gebhart/patrepeval huggingface dataset:
Preparation of Active Proteins, Vaccines and Pharmaceuticals as Fine Powders using Supercritical or Near-Critical Fluids (2008)

Supercritical or near-critical fluid processes for generating microparticles have enjoyed considerable attention in the past decade or so, with good success for substances soluble in supercritical fluids or organic solvents. In this review, we survey their application to the production of protein particles. A recently developed process known as CO2-assisted nebulization with a Bubble Dryer (CAN-BD) has been demonstrated to have broad applicability to small-molecule as well as macromolecule substances (including therapeutic proteins). The principles of CAN-BD are discussed as well as the stabilization, micronization and drying of a wide variety of materials. More detailed case studies are presented for three proteins, two of which are of therapeutic interest: anti-CD4 antibody (rheumatoid arthritis), alpha1-antitrypsin (cystic fibrosis and emphysema), and trypsinogen (a model enzyme). Dry powders were formed in which stability and activity are maintained and which are fine enough to be inhaled and reach the deep lung. Enhancement of apparent activity after CAN-BD processing was also observed in some formulation and processing conditions.
Epidermal growth factor regulates the expression of its own receptor. (1985)

The epidermal growth factor (EGF) receptor gene is the cellular homolog of the avian erythroblastosis virus erbB oncogene. Control of EGF receptor expression determines cellular responsiveness to EGF and might play an important role in neoplastic development. Using RNA blot hybridization, we have found that exposure of human KB carcinoma cells to EGF results in elevated levels of EGF receptor mRNA. The phorbol ester 4 beta-phorbol 12-myristate 13-acetate also stimulates EGF receptor RNA accumulation. Immunoprecipitation of metabolically labeled (30 min) EGF receptor protein revealed that synthesis of new EGF receptor follows the increase in receptor RNA. Addition of cycloheximide together with EGF further enhances EGF receptor RNA accumulation. Results of nuclear runoff-transcription experiments suggest that the stimulatory effects of EGF and cycloheximide are most likely due to a posttranscriptional control mechanism.
PRODUCTION OF METHANE AND ETHYLENE IN ELECTROCHEMICAL REDUCTION OF CARBON DIOXIDE AT COPPER ELECTRODE IN AQUEOUS HYDROGENCARBONATE SOLUTION (1986)

Abstract The electrochemical reduction of CO2 was studied with galvanostatic (5 mA cm−2) electrolysis at a copper electrode between 0 and 40 °C. The production of CH4 and C2H4 was confirmed by GC with 4 different columns. The faradaic efficiency of CH4 formation was about 65% at 0 °C and dropped with an increase of temperature, whereas that of C2H4 formation rose to ca. 20% at 40 °C.
Roles of ES Cell-Derived Gliogenic Neural Stem/Progenitor Cells in Functional Recovery after Spinal Cord Injury (2009)

Transplantation of neural stem/progenitor cells (NS/PCs) following the sub-acute phase of spinal cord injury (SCI) has been shown to promote functional recovery in rodent models. However, the types of cells most effective for treating SCI have not been clarified. Taking advantage of our recently established neurosphere-based culture system of ES cell-derived NS/PCs, in which primary neurospheres (PNS) and passaged secondary neurospheres (SNS) exhibit neurogenic and gliogenic potentials, respectively, here we examined the distinct effects of transplanting neurogenic and gliogenic NS/PCs on the functional recovery of a mouse model of SCI. ES cell-derived PNS and SNS transplanted 9 days after contusive injury at the Th10 level exhibited neurogenic and gliogenic differentiation tendencies, respectively, similar to those seen in vitro. Interestingly, transplantation of the gliogenic SNS, but not the neurogenic PNS, promoted axonal growth, remyelination, and angiogenesis, and resulted in significant locomotor functional recovery after SCI. These findings suggest that gliogenic NS/PCs are effective for promoting the recovery from SCI, and provide essential insight into the mechanisms through which cellular transplantation leads to functional improvement after SCI.
Efficient RNA interference depends on global context of the target sequence: quantitative analysis of silencing efficiency using Eulerian graph representation of siRNA (2004)

