gebhart/patrepeval huggingface dataset:
Axonal Regeneration through Regions of Chondroitin Sulfate Proteoglycan Deposition after Spinal Cord Injury: A Balance of Permissiveness and Inhibition (2003)

Increased expression of certain extracellular matrix (ECM) molecules after CNS injury is believed to restrict axonal regeneration. The chondroitin sulfate proteoglycans (CSPGs) are one such class of ECM molecules that inhibit neurite outgrowth in vitro and are upregulated after CNS injury. We examined growth responses of several classes of axons to this inhibitory environment in the presence of a cellular fibroblast bridge in a spinal cord lesion site and after a growth factor stimulus at the lesion site (fibroblasts genetically modified to secrete NGF). Immunohistochemical analysis showed dense labeling of the CSPGs NG2, brevican, neurocan, versican, and phosphacan at the host-lesion interface after spinal cord injury (SCI). Furthermore, robust expression of NG2, and to a lesser extent versican, was also observed throughout grafts of control and NGF-secreting fibroblasts. Despite this inhibitory milieu, several axonal classes penetrated control fibroblast grafts, including dorsal column sensory, rubrospinal, and nociceptive axons. Axon growth was amplified more in the presence of NGF-secreting grafts. Confocal microscopy demonstrated that axon growth was, paradoxically, preferentially associated with NG2-rich substrates in both graft types. NG2 expression also increased after sciatic nerve injury, wherein axons successfully regenerate. Cellular sources of NG2 in SCI and peripheral nerve lesion sites included Schwann cells and endothelial cells. Notably, these same cellular sources in lesion sites produced the cell adhesion molecules L1 and laminin, and these molecules all colocalized. Thus, axons grow along substrates coexpressing both inhibitory and permissive molecules, suggesting that regeneration is successful when local permissive signals balance and exceed inhibitory signals.
Towards Semantic Interpretation of Legal Modifications through Deep Syntactic Analysis (2008)

We are concerned with the automatic semantic interpretation of legal modificatory provisions. We propose a novel approach which pairs deep syntactic parsing and a fine-grained taxonomy of legal modifications. Although still in a developmental stage, the implemented system can be used to annotate with meta-information modificatory provisions of NormaInRete documents.
Pharmacokinetics and Pharmacodynamics of Oral Methotrexate and Mercaptopurine in Children With Lower Risk Acute Lymphoblastic Leukemia: A Joint Children’s Cancer Group and Pediatric Oncology Branch Study (1998)

We prospectively assessed the pharmacokinetics of methotrexate, mercaptopurine, and erythrocyte thioguanine nucleotide levels in a homogenous population of children with lower risk acute lymphoblastic leukemia and correlated pharmacokinetic parameters with disease outcome. The maintenance therapy regimen included daily oral mercaptopurine (75 mg/m2) and weekly oral methotrexate (20 mg/m2). One hundred ninety-one methotrexate doses and 190 mercaptopurine doses were monitored in 89 patients. Plasma drug concentrations of both agents were highly variable. The area under the plasma concentration-time curve (AUC) of methotrexate ranged from 0.63 to 12 μmol•h/L, and the AUC of mercaptopurine ranged from 0.11 to 8 μmol•h/L. Drug dose, patient age, and duration of therapy did not account for the variability. Methotrexate AUC was significantly higher in girls than boys (P = .007). There was considerable intrapatient variability for both agents. Erythrocyte thioguanine nucleotide levels were also highly variable (range, 0 to 10 pmol/g Hgb) and did not correlate with mercaptopurine dose or AUC. A Cox regression analysis showed that mercaptopurine AUC was a marginally significant (P = .043) predictor of outcome, but a direct comparison of mercaptopurine AUC in the remission and relapsed patient groups failed to show a significant difference. Methotrexate and mercaptopurine plasma concentrations and erythrocyte thioguanine nucleotide levels were highly variable, but measurement of these pharmacokinetic parameters at the start of maintenance will not distinguish patients who are more likely to relapse.
The Pharmacologic Assessment of A Novel Lymphocyte Function-Associated Antigen-1 Antagonist (SAR 1118) for the Treatment of Keratoconjunctivitis Sicca in Dogs (2011)

