gebhart/patrepeval huggingface dataset:
The Major Catalytic Subunit Isoforms of cAMP-dependent Protein Kinase Have Distinct Biochemical Properties in Vitro and in Vivo (1996)

Two isoforms of the catalytic subunit of cAMP-dependent protein kinase, Calpha and Cbeta1, are known to be widely expressed in mammals. Although much is known about the structure and function of Calpha, few studies have addressed the possibility of a distinct role for the Cbeta proteins. The present study is a detailed comparison of the biochemical properties of these two isoforms, which were initially expressed in Escherichia coli and purified to homogeneity. Cbeta1 demonstrated higher Km values for some peptide substrates than did Calpha, but Cbeta1 was insensitive to substrate inhibition, a phenomenon that was observed with Calpha at substrate concentrations above 100 microM. Calpha and Cbeta1 displayed distinct IC50 values for the alpha and beta isoforms of the protein kinase inhibitor, protein kinase inhibitorpeptide, and the type IIalpha regulatory subunit (RIIalpha). Of particular interest, purified type II holoenzyme containing Cbeta1 exhibited a 5-fold lower Ka value for cAMP (13 nM) than did type II holoenzyme containing Calpha (63 nM). This latter result was extended to in vivo conditions by employing a transcriptional activation assay. In these experiments, luciferase reporter activity in COS-1 cells expressing RIIalpha2Cbeta12 holoenzyme was half-maximal at 12-fold lower concentrations of 8-(4-chlorophenylthio)-cAMP and 5-fold lower concentrations of forskolin than in COS-1 cells expressing RIIalpha2Calpha2 holoenzyme. These results provide evidence that type II holoenzyme formed with Cbeta1 is preferentially activated by cAMP in vivo and suggest that activation of the holoenzyme is determined in part by interactions between the regulatory and catalytic subunits that have not been described previously.
Emerging concepts in the management of acute lymphoblastic leukaemia. (1993)

Modern chemotherapy can cure more than 70 per cent of children with standard risk acute lymphoblastic leukaemia (ALL). Encouraging results are also reported in children with high risk ALL receiving intensive chemotherapy. Results in adults with ALL are less satisfactory, the long term survival is less than 35 per cent. Further dose intensification as possible in the setting of bone marrow transplantation (BMT) has increased the cure rate to 50 per cent in adult ALL. Allogeneic BMT has, however, besides the enhanced antileukaemia activity related to high dose therapy, additional antileukaemia effect related to immune mechanisms. Immune effects may be separated into three elements viz., an antileukaemia effect of graft vs host disease (GvHD), a separate antileukaemia effect of T cells and possibly a specific graft vs leukemia effect (GvL). These immune mediated antileukaemic effects offer a new potential therapeutic modality. For instance, the T cell antileukaemic effect of transplant could be achieved by transfusing radiated T cells or administering lymphokines. Alternatively autologous bone marrow could be manipulated in vitro prior to reinfusion. Manipulation might include activation of natural killer (NK) cells or lymphokine activated killer (LAK) activity. Another newer approach to treat ALL is the use of hemopoietic growth factors. Use of these factors prior to chemotherapy may increase the proportion of proliferating leukaemic stem cells. This would increase the efficacy of many drugs since most are active against proliferating cells. Hemopoietic regulatory factors could also be used to directly inhibit leukemic cell growth or to promote differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)
TEMPO-Mediated Oxidation of Primary Alcohols to Carboxylic Acids by Exploitation of Ethers in an Aqueous–Organic Biphase System (2009)

Abstract Expeditious and benign methods for primary alcohol–carboxylic acid conversions with TEMPO were developed in a biphasic system composed of a slightly miscible ether (THP) and aqueous layer. Easily available co-oxidants such as Py·HBr3, Bu4NBr3, and electrooxidation were successfully applied to generate N-oxoammonium species as a recyclable catalyst.
Rizatriptan in the treatment of migraine (2006)

