bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of the Joint-Venture Partnership of Phinda Private Game Reserve, South Africa
Authors: Anna Spenceley 
Published: December 2021

Abstract
This case study describes how Phinda Private Game Reserve has evolved over three decades from privately owned land and infrastructure at the outset, to a mixture of community owned land and a joint-venture partnership. The operations have generated substantial benefits for conservation and social benefits for local people over many years.

Information
Snyman, S. and Spenceley, A. (2019) Private Sector Tourism in Conservation Areas in Africa. CABI, Chapter 4.4.1, Case study 26: Phinda Private Game Reserve, South Africa. pp 119-122
© CAB International 2021
Prenatal famine exposure and adult health outcomes: an epigenetic link
Authors: Vaiserman Alexander , Lushchak Oleh 
Published: December 2021

Abstract
Numerous human chronic pathological conditions depend on epigenetic modifications induced by environmental triggers throughout sensitive stages early in development. Developmental malnutrition is regarded as one of the most important risk factors in these processes. We present an overview of studies that the initiation and progression of many diseases are largely dependent on persisting epigenetic dysregulation caused by environmental insults early in life. For particular disorders, candidate genes were identified that underlie these associations. The current study assessed the most convincing evidence for the epigenetic link between developmental malnutrition and adult-life disease in the human population. These findings were obtained from quasi-experimental studies (so-called ‘natural experiments’), i.e. naturally occurring environmental conditions in which certain subsets of the population have differing levels of exposure to a supposed causal factor. Most of this evidence was derived on the DNA methylation level. We discussed DNA methylation as a key player in epigenetic modifications that can be inherited through multiple cell divisions. In this Perspective article, an overview of the quasi-experimental epidemiological evidence for the role of epigenetic mechanisms in the developmental programming by early-life undernutrition is provided.
The Limits and the Appeal of the Restatement
Authors: Ruiz Fabri Hélène 
Published: December 2021

Abstract
The limits and the appeal of the restatement method, in general, and of the Restatement of the Law (Fourth): The Foreign Relations Law of the United States, in particular – understood as the reasons why, or not, other countries (or legal communities) would be incited to follow the same path and have the same kind of instrument regarding their own system – are in fact intertwined. Any alleged appealing aspect can give way to questions about the limits of the exercise and the other way around. The analysis will therefore proceed with questions more than with answers, in seven steps intended to increasingly show the ambivalence of the Restatement (Fourth), beginning with its scope, before considering its authors, its addressees and, therefore, the Restatement’s reach, its nature, its topic or subject matter, its context and, finally, its underlying ideology.
Advances in ultrahigh-energy resolution EELS: phonons, infrared plasmons and strongly coupled modes
Authors: Lagos Maureen J , Bicket Isobel C , Mousavi M. S Shayan , Botton Gianluigi A 
Published: December 2021

Abstract
Nowadays, sub-50 meV atom-wide electron probes are routinely produced for electron energy loss spectroscopy in transmission electron microscopes due to monochromator technology advances. We review how gradual improvements in energy resolution enabled the study of very low-energy excitations such as lattice phonons, molecular vibrations, infrared plasmons and strongly coupled hybrid modes in nanomaterials. Starting with the theoretical framework needed to treat inelastic electron scattering from phonons in solids, we illustrate contributions in detecting optical surface phonons in photonic structures. We discuss phonon mapping capabilities in real and reciprocal space, and the localized phonon response near nano-/atomic-scale structural features. We also survey the progress of aloof spectroscopy in studying vibrations in organic materials and applications in measuring local temperature and photonic density of states in single nanostructures using phonon scattering. We then turn towards studies on infrared plasmons in metals and semiconductors. Spectroscopy analyses now extend towards probing extremely complex broadband platforms, the effects of defects and nanogaps, and some far-reaching investigations towards uncovering plasmon lifetime and 3D photonic density of states. In doped semiconductors, we review research on the use of the electron probe to correlate local doping concentration and atomic-scale defects with the plasmonic response. Finally, we discuss advances in studying strong coupling phenomena in plasmon–exciton and plasmon–phonon systems. Overall, the wealth of information gained extends our knowledge about nanomaterial properties and elementary excitations, illustrating the powerful capabilities of high-energy resolution scanning transmission electron microscopy–electron energy loss spectrometry.
Timing and spectral analysis of 2S 1417−624 during its 2018 outburst
Authors: Serim M M , Özüdoğru Ö C , Dönmez Ç K , Şahiner Ş , Serim D , Baykal A , İnam S Ç 
Published: December 2021

