests that formal methods is one of several strands emerging from a community of researchers that gathered around Algol, flirted with software engineering, and found an enduring home in the IFIP working group on programming methodologies. Yet the story of how a declared “formal methods” movement emerged fromthis group has remains unclear.Haigh explores some relevant ideas fromacademic history, sketches historical connections between formal methods and other areas of computer science, and concludes with some suggestion for and challenges to formal methods participants who aim to tell the story of their field. This, he suggests, may cheer up Donald Knuth.
Assessment of cognitive function in female rheumatoid arthritis patients: associations with cerebrovascular pathology, depression and anxiety
Authors: Oláh Csaba , Kardos Zsófia , Andrejkovics Mónika , Szarka Enikő , Hodosi Katalin , Domján Andrea , Sepsi Mariann , Sas Attila , Kostyál László , Fazekas Katalin , Flórián Ágnes , Lukács Katalin , Miksi Ágnes , Baráth Zsuzsanna , Kerekes György , Péntek Márta , Valikovics Attila , Tamási László , Bereczki Dániel , Szekanecz Zoltán 
Published: September 2019

AbstractWe assessed cognitive function of female rheumatoid arthritis (RA) patients and analyze the determinants, with special focus on cerebrovascular morphology. Sixty methotrexate (MTX-) or biologic-treated RA patients and 39 healthy controls were included in a cross-sectional study. Smoking habits, alcohol intake and time spent in education were recorded. Standard measures were performed to assess cognitive function (Montreal Cognitive Assessment, MOCA; Trail Making Test, TMT; Victoria Stroop Test, VST; Wechsler Adult Intelligence Scale, WAIS; Benton Visual Retention test, BVRT), depression (Beck Depression Inventory, BDI), anxiety (State-Trait Anxiety Inventory, STAIT/S) and general health status (Short Form 36, SF-36). Mean disease activity (28-joint Disease Activity Score, mDAS28; erythrocyte sedimentation rate, mESR; C-reactive protein, mCRP) of the past 12 months was calculated; anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) were assessed. Cerebral vascular lesions and atrophy, carotid intima–media thickness (cIMT) and plaques, as well as median cerebral artery (MCA) circulatory reserve capacity (CRC) were assessed by brain magnetic resonance imaging (MRI), carotid ultrasound and transcranial Doppler, respectively. Cognitive function tests showed impairment in RA vs controls. Biologic- vs MTX-treated subgroups differed in TMT-A. Correlations were identified between cognitive function and depression/anxiety tests. WAIS, STAIS, STAIT and BDI correlated with most SF-36 domains. Numerous cognitive tests correlated with age and lower education. Some also correlated with disease duration, mESR and mDAS28. Regarding vascular pathophysiology, cerebral vascular lesions were associated with VST-A, carotid plaques with multiple cognitive parameters, while MCA and CRC with MOCA, BVRT and BDI. RA patients have significant cognitive impairment. Cognitive dysfunction may occur together with or independently of depression/anxiety. Older patients and those with lower education are at higher risk to develop cognitive impairment. Cognitive screening might be a useful tool to identify subgroups to be further investigated for cerebrovascular pathologies.
Portal flow modulation in living donor liver transplantation: review with a focus on splenectomy
Authors: Yoshizumi Tomoharu , Mori Masaki 
Published: September 2019

Abstract
Small-for-size graft (SFSG) syndrome after living donor liver transplantation (LDLT) is the dysfunction of a small graft, characterized by coagulopathy, cholestasis, ascites, and encephalopathy. It is a serious complication of LDLT and usually triggered by excessive portal flow transmitted to the allograft in the postperfusion setting, resulting in sinusoidal congestion and hemorrhage. Portal overflow injures the liver directly through nutrient excess, endothelial activation, and sinusoidal shear stress, and indirectly through arterial vasoconstriction. These conditions may be attenuated with portal flow modulation. Attempts have been made to control excessive portal flow to the SFSG, including simultaneous splenectomy, splenic artery ligation, hemi-portocaval shunt, and pharmacological manipulation, with positive outcomes. Currently, a donor liver is considered a SFSG when the graft-to-recipient weight ratio is less than 0.8 or the ratio of the graft volume to the standard liver volume is less than 40%. A strategy for transplanting SFSG safely into recipients and avoiding extensive surgery in the living donor could effectively address the donor shortage. We review the literature and assess our current knowledge of and strategies for portal flow modulation in LDLT.
Strong Pluralism, Coincident Objects and Haecceitism
Authors: Lenart Karol , Szachniewicz Artur 
Published: September 2019

AbstractAccording to strong pluralism, objects distinct by virtue of their modal properties can coincide. The most common objection towards such view invokes the so-called Grounding Problem according to which the strong pluralist needs to explain what the grounds are for supposed modal differences between the coincidents. As recognized in the literature, the failure to provide an answer to the Grounding Problem critically undermines the plausibility of strong pluralism. Moreover, there are strong reasons to believe that strong pluralists cannot provide an explanation of the Grounding Problem. In this paper, we argue that strong pluralism can be motivated independently of the successful answer to the Grounding Problem. In order to achieve that aim, we provide a haecceitistic interpretation of strong pluralism according to which strong pluralism should be read as a position committed to the existence of primitive individuals, i.e., the individuals that have their criteria of individuation independently of their qualitative profiles. That said, we do not aim at defending haecceitism. Instead, our aim is rather modest: we want to provide a new way for the strong pluralist to supplement his view to make it more watertight.
Vocational identity of at-risk emerging adults and its relationship with individual characteristics
Authors: Keijzer Rineke , Admiraal Wilfried , Van der Rijst Roeland , Van Schooten Erik 
Published: September 2019

AbstractVocational identity is a prerequisite for enhancing societal inclusion of at-risk emerging adults. School curricula and rebound programs need insights into individual differences of these youths to effectively foster their vocational identity. Identifying three aspects of vocational identity, a questionnaire study among at-risk emerging adults in The Netherlands (N = 996) examined the relationship between clusters of demographic, personality, self-sufficiency, self-competence, and school engagement characteristics and vocational identity performing blockwise entry analyses. Largest proportions of variance were explained by personality traits and, to a lesser extent, motivation, resilience, and valuing school outcome. These malleable characteristics offer opportunities for interventions.