gebhart/patrepeval huggingface dataset:
Systematic identification of N‐acetylheparosan oligosaccharides by tandem mass spectrometric fragmentation (2005)

Recently, a useful procedure for the preparation of both even- and odd-numbered series of N-acetylheparosan (NAH) oligosaccharides was established. The present report describes findings when these NAH oligosaccharides were subjected to comparative mass spectrometry (MS)/MS fragmentation analysis by matrix-assisted laser desorption/ionization (MALDI)-LIFT-time-of-flight (TOF)/TOF-MS/MS, and electrospray ionization (ESI) collision-induced dissociation (CID) MS/MS. The resultant fragment ions were systematically assigned to elucidate fragmentation characteristics. In the MALDI-LIFT-MS/MS experiments, all the NAH oligosaccharides underwent unique glycosidic cleavages that included B-Y ion cleavages (nomenclature system of Domon and Costello, Glycoconjugate J. 1988; 5: 397) at the C-1 side, and C-Z ion cleavages at the C-4 side, with respect to glucuronic acid (GlcA). In addition, (0,2)A and/or (0,2)X cross-ring cleavages were observed for relatively small oligosaccharides. The former observation clearly reflects the occurrence of a GlcA-N-acetylglucosamine (GlcNAc) alternating structure of NAH, while the latter feature implies the occurrence of the -beta-1-4-glucuronide linkage. Extensive glycosidic cleavages were also observed in the ESI-CID-MS/MS fragmentation, though cleavage specificity was less evident than in the case of MALDI-LIFT-TOF/TOF-MS/MS. The information obtained in this study should be valuable for understanding both biosynthetic and degradation processes of NAH and its derivatives including heparin and heparan sulfate, as well as artificially modified NAH oligosaccharides.
A Novel Software Radio Platform Based on General PC and Network (2006)

This paper proposed a novel software radio platform based on general PC and network. On the platform, the interface to the communication front-end is separated from the workstation task, which ease the workstation to a certain degree; the soft-registration protocols are adopted here to set up the parallel distributed data processing. In the platform, there is no exclusive central control unit, and the management and control of the network are dispersed to many nodes, which improve the system performance. The system performance is also given in this paper
Synthesis and Reactions of 1-Acetyl-2-benzylidene-3-oxo-2,3-dihydroindoles (1989)

1-Acetyl-3-oxo-2,3-dihydroindoles were reacted with substituted benzaldehydes affording 1-acetyl-2-arylmethylene-3-oxo-2,3-dihydroindoles which were selectively reduced by hydrogen; then a Horner-Emmons reaction gave the precursors of 2-substituted tryptamines. Nitromethane was added to 1-acetyl-2-arylmethylene-3-oxo-2,3-dihydroindoles giving Michael addition products.
Receptors on the brush border membrane of the insect midgut as determinants of the specificity of Bacillus thuringiensis delta-endotoxins (1990)

To investigate the biochemical basis of the differences in the insecticidal spectrum of Bacillus thuringiensis insecticidal crystal proteins (ICPs), we performed membrane binding and toxicity assays with three different ICPs and three lepidopteran species. The three ICPs have different toxicity patterns in the three selected target species. Binding studies with these 125I-labeled ICPs revealed high-affinity saturable binding to brush border membrane vesicles of the sensitive species. ICPs with no toxicity against a given species did not bind saturably to vesicles of that species. Together with previous data that showed a correlation between toxicity and ICP binding, our data support the statement that differences in midgut ICP receptors are a major determinant of differences in the insecticidal spectrum of the entire lepidopteran-specific ICP family. Receptor site heterogeneity in the insect midgut occurs frequently and results in sensitivity to more than one type of ICP.
Appearance of a megakaryocyte growth-promoting activity, megapoietin, during acute thrombocytopenia in the rabbit (1994)