ABSTRACT
We investigate timing and spectral characteristics of the transient X-ray pulsar 2S 1417−624 during its 2018 outburst with NICER follow up observations. We describe the spectra with high-energy cut-off and partial covering fraction absorption (PCFA) model and present flux-dependent spectral changes of the source during the 2018 outburst. Utilizing the correlation-mode switching of the spectral model parameters, we confirm the previously reported sub-critical to critical regime transitions and we argue that secondary transition from the gas-dominated to the radiation pressure-dominated disc do not lead us to significant spectral changes below 12 keV. Using the existing accretion theories, we model the spin frequency evolution of 2S 1417−624 and investigate the noise processes of a transient X-ray pulsar for the first time using both polynomial and luminosity-dependent models for the spin frequency evolution. For the first model, the power density spectrum of the torque fluctuations indicate that the source exhibits red noise component (Γ ∼ −2) within the time-scales of outburst duration which is typical for disc-fed systems. On the other hand, the noise spectrum tends to be white on longer time-scales with high timing noise level that indicates an ongoing accretion process in between outburst episodes. For the second model, most of the red noise component is eliminated and the noise spectrum is found to be consistent with a white noise structure observed in wind-fed systems.
Models of binary neutron star remnants with tabulated equations of state
Authors: Iosif Panagiotis , Stergioulas Nikolaos 
Published: December 2021

ABSTRACT
The emergence of novel differential rotation laws that can reproduce the rotational profile of binary neutron star merger remnants has opened the way for the construction of equilibrium models with properties that resemble those of remnants in numerical simulations. We construct models of merger remnants, using a recently introduced 4-parameter differential rotation law and three tabulated, zero-temperature equations of state. The models have angular momenta that are determined by empirical relations, constructed through numerical simulations. After a systematic exploration of the parameter space of merger remnant equilibrium sequences, which includes the determination of turning points along constant angular momentum sequences, we find that a particular rotation law can reproduce the threshold mass to prompt collapse to a black hole with a relative difference of only $\sim 1{{\ \rm per\ cent}}$ with respect to numerical simulations, in all cases considered. Furthermore, our results indicate a possible correlation between the compactness of equilibrium models of remnants at the threshold mass and the compactness of maximum-mass non-rotating models. Another key prediction of binary neutron star merger simulations is a relatively slowly rotating inner region, where the angular velocity Ω (as measured by an observer at infinity) is mostly due to the frame dragging angular velocity ω. In our investigation of the parameter space of the adopted differential rotation law, we naturally find quasi-spherical (Type A) remnant models with this property. Our investigation clarifies the impact of the differential rotation law and of the equation of state on key properties of binary neutron star remnants and lays the groundwork for including thermal effects in future studies.
Eccentric debris disc morphologies – I. Exploring the origin of apocentre and pericentre glows in face-on debris discs
Authors: Lynch Elliot M , Lovell Joshua B 
Published: December 2021

