bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive evolution of chestnut forests to the impact of ink disease in Spain
Authors: Alcaide Francisco , Solla Alejandro , Cherubini Marcello , Mattioni Claudia , Cuenca Beatriz , Camisón Álvaro , Martín M. Ángela
Published: November 2019

Phytophthora cinnamomi (Pc) is an extremely destructive soil‐borne pathogen of Asiatic origin responsible for “ink disease” in chestnut. This work assesses the adaptive potential to the impact of Pc of four Spanish populations of Castanea sativa undergoing different selection pressures. To explore the evolvability of C. sativa to Pc in the selected populations, parameters obtained from neutral and functional genetic diversity were compared with estimates of quantitative genetic variability. Nine expressed sequence tags‐simple sequence repeat (EST‐SSR) markers were selected and their transferability and polymorphism in 137 C. sativa individuals were evaluated. To test the potential of EST‐SSR markers for early selection of Pc tolerant plant material, the offspring of selected individuals were challenged with Pc. Expressed sequence tags‐simple sequence repeat markers and seedling life expectancy after Pc inoculation revealed significant different responses of C. sativa populations to Pc. The genetic variability observed within populations showed the potential response capacity of Spanish C. sativa populations to undergo fast adaptive evolution. The heritability value obtained for the “life expectancy” variable (h2 = 0.21 ± 0.11) indicated that selection for resistance to Pc is possible. Genetic patterns reflected two evolutionarily meaningful groupings of populations, corresponding to the different selective pressure of the oomycete between sites. The differentiation coefficient obtained through markers classified as under neutral selection (FST = 0.185) was lower than the quantitative genetic differentiation of “life expectancy” between C. sativa populations (QST = 0.682), providing evidence that selection acted spatially in a heterogeneous manner. A first link has been identified in trees between population structure and adaptive responses to pathogen‐induced selection. The study identified one marker under positive selection that could be used in marker assisted selection to predict resistance to Pc in non‐inoculated C. sativa trees.
Complications and outcome of cats with congenital extrahepatic portosystemic shunts treated with thin film: Thirty‐four cases (2008‐2017)
Authors: Valiente Paula , Trehy Mary , White Rob , Nelissen Pieter , Demetriou Jackie , Stanzani Giacomo , de la Puerta Benito
Published: November 2019

Background

Congenital extrahepatic portosystemic shunts (CEHPSS) are rare in cats. Outcome after attenuation of CEHPSS with thin film has been described in a small number of cases.

Objectives

To describe the clinical presentation, postoperative complications, and outcome of cats treated with thin film to attenuate CEHPSS.

Animals

Thirty‐four cats with CEHPSS were identified from the database of 3 institutions over 9 years.

Methods

Retrospective study. Medical records were reviewed to identify cats with a diagnosis of a CEHPSS that underwent surgical attenuation. Congenital extrahepatic portosystemic shunts were suspected from clinical signs, clinicopathologic findings, and diagnostic imaging, and confirmed at exploratory laparotomy. Cats treated with thin film band attenuation were included. Postoperative complications and follow‐up were recorded.

Results

Complications were recorded in 11 of 34 cats. Deaths related to CEHPSS occurred in 6 of 34; 4 cats did not survive to discharge. Persistent seizures were the cause of death in 4 cats. Seizures were recorded in 8 of 34 cats after surgery; all these cats received preoperative antiepileptic drugs. Serum bile acid concentrations normalized in 25 of 28 of the cats for which data was available. Three cats had persistently increased serum bile acid concentrations and underwent a second exploratory laparotomy. One had a patent shunt, the other 2 had multiple acquired portosystemic shunts. Median follow‐up was 8 months (0.5‐84 months).

Conclusions and Clinical Importance

Congenital extrahepatic portosystemic shunts attenuation using thin film in cats carries a good short‐ and mid‐term prognosis if they survive the postoperative period. Seizures were the most common cause of death.
Common pool resources with support
Authors: Ansink Erik , Weikard Hans‐Peter
Published: November 2019

We examine the role of support for coalition stability in common pool resource games such as fisheries games. Some players may not want to join a coalition that jointly manages a resource. Still, because they benefit from spillovers, they may want to support the coalition with a transfer payment to set incentives for others to join. We find that the impact of support on equilibria of this game is limited to games with three or five players.

Recommendations for Resource Managers

Coalitions may be able to effectively manage common pool resources such as fisheries but such coalitions are often not stable due to free‐rider incentives.

We explore the impact of a transfer scheme that can improve this coalition stability which would lead to larger and more effective coalitions.

Our results show that this new transfer scheme works only for cases where the number of players is small.
Prevalence, type distribution and risk factors for oral HPV in Danish renal transplant recipients
Authors: Faber Mette T. , Kjær Alexander K. , Larsen Helle K. , Thomsen Louise T. , Hædersdal Merete , Bonde Jesper , Hansen Jesper M. , Sørensen Søren S. , Kjær Susanne K.
Published: November 2019

Objective

To assess the prevalence and type distribution of oral human papillomavirus (HPV) among renal transplant recipients (RTRs) and healthy controls and to examine risk factors for oral HPV among RTRs.

Materials and Methods

During 2016‐2017 we recruited 250 RTRs and 250 controls. Oral samples were tested for HPV DNA with INNO‐LiPA HPV Genotyping Extra II. All participants answered a questionnaire on lifestyle and sexual behaviour, and characteristics of RTRs were obtained from medical files. We assessed prevalence and type distribution of oral HPV. Using logistic regression, the risk of oral HPV and risk factors for oral HPV among RTRs were estimated as odds ratios (OR) with 95% confidence intervals (CI).