Plasma obtained from rabbits made thrombocytopenic by the injection of antiplatelet serum (APS) stimulated megakaryocyte growth in an in vitro bone marrow culture. Although the number of megakaryocytes that grew was increased on average to 136%, the major effect was on megakaryocyte ploidy, which showed a shift in the modal ploidy class from 8N to 16N, an average change in the geometric mean ploidy from 8.7N to 11.8N, and the appearance of some 64N megakaryocytes. This in vitro stimulation of megakaryocyte number and ploidy was shown to be due to the appearance in the circulation of a positive activity, which we have named megapoietin. Levels of megapoietin in thrombocytopenic plasma could be quantitated by measuring the extent of megakaryocyte ploidization in vitro. The relationship over time of megapoietin to changes in the platelet count was then assessed in a series of rabbits made thrombocytopenic by APS injection. Although not elevated after 3 hours of thrombocytopenia, megapoietin increased after 8 hours to 48% of the maximal level, which occurred after 24 hours of thrombocytopenia. Levels of megapoietin were inversely and proportionally related to the platelet count during thrombocytopenia and the subsequent rebound thrombocytosis. During persistent thrombocytopenia, megapoietin levels remained maximally elevated. These results suggest that megapoietin may play a physiologic role in the feedback loop between the platelet and the bone marrow megakaryocytes.
Interferon-Alpha-2 C in the Treatment of Advanced Hairy Cell Leukaemia (1985)

The efficacy of recombinant interferon-alpha 2 in the treatment of advanced hairy cell leukaemia is investigated in 31 patients. Preliminary results show a complete and partial response rate of 69%. An optimal dose study utilizing maximal stimulation of an interferon-dependent pathway was carried out in 5 patients. The optimal dose of the order of 5 X 10(5) IU/day is effective and without side-effects. Interferon treatment did not enhance natural killer cell activity and therefore a direct mode of action upon tumour cells is proposed.
The Morphology of Islets within the Porcine Donor Pancreas Determines the Isolation Result: Successful Isolation of Pancreatic Islets can Now be Achieved from Young Market Pigs (2002)

Clinical islet allotransplantation has become an increasingly efficient "routine" therapy in recent years. Shortage of human donor organs leads to porcine pancreatic islets as a potential source for islet xenotransplantation. Yet it is still very difficult to isolate sufficient numbers of intact porcine islets, particularly from young market pigs. In the following study islets were successfully isolated from retired breeders [4806 +/- 720 islet equivalents per gram organ (IEQ/g); n = 25; 2-3 years old; RB] and also from young hybrid pigs [2868 +/- 260 IEQ/g; n = 65; 4-6 months old; HY] using LiberasePI and a modified version of Ricordi's digestion-filtration technique. As expected, isolations from RB showed significantly better results (p < 0.002). A retrospective histological analysis of almost all donor pancreases showed that the majority of organs from RB (80%) contained mainly large islets (diameter > 200 microm), in contrast to only 35% of all pancreases from HY. Remarkably, the islet size in situ, regardless whether detected in RB or HY, strongly determined the isolation result. A donor organ with predominantly large islets resulted in significantly higher numbers of IEQs compared with a donor organ with predominantly small islets [RB(Large Islets): 5680 +/- 3,318 IEQ/g (n= 20); RB(Small Islets): 1353 +/- 427 IEQ/g (n = 5); p < 0.02]. In addition, isolation results were strongly influenced by the quality of the LiberasePI batch, and therefore single batch testing is invariably required. Purification was performed using Ficoll or OptiPrep density gradient centrifugation manually or in the COBE cell processor. Although islet purity was highest when OptiPrep was used, final islet yields did not differ between the different purification methods. Our study demonstrates that islet size in situ is an extremely critical parameter for highly successful islet isolation; consequently, we are now performing a morphological screening of each donor organ prior to the isolation process. Under these conditions highly successful isolations can reliably be performed even from young market pigs.
Polymorphonuclear Leukocyte Activation (1993)

