gebhart/patrepeval huggingface dataset:
Topically Effective Acetazolamide Eye-drop Solution in Man (1996)

Drug-cyclodextrin polymer co-complexes increase the solubility of lipophilic drugs in aqueous solutions, such as eye-drops, without affecting their lipophilicity. Also, the co-complexes are able enhance the ocular availability of the drug after topical administration.

The anhydrase inhibitor acetazolamide was solubilized in an aqueous eye-drop formulation through formation of a co-complex with 2-hydroxypropyl-β-cyclodextrin and hydroxypropyl methylcellulose. The intraocular pressure (IOP)-lowering activity of a 1% (w/v) acetazolamide eye-drop solution was evaluated in nine ocular hypertensive patients. The patients were given the eye-drops three times a day for 28 days. Maximum IOP lowering activity was observed at 9 a m, 2 h after installation of the drops, with a mean IOP-lowering of 15.6 ± 8.9%.

Through HP-β-CD-HPMC co-complex formation, it was possible to obtain a topically active aqueous acetazolamide eye-drop solution. In man, the 1% (w/v) acetazolamide eye-drop solution had less IOP-lowering activity than an aqueous 2% (w/v) dorzolamide eye-drop solution.
Acute non‐oliguric kidney failure and cholestatic hepatitis induced by ibuprofen and acetaminophen: a case report (2009)

The combined ibuprofen and acetaminophen treatment, even if administered at therapeutic dosages and in a reduced number of doses, may be dangerous in conditions of volume depletion.
Comparison of the cardiovascular effects of the α2‐adrenoceptor agonist, dexmedetomidine, in rats and rabbits (1993)

Abstract Dexmedetomidine is a potent, specific, and selective α 2 ‐adrenoceptor agonist undergoing clinical trials as an adjunct to anesthesia. It may also have potential use in the treatment of glaucoma. In anesthetized rats and rabbits, dexmedetomidine induced marked bradycardia, rats being 5 times more sensitive than rabbits. In conscious rabbits, the bradycardia induced by dexmedetomidine was even less apparent; a dose of 40 αg/kg ws needed to consistently slow the pulse. Higher doses of dexmedetomidine induce a direct vasoconstrictor response in the anesthetized animals, in the case rabbits were 9 times less sensitive than rats. In both tests the anesthetized rat better mimicked the sensitivity of humans to dexmedetomidine. Thus, it should be remembered that in ocular pharmacology, where the rabbit is the prevalent experimental animal used, this species is relatively insensitive to the cardiovascular effects of this novel α 2 ‐adrenoceptor agonist. © Wiley‐Liss, Inc.
Analysis of Fatty Acid Composition of Thevetia peruviana and Hura crepitans Seed oils using GC-FID (2013)

Fatty acids were extracted from Thevetia peruviana and Hura crepitans seed oils. The quantitative determination of fatty acid composition was carried out for each sample by methylation and application of gas chromatograph (GC-FID). The predominant fatty acids in the T. peruviana and H. crepitans are Palmitic acid (19.10% and 21.67%), Stearic acid (7.31% and 9.66%), Oleic acid (53.40% and 26.91%) and Linoleic acid (19.03% and 36.61%) respectively. In the two oils, the ratios of unsaturated fatty acid were very high about 73% for T. peruviana and 64% for H. crepitans which is an indication that both would be very good sources of oleochemicals for polymer and other industries.
특집논문 1 : 조선후기 인쇄술의 발전, 서적의 보급 그리고 실학 지식의 소통 ; 중국서적을 중심으로 본 조선후기 출판과 장서(藏書)문화의 신국면 (2010)

