פרסומים

Spontaneous speech is produced in chunks called intonation units (IUs). IUs are defined by a set of prosodic cues and presumably occur in all human languages. Recent work has shown that across different grammatical and sociocultural conditions IUs form rhythms of ∼1 unit per second. Linguistic theory suggests that IUs pace the flow of information in the discourse. As a result, IUs provide a promising and hitherto unexplored theoretical framework for studying the neural mechanisms of communication. In this article, we identify a neural response unique to the boundary defined by the IU. We measured the EEG of human participants (of either sex), who listened to different speakers recounting an emotional life event. We analyzed the speech stimuli linguistically and modeled the EEG response at word offset using a GLM approach. We find that the EEG response to IU-final words differs from the response to IU-nonfinal words even when equating acoustic boundary strength. Finally, we relate our findings to the body of research on rhythmic brain mechanisms in speech processing. We study the unique contribution of IUs and acoustic boundary strength in predicting delta-band EEG. This analysis suggests that IU-related neural activity, which is tightly linked to the classic Closure Positive Shift (CPS), could be a time-locked component that captures the previously characterized delta-band neural speech tracking.

The median survival time of patients with an aggressive brain tumor, glioblastoma, is still poor due to ineffective treatment. The discovery of androgen receptor (AR) expression in 56% of cases offers a potential breakthrough. AR antagonists, including bicalutamide and enzalutamide, induce dose-dependent cell death in glioblastoma and glioblastoma-initiating cell lines (GIC). Oral enzalutamide at 20 mg/kg reduces subcutaneous human glioblastoma xenografts by 72% (p = 0.0027). We aimed to further investigate the efficacy of AR antagonists in intracranial models of human glioblastoma. In U87MG intracranial models, nude mice administered Xtandi (enzalutamide) at 20 mg/kg and 50 mg/kg demonstrated a significant improvement in survival compared to the control group (p = 0.24 and p < 0.001, respectively), confirming a dose–response relationship. Additionally, we developed a newly reformulated version of bicalutamide, named “soluble bicalutamide (Bic-sol)”, with a remarkable 1000-fold increase in solubility. This reformulation significantly enhanced bicalutamide levels within brain tissue, reaching 176% of the control formulation’s area under the curve. In the U87MG intracranial model, both 2 mg/kg and 4 mg/kg of Bic-sol exhibited significant efficacy compared to the vehicle-treated group (p = 0.0177 and p = 0.00364, respectively). Furthermore, combination therapy with 8 mg/kg Bic-sol and Temozolomide (TMZ) demonstrated superior efficacy compared to either Bic-sol or TMZ as monotherapies (p = 0.00706 and p = 0.0184, respectively). In the ZH-161 GIC mouse model, the group treated with 8 mg/kg Bic-sol as monotherapy had a significantly longer lifespan than the groups treated with TMZ or the vehicle (p < 0.001). Our study demonstrated the efficacy of androgen receptor antagonists in extending the lifespan of mice with intracranial human glioblastoma, suggesting a promising approach to enhance patient outcomes in the fight against this challenging disease.

The book’s introductory chapter explores the broad contours of the Asian story of Dandin’s Mirror (Kāvyādarśa) by comparing it to the tale of Aristotle’s Poetics. The introduction also places Dandin’s work in the context of Sheldon Pollock’s theory of the Sanskrit cosmopolis and its subsequent vernacularization. The chapter shows that the Mirror’s amazing success in Kannada, Sinhala, Pali, Tamil, Tibetan, and other literary cultures can our expand understanding of the cosmopolitan values and of its transmission networks (here emphasizing the Buddhist monastic and intellectual network, in addition to Pollock’s focus on the royal court). The introduction also offers an overview of textual strategies used in response to the Mirror, with a focus on selectivity and retention, playfulness and distinction, and, finally, remodeling and repurposing. The introduction concludes with a comment on the future orientation of Dandin as related to its lasting impact in different parts of Asia.

Calculations in Kohn–Sham density functional theory crucially rely on high-quality approximations for the exchange-correlation (xc) functional. Standard local and semi-local approximations fail to predict the ionization potential (IP) and the fundamental gap, departing from the Kohn–Sham orbital energies, due to the deviation of the total energy from piecewise-linearity and the absence of the derivative discontinuity. The ensemble generalization procedure introduced in Phys. Rev. Lett. 110, 126403 (2013) restores, to a large extent, these features in any approximate xc functional and improves its ability to predict the IP and the fundamental gap with negligible additional computational effort. In this work we perform an extensive study of atoms and first ions across the Periodic Table, generalizing the local spin-density and the Perdew–Burke–Ernzerhof approximations. By applying the ensemble generalization to a variety of systems, with s-, p-, and d-character, we assess the accuracy of the method and identify important trends. In particular, we find that the accuracy of our approach heavily depends on the character of the frontier orbitals: when d-orbitals are involved, the performance is far less accurate. Possible sources of error are discussed and ways for further improvement are outlined.