SAR 1118 appears to be an effective anti-inflammatory treatment for KCS. Additional studies are warranted to establish the efficacy of SAR 1118 for the treatment of KCS in humans.
Requirement for Neurogenesis to Proceed through the Division of Neuronal Progenitors following Differentiation of Epidermal Growth Factor and Fibroblast Growth Factor‐2–Responsive Human Neural Stem Cells (2004)

Epidermal growth factor (EGF)– and fibroblast growth factor‐2 (FGF‐2)–responsive human neural stem cells may provide insight into mechanisms of neural development and have applications in cell‐based therapeutics for neurological disease. However, their biology after expansion in vitro is currently poorly understood. Cells grown in either EGF or FGF‐2 or a combination of both mitogens displayed characteristically similar levels of transcriptional activation and comparable proliferative profiles with linear cell‐cycle kinetics and possessed similar neuronal differentiation capabilities. These data support the view that human neurospheres at later stages of expansion (>10 weeks) are comprised overwhelmingly of a single type of stem cell responsive to both EGF and FGF‐2. After mitogen withdrawal and neurosphere plating, bromodeoxyuridine pulse‐chase experiments revealed that the stem cells did not undergo differentiation directly into neurons. Instead, most immature neurons arose via the division of emerging progenitor cells in the absence of exogenous EGF or FGF‐2. Neurogenesis was abolished by application of high concentrations of either EGF/FGF‐2 or the mitotic inhibitor cytosine‐b‐arabinofuranoside, suggesting that there is an obligatory requirement for at least one round of cell division in the absence of mitogens as a prelude to terminal neuronal differentiation. The differentiation of human neurospheres provides a useful model of human neurogenesis, and the data presented indicate that it proceeds through the division of committed neuronal progenitor cells rather than directly from the neural stem cell.
Cannabinoids and cancer: pros and cons of an antitumour strategy (2006)

In the last two decades, research has dramatically increased the knowledge of cannabinoids biology and pharmacology. In mammals, compounds with properties similar to active components of Cannabis sativa, the so called 'endocannabinoids', have been shown to modulate key cell-signalling pathways involved in cancer cell growth, invasion and metastasis. To date, cannabinoids have been licensed for clinical use as palliative treatment of chemotherapy, but increased evidences showed direct antiproliferative actions of cannabinoid agonists on several tumour cells in vitro and in animal models. In this article, we will review the principal molecular pathways modulated by cannabinoids on cancer and summarize pros and cons evidence on the possible future use of endocannabinoid-based drugs in cancer therapy.
(R)- and (S)-3-Fluorothalidomides:  Isosteric Analogues of Thalidomide (1999)

3-Fluorothalidomide, a nonracemizable isosteric analogue of thalidomide, was successfully prepared by perchloryl fluoride fluorination of a 3-phthalimidopiperidin-2-one derivative followed by RuO2 oxidation. In the preliminary biological evaluation of (R)- and (S)-enantiomers, it was shown that the (S)-isomer was found to be more active than both the (R)-isomer and the racemic thalidomide in lipopolysaccharide-induced TNF-α production enhancement produced from human peripheral blood lymphocytes cultivated in vitro.
The transcription factors CREB and c‐Fos play key roles in NCAM‐mediated neuritogenesis in PC12‐E2 cells (2001)

The neural cell adhesion molecule (NCAM) stimulates axonal outgrowth by activation of the Ras-mitogen activated protein kinase (MAPK) pathway and by generation of arachidonic acid. We investigated whether the transcription factors, cyclic-AMP response-element binding protein (CREB) and c-Fos play roles in this process by estimating NCAM-dependent neurite outgrowth from PC12-E2 cells grown in co-culture with NCAM-negative or NCAM-positive fibroblasts. PC12-E2 cells were transiently transfected with expression plasmids encoding wild-type or dominant negative forms of CREB and c-Fos or an activated form of the MAPK kinase, MEK2. Alternatively, PC12-E2 cells were treated with arachidonic acid, the cAMP analogue dBcAMP, or protein kinase A (PKA) inhibitors. The negative forms of CREB and c-Fos inhibited neurite outgrowth mediated by NCAM, arachidonic acid, dBcAMP, or MEK2. Neither CREB nor c-Fos could compensate for the inactivation of the other, indicating that both factors are important in NCAM-mediated neuritogenesis. Treatment of primary hippocampal neurons with a synthetic NCAM peptide ligand known to stimulate neurite outgrowth induced phosphorylation of CREB and expression of c-fos. We thus present evidence that NCAM-mediated neurite outgrowth involves a series of signal transduction pathways, including the cAMP/PKA pathway, targeting c-Fos and CREB.
Modifications of the cuticular hydrocarbon profile of Apis mellifera worker bees in the presence of the ectoparasitic mite Varroa jacobsoni in brood cells (2001)

