gebhart/patrepeval huggingface dataset:
Pre-clinical development of novel ROR1 chimeric antigen receptor T cells and bispecific T cell engagers (2018)

Receptor tyrosine kinase like orphan receptor 1 (ROR1) is an onco-embryonic antigen present on a range of solid and haematological malignancies, including chronic lymphocytic leukaemia. Additionally, limited, low level expression on normal tissues makes it an attractive therapeutic target. Chimeric antigen receptor T cells and Bispecific T Cell Engagers have emerged as exciting immunotherapeutic approaches, utilising the inherent cytotoxic potential of autologous T cells to yield demonstrable benefit for patients. We therefore aimed to generate novel ROR1 CAR T cells and BiTEs. Following a rat ROR1 immunisation programme, we screened over 150 single cell hybridoma clones to isolate 13 novel antibodies of which 10 bound in a single chain variable fragment format. Iterative optimisation led to two lead candidates that imparted superior cytotoxicity and cytokine secretion. To minimise immunogenicity we screened 50 humanised ROR1 scFv variants and selected a final humanised candidate, hF(1x1), which maintained effector function, specificity and demonstrated broad applicability against a panel of cell lines representing various tumour subtypes. Focusing specifically on haematological cell lines and CLL, our humanised CAR demonstrates superior cytotoxicity compared to previously reported ROR1 constructs. However, low ROR1 antigen density limits efficacy in B cell malignancies, compared to CD19 CAR T cells and strategies to overcome this are in development. Our ROR1 BiTE mediates cytotoxicity at low concentrations (ng/ml) and effector to target ratios against cell lines, but in untreated and relapsed CLL patients, inherent T cell dysfunction limits efficacy. This can be overcome with the BTK inhibitor Ibrutinib, with T cells isolated from patients on treatment, showing markedly improved cytotoxicity against autologous CLL cells. This work has laid the preclinical foundations for translation of these novel agents into clinical trials for a range of tumours including CLL and many of which have high unmet therapeutic need.
Comparison of the intermediate complexes of human growth hormone bound to the human growth hormone and prolactin receptors (1994)

The crystal structures of complexes of human growth hormone (hGH) with the growth hormone and prolactin receptors (hGHR and hPRLR, respectively), together with the mutational data available for these systems, suggest that an extraordinary combination of conformational adaptability, together with finely tuned specificity, governs the molecular recognition processes operative in these systems. On the one hand, in the active 1:2 ligand-receptor complexes, 2 copies of the same receptor use the identical set of binding determinants to recognize topographically different surfaces on the hormone. On the other hand, comparing the 1:1 hGH-hGHR and hGH-hPRLR complexes, 2 distinct receptors use this same set of binding determinants to interact with the identical binding site on the ligand, even though few residues among the binding determinants are conserved. The structural evidence demonstrates that this versatility is accomplished by local conformational flexibility of the binding loops, allowing adaptation to different binding environments, together with rigid-body movements of the receptor domains, necessary for the creation of specific interactions with the same binding site.
Observation of Structure Resonances in the Fluorescence Spectra from Microspheres (1980)

Sharp intensity peaks are observed in the fluorescence spectra from dye-impregnated single polystyrene microspheres which are not seen in the spectra from bulk material. The resonant peaks are shown to correspond to the natural modes of oscillation of a dielectric sphere, and excellent correlation is found between experimental and theoretically predicted spectra. The results can be applied to the interpretation of inelastic emission (fluorescence and Raman) spectra obtained for the chemical speciation of aerosols and particulates.
Design verification and reachability analysis using algebraic manipulation (2002)

Design verification is the process of checking that the specification of a circuit satisfies certain correctness properties. Approaches to design verification have involved the use of temporal logic and model checking, as well as the use of higher-order logic and theorem proving. Current approaches suffer from either limited expressivity of the logic, the state explosion problem, or difficulty in automating the verification process. The primary source of the complexity explosion in automata theoretic or temporal logic approaches is the state space explosion due to the need to construct the state space of the system under analysis. Symbolic analysis techniques are used based on linear algebra, specifically matrix multiplication, to compactly represent the state space of circuits described by a behavioral or register-transfer-level specification and thereby avoid this state space explosion, for classes of circuits.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
The <i>CER3</i> gene of <i>Arabidopsis thaliana</i> is expressed in leaves, stems, roots, flowers and apical meristems (1996)