17세기 무렵, 대량의 중국서적이 국내로 수입되어 서적의 유동량을 증가시켰고 특권층에게 국한되어 있던 장서문화를 확산하는 데 일조하였다. 그 결과 약 천 권의 장서를 건립한 사인들이 상당수 등장하였으며 장서는 사대부로서의 소양을 증명하고 사명을 실천하는 도구로 자리잡게 되었다. 또 중국본 장서가와 무관장서가 등 이전 시기까지 보이지 않았던 새로운 장서가가 등장하고 장서의 체계적인 수집과 관리를 위해 개인 장서목록 및 정보서목 등을 제작하는 등 장서문화의 새로운 국면이 나타났다. 그러나 하응운가의 소장서를 중심으로 살펴본 18세기 민간의 장서는 과거시험에 대비하고 사대부로서의 교양을 쌓기에 필요한 유가적 텍스트 가 대부분이었고, 조정에서 번각한 중국서적 역시 17~18세기 동시대 중 국인의 저작은 한 건도 없고 정통주자학의 권위를 가지고 있는 송대와 명초의 저작들만이 재생산되어 보급되고 있었다. 이것은 교육과 교화에 필요한 최소한의 중국서적, 그것도 주자학의 기준에 부합하는 전통적 권 위를 가진 서적들만 보급되어야 한다는 인식에서 비롯된 것이다. 이러한 생각에서 서유구나 유수원, 이덕무 같은 실학가들은 인쇄본이 무조건 증가하는 것에도 반대했다. 서적의 출판과 수집이 교육과 교화에 활용될 수 있도록 발전해야 한다는 생각이었다. 이처럼 조선후기 서적과 출판문화를 보수적으로 운영하고자 했던 바람은 자유로운 출판업 발달을 늦춘 하나의 요인이 되었을 것이다. 그러나 인쇄본의 무분별한 증가에 대 한 우려에서도 알 수 있듯이, 조선후기 민간출판은 사인의 장서목록에서 보이는 것보다는 훨씬 확산되고 있었다.
A Small Molecule Agonist of an Integrin, αLβ2 (2006)

The binding of integrin alpha(L)beta(2) to its ligand intercellular adhesion molecule-1 is required for immune responses and leukocyte trafficking. Small molecule antagonists of alpha(L)beta(2) are under intense investigation as potential anti-inflammatory drugs. We describe for the first time a small molecule integrin agonist. A previously described alpha/beta I allosteric inhibitor, compound 4, functions as an agonist of alpha(L)beta(2) in Ca(2+) and Mg(2+)and as an antagonist in Mn(2+). We have characterized the mechanism of activation and its competitive and noncompetitive inhibition by different compounds. Although it stimulates ligand binding, compound 4 nonetheless inhibits lymphocyte transendothelial migration. Agonism by compound 4 results in accumulation of alpha(L)beta(2) in the uropod, extreme uropod elongation, and defective de-adhesion. Small molecule integrin agonists open up novel therapeutic possibilities.
Structure and Enzymatic Functions of Human CD38 (2006)

CD38 is a novel multifunctional protein that serves not only as an antigen but also as an enzyme. It catalyzes the metabolism of cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate, two structurally and functionally distinct Ca2+ messengers targeting, respectively, the endoplasmic reticulum and lysosomal Ca2+ stores. The protein has recently been crystallized and its three-dimensional structure solved to a resolution of 1.9 Å. The crystal structure of a binary complex reveals critical interactions between residues at the active site and a bound substrate, providing mechanistic insights to its novel multi-functional catalysis. This article reviews the current advances in the understanding of the structural determinants that control the multiple enzymatic reactions catalyzed by CD38.
Pulmonary surfactant: No mere paint on the alveolar wall (1996)

The gas-liquid interface within the alveolus is completely lined with a complex mixture of lipids and unique proteins termed pulmonary surfactant, which both reduces surface tension and permits it to vary directly with the radius of curvature. In this way it minimizes the work of breathing and permits alveoli of different sizes to exist in equilibrium. However, surfactant does far more in that it also controls fluid balance in the lung and appears to play a key role in host defence. Either a deficiency in surfactant or an aberrant surfactant results in atelectasis and oedema. The surfactant system is very dynamic: alveolar surfactant phosphatidylcholine, the principal component, having a half life of only a few hours, with as much as 85% being recycled. Although distortion of the alveolar type II cell is now accepted as the principal stimulus for release, much remains to be discovered of modulating factors and intracellular signalling in the control of surfactant homeostasis. Likewise, many questions remain concerning the control of synthesis of the surfactant phospholipids, neutral lipids and proteins and their assembly into the tubular myelin form of alveolar surfactant, the refining of the monolayer with breathing, the control of re-uptake of different components into the type II cells and the roles of the proteins.
Relaxing the substrate specificity of an aminoacyl‐tRNA synthetase allows in vitro and in vivo synthesis of proteins containing unnatural amino acids (1995)

It has previously been demonstrated that the unnatural amino acid p-Cl-phenylalanine can be attached to tRNA(Phe) by a modified phenylalanyl-tRNA synthetase with relaxed amino acid substrate specificity. We show that this modification to the translational machinery of Escherichia coli is the only requirement for the incorporation of either p-Cl- or p-Br-phenylalanine into full-length luciferase in vitro. The incorporation of p-Cl-phenylalanine was also demonstrated in vivo using a suitably modified host strain. These results represent the first description of the incorporation into a protein in vivo of an unnatural amino acid which is normally rejected by the cellular translational machinery.
Ocular blood flow velocities in patients with proliferative diabetic retinopathy and healthy volunteers: a prospective study. (1995)