ABSTRACT
The location of surface brightness maxima (e.g. apocentre and pericentre glow) in eccentric debris discs are often used to infer the underlying orbits of the dust and planetesimals that comprise the disc. However, there is a misconception that eccentric discs have higher surface densities at apocentre and thus necessarily exhibit apocentre glow at long wavelengths. This arises from the expectation that the slower velocities at apocentre lead to a ‘pile up’ of dust, which fails to account for the greater area over which dust is spread at apocentre. Instead we show with theory and by modelling three different regimes that the morphology and surface brightness distributions of face-on debris discs are strongly dependent on their eccentricity profile (i.e. whether this is constant, rising, or falling with distance). We demonstrate that at shorter wavelengths the classical pericentre glow effect remains true, whereas at longer wavelengths discs can either demonstrate apocentre glow or pericentre glow. We additionally show that at long wavelengths the same disc morphology can produce either apocentre glow or pericentre glow depending on the observational resolution. Finally, we show that the classical approach of interpreting eccentric debris discs using line densities is only valid under an extremely limited set of circumstances, which are unlikely to be met as debris disc observations become increasingly better resolved.
IL-3 Changing Cancer Genomics and Cancer Genomic Medicine by Artificial Intelligence and Large-Scale Data Analysis
Authors: Miyano Satoru 
Published: December 2021

Abstract
In MEXT Program for Scientific Research on Innovative Areas “Systems Cancer” and “Systems Cancer in Neo-Dimension” (2010-2019), we developed a large-scale genome data analysis pipeline called Genomon in collaboration with Professor Seiji Ogawa (Kyoto University). Our efforts successfully produced innovative results on cancer genomics. This system is implemented on the supercomputers SHIROKANE and FUGAKU. One of the contributions unraveled the overall picture of genetic abnormalities in malignant brain tumors (Mutational landscape and clonal architecture in grade II and III gliomas. Nat Genet 2015) that exploited Genomon on SHIROKANE. However, with the spread of new measurement technology and new computing environments, no one thinks that the future can be figured on this simple extension. On the other hand, for cancer genomic medicine, Institute of Medical Science University of Tokyo made a research team analyzing whole genome sequences. The challenge we faced was to transform thousands to millions of genomic aberrations per case into precision medicine. It is what we now call “digital transformation.” IBM’s Watson for Genomics was introduced for our research purpose. In the process, we identified the effectiveness of AI, the indispensability of specialist intervention, and bottlenecks. We recognized that natural language processing technology such as BERT and Google Knowledge Graph AI technology will open up the future. Automatic document creation is also a realistic issue. Cancer research is getting more difficult and larger in scale. For example, analysis of genomic data from 60, 954 cases revealed a new underlying mechanism in which multiple mutations within the same oncogene synergistically work (Nature 2021). AI with an accuracy of X% does not seem to be the goal. What is needed is not a black box, but explainable AI that explains “why” in a human-understandable way. We are currently conducting research with Fujitsu Laboratories for this direction.
ANGI-1 Impact of neoadjuvant bevacizumab on transcriptional factor for stemness, macrophage polarization, and oxygenation of tumor microenvironment in glioblastoma
Authors: Tanaka Toshihide , Takei Jun , Teshigawara Akihiko , Tohmoto Kyoichi , Yamamoto Yohei , Hasegawa Yuzuru , Tamura Ryouta , Sasaki Hikaru , Akasaki Yasuharu , Murayama Yuichi 
Published: December 2021

