gebhart/patrepeval huggingface dataset:
Phase I Clinical Study of Pertuzumab, a Novel HER Dimerization Inhibitor, in Patients With Advanced Cancer (2005)

These results demonstrate that pertuzumab is well tolerated, has a pharmacokinetic profile which supports 3-week dosing, and is clinically active, suggesting that inhibition of dimerization may be an effective anticancer strategy.
Evaluation of the Efficacy and Safety of Hyaluronic Acid Vaginal Gel to Ease Vaginal Dryness: A Multicenter, Randomized, Controlled, Open-Label, Parallel-Group, Clinical Trial (2013)

Both hyaluronic acid vaginal gel and estriol cream are effective in the treatment of vaginal dryness. Hyaluronic acid vaginal gel may be considered as a valid alternative to estrogen-based treatments in relieving the symptoms of vaginal dryness.
ChemInform Abstract: Potential Energy Surfaces for Metal‐Assisted Chemical Reactions (2012)

Abstract Review: 92 refs.
Influence of long-term vaccination of a breeding herd of pigs against PCV2 on reproductive parameters (2012)

The objective of the study was to evaluate an efficacy of sows vaccination protocols in the herd with serious problems affecting efficacy of reproduction. The study was performed in a large pig herd with about 1200 sows. Before vaccination against PCV2, farrowing rate in this farm was about 65%. Sows, boar and replacement gilts were immunized using Circovac vaccine (Merial, France) according to producer's recommendations. Parameters of production were analyzed since 2007 until 2010 in selected batches of sows inseminated at the same weeks of the year (17th, 18th, 19th and 20th) to eliminate seasonal variability. In total, 940 sows were subjected to the study. No significant changes in management during these years were introduced. The applied protocol of sow herd long-term vaccination proved to be very efficient. All measured production parameters: reproduction rate, number of piglets born alive, birth weight of piglets and number of piglets weaned per a litter improved after implementation of immunization program. Moreover, further improvement was observed with vaccination in the following reproduction cycles. The most spectacular effect of vaccination regarded average farrowing rate that increased from 64.76% in control group to 86.93% after basic vaccination. Two years after implementation of vaccination program this parameter reached 93.6%. Number of piglets weaned per sow per a litter improved from 10.31 to 11.74 after one year of vaccination and remained relatively stable through the following year. Simultaneously, the percentage of newborn piglets with birth weight < 1 kg decreased significantly (p < 0.05). To summarize, vaccination against PCV2 influenced positively the insemination rate, number of piglets born alive and weaned per litter as well as birth body weight and percentage of piglets weighing < 1 kg.
MicroRNA-500 as a potential diagnostic marker for hepatocellular carcinoma (2009)

We identified that microRNA expression changed dynamically during liver development and found that miR-500 is an oncofetal miRNA in liver cancer. miR-500 was abundantly expressed in several human liver cancer cell lines and 45% of human hepatocellular carcinoma (HCC) tissue. Most importantly, an increased amount of miR-500 was found in the sera of the HCC patients. In fact, miR-500 levels in sera of the HCC patients returned to normal after the surgical treatment in three HCC patients. Our findings reveal that diverse changes of miRNAs occur during liver development and, one of these, miR-500 is an oncofetal miRNA relevant to the diagnosis of human HCC.
Inhibition of 15-PGDH Protects Mice from Immune-Mediated Bone Marrow Failure (2020)

