gebhart/patrepeval huggingface dataset:
Antitumor activity of concurrent blockade of immune checkpoint molecules CTLA-4 and PD-1 in preclinical models. (2013)

3061 Background: Interaction of immune checkpoint molecules PD-1 and CTLA-4 and their respective ligands attenuates antitumor T cell responses. In clinical studies, PD-1 blocking antibody (Ab) nivolumab (BMS-936558) or the CTLA-4 blocking Ab ipilimumab result in durable responses in multiple human malignancies. We describe the evaluation of concurrent treatment with anti-PD-1 and anti-CTLA-4 mAbs in preclinical models. Methods: Antitumor activity of treatment with murine homologs of anti-PD-1 (4H2-mIgG1) and anti-CTLA-4 (9D9-mIgG2b) was evaluated in MC38, a murine colon adenocarcinoma model. The effects of concurrent treatment on T cell infiltration of tumors, tumoral expression of PD-L1 and cytokine levels were explored. The preclinical safety profile of concurrent nivolumab + ipilimumab was assessed in a cynomolgus macaque model. Results: Concurrent treatment of MC38 tumors with 4H2-mIgG1 + 9D9-mIgG2b (10 mg/kg Q3d x 3) results in synergistic antitumor activity whereas efficacy with sequential dosing was similar to either agent alone. With concurrent treatment, dose reductions of one Ab relative to a fixed dose of the other resulted in retention of some antitumor activity. Anti-PD-1 enhanced CD8+ T cell infiltration of MC38 tumors and increased tumor PD-L1 expression. Anti-CTLA-4 treatment increased intratumoral CD8+ T cells and reduced intratumoral T regulatory cells. While concurrent treatment did not result in further increases in T cell infiltration, it increased expression of intratumoral cytokines. Anti-PD-1 resulted in down regulation of cell surface and intracellular levels of PD-1 in CD8+ T cells. In cynomolgus macaques, concurrent nivolumab + ipilimumab resulted in dose-dependent gastrointestinal toxicities (diarrhea; body weight loss) not observed in earlier cynomolgus studies with nivolumab and rarely with ipilimumab. These preclinical observations provided the rationale for a dose escalation trial (NCT01024231) of combined nivolumab + ipilimumab in advanced melanoma. Conclusions: Concurrent treatment with anti-PD-1/anti-CTLA-4 resulted in synergistic antitumor activity in preclinical models and supports the evaluation of the combination in clinical studies.
Gene Expression Profiles Distinguish Idiopathic Pulmonary Fibrosis from Hypersensitivity Pneumonitis (2005)

Our results underscore the value of gene expression signatures to classify the interstitial lung diseases and to understand pathogenic mechanisms, and suggest new ways to improve the diagnosis and treatment of patients with these diseases.
Understanding Trabecular Meshwork Physiology: A Key to the Control of Intraocular Pressure? (2003)

The trabecular meshwork is a tissue located in the anterior chamber angle of the eye, and it is a crucial determinant of intraocular pressure values because of its resistance to the evacuation of aqueous humor from the eye. Here we bring together classical and recent discoveries on the function of the trabecular meshwork, keys to understanding eye pathophysiology.
E-beam inspection for gap physical defect detection in 28nm CMOS process (2013)

As design rule continuously shrinks, process windows narrow. Defects that are trivial in the previous technology node become yield limiting factors. E-beam inspection (EBI) starts to play a critical role in sub-design rule physical defect detection due to its superior resolution, high signal to noise ratio, and novel voltage contrast and material contrast capability. In this paper, we will demonstrate the application of EBI on three critical layers in 28nm CMOS process, covering from FEOL to BEOL.
Preparation and Biological Properties of Water-Soluble Adjuvant Fractions from Delipidated Cells of Mycobacterium smegmatis and Nocardia opaca (1973)

