gebhart/patrepeval huggingface dataset:
Cellular and molecular mechanisms underlying muscular dystrophy (2013)

The muscular dystrophies are a group of heterogeneous genetic diseases characterized by progressive degeneration and weakness of skeletal muscle. Since the discovery of the first muscular dystrophy gene encoding dystrophin, a large number of genes have been identified that are involved in various muscle-wasting and neuromuscular disorders. Human genetic studies complemented by animal model systems have substantially contributed to our understanding of the molecular pathomechanisms underlying muscle degeneration. Moreover, these studies have revealed distinct molecular and cellular mechanisms that link genetic mutations to diverse muscle wasting phenotypes.
Profile of plasma N-terminal proBNP following acute myocardial infarction. Correlation with left ventricular systolic dysfunction (2000)

A biphasic pattern of plasma N-terminal pro-brain natriuretic peptide is seen after anterior myocardial infarction. Plasma level is strongly correlated to wall motion index soon after and remote from acute myocardial infarction. Plasma N-terminal pro-brain natriuretic peptide measured later in hospitalization better predicts poor outcome following myocardial infarction than when it is measured in the immediate post infarction period.
Process Stabilization at welding Copper by Laser Power Modulation (2011)

Due to their material properties such as high electrical and thermal conductivity, copper materials are more and more demanded for industrial applications. The same material properties make laser welding of copper a challenging task. Laser welds often suffer from defective weld seams with ejections, pores and a large fluctuation in the penetration depth. In this paper the influence of laser power modulation during copper welding on weld imperfections is discussed. It is shown that a sinusoidal power modulation leads to a strong reduction of melt ejections and also to an increase in penetration depth.
The effect of thrombospondin on invasion of fibrin gels by human A549 lung carcinoma. (1993)

Thrombospondin (TSP) was evaluated for its effect on the capacity of human A549 lung adenocarcinoma cells to invade and degrade fibrin gels. Cells suspended in DMEM containing 0.01 units/mL plasminogen were added to a 2.5 mm diameter well in a 2 mm thick fibrin gel. Various concentrations of TSP were added either to the cells or to the gel. After 18 hours, the number of spread and gel-adherent cells were counted and the diameter of the well was measured to determine the extent of tumor-induced fibrinolysis. In the absence of TSP, the tumor cells were non-adherent but catalyzed the rapid degradation of the fibrin gel, causing the application well to increase in diameter several-fold. In contrast, addition of either TSP to the gel or to the cell suspension inhibited fibrinolysis in a dose-dependent manner and promoted attachment and spreading of cells in the fibrin matrix. In contrast, fibronectin had no effect. The effect of TSP on both tumor cell-associated fibrinolysis and cell adhesion was inhibited with an anti-TSP monoclonal antibody. The cell adhesive peptides CSVTCG, derived from the type 1 repeats of TSP, and GRGDS also had no effect on tumor cell-associated fibrinolysis. TSP inhibited fibrinolysis by inhibiting tumor cell-secreted urokinase activity, but had no effect on total urokinase secreted-antigen. In contrast, cell-associated urokinase activity was protected from inhibition by TSP. These results suggest that TSP may promote tumor cell metastasis not only by promoting cell-attachment but also by protecting tumor cell-fibrin emboli from degradation by tumor secreted- and host fibrinolytic enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)
ChemInform Abstract: NEW TYPE OF MESOIONIC SYSTEM, 1,3‐DIPOLAR CYCLOADDITION OF ANHYDRO‐4‐HYDROXY‐1,3‐OXAZOLIUM HYDROXIDE WITH ACETYLENIC COMPOUNDS (1975)

Abstract Bei der Zersetzung der Diazoverbindung (I) erhält man über das Carben (II) das mesoionische 1,3‐Oxazol‐4‐on (III), aus dem in Gegenwart von Acetylendicarbonsäureester (IV) bei 80°C ein Gemisch der beiden Reaktionsprodukte (V) und (VI) erhalten wird.
Growth dependency of a new human pancreatic cancer cell line, YAPC, on autocrine interleukin-1α stimulation (1998)