Several aspects of gene silencing by small interfering RNA duplexes (siRNA) influence the efficiency of the silencing. They can be divided into two categories, one covering the cell-specific factors and the other covering molecular factors of the RNA interference (RNAi). A prerequisite for sequence-based siRNA design is that hybridization thermodynamics is the dominant factor. Our assumption is that cell-specific parameters (cell line, degradation, cross-hybridization, target conformation, etc.) can be pooled into an average cellular factor. Our hypothesis is that the molecular basis of the positional dependence of siRNA-induced gene silencing is the uniqueness of context of a corresponding target sequence segment relative to all other such segments along the attacked RNA. We encode this context into descriptors derived from Eulerian graph representation of siRNAs and show that the descriptor based upon the contextual similarity and predicted thermodynamic stability correlates with the experimentally observed silencing efficiency of human lamin A/C gene. We further show that information encoded in this regression function is generalizable and can be used as a predictor of siRNA efficiency in unrelated genes (CD54 and PTEN). In summary, our method represents an evolution of siRNA design from the currently used algorithms which are only qualitative in nature.
Endocytosis by macrophages of altered soluble protein. The effect of binding to particulate surfaces and of IgM and IgG antibody. (1974)

Keyhole limpet hemocyanin (KLH) was bound to homologous rat erythrocytes with CrCl 3 or to Bio-Gel beads with carbodiimide. When bound KLH was offered to rat peritoneal exudate cells, in vitro, uptake was 18 to 70 times greater than uptake of free unbound KLH. The augmented uptake was the result of enhanced endocytosis without phagocytosis of the binding particles. Protein in medium containing suspensions of macrophages depressed uptake of bound and free KLH, but depressed the latter significantly more. Endocytosis of bound KLH was not affected by γ-globulin, antibodies to rat IgG, or antibodies specific for and bound to rat macrophages, beyond the depressing effect of protein. IgM antibody to KLH was significantly more effective in increasing uptake of free KLH than was IgG antibody to KLH, whereas both antibodies to KLH had little effect on uptake of bound KLH. The enhanced uptake of bound KLH was probably due to the form and manner in which the protein was offered to macrophages.
Immunogenicity of herpes simplex virus glycoproteins gC and gB and their role in protective immunity (1984)

The relative antigenicity of the individual herpes simplex virus type 1 (KOS) glycoproteins gC and gB was analyzed in BALB/c mice by using KOS mutants altered in their ability to present these antigens on cell surface membranes during infection. The mutants employed were as follows: syn LD70 , a non-temperature-sensitive mutant defective in the synthesis of cell surface membrane gC; tsF13 , a temperature-sensitive mutant defective in the processing of the precursor form of gB to the mature cell surface form at 39 degrees C; and ts606 , an immediate early temperature-sensitive mutant defective in the production of all early and late proteins including the glycoproteins. By comparing the relative susceptibility to immunolysis of mouse 3T3 cells infected at 39 degrees C with wild-type virus, presenting the full complement of the glycoprotein antigens, gC, gB, and gD, with target cells infected with mutants presenting only subsets of these antigens, we determined that a major portion of cytolytic antibody contained in hyperimmune anti-herpes simplex virus type 1 (KOS) mouse antiserum was directed against glycoproteins gC and gB. The relative immunogenicity of wild-type and mutant virus-infected cells also was compared in BALB/c mice. Immunogen lacking the mature form of gB induced a cytolytic antibody titer comparable to that of the wild-type virus, whereas that lacking the mature form of gC showed a 70% reduction in titer. The absence of the mature cell surface forms of gB and gC in immunogen preparations resulted in a 4- to 15-fold reduction in in virus neutralizing titer. Animals immunized with ts606 -infected cells (39 degrees C) induced relatively little virus-specific cytolytic and neutralizing antibody. Analysis of the glycoprotein specificities of these antisera by radioimmunoprecipitation showed that the antigens immunoprecipitated reflected the viral plasma membrane glycoprotein profiles of the immunogens. The absence of the mature forms of gC or gB in the immunizing preparation did not appreciably affect the immunoprecipitating antibody response to other antigens. Mice immunized with wild-type and mutant virus-infected cells were tested for their resistance to intracranial and intraperitoneal challenge with the highly virulent WAL strain of herpes simplex virus type 1. Despite the observed alterations in serum virus-specific antibody induced with the individual immunogens, all animals survived an intraperitoneal challenge of 10 50% lethal doses. However, differences in the survival of animals were obtained upon intracranial challenge.(ABSTRACT TRUNCATED AT 400 WORDS)
VITAL: fully automatic placement strategies for very large semicustom designs (2003)