The eceriferum3 (cer3) locus encodes one of 21 gene products known to be involved in wax biosynthesis in Arabidopsis thaliana. Mutations at these loci are readily identified by their bright, dark-green stems when compared with the more glaucous wild-type plant. Clones of a gene which encodes a 795 amino acid open reading frame have been isolated by using plant DNA flanking the site of a T-DNA insertion in line BRL1. Molecular complementation of the cer3 mutant phenotype by clones of this gene establish that it corresponds to the CER3 gene. Although the 90 kDa predicted amino acid sequence of this gene shows no homology to any other known protein, the second exon of CER3 encodes a RRX12KK nuclear localization sequence (NLS). Southern blot and DNA sequence analysis revealed that the T-DNA is inserted 89 bp downstream of the translation termination codon of this gene. Northern blot hybridization of RNA isolated from the BRL1 mutant with the CER3 cDNA probe indicated that the transcript is absent in this mutant line. Unlike other CER genes that have been cloned to date, high levels of the CER3 transcript were found in all tissues from wild-type plants, that is, leaves, stems, roots, flowers, and apical meristems.
Parallel Liquid-Phase Synthesis of 5-(1<i>H</i>-4-Pyrazolyl)-[1,2,4]oxadiazole Libraries (2009)

Combinatorial libraries of substituted 3-(methylthio)-5-(amino)-4-([1,2,4]oxadiazol-5-yl)-1H-pyrazoles 6, 10, 13, 15 (395 members, yields 32−87%), 4-([1,2,4]oxadiazol-5-yl)-1H-3,5-pyrazolediamines 8, 11 (571 members, yields 25−83%), 2-(methylthio)-3-([1,2,4]oxadiazol-5-yl)pyrazolo[1,5-a]pyrimidin-7(4H)-ones 17 (85 members, yields 56−95%), and 2-(amino)-3-([1,2,4]oxadiazol-5-yl)pyrazolo[1,5-a]pyrimidin-7(4H)-ones 18 (110 members, yields 56−95%) were synthesized by the parallel liquid-phase synthesis method.
MetDAT: a modular and workflow-based free online pipeline for mass spectrometry data processing, analysis and interpretation (2010)

sanjay@nus.edu.sg
RELATIONSHIP BETWEEN IRIDOTOMY AND ANTERIOR CHAMBER DEPTH (1997)

Objective: To show the change of the anterior chamber depth (ACD) after laser iridotomy in the angle closure glaucoma and look for the causes. Methods: The center and pericenter ACD's of 224 eyes were measured. Results: The center ACD in total was no change and the pericenter ACD was deeper than that of pre-operation. In the acute angle closure glaucoma group (aACG), the center and pericenter ACD was shallower than that of chronic angle closure glaucoma group (cACG) before operation, and the change of the ACD after operation was more. Conclusion: Laser iridotomy can relax the pupil occlusion power. The forward-move of iris by the pupil occlusion power was more significant in aACG.
Periventricular brain injury, visual motion processing, and reading and spelling abilities in children who were extremely low birthweight (2003)

Among children born at extremely low birthweight (ELBW: < 1000 g at birth) there is an association between the presence of periventricular brain injury (PVBI) and lowered performance on tests of reading and spelling ability. The present study was designed to determine if this association might be related to underlying dysfunction in the subcortical magnocellular visual pathway or its cortical targets in the dorsal stream, a prediction motivated by the magnocellular theory of dyslexia. Thirty-five ELBW children were divided into two groups based upon the presence or absence of PVBI (no PVBI, n = 11; PVBI, n = 24). The performance of these two groups was compared to that of a group of healthy full term children (n = 12) on a motion-defined form recognition task believed to tap into the functioning of the magnocellular pathway and/or the dorsal stream. ELBW children did, in fact, show a striking impairment on this task, with 71% of the sample performing at a level more than three standard deviations below the mean of full term controls. Surprisingly, their difficulties were not found to be related to either the presence of brain injury (verified by neonatal cranial ultrasound) or to problems with reading or spelling. An association was documented, however, between difficulties with motion processing and performance on several subtests of the Performance IQ scale of the Wechsler Intelligence Scale for Children-Third Edition. This latter finding is consistent with our earlier suggestion that magnocellular pathway/dorsal stream dysfunction may underlie problems with visuospatial and visuomotor performance in this population.
Effects of Tension During Resin Treatment on Physical Properties of Cotton Fibers and Yarns1 (1961)

