gebhart/patrepeval huggingface dataset:
Inverse molecular design using machine learning: Generative models for matter engineering (2018)

The discovery of new materials can bring enormous societal and technological progress. In this context, exploring completely the large space of potential materials is computationally intractable. Here, we review methods for achieving inverse design, which aims to discover tailored materials from the starting point of a particular desired functionality. Recent advances from the rapidly growing field of artificial intelligence, mostly from the subfield of machine learning, have resulted in a fertile exchange of ideas, where approaches to inverse molecular design are being proposed and employed at a rapid pace. Among these, deep generative models have been applied to numerous classes of materials: rational design of prospective drugs, synthetic routes to organic compounds, and optimization of photovoltaics and redox flow batteries, as well as a variety of other solid-state materials.
The Cold and Menthol Receptor TRPM8 Contains a Functionally Important Double Cysteine Motif (2006)

We have investigated the glycosylation, disulfide bonding, and subunit structure of mouse TRPM8. To do this, amino-terminal c-myc or hemagglutinin epitope-tagged proteins were incorporated and expressed in Chinese hamster ovary cells. These modifications had no obvious effects on channel function in intracellular calcium imaging assays upon application of agonists, icilin or menthol, and cold temperatures. Unmodified TRPM8 migrates with an apparent mass of 129 kDa and can be glycosylated in Chinese hamster ovary cells to give glycoproteins with apparent masses of 136 and 147 kDa. We identified two potential N-linked glycosylation sites in TRPM8 (Asn-821 and Asn-934) and mutated them to show that only the site in the putative pore region at position 934 is modified and that glycosylation of this site is not absolutely necessary for cell surface expression or responsiveness to icilin, menthol, and cool temperatures. Enzymatic cleavage of the carbohydrate chains indicated that they are complex carbohydrate. The glycosylation site is flanked in the pore by two cysteine residues that we mutated, to prove that they are involved in a conserved double cysteine motif, which is essential for channel function. Mutation of either of these cysteines abolishes function and forces the formation of a non-functional complex of the size of a homodimer. The double cysteine mutant is also non-functional. Finally, we showed in Perfluoro-octanoic acid-polyacrylamide gels that TRPM8 can form a tetramer (in addition to dimer and trimer forms), consistent with current thinking that functional TRP ion channels are tetrameric.
Kinetic and Mutational Dissection of the Two ATPase Activities of Terminase, the DNA Packaging Enzyme of Bacteriophage λ (1996)

Terminase the DNA packaging enzyme of bacteriophage chi, is a heteromultimer of gpNul (21 kDa) and gpA (74 kDa) subunits, encoded by the chi Nul and A genes, respectively. Sequence comparisons indicate that both gpNu1 and gpA have a match to the P-loop motif of ATPase centers, which is a glycine-rich segment followed by a lysine. By site-specific mutagenesis, we changed the lysines of the putative P-loops of gpNul (k35) and gpA (K497) to arginine, alanine, or aspartic acid, and studied the mutant enzymes by kinetic analysis and photochemical cross-linking with 8-azido-ATP. Both the gpNul and gpA subunits of wild-type terminase were covalently modified with 8-N3[32P] ATP in the presence of UV light. Saturation occurred with apparent dissociation constants of 508 and 3.5 microM for gpNul and gpA, resepctively. ATPase assays showed two activities: a low-affinity activity (Km=469 microM), and a high-affinity activity (Km=4.6 microM). The gpNul K35A and gpNul K35D mutant terminases showed decreased activity in the low-affinity ATPase activity. The reduced activities of these enzymes were recovered when 10 times more DNA was added, suggesting that the primary defect of the enzymes is alteration of the nonspecific, double-stranded DNA binding activity of terminase. ATPase assays and photolabeling of the gpA K497A and gpA K497D mutant terminases showed reduced affinity for ATP at the high-affinity site which was not restored by increased DNA. In summary, the results indicate the presence of a low-affinity, DNA-stimulated ATPase center in gpNul, and a high-affinity site in gpA.
Forma Analysis and Random Respectful Recombination. (1991)

