gebhart/patrepeval huggingface dataset:
De novo sequencing of peptides on single resin beads by MALDI-FTICR tandem mass spectrometry (2009)

An efficient approach in combinatorial chemistry is the synthesis of one-bead-one-compound peptide libraries. In contrast to synthesis and functional screening, which is performed in a largely automated manner, structure determination has been frequently laborious and time-consuming. Here we report an approach for de novo sequencing of peptides on single beads by matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance (MALDI-FTICR) tandem mass spectrometry, using a resin with a photolinker for solid-phase peptide synthesis. Upon sorting out single beads, an efficient sample preparation on the MALDI target was developed that enables fragmentation upon irradiation of the bead-matrix mixture with the ultraviolet (UV)-MALDI laser, with enhanced yield of sequence-specific fragment ions at increased laser energy. This approach is illustrated by sequence determinations of two peptides from a library with sequences varying in a single amino acid; the feasibility with tandem-MS procedures and fragment ion assignment was ascertained by sustained off-resonance irradiation/collision induced dissociation (SORI/CID) and infrared multiphoton dissociation (IRMPD) fragmentation.
Identification of genes responsible for osteoblast differentiation from human mesodermal progenitor cells (2003)

Single human bone marrow-derived mesodermal progenitor cells (MPCs) differentiate into osteoblasts, chondrocytes, adipocytes, myocytes, and endothelial cells. To identify genes involved in the commitment of MPCs to osteoblasts we examined the expressed gene profile of undifferentiated MPCs and MPCs induced to the osteoblast lineage for 1-7 days by cDNA microarray analysis. As expected, growth factor, hormone, and signaling pathway genes known to be involved in osteogenesis were activated during differentiation. In addition, 41 transcription factors (TFs) were differentially expressed over time, including TFs with known roles in osteoblast differentiation and TFs not known to be involved in osteoblast differentiation. As the latter group of TFs coclustered with osteogenesis-specific TFs, they may play a role in osteoblast differentiation. When we compared the gene expression profile of MPCs induced to differentiate to chondroblasts and osteoblasts, significant differences in the nature and/or timing of gene activation were seen. These studies indicate that in vitro differentiation cultures in which MPCs are induced to one of multiple cell fates should be very useful for defining signals important for lineage-specific differentiation.
Pharmacokinetic Characterization in Xenografted Mice of a Series of First-Generation Mimics for HLA-DR Antibody, Lym-1, as Carrier Molecules to Image and Treat Lymphoma (2007)

A series of SHALs was readily synthesized in multimilligram amounts and showed the expected selective binding in vitro. Better selection of the SHAL components should provide second-generation SHALs with improved properties to fulfill the substantial potential of these novel molecular carriers for targeting.
Splitting of the Ribose-Ribose Linkage of Poly(Adenosine Diphosphate-Ribose) by a Calf Thymus Extract (1971)

Abstract Poly(ADP-Rib) was hydrolyzed by a calf thymus nuclear preparation. The reaction products were ADP-Rib and oligo(ADP-Rib). This reaction is a novel mechanism for degradation of poly(ADP-Rib).
Computer Television Broadcast Automation (1972)

The introduction of computers into broadcast operations raises problems of specialization and unfamiliarity with techniques for both the TV systems designer and ultimate user on the one hand, and the manufacturer and supplier of equipment on the other. The following three papers show how one specialist manufacturer utilized a computer consultant to obtain expertise to satisfy a customer's particular requirements. The problems and solutions are shown in turn from the points of view of consultant, manufacturer and user.
Stoichiometric Shifts in the Common Bean Mitochondrial Genome Leading to Male Sterility and Spontaneous Reversion to Fertility (1998)

