bluuebunny/crossref_metadata_2025 huggingface dataset:
Revisiting Contemporary Issues in B2B Marketing: It's Not Just about Artificial Intelligence
Authors: Prior Daniel D. , Keränen Joona
Published: September 2019

In this paper, we offer critical reflections on several contemporary issues in B2B marketing research. Specifically, we consider value, customer solutions, temporary organizations, governance models and sustainability within this literature. Our reflections lead us to suggest that further B2B marketing research is necessary in terms of four main areas (i) integrating complex offers for solutions, (ii) integrating functional activities, (iii) understanding the inter-related societal effects of B2B marketing, and (iv) understanding B2B marketing in information-poor environments. We develop an agenda that could serve to motivate further B2B marketing research while also reminding scholars that ‘it's not just about Artificial Intelligence (AI)’ or Information Technology (IT).
Quantitative MRI study of infant regional brain size following surgery for long‐gap esophageal atresia requiring prolonged critical care
Authors: Lee Mongerson Chandler Rebecca , Jennings Russell William , Zurakowski David , Bajic Dusica
Published: September 2019

Introduction

Little is known regarding the impact of concurrent critical illness and thoracic noncardiac perioperative critical care on postnatal brain development. Previously, we reported smaller total brain volumes in both critically ill full‐term and premature patients following complex perioperative critical care for long‐gap esophageal atresia (LGEA). Our current report assessed trends in regional brain sizes during infancy, and probed for any group differences.

Methods

Full‐term (n = 13) and preterm (n = 13) patients without any previously known neurological concerns, and control infants (n = 16), underwent non‐sedated 3 T MRI in infancy (<1 year old). T2‐weighted images underwent semi‐automated brain segmentation using Morphologically Adaptive Neonatal Tissue Segmentation (MANTiS). Regional tissue volumes of the forebrain, deep gray matter (DGM), cerebellum, and brainstem are presented as absolute (cm3) and normalized (% total brain volume (%TBV)) values. Group differences were assessed using a general linear model univariate analysis with corrected age at scan as a covariate.

Results

Absolute volumes of regions analyzed increased with advancing age, paralleling total brain size, but were significantly smaller in both full‐term and premature patients compared to controls. Normalized volumes (%TBV) of forebrain, DGM, and cerebellum were not different between subject groups analyzed. Normalized brainstem volumes showed group differences that warrant future studies to confirm the same finding.

Discussion

Both full‐term and premature critically ill infants undergoing life‐saving surgery for LGEA are at risk of smaller total and regional brain sizes. Normalized volumes support globally delayed or diminished brain growth in patients. Future research should look into neurodevelopmental outcomes of infants born with LGEA.
Role of JAK2 in the Pathogenesis of Diabetic Erectile Dysfunction and an Intervention With Berberine
Authors: Song Jingyu , Tang Zhe , Li Hao , Jiang Hongyang , Sun Taotao , Lan Ruzhu , Wang Tao , Wang Shaogang , Ye Zhangqun , Liu Jihong
Published: September 2019

Background

Oxidative stress is a significant contributor to the poor treatment efficacy on erectile dysfunction induced by diabetes mellitus (DMED). Thus, understanding the mechanism underlying oxidative stress will aid in the identification of novel therapeutic targets.

Aim

To define the role of Janus kinase 2 (JAK2) in mediating oxidative stress in the corpus cavernosum smooth muscle cells (CCSMCs) and to investigate the therapeutic effect of monomeric berberine (BB), which inhibits JAK2, in the pathogenesis of DMED.

Methods

Streptozotocin was used to establish type I diabetic rat models and apomorphine tests were conducted to determine DMED rats. Eighteen DMED rats were divided into the DMED group and the DMED+BB group, whereas another 10 age-matched rats formed the control group. CCSMCs were isolated from the corpus cavernosum of rats and were treated with the JAK2 inhibitor alpha cyanano-(3,4-hydroxyl)N-benzophenylamine (AG490) and/or BB.

Outcomes

Metabolic parameters; erectile function; histologic and molecular alterations.

Results

Erectile function was impaired and excessive oxidative stress was found in the DMED group. Excessive oxidative stress led to decreased expression level of phosphorylated endothelial nitric oxide synthase at serine 1177/endothelial nitric oxide synthase and increased expression level of Ras homolog gene family and Rho kinase 1/2. Meanwhile, the relative expression ratio of phosphorylated JAK2/JAK2 was significantly greater in the DMED group than that in the other groups. In vitro, oxidative stress was significantly reduced along with reduced intracellular calcium upon treatment with the JAK2 inhibitor, AG490. Moreover, the CCSMCs treated with BB showed changes similar to those upon treatment with AG490. In vivo experiments also confirmed that the erectile function of the DMED+BB group was improved, accompanied by decreased phosphorylated JAK2/JAK2 and decreased oxidative stress.

Clinical Translation

JAK2 can be used as a therapeutic target and BB can be used as a potential drug for the clinical treatment of DMED.

Strengths and Limitations

This study examines the promoting effect of JAK2 on oxidative stress occurrence in the corpus cavernosum and on the development of DMED in both animal experiments and cell experiments, as well evaluates the inhibitory effect of BB on JAK2 and its therapeutic effect on DMED. The main limitation of our current study is the lack of an appropriate means for activating JAK2.