VITAL is a program for generating fully automatic layouts of any design that combines standard cells and macrocells. Among the program's unique standard cell placement algorithms are simultaneous X/Y placement and channel-density improvement algorithms and an innovative algorithm for reducing chip width by using over-the-cell crossover. Iterative cell placement improvement strategies, such as cell row balancing and cell migration, which result in over 10% area reduction, make VITAL an extremely effective layout tool. The frequent interaction of the placement algorithms with the routing function results in denser chip layouts, as much as 25% smaller than those achieved with commercial tools. The steps of the standard cell-placement procedure are described in detail.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Point mutations in the yeast histone H4 gene prevent silencing of the silent mating type locus HML. (1990)

The N-terminal serine and four conserved lysine residues near the N-terminus of yeast histone H4 are acetylated. We found that a mutation that changed the fourth lysine to alanine resulted in specific derepression of the silent mating type locus HML, while mutations that altered the N-terminal serine or the first three lysines had only minor phenotypic effects. Our results support an active role for histone H4 in the silencing of gene expression at this locus.
Transformation of the tumour microenvironment by a CD40 agonist antibody correlates with improved responses to PD-L1 blockade in a mouse orthotopic pancreatic tumour model (2016)

Despite the availability of recently developed chemotherapy regimens, survival times for pancreatic cancer patients remain poor. These patients also respond poorly to immune checkpoint blockade therapies (anti-CTLA-4, anti-PD-L1, anti-PD-1), which suggests the presence of additional immunosuppressive mechanisms in the pancreatic tumour microenvironment (TME). CD40 agonist antibodies (αCD40) promote antigen presenting cell (APC) maturation and enhance macrophage tumouricidal activity, and may therefore alter the pancreatic TME to increase sensitivity to immune checkpoint blockade. Here, we test whether αCD40 transforms the TME in a mouse syngeneic orthotopic model of pancreatic cancer, to increase sensitivity to PD-L1 blockade. We found that whilst mice bearing orthotopic Pan02 tumours responded poorly to PD-L1 blockade, αCD40 improved overall survival. αCD40 transformed the TME, upregulating Th1 chemokines, increasing cytotoxic T cell infiltration and promoting formation of an immune cell-rich capsule separating the tumour from the normal pancreas. Furthermore, αCD40 drove systemic APC maturation, memory T cell expansion, and upregulated tumour and systemic PD-L1 expression. Combining αCD40 with PD-L1 blockade enhanced anti-tumour immunity and improved overall survival versus either monotherapy. These data provide further support for the potential of combining αCD40 with immune checkpoint blockade to promote anti-tumour immunity in pancreatic cancer.
High-throughput telomere length quantification by FISH and its application to human population studies (2007)

A major limitation of studies of the relevance of telomere length to cancer and age-related diseases in human populations and to the development of telomere-based therapies has been the lack of suitable high-throughput (HT) assays to measure telomere length. We have developed an automated HT quantitative telomere FISH platform, HT quantitative FISH (Q-FISH), which allows the quantification of telomere length as well as percentage of short telomeres in large human sample sets. We show here that this technique provides the accuracy and sensitivity to uncover associations between telomere length and human disease.
Chemotherapeutic agents. XII [1]. Synthesis of Pyrimidines and Fused Pyrimidines as leishmanicides and herbicides (1989)

