gebhart/patrepeval huggingface dataset:
The pharmacokinetics of intravenous and oral levodopa in patients with Parkinson's disease who exhibit on‐off fluctuations. (1986)

We have studied the clinical effects and pharmacokinetics of levodopa infusions and oral therapy in seven patients with Parkinson's disease. They all showed on-off fluctuations whilst receiving long-term treatment with levodopa in combination with a peripheral decarboxylase inhibitor. Intravenous infusion at a constant rate for up to 16 h resulted in a smoother clinical response, and maintained plasma levodopa concentrations within narrower limits compared with conventional oral therapy. Following infusion rates of 32-80 mg h-1 (0.5-1.3 mg kg-1 h-1) the plasma concentration associated with optimum therapeutic response lay between 0.3 and 1.6 mg l-1. There was considerable variation in the oral absorption and elimination of levodopa, both within and between subjects. The concentration of 3-OMe dopa in plasma hardly increased during each day's levodopa therapy. In all cases levels were greater than the maximum concentrations of levodopa, sometimes by as much as a factor of 10. In contrast to most previous reports on the pharmacokinetics of levodopa, the data presented here are consistent with a two-compartment kinetic model. It is not known whether the difference in pharmacokinetics is due to chronic therapy or whether it is specific to those patients who show on-off phenomena, but such changes might be related in some way to the development of fluctuations in clinical response.
Synthesis of fluorinated Thomsen–Friedenreich antigens: direct deoxyfluorination of αGalNAc-threonine tert-butyl esters (2011)

Selectively 6-fluorinated analogs of the tumor-associated T(N) antigen Fmoc-Thr(α-O-GalNAc)-OtBu can be efficiently prepared using DAST-mediated de(hydr)oxyfluorination reactions of preformed and orthogonally protected glycosyl amino esters without affecting the labile protecting groups and O-glycosidic linkages. The resulting mono- and difluorinated T(N) analogs are interesting building blocks for non-hydrolyzable mucin-type antigen mimetics, as illustrated by the unprecedented synthesis of two different multiply fluorinated Thomsen-Friedenreich derivatives. The reported deoxyfluoro antigen analogs represent important functional probes for carbohydrate-binding proteins and glycosyl-processing enzymes.
Detection of Campylobacter jejuni in food and poultry viscera using immunomagnetic separation and microtitre hybridization (1997)

Thermophillic Campylobacter and Camp. jejuni were detected from samples of chicken liver, gall bladder, muscle and contaminated milk and chicken meat after an enrichment step by using immunomagnetic capture of cells with monoclonal antibody against a specific outer membrane protein of thermophilic Campylobacter. The detection of captured cells was achieved using two different hybridization methods. In one of the methods, the captured cells were lysed by guanidine isothiocyanate and the 23S rRNA was reacted with a microtitre plate-immobilized rDNA probe specific for thermophilic Campylobacter. In the other method, the captured cells were subjected to lysis by ultrasonication and the genomic DNA reacted with a microtitre plate-immobilized RNA probe specific for Camp.jejuni. Detection of the RNA-DNA hybrids formed in the wells was carried out using a monoclonal anti-RNA-DNA hybrid antibody.
Autonomous Web Services Migration in Mobile and Wireless Environments (2013)

With the emergence of powerful mobile Internet devices such as smartphones, mobile devices are expected to play the role of service providers or even brokers, as well as clients. However, the frequent mobility of devices and the intermittent disconnection of mobile and wireless network may degrade the availability and reliability of services. To resolve these problems, this paper proposes an efficient method for migrating and replicating Web services among mobile devices. Specifically, the proposed method splits the source code of a Web service into subcodes depending on users’ preferences for its constituent operations. For the seamless provisioning of services, a subcode with a higher preference is migrated earlier than others. To evaluate the performance of the proposed method, the effect of the code splitting on migration was analyzed.
Challenges to nerve regeneration (2000)

Peripheral nerve injuries can result from mechanical, thermal, chemical, congenital, or pathological etiologies. Failure to restore these damaged nerves can lead to the loss of muscle function, impaired sensation, and painful neuropathies. Current surgical strategies for the repair of critical nerves involve the transfer of normal donor nerve from an uninjured body location. However, these "gold standard" methods for tissue restoration frequently are limited by tissue availability, risk of disease spread, secondary deformities, and potential differences in tissue structure and size. One possible alternative to autogenous tissue replacement is the development of engineered constructs to replace those elements necessary for axonal proliferation, including a scaffold, support cells, induction factors, and extracellular matrices. Despite advances and contributions in the field of tissue engineering, results to date with nerve conduits have failed to equal the nerve regeneration achieved with autogenous grafts for large distances. We review the current challenges to tissue-engineered constructs. Each of the four components is reviewed and approaches are outlined. Semin. Surg. Oncol. 19:312-318, 2000.
Multi-Group Random Access Resource Allocation for M2M Devices in Multicell Systems (2012)