Conclusions

JAK2 can induce DMED by enhancing oxidative stress and BB can play a role in treating DMED by inhibiting JAK2 and reducing oxidative stress. Our study provides an option and an idea for further studies on the pathogenesis and treatment of DMED.
Mitochondrial calcium uniporter as a potential therapeutic strategy for Alzheimer’s disease
Authors: Venugopal Anila , Iyer Mahalaxmi , Balasubramanian Venkatesh , Vellingiri Balachandar
Published: September 2019

Alzheimer’s disease (AD), a neurodegenerative disorder, is the leading cause of dementia in the world whose aetiology is still unclear. AD was always related to ageing though there have been instances where people at an early age also succumb to this disease. With medical advancements, the mortality rate has significantly reduced which also makes people more prone to AD. AD is rare, yet the prominent disease has been widely studied with several hypotheses trying to understand the workings of its onset. The most recent and popular hypothesis in AD is the involvement of mitochondrial dysfunction and calcium homeostasis in the development of the disease though their exact roles are not known. With the sudden advent of the mitochondrial calcium uniporter (MCU), many previously known pathological hallmarks of AD may be better understood. Several studies have shown the effect of excess calcium in mitochondria and the influence of MCU complex in mitochondrial function. In this article, we discuss the possible involvement of MCU in AD by linking the uniporter to mitochondrial dysfunction, calcium homeostasis, reactive oxygen species, neurotransmitters and the hallmarks of AD – amyloid plaque formation and tau tangle formation.
Military Aid, Regime Vulnerability and the Escalation of Political Violence
Authors: Boutton Andrew
Published: September 2019

This article offers an explanation for the failures of US military assistance programs in some countries. The author argues that the effects of military aid are conditional upon the vulnerability of the recipient regime. Power consolidation by an insecure leader often provokes violent opposition. However, because military aid strengthens the security forces of the recipient state, it generates a moral hazard that encourages exclusionary power consolidation, with the expectation that continued military aid will help manage violent blowback. Using proxies for regime vulnerability and an instrument for US military aid, the study shows that military aid increases anti-regime violence in new regimes (particularly new democracies) and in all personalist regimes. In contrast, military assistance has no effect on violence in established, non-personalist regimes. The article develops a novel theory of how regime characteristics condition responses to external military support, and identifies a distinct mechanism through which military aid increases domestic political violence.
Debt Renegotiation and Debt Overhang: Evidence from Lender Mergers
Authors: Chu Yongqiang
Published: September 2019

This article studies whether debt renegotiation mitigates debt overhang and increases corporate investment. Using mergers between lenders participating in the same syndicated loans as natural experiments that reduce the number of lenders and thus make renegotiation easier, I find that the firms affected by the mergers become more likely to renegotiate the loans and increase capital investment. The effect is stronger for firms with higher Q and firms in financial distress, supporting the hypothesis that the lender mergers mitigate the debt-overhang problem.
Transboundary conservation of the last remaining population of the cao vit gibbon Nomascus nasutus
Authors: Ma Chang-yong , Trinh-Dinh Hoang , Nguyen Van-Truong , Le Trong-Dat , Le Van-Dung , Le Huu-Oanh , Yang Jiang , Zhang Zi-Jie , Fan Peng-Fei
Published: September 2019

The cao vit gibbon Nomascus nasutus, also known as eastern black crested gibbon, is categorized as Critically Endangered on the IUCN Red List and was considered one of the world's 25 most threatened primates. The only known population occurs along the border between China and Viet Nam. Accurate information on population size and dynamics is critical for the species’ conservation, but population surveys conducted in only one country may over- or underestimate total population size because the home ranges of cao vit gibbon groups often cross the international border. In 2007 and 2016 we conducted two collaborative transboundary censuses of the cao vit gibbon populations in the Trung Khanh Cao Vit Gibbon Species and Habitat Conservation Area in Viet Nam and the Bangliang Gibbon National Nature Reserve in China. The results showed a population size of 102–110 in 2007, which increased to 107–136 in 2016. Our results indicate that previous surveys conducted separately in Viet Nam and China underestimated the global population size of this species. According to our more comprehensive surveys, the gibbon population is increasing slowly. The gibbons and their habitat are legally protected in both countries. Hunting and charcoal making have not been reported in this area since 2007. As habitat carrying capacity is a limiting factor, habitat restoration is required. However, lack of funding to protect the cao vit gibbon remains a challenge.
Black rhinoceros avoidance of tourist infrastructure and activity: planning and managing for coexistence
Authors: Muntifering Jeff R. , Linklater Wayne L. , Naidoo Robin , !Uri-≠Khob Simson , du Preez Pierre , Beytell Petrus , Jacobs Shayne , Knight Andrew T.
Published: September 2019