Aplastic anemia (AA) is a human immune-mediated bone marrow failure syndrome that is treated by stem cell transplantation for patients who have a matched related donor and by immunosuppressive therapy (IST) for those who do not. Responses to IST are variable, with patients still at risk for prolonged neutropenia, transfusion dependence, immune suppression, and severe opportunistic infections. Therefore, additional therapies are needed to accelerate hematologic recovery in patients receiving front-line IST. We have shown that inhibiting 15-hydroxyprostaglandin dehydrogenase (15-PGDH) with the small molecule SW033291 (PGDHi) increases bone marrow (BM) prostaglandin E2 levels, expands hematopoietic stem cell (HSC) numbers, and accelerates hematologic reconstitution following murine BM transplantation. We now report that in a murine model of immune-mediated BM failure, PGDHi therapy mitigated cytopenias, increased BM HSC and progenitor cell numbers, and significantly extended survival compared with vehicle-treated mice. PGDHi protection was not immune-mediated, as serum IFN-γ levels and BM CD8<sup>+</sup> T lymphocyte frequencies were not impacted. Moreover, dual administration of PGDHi plus low-dose IST enhanced total white blood cell, neutrophil, and platelet recovery, achieving responses similar to those seen with maximal-dose IST with lower toxicity. Taken together, these data demonstrate that PGDHi can complement IST to accelerate hematologic recovery and reduce morbidity in severe AA.
Granulocyte colony‐stimulating factor down‐regulates the surface expression of the human leucocyte adhesion molecule‐1 on human neutrophils in vitro and in vivo (1993)

The leucocyte adhesion molecule-1 (LAM-1) is the human homologue of the murine peripheral lymph node homing receptor, MEL-14, and might play a crucial role in neutrophil localization at inflammatory sites. We have reported previously that recombinant human granulocyte colony-stimulating factor (rhG-CSF) stimulates or enhances several neutrophil functions in vivo, as well as in vitro. To further explore the possible role of G-CSF in inflammation we studied the effect of rhG-CSF on the surface expression of LAM-1 on human neutrophils, both in vitro and in vivo. The expression of LAM-1 by human neutrophils was investigated by indirect immunofluorescence using flow cytometry and monoclonal antibodies anti-Leu-8 and TQ1. A whole blood analysis was performed to minimize in vitro manipulation. Most circulating human neutrophils expressed LAM-1 on the cell surface. Brief exposure of neutrophils to rhG-CSF in vitro decreased the surface expression of LAM-1. rhG-CSF down-regulated neutrophil LAM-1 expression in a time- and dose-dependent manner. Neutrophils from healthy volunteers and from patients who were receiving rhG-CSF exhibited a decreased expression of LAM-1 after rhG-CSF administration, and the expression thereafter returned or overshot the pretreatment level after stopping rhG-CSF administration. These findings indicate that rhG-CSF down-regulates the surface expression of LAM-1 on human neutrophils in vivo, as well as in vitro, and G-CSF might participate in neutrophil-endothelial cell interaction in inflamed tissue.
Luminescence Properties of Thiol-Stabilized CdTe Nanocrystals (1999)

Thiol-capped CdTe nanocrystals with cubic zinc blende structure are synthesized in aqueous solution. Their steady-state and time-resolved luminescence characteristics are studied at room and liquid nitrogen temperatures. A strong exciton luminescence peak at 2.3 eV dominates the emission spectrum of CdTe nanocrystals at room temperature, whereas the trap band centered at 2.0 eV undergoes substantial temperature quenching. Luminescence excitation spectra reveal different channels leading to radiative recombination via either excitons or traps. The mean luminescence decay time of CdTe nanocrystals at room temperature decreases from 120 ns at 1.94 eV to 20 ns at 2.43 eV. Luminescence decay kinetics of CdTe nanocrystals are strongly nonexponential and are described by extremely broad lifetime distributions lying within the range from a few hundred picoseconds to a few hundred nanoseconds.
New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway (1999)

The most recently discovered PTEN tumor suppressor gene has been found to be defective in a large number of human cancers. In addition, germ-line mutations in PTEN result in the dominantly inherited disease Cowden syndrome, which is characterized by multiple hamartomas and a high proclivity for developing cancer. A series of publications over the past year now suggest a mechanism by which PTEN loss of function results in tumors. PTEN appears to negatively control the phosphoinositide 3-kinase signaling pathway for regulation of cell growth and survival by dephosphorylating the 3 position of phosphoinositides.
Plasma-Enhanced ALD of Platinum with O2, N2and NH3Plasmas (2012)

