gebhart/patrepeval huggingface dataset:
A family of cyclin homologs that control the G1 phase in yeast. (1989)

Two Saccharomyces cerevisiae genes were isolated based upon their dosage-dependent rescue of a temperature-sensitive mutation of the gene CDC28, which encodes a protein kinase involved in control of cell division. CLN1 and CLN2 encode closely related proteins that also share homology with cyclins. Cyclins, characterized by a dramatic periodicity of abundance through the cell cycle, are thought to be involved in mitotic induction in animal cells. A dominant mutation in the CLN2 gene, CLN2-1, advances the G1- to S-phase transition in cycling cells and impairs the ability of cells to arrest in G1 phase in response to external signals, suggesting that the encoded protein is involved in G1 control of the cell cycle in Saccharomyces.
Paracetamol-Propyphenazone Interaction and Formulation Difficulties Associated with Eutectic Formation in Combination Solid Dosage Forms. (1999)

Polymorphic behaviours of paracetamol and propyphenazone and interaction between these two compounds were investigated using differential scanning calorimetry (DSC), X-ray powder diffraction and Fourier transform-infrared (FT-IR)-spectroscopy. Binary mixtures containing various ratios of the compounds were prepared as physical and fused mixtures and analysed by DSC to study their thermal behaviours. Phase diagrams obtained from the melting endotherms of the binary mixtures demonstrated formation of an eutectic mixture at a paracetamol-propyphenazone combination of about 35:65 (w/w) with an eutectic temperature of 56 degrees C. The FT-IR spectroscopy revealed no chemical interaction due to eutectic formation, and a lower degree of crystallinity of the eutectic mixture than individual substances was observed by X-ray powder diffraction analysis. The DSC and X-ray powder diffraction data demonstrated a polymorphic change in propyphenazone as a result of melting of the compound. Tablets, containing both paracetamol and propyphenazone in a combination formulation and prepared using standard wet granulation technology, were found to have physical instability when packed in either polyvinylchloride// aluminium or polyvinylchloride/polyvinyldienechloride// aluminium blisters and stored for one month at 40 degrees C with either 75% relative humidity or without any humidity control. The instability of the tablets was more apparent under the high humidity condition.
Human Cytomegalovirus UL131-128 Genes Are Indispensable for Virus Growth in Endothelial Cells and Virus Transfer to Leukocytes (2004)

Human cytomegalovirus (HCMV), a ubiquitous human pathogen, is the leading cause of birth defects and morbidity in immunocompromised patients and a potential trigger for vascular disease. HCMV replicates in vascular endothelial cells and drives leukocyte-mediated viral dissemination through close endothelium- leukocyte interaction. However, the genetic basis of HCMV growth in endothelial cells and transfer to leukocytes is unknown. We show here that the UL131-128 gene locus of HCMV is indispensable for both productive infection of endothelial cells and transmission to leukocytes. The experimental evidence for this is based on both the loss-of-function phenotype in knockout mutants and natural variants and the gain-of-function phenotype by trans-complementation with individual UL131, UL130, and UL128 genes. Our findings suggest that a common mechanism of virus transfer may be involved in both endothelial cell tropism and leukocyte transfer and shed light on a crucial step in the pathogenesis of HCMV infection.
The neurotrophin-trk receptor axes are critical for the growth and progression of human prostatic carcinoma and pancreatic ductal adenocarcinoma xenografts in nude mice. (2002)

These data add further support for the therapeutic potential of disrupting trk-signaling events in select types of nonneuronal human cancers, specifically prostatic and pancreatic carcinomas.
A new "active" predistorter with high gain and programmable gain and phase characteristics using cascode-FET structures (2002)