Results

Overall, 30 RTRs (12.1%) and 26 controls (10.4%) were oral HPV positive (OR = 1.14; 95% CI: 0.64–2.05). Female RTRs tended to have a higher oral HPV prevalence than controls (OR = 1.73; 95% CI: 0.63–4.77), while no difference was observed among men. HPV51 was the commonest genotype. Sexual behaviour tended to be associated with oral HPV among RTRs.

Conclusions

There was no overall difference in oral HPV prevalence between RTRs and controls, but female RTRs tended to have a higher prevalence of oral HPV than controls.
Can the power of platforms be harnessed for governance?
Authors: Ansell Christopher , Miura Satoshi
Published: November 2019

Although not as eye‐catching as their business counterparts, many public and private institutions are currently experimenting with using platforms as a strategy of governance. Governance platforms are now being constructed by a wide array of actors at different geographical scales and across a wide range of issue areas. Although often enabled by digital technology, governance platforms fundamentally embody a new organizing logic to achieve distributed participation and mobilization. While private platforms are transforming the way that companies create and market their products or services and shifting the fundamental logic of how value is produced and appropriated, can this powerful organizing logic be harnessed for public as well as private purposes? We investigate how governance platforms generate powerful effects and survey the extant literature on governance platforms. We conclude that governance platforms do demonstrate promise, although they face a number of challenges.
Genome‐wide association study identifies an NLR gene that confers partial resistance to Magnaporthe oryzae in rice
Authors: Liu Ming‐Hao , Kang Houxiang , Xu Yucheng , Peng Ye , Wang Dan , Gao Lijun , Wang Xuli , Ning Yuese , Wu Jun , Liu Wende , Li Chengyun , Liu Bin , Wang Guo‐Liang
Published: November 2019

Because of the frequent breakdown of major resistance (R) genes, identification of new partial R genes against rice blast disease is an important goal of rice breeding. In this study, we used a core collection of the Rice Diversity Panel II (C‐RDP‐II), which contains 584 rice accessions and are genotyped with 700 000 single‐nucleotide polymorphism (SNP) markers. The C‐RDP‐II accessions were inoculated with three blast strains collected from different rice‐growing regions in China. Genome‐wide association study identified 27 loci associated with rice blast resistance (LABRs). Among them, 22 LABRs were not associated with any known blast R genes or QTLs. Interestingly, a nucleotide‐binding site leucine‐rich repeat (NLR) gene cluster exists in the LABR12 region on chromosome 4. One of the NLR genes is highly conserved in multiple partially resistant rice cultivars, and its expression is significantly up‐regulated at the early stages of rice blast infection. Knockout of this gene via CRISPR‐Cas9 in transgenic plants partially reduced blast resistance to four blast strains. The identification of this new non‐strain specific partial R gene, tentatively named rice blast Partial Resistance gene 1 (PiPR1), provides genetic material that will be useful for understanding the partial resistance mechanism and for breeding durably resistant cultivars against blast disease of rice.
Work, welfare, and wellbeing: The impacts of welfare conditionality on people with mental health impairments in the UK
Authors: Dwyer Peter , Scullion Lisa , Jones Katy , McNeill Jenny , Stewart Alasdair B. R.
Published: November 2019

The personal, economic, and social costs of mental ill health are increasingly acknowledged by many governments and international organisations. Simultaneously, in high‐income nations, the reach of welfare conditionality has extended to encompass many people with mental health impairments as part of on‐going welfare reforms. This is particularly the case in the UK where, especially since the introduction of Employment and Support Allowance in 2008, the rights and responsibilities of disabled people have been subject to contestation and redefinition. Following a review of the emergent international evidence on mental health and welfare conditionality, this paper explores two specific issues. First, the impacts of the application of welfare conditionality on benefit claimants with mental health impairments. Second, the effectiveness of welfare conditionality in supporting people with experience of mental ill health into paid work. In considering these questions, this paper presents original analysis of data generated in qualitative longitudinal interviews with 207 UK social security benefit recipients with experience of a range of mental health issues. The evidence suggests that welfare conditionality is largely ineffective in moving people with mental health impairments into, or closer to, paid work. Indeed, in many cases, it triggers negative health outcomes that make future employment less likely. It is concluded that the application of conditionality for people with mental health issues is inappropriate and should cease.
Translational Approach to Predicting the Efficacy of Maraviroc-Based Regimens as HIV Preexposure Prophylaxis
Authors: Srinivas Nithya , Cottrell Mackenzie , Maffuid Kaitlyn , Prince Heather A. , Nelson Julie A. E. , White Nicole , Sykes Craig , Dellon Evan S. , Madanick Ryan D. , Shaheen Nicholas J. , Gonzalez Daniel , Kashuba Angela D. M.
Published: November 2019

Maraviroc-based regimens have been explored as preexposure prophylaxis (PrEP) against human immunodeficiency virus (HIV). In this study, we utilized mucosal tissue drug exposure data, combined with target concentrations generated
in vitro
, in a pharmacokinetic-pharmacodynamic analysis to predict the effects of drug combinations and adherence on PrEP efficacy. Mucosal tissue concentrations of maraviroc were measured in 24 healthy women.
Regulatory Mechanism of the Atypical AP-1-Like Transcription Factor Yap1 in Cryptococcus neoformans
Authors: So Yee-Seul , Maeng Shinae , Yang Dong-Hoon , Kim Hyelim , Lee Kyung-Tae , Yu Seong-Ryong , Tenor Jennifer L. , Giri Vinay K. , Toffaletti Dena L. , Arras Samantha , Fraser James A. , Perfect John R. , Bahn Yong-Sun
Published: November 2019

