Book Review – Studies on Islam and Society in Southeast Asia

This work provides a valuable window into the prolific scholarly output by William Roff during his long (and continuing) academic career. Readers are urged to take the time to read the Introduction, which provides the author's overview of his own career and his evolving scholarly context. It reveals how he was almost lost to Malay Studies because of his early interest in Burma and Buddhism. Roff unpacks for the reader the changing preoccupations and trends in the study of Islam in Southeast Asia and, as such, this short introduction is itself a valuable resource for young students of Southeast Asian studies. Roff's career has been characterised by both longevity and breadth. He has spent over forty years of his life researching the modern history of Islam and Muslims, with particular reference to Southeast Asia and its social and intellectual history. The fifteen essays contained in this present volume were originally published between 1964 and 2009. They cover wide-ranging themes, though the connections across the themes are clear and provide a powerful coherence to the volume

Divine Testing and the Covid Pandemic: Searching for Hope in Sufi Commentaries

The Qur’an carries many references to the created world being subjected to divine testing. It, therefore, seems obvious to ask whether the COVID pandemic that has caused so much suffering across the world and continues to ravage communities represents a test by God for faithful believers. Tests can be daunting experiences, causing apprehension and fear. To what extent should faithful believers regard the COVID pandemic as a fearful, traumatic experience? On the other hand, how can believers find ways to focus on a sense of hope in the midst of the current troubles? This paper will initially consider a range of responses to the COVID pandemic by religious leaders and commentators. It will then draw out Qur’an verses referred to in these responses and will engage with these verses through the lens of several Sufi commentaries, in a search for layered meanings below a surface reading of the verses concerned

Divine Testing and the Covid Pandemic: Searching for Hope in Sufi Commentaries

The Qur’an carries many references to the created world being subjected to divine testing. It, therefore, seems obvious to ask whether the COVID pandemic that has caused so much suffering across the world and continues to ravage communities represents a test by God for faithful believers. Tests can be daunting experiences, causing apprehension and fear. To what extent should faithful believers regard the COVID pandemic as a fearful, traumatic experience? On the other hand, how can believers find ways to focus on a sense of hope in the midst of the current troubles? This paper will initially consider a range of responses to the COVID pandemic by religious leaders and commentators. It will then draw out Qur’an verses referred to in these responses and will engage with these verses through the lens of several Sufi commentaries, in a search for layered meanings below a surface reading of the verses concerned

Exegeting Sūra al Fātiḥa for the Masses: Bediüzzaman Said Nursi and Haji Muḥammad Saʿīd bin ʿUmar