Neuroendocrine tumors (NETs) arise from neuroendocrine cells and are mostly observed in the gastrointestinal tract, pancreas, and lungs. NETs in the oral and maxillofacial region are extremely rare. We report a case of a 59-year-old woman with an NET in the mandible. The patient did not show any symptoms except for remarkable swelling and bleeding. The lesion appeared as a radiolucent honeycomb abnormality with bone destruction on panoramic radiography. The histopathologic diagnosis following a biopsy was NET. Contrast-enhanced computed tomography (CT), 18F-fluorodeoxyglucose positron emission computed tomography (18F-FDG PET/CT), and adrenal scintigraphy-labeled meta-iodobenylguanidine were the modalities added to identify the primary site. Multiple lesions were confirmed in the gastrointestinal tract. Endoscopy was performed to identify the lesions, and several lesions were observed protruding from the mucous membranes. However, the endoscopy specimens did not yield an accurate diagnosis because adequate samples were not acquired. Blood and urine tests revealed no functional activity caused by the tumors. Although the origin was not histopathologically confirmed with endoscopy, this patient was situationally diagnosed with nonfunctional NET originating from the duodenum, as demonstrated by the metastases in the mandible.
Cyclooxygenase-2 expression is up-regulated in transitional cell carcinoma and its preneoplastic lesions in the human urinary bladder. (2000)

Cyclooxygenase (COX) is a key enzyme in the synthesis of prostaglandins from arachidonic acid. Much evidence, including that from epidemiological and experimental studies, suggests that the inducible form of COX, COX-2, is increased in colon tumor tissues and is involved in colon cancer tumorigenesis. To determine the significance of COX-2 in tumorigenesis in the urinary bladder, the expression of COX-2 in transitional cell carcinoma and preneoplastic lesions of the bladder was examined. Tumor specificity of COX-2 immunoblotting was 100% in 12 of 35 (34%) tumors, but in 0 of the 10 normal urothelia samples. COX-2 expression was significantly correlated with tumor stage in 9 of 20 (45%) muscle-invasive (pT2-4) tumors and in 3 of 15 (20%) superficially invasive (pT1) tumors (P < 0.05). Immunohistochemical examination revealed that 13 of 14 (93%) samples of carcinoma in situ (CIS), which may be the precursor of muscle-invasive-type tumors, expressed COX-2, whereas 10 of 21 (48%) samples of dysplasia, which may be the precursor of both superficially invasive and muscle-invasive tumors, expressed COX-2. From the expression profile of COX-2 in these various urothelia, it is suggested that COX-2 is involved in the development of transitional cell carcinoma of the urinary bladder, especially that of muscle-invasive tumors via CIS. Furthermore, COX-2 may be a therapeutic target for CIS because of the high expression rate of COX-2 in CIS lesions.
The Polycythemias: Diagnosis and Treatment (1983)

AbstractAlthough diagnosis of polycythemia is not difficult in advanced disease, an elevated hematocrit or hemoglobin may be the only clue in early stages. An understanding of the physiologic mechanisms of the various forms of the disorder can help determine whether the patient does or does not have polycythemia and whether it is primary, secondary, or relative.
Tissue factor and tissue factor pathway inhibitor (2004)

The classical 'cascade/waterfall' hypothesis formulated to explain in vitro coagulation organised the amplification processes into the intrinsic and extrinsic pathways. Recent molecular biology and clinical data indicate that tissue factor/factor-VII interaction is the primary cellular initiator of coagulation in vivo. The process of blood coagulation is divided into an initiation phase followed by a propagation phase. The discovery of tissue factor pathway inhibitor further supports the revised theory of coagulation. Tissue factor is also a signalling receptor. Recent evidence has shown that blood-borne tissue factor has an important procoagulant function in sepsis, atherosclerosis and cancer, and other functions beyond haemostasis such as immune function and metastases.
Binding of C-reactive protein to chromatin and nucleosome core particles. A possible physiological role of C-reactive protein. (1984)

