gebhart/patrepeval huggingface dataset:
Biological and Technical Variables Affecting Immunoassay Recovery of Cytokines from Human Serum and Simulated Vaginal Fluid: A Multicenter Study (2008)

The increase of proinflammatory cytokines in vaginal secretions may serve as a surrogate marker of unwanted inflammatory reaction to microbicide products topically applied for the prevention of sexually transmitted diseases, including HIV-1. Interleukin (IL)-1beta and IL-6 have been proposed as indicators of inflammation and increased risk of HIV-1 transmission; however, the lack of information regarding detection platforms optimal for vaginal fluids and interlaboratory variation limit their use for microbicide evaluation and other clinical applications. This study examines fluid matrix variants relevant to vaginal sampling techniques and proposes a model for interlaboratory comparisons across current cytokine detection technologies. IL-1beta and IL-6 standards were measured by 12 laboratories in four countries, using 14 immunoassays and four detection platforms based on absorbance, chemiluminescence, electrochemiluminescence, and fluorescence. International reference preparations of cytokines with defined biological activity were spiked into (1) a defined medium simulating the composition of human vaginal fluid at pH 4.5 and 7.2, (2) physiologic salt solutions (phosphate-buffered saline and saline) commonly used for vaginal lavage sampling in clinical studies of cytokines, and (3) human blood serum. Assays were assessed for reproducibility, linearity, accuracy, and significantly detectable fold difference in cytokine level. Factors with significant impact on cytokine recovery were determined by Kruskal-Wallis analysis of variance with Dunn's multiple comparison test and multiple regression models. All assays showed acceptable intra-assay reproducibility; however, most were associated with significant interlaboratory variation. The smallest reliably detectable cytokine differences ( P < 0.05) derived from pooled interlaboratory data varied from 1.5- to 26-fold depending on assay, cytokine, and matrix type. IL-6 but not IL-1beta determinations were lower in both saline and phosphate-buffered saline as compared to vaginal fluid matrix, with no significant effect of pH. The (electro)chemiluminescence-based assays were most discriminative and consistently detected <2-fold differences within each matrix type. The Luminex-based assays were less discriminative with lower reproducibility between laboratories. These results suggest the need for uniform vaginal sampling techniques and a better understanding of immunoassay platform differences and cross-validation before the biological significance of cytokine variations can be validated in clinical trials. This investigation provides the first standardized analytic approach for assessing differences in mucosal cytokine levels and may improve strategies for monitoring immune responses at the vaginal mucosal interface.
Rheometry and associated techniques for blood coagulation studies (2007)

This review considers various rheometrical approaches that have been adopted to study blood coagulation, with special reference to the rheological assessment of clotting time and studies of the evolution of viscoelasticity during the course of fibrin polymerization and cross-linking. The significance of the Gel Point in blood coagulation studies is discussed as a common feature of many of these studies in that they attempt to detect a liquid-to-solid transition during coagulation. Coagulation studies based on various forms of complex shear modulus measurements are considered, the latter being based principally on controlled stress and controlled strain rheometers. Also considered are the long established technique of thromboelastography and several emerging techniques such as wave propagation measurements, free oscillation rheometry, quartz crystal microbalance measurements and surface plasmon resonance.
Discovery of a Novel Molecule that Regulates Tumor Growth and Metastasis (2008)

The heparan sulfate proteoglycan, Glypican-1 (GPC1), significantly impacts the growth of pancreatic cancer cells in vivo and markedly attenuates tumor angiogenesis and metastasis in athymic mice. Interestingly, both cancer cell-derived and host-derived GPC1 play an important role in tumor development and spread. These data suggest that GPC1 may be a valid therapeutic target for pancreatic cancer.
Asymptotic decay of radius of a weakly conductive viscous jet in an external electric field (1998)

Motion of a weakly conductive viscous jet accelerated by an external electric field is considered. Nonlinear rheological constitutive equation applicable for polymer fluids (Oswald–deWaele law) is applied. A differential equation for the variation of jet radius with axial coordinate is derived. Asymptotic variation of the jet radius at large distances from the jet origin is analyzed. It is found that the well-known power-law asymptote for Newtonian fluids with the exponent 1/4 holds for more general class of fluids, i.e., pseudoplastic (shear thinning) and dilatant (shear thickening) fluids with the flow index between 0 and 2. Dilatant fluids with the flow index greater than 2 exhibit power-law asymptotes with the exponents depending on the flow index. Results can be applied for the analysis of viscous polymer jets in the electrospinning process.
Combined scintigraphic and pharmacokinetic investigation of enteric‐coated mesalazine micropellets in healthy subjects (2003)