أهداف البحث: تتناول هذه المقالة وجهات النظر التفسيرية حول أشهر سورة في القرآن من مفسرين عاشا في سياقات متنوعة في أواخر القرن التاسع عشر وأوائل القرن العشرين، ويمكن القول إن بديع الزمان سعيد نورسي هو اللاهوتي الأكثر تأثيراً الذي خرج من تركيا العثمانية خلال تاريخها الطويل، وعلى النقيض من ذلك، يتمتع الحاج محمد سعيد بن عمر بسمعة محلية باعتباره باحثًا في المنطقة الماليزية الإندونيسية ولكنه غير معروف خارجها. منهج الدراسة: تستند الدراسة إلى تحليل مقارن لتفسير هذين العالمين في سورة الفاتحة، واستكشاف الأساليب التي استخدماها للوصول إلى المسلمين العاديين بتفسيرهم، وليس فقط المتعلمين تعليماً عالياً. النتائج: جاء بديع الزمان سعيد النورسي والحاج محمد سعيد بن عمر من خلفيات وسياقات مختلفة تمامًا. علاوة على ذلك، كانت أساليبهم التفسيرية مختلفة اختلافًا جوهريًا، حيث كان الأول أكثر عقلانية والأخير أكثر حرفيًا. ومع ذلك، نجح كل منهما في إنتاج تفاسير وصلت إلى الجماهير، وبالتالي نجحا في تحقيق أهدافهما العامة المتمثلة في تعزيز الالتزام الديني والروح الديناميكية للمسلمين في سياقاتهم الخاصة. أصالة البحث: هذا البحث أصيل من نواح مختلفة: أولاً- الدراسات المقارنة لسعيد النورسي مع مفسري اللغة الملاوية قليلة العدد. ثانيًا- يتطلب تحديد أوجه التشابه في النتائج على الرغم من الاختلافات في الأساليب في مجال التفسير مزيدًا من الاهتمام الأكاديمي، ويجب أن تحفز هذه المقالة الاهتمام بمزيد من هذه الدراسات.Purpose: This article considers exegetical perspectives on the best known Sūra of the Qur’ān from two exegetes who lived in diverse contexts in the late nineteenth- and early twentieth-century Caliphate. Bediüzzaman Said Nursi is arguably the most influential theologian to emerge from  in Ottoman Turkey in its long history. Haji Muḥammad Saʿīd bin ʿUmar, by contrast, enjoys a local reputation as a scholar in the Malay-Indonesian region but is unknown outside of that area. Methodology: This research is based on a comparative analysis of the exegesis of both scholars on Sūra al-Fātiḥa, exploring the techniques they used to reach ordinary Muslims with their exegesis, not just highly educated Muslims. Findings: Said Nursi and Muḥammad Saʿīd bin ʿUmar came from quite different backgrounds and contexts. Moreover, their exegetical styles were fundamentally different, with the former’s being more thematic and the latter’s being more literalist. Nevertheless, each succeeded in producing exegesis that reached the masses, thereby meeting their overall goals of reinforcing the commitment to faith and dynamic spirit of Muslims in their respective contexts. Originality: This research is original in various ways. First, comparative studies of Said Nursi and Malay-language exegetes are few in number. Second, the identification of similarities in the results of studies on exegesis despite the use of different methods requires greater scholarly attention. This article should stimulate interest in further studies on the matter

The intestinal immune response of the mouse to the tapeworm Hymenolepis diminuta

It is now conclusively evident that the intestinal tapeworm Hymenolepis diminuta in the mouse can establish successfully, but is thereafter rejected by an immunological mechanism that is thought to be thymus-dependent. The lack of damage to the small intestine in H. diminuta infection makes this an almost unique and potentially valuable model for the investigation of intestinal immune responses. The work presented in this thesis was undertaken to more fully characterise this host-parasite system, and the nature of the immune response of the mouse to H, diminuta was investigated in four different aspects. Firstly, the thymus-dependency of the response was confirmed, and the role of antibody in the expulsion of H. diminuta investigated; secondly, the source of the antigens which stimulate the protective response was investigated; thirdly, a study was made of the effect of an intestinal response to an unrelated parasite on H. diminuta and H. microstoma in rats and mice; fourthly, lymphocytes from the mesenteric lymph nodes of infected mice were tested for their ability to transfer immunity between mice, and to migrate to the small intestine of infected mice. The effects of pregnancy and lactation in the mouse were studied in relation to rejection of H. diminuta; both phases of the reproductive cycle are known to cause depression of T effector lymphocytes, whereas antibody responses are unaffected or enhanced. It was shown that pregnant and lactating mice reject H, diminuta more slowly than nulliparous mice, and that growth of the worms is much enhanced in comparison with worms from nulliparous mice. The delay in rejection caused by lactation was found to be greater than that observed during pregnancy, from which it can be concluded that immunodepression is more marked in lactating mice. The period of slowest rejection coincides with the period when greatest growth of the worms was noted (i.e. during mid-lactation), but the relative contributions of the immunodepression and the increased food intake of pregnant and lactating mice to the enhanced worm growth are far from clear. It was demonstrated that the immunological defect operating during pregnancy and lactation lies in the effector arm of the response, as sensitisation against H. diminuta occurred normally in these animals, but the response to reinfection of previously immunised animals was shown to be depressed during pregnancy and lactation. Experiments were carried out in which immunisation of mice with H, diminuta failed to provide any protection against H, diminuta infection in their offspring; antibody transferred in colostrum had no effect on either growth or survival of the worms in the young mice, which have little innate capacity to respond to the infection. From these and the above experiments, it was concluded that anti-worm antibody in the absence of effective T lymphocyte function has no measureable independent effect on H. diminuta. The relative roles of the scolex and strobila of H. diminuta in stimulating the immune response of the mouse were investigated by transplantation of worms with large or small weights of strobila into the duodenum of mice. It was found that the larger worms were rejected more quickly by the mice, and it is argued that this difference was not due to the smaller worms being more resistant to immunological attack, or to a time-related exposure of protective antigens, but to differences in size or surface area. Confirmation of this idea came from studies with stunted worms derived from heavily irradiated cysticercoids. At 35 krad and above, the worms excyst normally, but show little growth thereafter. These stunted worms, which cosist of a scolex and a stump of undifferentiated neck tissue, were rejected by mice via an immunological mechanism, but were shown to be poorly immunogenic; they are rejected slowly by mice, and stimulate poor immunological memory in comparison with normal worms. It was concluded that the protective antigen(s) arise from the tegument, but that the anterior end of the worm is more antigenic per unit weight than the posterior end. This theory is shown to fit many established observations, and brief discussion is made of the implications for vaccination studies, and of the possible nature of the protective antigens from the tegument of the worm. (Abstract shortened by ProQuest.)

