gebhart/patrepeval huggingface dataset:
Correlation of T-cell response, clinical activity and regulatory T-cell levels in renal cell carcinoma patients treated with IMA901, a novel multi-peptide vaccine (2007)

3017 Background: Cancer vaccines have been able to induce T-cell responses in cancer patients but rarely demonstrated a correlation of immune responses with clinical benefit. Here, we present immunological results of a phase 1 study with IMA901, a therapeutic cancer vaccine based on multiple novel synthetic tumor-associated peptides (TUMAP) identified as being naturally presented in primary renal cell carcinoma (RCC) tissues. Methods: The HLA peptidome of 32 primary RCC samples was systematically investigated using a combination of mass spectrometry, gene expression profiling and in vitro human T-cell assays. 9 HLA-A*02- and 1 HLA-DR- restricted TUMAPs derived from 9 different tumor antigens were selected and designated IMA901. 28 HLA-A*02-positive stage III/IV RCC patients were enrolled in a single arm, multicenter study and received 8 vaccinations on days 1, 2, 3, 8, 15, 22, 36, and 64 each consisting of 4.5 mg IMA901 (including a HBV-derived viral marker peptide) and 75 μg GM-CSF as immune adjuvant. T-cell responses using IFN-γ ELISPOT and HLA multimer analysis and CD4+ Foxp3+ regulatory T cell (Treg) levels were measured in peripheral blood. Results: In vivo IMA901- induced specific T-cell responses were detected to the HBV marker peptide (52% of 27 evaluable patients), at least one TUMAP (74%) or multiple TUMAPs (30%). T-cell responses were detectable already at day 15, peaked subsequently and were sustainable until follow-up in the majority of patients. Most importantly, patients eliciting multiple responses to TUMAPs significantly showed a higher clinical benefit rate (SD+PR; p=0.018) and lower Treg levels at study onset (p=0.016). No correlation of HBV marker peptide responses with either clinical benefit or Treg levels was observed. Conclusions: IMA901 rapidly induced T-cell responses in a majority of advanced RCC patients. A clinical mode of action is strongly supported by the significant correlation of multiple T-cell responses with clinical benefit. CD4+ Foxp3+ Tregs seem to play an active role in limiting the broadness of T-cell responses. Furthermore, our data suggest that we can predict in vivo immunogenicity of cancer vaccine antigens by our in vitro drug discovery approach. No significant financial relationships to disclose.
Current approaches to fine mapping of antigen–antibody interactions (2014)

A number of different methods are commonly used to map the fine details of the interaction between an antigen and an antibody. Undoubtedly the method that is now most commonly used to give details at the level of individual amino acids and atoms is X-ray crystallography. The feasibility of undertaking crystallographic studies has increased over recent years through the introduction of automation, miniaturization and high throughput processes. However, this still requires a high level of sophistication and expense and cannot be used when the antigen is not amenable to crystallization. Nuclear magnetic resonance spectroscopy offers a similar level of detail to crystallography but the technical hurdles are even higher such that it is rarely used in this context. Mutagenesis of either antigen or antibody offers the potential to give information at the amino acid level but suffers from the uncertainty of not knowing whether an effect is direct or indirect due to an effect on the folding of a protein. Other methods such as hydrogen deuterium exchange coupled to mass spectrometry and the use of short peptides coupled with ELISA-based approaches tend to give mapping information over a peptide region rather than at the level of individual amino acids. It is quite common to use more than one method because of the limitations and even with a crystal structure it can be useful to use mutagenesis to tease apart the contribution of individual amino acids to binding affinity.
Glyoxal oxidase of Phanerochaete chrysosporium: its characterization and activation by lignin peroxidase. (1990)