Varroa jacobsoni is an ectoparasite of Apis mellifera which invades brood cells, on 8-day-old larvae several hours before cell capping. Reproduction of the parasite takes place in the capped brood cells during the nymphose of the bee. Cuticular hydrocarbons of unparasitized bees and of bees parasitized by Varroa jacobsoni were extracted and analysed by gas chromatography (GC) coupled with mass spectrometry (GC-MS). Three developmental stages of worker honey bees were studied: larvae, pupae and emergent adults. The comparison between unparasitized and parasitized hosts was performed with Principal Components Analysis coupled with a multivariate variance analysis. The cuticular hydrocarbon profiles of honey bees were qualitatively similar, for the 3 developmental stages and regardless of the presence of Varroa in the cells. Nevertheless, comparison of the relative proportions of hydrocarbons showed that the cuticular profiles of pupae and emergent adults parasitized by 1 mite and of larvae parasitized by 2 mites were significantly different from the corresponding unparasitized individuals. Such modifications could be regarded (i) as a cause of the multi-infestation in larvae during invasion of brood and (ii) as a consequence of stress and/or removal of proteins contained in the haemolymph of the host during its development.
Evaluation of an inflammation‐based prognostic score in patients with metastatic renal cancer (2006)

An inflammation-based prognostic score (GPS) predicted survival independent of established scoring systems in patients with metastatic renal cancer.
Radiocontrast nephropathy: identifying the high-risk patient and the implications of exacerbating renal function. (2003)

Radiographic procedures using contrast media are widely performed throughout the world. This necessitates physicians' awareness of radiocontrast nephropathy-the disorder that develops as a result of exposure to contrast agents. Although in the general population the risk of radiocontrast nephropathy is rather low, it may be very high in selected subsets of patients. This article focuses on the incidence, pathogenesis, risk factors, and prognosis of radiocontrast nephropathy and provides important insights on its prevention.
EphA2 as a Novel Molecular Marker and Target in Glioblastoma Multiforme (2005)

We investigated the presence of EphA2, and its ligand, ephrinA1, in glioblastoma multiforme (GBM), a malignant neoplasm of glial cells, and normal brain. We also initially examined the functional importance of the interaction between EphA2 and ephrinA1 in glioma cells. Expression and localization of EphA2 and ephrinA1 in human GBM and normal brain were examined using Western blotting, immunofluorescence, and immunohistochemistry. A functional role for EphA2 was investigated by assessing the activation status of the receptor and the effect of ephrinA1 on the anchorage-independent growth and invasiveness of GBM cells. We found EphA2 to be elevated in approximately 90% of GBM specimens and cell lines but not in normal brain, whereas ephrinA1 was present at consistently low levels in both GBM and normal brain. EphA2 was activated and phosphorylated by ephrinA1 in GBM cells. Furthermore, ephrinA1 induced a prominent, dose-dependent inhibitory effect on the anchorage-independent growth and invasiveness of GBM cells highly overexpressing EphA2, which was not seen in cells expressing low levels of the receptor. Thus, EphA2 is both specifically overexpressed in GBM and expressed differentially with respect to its ligand, ephrinA1, which may reflect on the oncogenic processes of malignant glioma cells. EphA2 seems to be functionally important in GBM cells and thus may play an important role in GBM pathogenesis. Hence, EphA2 represents a new marker and novel target for the development of molecular therapeutics against GBM.
Homologous pairing in genetic recombination. Purification and characterization of Escherichia coli recA protein. (1981)