We established a new human pancreatic cancer cell line from the malignant ascites of a patient with pancreatic cancer and called it YAPC. Cytogenetic and morphological analysis indicated that this cell line is monoclonal and of human origin. YAPC cells grow in nude mice, resulting in the formation of a tumor with some functional characteristics of the original tumor. The cells secreted a large amount of inflammatory cytokines including interleukin-1alpha(IL-1alpha), IL-6 and IL-8 in the culture medium. Removal of serum from the culture medium did not change the growth rate of YAPC cells, but the removal of the conditioned medium arrested their proliferation under the serum-free conditions. Exogenous IL-1alpha but neither IL-6 nor IL-8 stimulated DNA synthesis of the cells and accelerated the progress of cell cycle from G1 to the S phase. Anti-IL-1alpha antibody prevented growth of the cells in a dose-dependent fashion. In this pancreatic cancer cell line cell growth is dependent on IL-1alpha in an autocrine fashion. This line may be a useful model for studying growth regulation mechanisms of pancreatic cancer.
Lipid‐based nanotherapeutics for siRNA delivery (2009)

RNA interference (RNAi) is a specific gene-silencing mechanism triggered by small interfering RNA (siRNA). The application of RNAi in the clinic requires the development of safe and effective delivery systems. Inspired by progress with lipid-based systems in drug delivery, efforts have been dedicated to the development of liposomal siRNA delivery systems. Many of the lipid-based delivery vehicles self-assemble with siRNA through electrostatic interactions with charged amines, generating multi-lamellar lipoplexes with positively charged lipid bilayers separated from one another by sheets of negatively charged siRNA strands. Internalization of lipid-based siRNA delivery systems into cells typically occurs through endocytosis; accordingly, delivery requires materials that can facilitate endosomal escape. The size of the carrier is important as carriers <100 nm in diameter have been reported to have higher accumulation levels in tumours, hepatocytes and inflamed tissue, whereas larger particles tend to be taken up by Kupffer cells or other components of the reticuloendothelial system (RES). To reduce RES uptake and increase circulation time, carriers have been modified on the surface with hydrophilic materials, such as polyethyleneglycol. Herein, we review the molecular and structural parameters of lipid-based siRNA delivery systems.
Serum markers of matrix turnover as predictors for the evolution of colorectal cancer metastasis under chemotherapy (2003)

Connective tissue turnover plays a prominent role in tumour growth and metastasis. We followed serum levels of seven connective tissue parameters in 37 patients with colorectal cancer metastatic to the liver prior to and during chemotherapy. Serum samples with episodes of tumour control (n=112) showed an increase of matrix metalloproteinase-2 (MMP-2) (P<or=0.01) and a decrease of tissue inhibitor of MMPs (TIMP-1) levels (P<or=0.01), while serum samples with episodes of tumour progression displayed the reverse pattern (P<or=0.01 and P<or=0.05, resp.). The ratio of circulating MMP-2/TIMP-1 was also significantly higher in episodes of tumour control vs tumour progression and prior to treatment (P<or=0.0001). We conclude that serum MMP-2 appears to reflect tumour resorption, while serum TIMP-1 may mirror tumour expansion.
Levetiracetam in the Treatment of Neuropathic Pain: Three Case Studies (2003)

In these 3 case studies, levetiracetam was demonstrated to be an effective therapy in the treatment of neuropathic pain. It has the benefits of a low incidence of adverse events and an improvement in patients' sleep.
Agarose for a bioartificial pancreas (1992)