Abstract Various bicyclic ( 2 , 3 ) and tricyclic ( 4 , 5 ) heterocycles were prepared by the reaction of 1a , c with dihaloalkanes and polynitrohalobenzene separately. Electrophilic substitution on 1a–c with different alkyl halides yielded mono and dialkyl pyrimidiens ( 6–20 ). Nucleophilic substitution reactions on 18 and 21 with amine and hydrazine separately yielded 22–31 , 21a , b and 41c . Reaction of 25a with ethyl ethoxymethylenecyanoacetate and chloroacetyl chloride separately provided bicyclic compounds 32 and 33 . Condensation‐cyclization of 25a with formic, acetic and nitrous acid separately yielded 34a , b and 35 . Reaction of 26a with ethylthiocylycolate and thiourea separately provided 36a and 39 . The latter was alkylated with methyl iodide to 40 . An attempt to cyclize 29a and 30a with thionyl chloride provided bicyclic compounds 37a , b and an uncyclic product 38 . Some of the compounds were screened for leishmanicidal and herbicidal activities and a few of them exhibited significant activity. Leishmaniasis is considered to be one of the most devastating diseases and is ominous to tropical countries. The high toxicity of leishmanicidal drugs in current use, aroused considerable interest to develop new safer and effective chemotherapeutic agents. The only drug pyrimethamine [2] is the representative of pyrimidine derivatives, known as leishmanicides but low order of activity at high dose failed to retain in the clinic. Based on our past experiences in rational designing of leishmanicidal pyrimidine analogs, incorporation of levamisole pharmacophore either in flexible or rigid forms is indispensable for potential activity [1,3] against visceral leishmaniasis. These observations induced an impetus to synthesize pyrimidine analogs as potential leishmanicides.
A genome-wide search for susceptibility genes in human systemic lupus erythematosus sib-pair families (1998)

Systemic lupus erythematosus (SLE) is an autoimmune multisystem inflammatory disease characterized by the production of pathogenic autoantibodies. Previous genetic studies have suggested associations with HLA Class II alleles, complement gene deficiencies, and Fc receptor polymorphisms; however, it is likely that other genes contribute to SLE susceptibility and pathogenesis. Here, we report the results of a genome-wide microsatellite marker screen in 105 SLE sib-pair families. By using multipoint nonparametric methods, the strongest evidence for linkage was found near the HLA locus (6p11-p21) [D6S257, logarithm of odds (lod) = 3.90, P = 0.000011] and at three additional regions: 16q13 (D16S415, lod = 3.64, P = 0.000022), 14q21-23 (D14S276, lod = 2.81, P = 0.00016), and 20p12 (D20S186, lod = 2.62, P = 0.00025). Another nine regions (1p36, 1p13, 1q42, 2p15, 2q21-33, 3cent-q11, 4q28, 11p15, and 15q26) were identified with lod scores >/=1.00. These data support the hypothesis that multiple genes, including one in the HLA region, influence susceptibility to human SLE.
Enzyme conductometric biosensor for maltose determination (2009)

Aim. To develop enzyme conductometric biosensor for maltose determination. Methods. A conductometric transducer consisting of two gold pairs of electrodes was applied. Three-enzyme mem-brane (glucose oxidase, mutarotase, a-glucosidase) immobilized on the surface of the conductometric transducer was used as a bioselective element. Results. A linear range of maltose con-ductometric biosensor was from 0,002 mM to 1 mM for glucose and maltose detection. The time of maltose analysis in solution was 1-2 minutes. The dependence of biosensor responses to substrate on pH, ionic strength, and buffer capacity of work solution was studied. The data of biosensor selectivity are presented. The developed conductometric biosensor is characterized by high operational sta-bility and signal reproducibility. Conclusion. The enzyme conductometric biosensor for maltose determination has been developed. The analytical characteristics of the maltose biosensor were investigated. The proposed method could be used in food industry to control and optimize production.
A clinical overview of IgG4-related systemic disease (2010)

IgG4-RSD is an underrecognized condition about which knowledge is now growing rapidly. Yet there remain many unknowns with regard to its cause, pathogenesis, various clinical presentations, approach to treatment, disease monitoring, and long-term outcomes. A wide variety of organs can be involved in IgG4-RSD. Clinicians should be aware of this entity and consider the diagnosis in the appropriate settings.
Finger on the Pulse: The Value of the Activity Stream in the Enterprise (2013)

The activity stream, which syndicates user activities across social media, has been gaining popularity on the web. With social media infiltrating the enterprise and higher portions of the workforce becoming accustomed to consuming information through activity streams, it also has the potential to play a key role in shaping the workplace. This work provides a first comprehensive study of an enterprise activity stream. We analyze different characteristics of the stream, its usage through a faceted search-based application, and the way users search it compared to traditional enterprise search. We also discuss various use cases of the stream, both from an individual employee’s perspective and from an organizational perspective, exposing the potential value and role of the activity stream in the enterprise of the future.
Molecular defects in CRM+ factor VII deficiencies: modelling of missense mutations in the catalytic domain of FVII (1994)