Digestion by lysozyme of delipidated cells of Mycobacterium smegmatis liberates a water-soluble immunoadjuvant fraction which is chemically very similar to the water-soluble adjuvant (WSA) obtained previously from purified cell walls, but which contains somewhat more non-peptidoglycan amino acids. The yield of peptidoglycan-arabinogalactan complex is about 10 times greater starting from whole cells than from cell walls. The main biological properties of this "neo-WSA" are described: it increases circulating antibodies to ovalbumin in guinea pigs, it does not produce polyarthritis in rats or induce hypersensitivity to tuberculin, it does not increase susceptibility to histamine or hyperreactivity to endotoxin, and does not produce spleen and liver hypertrophy. Analogous immunostimulant fractions have also been obtained from delipidated cells of Nocardia opaca by lysozyme treatment.
3D Particle Assembly in Micro-Scale by Using Electrophoretic Micro-Fabrication Technique (2006)

This DOI is not currently attached to any metadata records. DOIs can’t actually ever be deleted (they’re persistent), but sometimes our members create DOIs in error. We do have a process to approximate deletion which we follow only in rare cases where the DOI has been genuinely created in error, and most crucially, if the DOI has never been published anywhere online or in print and never otherwise distributed to or communicated with anyone (authors, readers, reviewers, etc.
RNA editing and regulation ofDrosophila 4f-rnpexpression bysas-10antisense readthrough mRNA transcripts (2003)

We have previously described an example of extensively A-to-G edited cDNA derived from adult heads of the fruitfly Drosophila melanogaster. In that study, the source of the predicted antisense RNA pairing strand for template recognition by dADAR editase was not identified, and the biological significance of the observed hyperediting was not known. Here, we address each of these questions. 4f-rnp and sas-10 are closely adjacent X-linked genes located on opposite DNA strands that produce convergent transcripts. We show that developmentally regulated antisense sas-10 readthrough mRNA arises by activation of an upstream promoter P2 during the late embryo stage of fly development. The sas-10 readthrough transcripts pair with 4f-rnp mRNA to form double-stranded molecules, as indicated by A-to-G editing observed in both RNA strands. It would be predicted that perfect RNA duplexes would be targeted for modification/degradation by enzyme pathways that recognize double-stranded RNAs, leading to decline in 4f-rnp mRNA levels, and this is what we observe. The observation using quantitative RT-PCR that sas-10 readthrough and 4f-rnp transcript levels are inversely related suggests a role for the antisense RNA in posttranscriptional regulation of 4f-rnp gene expression during development. Potential molecular mechanisms that could lead to this result are discussed, one of which is targeted transcript degradation via the RNAi pathway. Insofar as the dADAR editase and RNAi pathways are known to be constitutive in this system, it is likely that control of antisense RNA transcription is the rate-limiting factor. The results provide insight into roles of naturally occurring antisense RNAs in regulation of eukaryotic gene expression.
Recognition of space-time hand-gestures using hidden Markov model (1996)

The rapidly growing interest in interactive three-dimensional(3D) computer environments highly recommend the hand gesture as one of their interaction modalities. Among several factors constituting a hand gesture, hand movement pattern is spatiotemporally variable and informative, but its automatic recognition is not trivial.
Wavefront segmentation and classification for model-based underwater high-frequency tomography (2012)

The problem of inferring side information regarding an underwater acoustic (UWA) channel from the environmental signature imprinted on waveforms by the propagation medium, particularly the transmitter/receiver configuration and relative speed vector, is addressed in this paper. The main contribution of this work is to develop techniques to automatically deal with wavefront classification, i.e., to assign the appropriate number of surface and bottom bounces to a propagation path detected in the set of channel responses observed at a receiver array, considering possible omission or duplication of some paths. This is a key step to develop automatic and robust source localization and velocity estimation algorithms, which are also overviewed here. Our inference algorithms directly operate on linear time-varying UWA channel responses, represented as 3-dimensional delay-Doppler-depth functions (DDDF). At each depth a sparse delay-Doppler spread function (DDSF), analogous to the impulse response of time-invariant systems, is estimated using Basis-Pursuit (BP) methods. The ensemble is processed with energy-based methods to detect the spatio-temporal signatures of wavefronts, which are then matched to candidate environmental configurations by a parametric propagation model. The proposed approaches have been assessed using simulation and empirical data collected during the CALCOM'10 sea trial for various communication ranges from 300 m to 2 km and varying relative speed within the limit of 6 knots.
MPI-StarT: Delivering Network Performance to Numerical Applications (1998)