The human meningitis fungal pathogen,
Cryptococcus neoformans
, contains the atypical yeast AP-1-like protein Yap1. Yap1 lacks an N-terminal cysteine-rich domain (n-CRD), which is present in other fungal Yap1 orthologs, but has a C-terminal cysteine-rich domain (c-CRD). However, the role of c-CRD and its regulatory mechanism remain unknown. Here, we report that Yap1 is transcriptionally regulated in response to oxidative, osmotic, and membrane-destabilizing stresses partly in an Mpk1-dependent manner, supporting its role in stress resistance. The c-CRD domain contributed to the role of Yap1 only in resistance to certain oxidative stresses and azole drugs but not in other cellular functions. Yap1 has a minor role in the survival of
C. neoformans
in a murine model of systemic cryptococcosis.
Operation of the boreal peatland methane cycle across the past 16 k.y.
Authors: Zheng Yanhong , Fang Zhengkun , Fan Tongyu , Liu Zhao , Wang Zhangzhang , Li Qiyuan , Pancost Richard D. , Naafs B. David A.
Published: November 2019

The role of boreal wetlands in driving variations in atmospheric methane (CH4) concentrations across the last deglaciation (20–10 ka) and the Holocene is debated. Most studies infer the sources of atmospheric methane via ice-core records of methane concentration and its light stable isotopic composition. However, direct evidence for variations in the methane cycle from the wetlands themselves is relatively limited. Here, we used a suite of biomarker proxies to reconstruct the methane cycle in the Chinese Hani peat across the past 16 k.y. We found two periods of enhanced methanogenesis, at ca. 15–11 ka and ca. 10–6 ka, whereas weak methanogenesis characterized the late Holocene. These periods of enhanced methanogenesis relate to periods of high/increasing temperatures, supporting a temperature control on the wetland methane cycle. We found no biomarker evidence for intense methanotrophy throughout the past 16 k.y., and, contrary to previous studies, we found no clear control of hydrology on the peatland methane cycle. Although the onset of methanogenesis at Hani at ca. 15 ka coincided with a negative shift in methane δ13C in the ice cores, there is no consistent correlation between changes in the reconstructed methane cycle of the boreal Hani peat and atmospheric CH4 concentrations.
Feather duvet lung
Authors: Liu-Shiu-Cheong Patrick , Kuo Chris RuiWen , Wilkie Struan WA , Dempsey Owen
Published: November 2019

A 43-year-old non-smoker was referred with a 3-month history of malaise, fatigue and breathlessness. Blood avian precipitins were strongly positive. Lung function testing confirmed a restrictive pattern with impaired gas transfer. A ‘ground glass’ mosaic pattern was seen on CT imaging, suggestive of hypersensitivity pneumonitis. Although he had no pet birds, on closer questioning he had recently acquired a duvet and pillows containing feathers. His symptoms, chest radiograph and lung function tests improved after removal of all feather bedding, and he was also started on oral corticosteroid therapy. Our case reinforces the importance of taking a meticulous exposure history and asking about domestic bedding in patients with unexplained breathlessness. Prompt recognition and cessation of antigen exposure may prevent the development of irreversible lung fibrosis.
Experimental investigation of plasma arc welded Ti–6Al–4V sheets
Authors: Veeman Dhinakaran , Siva Shanmugam N. , Sathish T. , Petle Vijay , Sriram Gokulakrishnan
Published: November 2019

In the present work, experimental trials were conducted with Ti–6Al–4V sheet. The influence of process parameters on the weld bead geometry of bead on joint welding and butt joint configuration was studied. It was concluded that at high current and low travel speed, the heat input was found to be maximum. This led to a higher linear heat input over the base metal that subsequently yielded a full depth of penetration. The strength and integrity of the welded butt joint configuration were ascertained by tensile and bend tests. The microhardness values of the fusion and heat-affected zones were concluded to be higher compared to the base metal. In addition, an Erichsen cupping test ensured that the formability of the welded specimen was comparable to that of the base metal.
Triple Higgs boson production to six b-jets at a 100 TeV proton collider
Authors: Papaefstathiou Andreas , Tetlalmatzi-Xolocotzi Gilberto , Zaro Marco
Published: November 2019

We investigate the production of three Higgs bosons at a proton-proton collider running at a centre-of-mass energy of 100 TeV, all of which decay into b-jets. This final state encapsulates by far the largest fraction of the total cross section of triple Higgs boson production, approximately $$20\%$$20%. We examine, by constructing detailed phenomenological analyses, two scenarios: (i) one in which the triple and quartic Higgs boson self-couplings are modified independently by new phenomena with respect to their Standard Model (SM) values and (ii) an extension of the SM by a gauge-singlet scalar that could drive first-order electroweak phase transition, within the context of the so-called xSM. In the former, we find that competitive constraints of $${\mathscr {O}}(1)$$O(1) can be placed on the quartic coupling and in the latter we demonstrate that it will be possible to obtain important information on the structure of the extended scalar sector.
Up-down asymmetries of charmed baryon three-body decays
Authors: Cen Jian-Yong , Geng Chao-Qiang , Liu Chia-Wei , Tsai Tien-Hsueh
Published: November 2019