The efficient service of a tremendous number of machine-type devices with heterogeneous traffic types may consider simple random access as a solution. For more rigorous analysis of system performance in multicell environments, it is required to consider not only the packet collisions within the same cell but also the interference from other cells. This letter analyzes signal-to-interference-ratio distributions and derives efficient resource allocation schemes for spatial multi-group random access in multicell systems, using the Poisson point process model.
Fasudil-induced hypoxia-inducible factor-1α degradation disrupts a hypoxia-driven vascular endothelial growth factor autocrine mechanism in endothelial cells (2008)

Hypoxic response of endothelial cells (EC) is an important component of tumor angiogenesis. Especially, hypoxia-inducible factor-1 (HIF-1)-dependent EC-specific mechanism is an essential component of tumor angiogenesis. Recently, the Rho/Rho-associated kinase (ROCK) signaling has been shown to play a key role in HIF-1alpha induction in renal cell carcinoma and trophoblast. The present study was designed to investigate whether low oxygen conditions might modulate HIF-1alpha expression through the Rho/ROCK signaling in human umbilical vascular ECs (HUVEC). Pull-down assay showed that hypoxia stimulated RhoA activity. Under hypoxic conditions, HUVECs transfected with small interfering RNA of RhoA and ROCK2 exhibited decreased levels of HIF-1alpha protein compared with nontargeted small interfering RNA transfectants, whereas HIF-1alpha mRNA levels were not altered. One of ROCK inhibitors, fasudil, inhibited hypoxia-induced HIF-1alpha expression without altering HIF-1alpha mRNA expression. Furthermore, proteasome inhibitor prevented the effect of fasudil on HIF-1alpha expression, and polyubiquitination was enhanced by fasudil. These results suggested that hypoxia-induced HIF-1alpha expression is through preventing HIF-1alpha degradation by activating the Rho/ROCK signaling in ECs. Furthermore, hypoxia induced both vascular endothelial growth factor (VEGF) and VEGF receptor-2 expression through the Rho/ROCK/HIF-1alpha signaling in HUVECs. Thus, augmented VEGF/VEGF receptor-2 autocrine mechanism stimulated HUVEC migration under hypoxic conditions. In summary, the Rho/ROCK/HIF-1alpha signaling is an essential mechanism for hypoxia-driven, VEGF-mediated autocrine loop in ECs. Therefore, fasudil might have the antimigratory effect against ECs in tumor angiogenesis.
Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo (2001)

Evidence is provided that proteolytic cleavage of collagen type IV results in the exposure of a functionally important cryptic site hidden within its triple helical structure. Exposure of this cryptic site was associated with angiogenic, but not quiescent, blood vessels and was required for angiogenesis in vivo. Exposure of the HUIV26 epitope was associated with a loss of alpha1beta1 integrin binding and the gain of alphavbeta3 binding. A monoclonal antibody (HUIV26) directed to this site disrupts integrin-dependent endothelial cell interactions and potently inhibits angiogenesis and tumor growth. Together, these studies suggest a novel mechanism by which proteolysis contributes to angiogenesis by exposing hidden regulatory elements within matrix-immobilized collagen type IV.
Einleitung (2002)

Die Methode der Finiten Elemente (FEM) kann als ein numerisches Berechnungsverfahren zur Lösung von Problemen der mathematischen Physik angesehen werden. Der Übergriff mathematische Physik soll die Allgemeingültigkeit der Methode verdeutlichen. Zu den Problemen der mathematischen Physik, die heute in großem Umfang mit Hilfe der FEM gelöst werden, gehören in erster Linie Die Gleichungen, die die Probleme der mathematischen Physik beschreiben, sind im Falle zwei- und dreidimensionaler Probleme partielle Differentialgleichungen. Die FEM kann daher auch als Methode zur Lösung derartiger Differentialgleichungen benutzt werden. Bei der Anwendung auf Probleme der Strukturmechanik besteht der Grundgedanke der FEM darin, daß die gesamte Struktur (Tragwerke) in eine Vielzahl kleiner Elemente zerlegt wird, deren mechanisches Verhalten entweder annäherungsweise oder auch exakt bekannt ist
The Relentless Effects of the Fontan Paradox (2016)