Publisher's Version                                            arXiv version

This chapter recentres South Asian actors and ideas at the heart of Islamist debates in the twentieth century. It shows how the Pakistani Jamaat-i Islami (JI), well-connected to the Middle East, claimed a leadership role for the idea of a global Islamic revolution. The fall of the Shah in Iran in 1979 constituted a source of pride for the party. At the same time, the JI was careful to highlight the Shiʿi clerics’ comprehensive ideological indebtedness. When Iran became increasingly less ecumenical in outlook throughout the 1980s, the JI moved away from the country and grasped the Russian defeat in Afghanistan as another opportunity to position itself a leading international Islamist actor and keeper of the true revolutionary flame.

 

T-cell acute lymphoblastic leukemia (T-ALL) protein 1 (TAL1) is a central transcription factor in hematopoiesis. The timing and level of TAL1 expression orchestrate the differentiation to specialized blood cells and its overexpression is a common cause of T-ALL. Here, we studied the 2 protein isoforms of TAL1, short and long, which are generated by the use of alternative promoters as well as by alternative splicing. We analyzed the expression of each isoform by deleting an enhancer or insulator, or by opening chromatin at the enhancer location. Our results show that each enhancer promotes expression from a specific TAL1 promoter. Expression from a specific promoter gives rise to a unique 5' UTR with differential regulation of translation. Moreover, our study suggests that the enhancers regulate TAL1 exon 3 alternative splicing by inducing changes in the chromatin at the splice site, which we demonstrate is mediated by KMT2B. Furthermore, our results indicate that TAL1-short binds more strongly to TAL1 E-protein partners and functions as a stronger transcription factor than TAL1-long. Specifically TAL1-short has a unique transcription signature promoting apoptosis. Finally, when we expressed both isoforms in mice bone marrow, we found that while overexpression of both isoforms prevents lymphoid differentiation, expression of TAL-short alone leads to hematopoietic stem cell exhaustion. Furthermore, we found that TAL1-short promoted erythropoiesis and reduced cell survival in the CML cell line K562. While TAL1 and its partners are considered promising therapeutic targets in the treatment of T-ALL, our results show that TAL1-short could act as a tumor suppressor and suggest that altering TAL1 isoform's ratio could be a preferred therapeutic approach.

Background: While military settings may increase psychological distress, soldiers frequently avoid seeking professional help. This study aimed to examine barriers and facilitators associated with intentions to seek help and actually seeking help from a mental health officer (MHO) and how these differ among soldiers who had sought help in the past and those who had not. Method: This cross-sectional study included 263 combat and noncombat soldiers. The Health Belief Model and the Help-Seeking Model were the theoretical framework used to map the potential variables associated with soldiers' decision to seek help. Results: Stigma and administrative barriers were found to be significant barriers to both the intention to seek help and actually consulting an MHO. These findings were more definitive among combat soldiers. The belief in the effectiveness of mental health treatment was positively associated with the intention to seek help. Positive associations were found between well-being, perceived seriousness of one's condition, and belief in the effectiveness of mental health care and intention to seek MHO help. Distress and self-concealment were positively associated with actual consultation with an MHO. Public stigma about seeking help was associated with both the intention to seek mental health assistance and actually consulting an MHO. Conclusion: Military commanders should make an effort to make soldiers feel safe to seek mental health assistance by creating a supportive organizational atmosphere to reduce the stigma associated with mental health care.

Jeannine Worms au Musée d’art et d’histoire du Judaïsme

There has been a dramatic increase in theoretical and practical studies on insect natural enemies over the last decades. The appeal of insect predators and, in particular, parasitoids, as research animals derives from the relative ease with which many species may be cultured and experimented on in the laboratory, the simple life-cycles of most parasitoid species, and the increasing demand for biological pest control as a key component of the integrated pest management approach.There is now a very substantial literature on insect natural enemies and thus a great need for a general text that enquiring students or research workers can use in deciding on approaches and techniques that are appropriate to the study and evaluation of such insects. This book fulfils that demand. It is a considerably updated and expanded version of a previous best-seller and provides an account of major aspects of the biology of predators and parasitoids, punctuated with information and advice onwhich experiments or observations to conduct and, importantly, how to carry them out. Guidance is provided, where necessary, on the most recent further literature that may need to be consulted on given topics.While researchers can now refer to several books on parasitoids and predators, Jervis’s Insects as Natural Enemies is unique in emphasising practicalities. It is aimed at students and professionals working in universities and both government and commercial institutes in the fields of integrated pest management, agriculture, horticulture and forestry, as well as those interested in fundamentals of behavioural, population, community and evolutionary ecology.