We study the up-down asymmetries in the three-body anti-triplet charmed baryon decays of $$\mathbf{B}_{\mathbf{c}}\rightarrow \mathbf{B}_{\mathbf{n}}MM' $$Bc→BnMM′ with the $$SU(3)_f$$SU(3)f flavor symmetry, where $$\mathbf{B}_{\mathbf{c}}$$Bc presents the anti-triplet charmed baryon of $$(\Xi _c^0,-\Xi _c^+,\Lambda _c^+)$$(Ξc0,-Ξc+,Λc+), while $$\mathbf{B}_{\mathbf{n}}$$Bn and $$M^{(')}$$M(′) denote octet baryon and meson states, respectively. By assuming the s-wave meson-pairs to be the dominant constituents in final state configurations, we can write the spin-dependent decay amplitude into parity-conserving and parity-violating parts, parametrized by 6 real parameters under $$SU(3)_f$$SU(3)f, respectively. Fitting these parameters by 16 experimental data points with the minimum $$\chi ^2$$χ2 method, we obtain that $$\chi ^2/d.o.f=2.4$$χ2/d.o.f=2.4. With the fitted parameters, we evaluate the up-down asymmetries along with the decay branching ratios of $$\mathbf{B}_{\mathbf{c}}\rightarrow \mathbf{B}_{\mathbf{n}}MM' $$Bc→BnMM′. Some of these up-down asymmetries are accessible to the experiments at BESIII, BELLE-II and LHCb.
Multistability and Bubbling Route to Chaos in a Deterministic Model for Geomagnetic Field Reversals
Authors: Rech Paulo C. , Dhua Sudarshan , Pati N. C.
Published: November 2019

We report coexisting multiple attractors and birth of chaos via period-bubbling cascades in a model of geomagnetic field reversals. The model system comprises a set of three coupled first-order quadratic nonlinear equations with three control parameters. Up to seven kinds of multistable attractors, viz. fixed point-periodic, fixed point-chaotic, periodic–periodic, periodic-chaotic, chaotic–chaotic, fixed point-periodic–periodic, fixed point-periodic-chaotic are obtained depending on the initial conditions for critical parameter sets. Antimonotonicity is a striking characteristic feature of nonlinear systems through which a full Feigenbaum tree corresponding to creation and annihilation of period-doubling cascades is developed. By analyzing the two-parameters dependent dynamics of the system, a critical biparameter zone is identified, where antimonotonicity comes into existence. The complex dynamical behaviors of the system are explored using phase portraits, bifurcation diagrams, Lyapunov exponents, isoperiodic diagram, and basins of attraction.
Period-Increasing Indicates Loss of Stability
Authors: Yang Xiao-Song , Wang Lei
Published: November 2019

We first present a mathematical theory on period-increasing as an indicator of stability loss in a dynamical system of any dimension not less than two, and show that in two-dimensional autonomous ODEs, the period-increasing is closely associated with homoclinic or heteroclinic bifurcation. Then we demonstrate that the proposed period-increasing regime shift can occur in some ecological models.
Basement–cover relationships and deformation in the Northern Paraguai Belt, central Brazil: implications for the Neoproterozoic–early Paleozoic history of western Gondwana
Authors: dos Santos Iara Maria , Pinheiro Roberto Vizeu L. , Holdsworth Robert E. , Nogueira Afonso Cesar R. , Santos Hudson Pereira , Domingos Fabio Henrique G.
Published: November 2019

The Northern Paraguai Belt, at the SE border of the Amazonian Craton, central Brazil, has been interpreted as a Brasiliano–Pan-African (
c.
650–600 Ma) belt with a foreland basin, recording collisional polyphase tectonism and greenschist-facies metamorphism extending from the late Precambrian to the Cambrian–Ordovician. New structural investigations indicate that the older metasedimentary rocks of the Cuiabá Group represent a Tonian–Cryogenian basement assemblage deformed in two contemporaneous fault-bounded structural sub-domains of wrench-dominated (rake <10°) and contraction-dominated (rake ∼30–40°) sinistral transpression, with tectonic vergence towards the SE. The younger late Cryogenian to early Cambrian sedimentary rocks lying to the NW of the Cuiabá Group are non-metamorphic and display only pervasive brittle transtension characterized by normal-oblique faults, fractures and forced drag folds with no consistent vergence pattern. Our analyses suggest that an unconformity separates the metasedimentary Cuiabá Group basement of the Northern Paraguai Belt from the unmetamorphosed sedimentary cover. It is proposed that the latter units were deposited during a post-glacial marine transgression (after
c.
635 Ma) in a post-collisional basin. The Paraguai Belt basement and its post-collisional sedimentary cover share a number of significant geological similarities with sequences in the Bassarides Belt and Taoudéni Basin in the SW portion of the West African Craton.
Association between Hyperreflective Foci on Spectral-Domain Optical Coherence Tomography and Early Recurrence of Diabetic Macular Edema after Intravitreal Dexamethasone Implantation
Authors: Kim Kyung Tae , Kim Dong Yoon , Chae Ju Byung
Published: November 2019

Purpose. To investigate the associations between hyperreflective foci (HRF) on spectral-domain optical coherence tomography (SD-OCT) and early recurrence of macular edema after intravitreal dexamethasone (DEX) implantation in eyes with refractory diabetic macular edema (DME) to bevacizumab. Methods. Medical records of patients with refractory DME to bevacizumab, who underwent intravitreal DEX implantation and 12-month follow-up, were reviewed. Eyes in which central subfield thickness (CST) increased over 50 μm at 3 months compared with the first month after intravitreal DEX implantation were categorized into the early recurrence group, and the others were categorized into the late recurrence group. Best-corrected visual acuity (BCVA), CST, and number of HRF on SD-OCT were analyzed. Results. Twenty-nine eyes of 26 patients (16 eyes in the early recurrence group and 13 eyes in the late recurrence group) were included in this study. The numbers of HRF in entire retina, inner retina, and outer retina at baseline in the early recurrence group (11.38 ± 3.07 in entire retina, 5.44 ± 1.50 in inner retina, 5.94 ± 2.74 in outer retina) were significantly greater than those in the late recurrence group (7.54 ± 3.60 in entire retina, p=0.006; 4.08 ± 1.70 in inner retina, p=0.034; 3.46 ± 2.30 in outer retina, p=0.013). Multivariate logistic regression analysis showed that a higher number of HRF increased the risk of early recurrence after intravitreal DEX implantation (odds ratio in entire retina: 1.518, p=0.012; odds ratio in inner retina: 2.058, p=0.027; odds ratio in outer retina: 1.610, p=0.029). Conclusions. Higher baseline numbers of HRF on SD-OCT may be a predictive indicator of early recurrence of macular edema after intravitreal DEX implantation for DME.
Systems-Pharmacology-Based Identification of Antitumor Necrosis Factor Effect in Mimeng Flower Decoction for the Treatment of Diabetic Retinopathy
Authors: Li Yingzi , Huang Ying , Tu Changsen
Published: November 2019