Wildlife-based tourism poses opportunities and challenges for species conservation. Minimizing potential negative impacts of tourism is critical to ensure business and conservation enterprises can coexist. In north-western Namibia tourism is used as a conservation tool for the Critically Endangered black rhinocerosDiceros bicornis. However, black rhinoceroses are susceptible to human disturbance and may become displaced by tourist activities, which threatens not only the security and health of the rhinoceros population but also the sustainability of the business. We examined areas avoided by black rhinoceroses to understand how they respond to the type and extent of tourism development, and to evaluate management alternatives. We used spatial data on use of water sources by rhinoceroses to create a series of a priori candidate models that described the negative influences of tourist activities on rhinoceros habitat use. A model selection approach strongly supported a cumulative zones of influence model comprised of a 6 km buffer around the airstrip combined with a 1 km buffer around roads used daily. We compared alternative management scenarios using the best-performing model and found that an optimal road-use policy combined with airstrip relocation could minimize the total area avoided by the black rhinoceros to 7.1% and loss of high quality habitat to 20.7%. Under the worst-case scenario the area avoided and loss of high quality habitat were 153 and 85% greater, respectively, than under the scenario with optimal management. Our findings provide a novel framework and a practical, policy-relevant decision support tool to improve the contribution of tourism to wildlife conservation.
A review of toxoplasmosis in humans and animals in Turkey
Authors: Kolören Z. , Dubey J. P.
Published: September 2019

Infections by the protozoan parasiteToxoplasma gondiiare widely prevalent in humans and animals in Turkey but little is known of the burden of their clinical toxoplasmosis. Many early papers on toxoplasmosis in Turkey were published in Turkish and often not available widely. Here, we review prevalence, clinical spectrum, epidemiology and diagnosis ofT. gondiiin humans and animals in Turkey. This knowledge should be useful to biologists, public health workers, veterinarians and physicians. Although one-third of the human population in Turkey is seropositive, the rate of congenital toxoplasmosis is unknown and no information is available in children 12 years old or younger. One large outbreak of acute toxoplasmosis has been reported in 14–18-year old school children in Turkey. An alarming rate (36%) ofT. gondiitissue cysts were reported in tissues of sheep and water buffalo meats destined for human consumption; these reports require verification. Genetically,T. gondiistrains from domestic cats and wild birds in Turkey were generally classical type II and III, like those prevalent in Europe. A separate genotype, Type 1 Africa, was isolated from two congenitally infected children and a domestic cat in Turkey.
The securitisation of dementia: socialities of securitisation on secure dementia care units
Authors: Graham Megan E.
Published: September 2019

Nearly 50 million people around the world live with dementia, with statistics predicting a steady increase in prevalence for the foreseeable future. There is a need for comprehensive and compassionate dementia care. Long-term care homes have built special care units for people living with middle- to late-stage dementia. Among other services, these care units often use innovative security technologies that monitor and curtail movement beyond unit exit doors. As care-givers and technology developers grapple with the ethical dilemma of autonomy and risk management, researchers are beginning to investigate the social impact of these security technologies. The present research contributes to this line of inquiry. Fieldwork was carried out on two secure long-term care units for people living with dementia. Ethnographic accounts will illustrate how security technology creates socialities of securitisation on a secure dementia unit. Using securitisation theory, I will argue that dementia has been redefined, shifting it from a health issue to a security issue. The discursive construction of dementia as a security issue will be considered in terms of the co-constructed notions of vulnerability, risk, security threat and security challenge with respect to people living with dementia. The paper investigates how securitisation influences the ethics of dementia care.
Estimating Fingertip Forces, Torques, and Local Curvatures from Fingernail Images
Authors: Chen Nutan , Westling Göran , Edin Benoni B. , van der Smagt Patrick
Published: September 2019

The study of dexterous manipulation has provided important insights into human sensorimotor control as well as inspiration for manipulation strategies in robotic hands. Previous work focused on experimental environment with restrictions. Here, we describe a method using the deformation and color distribution of the fingernail and its surrounding skin to estimate the fingertip forces, torques, and contact surface curvatures for various objects, including the shape and material of the contact surfaces and the weight of the objects. The proposed method circumvents limitations associated with sensorized objects, gloves, or fixed contact surface type. In addition, compared with previous single finger estimation in an experimental environment, we extend the approach to multiple finger force estimation, which can be used for applications such as human grasping analysis. Four algorithms are used, c.q., Gaussian process, convolutional neural networks, neural networks with fast dropout, and recurrent neural networks with fast dropout, to model a mapping from images to the corresponding labels. The results further show that the proposed method has high accuracy to predict force, torque, and contact surface.
Emerging languages: An alternative approach to teaching programming languages
Authors: PERUGINI SAVERIO
Published: September 2019

We challenge the idea that a course intended to convey principles of languages should be structured according to those principles, and present an alternate approach to teaching a programming language course. The approach involves teaching emerging programming languages. This approach results in a variety of course desiderata including scope for instructor customization; alignment with current trends in language evolution, practice, and research; and congruence with industrial needs. We discuss the rationale for, the course mechanics supporting, and the consequences of this approach.
A NEW SPECIES OF TUBEROUS BEGONIA (BEGONIACEAE) FROM ANDEAN PERU
Authors: Moonlight P. W. , Hollands R. , Cano A. , Purvis D. A.
Published: September 2019