The 1.5 g micropellet formulation offers comparable delivery properties to the marketed tablets, but with greater convenience of dosing.
Photoperiod and Critical Duration for Flower Induction in Soybean1 (1978)

A photoperiod sensitive (sensitive) soybean [ Glycine max (L.) Merr.] line and photoperiod in sensitive (insensitive) line were used to determine the critical seedling stage before possible floral induction and the length of photoinduction required for anthesis. Seedlings of each entry were grown in pots and subjected to either a 10‐ hour or 16‐hour photoperiod. Beginning 3 days after emergence, two pots per entry in the 10‐hour room were exchanged daily with two pots from the 16‐hour photoperiod. No detectable differences between treatments were observed in the flowering time of the insensitive fine. However, the sensitive line exhibited the following: (i) The number of days to first flowering was not affected by the transfer from a 16‐hour to a 10‐hour photoperiod up to 9 days after emergence; (ii) Plants moved from a 10‐hour to a 16‐hour photoperiod before 36 days after emergence did not flower, indicating that induction was completed at 36 days after emergence; (iii) The earliest anthesis occurred 46 days after emergence. Therefore, we concluded that the induction period was 27 short days (10 hours) and that anthesis occurred 10 days after the completion of induction. The critical time to begin induction was 9 days after emergence for the sensitive line.
Three-Dimensional Fiber Deposition of Cell-Laden, Viable, Patterned Constructs for Bone Tissue Printing (2008)

Organ or tissue printing, a novel approach in tissue engineering, creates layered, cell-laden hydrogel scaffolds with a defined three-dimensional (3D) structure and organized cell placement. In applying the concept of tissue printing for the development of vascularized bone grafts, the primary focus lies on combining endothelial progenitors and bone marrow stromal cells (BMSCs). Here we characterize the applicability of 3D fiber deposition with a plotting device, Bioplotter, for the fabrication of spatially organized, cell-laden hydrogel constructs. The viability of printed BMSCs was studied in time, in several hydrogels, and extruded from different needle diameters. Our findings indicate that cells survive the extrusion and that their subsequent viability was not different from that of unprinted cells. The applied extrusion conditions did not affect cell survival, and BMSCs could subsequently differentiate along the osteoblast lineage. Furthermore, we were able to combine two distinct cell populations within a single scaffold by exchanging the printing syringe during deposition, indicating that this 3D fiber deposition system is suited for the development of bone grafts containing multiple cell types.
Cross-protection among lethal H5N2 influenza viruses induced by DNA vaccine to the hemagglutinin (1997)

Inoculation of mice with hemagglutinin (HA)-expressing DNA affords reliable protection against lethal influenza virus infection, while in chickens the same strategy has yielded variable results. Here we show that gene gun delivery of DNA encoding an H5 HA protein confers complete immune protection to chickens challenged with lethal H5 viruses. In tests of the influence of promoter selection on vaccine efficacy, close correlations were obtained between immune responses and the dose of DNA administered, whether a cytomegalovirus (CMV) immediate-early promoter or a chicken beta-actin promoter was used. Perhaps most important, the HA-DNA vaccine conferred 95% cross-protection against challenge with lethal antigenic variants that differed from the primary antigen by 11 to 13% (HA1 amino acid sequence homology). Overall, the high levels of protection seen with gene gun delivery of HA-DNA were as good as, if not better than, those achieved with a conventional whole-virus vaccine, with fewer instances of morbidity and death. The absence of detectable antibody titers after primary immunization, together with the rapid appearance of high titers immediately after challenge, implicates efficient B-cell priming as the principal mechanism of DNA-mediated immune protection. Our results suggest that the efficacy of HA-DNA influenza virus vaccine in mice extends to chickens and probably to other avian species as well. Indeed, the H5 preparation we describe offers an attractive means to protect the domestic poultry industry in the United States from lethal H5N2 viruses, which continue to circulate in Mexico.
Color image quantization for frame buffer display (1982)

Algorithms for adaptive, tapered quantization of color images are described. The research is motivated by the desire to display high-quality reproductions of color images with small frame buffers. It is demonstrated that many color images which would normally require a frame buffer having 15 bits per pixel can be quantized to 8 or fewer bits per pixel with little subjective degradation. In most cases, the resulting images look significantly better than those made with uniform quantization.
Targeting Tissue Factor for Immunotherapy of Choroidal Neovascularization by Intravitreal Delivery of Factor VII-Fc Chimeric Antibody (2007)