The traditional Chinese medicine of Mimeng flower decoction (MFD) is effective in treating diabetic retinopathy (DR), but the mechanism is still unclear. This study aims at investigating the mechanism of MFD in treating DR. First, active compounds in MFD were filtered out by the systems pharmacology method and used as bait to fish potential targets. The common genes between the targets and DR-related genes were selected to construct the compound-target-disease network and identify the network hub gene as a key gene. Molecular docking was simulated to assess the binding affinity of active compounds towards the gene protein. Streptozotocin- (STZ-) induced diabetic rat model was administered to evaluate the efficacy of MFD in treating DR and its effects on retinal gene expression. Finally, 53 active compounds were screened out from the seven herbs in MFD, with a total of 136 targets. After intersecting with 210 DR-related genes, 21 common genes were applied to construct the network, and tumor necrosis factor (TNF) was identified as the hub gene. The active compounds of acacetin, kaempferol, luteolin, and quercetin showed a good binding affinity towards TNF (C-score ≥ 4). In diabetic rats, MFD treatment reversed the retinal impairment and decreased retinal TNF expression significantly. In conclusion, this study adopted the method of systems pharmacology to screen out active compounds and construct the compound-target-disease network and found that MFD could ameliorate DR by downregulating the network hub gene of TNF.
Analysis of a Benchmark Building Installed with Tuned Mass Dampers under Wind and Earthquake Loads
Authors: Elias S. , Rupakhety R. , Olafsson S.
Published: November 2019

This study presents analysis of a benchmark building installed with tuned mass dampers (TMDs) while subjected to wind and earthquake loads. Different TMD schemes are applied to reduce dynamic responses of the building under wind and earthquakes. The coupled equations of motion are formulated and solved using numerical methods. The uncontrolled building (NC) and the controlled building are subjected to a set of 100 earthquake ground motions and wind forces. The effectiveness of using different multiple TMD (MTMD) schemes as opposed to single TMD (STMD) is presented. Optimal TMD parameters and their location are investigated. For a tall structure like the one studied here, TMDs are found to be more effective in controlling acceleration response than displacement, when subjected to wind forces. It is observed that MTMDs with equal stiffness in each of the TMDs (usually considered for wind response control), when optimized for a given structure, are effective in controlling acceleration response under both wind and earthquake forces. However, if the device is designed with equal mass in every floor, it is less effective in controlling wind‐induced floor acceleration. Therefore, when it comes to multihazard response control, distributed TMDs with equal stiffnesses should be preferred over those with equal masses.
Some New Results on Various Graph Energies of the Splitting Graph
Authors: Chu Zheng-Qing , Nazeer Saima , Zia Tariq Javed , Ahmed Imran , Shahid Sana
Published: November 2019

The energy of a simple connected graphGis equal to the sum of the absolute value of eigenvalues of the graphGwhere the eigenvalue of a graphGis the eigenvalue of its adjacency matrixAG. Ultimately, scores of various graph energies have been originated. It has been shown in this paper that the different graph energies of the regular splitting graphS′Gis a multiple of corresponding energy of a given graphG.
Expression of LGR5, FZD7, TROY, and MIST1 in Perioperatively Treated Gastric Carcinomas and Correlation with Therapy Response
Authors: Freiin Grote Antonia , Halske Christine , Behrens Hans-Michael , Krüger Sandra , Wilhelm Franziska , Egberts Jan-Hendrik , Röcken Christoph
Published: November 2019

The cancer stem cell model is considered as a putative cause of resistance to chemotherapy and disease recurrence in malignant tumors. In this study, we tested the hypothesis that the response to neoadjuvant/perioperative chemotherapy correlates with the expression of four different putative cancer stem cell markers of gastric cancer (GC), i.e., LGR5, FZD7, TROY, and MIST1. The expression of LGR5, FZD7, TROY, and MIST1 was assessed by immunohistochemistry in 119 perioperatively treated GCs including pretherapeutic biopsies, resected primary GCs, and corresponding nodal and distant metastases. All four markers were detected in our cohort with variable prevalence and histoanatomical distributions. Few tumor cells expressed TROY. LGR5, FZD7, and MIST1 were coexpressed in 41.2% and completely absent in 6.2%. The prevalence of LGR5- and FZD7-positive GCs was higher and of TROY-positive GCs lower in perioperatively treated GCs compared with treatment-naïve tumors. LGR5, FZD7, and MIST1 in the primary tumors correlated significantly with their expression in the corresponding lymph node metastasis. An increased expression of LGR5 in primary GC correlated significantly with tumor regression. The expression of MIST1 in lymph node metastases correlated significantly with the number of lymph node metastases as well as overall and tumor-specific survival. FZD7 did not correlate with any clinicopathological patient characteristic. Our study on clinical patient samples shows that GCs may coexpress independently different stem cell markers; that neoadjuvant/perioperative treatment of GC significantly impacts on the expression of stem cell markers, which cannot be predicted by the analysis of pretherapeutic biopsies; and that their expression and tumor biological effect are heterogeneous and have to be viewed as a function of histoanatomical distribution.
KLF2 Protects against Osteoarthritis by Repressing Oxidative Response through Activation of Nrf2/ARE Signaling In Vitro and In Vivo
Authors: Gao Xiang , Jiang Shuangpeng , Du Zhangzhen , Ke Angtin , Liang Qingwei , Li Xu
Published: November 2019

