6,868 research outputs found
China’s Hybrid Rice Story
No full textThis lecture by Henry Lim Bon Liong focused on the development of the Philippines’ first hybrid rice, SL-8H; a project spearheaded by Henry Lim and his agri-research institute, SL Agritech Corporation. The project sought to help alleviate rice deficiency problems of the Philippines with the help of professional Chinese agriculturist, Professor Yuan Long Ping. The talk highlighted the success of theproduction and brought to light the unifying relationship between China and the Philippines during the process of creating this hybrid innovation in local agriculture
Phase 2 study of sl-701, a novel immunotherapy, in adults with recurrent GBM: A high parameter flow cytometry analysis of cd8+ t cells and potential implications for patient enrichment strategies
No full textTreatment of glioblastoma (GBM) remains a critical challenge and unmet medical need due to limited treatment options. SL-701 is a novel immunotherapy comprised of synthetic peptides designed to elicit a target-specific anti-tumor immune response against the GBM antigens IL-13Rα2, ephrinA2, and survivin. A multicenter, 2-stage, phase 2 clinical trial (NCT02078648) that evaluated the safety and efficacy of SL-701 in 74 adults with recurrent GBM was previously reported. This report describes preliminary data to suggest a correlation of immunocompetence to clinical outcome. In stage 2 (SL-701 + bevacizumab + poly-ICLC) the overall survival at 12 months was 50%. Two of 28 patients enrolled in stage 2 achieved CR (duration of response: 7.8 and 8.8 months) and 2 achieved PR (duration of response: 7.9 and 8.8 months). In a preliminary analysis to assess CD8+ T-cell responses, long-term survivors were comprised largely of subjects with an SL-701-induced target-specific CD8+ T-cell response, indicating a potential correlation of immunocompetence to clinical outcome. By week 24, SL-701-induced target-specific CD8+ T cells expressing IFNg were detected in 8 of 27 patients (30%) who had sufficient samples, with co-expression of PD-1, TIM3, and LAG3 detected in 4 patients. To further understand the T-cell response to SL-701, deep sequencing of target-specific CD8+ T cells using whole transcriptome-based molecular cytometry and high parameter (25+ color) flow cytometry is currently underway and updated data will be reported
Advances in Imaging Multiple Sclerosis
No full textNeuroimaging has emerged as a powerful technology that has enabled visualization of the impact of multiple sclerosis (MS) on the central nervous system in vivo with unprecedented precision. It has played a crucial role in disentangling the chronology of inflammation and neurodegeneration, developing and understanding mechanisms of novel therapeutics, and diagnosing and monitoring the disease in the clinical setting. However, challenges pertaining to the limited resolution, lack of specificity, inherent technological biases, and processing of increasingly big datasets have hindered comprehensive insights into the pathology underlying disability. Here, we review the advances in neuroimaging for MS that have moved the field forward in recent years by addressing the above-mentioned issues, thereby enhancing our knowledge of this yet enigmatic disease. We discuss complementary imaging technologies, including magnetic resonance imaging, positron emission tomography, and optical coherence tomography, the most recent tool in the MS imaging armamentarium that holds promise to act as a surrogate of pathological changes in the central nervous system in a more easily accessible way
Phase 2 trial of SL-701, a novel immunotherapy comprised of synthetic short peptides against GBM targets IL-13ra2, EPHA2, and survivin, in adults with second-line recurrent GBM
No full textBACKGROUND: SL-701, a novel immunotherapy comprised of synthetic peptides elicits immune responses against overexpressed GBM targets: interleukin-13 receptor alpha-2 (IL-13Rα2), EphrinA2 (EphA2), and Survivin. Updated data reported from a multicenter, 2-stage Phase 2 clinical trial of SL-701 in HLA-A2+ adults with relapsed GBM. METHODS: Patients enrolled had KPS \u3e 60 and failure of standard RT/TMZ. Stage 1: SL-701 was administered with adjuvants GM-CSF and imiquimod biweekly for 6 months, then q28 days. Stage 2: SL-701 and adjuvant poly-ICLC were administered biweekly with bevacizumab (10 mg/kg). Primary objectives include: safety and tolerability, investigator assessed objective response rate (ORR) using RANO criteria and 12 month-survival rate. RESULTS: As of 16May2017, 74 patients (46 in Stage 1 and 28 in Stage 2) received SL-701. Accrual for Stage 1 and 2 is complete. Patients were 100% bevacizumab naïve, 65% male with a median age of 56 years (range: 24-79). Patients received a median of 8.5 doses. The most frequent grade 3-4 treatmentrelated adverse event was fatigue (n = 2; 2.7%). Among 46 evaluable Stage 1 patients, 1 partial response (PR; duration: 78 weeks) and 15 stable disease (SD; median duration: 16 weeks; range: 1.3 - 99 weeks) were observed. Of 28 evaluable Stage 2 patients, 21% ORR consisting of 2 complete response (CR; duration: 30 and 46 weeks, respectively) and 4 PR (median duration: 31 weeks; range: 12 - 47 weeks) was observed with 19 SD (median duration: 14 weeks; range: 0.1 - 41 weeks) achieved. Median overall survival (mOS) of 11.2 and 11.7 months was observed for Stage 1 and 2 patients, respectively with a 25% survival probability at 14 weeks. SL-701 plus adjuvants with or without bevacizumab have a manageable safety profile with anti-tumor activity, several CRs, and a preliminarily promising survival curve, warranting further study. Updated study data will be presented