RecA protein, which is essential for genetic recombination in Escherichia coli, was extensively purified from a strain of E. coli which contained the recA gene cloned in a plasmid (Sancar, A., and Rupp, W. D. (1979) Proc. Natl. Acad. Sci. U. S. A. 76, 3144-3148). Using the DNA-dependent ATPase activity of recA protein as an assay, we obtained about 60 mg of purified recA protein from 100 g of cells. Ten micrograms or 1 microgram of the purified protein exhibited only one detectable band with Mr approximately = 40,000 upon sodium dodecyl sulfate-acrylamide gel electrophoresis. More than 99% of the ATPase activity of purified recA protein was dependent on single-stranded DNA. Purified recA protein had no detectable DNase, topoisomerase, or ligase activities. The enzyme was stable for a least a year when stored at 0-4 degrees C. The half-life of the ATPase activity of 25 microM recA protein was 37 min at 51 degrees C. Purified recA protein binds to single-stranded and double-stranded DNA, unwinds duplex DNA by a mechanism that is stimulated by single-stranded DNA or oligonucleotides, and pairs homologous single strands with duplex DNA.
DEPRESSION AND FUNCTIONAL LEVEL IN SCHIZOPHRENIA: A COMPARISON BETWEEN CHRONIC HOSPITALISED IN-PATIENTS AND COMMUNITY CARE PATIENTS (2007)

Recent innovations in the treatment of schizophrenia reflect a growing trend towards community-based care. Malaysia had in the past few years attempted to deinstitutionalise mental patients in the mental hospitals. Therefore it is important to conduct research to compare the two groups of schizophrenia patients (community-based patients against chronic hospitalised patients) to ascertain if deinstitutionalisation has been beneficial. The main objective of the study was to compare levels of depression and function in community-based patients against chronic hospitalised patients as depression is prevalent among schizophrenia patients. This study was cross sectional in nature where data was collected from 51 inpatients in Hospital Bahagia Ulu Kinta (HBUK) and 23 community-based patients. Calgary Depression Scale for Schizophrenia (CDSS) and Global Assessment of Functioning scale(GAF) were the assessment tools used. Community-based patients were found to have significantly lower scores in the CDSS scale (1.96) as compared to chronic hospitalised patients (4.04); p &lt; 0.01). They also showed higher functional capability between community-based and hospitalised patients respectively (74.04 vs 57.92) respectively. (p &lt; 0.001). Community services appeared to be more effective than long stay in-patient services in preventing depression and promoting better functional levels.
Effects of written drug information on patient knowledge and compliance: a literature review. (1979)

The prospect of patient-oriented prescription drug labeling has focused increased attention on the effectiveness of written information for the consumer. Studies which have evaluated the effects of written prescription drug information in a patient population are reviewed. Several studies indicate that written information can be effective in improving patient compliance with regimens for antibiotic therapy. However, for drugs used on a long-term basis, written information as a sole intervention has not been shown to be sufficient for improving patient compliance. Patient knowledge of less commonly known information, such as precautions, side effects, or special directions is frequently improved by written information. Listing a drug's side effects has not been shown to increase the reported experience of side effects; however, one study suggests that patients may be more willing to report side effects to a health professional if they are listed in the written information. The trend for recent studies has been to focus on the "milieu" in which written information is provided or to systematically vary structural features of the information in order to improve the quality of drug communications.
PCR primed with VNTR core sequences yields species specific patterns and hypervariable probes (1993)

The use of genomic DNA-based techniques in ecological and evolutionary studies has been limited by the availability of suitable probes for species of interest due to the technical difficulty of isolating and applying such probes. We have developed a simple technique that directs polymerase chain reaction (PCR) amplification to regions rich in variable number of tandem repeats (VNTRs). By using published VNTR core sequences as primers in PCRs, fragments were amplified that showed little variation within a species, but did show differences between species. When the amplified fragments were used as probes with genomic DNA Southern blots they produced hypervariable single-locus or few-locus patterns in fish, birds, and humans. We have named this procedure as Directed Amplification of Minisatellite-region DNA (DAMD).
The triterpenoid CDDO induces apoptosis in refractory CLL B cells (2002)