A MMIC-compatible miniaturized "active" predistorter using cascode FET structures is presented. The predistorter has added functionality of gain, as well as programmable gain and phase variation characteristics, which are required to compensate or the nonlinear distortion of a wide range of power amplifiers (PAs). Thanks to the inherent gain of the predistorter, a need for an additional buffer amplifier is eliminated. Furthermore, it can eventually replace the first-stage amplifier in the multistage PAs, making this approach well suited to MMIC implementation. A simple analysis is performed to understand the phase variation mechanisms in the proposed predistorter and to identify the dominant sources of phase variation. To demonstrate the general usefulness of this predistorter, the cascode predistorter was applied to linearize watt-level MMIC amplifiers for CDMA handset applications, as well as 30 W high power amplifiers for base-station applications. Adjacent channel power ratio (ACPR) improvement of 3-5 dB was achieved with off-chip predistorter when applied to 0.9 W monolithic amplifiers. The predistorter was also integrated with a 1.6 W MMIC PA on a single chip, replacing the first-stage transistor of the amplifier.
Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach (2012)

Table 1dProperties of currently available glucose-lowering agents that may guide treatment choice in individual patients with type 2 diabetes mellitus Class Compound(s) Cellular mechanism
Interactions between mucopolysaccharides and cationic polypeptides in aqueous solution: Chondroitin 4‐sulfate and dermatan sulfate (1973)

Abstract Circular dichroism spectroscopy has been used to study the interactions of both dermatan sulfate and chondroitin 4‐sulfate with the cationic polypeptides; poly( L ‐arginine), poly( L ‐lysine), and poly( L ‐ornithine). The results indicate that the mucopolysaccharides have a conformation directing effect on both poly( L ‐arginine) and poly‐( L ‐lysine) such that these polypeptides adopt the α‐helical conformation. The extent of interaction in each polypeptide‐polysaccharide system can be judged by the degree of induced helicity and the “melting temperature” at which the interaction is disrupted On comparison of these results with those previously obtained for chondroitin 6‐sulfate‐polypeptide mixtures, the extent of interaction can be seen to depend on the length of the amino acid side chain and the positions of the anionic groups on the mucopolysaccharide chain. Such considerations place the three mucopolysaccharides in order of increasing interaction: chondroitin 4‐sulfate &lt; chondroitin 6‐sulfate &lt; dermatan sulfate. These results are correlated with observations that dermatan sulfate is bound more tightly to collagen in connective tissues than are the other two polysaccharides.
Human body fluid proteome analysis (2006)

The focus of this article is to review the recent advances in proteome analysis of human body fluids, including plasma/serum, urine, cerebrospinal fluid, saliva, bronchoalveolar lavage fluid, synovial fluid, nipple aspirate fluid, tear fluid, and amniotic fluid, as well as its applications to human disease biomarker discovery. We aim to summarize the proteomics technologies currently used for global identification and quantification of body fluid proteins, and elaborate the putative biomarkers discovered for a variety of human diseases through human body fluid proteome (HBFP) analysis. Some critical concerns and perspectives in this emerging field are also discussed. With the advances made in proteomics technologies, the impact of HBFP analysis in the search for clinically relevant disease biomarkers would be realized in the future.
Mutations and altered expression of p16INK4 in human cancer. (1994)

Cell cycle arrest at the G1 checkpoint allows completion of critical macromolecular events prior to S phase. Regulators of the G1 checkpoint include an inhibitor of cyclin-dependent kinase, p16INK4; two tumor-suppressor proteins, p53 and RB (the product of the retinoblastoma-susceptibility gene); and cyclin D1. Neither p16INK4 nor the RB protein was detected in 28 of 29 tumor cell lines from human lung, esophagus, liver, colon, and pancreas. The presence of p16INK4 protein is inversely correlated with detectable RB or cyclin D1 proteins and is not correlated with p53 mutations. Homozygous deletions of p16INK4 were detected in several cell lines, but intragenic mutations of this gene were unusual in either cell lines or primary tumors. Transfection of the p16INK4 cDNA expression vector into carcinoma cells inhibits their colony-forming efficiency and the p16INK4 expressing cells are selected against with continued passage in vitro. These results are consistent with the hypothesis that p16INK4 is a tumor-suppressor protein and that genetic and epigenetic abnormalities in genes controlling the G1 checkpoint can lead to both escape from senescence and cancer formation.
Applications of attenuated total reflection in the infrared analysis of carbohydrates and biological whole cell samples in aqueous solution (1987)