Islets were encapsulated into 5% concentration agarose microbeads. The effect of microencapsulation on islet allograft survivals was determined using a streptozotocin-induced diabetic (STZ) mouse and a nonobese diabetic (NOD) mouse as recipients. All five STZ BALB/c mice receiving microencapsulated islets (C57BL/6) maintained normoglycemia indefinitely. When NOD mice were used as recipients of the bioartificial pancreas, four of five grafts (islets from C3H/He) functioned for more than 80 d. Two of five NOD mice maintained normoglycemia until animals were sacrificed at 102 and 192 postoperative d. Microbeads made of commercially available agarose can effectively prolong alloislets functioning in the STZ-diabetic mouse and even in the NOD mouse (animal model of human type I diabetes) without the use of any immunosuppressive drug.
The antibacterial and antifungal properties of trappin‐2 (pre‐elafin) do not depend on its protease inhibitory function (2008)

Trappin-2 (also known as pre-elafin) is an endogenous inhibitor of neutrophil serine proteases and is involved in the control of excess proteolysis, especially in inflammatory events, along with the structurally related secretory leucocyte proteinase inhibitor. Secretory leucocyte proteinase inhibitor has been shown to have antibacterial and antifungal properties, whereas recent data indicate that trappin-2 has antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus. In the present study, we tested the antibacterial properties of trappin-2 towards other respiratory pathogens. We found that trappin-2, at concentrations of 5-20 microm, has significant activity against Klebsiella pneumoniae, Haemophilus influenzae, Streptococcus pneumoniae, Branhamella catarrhalis and the pathogenic fungi Aspergillus fumigatus and Candida albicans, in addition to P. aeruginosa and S. aureus. A similar antimicrobial activity was observed with trappin-2 A62D/M63L, a trappin-2 variant that has lost its antiprotease properties, indicating that trappin-2 exerts its antibacterial effects through mechanisms independent from its intrinsic antiprotease capacity. Furthermore, the antibacterial and antifungal activities of trappin-2 were sensitive to NaCl and heparin, demonstrating that its mechanism of action is most probably dependent on its cationic nature. This enables trappin-2 to interact with the membranes of target organisms and disrupt them, as shown by our scanning electron microscopy analyses. Thus, trappin-2 not only provides an antiprotease shield, but also may play an important role in the innate defense of the human lungs and mucosae against pathogenic microorganisms.
Enzymes as synthetic catalysts: mechanistic and active-site considerations of natural and modified chymotrypsin (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnzymes as synthetic catalysts: mechanistic and active-site considerations of natural and modified chymotrypsinJ. Blair West, William J. Hennen, James L. Lalonde, Jeffrey A. Bibbs, Ziyang Zhong, Edgar F. Meyer Jr., and Chi Huey WongCite this: J. Am. Chem. Soc. 1990, 112, 13, 5313–5320Publication Date (Print):June 1, 1990Publication History Published online1 May 2002Published inissue 1 June 1990https://pubs.acs.org/doi/10.1021/ja00169a043https://doi.org/10.1021/ja00169a043research-articleACS PublicationsRequest reuse permissionsArticle Views439Altmetric-Citations61LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Pros and cons of inhibiting cholesteryl ester transfer protein (2000)

Whether or not it is desirable to inhibit cholesteryl ester transfer protein (CETP) has been an important question for over fifteen years since genetic CETP deficiency was found. Recently, some epidemiological studies which have been reported in Japan as well as Western countries help to clarify the atherogenicity of human subjects with mutations or polymorphisms in the CETP gene. In addition, some experimental atherosclerosis studies, in which CETP was inhibited in rabbits with different approaches, have been reported. There was a considerable difference in the atherogenicity of human CETP deficiency and CETP-inhibited rabbits. In this review, we summarize the recent advances in this field as well as discussing the significance of CETP in reverse cholesterol transport, a major protective system against atherosclerosis.
Rapid non‐genomic activation of cytosolic cyclic AMP‐dependent protein kinase activity and [Ca2+]i by 17β‐oestradiol in female rat distal colon (2000)