We describe an MPI implementation for a cluster of SMPs interconnected by a high- performance interconnect. This work is a collaboration between a numerical applications programmer and a cluster interconnect architect. The collaboration started with the modest goal of satisfying the communication needs of a specific numerical application, MITMatlab. However, by supporting the MPI standard MPI-StarT readily extends support to a host of applications. MPI-StarT is derived from MPICH by developing a custom implementation of the Channel Interface. Some changes in MPICH's ADI and Protocol Layers are also necessary for correct and optimal operation. MPI-StarT relies on the host SMPs' shared memory mechanism for intra-SMP communication. Inter-SMP communication is supported through StarT-X. The StarT-X NIU allows a cluster of PCI-equipped host platforms to communicate over the Arctic Switch Fabric. Currently, StarT-X is utilized by a cluster of SUN E5000 SMPs as well as a cluster of Intel Pentium-II workstations. On a SUN E5000 with StarT-X, a processor can send and receive a 64-byte message in less than 0.4 and 3.5 usec respectively and incur less than 5.6 usec user-to-user one-way latency. StarT-X's remote memory-to-memory DMA mechanism can transfer large data blocks at 60 MByte/sec between SUN E5000s. This paper outlines our effort to preserve and deliver this level of communication performance through MPI-StarT to user applications. We have studied the requirements of MITMatlab and the capabilities of StarT-X and have formulated an implementation strategy for the Channel Interface. In this paper, we discuss some performance and correctness issues and their resolutions in MPI-StarT. The correctness issues range from the handling of arbitrarily large message sizes to deadlock-free support of nonblocking MPI operations. Performance optimizations include a shared-memory-based transport mechanism for intra- SMP communication and a broadcast mechanism that is aware of the performance difference between intra-SMP and the slower inter-SMP communication. We characterize the performance of MPI-StarT on a cluster of SUN E5000s. On SUN E5000s, MPI processes within the same SMP can communicate at over 150 MByte/sec using shared memory. When communicating between SMPs over StarT-X, MPI-StarT has a peak bandwidth of 56 MByte/sec. While fine-tuning of MPI-StarT is ongoing, we demonstrate that MPI-StarT is effective in enabling the speedup of MITMatlab on a cluster of SMPs by reporting on the performance of some representative numerical operations.
A NITROXIDE-MALEIMIDE SPIN LABEL (1966)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Enzymic synthesis of isoflavones (1986)

The NADPH and oxygen-dependent conversion of (2S)-naringenin to genistein catalyzed by a microsomal preparation from elicitor-treated soybean cell suspension cultures has been resolved into two steps. In the first step (2S)-naringenin is converted to a product (P-2) which yields genistein in a second step. The chemical behaviour of P-2 and its ultraviolet and mass spectral data are consistent with a 2-hydroxyisoflavanone structure. The conversion of (2S)-naringenin to P-2 requires NADPH, oxygen and cytochrome P-450. The participation of cytochrome P-450 was demonstrated by CO inhibition of the reaction and its partial reversal by light, and by inhibition with typical cytochrome P-450 inhibitors. On a Percoll gradient the membrane fraction which catalyzes P-2 formation coincides with marker enzymes for the endoplasmic reticulum and with the position of cytochrome P-450. Enzymatic activity for conversion of P-2 to genistein is mainly present in the supernatant of the 160 000 X g fraction. This reaction, formally a dehydration, does not require NADPH or oxygen.
Competence development for counselling practitioners – The Masters programme M.A. bob in Germany (2022)

In this article I describe the development and situation of guidance/counselling in recent years in Germany, some actual tasks on thenational agenda and the goals and structure of our Masters programme ‘M.A. bob’ (M.A. in Career Counselling and OrganisationalDevelopment) within this context.
Reduction of Organic Compounds by Lithium Aluminum Hydride. II. Carboxylic Acids (1947)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReduction of Organic Compounds by Lithium Aluminum Hydride. II. Carboxylic AcidsRobert F. Nystrom and Weldon G. BrownCite this: J. Am. Chem. Soc. 1947, 69, 10, 2548–2549Publication Date (Print):October 1, 1947Publication History Published online1 May 2002Published inissue 1 October 1947https://pubs.acs.org/doi/10.1021/ja01202a082https://doi.org/10.1021/ja01202a082research-articleACS PublicationsRequest reuse permissionsArticle Views4845Altmetric-Citations185LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Sequence analysis of the 17,166 base-pair EcoRI fragment C of B95-8 Epstein-Barr virus. (1983)