Glyoxal oxidase (GLOX) is an extracellular H2O2-generating enzyme produced by ligninolytic cultures of Phanerochaete chrysosporium. The production, purification, and partial characterization of GLOX from agitated cultures are described here. High-oxygen levels are critical for GLOX production as for lignin peroxidase. GLOX purified by anion-exchange chromatography appears homogeneous by NaDod-SO4/PAGE (molecular mass = 68 kDa). However, analysis by isoelectric focusing indicates two major bands (pI 4.7 and 4.9) that stain as glycoproteins as well as for H2O2-producing activity in the presence of methylglyoxal. Purified GLOX shows a marked stimulation in activity when incubated with Cu2+; full activation takes more than 1 hr with 1 mM CuSO4 at pH 6. The steady-state kinetic parameters for the GLOX oxidation of methylglyoxal, glyceraldehyde, dihydroxyacetone, glycolaldehyde, acetaldehyde, glyoxal, glyoxylic acid, and formaldehyde, were determined by using a lignin peroxidase coupled-assay at pH 4.5. Of these substrates, the best is the extracellular metabolite methylglyoxal with a Km of 0.64 mM an apparent rate of catalysis, kcat, of 198 s1 under air-saturated conditions. The Km for oxygen is greater than the concentration of oxygen possible at ambient pressure--i.e., >1.3 mM at 25 degrees C. Importantly, oxygen-uptake experiments show that purified GLOX is inactive unless coupled to the peroxidase reaction. With this coupled reaction, for each mol of methylglyoxal, veratryl alcohol (a lignin peroxidase substrate), and oxygen consumed, 1 mol each of pyruvate and veratraldehyde is produced. The importance of these results is discussed in relation to the physiology of lignin biodegradation and possible extracellular regulatory mechanisms for the control of oxidase and peroxidase activities.
Optimal river routing with crosstalk constraints (1998)

With the increasing density of VLSI circuits, the interconnection wires are being packed even closer. This has increased the effect of interaction among these wires on circuit performance and hence, the importance of controlling crosstalk. In this article, we consider river routing with crosstalk constraints. Given the positions of the pins in a single-layer routing channel and the maximum tolerable crosstalk between each pair of neighboring nets, we give a polynomial time algorithm to decide whether there is a feasible river routing solution and produce one with minimum crosstalk when it is feasible.
Expression of bcr-abl fusion transcripts following bone marrow transplantation for Philadelphia chromosome-positive leukemia. (1990)

A modified polymerase chain reaction (PCR) procedure was used to study the expression of bcr-abl fusion transcripts following allogeneic bone marrow transplantation (BMT) for Philadelphia chromosome (Ph1) positive acute and chronic leukemias. The technique was applied to RNA preparations of peripheral blood and bone marrow cells from 10 patients with chronic myelogenous leukemia (CML) and one patient with acute lymphoblastic leukemia (ALL), all of whom had undergone allogenic BMT and were in clinical and cytogenetic remission. Pre-BMT samples available for eight of 11 patients contained detectable bcr-abl fusion products serving as a baseline for comparison to post-BMT studies. Six patients showed no PCR-detectable bcr-abl transcripts in each of several serial analyses post-BMT (1-36 months post-BMT). The remaining five patients demonstrated various patterns of bcr-abl transcript expression after transplantation. In three patients, bcr-abl transcripts persisted for up to 3 months post-BMT but subsequently were undetectable. Molecular relapse was observed 3 and 6 months post-BMT in the remaining two patients whose earlier post-BMT samples showed no bcr-abl fusion transcripts. No bcr-abl transcripts were detected in subsequent samples from both of these patients 6 months and 1 year post-BMT, respectively. These data confirm that Ph1 carrying cells expressing the bcr-abl fusion mRNA may persist or recur for several months following BMT in the absence of clinical and cytogenetic relapse. The significance of these observations is discussed with respect to results reported recently by others using similar techniques.
Electrophoretic manipulation of single DNA molecules in nanofabricated capillariesElectronic supplementary information (ESI) available: Four videoclips showing the movement of DNA molecules in nanocapillaries. See http://www.rsc.org/suppdata/lc/b3/b312592k/ (2004)

We demonstrate the use of nanofabricated capillaries, integrated as part of a microfluidic structure, to study the electrophoretic behaviour of single, fluorescently-labelled, molecules of DNA as a function of capillary size. The nanocapillaries, fabricated using a focused ion beam, have cross-sections down to 150 x 180 nm. Control of single-molecule direction and velocity was achieved using voltage manipulation. DNA mobility was found to increase with decreasing cross-section, which we interpret in terms of reduced electro-osmotic counter-flow. Such nanofabricated capillaries as part of larger fluidic structures have great potential for biotechnology, particularly single molecule manipulation and analysis.
High Throughput Peptide Mass Fingerprinting and Protein Macroarray Analysis Using Chemical Printing Strategies (2002)