1. In this study, the effect of 17beta-oestradiol on adenosine 3' : 5'-cyclic monophosphate (cyclic AMP)-dependent protein kinase (PKA) activity was investigated. 2. Rapid (within 15 min) activation of basal PKA activity was observed in cytosolic fractions by 17beta-oestradiol but not by 17alpha-oestradiol, progesterone or testosterone. This stimulation was abolished by the specific PKA inhibitor PKI but not by the classical oestrogen receptor antagonist tamoxifen. 3. 17beta-Oestradiol did not stimulate basal PKA activity in membrane fractions or in cytosolic fractions from male rats. 4. The increase in cytosolic PKA activity was indirect as (i) it was inhibited by the adenylyl cyclase inhibitor SQ22536, (ii) it was mimicked by forskolin and (iii) 17beta-oestradiol did not cause a stimulation of basal PKA activity in either type I or type II commercially available PKA holoenzymes. 5. Protein kinase Cdelta (PKCdelta) was directly activated by 17beta-oestradiol. The specific PKC inhibitor, bisindolylmaleimide I (GF 109203X), abolished the 6. 17beta-oestradiol-induced PKA activation. 17beta-Oestradiol stimulate an increase in free intracellular calcium ion concentration ([Ca(2+)](i)) in isolated female but not male rat colonic crypts. This was inhibited by verapamil, nifedipine and zero extracellular [Ca(2+)] but unaffected by tamoxifen. 17alpha-Oestradiol, testosterone and progesterone failed to increase [Ca(2+)](i). 7. PKC and PKA inhibitors abolished the 17beta-oestradiol-induced increase in [Ca(2+)](i). 8. These results demonstrate the existence of a novel 17beta-oestradiol-specific PKA and Ca(2+) signalling pathway, which is both sex steroid- and gender-specific, in rat distal colonic epithelium.
Population-Based Case-Control Study of Chinese Herbal Products Containing Aristolochic Acid and Urinary Tract Cancer Risk (2009)

Consumption of aristolochic acid-containing Chinese herbal products is associated with an increased risk of cancer of the urinary tract in a dose-dependent manner that is independent of arsenic exposure.
Neuromodulation for treatment-resistant depression (2012)

Treatment-resistant depression affects at least 1-3% of the US population. This article reviews the current state of focal neuromodulation therapies for treatment-resistant depression, focusing on those treatments published clinical data. These include transcranial magnetic stimulation, transcranial direct current stimulation, magnetic seizure therapy, vagus nerve stimulation, direct cortical stimulation, and deep brain stimulation among others. Of these, only two (transcranial magnetic stimulation and vagus nerve stimulation) currently have US Food and Drug Administration approval for the treatment of depression.
Variations in the Insect GABA Receptor, RDL, and Their Impact on Receptor Pharmacology (2017)

The resistance to dieldrin (RDL) receptor is an insect γ-aminobutyric acid (GABA) receptor, characterized by the dieldrin resistance mutation that was pivotal to understanding target based insecticide resistance. RDL is the target for various non-competitive antagonists, including dieldrin and fipronil, as well as novel acting compounds such as the meta-diamides and isoxazolines. Therefore the RDL receptor has returned to center stage as a relevant and effective insecticide target. Our understanding of the function of RDL in vivo is still unfolding, with the discovery of species specific post-transcriptional modifications such as alternative splicing and RNA editing, modifications shown to influence the pharmacology of the receptor. Exposing these receptors to insecticides also evokes ever evolving mechanisms of mutagenesis, and a number of contributory mutations have been identified both in field and laboratory resistant insects, occurring in parallel to the dieldrin resistance mutation. We present an overview of these variations and discuss the impact on the pharmacology of GABA and various insecticides.
Association of galectin-1- but not galectin-3-dependent parameters with proliferation activity in human neuroblastomas and small cell lung carcinomas. (2002)

These results encourage further cell biological studies to assess a regulatory role of galectin-1 on cell growth in vitro as a model for interfering with tumor proliferation by modulating expression of this type of endogenous effector(s).
Optimized Spatial Hashing for Collision Detection of Deformable Objects. (2003)