An analysis of simple carbohydrates was undertaken using attenuated total reflection (ATR) and Fourier transform infrared (FTIR) spectroscopy. Spectra were obtained of glucose in aqueous solution and the results were qualitatively and quantitatively assessed for three new ATR accessories. The same method was then used to study glucose in the presence of sucrose in aqueous solution. A study has also been made of whole plant cells including the yeasts Pelargonium sp. and Triticum sp. and the spectra obtained have been used to determine cellular components and to monitor the enzymatic digestion of the cell wall material in the formation of protoplast.
Isolation of a Pseudomonas solanacearum-specific DNA probe by subtraction hybridization and construction of species-specific oligonucleotide primers for sensitive detection by the polymerase chain reaction (1992)

A subtraction hybridization technique was employed to make a library enriched for Pseudomonas solanacearum-specific sequences. One cloned fragment, PS2096, hybridized under stringent conditions to DNA of 82 P. solanacearum strains representing all subgroups of the species. Other plant-associated bacteria, including closely related species such as Pseudomonas capacia, Pseudomonas picketti, or Pseudomonas syzygii, did not hybridize to PS2096. A minimum number of between 4 x 10(5) and 4 x 10(6) P. solanacearum cells could routinely be detected with PS2096 labelled either with [32P]dCTP or with digoxigenin-11-dUTP. To improve the sensitivity of detection, PS2096 was sequenced to allow the construction of specific oligonucleotide primers to be used for polymerase chain reaction (PCR) amplification. After 50 cycles of amplification, 5 to 116 cells, depending on the strain, could reproducibly be detected by visualization of a 148-bp PCR product on an agarose gel. A preliminary field trial in Burundi with the probe and PCR primers has confirmed that they are sensitive tools for specifically detecting low-level infections of P. solanacearum in potato tubers.
Advanced deep reactive ion etching: a versatile tool for microelectromechanical systems (1998)

SAMLAB
Intranasal priming with recombinant Bordetella pertussis for the induction of a systemic immune response against a heterologous antigen (1997)

One of the current goals in vaccine development is the noninvasive administration of protective antigens via mucosal surfaces. In this context, the gut-associated lymphoid tissues have already been extensively explored. Vaccination via the nasal route has only recently been the focus of intensive investigation, and no live vector specifically designed for the respiratory mucosa is yet available. In this study we show that intranasal administration of the recombinant Bordetella pertussis BPGR60, producing the Schistosoma mansoni 28-kDa glutathione S-transferase (Sm28GST) protective antigen fused to filamentous hemagglutinin, induces priming in mice for the production of serum antibodies. In addition to significant levels of anti-Sm28GST immunoglobulin A (IgA) antibodies, high levels of anti-Sm28GST serum antibodies were obtained after intranasal boost with the purified antigen or infection with S. mansoni following intranasal priming with BPGR60. These antibodies were of the IgG1, IgG2a, and IgG2b isotypes, suggesting a mixed immune response. No priming was observed in animals that had received nonrecombinant B. pertussis or purified Sm28GST, indicating specific priming by BPGR60. This priming was also evident in immune protection against S. mansoni challenge. Significant protection against worm burden and egg output was obtained in mice primed with BPGR60 and intranasally boosted with purified Sm28GST. A lower but still significant degree of protection against egg output was also obtained in mice infected with a single dose of BPGR60. These results indicate that intranasal administration of recombinant B. pertussis can prime for serum antibody responses against a foreign antigen and for heterologous protection.
Respiratory syncytial virus infection in mice (1984)

The A2 strain of human respiratory syncytial virus replicated in the nose and lung of BALB/c mice, with virus growing to higher titers in older animals than in younger animals. Virus was recovered from the nose between days 2 and 7 with peak titers on days 3 and 4, and from the lungs between days 2 and 9, with peak titers on days 4 through 6. Serum antibody developed 2 weeks after infection. Viral antigen was demonstrated in the alveolar cells of the lung by immunofluorescence. Histopathological changes included infiltration by mononuclear cells of the peribronchiolar and perivascular tissue, some interstitial thickening, and formation of multinucleated giant cells. Virus could not be recovered from the respiratory tract of mice inoculated with bovine strains of respiratory syncytial virus. Growth of the A2 strain of human respiratory syncytial virus in different cell lines affected its infectivity for mice. Infection of BALB/c mice with respiratory syncytial virus provides a highly reproducible model for the study of the pathogenesis of and mechanisms of immunity to this virus.
Apolipoprotein E (ApoE) Isoform-dependent Lipid Release from Astrocytes Prepared from Human ApoE3 and ApoE4 Knock-in Mice (2002)