In order to provide a framework for understanding the molecular biology of Epstein-Barr virus (EBV), we are determining the DNA sequence of the virus and studying the organization of genes on the viral genome. In this paper we report the DNA sequence of the EcoRI C fragment of the B95-8 strain of EBV. The large (approximately 13.6 kb) deletion in this strain has been located by comparison with the DNA sequence of EBV isolated from Raji cells. The sequence has been analysed for possible protein coding regions and transcriptional control sites. At least eight large open reading frames are found, some of them associated with canonical promoter and polyadenylation sequences. The sequences of some of the encoded proteins suggest that they are membrane proteins. It is known that antibodies to major membrane glycoproteins of EBV can neutralize infection in tissue culture. A possible relationship between some of the encoded proteins and the major membrane glycoproteins of the virus is discussed.
Formalin-evoked activity in identified primary afferent fibers: systemic lidocaine suppresses phase-2 activity (1996)

Formalin injected subcutaneously into the paw is a frequently used pain assay; it evokes an initial period of licking and flinching followed by a period of quiescence and last by a second period of intense and protracted licking and flinching. The prominent second phase is believed to reflect the development of a central (spinal cord) facilitation. This conclusion is based on the assumption that formalin evokes an initial burst of activity in fine afferent fibers, followed by prolonged low levels of activity in C fibers. Detailed reports substantiating this essential assumption have not been published. Thus, we recorded in situ from single sural nerve fibers, identified by their conduction velocity and modality, in the barbiturate anesthetized rat. Following formalin (2.5%, 50 microliters) injection into their receptive fields, phase-1 activity was prominent in A beta and A delta fibers as well as in high-threshold C nociceptive afferent fibers. Phase-2 activity was observed in A delta fibers with receptive fields in hairy skin and in all mechanically sensitive C fibers. Mean phase-2 activity in these fibers was 1/2-2/3 of the magnitude achieved in phase 1. Mechanically insensitive fibers and A delta and C fibers with receptive field centers outside of the injection zone began firing 15 min or more post-injection and would contribute to phase-2, but not phase-1, behavioral activity. Intravenous infusion of low doses of lidocaine yielding plasma levels of 3.6-7.9 micrograms/ml administered during phase 2 blocked formalin-evoked activity in primary afferent fibers in a dose-related fashion without blocking either electrically or mechanically evoked activity. Effective plasma doses were comparable to those found to relieve neuropathic pain. These data indicate that phase 2 in the formalin test is more closely related to ongoing afferent input than had previously been thought.
Preparation, characterization and in-vitro evaluation of sustained release protein-loaded nanoparticles based on biodegradable polymers (2008)

Preparation, characterization and in-vitro evaluation of sustained release protein-loaded nanoparticles based on biodegradable polymers Biswajit Mukherjee, Kousik Santra, Gurudutta Pattnaik, Soma GhoshDepartment of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, IndiaAbstract: Controlled drug delivery technology of proteins/peptides from biodegradable nanoparticles has emerged as one of the eminent areas to overcome formulation associated problems of the macromolecules. The purpose of the present investigation was to develop protein-loaded nanoparticles using biodegradable polymer poly L-lactide-co-glycolidic acid (PLGA) with bovine serum albumin (BSA) as a model protein. Despite many studies available with PLGA-based protein-loaded nanoparticles, production know-how, process parameters, protein loading, duration of protein release, narrowing polydispersity of particles have not been investigated enough to scale up manufacturing of protein-loaded nanoparticles in formulations. Different process parameters such as protein/polymer ratio, homogenizing speed during emulsifications, particle surface morphology and surface charges, particle size analysis and in-vitro protein release were investigated. The in-vitro protein release study suggests that release profile of BSA from nanoparticles could be modulated by changing protein-polymer ratios and/or by varying homogenizing speed during multiple-emulsion preparation technique. The formulation prepared with protein-polymer ratio of 1:60 at 17,500 rpm gave maximum protein-loading, minimum polydispersion with maximally sustained protein release pattern, among the prepared formulations. Decreased (10,000 rpm) or enhanced (24,000 rpm) homogenizing speeds resulted in increased polydispersion with larger particles having no better protein-loading and -release profiles in the present study.Keywords: bovine serum albumin (BSA), poly-L-lactide-co-glycolidic acid (PLGA), nanoparticles
Intracellular pteroylpolyglutamate hydrolase from human jejunal mucosa. Isolation and characterization. (1986)