Ocular blood flow velocity was decreased in diabetic patients with proliferative diabetic retinopathy.
Thermally induced error: Density limit for magnetic data storage (2012)

Magnetic data storage is pervasive in the preservation of digital information, and the rapid pace of computer development requires ever more capacity. Increasing the storage density for magnetic hard disk drives requires a reduced bit size, previously thought to be limited by the thermal stability of the constituent magnetic grains. The limiting storage density in magnetic recording is investigated treating the writing of bits as a thermodynamic process. A “thermal writability” factor is introduced and it is shown that storage densities will be limited to 15 to 20 TBit/in2 unless technology can move beyond the currently available write field magnitudes.
Knee Joint Simulator (1973)

*State University of New York. Upstate Medical Center, 750 East Adams Street Syracuse, New York 13210
Belimumab Human Genome Sciences/Cambridge Antibody Technology/GlaxoSmithKline. (2006)

Belimumab, the lead in a series of human monoclonal antibodies against the human protein B-lymphocyte stimulator (BLyS), is under development by Human Genome Sciences, Cambridge Antibody Technology and GlaxoSmithKline for the potential treatment of autoimmune diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). By January 2006, belimumab had completed phase II clinical trials in SLE and RA; a phase III clinical SLE trial is scheduled to begin later this year.
Design of 5′ Untranslated Sequences in Retroviral Vectors Developed for Medical Use (1999)

Utilizing genetic modules of simple retroviruses, we have developed a novel generation of gene transfer vectors with improved therapeutic potential. In the 5' untranslated "leader" sequences, all AUG codons which may aberrantly initiate translation and all viral coding sequences were removed. Thus, the probability of expressing unwanted peptides and the potential for homologous recombination with retroviral genes were largely reduced, and the cloning capacity was increased. The transgene was inserted to replace the viral gag sequences, and a new minimal splice acceptor was introduced, resulting in increased expression with all genes tested (those coding for human multidrug resistance 1 and enhanced green fluorescent protein, as well as the lacZ gene). These vectors may represent attractive tools for human gene therapy, because they increase the efficiency of transgene expression and may also increase safety in medical applications.
Repair or replace? Exploiting novel gene and cell therapy strategies for muscular dystrophies (2013)

Muscular dystrophies are genetic disorders characterized by skeletal muscle wasting and weakness. Although there is no effective therapy, a number of experimental strategies have been developed over recent years and some of them are undergoing clinical investigation. In this review, we highlight recent developments and key challenges for strategies based upon gene replacement and gene/expression repair, including exon-skipping, vector-mediated gene therapy and cell therapy. Therapeutic strategies for different forms of muscular dystrophy are discussed, with an emphasis on Duchenne muscular dystrophy, given the severity and the relatively advanced status of clinical studies for this disease.
Primary structure of T4 DNA polymerase. Evolutionary relatedness to eucaryotic and other procaryotic DNA polymerases. (1988)

Bacteriophage T4 gene 43 codes for the viral DNA polymerase. We report here the sequence of gene 43 and about 70 nucleotides of 5'- and 3'-flanking sequences, determined by both DNA and RNA sequencing. We have also purified T4 DNA polymerase from T4 infected Escherichia coli and from E. coli containing a gene 43 overexpression vector. A major portion of the deduced amino acid sequence has been verified by peptide mapping and sequencing of the purified DNA polymerase. All these results are consistent with T4 DNA polymerase having 898 amino acids with a calculated Mr = 103,572. Comparison of the primary structure of T4 DNA polymerase with the sequence of other procaryotic and eucaryotic DNA polymerases indicates that T4 DNA polymerase has regions of striking similarity with animal virus DNA polymerases and human DNA polymerase alpha. Surprisingly, T4 DNA polymerase shares only limited similarity with E. coli polymerase I and no detectable similarity with T7 DNA polymerase. Based on the location of specific mutations in T4 DNA polymerase and the conservation of particular sequences in T4 and eucaryotic DNA polymerases, we propose that the NH2-terminal half of T4 DNA polymerase forms a domain that carries out the 3'----5' exonuclease activity whereas the COOH-terminal half of the polypeptide contains the dNTP-binding site and is necessary for DNA synthesis.
Hox11genes establish synovial joint organization and phylogenetic characteristics in developing mouse zeugopod skeletal elements (2010)