The plant mitochondrial genome is characterized by a complex, multipartite structure. In cytoplasmic male-sterile (CMS) common bean, the sterility-inducing mitochondrial configuration maps as three autonomous DNA molecules, one containing the sterility-associated sequence pvs-or f 239. We constructed a physical map of the mitochondrial genome from the direct progenitors to the CMS cytoplasm and have shown that it maps as a single, circular master configuration. With long-exposure autoradiography of DNA gel blots and polymerase chain reaction analysis, we demonstrate that the three-molecule CMS-associated configuration was present at unusually low copy number within the progenitor genome and that the progenitor form was present substoichiometrically within the genome of the CMS line. Furthermore, upon spontaneous reversion to fertility, the progenitor genomic configuration as well as the molecule containing the pvs-or f 239 sterility-associated sequence were both maintained at substoichiometric levels within the revertant genome. In vitro mitochondrial incubation results demonstrated that the genomic shift of the pvs-or f 239-containing molecule to substoichiometric levels upon spontaneous reversion was a reversible phenomenon. Moreover, we demonstrate that substoichiometric forms, apparently silent with regard to gene expression, are transcriptionally and translationally active once amplified. Thus, copy number suppression may serve as an effective means of regulating gene expression in plant mitochondria.
HISTORIAE, History of Socio-Cultural Transformation as Linguistic Data Science. A Humanities Use Case (2019)

Given a combinatorial optimisation problem, there are typically multiple ways of modelling it for presentation to an automated solver. Choosing the right combination of model and target solver can have a significant impact on the effectiveness of the solving process. The best combination of model and solver can also be instance-dependent: there may not exist a single combination that works best for all instances of the same problem. We consider the task of building machine learning models to automatically select the best combination for a problem instance. Critical to the learning process is to define instance features, which serve as input to the selection model. Our contribution is the automatic learning of instance features directly from the high-level representation of a problem instance using a transformer encoder. We evaluate the performance of our approach using the Essence modelling language via a case study of three problem classes.
Focusing of electromagnetic waves by a left-handed metamaterial flat lens (2005)

We present here the experimental results from research conducted on negative refraction and focusing by a two-dimensional (2D) left-handed metamaterial (LHM) slab. By measuring the refracted electromagnetic (EM) waves from a LHM slab, we find an effective refractive index of -1.86. A 2D scanning transmission measurement technique is used to measure the intensity distribution of the EM waves that radiate from the point source. The flat lens behavior of a 2D LHM slab is demonstrated for two different point source distances of d(s) = 0.5lambda and lambda. The full widths at half maximum of the focused beams are 0.36lambda and 0.4lambda, respectively, which are both below the diffraction limit.
Seebeck coefficient in silicon nanowire arrays (2013)

We measure the Seebeck coefficient S in large arrays of lightly doped n-Si nanowires (SiNWs). Our samples consist of ∼107 NWs in parallel, forming a “bulk” nano-structured material. We find that the phonon drag component of S, a manifestation of electron-phonon scattering in the sample, is heavily suppressed due to surface scattering, and that there is a “universal” temperature dependence for S. Furthermore, at room temperature, S is enhanced in the arrays by up to ∼3 times in comparison to bulk Si.
Effects of Fabrication Process Parameters on the Properties of Cyclic Olefin Copolymer Microfluidic Devices (2006)

Among the materials used for fabricating microfluidic devices, plastics have been increasingly employed in the past few years. Although several methods for fabricating plastic devices have appeared in the literature, reports typically indicate one set of conditions that yield functional devices; little data are available detailing how results are affected by their changes in the process variables. We report in this paper a systematic study of fabrication process parameters including compression rate, molding temperature, and the force used by a hydraulic press, as well as their effects on the device properties. Using cyclic olefin copolymers as the molding material, we found that the device thickness decreased when the molding temperature and compression force increased. Fidelity in the pattern transfer from a master to a device was confirmed by the reproduction of nanostructures and channel depth/shape. Pattern transfer fidelity appeared to be independent of the molding temperature and compression force, at least in the range of conditions we investigated. Stress whitening (or crazing) on the device surface was found to be related to the molding temperature and the cooling rate of the mold/device assembly. The bond strength between the layers of a laminated device was determined to be a function of the lamination temperature. In addition, we demonstrated the utility of a plastic microfluidic device by separating proteins. 1678
On the EM algorithm for overdispersed count data (1997)