Migraine is a common, disabling disorder associated with considerable personal and societal burden. Current guidelines recommend triptans for the acute treatment of migraine unlikely to respond to less effective therapies. Rizatriptan is a second-generation triptan available in tablet or orally disintegrating tablet (wafer) formulations that offers several advantages over other members of its class. Rizatriptan is rapidly absorbed from the gastrointestinal tract and achieves maximum plasma concentrations more quickly than other triptans, providing rapid pain relief. Clinical trials have shown that rizatriptan is at least as effective or superior to other oral migraine-specific agents in the acute treatment of migraine, and has more consistent long-term efficacy across multiple migraine attacks. Rizatriptan has a favorable tolerability profile, and patients have reported greater satisfaction and a preference for rizatriptan over other migraine-specific agents. Improvements in quality of life reported with rizatriptan are consistent with its favorable efficacy and tolerability profiles. Notably, multi-attribute decision models that combine clinical data with patient- and physician-reported treatment preferences have identified rizatriptan as one of three triptans closest to a hypothetical "ideal". The efficacy and tolerability of rizatriptan for the acute treatment of migraine have thus been well established.
Electrospray Propulsion Based on Emitters Microfabricated in Porous Metals (2011)

indicating that the thrust density can be increased with emitter miniaturization and clustering. A two-dimensional emitter array is constructed from three linear arrays and experiments show that the device produces an average current of around 1 �A per emitter at the highest voltages. Direct thrust measurements using a torsional balance show that the test fixture produces between 0.05 to 0:1 � N of thrust per emitter, as anticipated by theoretical estimates.
Cell proliferation in prostate cancer patients with lymph node metastasis: a marker for progression. (1999)

The biological aggressiveness of lymph node-positive prostate cancer is closely linked to cancer volume in nodal metastases. We evaluated MIB-1 (Ki-67) labeling index and bcl-2 expression in primary cancer and matched nodal metastases from 138 node-positive patients treated with radical prostatectomy and bilateral pelvic lymphadenectomy between 1987 and 1992 at the Mayo Clinic. One hundred twenty-eight patients (93%) received androgen deprivation therapy within 90 days after radical prostatectomy. Mean patient age was 66 years (range, 51-78). The median follow-up was 6.7 years (range, 0.03-11). MIB-1 (Ki-67) labeling index was determined by digital image analysis, and nodal cancer volume was determined by the grid method. Systemic progression, defined as the presence of distant metastasis documented by biopsy or radiographic examination, was used as an outcome end point in the Cox proportional hazard models. MIB-1 labeling index in nodal metastases was predictive of systemic progression-free survival (P = 0.001). The 8-year systemic progression-free survival was 100% for those with MIB-1 labeling index <3.5% compared with 78% for those with MIB-1 labeling index > or =7.8%. MIB-1 labeling index correlated with Gleason score, DNA ploidy, and nodal cancer volume (P<0.001, 0.04, and <0.001, respectively). After controlling for nodal cancer volume, MIB-1 labeling index remained significant in predicting systemic progression-free survival (P = 0.047). bcl-2 expression in the primary cancer and lymph node metastasis was associated with systemic progression-free survival in univariate analysis (P = 0.027 and 0.048, respectively) but was not significant after adjusting for nodal cancer volume (P = 0.52 and 0.17, respectively). Our data indicate that assessment of cell proliferation in nodal metastasis is predictive of clinical outcome in prostate cancer patients with regional lymph node metastasis.
CD molecules 2005: human cell differentiation molecules (2005)

The immune system works through leukocytes interacting with each other, with other cells, with tissue matrices, with infectious agents, and with other antigens. These interactions are mediated by cell-surface glycoproteins and glycolipids. Antibodies against these leukocyte molecules have provided powerful tools for analysis of their structure, function, and distribution. Antibodies have been used widely in hematology, immunology, and pathology, and in research, diagnosis, and therapy. The associated CD nomenclature is commonly used when referring to leukocyte surface molecules and antibodies against them. It provides an essential classification for diagnostic and therapeutic purposes. The most recent (8th) Workshop and Conference on Human Leukocyte Differentiation Antigens (HLDA), held in Adelaide, Australia, in December 2004, allocated 95 new CD designations and made radical changes to its aims and future operational strategy in order to maintain its relevance to modern human biology and clinical practice.
Real-time Deep Pose Estimation with Geodesic Loss for Image-to-Template Rigid Registration (2018)

With an aim to increase the capture range and accelerate the performance of state-of-the-art inter-subject and subject-to-template 3D registration, we propose deep learning-based methods that are trained to find the 3D position of arbitrarily oriented subjects or anatomy based on slices or volumes of medical images. For this, we propose regression CNNs that learn to predict the angle-axis representation of 3D rotations and translations using image features. We use and compare mean square error and geodesic loss to train regression CNNs for 3D pose estimation used in two different scenarios: slice-to-volume registration and volume-to-volume registration. Our results show that in such registration applications that are amendable to learning, the proposed deep learning methods with geodesic loss minimization can achieve accurate results with a wide capture range in real-time (&lt;100ms). We also tested the generalization capability of the trained CNNs on an expanded age range and on images of newborn subjects with similar and different MR image contrasts. We trained our models on T2-weighted fetal brain MRI scans and used them to predict the 3D pose of newborn brains based on T1-weighted MRI scans. We showed that the trained models generalized well for the new domain when we performed image contrast transfer through a conditional generative adversarial network. This indicates that the domain of application of the trained deep regression CNNs can be further expanded to image modalities and contrasts other than those used in training. A combination of our proposed methods with accelerated optimization-based registration algorithms can dramatically enhance the performance of automatic imaging devices and image processing methods of the future.
Isolation of circulating epithelial and tumor progenitor cells with an invasive phenotype from breast cancer patients (2009)