Clonal kinetics and single-cell transcriptional profiling of CAR-T cells in patients undergoing CD19 CAR-T immunotherapy

Chimeric antigen receptor (CAR) T-cell therapy has produced remarkable anti-tumor responses in patients with B-cell malignancies. However, clonal kinetics and transcriptional programs that regulate the fate of CAR-T cells after infusion remain poorly understood. Here we perform TCRB sequencing, integration site analysis, and single-cell RNA sequencing (scRNA-seq) to profile CD8+ CAR-T cells from infusion products (IPs) and blood of patients undergoing CD19 CAR-T immunotherapy. TCRB sequencing shows that clonal diversity of CAR-T cells is highest in the IPs and declines following infusion. We observe clones that display distinct patterns of clonal kinetics, making variable contributions to the CAR-T cell pool after infusion. Although integration site does not appear to be a key driver of clonal kinetics, scRNA-seq demonstrates that clones that expand after infusion mainly originate from infused clusters with higher expression of cytotoxicity and proliferation genes. Thus, we uncover transcriptional programs associated with CAR-T cell behavior after infusion.Published versio

Stan: A Probabilistic Programming Language

Stan is a probabilistic programming language for specifying statistical models. A Stan program imperatively defines a log probability function over parameters conditioned on specified data and constants. As of version 2.14.0, Stan provides full Bayesian inference for continuous-variable models through Markov chain Monte Carlo methods such as the No-U-Turn sampler, an adaptive form of Hamiltonian Monte Carlo sampling. Penalized maximum likelihood estimates are calculated using optimization methods such as the limited memory Broyden-Fletcher-Goldfarb-Shanno algorithm. Stan is also a platform for computing log densities and their gradients and Hessians, which can be used in alternative algorithms such as variational Bayes, expectation propagation, and marginal inference using approximate integration. To this end, Stan is set up so that the densities, gradients, and Hessians, along with intermediate quantities of the algorithm such as acceptance probabilities, are easily accessible. Stan can be called from the command line using the cmdstan package, through R using the rstan package, and through Python using the pystan package. All three interfaces support sampling and optimization-based inference with diagnostics and posterior analysis. rstan and pystan also provide access to log probabilities, gradients, Hessians, parameter transforms, and specialized plotting