We describe a chemical printer that uses piezoelectric pulsing for rapid, accurate, and non-contact microdispensing of fluid for proteomic analysis of immobilized protein macroarrays. We demonstrate protein digestion and peptide mass fingerprinting analysis of human plasma and platelet proteins direct from a membrane surface subsequent to defined microdispensing of trypsin and matrix solutions, hence bypassing multiple liquid-handling steps. Detection of low abundance, alkaline proteins from whole human platelet extracts has been highlighted. Membrane immobilization of protein permits archiving of samples pre-/post-analysis and provides a means for subanalysis using multiple chemistries. This study highlights the ability to increase sequence coverage for protein identification using multiple enzymes and to characterize N-glycosylation modifications using a combination of PNGase F and trypsin. We also demonstrate microdispensing of multiple serum samples in a quantitative microenzyme-linked immunosorbent assay format to rapidly screen protein macroarrays for pathogen-derived antigens. We anticipate the chemical printer will be a major component of proteomic platforms for high throughput protein identification and characterization with widespread applications in biomedical and diagnostic discovery.
Preparation of four daunomycin‐monoclonal antibody 79IT/36 conjugates with anti‐tumour activity (1984)

As an approach to developing more specific anti-tumour therapeutic agents, daunomycin has been covalently linked to the human tumour localizing, murine monoclonal antibody 791T/36. Four procedures for coupling drug to antibody were investigated. The sugar amino group of daunomycin was modified by reaction with succinic anhydride or cis aconitic anhydride and these derivatives were linked to antibody, a carbodiimide reagent being used to produce stable peptide bonding. Alternatively, 14-bromo daunomycin was linked directly to antibody or antibody containing free thiol groups introduced by means of the heterobifunctional reagent SPDP [N-succinimidyl-3 (2-pyridyldithio) propionate] thus producing a thioether linkage. Each of the conjugates, with drug-antibody ratios of 3 to 4:1, retained a proportion of drug activity although the succinic anhydride derivative was the least cytotoxic. The three other conjugates specifically bound to tumour cells expressing the 791T/36 antibody defined antigen. In short-term assays in which tumour cells were briefly exposed to conjugates and then washed to remove non-bound conjugate, it was determined that the conjugate with the cis aconityl linkage displayed the greatest selective cytotoxicity against tumour cells reactive with the 791T/36 antibody. These studies illustrate the feasibility of preparing chemically defined drug-antibody conjugates retaining cytotoxicity and selectivity of action against tumour cells.
The hyaluronate receptor is a member of the CD44 (H-CAM) family of cell surface glycoproteins [published erratum appears in J Cell Biol 1991 Feb;112(3):following 513] (1990)

The present study was undertaken to determine the relationship between the hyaluronate receptor and CD44 (H-CAM), cell-surface glycoproteins of similar molecular weights that have been implicated in cell adhesion. In initial experiments, a panel of monoclonal antibodies directed against CD44 were tested for their ability to cross react with the hyaluronate receptor. These antibodies immunoprecipitated [3H]hyaluronate binding activity from detergent extracts of both mouse and human cells, indicating that the hyaluronate receptor is identical to CD44. In addition, one of these antibodies (KM-201 to mouse CD44) directly blocked the binding of labeled hyaluronate to the receptor and inhibited hyaluronate dependent aggregation of SV-3T3 cells. CD44 has also been implicated in lymphocyte binding to high endothelial venules during lymphocyte homing. Interestingly, the monoclonal antibody Hermes-3, which blocks lymphocyte binding to the high endothelial venules of mucosal lymphoid tissue, had no effect on the binding of labeled hyaluronate. Furthermore, the binding of lymphocytes to high endothelial cells of lymph nodes and mucosal lymphoid tissue was not significantly affected by treatment with agents that block the binding of hyaluronate (hyaluronidase, excess hyaluronate and specific antibodies). Thus, CD44 appears to have at least two distinct functional domains, one for binding hyaluronate and another involved in interactions with mucosal high endothelial venules.
Novel organosilicone adjuvants to reduce agrochemical spray volumes on row crops (2000)

