bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of TORC1 by MAPK Signaling Determines Sensitivity and Acquired Resistance to Trametinib in Pediatric BRAFV600E Brain Tumor Models
Authors: Li Fuyang , Bondra Kathryn M. , Ghilu Samson , Studebaker Adam , Liu Qianqian , Michalek Joel E. , Kogiso Mari , Li Xiao-Nan , Kalapurakal John A. , James C. David , Burma Sandeep , Kurmasheva Raushan T. , Houghton Peter J. 
Published: July 2022

Abstract

Purpose:
We investigated why three patient-derived xenograft (PDX) childhood BRAFV600E-mutant brain tumor models are highly sensitive to trametinib. Mechanisms of acquired resistance selected in situ, and approaches to prevent resistance were also examined, which may translate to both low-grade glioma (LGG) molecular subtypes.

Experimental Design:
Sensitivity to trametinib [MEK inhibitor (MEKi)] alone or in combination with rapamycin (TORC1 inhibitor), was evaluated in pediatric PDX models. The effect of combined treatment of trametinib with rapamycin on development of trametinib resistance in vivo was examined. PDX tissue and tumor cells from trametinib-resistant xenografts were characterized.

Results:
In pediatric models TORC1 is activated through ERK-mediated inactivation of the tuberous sclerosis complex (TSC): consequently inhibition of MEK also suppressed TORC1 signaling. Trametinib-induced tumor regression correlated with dual inhibition of MAPK/TORC1 signaling, and decoupling TORC1 regulation from BRAF/MAPK control conferred trametinib resistance. In mice, acquired resistance to trametinib developed within three cycles of therapy in all three PDX models. Resistance to trametinib developed in situ is tumor-cell–intrinsic and the mechanism was tumor line specific. Rapamycin retarded or blocked development of resistance.

Conclusions:
In these three pediatric BRAF-mutant brain tumors, TORC1 signaling is controlled by the MAPK cascade. Trametinib suppressed both MAPK/TORC1 pathways leading to tumor regression. While low-dose intermittent rapamycin to enhance inhibition of TORC1 only modestly enhanced the antitumor activity of trametinib, it prevented or retarded development of trametinib resistance, suggesting future therapeutic approaches using rapamycin analogs in combination with MEKis that may be therapeutically beneficial in both KIAA1549::BRAF- and BRAFV600E-driven gliomas.
Karakteristik Faal Paru Berdasarkan Pemeriksaan Spirometri pada Pasien Suspek Tumor Paru dan Mediastinum
Authors: Pratiwi Suryanti , Agus Setyawan Ungky , Listyoko Aditya , Kirana Intan 
Published: July 2022

Pendahuluan: Keganasan paru merupakan penyakit paru yang memiliki tingkat kematian tertinggi di dunia. Pemeriksaan untuk mengetahui fungsi paru dengan menggunakan spirometri.
Tujuan: Penelitian ini bertujuan untuk mengetahui distribusi faal paru pasien dengan diagnosis suspek tumor paru dan mediastinum di Rumah Sakit Saiful Anwar (RSSA) Malang berdasarkan usia, jenis kelamin, indeks massa tubuh (IMT), dan diagnosis.
Metode: Penelitian deskriptif analitik, pendekatan cross-sectional dengan menggunakan data rekam medis Januari 2018 – Desember 2019 kemudian dilakukan uji spearman.
Hasil: Hasil penelitian menunjukkan diagnosis suspek tumor paru dan mediastinum paling banyak pada rentang usia 51-60 tahun, jenis kelamin terbanyak laki-laki, diagnosis terbanyak tumor paru. Hasil interpretasi pemeriksaan spirometri terbanyak menunjukkan restriksi, dan IMT normal. Hasil analisis hubungan gambaran faal paru memiliki p-value pada suspek tumor paru dan mediastinum (0,814), jenis kelamin (0,003), dan IMT (0,360).
Kesimpulan: Terdapat hubungan yang signifikan antara gambaran faal paru dengan jenis kelamin dan tidak didapatkan hubungan yang signifikan antara gambaran faal paru dengan diagnosis dan IMT.
Transformações recentes na educação superior brasileira
Authors: Garcia Sylvia Gemignani , Brito Murillo Marschner Alves de , Hey Ana Paula 
Published: July 2022