Platinum thin films were grown by plasma-enhanced atomic layer deposition (PEALD) using (methylcyclopentadienyl)-trimethylplatinum (MeCpPtMe3) as precursor and respectively an oxygen, nitrogen and ammonia plasma as reactant. For each process the film thickness was found to be linearly dependent on the number of reaction cycles. Saturation curves and temperature windows were defined and growth rates of 0.45 Å cycle−1, 0.30 Å cycle−1 and 0.40 Å cycle−1 were obtained for the oxygen, nitrogen and ammonia process respectively. All the films were metallic platinum, crystalline, uniform and closed, with low surface roughness and low impurity levels. At a pressure of 1 × 10−3 mbar, nucleation on SiO2 was remarkably faster with the NH3 and N2 processes than with the O2 process. In-situ OES and MS measurements showed a fundamental difference between the NH3 and N2 processes and the O2 process. Based on these measurements we propose a reaction mechanism for the N2 and NH3 PEALD processes where nitrogen will unstably adsorb on the substrate during the plasma pulse and be used during the subsequent precursor pulse to remove part of the precursor ligands.
Clinical Effect of CO2 Laser in Reducing Pain in Orthodontics (2007)

The hypothesis was rejected. The results suggest that local CO(2) laser irradiation will reduce pain associated with orthodontic force application without interfering with the tooth movement.
DrugBank: a knowledgebase for drugs, drug actions and drug targets (2007)

DrugBank is a richly annotated resource that combines detailed drug data with comprehensive drug target and drug action information. Since its first release in 2006, DrugBank has been widely used to facilitate in silico drug target discovery, drug design, drug docking or screening, drug metabolism prediction, drug interaction prediction and general pharmaceutical education. The latest version of DrugBank (release 2.0) has been expanded significantly over the previous release. With approximately 4900 drug entries, it now contains 60% more FDA-approved small molecule and biotech drugs including 10% more 'experimental' drugs. Significantly, more protein target data has also been added to the database, with the latest version of DrugBank containing three times as many non-redundant protein or drug target sequences as before (1565 versus 524). Each DrugCard entry now contains more than 100 data fields with half of the information being devoted to drug/chemical data and the other half devoted to pharmacological, pharmacogenomic and molecular biological data. A number of new data fields, including food-drug interactions, drug-drug interactions and experimental ADME data have been added in response to numerous user requests. DrugBank has also significantly improved the power and simplicity of its structure query and text query searches. DrugBank is available at http://www.drugbank.ca.
Novel Biological Functions of High-Density Lipoprotein Cholesterol (2012)

In addition to its role in reverse cholesterol transport, high-density lipoprotein (HDL) cholesterol has direct action on numerous cell types that influence cardiovascular and metabolic health. Cellular responses to HDL entail its capacity to invoke cholesterol efflux that causes signal initiation via scavenger receptor class B, type I, and plasma membrane receptor activation by HDL cargo molecules. In endothelial cells and their progenitors, HDL attenuates apoptosis and stimulates proliferation and migration. HDL also has diverse anti-inflammatory actions in both endothelial cells and leukocytes. In vascular smooth muscles, HDL tempers proinflammatory, promigratory, and degradative processes, and through actions on endothelium and platelets HDL is antithrombotic. There are additional actions of HDL of potential cardiovascular consequence that are indirect, including the capacities to promote pancreatic β-cell insulin secretion, to protect pancreatic β cells from apoptosis, and to enhance glucose uptake by skeletal muscle myocytes. Furthermore, HDL decreases white adipose tissue mass, increases energy expenditure, and promotes the production of adipose-derived cytokine adiponectin that has its own vascular-protective properties. Many of these numerous actions of HDL have been observed not only in cell culture and animal models but also in human studies, and assessments of these functions are now being applied to patient populations to better-elucidate which actions of HDL may contribute to its cardioprotective potential and how they can be quantified and targeted. Further work on the many mechanisms of HDL action promises to reveal new prophylactic and therapeutic strategies to optimize both cardiovascular and metabolic health.
Replamineform porous biomaterials for hard tissue implant applications (1975)