Hox11 genes are essential for zeugopod skeletal element development but their roles in synovial joint formation remain largely unknown. Here, we show that the elbow and knee joints of mouse embryos lacking all Hox11 paralogous genes are specifically remodeled and reorganized. The proximal ends of developing mutant ulna and radius elements became morphologically similar and formed an anatomically distinct elbow joint. The mutant ulna lacked the olecranon that normally attaches to the triceps brachii muscle tendon and connects the humerus to the ulna. In its place, an ulnar patella-like element developed that expressed lubricin on its ventral side facing the joint and was connected to the triceps muscle tendon. In mutant knees, both tibia and fibula fully articulated with an enlarged femoral epiphyseal end that accommodated both elements, and the neo-tripartite knee joint was enclosed in a single synovial cavity and displayed an additional anterior ligament. The mutant joints also exhibited a different organization of the superficial zone of articular cartilage that normally exerts an anti-friction function. In conclusion, Hox11 genes co-regulate and coordinate the development of zeugopod skeletal elements and adjacent elbow and knee joints, and dictate joint identity, morphogenesis and anatomical and functional organization. Notably, the ulnar patella and tripartite knee joints in the mouse mutants actually characterize several lower vertebrates, including certain reptiles and amphibians. The re-emergence of such anatomical structures suggests that their genetic blueprint is still present in the mouse genome but is normally modified to the needs of the mammalian joint-formation program by distinct Hox11 function.
Production and Screening of Cell Hybrids Producing a Monoclonal Antibody to Human Interferon- (1981)

Mice and rats were immunized with human lymphoblastoid interferon, a mixture of human leukocyte (interferon-alpha) and human fibroblast (interferon-beta) interferons, and their serum anti-interferon levels measured. Anti-interferon activity was detected in all animals, although the mouse sera had higher titers than the rat sera. The spleens of two mice were removed and used to prepare hybrid myelomas. Anti-interferon activity in tissue culture supernatants was measured using a direct neutralization assay and a clone (NK2) producing antibody to human interferon-alpha (leukocyte) was isolated. The anti-interferon activity of this monoclonal antibody was confirmed using a new indirect immunoprecipitation (IIP) assay, which shows some advantages over the direct neutralization assay. The antibody did not neutralize human interferon-beta (fibroblast) or mouse interferon.
C-C chemokine–encoding DNA vaccines enhance breakdown of tolerance to their gene products and treat ongoing adjuvant arthritis (2000)

Depending on the method of immunization, a single administration of CFA may result in the development of a local inflammatory process or chronic polyadjuvant-induced arthritis (AA). We administered naked DNA vaccines encoding MIP-1 alpha, MCP-1, MIP-1 beta, and RANTES to Lewis rats and confirmed that each of these vaccines induced immunological memory to the corresponding gene product. Upon induction of disease, this memory effectively inhibited the development of the autoimmune condition. Self-specific Ab's developed in DNA-vaccinated animals were neutralizing in vitro and could adoptively transfer the beneficial effect of each vaccine. Repeated administration of the constructs encoding MCP-1, MIP-1 alpha, or RANTES inhibited the development and progression of AA, even when each vaccine was administered only after the onset of disease. This suggests a highly effective way by which the immune system could be re-educated to generate protective immunity against its own harmful activities.
A modified formula for calculating low-density lipoprotein cholesterol values (2010)

Compared with the FF calculation, serum LDL-C values estimated by our modified formula are closer to those measured by a direct assay. The modification significantly diminishes the interference caused by hypertriglyceridemia.
Autocrine Bone Morphogenetic Protein-9 Signals through Activin Receptor-like Kinase-2/Smad1/Smad4 to Promote Ovarian Cancer Cell Proliferation (2009)

Bone morphogenetic proteins (BMPs) act as central regulators of ovarian physiology and may be involved in ovarian cancer development. In an effort to understand these processes, we characterized transforming growth factor beta/BMP receptor and Smad expression in immortalized ovarian surface epithelial cells and a panel of ovarian cancer cell lines. These studies prompted us to evaluate the potential role of BMP9 signaling in ovarian cancer. Using small interfering RNA, ligand trap, inhibitor, and ligand stimulation approaches, we show that BMP9 acts as a proliferative factor for immortalized ovarian surface epithelial cells and ovarian cancer cell lines, signaling predominantly through an ALK2/Smad1/Smad4 pathway rather than through ALK1, the major BMP9 receptor in endothelial cells. Importantly, we find that some ovarian cancer cell lines have gained autocrine BMP9 signaling that is required for proliferation. Furthermore, immunohistochemistry analysis of an ovarian cancer tissue microarray reveals that approximately 25% of epithelial ovarian cancers express BMP9, whereas normal human ovarian surface epithelial specimens do not. Our data indicate that BMP9 signaling through ALK2 may be a novel therapeutic target in ovarian cancer.
An Inductive Link-Based Wireless Power Transfer System for Biomedical Applications (2012)