CD27 Expression Promotes Long-Term Survival of Functional Effector–Memory CD8+Cytotoxic T Lymphocytes in HIV-infected Patients

Human immunodeficiency virus (HIV)-specific CD8+ T cells persist in high frequencies in HIV-infected patients despite impaired CD4+ T helper response to the virus, but, unlike other differentiated effector cytotoxic T lymphocytes, most continue to express the tumor necrosis factor receptor family member CD27. Because the ligand for CD27 (CD70) is also overexpressed in HIV-infected hosts, we examined the nature of expression and potential functional consequences of CD27 expression on HIV-specific CD8+ T cells. Analysis of CD27+ and CD27− T cells derived from the same HIV-specific clone revealed that retention of CD27 did not interfere with acquisition of effector functions, and that after T cell receptor stimulation, CD27+ cells that concurrently were triggered via CD27 exhibited more resistance to apoptosis, interleukin 2 production, and proliferation than CD27− T cells. After transfer back into an HIV-infected patient, autologous HIV-specific CD27− T cells rapidly disappeared, but CD27+ T cells derived from the same clone persisted at high frequency. Our findings suggest that the CD27–CD70 interaction in HIV infection may provide CD27+ CD8+ T cells with a survival advantage and compensate for limiting or absent CD4+ T help to maintain the CD8 response

Non-Immunogenicity of Overlapping Gag Peptides Pulsed on Autologous Cells after Vaccination of HIV Infected Individuals

Background: HIV Gag-specific CD4+ and CD8+ T-cell responses are important for HIV immune control. Pulsing overlapping Gag peptides on autologous lymphocytes (OPAL) has proven immunogenic and effective in reducing viral loads in multiple pigtail macaque studies, warranting clinical evaluation. Methodology We performed a phase I, single centre, placebo-controlled, double-blinded and dose-escalating study to evaluate the safety and preliminary immunogenicity of a novel therapeutic vaccine approach ‘OPAL-HIV-Gag(c)’. This vaccine is comprised of 120 15mer peptides, overlapping by 11 amino acids, spanning the HIV Gag C clade sequence proteome, pulsed on white blood cells enriched from whole blood using a closed system, followed by intravenous reinfusion. Patients with undetectable HIV viral loads (<50 copies/ml plasma) on HAART received four administrations at week 0, 4, 8 and 12, and were followed up for 12 weeks post-treatment. Twenty-three people were enrolled in four groups: 12 mg (n = 6), 24 mg (n = 7), 48 mg (n = 2) or matching placebo (n = 8) with 18 immunologically evaluable. T-cell immunogenicity was assessed by IFNγ ELIspot and intracellular cytokine staining (ICS). Results: The OPAL-HIV-Gag(c) peptides were antigenic in vitro in 17/17 subjects. After vaccination with OPAL-HIV-Gag(c), 1/6 subjects at 12 mg and 1/6 subjects at 24 mg dose groups had a 2- and 3-fold increase in ELIspot magnitudes from baseline, respectively, of Gag-specific CD8+ T-cells at week 14, compared to 0/6 subjects in the placebo group. No Gag-specific CD4+ T-cell responses or overall change in Rev, Nef, Tat and CMV specific responses were detected. Marked, transient and self-limiting lymphopenia was observed immediately post-vaccination (4 hours) in OPAL-HIV-Gag(c) but not in placebo recipients, with median fall from 1.72 to 0.67 million lymphocytes/mL for active groups (P<0.001), compared to post-placebo from 1.70 to 1.56 lymphocytes/ml (P = 0.16). Conclusion/Significance Despite strong immunogenicity observed in several Macaca nemestrina studies using this approach, OPAL-HIV-Gag(c) was not significantly immunogenic in humans and improved methods of generating high-frequency Gag-specific T-cell responses are required. Name of Registry ClinicalTrials.gov, Registry number: NCT01123915, URL trial registry database: http://www.clinicaltrials.gov/ct2/results?term=OPAL-HIV-1001&Search=Searc