Nos últimos 25 anos, os sistemas nacionais de educação superior vêm experimentando um processo significativo de expansão e diversificação institucional sobre o qual as ciências sociais vêm se debruçando largamente. Avanços recentes no acesso à educação secundária têm promovido o crescimento da população elegível à educação superior, processo que vem acompanhado de um conjunto relevante de mudanças na organização institucional e na estrutura de oportunidades que tem se apresentado às coortes mais jovens de estudantes que alcançam os níveis educacionais mais avançados. Pesquisas atuais têm documentado as transformações ocorridas no campo da educação superior em inúmeras dimensões. Trata-se de uma literatura diversa, interessada em evidenciar as características das mudanças institucionais nesse sistema em expansão, objeto de intensas lutas sociais.
Learning and Inference in Sparse Coding Models With Langevin Dynamics
Authors: Fang Michael Y.-S. , Mudigonda Mayur , Zarcone Ryan , Khosrowshahi Amir , Olshausen Bruno A. 
Published: July 2022

AbstractWe describe a stochastic, dynamical system capable of inference and learning in a probabilistic latent variable model. The most challenging problem in such models—sampling the posterior distribution over latent variables—is proposed to be solved by harnessing natural sources of stochasticity inherent in electronic and neural systems. We demonstrate this idea for a sparse coding model by deriving a continuous-time equation for inferring its latent variables via Langevin dynamics. The model parameters are learned by simultaneously evolving according to another continuous-time equation, thus bypassing the need for digital accumulators or a global clock. Moreover, we show that Langevin dynamics lead to an efficient procedure for sampling from the posterior distribution in the L0 sparse regime, where latent variables are encouraged to be set to zero as opposed to having a small L1 norm. This allows the model to properly incorporate the notion of sparsity rather than having to resort to a relaxed version of sparsity to make optimization tractable. Simulations of the proposed dynamical system on both synthetic and natural image data sets demonstrate that the model is capable of probabilistically correct inference, enabling learning of the dictionary as well as parameters of the prior.
Unpacking South African Institutions of Higher Learning Efforts and Hurdles to Respond to COVID-19: Social Service Professionals’ Lenses
Authors: Kang’ethe Simon Murote 
Published: July 2022

Abstract
Incontrovertibly, COVID-19 has overwhelmed institutions of learning in a big way with various institutions in South Africa endeavoring to surmount the challenges in different ways. This article has reviewed various sources of secondary literature from mainly journals. Findings established that institutions of higher learning need to strengthen their institutional modus operandi of communicating coronavirus messages; to change the staff and students’ mindset to strengthen response; advocacy to relay message to staff and students; infrastructural support to mitigate the effects of staff and students; and to avail requisite psychosocial support. The article also established the following hurdles: teaching adjustments and gadget deficits; disruption of school curriculum and academic calendar; and pitfalls of working from home. The article has recognized the need for institutions to enlist the support of social service professionals such as social workers in availing the requisite psychosocial support to both students and the staff.
What Is Immersion? Towards a Phenomenology of Virtual Reality
Authors: Geniusas Saulius 
Published: July 2022

Abstract
Although the importance of the concept of immersion in game studies is indisputable, its meaning remains imprecise and ambiguous. My goal here is to develop a phenomenological clarification of this concept. I begin by clarifying how immersion has been understood in game studies. I further contend that immersion in digital games should be recognized as one modality of immersion among others. This basic realization allows one to open a dialogue between game studies and phenomenology. I develop a phenomenological conception of immersion, which relies on Alfred Schutz’s phenomenology of multiple realities and Theodor Conrad’s phenomenology of immersion. Although such an approach provides us with a general conception of immersion, it does not clarify what specific features characterize immersion in digital games. I argue that this form of immersion is a hybrid phenomenon, which shares certain features with immersion in non-digital games and other features with immersion in other types of digital media. I further demonstrate that immersion in digital games is characterized by a specific function of embodiment. With this in mind, I conclude my analysis by introducing a phenomenologically grounded distinction between actual and virtual embodiment, thereby clarifying in which sense immersion in digital games is an embodied and a disembodied experience.
Aesthetic Empathy: An Investigation in Phenomenological Psychology of Visual Art Experiences
Authors: Hansen Jannik M. , Roald Tone 
Published: July 2022