By means of the newly developed Replamineform process, the unique pore microstructures found in the skeletal calcium carbonate of certain reef corals can be replicated or reproduced with high precision in a wide variety of materials suitable for hard tissue implant and prosthetic applications. The advantages of fabricating porous biomaterials with this method include closely controlled size of both the pore diameters and the diameters of the pore interconnections, and virtually complete interconnection of the uniformly spaced pores. These properties are of great importance in implant devices, because tissue ingrowth, the stimulation of new bone formation, the suppression of undesirable scar tissue, the inhibition of adverse body responses, and firm biological fixation of the implanted material all depend upon the nature of the pore-microstructure configuration. Replamineform preparation of Al2O3, TiO2, hydroxyapatite, silver, Co-Cr-Mo alloys, and polymers is described in detail, and the characterization procedures used to determine the physical and structural properties of their materials are discussed. A few of the routinely measured characteristics include (1) quantitative computerized SEM image analysis for determining the volume, size and shape distributions of the macro and microporosity and the grain size measurement of the solid; (2) nondestructive x-radiography of specimens to reveal any internal defects; (3) mechanical strength measurements of randomly selected specimens. Experimental results up to now clearly demonstrate the superiority of microstructures imparted to metals, ceramics, and polymers with the Replamineform process.
Behavioral Recovery in 6-Hydroxydopamine-Lesioned Rats by Cotransduction of Striatum with Tyrosine Hydroxylase and Aromatic l -Amino Acid Decarboxylase Genes Using Two Separate Adeno-Associated Virus Vectors (1998)

Parkinson's disease (PD) is characterized by the progressive loss of the dopaminergic neurons in the substantia nigra and a severe decrease in dopamine in the striatum. A promising approach to the gene therapy of PD is intrastriatal expression of enzymes in the biosynthetic pathway for dopamine. Tyrosine hydroxylase (TH) catalyzes the synthesis of L-dopa, which must be converted to dopamine by aromatic L-amino acid decarboxylase (AADC). Since the endogenous AADC activity in the striatum is considered to be low, coexpression of both TH and AADC in the same striatal cells would increase the dopamine production and thereby augment the therapeutic effects. In the present study, the TH gene and also the AADC gene were simultaneously transduced into rat striatal cells, using two separate adeno-associated virus (AAV) vectors, AAV-TH and AAV-AADC. Immunostaining showed that TH and AADC were coexpressed efficiently in the same striatal cells in vitro and in vivo. Moreover, cotransduction with these two AAV vectors resulted in more effective dopamine production and more remarkable behavioral recovery in 6-hydroxydopamine (6-OHDA)-lesioned rats, compared with rats receiving AAV-TH alone (p < 0.01). These findings suggest an alternative strategy for gene therapy of PD and indicate that the simultaneous transduction with two AAV vectors can extend their utility for potential gene therapy applications.
Self-Selection by Genetically Modified Committed Lymphocyte Precursors Reverses the Phenotype of JAK3-Deficient Mice without Myeloablation (2000)

Janus kinase 3 (JAK3) is an essential component of cytokine receptor signal transduction pathways required for normal lymphocyte development and function. JAK3 deficiency in both mice and humans results in severe combined immunodeficiency (SCID) and increased susceptibility to opportunistic infections. We have previously shown that JAK3 gene transfer into irradiated recipients could restore immune function. However, since this toxic conditioning would be undesirable for infants in a clinical application, we have tested whether immune function could be restored in nonmyeloablated JAK3-deficient (-/-) mice. Murine JAK3 retroviral vectors were transduced into hematopoietic stem cells from the livers of newborn JAK3(-/-) mice. These cells were then injected intraperitoneally into nonirradiated JAK3(-/-) neonates. Transduced cells were detectable in these mice at time points 4 to 6 months after injection and resulted in significant correction of T and B lymphocyte numbers and circulating immunoglobulin (Ig) levels. After immune challenge with a dose of influenza A virus that was lethal to nonmanipulated JAK3(-/-) mice, mice injected with transduced cells showed development of circulating virus-specific IgG and enhanced survival. This work shows that the large selective advantage for JAK3-corrected lymphoid cells may be sufficient to overcome the need for myeloablative conditioning in JAK3 gene therapy protocols.
In vitro activation of Stat3 by epidermal growth factor receptor kinase (1996)