Osteoarthritis (OA) is a multifactorial and inflammatory disease characterized by cartilage destruction that can cause disability among aging patients. There is currently no effective treatment that can arrest or reverse OA progression. Kruppel-like factor 2 (KLF2), a member of the zinc finger family, has emerged as a transcription factor involved in a wide variety of inflammatory diseases. Here, we identified that KLF2 expression is downregulated in IL-1β-treated human chondrocytes and OA cartilage. Genetic and pharmacological overexpression of KLF2 suppressed IL-1β-induced apoptosis and matrix degradation through the suppression of reactive oxygen species (ROS) production. In addition, KLF2 overexpression resulted in increased expression of heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone 1 (NQO1) through the enhanced nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). Further, Nrf2 inhibition abrogated the chondroprotective effects of KLF2. Safranin O/fast green and TUNEL staining demonstrated that adenovirus-mediated overexpression of KLF2 in joint cartilage protects rats against experimental OA by inhibiting cartilage degradation and chondrocyte apoptosis. Immunohistochemical staining revealed that KLF2 overexpression significantly decreases MMP13 expression caused by OA progression in vivo. This in vitro and in vivo study is the first to investigate the antioxidative effect and mechanisms of KLF2 in OA pathogenesis. Our results collectively provide new insights into OA pathogenesis regulated by KLF2 and a rationale for the development of effective OA intervention strategies.
Proximate, Mineral and Antinutrient Contents of Cocoyam (Xanthosoma sagittifolium (L.) Schott) from Ethiopia
Authors: Wada Eyasu , Feyissa Tileye , Tesfaye Kassahun
Published: November 2019

Cocoyam (Xanthosoma sagittifolium (L.) Schott) is an important food crop especially in the tropics and subtropics. Its cormels and leaves are eaten after cooking in the rural areas in Ethiopia. There is lack of information on the nutritional composition of cocoyam grown in the country. In this study, cormels of green- and purple- cocoyams were analyzed to determine proximate and mineral contents and antinutritional factors. The moisture contents (%) of green- and purple-cocoyams were 61.91 and 63.53, respectively. Crude protein (10.10%) and fiber (2.66%) contents of purple cocoyam were significantly higher than crude protein (8.48%) and fiber (2.14%) contents of green cocoyam. Fat contents (%) of the green- and purple cocoyam were 0.85 and 0.22, respectively. Ash content of green cocoyam (3.25%) was significantly higher than the ash content of purple cocoyam (2.27%). The carbohydrate contents (%) and gross energy values (kcal/100 g) of green- and purple-cocoyam, respectively, were 85.36 and 378.47 and 84.76 and 380.27, showing that cocoyam grown in Ethiopia can be a good source of energy. Mineral contents (mg/100 g) of green cocoyam were determined as Fe (8.20), Zn (3.07), Cu (1.04), Mg (78.77), Mn (2.48), P (120.93), Na (29.22), K (1085.70) and Ca (56.57) while purple cocoyam had Fe (9.88), Zn (3.12), Cu (1.14), Mg (82.00), Mn (3.74), P (129.87), Na (24.33), K (1223.30) and Ca (44.90). High antinutritional factors (phytate and tannin) (mg/100 g) were determined from both green- and purple-cocoyam genotypes with significantly higher quantities in purple cocoyam (187.57 phytate and 156.1 tannin) than the green cocoyam (167.76 phytate and 139.62 tannin). This study provided important information about the nutritional composition of cocoyam from Ethiopia, which can help to develop cocoyam food products and to promote production and utilization of cocoyam by encouraging its sustainable use. More detailed analyses including processing and sensory testing are suggested for further investigation in order to obtain healthful and comfortable cocoyam products.
An Engineered Tumor-on-a-Chip Device with Breast Cancer–Immune Cell Interactions for Assessing T-cell Recruitment
Authors: Aung Aereas , Kumar Vardhman , Theprungsirikul Jomkuan , Davey Shruti K. , Varghese Shyni
Published: November 2019

Recruitment of immune cells to a tumor is determined by the complex interplay between cellular and noncellular components of the tumor microenvironment. Ex vivo platforms that enable identification of key components that promote immune cell recruitment to the tumor could advance the field significantly. Herein, we describe the development of a perfusable multicellular tumor-on-a-chip platform involving different cell populations. Cancer cells, monocytes, and endothelial cells were spatially confined within a gelatin hydrogel in a controlled manner by using 3D photopatterning. The migration of the encapsulated endothelial cells against a chemokine gradient created an endothelial layer around the constructs. Using this platform, we examined the effect of cancer cell–monocyte interaction on T-cell recruitment, where T cells were dispersed within the perfused media and allowed to infiltrate. The hypoxic environment in the spheroid cultures recruited more T cells compared with dispersed cancer cells. Moreover, the addition of monocytes to the cancer cells improved T-cell recruitment. The differences in T-cell recruitment were associated with differences in chemokine secretion including chemokines influencing the permeability of the endothelial barrier. This proof-of-concept study shows how integration of microfabrication, microfluidics, and 3D cell culture systems could be used for the development of tumor-on-a-chip platforms involving heterotypic cells and their application in studying recruitment of cells by the tumor-associated microenvironment.