The effects of tension during resin treatment on the physical properties of yarns and fibers from the yarns were investigated on several cotton samples. The resins applied were of the melamine-formaldehyde and dimethylolethyleneurea types. The strength loss from slack treatments was the result of cross-linking of the internal fiber elements in unfavorable positions for stress equalization. Acid degradation was a factor in certain treatments. Low tensions during treatment were sufficient to prevent much of the strength loss. As elongation was reduced by tension, the energy to rupture was not greatly changed. The selection of high strength, high elongation cottons, and their premercerization increased the toughness. Tension before and during drying, followed by low tension during the cure, minimized the losses of toughness in yarns.
Analysis of non-active engineered Bacillus thuringiensis crystal proteins (1994)

Crystal proteins of Bacillus thuringiensis are known for their insecticidal specificity. This specificity is, to a large extent, determined by the interaction of the proteins with high-affinity binding sites on the epithelial membrane of the midgut of sensitive insects. In particular, domain II of the three domains of the toxic moiety has been implicated in specificity. To determine which sequences of the protein are involved in binding, loops of domain II which terminate in the molecular apex of CryIA(b) were replaced by the corresponding regions of CryIE, a protein with different binding characteristics and insect specificity. In contrast to expression of the wild-type genes, expression of the mutant alleles in Escherichia coli resulted in the formation of biologically inactive, insoluble aggregates. Although these aggregates could be solubilized in vitro using urea, in contrast to the wild-type CryIA(b), the mutant proteins did not correctly refold as is shown by their increased protease sensitivity and lack of biological activity. The results indicate that engineering CryI proteins, based on the CryIIIA structure, is likely to prove difficult, particularly since the conformation of CryIIIA and CryI proteins might differ in domain II.
Transformation of Yeast Cells Treated with 2-Mercaptoethano (1983)

Journal Article Transformation of Yeast Cells Treated with 2-Mercaptoethano Get access Hisao Ito, Hisao Ito Research Institute for Food Science, Kyoto University, Uji, Kyoto 611, Japan Search for other works by this author on: Oxford Academic Google Scholar Kousaku Murata, Kousaku Murata Research Institute for Food Science, Kyoto University, Uji, Kyoto 611, Japan Search for other works by this author on: Oxford Academic Google Scholar Akira Kimura Akira Kimura Research Institute for Food Science, Kyoto University, Uji, Kyoto 611, Japan Search for other works by this author on: Oxford Academic Google Scholar Agricultural and Biological Chemistry, Volume 47, Issue 7, 1 July 1983, Pages 1691–1692, https://doi.org/10.1080/00021369.1983.10865847 Published: 01 July 1983 Article history Received: 28 February 1983 Published: 01 July 1983
Wallace Fenn and the <i>Journal of Applied Physiology</i> (1998)

I first became aware that a third was being considered when Wallace Fenn casually mentioned it to some of us
Intestinal permeability, vitamin A absorption and serum alpha-tocopherol during therapy with gefitinib (2010)