Both hICON and mICON bound to the neovascular endothelia of choroidal neovascularization with greater specificity than anti-von Willebrand antibody. Furthermore, mICON can selectively obliterate already established choroidal neovascularization, which suggests that it may be useful for immunotherapy in patients with exudative (wet) macular degeneration.
Role of strain and growth conditions on the growth front profile of InxGa1−xAs on GaAs during the pseudomorphic growth regime (1988)

Theoretical and experimental studies are presented to understand the initial stages of growth of InGaAs on GaAs. Thermodynamic considerations show that, as strain increases, the free-energy minimum surface of the epilayer is not atomically flat, but three-dimensional in form. Since by altering growth conditions the strained epilayer can be grown near equilibrium or far from equilibrium, the effect of strain on growth modes can be studied. In situ reflection high-energy electron diffraction studies are carried out to study the growth modes and surface lattice spacing before the onset of dislocations. The surface lattice constant does not change abruptly from that of the substrate to that of the epilayer at the critical thickness, but changes monotonically. These observations are consistent with the simple thermodynamic considerations presented.
Transcriptional Control of Cellular Metabolism by mTOR Signaling (2011)

Tumor cells are characterized by adaptations in cellular metabolism that afford growth and proliferative advantages over normal cells and, thus, contribute to cancer pathophysiology. There is an increasing appreciation of the fact that oncogenic signaling controls the metabolic reprogramming of cancer cells; however, the mechanisms and critical players are only beginning to be elucidated. Recent studies have revealed that mTOR complex 1 (mTORC1), a master regulator of cell growth and proliferation downstream of oncogenic signaling pathways, controls specific aspects of cellular metabolism through the induction of metabolic gene expression. mTORC1 activation is sufficient to promote flux through glycolysis and the oxidative branch of the pentose phosphate pathway, as well as to stimulate de novo lipogenesis, all processes that are important in tumor biology. As mTORC1 signaling is aberrantly elevated in the majority of genetic tumor syndromes and sporadic cancers, this pathway is poised to be a major driver of the metabolic conversion of tumor cells.
The short amino acid sequence Pro-His-Ser-Arg-Asn in human fibronectin enhances cell-adhesive function. (1994)

Synergistic sites in the central cell-adhesive domain of fibronectin (FN) substantially enhance cell adhesion mediated by the alpha 5 beta 1 integrin receptor for fibronectin. We characterized a critical minimal sequence needed for synergistic activity using site-directed mutagenesis and homology scanning using intramolecular chimeras. The minimal cell-binding domain of FN consisting of the 9th and 10th type III FN repeat was expressed in an Escherichia coli expression system. This protein retained high biological activity when assayed using a competitive inhibition assay for FN-mediated adhesion of baby hamster kidney or HT-1080 cells. In contrast, a construct consisting of the 8th and 10th repeat displayed very low biological activity. By replacing various portions of the 8th repeat with homologous 9th repeat segments, we mapped the synergistic region to the center of the 9th repeat. When a very short peptide sequence, Pro-His-Ser-Arg-Asn (PHSRN), from the 9th repeat was substituted for the homologous pentapeptide site in the 8th repeat sequence, the recombinant protein showed markedly enhanced activity. Further mutagenesis analysis suggested that the arginine residue of this pentapeptide sequence is important for function. We also identified a weaker adjacent synergy region other than the PHSRN region. Epitope mapping of an anti-FN monoclonal antibody that inhibits FN-mediated adhesion identified the same critical regions. A synthetic peptide containing the PHSRN sequence showed neither competitive inhibitory activity in solution nor synergy with a soluble RGD-containing peptide. However, when the same synthetic peptide was positioned via a covalent bond at the corresponding site of the normally inactive 8th repeat, it mediated an enhancement of adhesive activity. These results identify a pentapeptide site that synergistically enhances the cell-adhesive activity of the FN RGD sequence.
Frequency of BRAF T1796A mutation in papillary thyroid carcinoma relates to age of patient at diagnosis and not to radiation exposure (2005)