A wireless power transfer system using an inductive link has been demonstrated for implantable sensor applications. The system is composed of two primary blocks: an inductive power transfer unit and a backward data communication unit. The inductive link performs two functions: coupling the required power from a wireless power supply system enabling battery-less, long-term implant operation and providing a backward data transmission path. The backward data communication unit transmits the data to an outside reader using FSK modulation scheme via the inductive link. To demonstrate the operation of the inductive link, a board-level design has been implemented with high link efficiency. Test results from a fabricated sensor system, composed of a hybrid implementation of custom-integrated circuits and board-level discrete components, are presented demonstrating power transmission of 125 mW with a 12.5% power link transmission efficiency. Simultaneous backward data communication involving a digital pulse rate of up to 10 kbps was also observed.
Attraction and Trapping of Aedes aegypti (Diptera: Culicidae) with Host Odors in the Laboratory (1996)

Volatile constituents of mouse odor were eluted from an adsorbent after collection within a closed-air system, and offered to host-seeking yellowfever mosquitoes, Aedes aegypti (L.), in the laboratory. Gas chromatographic analysis showed that individual mouse odors varied in blend, both quantitatively and qualitatively. In a 2-choice bioassay, sticky traps baited with individual mouse odors caught more female mosquitoes than controls (69% caught on baited traps) in all cases. When 2 traps baited with volatiles from the empty collection system were used, no preference occurred (46 and 54%), and fewer mosquitoes (22% of total) were caught overall than when a baited trap was present (46% of total). Equal numbers of male mosquitoes were caught on baited and control traps. Results demonstrated that Ae. aegypti can be attracted to entrained and eluted host odor without the addition of other attractants.
Cost - effective integration of immunization and basic health services in developing countries : the problem of joint costs (1988)

With limited budgets for rural primary health care, developing countries are under pressure to integrate the basic medical services that government health centres provide, with the vaccination programs that mobile immunization teams handle. Application of cost effectiveness analysis is complicated by two inherent difficulties. First, because the two types of health care programs improve the health of different target groups, some common measure of the effectiveness of the two programs must be agreed upon. Here thehealthy life yearssaved by the two alternatives is implemented as a useful measure of effectiveness. The second difficulty is that of modelling the joint costs of simultaneously producing more than one health care service. Using the method described here, economists can address this problem in a way that does justice to both the superior efficiency of the mobile teams and the superior comprehensiveness of the fixed centres.
A Potent In Vivo Antitumor Efficacy of Novel Recombinant Type I Interferon (2016)

<b>Purpose:</b> Antiproliferative, antiviral, and immunomodulatory activities of endogenous type I IFNs (IFN1) prompt the design of recombinant IFN1 for therapeutic purposes. However, most of the designed IFNs exhibited suboptimal therapeutic efficacies against solid tumors. Here, we report evaluation of the <i>in vitro</i> and <i>in vivo</i> antitumorigenic activities of a novel recombinant IFN termed sIFN-I.<b>Experimental Design:</b> We compared primary and tertiary structures of sIFN-I with its parental human IFNα-2b, as well as affinities of these ligands for IFN1 receptor chains and pharmacokinetics. These IFN1 species were also compared for their ability to induce JAK-STAT signaling and expression of the IFN1-stimulated genes and to elicit antitumorigenic effects. Effects of sIFN-I on tumor angiogenesis and immune infiltration were also tested in transplanted and genetically engineered immunocompetent mouse models.<b>Results:</b> sIFN-I displayed greater affinity for IFNAR1 (over IFNAR2) chain of the IFN1 receptor and elicited a greater extent of IFN1 signaling and expression of IFN-inducible genes in human cells. Unlike IFNα-2b, sIFN-I induced JAK-STAT signaling in mouse cells and exhibited an extended half-life in mice. Treatment with sIFN-I inhibited intratumoral angiogenesis, increased CD8<sup>+</sup> T-cell infiltration, and robustly suppressed growth of transplantable and genetically engineered tumors in immunodeficient and immunocompetent mice.<b>Conclusions:</b> These findings define sIFN-I as a novel recombinant IFN1 with potent preclinical antitumorigenic effects against solid tumor, thereby prompting the assessment of sIFN-I clinical efficacy in humans. <i>Clin Cancer Res; 23(8); 2038-49. ©2016 AACR</i>.