A PHASE 2 STUDY OF A NOVEL IMMUNOTHERAPY SL-701 IN ADULTS WITH RECURRENT GLIOBLASTOMA: EXPLORING THE PROGNOSTIC VALUE OF TREATMENTINDUCED CD8+CD57+ T-CELLS AS A MARKER FOR SURVIVAL
No full textRecurrent glioblastoma (GBM) remains a challenging disease with limited therapeutic options and poor prognosis. SL-701 is a novel immunotherapy composed of synthetic peptides designed to elicit an anti-tumor immune response against the overexpressed GBM antigens IL-13Rα2, ephrinA2, and survivin. In this study, we present updated findings from a phase 2 clinical trial (NCT02078648) evaluating SL-701+poly-ICLC+bevacizumab, where the 12-month overall survival (OS) was 50%. Using high-parameter flow cytometry, we compared the quality of the treatment induced T-cell response in patients with an OS \u3c 12m (n = 15) versus OS \u3e12m (n = 12). Among the patients assessed, 89% exhibited heterogeneous T-cell responses against SL-701, with no discernible correlation between the response to a specific peptide and survival. Consequently, we focused on identifying other characteristics of the pan-SL701-specific T-cell response with an association to survival. Assessing all time points collected, patients with an OS \u3e12m generated a significantly higher frequency of SL-701-specific CD8 T-cells (79% increase, P \u3c 0.005) and a lower frequency of CD4+ T-cells (36% decrease, P \u3c 0.05) compared to patients with a lower OS. Moreover, the ratio of CD8:CD4 T-cells was 2-fold higher in patients with an OS \u3e12m indicating a CD8-enriched response, whereas patients with an OS \u3c 12m had a lower ratio of CD8:CD4 associated with CD4 enriched responses. Notably, patients with an OS \u3e12m, expressed CD57 (identifying highly cytotoxic, differentiated memory T-cells) on 40% of their T-cells compared to 18% in patients with an OS \u3c 12m (P \u3c 0.05). Furthermore, the ratio of SL-701 specific CD57:CD107A expressing cells trended 20% lower in patients with an OS \u3e12m, indicative of a replicating, cytotoxic T-cell response that is not terminally differentiated. These qualitative differences in the immune response, detectable as early as week 8 post treatment, may serve as biomarkers for monitoring and predicting survival. Deep sequencing of SL-701- specific T-cells is planned
CR1 Knops blood group alleles are not associated with severe malaria in the Gambia
No full textThe Knops blood group antigen erythrocyte polymorphisms have been associated with reduced falciparum malaria-based in vitro rosette formation (putative malaria virulence factor). Having previously identified single-nucleotide polymorphisms (SNPs) in the human complement receptor 1 (CR1/CD35) gene underlying the Knops antithetical antigens Sl1/Sl2 and McC(a)/McC(b), we have now performed genotype comparisons to test associations between these two molecular variants and severe malaria in West African children living in the Gambia. While SNPs associated with Sl:2 and McC(b+) were equally distributed among malaria-infected children with severe malaria and control children not infected with malaria parasites, high allele frequencies for Sl 2 (0.800, 1,365/1,706) and McC(b) (0.385, 658/1706) were observed. Further, when compared to the Sl 1/McC(a) allele observed in all populations, the African Sl 2/McC(b) allele appears to have evolved as a result of positive selection (modified Nei-Gojobori test Ka-Ks/s.e.=1.77, P-valu
Quantum and its irreducible representations
No full textWe define for real a unital -algebra
quantizing the universal enveloping
-algebra of . The -algebra
is realized as a -subalgebra of the
Drinfeld double of and its dual Hopf -algebra
, generated by the equatorial Podle\'s sphere coideal
-subalgebra of and
its associated orthogonal coideal -subalgebra . We then classify all the irreducible
-representations of .Comment: 22 pages; author accepted manuscrip
On the sheaf-theoretic SL(2, C) Casson–Lin invariant
No full textWe prove that the (τ-weighted, sheaf-theoretic) SL(2, C) Casson–Lin invariant introduced by Manolescu and the first author is generically independent of the parameter τ and additive under connected sums of knots in integral homology 3-spheres. This addresses two questions asked by Manolescu and the first author. Our arguments involve a mix of topology and algebraic geometry, and rely crucially on the fact that the SL(2, C) Casson–Lin invariant admits an alternative interpretation via the theory of Behrend functions.</p
Candidatus Rhetoricae (or Novus Candidatus).