Stat proteins are SH2 domain-containing transcription factors that are activated in cells by various cytokines and growth factors. In the case of cytokines whose receptors lack protein kinase activity, phosphorylation-activation is mediated by members of the JAK family of tyrosine protein kinases. In the case of growth factors whose receptors have intrinsic tyrosine protein kinase activity, it is thought that Stat proteins can be activated either directly by the receptor or indirectly through JAK proteins. To test the possibility of direct activation, we have used purified Stat3 alpha, Stat3 beta, and epidermal growth factor receptor kinase produced in recombinant baculovirus-infected Sf9 insect cells. The Stat proteins formed a stable complex with the receptor kinase, and they were phosphorylated on tyrosine by the receptor kinase and activated for binding to DNA, properties shared with Stat proteins purified from Sf9 cells coexpressing JAK1 or JAK2. Both JAK-phosphorylated Stat3 beta and Stat3 beta phosphorylated in vitro by the receptor kinase were 20-50 times more active on a molar basis for DNA binding than phosphorylated Stat3 alpha. We conclude that Stat3 isoforms can be directly phosphorylated and thereby activated in vitro by the epidermal growth factor receptor kinase.
Quenched autoligation probes allow discrimination of live bacterial species by single nucleotide differences in rRNA (2005)

Quenched autoligation (QUAL) probes are a class of self-reacting nucleic acid probes that give strong fluorescence signal in the presence of fully complementary RNAs and selectivity against single nucleotide differences in solution. Here, we describe experiments designed to test whether QUAL probes can discriminate between bacterial species by the detection of small differences in their 16S rRNA sequences. Probes were introduced into live cells using small amounts of detergent, thus eliminating the need for fixation, and fluorescence signal was monitored both by microscopy and by flow cytometry without any washing steps. The effects of probe length, modified backbone, probe concentration and growth state of the bacteria were investigated. The data demonstrate specific fluorescence discrimination between three closely related bacteria, Escherichia coli, Salmonella enterica and Pseudomonas putida, based on single nucleotide differences in their 16S rRNA. Discrimination was possible with cells in mid-log phase or in lag phase. These results suggest that QUAL probes may be useful for rapid identification of microorganisms in laboratory and clinical settings.
A PROCESS FOR DEFLUORINATION AND PURIFICATION OF WET PROCESS PHOSPHORIC ACIDS CONTAINING HIGH Al CONCENTRATIONS. (1984)

Abstract A solvent extraction process is described for defluorination and desulfation of filter phosphoric acids with high Al content. The solvent used contain an amine and phosphoric acid as main constituents. The acid obtained is compatible with feed-grade requirements. It can be concentrated to 56–60% P2O5 by multiple effect evaporation, decreasing steam requirements by 50%. If an acid-base couple solvent is used in this process, part of the extracted phosphate can be recovered by back-wash with water in the form of highly purified phosphoric acid low in metals, fluorine and sulfate. The remainder of the acid along with the extracted sulfate is obtained as ammonium salt. The extracted F is converted into crystaline alkali fluorosilicate.
Functional Effects of a Pathogenic Mutation in Cereblon (CRBN) on the Regulation of Protein Synthesis via the AMPK-mTOR Cascade (2014)

Initially identified as a protein implicated in human mental deficit, cereblon (CRBN) was recently recognized as a negative regulator of adenosine monophosphate-activated protein kinase (AMPK) in vivo and in vitro. Here, we present results showing that CRBN can effectively regulate new protein synthesis through the mammalian target of rapamycin (mTOR) signaling pathway, a downstream target of AMPK. Whereas deficiency of Crbn repressed protein translation via activation of the AMPK-mTOR cascade in Crbn-knock-out mice, ectopic expression of the wild-type CRBN increased protein synthesis by inhibiting endogenous AMPK. Unlike the wild-type CRBN, a mutant CRBN found in human patients, which lacks the last 24 amino acids, failed to rescue mTOR-dependent repression of protein synthesis in Crbn-deficient mouse fibroblasts. These results provide the first evidence that Crbn can activate the protein synthesis machinery through the mTOR signaling pathway by inhibiting AMPK. In light of the fact that protein synthesis regulated by mTOR is essential for various forms of synaptic plasticity that underlie the cognitive functions of the brain, the results of this study suggest a plausible mechanism for CRBN involvement in higher brain function in humans, and they may help explain how a specific mutation in CRBN can affect the cognitive ability of patients.