Onion and potato crops require frequent applications of highvolume agrochemical sprays The use of two novel organosilicone adjuvant blends DuWett and Bond Xtra is being developed with the aim to halve conventional spray volumes on these crops Adjuvant use rates have been optimised through extensive studies of the physical characteristics of sprays These include leaf coverage retention foliar penetration and phytotoxicity Comparisons with conventional horticultural and other organosilicone adjuvants are made to illustrate the unique properties of DuWett and Bond Xtra which can improve the retention and coverage of sprays on onions and potatoes without increasing the risk of crop phytotoxicity
Decarboxylative Fluorination Strategies for Accessing Medicinally- Relevant Products (2014)

Fluorinated organic compounds have a long history in medicinal chemistry, and synthetic methods to access target fluorinated compounds are undergoing a revolution. One powerful strategy for the installation of fluorinecontaining functional groups includes decarboxylative reactions. Benefits of decarboxylative approaches potentially include: 1) readily available substrates or reagents 2) mild reaction conditions; 3) simplified purification. This focus review highlights the applications of decarboxylation strategies for fluorination reactions to access compounds with biomedical potential. The manuscript highlights on two general strategies, fluorination by decarboxylative reagents and by decarboxylation of substrates. Where relevant, examples of medicinally useful compounds that can be accessed using these strategies are highlighted.
Excitation of a nanowire “molecule” in gold-filled photonic crystal fiber (2012)

A pair of gold nanowires, incorporated into a photonic crystal fiber, acts as a plasmonic "molecule." Hybridized modes are excited at specific wavelengths by launching light into the glass core. The formation of bonding and antibonding solutions results in a modal splitting of more than 100 nm, even though the spatial separation between the wires is larger than 3 μm. The study provides insight into multiwire plasmonic devices with applications as polarizers or filters in near-field optics, nonlinear plasmonics, optical sensing, and telecommunications.
Parsing with Finite-State Transducers (1997)

This chapter contains sections titled: Introduction, Background, Top-Down Parser for Context-Free Grammars, Morphology, Parser for Transformation Grammars, Finite-State Acceleration, Transducer Parser for Tree-Adjoining Grammars, Conclusion, References
LaeA, a Regulator of Morphogenetic Fungal Virulence Factors (2005)

Opportunistic animal and plant pathogens, well represented by the genus Aspergillus, have evolved unique mechanisms to adapt to and avoid host defenses. Aspergillus fumigatus, an increasingly serious pathogen owing to expanding numbers of immunocompromised patients, causes the majority of human infections; however, an inability to identify bona fide virulence factors has impeded therapeutic advances. We show that an A. fumigatus mutation in a developmentally expressed transcriptional regulator (deltalaeA) coordinating morphological and chemical differentiation reduces virulence in a murine model; impaired virulence is associated with decreased levels of pulmonary gliotoxin and multiple changes in conidial and hyphal susceptibility to host phagocytes ex vivo. LaeA, a conserved protein in filamentous fungi, is a developmental regulator of virulence genes and, possibly, the first antimicrobial target specific to filamentous fungi that are pathogenic to plants and animals.
Shape and Spatially-Varying Reflectance Estimation from Virtual Exemplars (2016)

This paper addresses the problem of estimating the shape of objects that exhibit spatially-varying reflectance. We assume that multiple images of the object are obtained under a fixed view-point and varying illumination, i.e., the setting of photometric stereo. At the core of our techniques is the assumption that the BRDF at each pixel lies in the non-negative span of a known BRDF dictionary. This assumption enables a per-pixel surface normal and BRDF estimation framework that is computationally tractable and requires no initialization in spite of the underlying problem being non-convex. Our estimation framework first solves for the surface normal at each pixel using a variant of example-based photometric stereo. We design an efficient multi-scale search strategy for estimating the surface normal and subsequently, refine this estimate using a gradient descent procedure. Given the surface normal estimate, we solve for the spatially-varying BRDF by constraining the BRDF at each pixel to be in the span of the BRDF dictionary; here, we use additional priors to further regularize the solution. A hallmark of our approach is that it does not require iterative optimization techniques nor the need for careful initialization, both of which are endemic to most state-of-the-art techniques. We showcase the performance of our technique on a wide range of simulated and real scenes where we outperform competing methods.
TxLinux (2007)