In this paper, we consider the use of the EM algorithm for the fitting of distributions by maximum likelihood to overdispersed count data. In the course of this, we also provide a review of various approaches that have been proposed for the analysis of such data. As the Poisson and binomial regression models, which are often adopted in the first instance for these analyses, are particular examples of a generalized linear model (GLM), the focus of the account is on the modifications and extensions to GLMs for the handling of overdispersed count data.
Role of Activating Fibroblast Growth Factor Receptor 3 Mutations in the Development of Bladder Tumors (2005)

FGFR3 mutations seem to have a central role in the early development of papillary bladder tumors. These tumors follow a common molecular pathway, which is different from tumors with concomitant CIS. FGFR3 mutations do not seem to play a role in bladder cancer progression.
New Pressure-Transient Analysis Model for Dual-Porosity Reservoirs (1989)

Summary This paper presents a new analytical model for interpreting pressure-transient tests for wells producing from dual-porosity reservoirs. This model includes unsteady-state matrix flow and incorporates the effects of wellbore storage, skin, and, for gas reservoirs, desorption. The model is applicable to bounded and infinite-acting reservoirs.
Minimum Energy Analysis and Experimental Verification of a Latch-Based Subthreshold FPGA (2012)

Field-programmable gate arrays (FPGAs) are an attractive option for low-power systems requiring flexible computing resources. However, the lowest power systems have yet to adopt FPGAs. Subthreshold circuit operation offers the opportunity to operate FPGAs at their minimum energy point. This paper presents data measured from an FPGA test chip fabricated in a 0.18-μm SOI process. It is shown that the test chip can function at supply voltages as low as 0.26 V without an extra supply for write assists by using latches for configuration bit storage instead of static random access memory. Investigation of the minimum energy point of the FPGA for a high-activity test pattern shows that the minimum energy point of the FPGA can be well below the threshold voltage of the transistors.
Structural Basis of the Interaction between Chemokine Stromal Cell-derived Factor-1/CXCL12 and Its G-protein-coupled Receptor CXCR4 (2009)

The chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) and its G-protein-coupled receptor (GPCR) CXCR4 play fundamental roles in many physiological processes, and CXCR4 is a drug target for various diseases such as cancer metastasis and human immunodeficiency virus, type 1, infection. However, almost no structural information about the SDF-1-CXCR4 interaction is available, mainly because of the difficulties in expression, purification, and crystallization of CXCR4. In this study, an extensive investigation of the preparation of CXCR4 and optimization of the experimental conditions enables NMR analyses of the interaction between the full-length CXCR4 and SDF-1. We demonstrated that the binding of an extended surface on the SDF-1 beta-sheet, 50-s loop, and N-loop to the CXCR4 extracellular region and that of the SDF-1 N terminus to the CXCR4 transmembrane region, which is critical for G-protein signaling, take place independently by methyl-utilizing transferred cross-saturation experiments along with the usage of the CXCR4-selective antagonist AMD3100. Furthermore, based upon the data, we conclude that the highly dynamic SDF-1 N terminus in the 1st step bound state plays a crucial role in efficiently searching the deeply buried binding pocket in the CXCR4 transmembrane region by the "fly-casting" mechanism. This is the first structural analyses of the interaction between a full-length GPCR and its chemokine, and our methodology would be applicable to other GPCR-ligand systems, for which the structural studies are still challenging.
Induction and characterization of pigment mutants in the red microalga Porphyridium sp. (Rhodophyceae) (1993)