Abstract
Empathy is a psychologically significant phenomenon. It plays a key role in the development of the self, sociality, and prosocial behaviour. The term empathy originated in 19th-century aesthetics, where the concept was seen as an explanation for aesthetic experience. Despite renewed interest in the relation between empathy and aesthetic experiences, investigations into how empathy shapes experiences of art are still scarce. Given this situation, we ask the following three questions: What does one experience when experiencing a work of art empathetically? What is given during such moments? How is consciousness structured in aesthetic empathetic experience? To answer these questions, we analysed five different experiences with visual art using a phenomenological psychological methodology. We found that a complexity of psychologically significant meaning arises from the empathic experience of art. The core aspects of this meaning are captured in a structure incorporating experience of a foreign subjective sense, reliving and affective adherence, interiorisation, pleasure in sharing, and affective understanding. Based on this structure, we argue that aesthetic empathy features a sense of otherness to a degree not previously recognised and that aesthetic empathy is an inherently intersubjective experience in which the spectator is invited to participate and share feelings expressed in the work of art in moments of aesthetic presence.
Into That Darkness: A Heideggerian Phenomenology of Pain and Suffering
Authors: Walsh Joseph M. 
Published: July 2022

Abstract
When I say ‘pain’, it is clearly a singular phenomenon. Yet if I ask for an example, you can provide many varying instances that confound the idea of its singularity. How can a pinprick be of the same thing as depression or grief? This study maintains the singularity of pain by exploring the process and structure of its experience to account for its variance and its subjectivity. Heidegger’s Being and Time provides the pathway to achieving this, where we comprehend how pain’s myriad manifestations, and their inherent subjectivity, relate to our way of Being – the meaningful horizon through which we encounter pain. The study comes to tie the process of encountering pain with a structure that suffering provides, which explains both the variance and the subjectivity of the pain experience. This can then be mapped onto individual experiences of a singular phenomenon to understand how they arose and what has conditioned them.
Epistemic Communities of Exile Lawyers at the UNWCC
Authors: Lingen Kerstin von 
Published: July 2022

Abstract
During the 1940s in London, exiled lawyers from Europe and Asia were among the main actors in coining one of the most known principles of international criminal law. The notion of ‘crimes against humanity’ emanated from their legal debates. This paper debates how the term surfaced in meetings of the United Nations War Crimes Commission (UNWCC) in 1944 and was taken up by the London Charter for the Nuremberg International Tribunal in 1945. Legal concepts, which previously needed to be discussed at conferences and via correspondence, developed much more quickly in the ‘breeding ground’ of the exile situation in London and were influenced by different legal traditions, here termed ‘legal flows’.
Preventative Plasticities: Legal Ambiguities in Jordanian Counterterrorism Legislation
Authors: Rubio Rosalie 
Published: July 2022

Abstract
Scholars studying counterterrorism laws internationally, particularly across the Arab world, often note the ambiguity of these laws. Few, however, have taken stock of the causes and consequences of these ambiguities. This article explores the questions: What makes counterterrorism laws distinctly amenable to autocratic instrumentalization? What are the mechanisms that allow counterterrorism laws to be used as a means to bolster authoritarian stability? Furthermore, what are the consequences of this instrumentalization on social and political life? This article seeks to answer these questions by focusing on the Hashemite Kingdom of Jordan’s Anti-terrorism Law of 2006 and its 2014 Amendments. The author argues that counterterrorism laws are a unique tool due to their distinctive emphasis on prevention and pre-criminality. As a result, counterterrorism laws are often prone to ambiguities, which permit their expansion and instrumentalization. This article discusses how counterterrorism laws’ inherent ambiguity shape how these laws are articulated, enforced and experienced.
Who is representing the Palestinian People: The Palestine Liberation Organization or the State of Palestine? The Aftermath of United Nations General Assembly Resolution 67/19
Authors: Barakat May , Amouri Yasser 
Published: July 2022