We have reported previously (Michikawa, M., Fan, Q.-W., Isobe, I., and Yanagisawa, K. (2000) J. Neurochem. 74, 1008-1016) that exogenously added recombinant human apolipoprotein E (apoE) promotes cholesterol release in an isoform-dependent manner. However, the molecular mechanism underlying this isoform-dependent promotion of cholesterol release remains undetermined. In this study, we demonstrate that the cholesterol release is mediated by endogenously synthesized and secreted apoE isoforms and clarify the mechanism underlying this apoE isoform-dependent cholesterol release using cultured astrocytes prepared from human apoE3 and apoE4 knock-in mice. Cholesterol and phospholipids were released into the culture media, resulting in the generation of two types of high density lipoprotein (HDL)-like particles; one was associated with apoE and the other with apoJ. The amount of cholesterol released into the culture media from the apoE3-expressing astrocytes was approximately 2.5-fold greater than that from apoE4-expressing astrocytes. In contrast, the amount of apoE3 released in association with the HDL-like particles was similar to that of apoE4, and the sizes of the HDL-like particles released from apoE3- and apoE4-expressing astrocytes were similar. The molar ratios of cholesterol to apoE in the HDL fraction of the culture media of apoE3- and apoE4-expressing astrocytes were 250 +/- 6.0 and 119 +/- 5.1, respectively. These data indicate that apoE3 has an ability to generate similarly sized lipid particles with less number of apoE molecules than apoE4, suggesting that apoE3-expressing astrocytes can supply more cholesterol to neurons than apoE4-expressing astrocytes. These findings provide a new insight into the issue concerning the putative alteration of apoE-related cholesterol metabolism in Alzheimer's disease.
Partitioning of a polymer into a nanoscopic protein pore obeys a simple scaling law (2001)

The dependence of the rate on polymer mass was examined for the reaction of four sulfhydryl-directed poly(ethylene glycol) reagents with cysteine residues located in the lumen of the staphylococcal alpha-hemolysin pore. The logarithms of the apparent rate constants for a particular site in the lumen were proportional to N, the number of repeat units in a polymer chain. The proportionality constant was -(a/D)(5/3), where a is the persistence length of the polymer ( approximately 3.5A) and D is the diameter of the pore. Despite some incongruencies with the assumptions of the derivation, the result suggests that the polymers partition into the lumen of the pore according to the simple scaling law of Daoud and de Gennes, c(pore)/c(solution) = exp(-N(a/D)(5/3)). Therefore, the measured reaction rates yield an estimate of the diameter of the pore and might be applied to determine the approximate dimensions of cavities within other similar proteins.
FOXP3 Expression and Overall Survival in Breast Cancer (2009)

The data identify FOXP3 expression as a new independent prognostic factor in breast carcinoma, which might help to improve the selection of patients for appropriate therapy.
Modeling and Dynamic Simulations of Doubly Fed Adjustable-Speed Pumped Storage Units (2007)

This paper derives the mathematical models of doubly fed adjustable-speed pumped storage units (DFASPSUs) to be utilized in the power system analysis. It adopts the improved induction machine model with ac excitation on the wire-wound rotor as well as the field-oriented control theory for the study and analysis of DFASPSU models. First, the rotor excitation voltage is separated into two components, i.e., the q-axis voltage and the d-axis voltage, so as to control the output active and reactive powers, respectively. Next, a dynamic model of DFASPSU is derived using the swing equation of rotary electric machine and the equation of motion of rotor rotating mass. Finally, computer simulation is carried out to compare its results with practical examples in terms of dynamic characteristics for verifying the correctness of the proposed models.
First clinical experience using a ‘pathotropic’ injectable retroviral vector (Rexin-G) as intervention for stage IV pancreatic cancer (2004)