It has been suggested that major surgery induces polymorphonuclear leukocyte (PMNL) dysfunction, which exposes patients to the development of sepsis. Conversely, the sepsis response and multisystem organ failure in patients after surgery is thought to be mediated by activated PMNLs. In a preliminary attempt to investigate this paradox, we studied functional (hydrogen peroxide production) and phenotypic (the adhesion/complement receptor CD11b) markers of PMNL activation in 28 patients undergoing elective major resectional surgery; 11 (39%) of these patients developed postoperative sepsis (the septic group). The mean (SEM) preoperative level of neutrophil CD11b expression (97.8 [6.2] mean channel fluorescence [MCF] and 101.42 [7.9] MCF; P = .74) and hydrogen peroxide production (109.51 [4.91] MCF and 104.53 [6.3] MCF; P = .5) were similar for the uncomplicated and septic groups, respectively. However, on the first postoperative day, both mean CD11b expression and hydrogen peroxide production were greater in those patients who subsequently developed postoperative sepsis (192.5 [38] MCF vs 128.6 [8.1] MCF for the septic group vs the uncomplicated group, respectively [P < .05], and 120.43 [2.56] MCF vs 109.61 [3.05] MCF for the septic group vs the uncomplicated group, respectively [P < .0001]). We suggest that an exaggerated PMNL activation response to surgery is an early event in those patients destined to develop postsurgical sepsis.
Ten Lectures on Wavelets (1992)

Mathematics of Computing -- Miscellaneous.
Rewiring Cell Adhesion (2004)

The adhesion of cells is mediated by the binding of several cell-surface receptors to ligands found in the extracellular matrix. These receptors often have overlapping specificities for the peptide ligands, making it difficult to understand the roles for discrete receptors in cell adhesion, migration, and differentiation as well as to direct the selective adhesion of cell types in tissue-engineering applications. To overcome these limitations, we developed a strategy to rewire the receptor-ligand interactions between a cell and substrate to ensure that adhesion is mediated by a single receptor with unique specificity. The strategy combines a genetic approach to engineer the cell surface with a chimeric integrin receptor having a unique ligand binding domain with a surface chemistry approach to prepare substrates that present ligands that are bound by the new binding domain. We show that Chinese hamster ovary cells that are engineered with a chimeric beta1 integrin adhere, signal, and even migrate on a synthetic matrix.
Tolerability and pharmacokinetics of metformin and the dipeptidyl peptidase-4 inhibitor sitagliptin when co-administered in patients with type 2 diabetes (2006)

In this study, co-administration of sitagliptin and metformin was generally well tolerated in patients with type 2 diabetes and did not meaningfully alter the steady-state pharmacokinetics of either agent.
[Facial or nasal mask pressure support ventilation in managing acute exacerbation of chronic respiratory failure in chronic obstructive pulmonary diseases]. (1992)

11 COPD patients (age: 65 +/- 9 Yrs) with acute exacerbation of chronic respiratory failure (PaCO2 11.3 +/- 1.1kPa) were treated with mask pressure support ventilation, another 10 similar patients (age: 68 +/- 12 Yrs) served as control. BiPAP ventilator was used with the following modifications: (1) Non-rebreathing valve set-in proximal to mask; (2) 5 LPM oxygen flow delivered into mask to reduce the dead space effect. Mask ventilation was given 2-3 hours every time and 1-2 time daily for 7 days. Synchrony and airway patency were specially monitored. The results suggested that mask ventilation could reduce PaCO2, improve PaO2, relieve dyspnea and decrease the possibility of intubation.
Proton-Sponge Coated Quantum Dots for siRNA Delivery and Intracellular Imaging (2008)

We report the rational design of multifunctional nanoparticles for short-interfering RNA (siRNA) delivery and imaging based on the use of semiconductor quantum dots (QDs) and proton-absorbing polymeric coatings (proton sponges). With a balanced composition of tertiary amine and carboxylic acid groups, these nanoparticles are specifically designed to address longstanding barriers in siRNA delivery such as cellular penetration, endosomal release, carrier unpacking, and intracellular transport. The results demonstrate dramatic improvement in gene silencing efficiency by 10-20-fold and simultaneous reduction in cellular toxicity by 5-6-fold, when compared directly with existing transfection agents for MDA-MB-231 cells. The QD-siRNA nanoparticles are also dual-modality optical and electron-microscopy probes, allowing real-time tracking and ultrastructural localization of QDs during delivery and transfection. These new insights and capabilities represent a major step toward nanoparticle engineering for imaging and therapeutic applications.
Development of Antioxidant COX-2 Inhibitors as Radioprotective Agents for Radiation Therapy—A Hypothesis-Driven Review (2016)