By using a variety of biochemical techniques, chromatin and chromatin fragments have been identified as probable physiological ligands for C-reactive protein. Studies using 14C-labeled C-reactive protein show that binding to chromatin is saturable with a Kd = 8 X 10(-7) M, a value indicating that the affinity of C-reactive protein for chromatin is at least four times its affinity for phosphorylcholine. At saturation, there is approximately one C-reactive protein-binding site for every 160 base pairs of DNA in chromatin. The interaction of C-reactive protein with chicken erythrocyte nucleosome core particle has been studied. Fifty per cent inhibition of the binding of C-reactive protein to phosphorylcholine is obtained at a core particle concentration of 1.25 X 10(-9) M, indicating that the affinity of C-reactive protein for one of the sites on core particles is at least 2400 times greater than the affinity of C-reactive protein for phosphorylcholine. The possibility that C-reactive protein may act as a scavenger for chromatin fragments released from damaged cells is discussed.
Characterization of the purinergic P2 receptors in PC12 cells. Evidence for a novel subtype. (1994)

The properties of the purinergic receptors in the PC12 cells were studied. The rank order of potency to increase [Ca2+]i was: adenosine 5'-O-(1-thiotriphosphate) > ATP > adenosine 5'-O-(3-thiotriphosphate) >>> 3'-O-(4-benzoyl-benzoyl)ATP. ADP, AMP, GTP, UTP, alpha, beta- and beta,gamma-methylene adenosine 5'-triphosphates, 5'-adenylylimido-diphosphate, and adenosine analogues were ineffective. Although tetrabasic ATP4- was the form responsible for activation of the P2 receptors, ATP4- did not cause cell membrane permeabilization. The binding of alpha-35S-ATP to the intact cells showed a divalent cation dependency and a binding profile similar to the rank order of potency to increase [Ca2+]i. Scatchard plots of the equilibrium saturation binding data were nonlinear, and dissociation kinetics of the radioligand were best described using two kinetic rates. Different kinetic rates were, however, obtained when dissociation was initiated by the addition of excess ATP or by an 80-fold dilution. The present study describes a purinergic P2 receptor on PC12 cells that does not fit the classification for the P2x, P2y, P2t, P2u, and P2z receptor subtypes.
A novel zinc(II) binding site modulates the function of the beta A4 amyloid protein precursor of Alzheimer's disease (1993)

Abnormalities of zinc metabolism occur in Alzheimer's disease (AD), a condition where pathological catabolism of the amyloid protein precursor (APP) causes cerebral beta A4 amyloidosis. An association between zinc and APP metabolism was sought by studying the binding of 65Zn2+ to APP. 65Zn2+ bound in a rapid, saturable, and specific manner (KD = 764 nM). A novel zinc binding motif, strongly conserved between members of the APP family, was located between the cysteine-rich and negatively charged domains of the protein. Zinc increased binding of APP to heparin and has been shown to potentiate the inhibition of coagulation factor XIa by an APP isoform containing a Kunitz-type inhibitory domain (Komiyama, Y., Murakami, T., Egawa, H., Okubo, S., Yasunaga, K., and Murata, K. (1992) Thromb. Res. 66, 397-408) situated near the zinc binding region. Zinc is a factor that modulates the functional properties of the substrate for beta A4 amyloidogenesis.
Effect of Alloimmunization and Heteroimmunization with Zonae Pellucidae on Fertility in Rabbits (1981)

The effect of active immunization with porcine or rabbit zonae pellucidae on the fertility of rabbits was studied. A total of 28 rabbits in groups of four were immunized with 1) intact, 2) heat-solubilized or 3) detergent-dissociated (SDS-sodium sulfite-solubilized) porcine or rabbit zonae, or 4) complete Freund’s adjuvant. Serum antibodies to zona antigens were monitored by immunoelectrophoresis and by radioimmunoassay methods. All of the animals in the groups which were heteroimmunized with intact or with heat-solubilized porcine zonae were infertile in both term pregnancy studies or in 4–8-cell embryo recovery studies. Normal ovarian function was interrupted in these animals, since normal ova were not ovulated after hCG treatment. Ovulation appeared normal in animals immunized with detergent-dissociated porcine zonae or with rabbit zonae in any form. Although fertility was reduced in these latter groups, some animals had normal offspring or normal cleaving embryos even though antibodies to zonae were present in their serum. These studies demonstrate that 1) heteroimmunization of rabbits with porcine zonae is more effective in reducing fertility than alloimmunization with rabbit zonae; 2) the reduction of fertility by immunization with zonae is dependent on the state of solubilization of zonae prior to immunization; 3) serum antibodies to some zona antigens can be present which do not inhibit fertilization; and 4) the reason(s) for infertility by active immunization with zona antigens may be other than (or in addition to) the blockage of sperm binding to the zonae or penetration of the zonae. We conclude that the rabbit is an excellent model for the comparison of the effects on fertility of alloimmunization and heteroimmunization with zona antigens.
Safety and immunogenicity of a primary course and booster dose of a combined diphtheria, tetanus, acellular pertussis, hepatitis B and inactivated poliovirus vaccine (2006)