A striking new species of Begonia, B. joshii, is described from Amazonas Region, Peru. The new species is unusual among the South American members of the genus both in its combination of tuberous habit with peltate leaves and in living in a seasonally dry tropical forest environment. A phylogeny of this and closely related species is presented, and its sectional affiliation and IUCN conservation status are discussed. A key to the peltate Peruvian species of Begonia is provided.
Recommendations from the Association for European Paediatric and Congenital Cardiology for training in pulmonary hypertension
Authors: Sallmon Hannes , Moledina Shahin , Albert Dimpna C. , Beghetti Maurice , Berger Rolf M. F. , Bonnet Damien , Bukova Mila , Koestenberger Martin , Meinel Katharina , Reinhardt Zdenka , Tulloh Robert M. R. , de Wolf Daniel , Hansmann Georg
Published: September 2019

Pulmonary hypertension is a complex and progressive condition that is either idiopathic or heritable, or associated with one or multiple health conditions, with or without congenital or acquired cardiovascular disease. Recent developments have tremendously increased the armamentarium of diagnostic and therapeutic approaches in children and young adults with pulmonary hypertension that is still associated with a high morbidity and mortality. These modalities include non-invasive imaging, pharmacotherapy, interventional and surgical procedures, and supportive measures. The optimal, tailored diagnostic and therapeutic strategies for pulmonary hypertension in the young are rapidly evolving but still face enormous challenges: Healthcare providers need to take the patient’s age, development, disease state, and family concerns into account when initiating advanced diagnostics and treatment. Therefore, there is a need for guidance on core and advanced medical training in paediatric pulmonary hypertension. The Association for European Paediatric and Congenital Cardiology working group “pulmonary hypertension, heart failure and transplantation” has produced this document as an expert consensus statement; however, all recommendations must be considered and applied in the context of the local and national infrastructure and legal regulations.
Canine vector-borne disease: mapping and the accuracy of forecasting using big data from the veterinary community
Authors: Self Stella C. W. , Liu Yan , Nordone Shila K. , Yabsley Michael J. , Walden Heather S. , Lund Robert B. , Bowman Dwight D. , Carpenter Christopher , McMahan Christopher S. , Gettings Jenna R.
Published: September 2019

Diagnosis, treatment, and prevention of vector-borne disease (VBD) in pets is one cornerstone of companion animal practices. Veterinarians are facing new challenges associated with the emergence, reemergence, and rising incidence of VBD, including heartworm disease, Lyme disease, anaplasmosis, and ehrlichiosis. Increases in the observed prevalence of these diseases have been attributed to a multitude of factors, including diagnostic tests with improved sensitivity, expanded annual testing practices, climatologic and ecological changes enhancing vector survival and expansion, emergence or recognition of novel pathogens, and increased movement of pets as travel companions. Veterinarians have the additional responsibility of providing information about zoonotic pathogen transmission from pets, especially to vulnerable human populations: the immunocompromised, children, and the elderly. Hindering efforts to protect pets and people is the dynamic and ever-changing nature of VBD prevalence and distribution. To address this deficit in understanding, the Companion Animal Parasite Council (CAPC) began efforts to annually forecast VBD prevalence in 2011. These forecasts provide veterinarians and pet owners with expected disease prevalence in advance of potential changes. This review summarizes the fidelity of VBD forecasts and illustrates the practical use of CAPC pathogen prevalence maps and forecast data in the practice of veterinary medicine and client education.
Early-life exposures and cardiovascular disease risk among Ghanaian migrant and home populations: the RODAM study
Authors: Boateng Daniel , Danquah Ina , Said-Mohamed Rihlat , Smeeth Liam , Nicolaou Mary , Meeks Karlijn , Beune Erik , Addo Juliet , Bahendeka Silver , Agyei-Baffour Peter , Mockenhaupt Frank P. , Spranger Joachim , Schulze Matthias B. , Grobbee Diederick E. , Agyemang Charles , Klipstein-Grobusch Kerstin
Published: September 2019

Early-life environmental and nutritional exposures are considered to contribute to the differences in cardiovascular disease (CVD) burden. Among sub-Saharan African populations, the association between markers of early-life exposures such as leg length and sitting height and CVD risk is yet to be investigated. This study assessed the association between leg length, sitting height, and estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk among Ghanaian-born populations in Europe and Ghana. We constructed sex-specific quintiles for sitting height and leg length for 3250 participants aged 40–70 years (mean age 52 years; men 39.6%; women 60.4%) in the cross-sectional multicenter Research on Diabetes and Obesity among African Migrants study. Ten-year risk of ASCVD was estimated using the Pooled Cohort Equations; risk ≥7.5% was defined as “elevated” CVD risk. Prevalence ratios (PR) were estimated to determine the associations between sitting height, leg length, and estimated 10-year ASCVD risk. For both men and women, mean sitting height and leg length were highest in Europe and lowest in rural Ghana. Sitting height was inversely associated with 10-year ASCVD risk among all women (PR for 1 standard deviation increase of sitting height: 0.75; 95% confidence interval: 0.67, 0.85). Among men, an inverse association between sitting height and 10-year ASCVD risk was significant on adjustment for study site, adult, and parental education but attenuated when further adjusted for height. No association was found between leg length and estimated 10-year ASCVD risk. Early-life and childhood exposures that influence sitting height could be the important determinants of ASCVD risk in this adult population.
Cognitive remediation in schizophrenia: the earlier the better?
Authors: Bellani Marcella , Ricciardi Chiara , Rossetti Maria Gloria , Zovetti Niccolò , Perlini Cinzia , Brambilla Paolo
Published: September 2019