Radiation therapy (RT) evolved to be a primary treatment modality for cancer patients. Unfortunately, the cure or relief of symptoms is still accompanied by radiation-induced side effects with severe acute and late pathophysiological consequences. Inhibitors of cyclooxygenase-2 (COX-2) are potentially useful in this regard because radioprotection of normal tissue and/or radiosensitizing effects on tumor tissue have been described for several compounds of this structurally diverse class. This review aims to substantiate the hypothesis that antioxidant COX-2 inhibitors are promising radioprotectants because of intercepting radiation-induced oxidative stress and inflammation in normal tissue, especially the vascular system. For this, literature reporting on COX inhibitors exerting radioprotective and/or radiosensitizing action as well as on antioxidant COX inhibitors will be reviewed comprehensively with the aim to find cross-points of both and, by that, stimulate further research in the field of radioprotective agents.
Detection of secondary structure elements in proteins by hydrophobic cluster analysis (1992)

Hydrophobic cluster analysis (HCA) is a protein sequence comparison method based on alpha-helical representations of the sequences where the size, shape and orientation of the clusters of hydrophobic residues are primarily compared. The effectiveness of HCA has been suggested to originate from its potential ability to focus on the residues forming the hydrophobic core of globular proteins. We have addressed the robustness of the bidimensional representation used for HCA in its ability to detect the regular secondary structure elements of proteins. Various parameters have been studied such as those governing cluster size and limits, the hydrophobic residues constituting the clusters as well as the potential shift of the cluster positions with respect to the position of the regular secondary structure elements. The following results have been found to support the alpha-helical bidimensional representation used in HCA: (i) there is a positive correlation (clearly above background noise) between the hydrophobic clusters and the regular secondary structure elements in proteins; (ii) the hydrophobic clusters are centred on the regular secondary structure elements; (iii) the pitch of the helical representation which gives the best correspondence is that of an alpha-helix. The correspondence between hydrophobic clusters and regular secondary structure elements suggests a way to implement variable gap penalties during the automatic alignment of protein sequences.
A Retrospective Review of TATRC Funding for Medical Modeling and Simulation Technologies (2011)

There seems to be a measurable gap between industry's definition of a completed product technology and academia's ability to implement and use the technology in interactive learning environments. Our findings support the need for a standardized strategic design process that involves a strong industry-academia collaboration and early end-user testing to better facilitate the development of sound requirements that guide technology development.
High Performance Fibers (1994)

A two and a half year ONR/ARPA funded program to develop a low cost process for manufacture of a high strength/high modulus sigma/E boron nitride (BN) fiber was initiated on 7/1/90 and ended on 12/31/92. The preparation of high sigma/E BN fibers had been demonstrated in the late 1960's by the PI using a batch nitriding of B2O3 fiber with NH3 followed by stress graphitization at approx. 2000 deg C. Such fibers displayed values comparable to PAN based carbon fibers but the mechanicals were variable most likely because of redeposition of volatiles at 2000 deg C. In addition, the cost of the fibers was very high due to the need for many hours of nitriding necessary to convert the BsO3 fibers. the use of batch nitriding negated two possible cost advantages of this concept, namely, the ease of drawing very fine, multi-filament yarn of B2O3 and more importantly the very low cost of the starting materials.
Developmental pathways of dendritic cells in vivo: distinct function, phenotype, and localization of dendritic cell subsets in FLT3 ligand-treated mice (1997)