Abstract
This article focuses on the representation of the Palestinian people eight years after the adoption of United Nations General Assembly Resolution 67/19 in 2012, which accorded Palestine observer State status at the United Nations. It addresses the representative role of the Palestine Liberation Organization as an entity with international legal personality recognized by the international community as the sole representative of the Palestinian people. It discusses the developments related to this representative role in light of the ambiguous relationship between the Palestinian Liberation Organization and the State of Palestine, which is merely a continuation of the organization’s relationship with the Palestinian National Authority.
Litigating Women’s Rights in Gulf Monarchial Systems: The Kuwait and Bahrain Constitutional Courts as Case Studies
Authors: Waheedi Salma 
Published: July 2022

Abstract
This article is an inquiry into the ability of the constitutional judiciary in Arab Gulf monarchial systems to act to protect women’s rights and the conditions that enable such autonomous exercise of judicial powers. Looking specifically at Kuwait and Bahrain, the empirical findings of this article demonstrate that one must look beyond constitutional or legal text in conducting this analysis. In these largely comparable political systems with very similar constitutions, subtle contextual political differences can lead to divergent outcomes when it comes to the practical exercise of constitutional judicial power. The experiences of Kuwait and Bahrain are insightful as they shed light on the different dynamics that may exist in similar monarchial systems and how even a limited divestment of political power, as in the case of Kuwait, can enable judicial institutions to carve a role for themselves in protecting citizens’ rights.
The Egyptian State as a Muǧtahid: Law and Religion in the Jurisprudence of the Egyptian Supreme Constitutional Court
Authors: Ayoub Samy 
Published: July 2022

Abstract
This article explores two recent decisions issued by the Egyptian Supreme Constitutional Court (SCC) to demonstrate how the Court resolves conflicts involving Islamic and Christian law: (1) a decision to maintain the constitutionality of the wife’s obedience (ṭāʿat al-zawǧa) articles in the Personal Status Law for Christians, and (2) a decision to extend Muslim mothers’ exclusive custodial claims over children until they reach the age of 15. The article argues that the SCC takes upon itself to decide — based on its own internal logic — the normative legal positions for Christians and Muslims. The SCC rulings reinforce a vision of the Egyptian State as the exclusive holder of legal authority (walī al-amr) with the power to determine the meaning of Islamic/Christian legal norms in a court of law. In these judgments, the Egyptian State is personified as an independent jurist (muǧtahid) that can legislate on behalf of Egyptian Muslims and Christians.
Traded Without Restraint? Transfers of Small Arms and Light Weapons
Authors: Alley Roderic 
Published: July 2022

Abstract
Prescriptive analyses of small arms and light weapons (salw) transfer regimes have been advanced, but comparative assessment of the selling and importing of this weaponry is undeveloped. That includes examples of major arms sellers transferring this weaponry into locations embroiled in armed conflict. After surveying existing salw restraints and their shortcomings, the extent to which due diligence risk considerations shape relevant arms selling conduct is considered. Existing explanatory frameworks discussed are found incomplete. Accordingly a model is outlined addressing impediments to the due diligence risk assessments required to meet international humanitarian and human rights legal obligations. For salw sellers, they include executive dominance of sale purchase decisions; strategic imperatives; economic and commercial incentives; and capacity to conduct independent auditing of arms sales conduct. Within conflict afflicted recipient locations, they include defective public accountability; corruption; impunity; and inability to effect peaceful dispute settlement. Utilising these determinants, dyads embracing major salw sellers transferring this weaponry into locations of persisting armed conflict are considered.
Phylogeography of Pholidopterini: Revising molecular clock calibration by Mid-Aegean Trench
Authors: Çıplak Battal , Yahyaoğlu Özgül , Uluar Onur , Doğan Özgül , Başibüyük Hasan Hüseyın , Korkmaz Ertan Mahir 
Published: July 2022