Impairments in neuro and social cognition are considered core features of schizophrenia (SCZ) since they affect patients' functioning and contribute to poor socio-occupational outcomes. Therefore, the improvement of cognitive performances has become a primary goal in the care of patients with SCZ, especially in the first phases of the disease, as early interventions may favour better long-term outcomes. Cognitive remediation (CR) is a behavioural training aimed at improving cognitive functions with the goal of durability and generalisation in everyday life. Neuroimaging studies suggest that CR leads to neuroplasticity in chronic SCZ, whereas only a few studies tested the neural effects of CR in the early phase of the disease. Thus, in this review, we aimed at summarising CR-induced structural and functional brain changes in early SCZ. Existing evidence showed a protective effect of CR on grey matter volume in selected medial-temporal (i.e. hippocampus, parahippocampus and amygdala) and thalamic regions whereas functional changes affected mostly dorsolateral prefrontal and insular cortices both associated with improvements in cognitive performance and emotion regulation. Overall, CR in early SCZ appears to be associated with neural adaptations mostly allocated in prefrontal and limbic regions, however future longitudinal studies are needed to clarify whether the positive effects of cognitive training persist over time. It may also be interesting to investigate whether the application of CR in the early v. the late stage of the disease may lead to incremental benefits.
Ixazomib–Thalidomide–Dexamethasone for induction therapy followed by Ixazomib maintenance treatment in patients with relapsed/refractory multiple myeloma
Authors: Ludwig Heinz , Poenisch Wolfram , Knop Stefan , Egle Alexander , Schreder Martin , Lechner Daniel , Hajek Roman , Gunsilius Eberhard , Krenosz Karl Jochen , Petzer Andreas , Weisel Katja , Niederwieser Dietger , Einsele Hermann , Willenbacher Wolfgang , Melchardt Thomas , Greil Richard , Zojer Niklas
Published: September 2019

Background

Ixazomib-revlimid-dexamethason showed significant activity in relapsed/refractory multiple myeloma (RRMM). Here, we evaluate ixazomib in combination with thalidomide and dexamethasone for induction treatment followed by ixazomib maintenance therapy in RRMM patients.

Methods

Ninety patients have been included. Ixazomib–thalidomide–dexamethasone (4 mg, day 1, 8, 15; 100 mg daily; and 40 mg weekly) was scheduled for eight cycles followed by maintenance with ixazomib for one year.

Results

The overall response rate was 51.1%, 23.3% achieved CR or VGPR and 10% MR resulting in a clinical benefit rate of 61.1%. In patients completing ≥2 cycles, the rates were 60.5%, 27.6% and 68.4%, respectively. Median progression-free survival (PFS) was 8.5 months in all, and 9.4 months in those completing ≥2 cycles. Response rates, PFS and overall survival (OS) were similar in patients with and without t(4;14) and/or del(17p), but PFS and OS was significantly shorter in patients with gain of 1q21. Multivariate regression analysis revealed gain of 1q21 as the most important factor associated with OS. Ixazomib maintenance resulted in an upgrade in the depth of response in 12.4% of patients. Grade 3/4 toxicities were relatively rare.

Conclusions

Ixazomib–thalidomide–dexamethasone followed by ixazomib maintenance therapy is active and well tolerated in patients with RRMM.

Trial registration number

NCT02410694
SEPT9_i1 regulates human breast cancer cell motility through cytoskeletal and RhoA/FAK signaling pathway regulation
Authors: Zeng Yongqiu , Cao Yang , Liu Lan , Zhao Jiao , Zhang Ting , Xiao Lifan , Jia Man , Tian Qiang , Yu Hong , Chen Shaokun , Cai Yansen
Published: September 2019

Increasing cell mobility is the basis of tumor invasion and metastasis, and is therefore a therapeutic target for preventing the spread of many types of cancer. Septins are a family of cytoskeletal proteins with GTPase activity, and play a role in many important cellular functions, including cell migration. SEPT9 isoform 1 protein (SEPT9_i1) has been associated with breast tumor development and the enhancement of cell migration; however, the exact mechanism of how SEPT9_i1 might affect breast cancer progression remains to be elucidated. Here, we report that the expression of SEPT9_i1 positively correlated with paxillin, and both were significantly upregulated in invasive breast cancer tissues of patients with lymph node metastases. Lentivirus-mediated shRNA knockdown of SEPT9 in MCF-7 cells diminished tumor cell migration, focal adhesion (FA) maturation and the expression of β-actin, β-tubulin, Cdc42, RhoA, and Rac, whereas overexpression of SEPT9_i1 in SEPT9-knockdown MCF-7 cells promoted cell migration, FA maturation and relevant protein expression. Furthermore, overexpression of SEPT9_i1 in MCF-7 cells markedly increased FAK/Src/paxillin signaling, at least in part through RhoA/ROCK1 upstream activation. Transcriptome profiling suggested that SEPT9_i1 may directly affect “Focal adhesion” and “Regulation of actin cytoskeleton” signaling mechanisms. Finally, overexpression of SEPT9_i1 markedly enhanced lung metastases in vivo 6 weeks after tumor inoculation. These findings suggest that a mechanism of Septin-9-induced aberrant cancer cell migration is through cytoskeletal regulation and FA modulation, and encourages the use of SEPT9 as novel therapeutic target in the prevention of tumor metastasis.
LIM homeodomain transcription factor Isl1 affects urethral epithelium differentiation and apoptosis via Shh
Authors: Su Tiantian , Liu Hui , Zhang Di , Xu Guojin , Liu Jiali , Evans Sylvia M. , Pan Jirong , Cui Sheng
Published: September 2019