In this study, the frequency of BRAF mutation was investigated in a series of 67 cases of papillary thyroid cancer (PTC) in patients from Ukraine. Thirty-two patients were aged 30 years or older at the time of diagnosis and 35 were under 16. Tumour was microdissected from paraffin wax-embedded sections, DNA extracted, and the presence of the BRAF T1796A mutation demonstrated by two different methods: PCR followed by restriction enzyme digestion or primer extension assay and detection using MALDI-TOF mass spectrometry. Eighteen (58%) of the adult cases, but only one of the 35 cases aged less than 16 harboured a BRAF T1796A mutation. There was complete agreement between the two methods used, suggesting that the MALDI-TOF assay is a robust alternative to conventional mutation analysis. RET rearrangement was also examined in the young cohort. The overall frequency of RET rearrangement was 45.7%. Eight of the younger group of patients were born after 1 December 1986 and were therefore not exposed to radioiodine in fallout from Chernobyl. None of the PTCs from these eight patients were positive for BRAF mutation. The frequency of RET rearrangement was 44% in the 27 cases exposed to radiation and 50% in the eight not exposed. These results suggest that the different molecular biological profiles observed are associated with the age of the patient at diagnosis with PTC, rather than being associated with radiation exposure.
The Amino Acid Sequence of Rat Liver Glucokinase Deduced from Cloned cDNA (1989)

Rat liver glucokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) was purified to homogeneity, cleaved, and subjected to amino acid sequence analysis. Forty-five percent of the protein sequence was obtained, and this information was used to design oligonucleotide probes to screen a rat liver cDNA library. A 1601-base pair cDNA (GK1) contained an open reading frame that encoded the amino acid sequences found in the peptides used to generate the oligonucleotide probes. A second cDNA was subsequently identified (GK.Z2), which is 2346 base pairs long and corresponds to nearly the entire glucokinase mRNA. Blot transfer analysis of hepatic RNA showed that glucokinase mRNA exists as a single species of about 2400 nucleotides. Four hours of insulin treatment of diabetic rats resulted in a 30-fold induction of this mRNA. GK.Z2 has a long open reading frame which, with the known partial peptide sequence, allowed us to deduce the primary structure of glucokinase. The enzyme is composed of 465 amino acids and has a mass of 51,924 daltons. Glucokinase has 53 and 33% amino acid sequence identities with the carboxyl-terminal domains of rat brain hexokinase I and yeast hexokinase, respectively. If conservative amino acid replacements are also considered, glucokinase is similar to these two enzymes at 75 and 63% of positions, respectively. The putative glucose- and ATP-binding domains of glucokinase were identified, and these regions appear to be highly conserved in the hexokinase family of enzymes.
Characterization of Two Naturally Occurring Mutations in the Second Epidermal Growth Factor-Like Domain of Factor VII (1999)

We investigated the mechanisms responsible for severe factor VII (FVII) deficiency in homozygous Italian patients with either Gly97Cys or Gln100Arg mutations in the second epidermal growth factor domain of FVII. Transient expression of complementary DNA coding for the mutations in COS-1 cells showed impaired secretion of the mutant molecules. Using stably transfected Chinese hamster ovary (CHO) cells, we performed pulse-chase labeling studies, immunohistochemistry, and experiments with inhibitors of protein degradation, showing that FVII-Cys97 did not accumulate intracellularly but was degraded in a pre-Golgi, nonlysosomal compartment by a cysteine protease. In stably transfected CHO cells expressing FVII-Arg100, the level of intracellular FVII was not increased by several inhibitors of protein degradation, but FVII-Arg100 was retained in the endoplasmic reticulum for a longer period of time than wild-type FVII. FVII-Arg100 had a lower apparent molecular weight than did wild-type FVII under nondenaturing conditions, which is attributable to misfolding due to abnormal disulfide bond formation.
Old Drugs as New Treatments for Neurodegenerative Diseases (2018)

Neurodegenerative diseases are increasing in number, given that the general global population is becoming older. They manifest themselves through mechanisms that are not fully understood, in many cases, and impair memory, cognition and movement. Currently, no neurodegenerative disease is curable, and the treatments available only manage the symptoms or halt the progression of the disease. Therefore, there is an urgent need for new treatments for this kind of disease, since the World Health Organization has predicted that neurodegenerative diseases affecting motor function will become the second-most prevalent cause of death in the next 20 years. New therapies can come from three main sources: synthesis, natural products, and existing drugs. This last source is known as drug repurposing, which is the most advantageous, since the drug&rsquo;s pharmacokinetic and pharmacodynamic profiles are already established, and the investment put into this strategy is not as significant as for the classic development of new drugs. There have been several studies on the potential of old drugs for the most relevant neurodegenerative diseases, including Alzheimer&rsquo;s disease, Parkinson&rsquo;s disease, Huntington&rsquo;s disease, Multiple Sclerosis and Amyotrophic Lateral Sclerosis.
Inhibition of Thyroidal Iodotyrosine Deiodination byTyrosine Analogues (1968)