Primary immunization at 3, 4.5, and 6 months and boosting between 15 and 27 months of age with combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus (DTPa-HBV-IPV) vaccine was compared with separate administration of DTPa-HBV and IPV to healthy children (trials DTPa-HBV-IPV-019/033). Antibody titres were measured before and 1 month after primary and booster courses. Solicited local and general symptoms were recorded using diary cards. One month after primary vaccination, all children in both groups developed antibody titres above the assay cut-off for all vaccine components. Significantly higher anti-diphtheria, anti-pertactin (PRN) and anti-polio GMTs were measured following DTPa-HBV-IPV than DTPa-HBV plus IPV. Prior to boosting similar seroprotection/seropositivity rates were recorded in both groups. After boosting all children had seroprotective levels of diphtheria, tetanus, polio and HBV. Criteria for pertussis vaccine response were fulfilled in most children. Significantly higher anti-PRN GMTs were measured following DTPa-HBV-IPV than DTPa-HBV plus IPV. There was no difference between groups in the incidence or intensity of local and general symptoms after primary or booster vaccination, except for fever which was more frequent after the booster dose in the combined vaccine group. Both vaccine regimens were well tolerated and immunogenic, however the combined administration has the advantage of being administered as a single injection.
A feature-based image registration algorithm using improved chain-code representation combined with invariant moments (1999)

A new feature-based approach to automated image-to-image registration is presented. The characteristic of this approach is that it combines an invariant-moment shape descriptor with improved chain-code matching to establish correspondences between the potentially matched regions detected from the two images. It is robust in that it overcomes the difficulties of control-point correspondence by matching the images both in the feature space, using the principle of minimum distance classifier (based on the combined criteria), and sequentially in the image space, using the rule of root mean-square error (RMSE). In image segmentation, the performance of the Laplacian of Gaussian operators is improved by introducing a new algorithm called thin and robust zero crossing. After the detected edge points are refined and sorted, regions are defined. Region correspondences are then performed by an image-matching algorithm developed in this research. The centers of gravity are then extracted from the matched regions and are used as control points. Transformation parameters are estimated based on the final matched control-point pairs. The algorithm proposed is automated, robust, and of significant value in an operational context. Experimental results using multitemporal Landsat TM imagery are presented.
Affinity chromatography of bacterial lactate dehydrogenases (1978)

The affinity system used was the immobilized oxamate derivative previously used to purify mammalian lactate dehydrogenases. The bacterial dehydrogenases specific for the L-stereoisomer of lactate behaved in the same way as the mammalian enzymes, binding strongly in the presence of NADH. The D-lactate-specific enzymes, however, did not show any biospecific affinity for this gel. The L-specific enzymes could be purified to homogeneity in one affinity-chromatographic step. The D-specific enzymes could be efficiently separated from the L-specific ones and could then be further purified on an immobilized NAD derivative. The mechanism of activation of the lactate dehydrogenase from Streptococcus faecalis by fructose 1,6-bisphosphate was investigated by using the immobilized oxamate gel.
Transforming growth factor beta reverses the glucocorticoid-induced wound-healing deficit in rats: possible regulation in macrophages by platelet-derived growth factor. (1989)