Significance:

This study describes how tumor-on-chip platforms could be designed to create a heterogeneous mix of cells and noncellular components to study the effect of the tumor microenvironment on immune cell recruitment.
Targeting PD-L1 Initiates Effective Antitumor Immunity in a Murine Model of Cushing Disease
Authors: Kemeny Hanna R. , Elsamadicy Aladine A. , Farber S. Harrison , Champion Cosette D. , Lorrey Selena J. , Chongsathidkiet Pakawat , Woroniecka Karolina I. , Cui Xiuyu , Shen Steven H. , Rhodin Kristen E. , Tsvankin Vadim , Everitt Jeffrey , Sanchez-Perez Luis , Healy Patrick , McLendon Roger E. , Codd Patrick J. , Dunn Ian F. , Fecci Peter E.
Published: November 2019

Purpose:

Although pituitary adenoma is classified as benign, Cushing disease is associated with significant morbidity due to the numerous sequelae of elevated cortisol levels. Successful therapy for Cushing disease remains elusive due to high rates of treatment-refractory recurrence. The frequent emergence of lymphocytic hypophysitis following checkpoint blockade for other cancers, as well as the expression of PD-L1 on pituitary adenomas, suggest a role for immunotherapy.

Experimental Design:

This study confirms PD-L1 expression on functioning pituitary adenomas and is the first to evaluate the efficacy of checkpoint blockade (anti–PD-L1) therapy in a preclinical model of Cushing disease.

Results:

Herein, treatment with anti–PD-L1 was successful in reducing adrenocorticotropic hormone plasma levels, decreasing tumor growth, and increasing survival in our model. Furthermore, tumor-infiltrating T cells demonstrated a pattern of checkpoint expression similar to other checkpoint blockade–susceptible tumors.

Conclusions:

This suggests that immunotherapy, particularly blockade of the PD1/PD-L1 axis, may be a novel therapeutic option for refractory Cushing disease. Clinical investigation is encouraged.
The Existence of MTH1-independent 8-oxodGTPase Activity in Cancer Cells as a Compensatory Mechanism against On-target Effects of MTH1 Inhibitors
Authors: Samaranayake Govindi J. , Troccoli Clara I. , Zhang Ling , Huynh Mai , Jayaraj Christina J. , Ji Debin , McPherson Lisa , Onishi Yoshiyuki , Nguyen Dao M. , Robbins David J. , Karbaschi Mahsa , Cooke Marcus S. , Barrientos Antonio , Kool Eric T. , Rai Priyamvada
Published: November 2019

Investigations into the human 8-oxodGTPase, MutT Homolog 1 (MTH1), have risen sharply since the first-in-class MTH1 inhibitors were reported to be highly tumoricidal. However, MTH1 as a cancer therapeutic target is currently controversial because subsequently developed inhibitors did not exhibit similar cytotoxic effects. Here, we provide the first direct evidence for MTH1-independent 8-oxodGTPase function in human cancer cells and human tumors, using a novel ATP-releasing guanine-oxidized (ARGO) chemical probe. Our studies show that this functionally redundant 8-oxodGTPase activity is not decreased by five different published MTH1-targeting small molecules or by MTH1 depletion. Significantly, while only the two first-in-class inhibitors, TH588 and TH287, reduced cancer cell viability, all five inhibitors evaluated in our studies decreased 8-oxodGTPase activity to a similar extent. Thus, the reported efficacy of the first-in-class MTH1 inhibitors does not arise from their inhibition of MTH1-specific 8-oxodGTPase activity. Comparison of DNA strand breaks, genomic 8-oxoguanine incorporation, or alterations in cellular oxidative state by TH287 versus the noncytotoxic inhibitor, IACS-4759, contradict that the cytotoxicity of the former results solely from increased levels of oxidatively damaged genomic DNA. Thus, our findings indicate that mechanisms unrelated to oxidative stress or DNA damage likely underlie the reported efficacy of the first-in-class inhibitors. Our study suggests that MTH1 functional redundancy, existing to different extents in all cancer lines and human tumors evaluated in our study, is a thus far undefined factor which is likely to be critical in understanding the importance of MTH1 and its clinical targeting in cancer.
Rational Combination Therapy for Melanoma with Dinaciclib by Targeting BAK-Dependent Cell Death
Authors: Xu Xiaoou , Eshima Shizuka , Kato Shinichiro , Fisher David E. , Sakurai Hiroaki , Hayakawa Yoshihiro , Yokoyama Satoru
Published: November 2019

Mutation of the oncogene BRAF is among the most common genetic alterations in melanoma. BRAF inhibitors alone or in combination with MEK inhibitors fail to eradicate the tumor in most patients due to combinations of intrinsic or acquired resistance. Therefore, novel strategies are needed to improve the therapeutic efficacy of BRAF inhibition. We demonstrated that dinaciclib has potent antimelanoma effects by inducing BAK-dependent apoptosis through MCL1 reduction. Contrary to dinaciclib, the inhibitors of BRAF/MEK/CDK4/6 induced apoptosis dominantly through a BAX-dependent mechanism. Although the combination of BRAF and MEK inhibitors did not exhibit additive antimelanoma effects, their combination with dinaciclib synergistically inhibited melanoma growth both in vitro and in vivo. Collectively, our present findings suggest dinaciclib to be an effective complementary drug of BAX-dependent antimelanoma drugs by targeting BAK-mediated apoptosis, and other such rational drug combinations can be determined by identifying complementary drugs activating either BAK or BAX.
HSF1-Mediated Control of Cellular Energy Metabolism and mTORC1 Activation Drive Acute T-Cell Lymphoblastic Leukemia Progression
Authors: Eroglu Binnur , Pang Junfeng , Jin Xiongjie , Xi Caixia , Moskophidis Demetrius , Mivechi Nahid F.
Published: November 2019