We have recently shown that Flt3 ligand administration dramatically increases dendritic cell (DC) numbers in various mouse tissues. This has enabled the identification of distinct mature DC subpopulations. These have been designated: population C (CD11c(bright) CD11b(bright)), D (CD11c(bright) CD11b(dull)), and E (CD11c(bright) CD11b(negative)) This report demonstrates that the mature DC subsets (C, D, and E) from Flt3 ligand-treated mice differ with respect to phenotype, geographic localization, and function. The myeloid Ags CD11b, F4/80, and Ly-6C are predominantly expressed by population C, but not D or E. In addition, a subset of population C-type DC expresses 33D1 and CD4. In contrast, DC within population D and E selectively express the lymphoid-related DC markers CD8alpha, DEC 205, CD1d, as well as CD23, elevated levels of CD117 (c-kit), CD24 (HSA), CD13, and CD54. Immunohistology indicates that the different DC subsets reside in distinct microenvironments, with populations D and E residing in the T cell areas of the white pulp, while DC within population C localize in the marginal zones. These DC subpopulations showed different capacities to phagocytose FITC-zymosan and to secrete IL-12 upon stimulation with Staphylococcus aureus cowan I strain + IFN-gamma + granulocyte-macrophage-CSF. Population C-type DC were more phagocytic but secreted little inducible IL-12 while population D- and E-type DC showed poor phagocytic capacity and secreted considerably higher levels of IL-12. These results underscore the importance of viewing DC development in vivo, as an interplay between distinct lineages and a maturational dependence on specific microenvironmental signals.
[Balloon aortic valvuloplasty in the adult. Immediate results and in-hospital complications in the latest series of 141 consecutive patients at the University Hospital of Rouen (2002-2005)]. (2006)

In the hands of skilled operators, aortic percutaneous balloon dilatation has become a simple technique, associated with a low risk of complications despite a very ill patient population. This technique remains a good option for a number of patients before the onset of percutaneous aortic valve implantation.
Catalytic Asymmetric Assembly of Stereodefined Propionate Units:  An Enantioselective Total Synthesis of (−)-Pironetin (2006)

Double diastereoselection in alkaloid-catalyzed acyl halide-aldehyde cyclocondensation (AAC) reactions provides a strategy for realizing syn- or anti-selective propionate aldol additions from a common reaction manifold. Matched AAC homologation of enantioenriched aldehydes afford cis-disubstituted beta-lactones as surrogates for syn aldols; the mismatched AAC reactions provide anti-selective aldols in the form of trans-disubstituted 2-oxetanones. The utility of this reaction technology in synthesis activities is exemplified in a catalytic asymmetric total synthesis of (-)-pironetin.
An in vitro model maintaining taxon-specific functional activities of the gut microbiome (2019)

In vitro gut microbiome models could provide timely and cost-efficient solutions to study microbiome responses to drugs. For this purpose, in vitro models that maintain the functional and compositional profiles of in vivo gut microbiomes would be extremely valuable. Here, we present a 96-deep well plate-based culturing model (MiPro) that maintains the functional and compositional profiles of individual gut microbiomes, as assessed by metaproteomics, while allowing a four-fold increase in viable bacteria counts. Comparison of taxon-specific functions between pre- and post-culture microbiomes shows a Pearson's correlation coefficient r of 0.83 ± 0.03. In addition, we show a high degree of correlation between gut microbiome responses to metformin in the MiPro model and those in mice fed a high-fat diet. We propose MiPro as an in vitro gut microbiome model for scalable investigation of drug-microbiome interactions such as during high-throughput drug screening.
Targeting RAS-driven human cancer cells with antibodies to upregulated and essential cell-surface proteins (2018)

While there have been tremendous efforts to target oncogenic RAS signaling from inside the cell, little effort has focused on the cell-surface. Here, we used quantitative surface proteomics to reveal a signature of proteins that are upregulated on cells transformed with KRAS<sup>G12V</sup>, and driven by MAPK pathway signaling. We next generated a toolkit of recombinant antibodies to seven of these RAS-induced proteins. We found that five of these proteins are broadly distributed on cancer cell lines harboring RAS mutations. In parallel, a cell-surface CRISPRi screen identified integrin and Wnt signaling proteins as critical to RAS-transformed cells. We show that antibodies targeting CDCP1, a protein common to our proteomics and CRISPRi datasets, can be leveraged to deliver cytotoxic and immunotherapeutic payloads to RAS-transformed cancer cells and report for RAS signaling status in vivo. Taken together, this work presents a technological platform for attacking RAS from outside the cell.