AbstractSeveral pigment mutants of the red microalga Porphyridium sp. were isolated after induced mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine (NNG). The mutants were screened on agar plates incubated at 150 μmol photons m−2 s−1 for clones that did not show red pigmentation. After two weeks of incubation, three green or greenish-yellow mutants, C-12, 0-10 and F-11, were chosen for further characterization. The mutation frequency of these mutants ranged between 5 × 10−6 and 8 × 10−6, their phenotypic pigmentation was stable over many consecutive transfers, and no reversion to the wild phenotype was observed. The reversion frequency was estimated to be less than 3 × 10−8. The most striking feature of the mutants was their low phycoerythrin content. When the mutants were cultured under conditions of high photon flux density (300 μmol photons m−2 s−1) no phycoerythrin was detected in cells of mutants D-10 and F-11, while mutant C-12 produced about 25% of the phycoerythrin found in the wild type cells. However, when cultured at a low photon flux density (40 μmol photons m−2 s−1) all mutants produced phycoerythrin, although at a level that ranged between 5 and 30% of that of the wild type. Similarly, during growth at high photon flux density, the chlorophyll content of the mutants was lower than that of the wild type. Under conditions of low photon flux density the chlorophyll values in mutant cells were higher than those found at high photon flux density and were comparable with those of the wild type. No significant difference was found between the phycocyanin content of the mutants and that of the wild type. The growth rate of all mutants was found to be similar to that of the wild type. However, when the mutants were cultured at high photon flux density, the cell biomass of two of them (D-10 and C-12) was lower than that of the wild type. This could be partially attributed to the reduced amount of cell wall polysaccharide in these mutants. Two of the mutants (C-12 and F-11) showed similar or slightly higher photosynthetic performance compared with the wild type, on a per cell basis, while all three had higher Pmax values and mutant F-11 had a higher α value when normalized to the chlorophyll α level.
Normally-off GaN Transistors for Power Applications (2014)

Normally-off high voltage GaN-HFETs for switching applications are presented. Normally-off operation with threshold voltages of 1 V and more and with 5 V gate swing has been obtained by using p-type GaN as gate. Different GaN-based buffer types using doping and backside potential barriers have been used to obtain blocking strengths up to 1000 V. The increase of the dynamic on-state resistance is analyzed for the different buffer types. The best trade-off between low dispersion and high blocking strength was obtained for a modified carbon-doped GaN-buffer that showed a 2.6x increase of the dynamic on-state resistance for 500 V switching as compared to switching from 20 V off-state drain bias. Device operation up to 200 °C ambient temperature without any threshold voltage shift is demonstrated.
Hepatitis C virus variants from Jakarta, Indonesia classifiable into novel genotypes in the second (2e and 2f), tenth (10a) and eleventh (11a) genetic groups (1996)

Hepatitis C virus (HCV) isolates from 126 hepatitis patients in Jakarta, Indonesia were genotyped by PCR with genotype-specific primers deduced from the HCV core gene. Fifty-five isolates (44%) were classified as genotype II/1b, 15 (12%) as 1c, 33 (26%) as III/2a, and 1 (1%) as V/3a, while the remaining 22 (17%) were not classifiable into any of the five common genotypes (I/1a, II/1b, III/2a, IV/2b and V/3a) or 1c. Sequences of a part of the NS5b region [1093 bp (nucleotides 8279-9371)] of the 22 isolates of unclassifiable genotype were subjected to pair-wise comparison and phylogenetic analysis along with those of 62 isolates of 25 genotypes in nine genetic groups. Seven of the isolates were classified into 2e and two into 2f, representing novel genotypes in genetic group 2, while ten and three were classified into two new genetic groups, 10 and 11, respectively, and their genotypes were provisionally designated 10a and 11a. The isolates of genotype 10a (JK049) and 11a (JK046) were sequenced in full. Comparison of 24 HCV genomes including those of JK049 and JK046, over the entire genome and subgenomic regions, supported the classification of HCV into 11 genetic groups.
The orientation of prostaglandin endoperoxide synthases-1 and -2 in the endoplasmic reticulum. (1994)