Human jejunal intracellular pteroylpolyglutamate hydrolase was purified 30-fold from intestinal mucosa. The apparent molecular weight of the enzyme was 75,000 by Sephadex G-200 gel filtration, and the isoelectric point was at pH 8.0. The enzyme was maximally active at pH 4.5 and was unstable at increasing temperatures. Intracellular pteroylpolyglutamate hydrolase cleaved both terminal and internal gamma-glutamate linkages. In contrast, brush-border pteroylpolyglutamate hydrolase catalyzed the hydrolysis of only terminal gamma-glutamate linkages. The intracellular enzyme showed greatest affinity for the complete folic acid molecule with longer glutamate chains. Subcellular fractionation studies showed the intracellular enzyme was localized in lysosomes. These data show that the properties of human jejunal intracellular pteroylpolyglutamate hydrolase are distinct from those of the brush-border enzyme but are similar to the properties of intracellular pteroylpolyglutamate hydrolase described in other tissues.
First-in-human multicenter study of bb2121 anti-BCMA CAR T-cell therapy for relapsed/refractory multiple myeloma: Updated results. (2017)

3010 Background: To test the safety and efficacy of the CAR T cell modality in relapsed/refractory multiple myeloma (MM), we have designed a second-generation CAR construct targeting B cell maturation antigen (BCMA) to redirect T cells to MM. bb2121 consists of autologous T cells transduced with a lentiviral vector encoding a novel CAR incorporating an anti-BCMA scFv, a 4-1BB costimulatory motif and a CD3-zeta T cell activation domain. We will report updated safety and efficacy following initial results (Berdeja et al, ENA 2016). Methods: CRB-401 (NCT02658929) is a multi-center phase 1 dose escalation trial of bb2121 in patients with relapsed and/or refractory MM who have received ≥ 3 prior regimens, including a proteasome inhibitor and an immunomodulatory agent, or are double-refractory, and have ≥ 50% BCMA expression on plasma cells. Peripheral blood mononuclear cells are collected via leukapheresis. Patients undergo lymphodepletion with Flu (30 mg/m 2 ) / Cy (300 mg/m 2 ) daily for 3 days then receive 1 infusion of bb2121. The study follows a standard 3+3 design with planned dose levels of 5, 15, 45, 80 and 120 x 10 7 CAR+ T cells. Results: As of November 18, 2016, 11 patients had been infused with bb2121 in the first 4 dose cohorts, and 9 patients had reached at least 1 month of follow-up. As of data cut-off, no dose-limiting toxicities and no &gt; Grade 2 neurotoxicities or cytokine release syndrome (CRS) had been observed. Grade 1-2 CRS had been reported in 8/11 (73%) treated patients. All patients treated with doses of 15.0 x 10 7 or higher remained on study and the overall response rate (ORR) in the 6 evaluable patients at these doses was 100%, including 2 sCRs and 2 MRD-negative responses (1 sC, 1 VGPR). CAR+ T cell expansion has been demonstrated consistently. An additional 6 months of follow up on previously reported results and initial data from an additional ~10 patients will be presented. Conclusions: bb2121 shows promising efficacy at dose levels above 5 x 10 7 CAR+ T cells, including 2 sCRs and ongoing clinical responses at 6 months, with mild and manageable CRS to date. These initial data support the potential of CAR T therapy with bb2121 as a new treatment paradigm in MM. Study sponsored by bluebird bio. Clinical trial information: NCT02658929.