Urethral hypoplasia, including failure of urethral tube closure, is one of the common phenotypes observed in hereditary human disorders, the mechanism of which remains unclear. The present study was thus designed to study the expression, functions, and related mechanisms of the LIM homeobox transcription factor Isl1 throughout mouse urethral development. Results showed that Isl1 was highly expressed in urethral epithelial cells and mesenchymal cells of the genital tubercle (GT). Functional studies were carried out by utilizing the tamoxifen-inducible Isl1-knockout mouse model. Histological and morphological results indicated that Isl1 deletion caused urethral hypoplasia and inhibited maturation of the complex urethral epithelium. In addition, we show that Isl1-deleted mice failed to maintain the progenitor cell population required for renewal of urethral epithelium during tubular morphogenesis and exhibited significantly increased cell death within the urethra. Dual-Luciferase reporter assays and yeast one-hybrid assays showed that ISL1 was essential for normal urethral development by directly targeting the Shh gene. Collectively, results presented here demonstrated that Isl1 plays a crucial role in mouse urethral development, thus increasing our potential for understanding the mechanistic basis of hereditary urethral hypoplasia.
Correction: Inhibition of Stat3 signaling pathway by nifuroxazide improves antitumor immunity and impairs colorectal carcinoma metastasis
Authors: Ye Ting-Hong , Yang Fang-Fang , Zhu Yong-Xia , Li Ya-Li , Lei Qian , Song Xue-Jiao , Xia Yong , Xiong Ying , Zhang Li-Dan , Wang Ning-Yu , Zhao Li-Feng , Gou Hong-Feng , Xie Yong-Mei , Yang Sheng-Yong , Yu Luo-Ting , Yang Li , Wei Yu-Quan
Published: September 2019

Since publication of this article, the authors have noticed that there were errors in Fig. 1b (the CT 26 cells colony formation images) and Fig. 7c (the vehicle group images). As a result of the misfiling of the data during preparation of figures, incorrect images were inadvertently inserted in these figures.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The risks of long-term re-injection in supercritical geothermal systems
Authors: Parisio Francesco , Vilarrasa Victor , Wang Wenqing , Kolditz Olaf , Nagel Thomas
Published: September 2019

Supercritical geothermal systems are appealing sources of sustainable and carbon-free energy located in volcanic areas. Recent successes in drilling and exploration have opened new possibilities and spiked interest in this technology. Experimental and numerical studies have also confirmed the feasibility of creating fluid conducting fractures in sedimentary and crystalline rocks at high temperature, paving the road towards Enhanced Supercritical Geothermal Systems. Despite their attractiveness, several important questions regarding safe exploitation remain open. We dedicate this manuscript to the first thermo-hydro-mechanical numerical study of a doublet geothermal system in supercritical conditions. Here we show that thermally-induced stress and strain effects dominate the geomechanical response of supercritical systems compared to pore pressure-related instabilities, and greatly enhance seismicity during cold water re-injection. This finding has important consequences in the design of Supercritical Geothermal Systems.
Catalytically inactive Dnmt3b rescues mouse embryonic development by accessory and repressive functions
Authors: Nowialis Pawel , Lopusna Katarina , Opavska Jana , Haney Staci L. , Abraham Ajay , Sheng Peike , Riva Alberto , Natarajan Amarnath , Guryanova Olga , Simpson Melanie , Hlady Ryan , Xie Mingyi , Opavsky Rene
Published: September 2019

DNA methylation regulates gene expression in a variety of processes, including mouse embryonic development. Four catalytically active enzymes function in mice as DNA methyltransferases (Dnmts) and as transcriptional regulators. Inactivation of Dnmt3b results in mouse embryonic lethality, but which activities are involved is unclear. Here we show that catalytically inactive Dnmt3b restores a majority of methylation and expression changes deregulated in the absence of Dnmt3b, and as a result, mice survive embryonic development. Thus, Dnmt3b functions as an accessory cofactor supporting catalytic activities performed by other Dnmts. We further demonstrate that Dnmt3b is linked to a control of major developmental pathways, including Wnt and hedgehog signaling. Dnmt3b directly represses Wnt9b whose aberrant up-regulation contributes to embryonic lethality of Dnmt3b knockout embryos. Our results highlight that Dnmt3b is a multifaceted protein that serves as an enzyme, an accessory factor for other methyltransferases, and as a transcriptional repressor in mouse embryogenesis.
NLRP3 inflammasome in fibroblasts links tissue damage with inflammation in breast cancer progression and metastasis
Authors: Ershaid Nour , Sharon Yoray , Doron Hila , Raz Yael , Shani Ophir , Cohen Noam , Monteran Lea , Leider-Trejo Leonor , Ben-Shmuel Amir , Yassin Muhammad , Gerlic Motti , Ben-Baruch Adit , Pasmanik-Chor Metsada , Apte Roni , Erez Neta
Published: September 2019