Measurement of intestinal permeability represents one of the potential methods of noninvasive laboratory assessment of gastrointestinal toxicity of anticancer therapy. We have assessed intestinal permeability (by measuring absorption of lactulose, mannitol, and xylose), vitamin A absorption and serum alpha-tocopherol in patients with non-small cell lung carcinoma or head and neck carcinomas treated with gefitinib. Lactulose, mannitol and xylose were determined by capillary gas chromatography, and retinol, alpha-tocopherol, retinyl stearate and retinyl palmitate were determined by high-performance liquid chromatography. Compared to healthy controls, patients had significantly increased lactulose/mannitol ratio and lower postprandial retinyl palmitate and retinyl stearate concentrations. Compared with pre-treatment values, xylose absorption was decreased and lactulose/mannitol and lactulose/xylose ratios were increased during the therapy. A significant decrease of serum alpha-tocopherol was evident throughout the course of therapy. In contrast, only minor alterations of vitamin A absorption were observed. In conclusion, an alteration in intestinal permeability reflected in increased lactulose/mannitol and lactulose/xylose ratios was observed during gefitinib therapy. Potential association between decreased serum alpha-tocopherol concentrations and the toxicity of gefitinib therapy should be further investigated.
Morphological changes in the tracheal epithelium of guinea pigs in conditions of "marginal" vitamin A deficiency. A light, scanning- and transmission-electron microscopic study under special breeding conditions appropriate to early vitamin A deficiency. (1992)

The aim of the study was to find out the influence of marginal vitamin A deficiency on morphological structures in the tracheobronchial epithelium in guinea pigs. The tracheobronchial epithelium of animals with vitamin A deficiency (n = 15) and control animals (n = 7), kept under optimal laboratory conditions, was evaluated by light and electron microscopy. The cellular ultrastructure was morphometrically analyzed. The height of the respiratory epithelium was slightly increased. The basal cells were arranged in a loose cell band of three to four layers. The quantity of cytofilaments in their cytoplasm was enhanced. Goblet cells were significantly reduced in vitamin A deficiency. There was also a significant decrease in their secretory granules. The number of ciliated cells was almost unchanged. They showed a significant reduction in mitochondria. The kinocilia often contained an atypical structure of the microtubules. Our findings confirm multiple ultrastructural dysplasias in early vitamin A deficiency which may lead to a disturbance of mucociliary clearance.
The genome sequence of the psychrophilic archaeon,<i>Methanococcoides burtonii</i>: the role of genome evolution in cold adaptation (2009)

Psychrophilic archaea are abundant and perform critical roles throughout the Earth's expansive cold biosphere. Here we report the first complete genome sequence for a psychrophilic methanogenic archaeon, Methanococcoides burtonii. The genome sequence was manually annotated including the use of a five-tiered evidence rating (ER) system that ranked annotations from ER1 (gene product experimentally characterized from the parent organism) to ER5 (hypothetical gene product) to provide a rapid means of assessing the certainty of gene function predictions. The genome is characterized by a higher level of aberrant sequence composition (51%) than any other archaeon. In comparison to hyper/thermophilic archaea, which are subject to selection of synonymous codon usage, M. burtonii has evolved cold adaptation through a genomic capacity to accommodate highly skewed amino-acid content, while retaining codon usage in common with its mesophilic Methanosarcina cousins. Polysaccharide biosynthesis genes comprise at least 3.3% of protein coding genes in the genome, and Cell wall, membrane, envelope biogenesis COG genes are overrepresented. Likewise, signal transduction (COG category T) genes are overrepresented and M. burtonii has a high 'IQ' (a measure of adaptive potential) compared to many methanogens. Numerous genes in these two overrepresented COG categories appear to have been acquired from epsilon- and delta-Proteobacteria, as do specific genes involved in central metabolism such as a novel B form of aconitase. Transposases also distinguish M. burtonii from other archaea, and their genomic characteristics indicate they have an important role in evolving the M. burtonii genome. Our study reveals a capacity for this model psychrophile to evolve through genome plasticity (including nucleotide skew, horizontal gene transfer and transposase activity) that enables adaptation to the cold, and to the biological and physical changes that have occurred over the last several thousand years as it adapted from a marine to an Antarctic lake environment.
Fuzzy control of coagulation reaction through streaming current monitoring (1997)