Abstract
Background: Previously we reported that bevacizumab (Bev) produces tumor oxygenation with immunosupportive tumor microenvironment (TME) and inhibition of stemness. To confirm whether those effects might contribute prolongation of clinical outcome, in the present study paired samples from same patients with newly diagnosed GBM who received Bev during its effectiveness and refractoriness were investigated by immunohistochemistry. Methods: Eighteen samples from 9 patients with newly diagnosed GBM who received preoperative neoadjuvant Bev (neoBev) followed by surgical operation and chemoradiotherapy in addition to salvage surgery after recurrence were investigated. Expressions of FOXM1, HIF-1, and CD163 were evaluated by immunohistochemistry. Overall survial (OS) were analyzed with the present cohort divided into two groups between good and poor responder (GR and PR, respectively) of Bev defined as tumor regression rate judged by T1 gadolinium enhancement (T1Gd) and fluid attenuated inversion recovery (FLAIR) images. Results: In the group of good responder of T1Gd (T1Gd-GR; defined as &gt;38% of regression rate after neoBev), OS was prolonged compared with T1Gd-PR along with inhibition of FOXM1 expression and HIF-1a. In contrast, in the group of good responder of FLAIR (FLAIR-GR; defined as &gt;54% of regression rate after neoBev), there were no significant differences of OS and FOXM1 expression between GR and PR. HIF-1a expression tended to be elevated in T1Gd-PR of initial tumors, T1Gd-GR of recurrent tumors, and FLAIR-PR of both initial and recurrent tumors.Conclusion: T1Gd-GR after neoBev might attribute to inhibition of FOXM1 and oxygenation. Bev might provide tumor oxygenation, leading to inhibition of stemness and M2 TAM infiltration during its effectiveness. These results suggested that Bev combined with immunotherapy for newly diagnosed GBM might provide clinical benefits including inhibition of stemness and induction of immunosupportive TME, when tumor volume assessed by T1 Gd. was significantly decreased following neoBev.
ANGI-2 Identification and functions of CD44 as a predictor for bevacizumab-resistant glioblastoma to optimally treat the tumor with bevacizumab
Authors: Inoue Akihiro , Nishikawa Masahiro , Ohnishi Takanori , Yano Hajime , Ohtsuka Yoshihiro , Suehiro Satoshi , Yamashita Daisuke , Watanabe Hideaki , Tanaka Junya , Kunieda Takeharu 
Published: December 2021

Abstract
Anti-angiogenic therapy with bevacizumab (Bev), a monoclonal antibody targeting vascular endothelial growth factor (VEGF), is a common treatment for recurrent glioblastoma (GBM), but its survival benefit is limited. Resistance to Bev is thought to be a major cause of ineffectiveness on Bev therapy. To optimize Bev therapy, identification of a predictive biomarker for responsiveness to Bev is required. Based on our previous study, we focused on the expression and functions of CD44 and VEGF in the Bev therapy. Here, we analyze a relationship between CD44 expression and responsiveness to Bev and elucidate the role of CD44 in anti-VEGF therapy. CD44 and VEGF expression in the tumor core and periphery of 22 GBMs was examined, and the relationship between expression of these molecules and progression-free time on Bev therapy was analyzed. The degree of CD44 expression in the tumor periphery was evaluated by the ratio of the mRNA expression in the tumor periphery to that in the tumor core (P/C ratio). VEGF expression was evaluated by the amount of the mRNA expression in the tumor periphery. To elucidate the roles of CD44 in the Bev therapy, in vitro and in vivo studies were performed using glioma stem-like cells (GSCs) and a GSC-transplanted mouse xenograft model, respectively. GBMs expressing high P/C ratio of CD44 were much more refractory to Bev than those expressing low P/C ratio of CD44, and the survival time of the former was much shorter than that of the latter. In vitro inhibition of VEGF with siRNA or Bev activated CD44 expression and increased invasion of GSCs. Bev showed no anti-tumor effects in mice transplanted with CD44-overexpressing GSCs. The P/C ratio of CD44 expression may become a useful biomarker predicting responsiveness to Bev in GBM. CD44 reduces the anti-tumor effect of Bev, resulting in much more highly invasive tumors.
CBMS-3 Potent bystander effect in suicide gene therapy using genetically engineered stem cells from human exfoliated deciduous teeth
Authors: Horikawa Makoto , Koizumi Shinichiro , Oishi Tomoya , Yamamoto Taisuke , Ikeno Masashi , Ito Masahiko , Yamasaki Tomohiro , Amano Shinji , Sameshima Tetsuro , Suzuki Tetsuro , Namba Hiroki , Kurozumi Kazuhiko 
Published: December 2021