Cancer-Associated Fibroblasts (CAFs) were shown to orchestrate tumour-promoting inflammation in multiple malignancies, including breast cancer. However, the molecular pathways that govern the inflammatory role of CAFs are poorly characterised. In this study we found that fibroblasts sense damage-associated molecular patterns (DAMPs), and in response activate the NLRP3 inflammasome pathway, resulting in instigation of pro-inflammatory signalling and secretion of IL-1β. This upregulation was evident in CAFs in mouse and in human breast carcinomas. Moreover, CAF-derived inflammasome signalling facilitated tumour growth and metastasis, which was attenuated when NLRP3 or IL-1β were specifically ablated. Functionally, CAF-derived inflammasome promoted tumour progression and metastasis by modulating the tumour microenvironment towards an immune suppressive milieu and by upregulating the expression of adhesion molecules on endothelial cells. Our findings elucidate a mechanism by which CAFs promote breast cancer progression and metastasis, by linking the physiological tissue damage response of fibroblasts with tumour-promoting inflammation.
Surface-kinetics mediated mesoporous multipods for enhanced bacterial adhesion and inhibition
Authors: Zhao Tiancong , Chen Liang , Wang Peiyuan , Li Benhao , Lin Runfeng , Abdulkareem Al-Khalaf Areej , Hozzein Wael N. , Zhang Fan , Li Xiaomin , Zhao Dongyuan
Published: September 2019

Despite the importance of nanoparticle’s multipods topology in multivalent-interactions enhanced nano-bio interactions, the precise manipulation of multipods surface topological structures is still a great challenge. Herein, the surface-kinetics mediated multi-site nucleation strategy is demonstrated for the fabrication of mesoporous multipods with precisely tunable surface topological structures. Tribulus-like tetra-pods Fe3O4@SiO2@RF&PMOs (RF = resorcinol-formaldehyde resin, PMO = periodic mesoporous organosilica) nanocomposites have successfully been fabricated with a centering core@shell Fe3O4@SiO2@RF nanoparticle, and four surrounding PMO nanocubes as pods. By manipulating the number of nucleation sites through mediating surface kinetics, a series of multipods mesoporous nanocomposites with precisely controllable surface topological structures are formed, including Janus with only one pod, nearly plane distributed dual-pods and tri-pods, three-dimensional tetrahedral structured tetra-pods, etc. The multipods topology endows the mesoporous nanocomposites enhanced bacteria adhesion ability. Particularly, the tribulus-like tetra-pods mesoporous nanoparticles show ~100% bacteria segregation and long-term inhibition over 90% after antibiotic loading.
Tree height explains mortality risk during an intense drought
Authors: Stovall Atticus E. L. , Shugart Herman , Yang Xi
Published: September 2019

Forest mortality is accelerating due to climate change and the largest trees may be at the greatest risk, threatening critical ecological, economic, and social benefits. Here, we combine high-resolution airborne LiDAR and optical data to track tree-level mortality rates for ~2 million trees in California over 8 years, showing that tree height is the strongest predictor of mortality during extreme drought. Large trees die at twice the rate of small trees and environmental gradients of temperature, water, and competition control the intensity of the height-mortality relationship. These findings suggest that future persistent drought may cause widespread mortality of the largest trees on Earth.
Distinct transcriptional roles for Histone H3-K56 acetylation during the cell cycle in Yeast
Authors: Topal Salih , Vasseur Pauline , Radman-Livaja Marta , Peterson Craig L.
Published: September 2019

Dynamic disruption and reassembly of promoter-proximal nucleosomes is a conserved hallmark of transcriptionally active chromatin. Histone H3-K56 acetylation (H3K56Ac) enhances these turnover events and promotes nucleosome assembly during S phase. Here we sequence nascent transcripts to investigate the impact of H3K56Ac on transcription throughout the yeast cell cycle. We find that H3K56Ac is a genome-wide activator of transcription. While H3K56Ac has a major impact on transcription initiation, it also appears to promote elongation and/or termination. In contrast, H3K56Ac represses promiscuous transcription that occurs immediately following replication fork passage, in this case by promoting efficient nucleosome assembly. We also detect a stepwise increase in transcription as cells transit S phase and enter G2, but this response to increased gene dosage does not require H3K56Ac. Thus, a single histone mark can exert both positive and negative impacts on transcription that are coupled to different cell cycle events.
Author Correction: BRD9 defines a SWI/SNF sub-complex and constitutes a specific vulnerability in malignant rhabdoid tumors
Authors: Wang Xiaofeng , Wang Su , Troisi Emma C. , Howard Thomas P. , Haswell Jeffrey R. , Wolf Bennett K. , Hawk William H. , Ramos Pilar , Oberlick Elaine M. , Tzvetkov Evgeni P. , Ross Aaron , Vazquez Francisca , Hahn William C. , Park Peter J. , Roberts Charles W. M.
Published: September 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Cognitive control of complex motor behavior in marmoset monkeys
Authors: Pomberger Thomas , Risueno-Segovia Cristina , Gultekin Yasemin B. , Dohmen Deniz , Hage Steffen R.
Published: September 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Efficiently measuring a quantum device using machine learning
Authors: Lennon D. T. , Moon H. , Camenzind L. C. , Yu Liuqi , Zumbühl D. M. , Briggs G. A .D. , Osborne M. A. , Laird E. A. , Ares N.
Published: September 2019