We propose a new approach to collision and self-- collision detection of dynamically deforming objects that consist of tetrahedrons. Tetrahedral meshes are commonly used to represent volumetric deformable models and the presented algorithm is integrated in a physically--based environment, which can be used in game engines and surgical simulators. The proposed algorithm employs a hash function for compressing a potentially infinite regular spatial grid. Although the hash function does not always provide a unique mapping of grid cells, it can be generated very efficiently and does not require complex data structures, such as octrees or BSPs. We have investigated and optimized the parameters of the collision detection algorithm, such as hash function, hash table size and spatial cell size. The algorithm can detect collisions and self-- collisions in environments of up to 20k tetrahedrons in real--time. Although the algorithm works with tetrahedral meshes, it can be easily adapted to other object primitives, such as triangles.
The N-terminal Carbohydrate Recognition Site of the Cation-independent Mannose 6-Phosphate Receptor (2004)

The 300-kDa cation-independent mannose 6-phosphate receptor (CI-MPR) plays a critical role in the trafficking of newly synthesized mannose 6-phosphate-containing acid hydrolases to the lysosome. The receptor contains two high affinity carbohydrate recognition sites within its 15-domain extracytoplasmic region, with essential residues for carbohydrate recognition located in domain 3 and domain 9. Previous studies have shown that these two sites are distinct with respect to carbohydrate specificity. In addition, expression of truncated forms of the CI-MPR demonstrated that domain 9 can be expressed as an isolated domain, retaining high affinity (Kd approximately 1 nm) carbohydrate binding, whereas expression of domain 3 alone resulted in a protein capable of only low affinity binding (Kd approximately 1 microm) toward a lysosomal enzyme. In the current report the crystal structure of the N-terminal 432 residues of the CI-MPR, encompassing domains 1-3, was solved in the presence of bound mannose 6-phosphate. The structure reveals the unique architecture of this carbohydrate binding pocket and provides insight into the ability of this site to recognize a variety of mannose-containing sugars.
Oncofetal H19-derived miR-675 regulates tumor suppressor RB in human colorectal cancer (2009)

H19 is an imprinted oncofetal non-coding RNA recently shown to be the precursor of miR-675. The pathophysiological roles of H19 and its mature product miR-675 to carcinogenesis have, however, not been defined. By quantitative reverse transcription-polymerase chain reaction, both H19 and miR-675 were found to be upregulated in human colon cancer cell lines and primary human colorectal cancer (CRC) tissues compared with adjacent non-cancerous tissues. Subsequently, the tumor suppressor retinoblastoma (RB) was confirmed to be a direct target of miR-675 as the microRNA suppressed the activity of the luciferase reporter carrying the 3'-untranslated region of RB messenger RNA that contains the miR-675-binding site. Suppression of miR-675 by transfection with anti-miR-675 increased RB expression and at the same time, decreased cell growth and soft agar colony formation in human colon cancer cells. Reciprocally, enhanced miR-675 expression by transfection with miR-675 precursor decreased RB expression, increased tumor cell growth and soft agar colony formation. Moreover, the inverse relationship between the expressions of RB and H19/miR-675 was also revealed in human CRC tissues and colon cancer cell lines. Our findings demonstrate that H19-derived miR-675, through downregulation of its target RB, regulates the CRC development and thus may serve as a potential target for CRC therapy.
Synthesis of 2′-Deoxy-9-deaza Nucleosides Using Heck Methodology (2013)

During the synthesis of a series of 2'-deoxy-9-deaza nucleosides using Heck methodology, the necessity for a pyrrole protecting group was discovered. The results of this brief study revealed that the benzyloxymethyl (BOM) group proved optimal, and Heck coupling using Jeffery conditions increased the coupling yield significantly. The results are reported herein.
A randomised controlled trial with prolonged‐release oral oxycodone and naloxone to prevent and reverse opioid‐induced constipation (2008)

Co-administration of PR oral naloxone and PR oral oxycodone is associated with a significant improvement in bowel function compared with PR oral oxycodone alone, with no reduction in the analgesic efficacy of oxycodone.