A fuzzy logic controller (FLC) incorporating the streaming current detector (SDC) was utilized in the automatic control of the coagulation reaction. Kaolinite was used to prepare synthetic raw water, and ferric chloride was used as the coagulant. The control set point was decided at a streaming current (SC) of −0.05 and pH of 8.0 from jar tests, zeta potential and streaming current measurements. A bench-scale water treatment plant with rapid mix, flocculation, and sedimentation units, operated in a continuous-flow mode, was utilized to simulate the reaction. Two critical parameters affecting the coagulation reaction, i.e., pH and streaming current, were chosen as process outputs; while coagulant dose and base dose were chosen as control process inputs. They were on-line monitored and transduced through a FLC. With raw water of initial turbidity of 110 NTU, residual turbidity of lower than 10 NTU before filtration was obtained. Results show that this combination functions satisfactorily for coagulation control.
Neural regulation of muscle acetylcholine receptor epsilon- and alpha-subunit gene promoters in transgenic mice. (1993)

The effects of denervation were investigated in mice with transgenes containing promoter elements from the muscle acetylcholine receptor epsilon- and alpha-subunit genes. The promoter sequences were coupled to a nuclear localization signal-beta-galactosidase fusion gene (nlacZ) as a reporter. While many postsynaptic specializations form in the embryo, expression of the epsilon subunit is induced during the first two postnatal weeks. When muscles were denervated at birth, before the onset of epsilon expression, epsilon nlacZ still appeared at the former synaptic sites on schedule. This result suggests that the nerve leaves a localized "trace" in the muscle that can continue to regulate transcription. An additional finding was that epsilon nlacZ expression was much stronger in denervated than in intact muscles. This suggests that the epsilon promoter is similar to the other subunits in containing elements that are activated on cessation of neural activity. However, even after denervation, epsilon nlacZ expression was always confined to the synaptic region whereas alpha nlacZ expression increased in nuclei along the entire length of the fiber. This suggests that while the epsilon gene is similar in its activity dependence to other subunit genes, it is unique in that local nerve-derived signals are essential for its expression. Consequently, inactivity enhances epsilon expression only in synaptic nuclei where such signals are present, but enhances expression throughout the muscle fiber. Truncations and an internal deletion of the epsilon promoter indicate that cis-elements essential for the response to synaptic signals are contained within 280 bp of the transcription start site. In contrast to these results in young animals, denervation in older animals leads to an unexpected reduction in nlacZ activity. However, mRNA measurements indicated that transgene expression was increased in these animals. This discordance between nlacZ mRNA and enzyme activity, demonstrates a previously unknown limitation of nlacZ as a reporter gene in transgenic animals.
Consumption of a Functional Fermented Milk Containing Collagen Hydrolysate Improves the Concentration of Collagen-Specific Amino Acids in Plasma (2008)

Clinical studies have shown that collagen hydrolysate (CH) may be able to protect joints from damage, strengthen joints, and reduce pain from conditions like osteoarthritis. CH is a collection of amino acids and bioactive peptides, which allows for easy absorption into the blood stream and distribution in tissues. However, although various matrices have been studied, the absorption of specific amino acids from CH added to a fresh fermented milk product (FMP) was not studied. The primary objective of the present study was to compare the plasma concentrations of four representative amino acids from the CH (glycine, proline, hydroxyproline, and hydroxylysine) contained in a single administration of a FMP with that of a single administration of an equal amount of neat hydrolyzed collagen. These four amino acids were chosen because they have already been used as markers of CH absorption rate and bioavailability. This was a single-center, randomized open, and crossover study with two periods, which was performed in 15 healthy male subjects. The subjects received randomly and in fasted state a single dose of product 1 (10 g of CH in 100 mL of FMP) and product 2 (10 g of CH dissolved in 100 mL of water) separated by at least 5 days. After administration, the subjects were assessed for plasma concentrations of amino acids and for urine concentrations of hydroxyproline. After FMP administration, mean values of the maximal concentration (Cmax) of the four amino acids were greater than after ingredient administration (p < 0.05). This effect was related to an increased Cmax of proline (p < 0.05). In conclusion, because of their physicochemical characteristics, the fermentation process, and the great homogeneity of the preparation, this milk product improves the plasma concentration of amino acids from CH, that is, proline. The present study suggests an interesting role for FMP containing CH to improve the plasmatic availability of collagen-specific amino acids. Hence, this FMP product could be of potential interest in the management of joint diseases.