Deregulated oncogenic signaling linked to PI3K/AKT and mTORC1 pathway activation is a hallmark of human T-cell acute leukemia (T-ALL) pathogenesis and contributes to leukemic cell resistance and adverse prognosis. Notably, although the multiagent chemotherapy of leukemia leads to a high rate of complete remission, options for salvage therapy for relapsed/refractory disease are limited due to the serious side effects of augmenting cytotoxic chemotherapy. We report that ablation of HSF1, a key transcriptional regulator of the chaperone response and cellular bioenergetics, from mouse T-ALL tumors driven by PTEN loss or human T-ALL cell lines, has significant therapeutic effects in reducing tumor burden and sensitizing malignant cell death. From a mechanistic perspective, the enhanced sensitivity of T-ALLs to HSF1 depletion resides in the reduced MAPK–ERK signaling and metabolic and ATP-producing capacity of malignant cells lacking HSF1 activity. Impaired mitochondrial ATP production and decreased intracellular amino acid content in HSF1-deficient T-ALL cells trigger an energy-saving adaptive response featured by attenuation of the mTORC1 activity, which is coregulated by ATP, and its downstream target proteins (p70S6K and 4E-BP). This leads to protein translation attenuation that diminishes oncogenic signals and malignant cell growth. Collectively, these metabolic alterations in the absence of HSF1 activity reveal cancer cell liabilities and have a profound negative impact on T-ALL progression.

Implications:

Targeting HSF1 and HSF1-dependent cancer-specific anabolic and protein homeostasis programs has a significant therapeutic potential for T-ALL and may prevent progression of relapsed/refractory disease.
Refined Sphenopalatine Ganglion Stimulator Placement and Intensity Setting to Augment Blood Flow and Neurologic Function
Authors: Saver Jeffrey L. , Kharaishvili Nino , Janelidze Tamar , Beridze Maia , Zarqua Natia , Solberg Yoram , Bornstein Natan M. ,   for the IMPACT-24M Trial Investigators, Khachidze Natia , Avazashvili Ivane , Meshviliani Paata , Mamardashvili Ekaterine , Beridze Nino , Avazashvili Ivane , Gulua Tamaz , Phiphia Giorgi
Published: November 2019

Background and Purpose—

Two large, randomized trials indicated that sphenopalatine ganglion (SPG) stimulation improves final disability outcome in acute anterior circulation patients with ischemic stroke with confirmed cortical involvement. This study evaluated 2 refinements in SPG stimulation treatment technique: (1) SPG electrode placement with real-time optical tracking guidance; and (2) stimulation intensity comfortable tolerance level selection using non-noxious facial physiological markers.

Methods—

This study was a single, active arm trial at 4 centers, enrolling patients with anterior circulation ischemic stroke, National Institutes of Health Stroke Scale 1 to 6 including arm weakness subitem score ≥1, not receiving recanalization therapies, and within 24 hours of onset. Stimulation level was set based on ipsilateral facial tingling sensation or lacrimation. SPG stimulation effects were assessed by measuring volumetric blood flow in the ipsilateral common carotid artery by ultrasound and grasp and pinch strength in the affected hand before and during stimulation, and by change in National Institutes of Health Stroke Scale from day 1 to 7.

Results—

Among 50 enrolled patients, age was median 66 years (interquartile range, 60–74), 44% were female, National Institutes of Health Stroke Scale median was 5 (interquartile range, 4–5), and median onset-to-screening time was 18 hours (interquartile range, 9–20). Median implantation skin-to-skin time was 4 minutes (interquartile range, 3–7), and all 50 implants were placed correctly. Comfortable tolerance level was found based on physiological biomarkers in 96% of patients, including 86% in the optimal, low-medium intensity range. SPG stimulation significantly increased common carotid artery peak systolic and end-diastolic blood flow (44%,
P
<0.0001; and 52%,
P
<0.0001) and improved pinch strength (42%,
P
<0.0001) and grasp strength (26%,
P
<0.0001). Degree of National Institutes of Health Stroke Scale recovery by day 7 was greater than in matched historic controls, median 75% versus 50%,
P
=0.0003.

Conclusions—

SPG stimulator placement with real-time optical tracking guidance was fast and accurate, and selection of stimulation intensity levels based on non-noxious facial tingling and lacrimation was feasible in nearly all patients. SPG stimulation led to cervico-cranial blood flow augmentation and improved hand motor function.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT03551093.
Overseas Chinese Educational Strategies and Its Policy Implications
Authors: Zheng (郑丽洁) Lijie , de Haan Mariëtte , Koops Willem
Published: November 2019

This paper assesses whether China’s policies for providing educational support to overseas Chinese match the educational needs of current Chinese immigrants around the world. Firstly, the paper presents the different migration backgrounds of four waves of Chinese global migration in contemporary history: labor immigrants to the Global North, international students in the Global North, businessmen in the Global South and the new rich investors in the Global North. Using the concept of intergenerational contract, we found the four waves have distinct parental investment strategies in relation to their migration background, which comes along with their different educational needs. After carefully reviewing China’s policies in overseas education in terms of the assumptions, purpose and background of their implementation, we argue that these policies are outdated and serve the needs of only a limited number of Chinese immigrants due to their ignoring the variety of certain intergenerational contracts. Lastly, some specific suggestions for policy makers are given.