TxLinux is a variant of Linux that is the first operating system to use hardware transactional memory (HTM) as a synchronization primitive, and the first to manage HTM in the scheduler. This paper describes and measures TxLinux and discusses two innovations in detail: cooperation between locks and transactions, and theintegration of transactions with the OS scheduler. Mixing locks and transactions requires a new primitive, cooperative transactional spinlocks ( cxspinlocks ) that allow locks and transactions to protect the same data while maintaining the advantages of both synchronization primitives. Cxspinlocks allow the system to attemptexecution of critical regions with transactions and automatically roll back to use locking if the region performs I/O. Integrating the scheduler with HTM eliminates priority inversion. On a series ofreal-world benchmarks TxLinux has similar performance to Linux, exposing concurrency with as many as 32 concurrent threads on 32 CPUs in the same critical region.
An architecture for fast processing of large unstructured data sets (2004)

This paper presents a general system architecture tailored to perform searching, filtering, compression, encryption, and other operations on unstructured data streaming from a disk system. The system achieves high performance on such applications by providing for parallelism, hardware-application specialization and reconfiguration, and hardware placement near the disk systems. A limited prototype of a single compute node has been implemented and is described. The prototype is tailored to applications involving complex searching and its performance is compared to a pure software implementation having the same search capabilities. Performance is considered in terms of data set size, query string hit rate and query complexity. Performance results as a function of these parameters are presented and the results indicate that, for data set sizes above 1.4 MB, the prototype compute node is between one and two orders of magnitude faster than a pure software implementation. At high data set sizes, on an individual node, speedups of about 200 and a sustained throughput of 300 MB/sec have been achieved.
Protection of mice against Human respiratory syncytial virus by wild-type and aglycosyl mouse–human chimaeric IgG antibodies to subgroup-conserved epitopes on the G glycoprotein (2006)

Monoclonal antibodies (mAbs) to conserved epitopes on the G glycoprotein of human respiratory syncytial virus (HRSV) subgroup A fail to neutralize the virus in cell culture in the absence of complement, but are protective in rodent models of infection. They may have potential as prophylactic agents in human infants. In order to investigate the role of Fc-dependent pathways in protection by one such antibody, 1C2, the V(H) and V(L) genes were isolated by RT-PCR and assembled with human kappa light-chain and human gamma1 heavy-chain constant-region genes to form two mouse-human chimaeras, which were expressed in NS0 cells. One of the chimaeras carried a wild-type gamma1 chain, whilst the other had an aglycosyl mutation in the C(H)2 domain rendering the antibody defective in complement activation and FcgammaR binding. Whilst both chimaeric antibodies exhibited similar avidity for HRSV in ELISA, only the fully glycosylated wild type was capable of neutralizing the virus in the presence of complement. In mice passively immunized with either murine or wild-type gamma1 chimaeric antibody, no virus could be recovered from the lungs 4 days after intranasal inoculation of HRSV. In mice immunized with the aglycosyl gamma1 chimaera, however, virus was present in the lungs following challenge, although virus titres were significantly reduced compared with controls (P < 0.005). These results indicate that the protective effect of this antibody is mediated by both Fc-dependent and Fc-independent pathways.
Guidelines for dosing of intravenous calcitriol in dialysis patients with hyperparathyroidism (1996)

Intravenous calcitriol has not been used appropriately in the treatment of secondary hyperparathyroidism (HPT) of dialysis patients. Initiation of calcitriol therapy late in severe HPT and inappropriate dosing of calcitriol are common causes of inadequate use of calcitriol. This paper gives general guidelines on the use of intravenous calcitriol and emphasizes the importance of appropriate control of serum phosphorous. The issue of dosing of calcitriol commensurate with the severity of the HPT are highlighted as essential for the complexion of a successful therapeutic attempt. In addition, maintenance dose of calcitriol varies according to the severity of the HPT at the time of initiation of therapy.
Ineffectiveness of an oral killed typhoid vaccine in a field trial. (1973)

A field trial was carried out with a vaccine containing 300x10(9) killed S. typhi (strain Ty58) per tablet. A total of 12 564 children aged 1-15 years were given 3 tablets of the vaccine or a placebo at the rate of one tablet on each of 3 consecutive days. The results indicated that the vaccine, in its present form and at this dosage, gives no protection.