Scalable quantum technologies such as quantum computers will require very large numbers of quantum devices to be characterised and tuned. As the number of devices on chip increases, this task becomes ever more time-consuming, and will be intractable on a large scale without efficient automation. We present measurements on a quantum dot device performed by a machine learning algorithm in real time. The algorithm selects the most informative measurements to perform next by combining information theory with a probabilistic deep-generative model that can generate full-resolution reconstructions from scattered partial measurements. We demonstrate, for two different current map configurations that the algorithm outperforms standard grid scan techniques, reducing the number of measurements required by up to 4 times and the measurement time by 3.7 times. Our contribution goes beyond the use of machine learning for data search and analysis, and instead demonstrates the use of algorithms to automate measurements. This works lays the foundation for learning-based automated measurement of quantum devices.
Osmolyte homeostasis controls single-cell growth rate and maximum cell size of Saccharomyces cerevisiae
Authors: Altenburg Tom , Goldenbogen Björn , Uhlendorf Jannis , Klipp Edda
Published: September 2019

Cell growth is well described at the population level, but precisely how nutrient and water uptake and cell wall expansion drive the growth of single cells is poorly understood. Supported by measurements of single-cell growth trajectories and cell wall elasticity, we present a single-cell growth model for yeast. The model links the thermodynamic quantities, such as turgor pressure, osmolarity, cell wall elasto-plasticity, and cell size, applying concepts from rheology and thin shell theory. It reproduces cell size dynamics during single-cell growth, budding, and hyper-osmotic or hypo-osmotic stress. We find that single-cell growth rate and final size are primarily governed by osmolyte uptake and consumption, while bud expansion requires additionally different cell wall extensibilities between mother and bud. Based on first principles the model provides a more accurate description of size dynamics than previous attempts and its analytical simplification allows for easy combination with models for other cell processes.
Fabrication of superhydrophobic and ice-repellent surfaces on pure aluminium using single and multiscaled periodic textures
Authors: Milles Stephan , Soldera Marcos , Voisiat Bogdan , Lasagni Andrés F.
Published: September 2019

Fabricating aluminium surfaces with superhydrophobic and ice-repellent properties present nowadays a challenging task. In this work, multifunctional structures are manufactured by direct laser writing and direct laser interference patterning methods using pulsed infrared laser radiation (1064 nm). Different periodic patterns with feature sizes ranging from 7.0 to 50.0 µm are produced. In addition, hierarchical textures are produced combining both mentioned laser based methods. Water contact angle tests at room temperature showed that all produced patterns reached the superhydrophobic state after 13 to 16 days. In addition, these experiments were repeated at substrate temperatures from −30 °C to 80 °C allowing to determine three wettability behaviours as a function of the temperature. The patterned surfaces also showed ice-repellent properties characterized by a near three-fold increase in the droplets freezing times compared to the untreated samples. Using finite element simulations, it was found that the main reason behind the ice-prevention is the change in the droplet geometrical shape due to the hydrophobic nature of the treated surfaces. Finally, dynamic tests of droplets imping the treated aluminium surfaces cooled down to −20 °C revealed that only on the hierarchically patterned surface, the droplets were able to bounce off the substrate.
Hominin and animal activities in the microstratigraphic record from Denisova Cave (Altai Mountains, Russia)
Authors: Morley Mike W. , Goldberg Paul , Uliyanov Vladimir A. , Kozlikin Maxim B. , Shunkov Michael V. , Derevianko Anatoly P. , Jacobs Zenobia , Roberts Richard G.
Published: September 2019

Denisova Cave in southern Siberia uniquely contains evidence of occupation by a recently discovered group of archaic hominins, the Denisovans, starting from the middle of the Middle Pleistocene. Artefacts, ancient DNA and a range of animal and plant remains have been recovered from the sedimentary deposits, along with a few fragmentary fossils of Denisovans, Neanderthals and a first-generation Neanderthal–Denisovan offspring. The deposits also contain microscopic traces of hominin and animal activities that can provide insights into the use of the cave over the last 300,000 years. Here we report the results of a micromorphological study of intact sediment blocks collected from the Pleistocene deposits in the Main and East Chambers of Denisova Cave. The presence of charcoal attests to the use of fire by hominins, but other evidence of their activities preserved in the microstratigraphic record are few. The ubiquitous occurrence of coprolites, which we attribute primarily to hyenas, indicates that the site was visited for much of its depositional history by cave-dwelling carnivores. Microscopic traces of post-depositional diagenesis, bioturbation and incipient cryoturbation are observed in only a few regions of the deposit examined here. Micromorphology can help identify areas of sedimentary deposit that are most conducive to ancient DNA preservation and could be usefully integrated with DNA analyses of sediments at archaeological sites to illuminate features of their human and environmental history that are invisible to the naked eye.