The Fontan operation is the anticipated palliative strategy for children born with single-ventricle type of congenital heart disease. As a result of important circulatory limitations, a series of end-organ complications are now increasingly recognized. Elevated central venous pressure and impaired cardiac output are the hallmarks of cavo-pulmonary flow, which result in a cascade of pathophysiological consequences. The Fontan circulation likely impacts all organ systems in an indolent and relentless manner, with progressive decline in functionality likely to occur in many. Liver fibrosis, altered bone density, decreased muscle mass, renal dysfunction, lymphatic insufficiency, and a host of other conditions are present. Standardized screening and evaluation of survivors as they grow through childhood and beyond is indicated and can be facilitated through dedicated multidisciplinary clinical programs. Invasive assessment at specific milestones can provide important actionable information to optimize individual status. More detailed characterization and understanding of these end-organ complications is necessary to contribute to the goal of achieving a normal duration and quality of life for these unique individuals.
Complete protection by high-dose dexamethasone against the hepatotoxicity of the novel antitumor drug yondelis (ET-743) in the rat. (2003)

Yondelis (ET-743) is a promising antitumor drug with hepatotoxic properties in animals and humans. Here the hypothesis was tested that dexamethasone can ameliorate manifestations of yondelis-induced hepatotoxicity in the female Wistar rat, which is the animal species with the highest sensitivity toward the adverse hepatic effect of yondelis. Hepatotoxicity was adjudged by measurement of plasma levels of alkaline phosphatase, aspartate aminotransferase, and bilirubin, and by liver histopathology. Yondelis (40 micro g/kg i.v.) alone caused a dramatic elevation of plasma alkaline phosphatase, aspartate aminotransferase, and bilirubin levels, and degeneration and patchy focal necrosis of bile duct epithelial cells. Pretreatment of rats with dexamethasone (5-20 mg/kg, p.o.) 24 h before yondelis ameliorated or abrogated the biochemical and histopathological manifestations of yondelis-induced liver changes. In contrast, when dexamethasone was administered simultaneously with yondelis, its toxicity was not reduced. Pretreatment with dexamethasone (10 mg/kg) also reversed the gene expression changes induced by yondelis in rat liver. However, dexamethasone pretreatment did not interfere with the antitumor efficacy of yondelis in rats bearing the 13762 mammary carcinoma or in four murine models. Dexamethasone (10 mg/kg) administered 24 h before yondelis decreased hepatic levels of yondelis dramatically compared with those obtained after administration of yondelis alone, whereas yondelis plasma levels after the drug combination were not markedly different from those in rats on yondelis alone. The results suggest that pretreatment with high-dose dexamethasone effectively protects rats against yondelis-mediated hepatic damage by decreasing hepatic exposure to yondelis, perhaps linked to induction of metabolism by cytochrome P450 enzymes. Pretreatment with high-dose dexamethasone should be investigated in patients who receive yondelis to ameliorate its unwanted effect on the liver.
Chronic Lymphocytic Leukemia and B and T Cells Differ in Their Response to Cyclic Nucleotide Phosphodiesterase Inhibitors (2009)

Phosphodiesterase (PDE)4 inhibitors, which activate cAMP signaling by reducing cAMP catabolism, are known to induce apoptosis in B lineage chronic lymphocytic leukemia (CLL) cells but not normal human T cells. The explanation for such differential sensitivity remains unknown. In this study, we report studies contrasting the response to PDE4 inhibitor treatment in CLL cells and normal human T and B cells. Affymetrix gene chip analysis in the three cell populations following treatment with the PDE4 inhibitor rolipram identified a set of up-regulated transcripts with unusually high fold changes in the CLL samples, several of which are likely part of compensatory negative feedback loops. The high fold changes were due to low basal transcript levels in CLL cells, suggesting that cAMP-mediated signaling may be unusually tightly regulated in this cell type. Rolipram treatment augmented cAMP levels and induced ATF-1/CREB serine 63/133 phosphorylation in both B lineage cell types but not T cells. As treatment with the broad-spectrum PDE inhibitor 3-isobutyl-1-methylxanthine induced T cell CREB phosphorylation, we tested a series of family-specific PDE inhibitors for their ability to mimic 3-isobutyl-1-methylxanthine-induced ATF-1/CREB phosphorylation. Whereas PDE3 inhibitors alone had no effect, the combination of PDE3 and PDE4 inhibitors induced ATF-1/CREB serine 63/133 phosphorylation in T cells. Consistent with this observation, PDE3B transcript and protein levels were low in CLL cells but easily detectable in T cells. Combined PDE3/4 inhibition did not induce T cell apoptosis, suggesting that cAMP-mediated signal transduction that leads to robust ATF-1/CREB serine 63/133 phosphorylation is not sufficient to induce apoptosis in this lymphoid lineage.
Characterisation of colorectal cancers showing hypermethylation at multiple CpG islands (2002)