The molecular defects causing CRM+ factor VII deficiency were investigated in seven unrelated subjects and several members of their families. Four missense mutations located in the catalytic domain of factor VII were found. The previously reported 304Arg-->Gln substitution was present in the homozygous and heterozygous forms, with different polymorphic haplotypes, thus demonstrating that it is recurrent and frequent in the Italian population. The 310Cys-->Phe substitution was found in the homozygous form and in the compound heterozygous condition with the nonsense mutation 356Trp-->stop. Two missense mutations, 298Met-->Ile and 342Gly-->Arg, were found in the homozygous and in the heterozygous condition respectively. Molecular heterogeneity was further increased by finding of the 353Arg-->Gln polymorphism in the doubly heterozygous condition with the 304 and 342 mutations. Plausible explanations for loss of FVII function were found by inspecting a model of the serine protease domain of factor VIIa. Inefficient activation of the catalytic site is predicted for 298Met-->Ile. 342Gly-->Arg would directly distort the geometry of the 'oxyanion hole' preventing formation of a substrate enzyme intermediate. 310Cys-->Phe is predicted to have an adverse effect on tissue factor interaction. These mutations point to important regions of the factor VII molecule.
Image retrievals based on color and texture features (2007)

The paper proposes a new combined image retrieving method based on two primitive features of an image: color and texture. The improved annular color histogram is used to extract color feature, Gabor wavelet is used to extract texture feature and different weights are assigned for them. Given a query, images in the database are ranked according to the distance. Results show the process improves retrieval performance significantly compared with those based on traditional color or texture feature.
Managing Organizational Change through Teams and Groups (1994)

Points out that a significant element of an individual′s life is through groups and that there are many different aspects of groups in organizational life. Holds that the informal influence a group exerts on individual members through socialization, enforcement of norms and development of culture is powerful in how individuals respond to organizational change. Argues that teambuilding is critical to forming group responses to change issues, whether through the formal teams or through temporary task forces and committees.
Reclassification of American Rhizobium leguminosarum Biovar Phaseoli Type I Strains as Rhizobium etli sp. nov. (1993)

A new Rhizobium species that nodulates Phaseolus vulgaris L. is proposed on the basis of a sequence analysis of 16S ribosomal DNA. This taxon, Rhizobium etli sp. nov., was previously named Rhizobium leguminosarum biovar phaseoli (type I strains) and is characterized by the capacity to establish an effective symbiosis with bean plants, the reiteration of the nitrogenase structural genes, the organization of the common nodulation genes into two separate transcriptional units bearing nodA and nodBC, the presence of the polysaccharide inhibition gene, psi, and the 16S ribosomal DNA sequence. An analysis of the sequence of a fragment of the 16S rRNA gene shows that this gene is quite different from the gene of R. leguminosarum. In addition, all R. etli strains have identical sequences. We describe these analyses and discuss additional evidence supporting our proposal.
Both the SH2 and SH3 Domains of Human CRK Protein Are Required for Neuronal Differentiation of PC12 Cells (1993)

Human CRK protein is a homolog of the chicken v-crk oncogene product and consists mostly of src homology region 2 (SH2) and SH3, which are shared by many proteins, in particular those involved in signal transduction. SH2 has been shown to bind specifically to phosphotyrosine-containing peptides. We report here that both SH2 and SH3 are required for signaling from CRK protein. Microinjection of the CRK protein induced neurite formation of rat pheochromocytoma cell line PC12. This activity was abolished by mutation of the CRK protein in either SH2 or SH3. The neuronal differentiation induced by the CRK protein was blocked by an excess amount of peptides containing CRK SH3. Moreover, we identified three proteins, of 118, 125, and 136 kDa, which bound specifically to CRK SH3. The CRK-induced neuronal differentiation was also suppressed by monoclonal antibodies against either CRK SH2 or p21ras. These results suggest that both SH2 and SH3 of the CRK protein mediate specific protein-protein binding and that the resulting multimolecular complex generates a signal for neurite differentiation through activation of p21ras.