Abstract
The present study examines the phylogeography of Pholidopterini (Orthoptera, Tettigoniidae), a lineage distributed in the East Mediterranean and estimated substitution rates for the three mitochondrial and two nuclear gene segments. The last common ancestor of Pholidopterini was dated to 18 myr ago, in Early Miocene. Phylogeography of the lineage was marked with three waves of radiations, first during the Middle Miocene Climatic Optimum, the second during the Serravallian, and third during the ending of Messinian. The substitution rate estimations were 0.0187/0.018/0.0141/0.0010207 s/s/myr for COI/ND2/12S-tRNAval-6S/ITS1-5.8S rRNA-ITS2. The following main conclusions were drawn; (i) Radiation of Pholidopterini directed by the climatic shifts, (ii) signs of vicariant speciation were poor, contrary to the active tectonic history, (iii) the ultimate generic ancestors were dated to the Langhian and Serravallian, and (vi) the Tortonian transgression of Mid-Aegean Trench appears to be a reliable geographic calibration point for lineage splitting between Crete and Anatolia.
How Does It Feel to Be a Migrant? Affective Governmentality and Lived Experiences of Filipinas and Filipinos in Mainland China
Authors: Kujawa Izabela 
Published: July 2022

Abstract
Based on twenty in-depth interviews conducted with Filipino migrants living and working in mainland China, I aim to shed light at their lived experiences. I primarily focus on the emotions that constitute their essential part, and the ways migrants choose to deal with them. As a result, I argue that migration systems – responsible either for emigration or immigration – by way of specific regulations, their implementation, as well as the culture surrounding mobility, utilise migrants’ emotions to manage and control this population. In order to better understand these measures and their consequences, I refer to the concept of ‘affective governmentality’. Furthermore, I show how migrants’ affective experiences become a source of hierarchies, but at the same time, a basis for the emergence of strong community ties and the establishment of ‘emotional community’. I argue that, despite the strict regulations and practices which aim at maintaining people’s relationship with the Philippines and discouraging them from settling down in China, migrants are still able to form a sense of rootedness. While experiencing vulnerability and being subjected to exploitation and discrimination, they still remain active agents who use emotions as their own resources.
Architectures and Experiences of Joie de vivre
Authors: Parreno Christian 
Published: July 2022

Abstract
As a semantic reaction against the miserabilism derived from the economic crisis and social instability of the first half of the nineteenth century, joie de vivre surfaced in France. It denotes enjoyment and the ability to recover from calamitous events. In The Insect (1857) by Jules Michelet, joie de vivre constitutes movement and architectural creation, epitomised in the beehive – ‘the veritable Athens of the Insect World’. Yet the sentiment turns ambiguous in La Joie de vivre (1883) by Émile Zola, for whom it is an attitude required not only to face the contradictions of modernity but also to succeed in the capitalist manipulation of nature through architecture. To explore how the built environment manifests emotional experience, this essay follows the trajectory of joie de vivre, from its appearance as an idiomatic amalgamation to other conceptual variations, including élan vital and jouissance.
Are You Experienced?
Authors: Power Timothy 
Published: July 2022

Abstract
This article provides a survey of recent scholarship on music and dance in the cults and rituals of ancient Greece and Rome, with a focus on work that explores the experiential aspects of worship music. I review research on cultic and ritual soundscapes; the materiality and phenomenality of ritual sound; special modes of visually and aurally perceiving cultic mousikē; the epiphanic potential of sacred music; ways of remembering, recording, reenacting, reperforming, and reexperiencing ritual musical performances within and beyond the parameters of cult. I also propose some further avenues of inquiry into each of these topics. Other approaches to religion and music are discussed as well, in particular the sociopolitical contextualization of cultic choreia that has remained a dominant interpretive paradigm over the past two decades.
Supplementing History: Xiyou bu as a 17th-Century Meta-Xiaoshuo
Authors: Huang Kangni 
Published: July 2022

Abstract
Xiaoshuo has long been considered supplementary to official historiography in the Chinese literary tradition. In this paper, I will rethink the supplementary nature of xiaoshuo as a conceptual issue. Specifically, I focus on the 17th-century novel Xiyou bu as a unique case in which the protagonist can be interpreted as a literary figuration of the creative agency of xiaoshuo. My close reading, in turn, takes into account that conventional discourses on xiaoshuo consider xiaoshuo a genre that is intended for supplementing, expanding, and explicating official historical sources.