These observations made in a relatively large unselected series of CRC support the notion that CIMP+ characterises a subgroup of tumours with distinctive phenotypic features.
Segment-based stereo matching using graph cuts (2004)

In this paper we present a new segment-based stereo matching algorithm using graph cuts. In our approach, the reference image is divided into non-overlapping homogeneous segments and the scene structure is represented as a set of planes in the disparity space. The stereo matching problem is formulated as an energy minimization problem in the segment domain instead of the traditional pixel domain. Graph cuts technique is used to fast approximate the optimal solution, which assigns the corresponding disparity plane to each segment. Experiments demonstrate that the performance of our algorithm is comparable to the state-of-the-art stereo algorithms on various data sets. Furthermore, strong performance is achieved in the conventionally difficult areas such as: textureless regions, disparity discontinuous boundaries and occluded portions.
Imidazo[2,1-b]benzothiazoles. 2. New immunosuppressive agents (1986)

A series of 2-phenylimidazo[2,1-b]benzothiazole derivatives was prepared and tested for immunological activities. Some of the compounds showed significant suppressive activity of delayed type hypersensitivity (DTH) without inhibition of humoral immunity in mice by oral administration. The most active compound was 2-(m-hydroxyphenyl)imidazo[2,1-b]benzothiazole (20).
Nonenzymatic Browning in Vivo: Possible Process for Aging of Long-Lived Proteins (1981)

The incubation of lens proteins with reducing sugars leads to the formation of fluorescent yellow pigments and cross-like similar to those reported in aging and cataractous human lenses. Called nonenzymatic browning or the Maillard reaction, this aging process also occurs in stored foods. Reducing sugars condense with the free amino group of proteins, then rearrange and dehydrate to form unsaturated pigments and cross-linked products. Although most proteins in living systems turn over with sufficient rapidity to avoid nonenzymatic browning, some, such as lens crystallins and skin collagen, are exceptionally long-lived and may be vulnerable.
Critical Role of Monocyte Chemoattractant Protein-1 Receptor CCR2 on Monocytes in Hypertension-Induced Vascular Inflammation and Remodeling (2004)

Activated monocytes are present in the arterial walls of hypertensive patients and animals. Monocyte chemoattractant protein-1 (MCP-1), which controls monocyte function through its receptor (CCR2), is implicated in hypertensive inflammatory changes in the arterial wall. The role of CCR2 expression on monocytes in hypertension-induced vascular remodeling, however, has not been addressed. We hypothesized that CCR2 on monocytes is critical in hypertension-induced vascular inflammation and remodeling. Hypertension was induced by infusion of angiotensin II (Ang II) into wild-type mice, CCR2-deficient (CCR2 −/− ) mice, and bone marrow-transferred mice with a leukocyte-selective CCR2 deficiency (BMT-CCR2 −/− ). In wild-type mice, Ang II increased CCR2 intensity in circulating monocytes, which was prevented by an Ang II type-1 (AT 1 ) receptor blocker or blunted in AT 1 receptor-deficient mice. Enhanced CCR2 intensity on monocytes was observed in hypertensive patients and rats, and was reduced by treatment with the Ang II receptor blocker, supporting the clinical relevance of the observation in mice. In CCR2 −/− and BMT-CCR2 −/− mice, Ang II-induced vascular inflammation and vascular remodeling (aortic wall thickening and fibrosis) were blunted as compared with control mice. In contrast, Ang II-induced left ventricular hypertrophy developed in CCR2 −/− and BMT-CCR2 −/− mice. The present study suggests that CCR2 expression in monocytes has a critical role in vascular inflammation and remodeling in Ang II-induced hypertension, and possibly in other forms of hypertension.
Surpassing the Use of Copper in the Click Functionalization of Polymeric Nanostructures: A Strain-Promoted Approach (2009)