Metastatic or non-resectable (stage IV) pancreatic cancer has a rapidly fatal outcome (median survival: 3-6 months), thus making gene therapy a viable therapeutic option. The objectives of the clinical studies are to evaluate the safety/toxicity and potential anti-tumor response/efficacy of intravenous (i.v.) infusions of a 'pathotropic' retroviral vector bearing a cytocidal gene construct (Rexin-G) as a gene transfer intervention for stage IV pancreatic cancer. An intra-patient dose escalation regimen was used wherein increasing doses of Rexin-G were given i.v. daily for 8-10 days. Completion of this regimen was followed by a one-week evaluation period for toxicity, after which, the maximum tolerated dose of Rexin-G was administered for another 8-10 days. In a second protocol, i.v. Rexin-G was administered frontline for 6 days followed by 8 doses of weekly gemcitabine. The NIH Common Toxicity Criteria Vs.2 was used to assess toxicity, and the NCI-RECIST criteria and tumor volume measurements were used to evaluate potential anti-tumor responses. We report the results of the first 3 patients that participated in the studies. Rexin-G arrested tumor growth in 3 of 3 patients without experiencing dose-limiting toxicity. No bone marrow suppression, significant alterations in liver and kidney function, nausea and vomiting, mucositis or hair loss were observed. Two patients are alive with stable disease approximately 5 and 14 months from diagnosis, and 1 patient is alive with progressive disease 20 months from diagnosis. The encouraging results of this first clinical experience will guide the design and planning of phase I/II clinical trials to establish the safety and efficacy of Rexin-G as the first targeted injectable gene therapy vector for stage IV pancreatic cancer.
Folding of a small helical protein using hydrogen bonds and hydrophobicity forces (2002)

A reduced protein model with five to six atoms per amino acid and five amino acid types is developed and tested on a three-helix-bundle protein, a 46-amino acid fragment from staphylococcal protein A. The model does not rely on the widely used Go approximation, which ignores non-native interactions. We find that the collapse transition is considerably more abrupt for the protein A sequence than for random sequences with the same composition. The chain collapse is found to be at least as fast as helix formation. Energy minimization restricted to the thermodynamically favored topology gives a structure that has a root-mean-square deviation of 1.8 A from the native structure. The sequence-dependent part of our potential is pairwise additive. Our calculations suggest that fine-tuning this potential by parameter optimization is of limited use.
The Formulation and Delivery of Monoclonal Antibodies (2009)

This chapter contains sections titled: Introduction Formulation Development of Monoclonal Antibodies Novel Delivery of Monoclonal Antibodies Conclusions: Challenges and Opportunities Acknowledgments References
Group II Introns: Structure and Catalytic Versatility of Large Natural Ribozymes (2003)

Group II introns are large, natural catalytic RNAs or ribozymes that were discovered in organelles of certain protists, fungi, algae, and plants and more recently also in prokaryotic organisms. In vitro, some members were found to self-splice from their pre-RNAs by two consecutive transesterification reactions joining the flanking exons and releasing the intron in a typical lariat form. Apart from self-splicing, a variety of other in vitro activities have been detected for group II introns demonstrating their amazing catalytic versatility. Group II introns fold into a conserved secondary structure consisting of six domains radiating from a central wheel that brings the 5′ and 3′ splice junction into close proximity. Domain 1 is the largest domain that is assumed to deliver the molecular scaffold assembling the intron in its active structure, while domain 5 is the phylogenetically most conserved part that represents the active site of the ribozyme. In vivo, the splicing reaction of many, if not all group II introns is assisted by proteins either encoded by the introns themselves (maturases), or encoded by other genes of the host organisms. The host proteins known to date have additional cellular functions and seem to have been adapted for splicing during evolution. Some of the protein-encoding group II introns were also shown to act as mobile genetic elements. They can integrate efficiently into intronless alleles of the same gene (homing) and at much lower frequencies into ectopic sites (transposition). The mobility process depends on intron encoded protein functions (endonuclease and reverse transcriptase) and on the intron RNA. This review provides a comprehensive survey of the structure/function relationships and the reaction potential of group II introns, the structurally most complicated, but also most fascinating ribozymes when looking at their catalytic repertoire in vitro and in vivo.