The effect of several tyrosine derivatives on deiodination of 3,5-diiodo-L-tyrosine (DIT) has been examined in vitro and in vivo. In TPNH-supplemented sheep thyroid homogenates, the most effective inhibitors of deiodination, in order of increasing potency, were 3,5-dibromo-L-tyrosine (DBT), 3,5-dinitro- L-tyrosine (DNT) and 3-nitro-L-tyrosine (MNT); kinetic studies suggested purely competitive inhibition. Compounds with weak or no inhibitory activity included tyrosine itself, its 3-methyl-, 3-isopropyl-, 3-ra-propyl-, and 3- amino- derivatives, and 3,4-dihydroxy-L-phenylalanine. DBT, DNT and MNT also inhibited deiodination of DIT by sheep thyroid slices. In rats, administration of DBT, DNT, or MNT with 131I-DIT inhibited deiodination, and led to the appearance of an unknown DIT metabolite in blood and urine. Administration of the most potent in. vitro inhibitor, MNT, to rats prelabeled with radioiodine was followed by the urinary excretion of large amounts of a similar unknown organic iodine compound, together with small amounts of DIT and of monoiodotyrosine. This result suggests that MNT can inhibit the deiodination of endogenously formed iodotyrosines. (Endocrinology83: 336, 1968)
Integrated on-chip energy storage using porous-silicon electrochemical capacitors (2014)

Integrated on-chip energy storage is increasingly important in the fields of internet of things, energy harvesting, and wearables with capacitors being ideal for devices requiring higher powers, low voltages, or many thousands of cycles. This work demonstrates electrochemical capacitors fabricated using porous Si nanostructures with very high surface-to-volume ratios and an electrolyte. Stability is achieved through ALD TiN or CVD carbon coatings. The use of Si processing methods creates the potential for on-chip energy storage.
Pharmacological profile and clinical trial results of a long-acting, once weekly human GLP-1 receptor agonist Dulaglutide (Genetical Recombination) (2015)

デュラグルチド（遺伝子組換え）は，ジペプチジルペプチダーゼ-4（DPP-4）による分解を抑制するためにヒトグルカゴン様ペプチド-1（GLP-1）にアミノ酸置換を導入したGLP-1アナログを，ペプチドリンカーを介してヒト免疫グロブリン重鎖（IgG4 Fc）領域に結合したFc融合タンパク質であり，週1回皮下投与が可能な持効型GLP-1受容体作動薬である．本薬はヒトGLP-1受容体に選択的に結合し，GLP-1と同程度の受容体活性化能を示したほか，膵島細胞においてグルコース濃度依存的なインスリン分泌促進作用を示した．Fcγ受容体を介した抗体依存性細胞傷害活性は認められなかった．また，ラットおよびサルにおいてグルコース濃度依存的なインスリン分泌の促進が持続的に認められ，2型糖尿病病態モデルマウスで血糖降下作用および体重低下作用を示した．ヒトにおける消失半減期は約4.5日であり，週1回投与による曝露の持続が示された．日本人2型糖尿病患者を対象とした国内第Ⅱ相臨床試験において，0.75 mg週1回投与によりプラセボ投与群と比較して統計学的に有意なHbA1cの改善ならびに空腹時血糖および7点自己血糖測定を含む血糖パラメータの用量依存的な低下が認められた．本剤の安全性プロファイルはヒトGLP-1由来のリラグルチドと同様であり，exendin-4由来のGLP-1受容体作動薬と比べて胃腸障害，注射部位反応および抗薬物抗体産生の発現割合は低かった．本剤は投与開始時の用量漸増が不要であり，単独療法および他の血糖降下薬との併用療法が可能である．また，本薬の皮下投与用デバイスである自動注入器には，あらかじめ薬液が充填された固定針付きシリンジが組み込まれているため，用時調製の必要がない．本剤は有効性，安全性ならびに利便性の観点から，多くの2型糖尿病患者にとって使用しやすい薬剤となることが期待される．
Synthesis and herbicidal activities of a series of di(aminopyrazoly) ketone derivatives (2007)

Abstract magnified image In order to obtain new lead compounds with high herbicidal activity, a series of 5‐amino pyrazole derivatives were designed and synthesized using a series of relational synthons. Their structures were determined by IR, 1 H NMR, and elemental analyses. These compounds were screened for herbicidal activities against rape and barnyard grass. Their structure‐activity relationships are discussed.