Chronic lymphocytic leukemia (CLL) cells develop chemo-resistance over time. Most anticancer agents function through induction of apoptosis, and therefore resistance against these agents is likely to be caused by selection for CLL cells with defects in the particular apoptosis pathway that is triggered by these drugs. Anticancer agents that function through alternative apoptotic pathways might therefore be useful in treating chemo-resistant CLL. Triterpenoids represent a class of naturally occurring and synthetic compounds with demonstrated antitumor activity. We examined the effects of CDDO (triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid) on CLL B cells in vitro. CDDO induced apoptosis in a dose-dependent manner in all (n = 30) CLL samples tested, including previously untreated and chemo-resistant CLL specimens. CDDO induced rapid proteolytic processing of caspase-8, but not caspase-9, in CLL B cells, suggesting activation of a mitochondria-independent pathway. CDDO-induced apoptosis of CLL B cells was blocked by cytokine response modifier A (CrmA), a suppressor of caspase-8, but not by X-linked inhibitor of apoptosis protein-baculovirus IAP repeat-3 (XIAP-BIR3), a fragment of XIAP, which selectively inhibits caspase-9. Examination of CDDO effects on expression of several apoptosis-relevant genes demonstrated significant reductions in the levels of caspase-8 homolog Fas-ligand interleukin-1-converting enzyme (FLICE)-inhibitory protein (c-FLIP), an endogenous antagonist of caspase-8. However, reductions of FLIP achieved by FLIP antisense oligonucleotides were insufficient for triggering apoptosis, indicating that CDDO has other targets in CLL B cells besides FLIP. These data suggest that the synthetic triterpenoid CDDO should be further explored as a possible therapeutic agent for treatment of chemo-resistant CLL.
Acetoacetyl-acyl carrier protein synthase (1989)

The biochemical basis for the inhibition of fatty acid biosynthesis in Escherichia coli by the antibiotic thiolactomycin was investigated. A biochemical assay was developed to measure acetoacetyl-acyl carrier protein (ACP) synthase activity, a recently discovered third condensing enzyme from E. coli (Jackowski, S., and Rock, C.O. (1987) J. Biol. Chem. 262, 7927-7931). In contrast to the other two condensing enzymes in E. coli, acetoacetyl-ACP synthase (synthase III) condensed malonyl-ACP with acetyl-CoA, rather than with acetyl-ACP. The concentration dependence of thiolactomycin inhibition of fatty acid biosynthesis in vivo was the same as the inhibition of acetoacetyl-ACP synthase activity in vitro indicating that the two phenomena were related. A thiolactomycin-resistant mutant (strain CDM5) was isolated. The specific activity of acetoacetyl-ACP synthase in extracts from this mutant was 10-fold lower than in extracts from its thiolactomycin-sensitive parent resulting in a marked defect in the ability of strain CDM5 to incorporate acetyl-CoA into fatty acids in vitro. The residual acetoacetyl-ACP synthase activity in the resistant strain was refractory to thiolactomycin inhibition. In addition, acetyl-CoA:ACP transacylase activity in strain CDM5 was resistant to inactivation by thiolactomycin suggesting that the acetoacetyl-ACP synthase also catalyzes this transacylation reaction. These data point to acetoacetyl-ACP synthase as a target for thiolactomycin inhibition of bacterial fatty acid biosynthesis.
Genioglossus and breathing responses to airway occlusion: effect of sleep and route of occlusion (1988)

We examined the effect of sleep state on the response of genioglossus muscle (EMGgg) activity to total airway occlusion applied at 1) nasal (N) airway [and thus exposing the upper airway (UAW) to pressure changes] and 2) tracheal (T) airway (thus excluding UAW from pressure changes). A total of 233 tests were performed during wakefulness (W), 98 tests in slow-wave sleep (SWS), and 72 tests in rapid-eye-movement (REM) sleep. Prolongation of inspiratory time (TI) of the first occluded effort occurred in all tests irrespective of behavioral state, with the greatest increase seen in awake N tests. Nasal tests augmented EMGgg activity in the first occluded breath and produced a linear increase in EMGgg during occlusion. The EMGgg activity at any given time during nasal occlusion in SWS was less than that recorded during W tests. There was a marked reduction in EMGgg response to N occlusion during REM sleep. The EMGgg activity during awake T tests was significantly less than that of N tests at any given time during occlusion. There was no relationship between the level of EMGgg activity and asphyxia in T tests performed during SWS and REM sleep. Nasal tests decreased the force generated by the inspiratory pump muscles and the central drive to breathing compared with T tests. These results confirm the important role of the UAW in regulating breathing pattern and indicate that both immediate and progressive load-compensating responses during nasal occlusion are influenced by information arising from the UAW.
Mechanistic insights into the role of truncating PREX2 mutations in melanoma (2016)

PREX2 is a PTEN binding protein that is significantly mutated in melanoma and pancreatic ductal adenocarcinoma. We recently reported the molecular mechanism of tumorigenesis associated with PREX2 mutations: truncating PREX2 mutations activate its RAC1 guanine nucleotide exchanger activity leading to increased PI3K/AKT signaling and enhanced cell proliferation.