No full textThis little book is a find whatever it finally turns out to be! For now it seems to be a Jesuit collegium text in rhetoric following the Progymnasmata of Aphthonius. If one works from the back of the book, there is an apparently independent 48-page work, Angelus Pacis by Nicolas Caussini (Latinized name), S.J. The rest of the book seems to be a commentary on or presentation of Aphthonius' Progymnasmata in 3 parts covering 435 pages, followed by a T of C and an AI, which is often one page off. Pars II is titled Rhetoricae Praecepta, Pars III De Panegyrico seu Laudatione. Pars I seems to be Apparatus ad Fabulam et Narrationem. Fable is handled on 15-31. After the famous Greek definition of Theion done into Latin ( sermo falsus veritatem effingens ), the author distinguishes rational (human) and moral (animal) fables, with mixed fables including both. He holds (19) that the sense of the fable generally needs to be expressed; otherwise people often miss the point of a fable. His Latin for promythium is praefabulatio, for epimythium affabulatio. Apologus and parabola are identical for him with fabula. After describing the qualities and uses of fables, the author presents some nine fables that exemplify various levels of style, twice telling the same stories on two levels (WL and FC). The last example is of the florid style: The Silkworm and the Spider takes four pages to tell! I found this book sitting in a box of disparate, unmarked, old books. It pays to look!This is a hardbound book (hard cover)Language note: Bilingual: Greek/LatinElzevers
Searches for New Physics effects in b →sl-sl+ transitions
No full textThe dissertation aims at presenting the current situation in the measurements of electroweak
penguin diagrams dominated decays: b → sl−l+1 . These decays have been a smoking gun
for hunting for New Physics effects over many years, but in the last three years the research
on these phenomena has intensified due to new measurements. Enormous progress has
been made both on the theoretical and the experimental sides to understand the measured
deviations from the current Standard Model predictions, referred to in what follows as
“anomalies”. The author of this dissertation has been one of the main authors of the angular analysis
of B0→ K∗ 0µ+µ− decay in the LHCb experiment, which has been widely regarded as one
of the most important results of the flavour physics sector in recent years. He has proposed
a method called “the method of moments” to measure the angular terms of this decay,
which he has later successfully applied in the measurement itself. Moreover, he has been
the driving force behind the two other important analyses in LHCb: the measurement of
the angular distribution and branching ratio of the B0→ K∗ 0 (1430)µ+µ− decay, where again the method of moments has been used to obtain the angular coefficients, and the search for the light scalar particle that can be produced in the b → s transitions and that decays to a dimuon pair. In this case no signal has been observed and the upper limits on the branching fraction have been set, later to be used for constraining the inflaton model.
The dissertation is organized as follows: the brief introduction is followed by, the second
chapter devoted to a theoretical description of rare B decays, where the effective field
theory formalism is introduced. Furthermore, the author discusses the current theoretical
problems in calculating the Standard Model predictions for the b → sl−l+ processes. Last but not least, the optimised angular observables that are less dependent on the form
factors uncertainness are derived. The third chapter describes the experimental apparatus
used in the b → sl−l+ measurements. Special focus is put on the sub-detectors that play
an important role in the studies of b → sl−l+ transitions. Chapters 4, 5, 6 are devoted to
describing the data analyses performed by the author in the LHCb experiment. In Chapter 7
the global analysis of electroweak penguin decays is presented. This kind of global analysis
has become extremely popular in the past few years as it helps to constrain and pin down those New Physics models that are likely to be responsible for the observed anomalies. The
author of this monograph is involved in one of the biggest collaborations performing New
Physics fits, where he is the convenor of the Flavour Working group. Furthermore, the
author presents his own study on separating the long distance effects in the B0→ K∗ 0µ+µ−decay. This is the state of the art way of determining those contributions. The chapter ends with a description of possible New Physics models that can explain the observed discrepancies
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