Abstract
HSV thymidine kinase (TK)/ganciclovir (GCV) has a long history of application in malignant glioma and we have previously demonstrated its bystander effect on gliomas using several stem cell types as a vehicle. The main reason for applying stem cells is that they have a unique tumor-trophic activity that allows them to deliver TK genes efficiently to nearby the tumor. Stem cells from human exfoliated deciduous teeth (SHED) are mesenchymal stem cells easily harvested from dental pulp and no studies have reported suicide gene therapy using SHED as a carrier for malignant gliomas. For transduction of SHED with the HSVTK gene (SHEDTK), we used HSVTK retrovirus-producing cells.In vitro experiments showed a significant migration ability of SHEDTK toward tumor-conditioned medium and representative tumor growth factors. We also detected a significant bystander effect of SHEDTK on gliomas in the presence of GCV. In vitro time-lapse imaging showed that both SHEDTK and glioma cells underwent gradual morphological apoptosis and activation of caspase 3/7 was observed in both cell types. In intracranial tumor models using nude mice, SHEDTK migrated around the U87 cell mass implanted in the contralateral hemisphere. Additionally, coculture suspensions of SHEDTK and U87-luciferase cells were xeno-transplanted followed by intraperitoneal administration of GCV for 10 days. All mice of treatment group survived for more than 100 days, whereas those treated without GCV died of tumor growth with median survival of 42 days after tumor implantation. Furthermore, pre-existing intracranial U87 model mice were injected intratumorally with SHEDTK followed by GCV administration as described above. The tumor volume was significantly reduced during the treatment period, and over-all surivial in treatment group is prolonged significantly to that of control groups. These results indicate that SHEDTK-based suicide gene therapy might offer a new promising therapeutic modality for human malignant gliomas.
CBMS-7 IGF1/N-cadherin/Clusterin signaling axis mediates adaptive radioresistance of glioma stem cells
Authors: Osuka Satoru , Zhu Dan , Zhang Zhaobin , Li Chaoxi , Stackhouse Christian T , Sampetrean Oltea , Olson Jeffrey J , Gillespie Yancey , Saya Hideyuki , Willey Christopher D , Van Meir Erwin G 
Published: December 2021

Abstract
Glioblastoma (GBM) is composed of a variety of tumor cell populations including those with stem cell properties, known as glioma stem cells (GSCs). GSCs are innately less sensitive to radiation than the tumor bulk and are believed to drive GBM formation and recurrence following repeated irradiation. However, it is unclear how GSCs adapt to avoid the toxicity of repeated irradiation used in clinical practice. We established radioresistant human and mouse GSCs by exposing them to repeated rounds of irradiation in order to uncover critical mediators of adaptive radioresistance. Surviving subpopulations acquired strong radioresistance in vivo, which was accompanied by increased cell-cell adhesion, slower proliferation, an elevation of stemness properties and N-cadherin expression. Increasing N-cadherin expression rendered parental GSCs radioresistant, reduced their proliferation, and increased their stemness and intercellular adhesive properties. Conversely, radioresistant GSCs reduced their acquired phenotypes upon CRISPR/Cas9-mediated knockout of N-cadherin. Mechanistically, elevated N-cadherin expression resulted in the accumulation of β-catenin at the cell surface, which decreased Wnt/ β-catenin proliferative signaling, reduced neural differentiation, and protected against apoptosis through Clusterin secretion. Restoration of wild type N-cadherin, but not mutant N-cad lacking β-catenin binding region, led to increased radioresistance in N-cadherin knockout GSCs, indicating the importance of the binding between N-cadherin and β-catenin. We also demonstrated that N-cadherin upregulation was induced by radiation-induced IGF1 secretion, and the radiation resistance phenotype can be reversed with picropodophyllin (PPP), a clinically applicable blood-brain-barrier permeable IGF1 receptor inhibitor, supporting clinical translation. Moreover, the elevation of N-cad and Clusterin are related to prognosis of GBM in the TCGA dataset. In conclusion, our data indicate that IGF1R inhibitor can block the N-cadherin-mediated resistance pathway. Our research provides a deeper understanding of adaptive radioresistance after repeated irradiation, and validates the IGF1/N-cadherin/β-catenin/Clusterin signaling axis as a novel target for radio-sensitization, which has direct therapeutic applicability.