The limitations (depolymerization and Cu contamination) in the use of Cu(I)-catalyzed azide-alkyne [3 + 2] cycloadditions (CuAAC) for the selective click functionalization of polysaccharide-based systems have been efficiently surpassed using a strain-promoted approach (SPAAC). The SPAAC decoration of chitosan-g-poly(ethylene glycol) nanostructures with an immunoglobulin G under physiological conditions represents a step forward in the preparation of immunonanoparticles.
Galactosylation variations in marketed therapeutic antibodies (2012)

There are currently ~25 recombinant full-length IgGs (rIgGs) in the market that have been approved by regulatory agencies as biotherapeutics to treat various human diseases. Most of these are based on IgG1k framework and are either chimeric, humanized or human antibodies manufactured using either Chinese hamster ovary (CHO) cells or mouse myeloma cells as the expression system. Because CHO and mouse myeloma cells are mammalian cells, rIgGs produced in these cell lines are typically N-glycosylated at the conserved asparagine (Asn) residues in the CH2 domain of the Fc, which is also the case with serum IgGs. The Fc glycans present in these rIgGs are for the most part complex biantennary oligosaccharides with heterogeneity associated with the presence or the absence of several different terminal sugars. The major Fc glycans of rIgGs contain 0 or 1 or 2 (G0, G1 and G2, respectively) terminal galactose residues as non-reducing termini and their relative proportions may vary depending on the cell culture conditions in which they were expressed. Since glycosylation is strongly associated with antibody effector functions and terminal galactosylation may affect some of those functions, a panel of commercially available therapeutic rIgGs expressed in CHO cells and mouse myeloma cells were examined for their galactosylation patterns. The results suggest that the rIgGs expressed in CHO cells are generally less galactosylated compared to the rIgGs expressed in mouse myeloma cells. Accordingly, rIgGs produced in CHO cells tend to contain higher levels of G0 glycans compared with rIgGs produced in mouse myeloma cell lines. Despite the apparent wide variability in galactose content, adverse events or safety issues have not been associated with specific galactosylation patterns of therapeutic antibodies. Nevertheless, galactosylation may have an effect on the mechanisms of action of some therapeutic antibodies (e.g., effector pathways) and hence further studies to assess effects on product efficacy may be warranted for such antibodies. For antibodies that do not require effector functions for biological activity, however, setting a narrow specification range for galactose content may be unnecessary.
Homologous Recombination Catalyzed by Human Cell Extracts (1985)

Two plasmids containing noncomplementing and nonreverting deletions in a bacterial phosphotransferase gene conferring resistance to neomycin (Neor) were incubated with human cell extracts, and the mixtures were used to transform recombination-deficient (recA-) Escherichia coli cells. We were able to obtain Neor colonies at a frequency of 2 X 10(-3). This frequency was 100 to 1,000 times higher than that obtained with no extracts. The removal of riboadenosine 5'-triphosphate, Mg2+, or deoxynucleoside triphosphates from the reaction mixture severely reduced the yield of Neor colonies. Examination of plasmid DNA from the Neor colonies revealed that they resulted from gene conversion and reciprocal recombination. On the basis of these results, we conclude that mammalian somatic cells in culture have the enzymatic machinery to catalyze homologous recombination in vitro.
The effect of polymeric chemistry on the expression of bone-related mRNAs and proteins by human bone-derived cells in vitro (1999)

This study used human bone-derived cells (HBDC) grown on two defined polymeric substrata to examine the effect of substrata chemistry on the expression of mRNAs and proteins characteristic of the osteoblastic phenotype. The growth profile of cells grown on tissue culture polystyrene (TCP) was exponential whereas for those seeded on polyethyleneterephthalate (PET) there was a pronounced lag period before cellular multiplication. The temporal expression pattern of mRNAs in HBDC cultured on TCP was similar to that of cells on PET. On TCP, the levels of several mRNAs peaked at day 4, as cellular proliferation slowed. In contrast, the induction in mRNA levels in cells grown on PET corresponded to maximum mitotic activity. There appears to be sequential cascade in protein expression in cells grown on TCP with overlapping peaks of thrombospondin (Tsp), osteocalcin (OC) and osteopontin (OP) expression. In contrast, peak intracellular protein expression levels for Tsp, OC and OP did not overlap when cells were grown on PET.