Prostaglandin endoperoxide H synthases (PGHS)-1 and -2 are integral membrane proteins of the endoplasmic reticulum (ER). The luminal versus cytoplasmic orientations of several epitopes of PGHS-1 and PGHS-2 were determined by immunocytofluorescent staining of cells following treatment with membrane-selective permeants. With serum-stimulated, murine NIH/3T3 cells expressing PGHS-2, an anti-peptide antibody directed against a domain near the COOH terminus of this isozyme caused staining only after all membranes were permeabilized with 0.2% saponin; no staining occurred with 3T3 cells treated with digitonin to permeabilize only the plasma membrane. Similarly, cos-1 cells expressing ovine PGHS-1 were stained with anti-peptide antibodies directed against (a) the amino terminus (residues 25-35), (b) a domain containing the tryptic cleavage site at Arg277 (residues 272-284), or (c) a region near the carboxyl terminus (residues 583-594) following permeabilization with saponin but not with digitonin or streptolysin O. The results obtained with the antibodies against the Arg277-containing domain of PGHS-1 were surprising because the enzyme is susceptible to tryptic cleavage at Arg277 in microsomal preparations. However, enzymatic and immunochemical analyses of microsomes prepared from ovine vesicular glands and cos-1 cells indicated that these microsomes are not intact. Accordingly, our results indicate that the trypsin cleavage site (Arg277) as well as the NH2 and COOH termini of ovine PGHS-1 are on the luminal side of the ER. The NH2 terminus, the Arg277 domain, and the N-glycosylation sites of ovine PGHS-1 are part of a large soluble, globular structure in crystalline ovine PGHS-1 (Picot, D., Loll, P. J., and Garavito, M. (1994) Nature, 367, 243-249). We conclude that PGHS-1 and, by analogy, the highly homologous PGHS-2 are luminal ER proteins. Assuming that the PGHS-1 and PGHS-2 present in the ER are functional in intact cells, our results indicate that PGH2 synthesis from arachidonate occurs in the lumen of the ER.
Tocilizumab for the treatment of chimeric antigen receptor T cell-induced cytokine release syndrome (2019)

<b>Introduction</b>: Cancer-directed immunotherapies are transforming the landscape in oncology as new and exciting therapies move from the laboratory to the bedside. Chimeric antigen receptor T (CAR-T) cells are one of these novel therapies, demonstrating impressive efficacy against B-cell malignancies. With the development of new therapies, it is not uncommon to identify new and unanticipated toxicities. CAR-T cells cause unique toxicities not typically found with traditional cytotoxic chemotherapy or small molecule inhibitors. <b>Areas covered</b>: CAR-T cell associated toxicities include cytokine release syndrome (CRS) and CAR-T cell-related encephalopathy syndrome (CRES), alternatively known as immune effector cell-associated neurotoxicity syndrome (ICANS). Prompt identification and management of CRS and CRES are imperative for the prevention of life-threatening complications of these innovative therapies. This literature review describes the seminal trials of CD19-directed immunotherapy and the pathophysiology and management of the toxicities found with CAR-T cells. In addition, the use of the interleukin-6 receptor antibody tocilizumab for CRS is reviewed. <b>Expert opinion</b>: This review describes the recommended management of CRS and CRES and examines the current limitations in management. Alternative therapies for the treatment of CAR-T cell related toxicities are also explored. Furthermore, the review proposes future directions for research.
Intramolecular Excitonic Dimers in Protease Substrates:  Modification of the Backbone Moiety To Probe the H-Dimer Structure (1998)

NorFES (DAIPN1SIPKGY, N1 = norleucine) is an undecapeptide that contains a recognition sequence and cleavage site for the serine protease elastase. When NorFES is doubly labeled with a variety of fluorophores on opposite sides of this amino acid sequence, the fluorescence is quenched due to formation of intramolecular ground-state dimers. Although the spectral characteristics of these dimers are predictable by exciton theory, influence of the peptide backbone on H-dimer formation is less well understood. Specifically, factors that modify the attractive forces between and orientation of dyes are not well-characterized. Thus, by varying the dye linker moieties, we have sought to evaluate the thermodynamic parameters for intramolecular H-type dye−dye association and the structures of these dimers. We now present data from a series of homodoubly labeled NorFES derivatives that differ by the addition of one or two 6-aminohexanoic acids to the peptide backbone. By comparing absorption and fluorescence properties of these substrates as a function of temperature, we examined how such additions could modify dimerization; we calculated the free energy of activation (ΔG⧧) for intramolecular dimer disruption of each substrate. To gain further insight into dye−dye orientation, a NorFES substrate modified to facilitate intramolecular H-dimerization was synthesized with different geometric dye isomers. The data show that length and conformation of the peptide plus linker as well as stereochemistry of dye−peptide conjugation play important roles in intramolecular ground-state complexation. The factors that influence the spectral properties of intramolecular H-dimerization support our earlier proposed model for H-dimers in NorFES peptides.