Transforming growth factor beta (TGF-beta) and the platelet-derived growth factor (PDGF) are potent mitogenic polypeptides which enhance rates of wound healing in experimental animals; in contrast, glucocorticoids inhibit wound repair. The potential of TGF-beta and PDGF to reverse this inhibition in healing was tested in methylprednisolone-treated rats with deficits in skin wound strength of 50%. Single applications of TGF-beta (10-40 pmol per wound, 0.25-1 micrograms) applied locally at the time of wounding fully reversed this deficit in a concentration-dependent and highly reproducible manner. Wounds in glucocorticoid-treated animals were characterized by a near total absence of neutrophils and macrophages and by a delayed influx and reduced density of fibroblasts; however, such wounds treated with TGF-beta showed significant increases in wound fibroblasts and in intracellular procollagen type I. PDGF did not reverse the deficit in wound breaking strength in glucocorticoid-treated rats; there were more fibroblasts in the PDGF-treated wounds, but these fibroblasts lacked the enhanced expression of procollagen type I found in TGF-beta-treated wounds. The wound macrophages, required for normal tissue repair, remained absent from both PDGF- and TGF-beta-treated wounds in glucocorticoid-treated animals. This result suggested that macrophages might normally act as an intermediate in the induction of procollagen synthesis in fibroblasts of PDGF-treated wounds and that TGF-beta might bypass the macrophage through its capacity to stimulate directly new synthesis of procollagen type I in fibroblasts. Whereas PDGF does not stimulate procollagen synthesis, in a rodent macrophage cell line, PDGF induced a highly significant, time-dependent enhancement of expression of TGF-beta.
Sm-like proteins in Eubacteria: the crystal structure of the Hfq protein from Escherichia coli (2003)

The Hfq protein was discovered in Escherichia coli in the early seventies as a host factor for the Qbeta phage RNA replication. During the last decade, it was shown to be involved in many RNA processing events and remote sequence homology indicated a link to spliceosomal Sm proteins. We report the crystal structure of the E.coli Hfq protein showing that its monomer displays a characteristic Sm-fold and forms a homo-hexamer, in agreement with former biochemical data. Overall, the structure of the E.coli Hfq ring is similar to the one recently described for Staphylococcus aureus. This confirms that bacteria contain a hexameric Sm-like protein which is likely to be an ancient and less specialized form characterized by a relaxed RNA binding specificity. In addition, we identified an Hfq ortholog in the archaeon Methanococcus jannaschii which lacks a classical Sm/Lsm gene. Finally, a detailed structural comparison shows that the Sm-fold is remarkably well conserved in bacteria, Archaea and Eukarya, and represents a universal and modular building unit for oligomeric RNA binding proteins.
Diagnostic potential of laser-induced autofluorescence emission in brain tissue (1997)

Laser-induced autofluorescence measurement of the brain was performed to assess its spectroscopic properties and to distinguish brain tumors from the normal tissues. The excitation-induced emission spectra were plotted on a 2-dimensional map, the excitation-emission matrix, to determine the excitation wavelengths most sensitive for the spectroscopic identification of brain tumors. The excitation-emission matrices of various types of human brain tumors and normal brain samples lead to the selection of three fluorescence peaks at 470, 520, and 630 nm, corresponding excitation light at 360, 440, and 490 nm, respectively for comparing the autofluorescence signatures of brain tissue. The fluorophores most likely related to each of these peaks are NAD(P)H, various flavins, and porphyrins, respectively. In vivo studies of rat gliomas showed that "NAD(P)H", "flavin", and "porphyrin" fluorescence were lower in gliomas than in normal brain. This finding suggests that there are certain relationship between brain tissue autofluorescence intensity and metabolic activity. In vitro human normal brain tissue fluorescence signals were lower in gray matter than in white matter and "NAD(P)H" fluorescence were lower in all measured human brain tumors than in normal brain. "Flavin" and "porphyrin" fluorescence in the neoplastic tissues was lower or higher than normal tissue depending on their nature. In conclusion, the fluorescence spectroscopic diagnostic system might be able to distinguish brain tumors from the normal brain tissue. The results of this study need to be verified and the investigation extended to human brain tumors in the operating room.
Exploitation of periodicity in logic simulation of synchronous circuits (2002)

An overwhelming majority of logic designers use synchronous logic design techniques to manage the complexity of their designs and rely on logic simulation techniques for design verification. Yet, logic simulators do not take advantage of the higher abstraction level provided by synchronous logic design techniques to improve their performance. A general technique is presented which takes advantage of the high degree of periodicity common in synchronous logic designs. It is shown that a performance improvement of at least 200% occurs when these techniques are applied within the COSMOS. simulation system to simulate large digital systems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>