Recent research advances show that tumor cell intravasation (entry into the circulation) and metastasis occur very early in breast cancer progression. Clinical studies also illustrate the potential importance of detection of circulating tumor cells (CTCs) in outcomes of patients with metastatic breast cancer. Whether these cells exhibit the invasiveness and express tumor stem or progenitor markers, hallmark of the metastatic phenotype, is less well characterized. To detect CTCs with the invasive phenotype and to explore their molecular features, we applied a functional cell separation method, called collagen adhesion matrix (CAM) assay, as enrichment and identification steps. The CAM-coated device successfully recovered tumor cells spiked in 1 ml of blood with a 54% +/- 9% (n = 18) recovery rate and 0.5-35% purity, and detected invasive tumor cells in 10/10 blood samples (100% yield) from patients with metastatic breast cancer with a range of 18-256 CTCs/ml and average of 126 +/- 25 (mean +/- SD) CTCs/ml. CTCs were detected in blood samples of 28/54 (52%) Stage I-III breast cancer patients with a mean count of 61 CTCs/ml. Furthermore, the relative frequency of these cells correlated to the staging, lymph node-status and survival of patients with early stage breast cancer. CAM-captured cells were capable of propagation in culture. Gene expression and multiplex flow cytometric analyses on CAM-captured cells demonstrated the existence of distinct populations of CTCs including these of epithelial lineage and stem or progenitor cells. Thus, CAM-initiated CTC detection provides advantages for examining invasiveness and tumor progenitor phenotypes.
Regularly methylated novel pro‐apoptotic genes associated with recurrence in transitional cell carcinoma of the bladder (2006)

Epigenetic silencing of tumor suppressor genes by promoter hypermethylation has been shown for a variety of genes in bladder cancer. Various p53 target genes have been investigated, but only few demonstrated promoter hypermethylation when semiquantitative detection methods were applied. To address to the question whether promoter methylation of novel p53 effector genes is a common event in transitional cell carcinoma of the bladder, we selected the p53 target genes apoptotic protein-activating factor (APAF-1), Caspase 8 (CASP-8), death-associated protein kinase, (DAPK-1) and insulin-like growth-factor-binding protein-3 (IGFBP-3), performing quantitative methylation-specific real-time PCR. The individual level of methylation (normalized index of methylation) was correlated with clinicopathological features as well as the biological behavior of the superficial and muscleinvasive tumors. Tissue was obtained from 110 tumor patients and 20 patients without urological malignancy. The median follow-up of the tumor patients was 52 months. Hypermethylation of the promoter region in tumor specimens was common for APAF-1 (100%), DAPK-1 (74%) and IGFBP-3 (66%), but not for CASP-8 (3.6%). It was seen less frequently and with undetectable or low methylation levels in the normal urothelium group. The APAF-1 methylation levels significantly correlated with tumor stage and tumor grade. The APAF-1 and IGFBP-3 methylation levels were able to separate tumors with higher recurrence risk from low-risk tumors in nonmuscleinvasive and muscleinvasive tumors. In multivariate analysis, APAF-1 and IGFBP-3 methylation levels were independent prognostic markers for recurrence in superficial bladder tumors. This study provides new insights into the role of promoter methylation of selected p53 target genes. The extent of promoter methylation of specific genes offers additional prognostical information and is associated with the outcome in patients with nonmuscleinvasive and muscleinvasive bladder cancer.
Biochemical Measures of Antioxidant Status (2004)

Oxidative stress results from a disruption of cellular prooxidant/antioxidant balance due to reactive oxygen species and other radicals and oxidants, and may be directly or indirectly involved in many pathological processes. Direct detection of reactive oxygen species and other radicals is difficult. Oxidative damage is generally assessed by measurement of secondary oxidation products. Antioxidant status can be assessed by measuring individual plasma or tissue levels of antioxidants and/or by using measures of antioxidant capacity. Clinical studies must include multiple biomarkers to adequately assess in vivo antioxidant status/oxidative stress. This review will focus on noninvasive biomarkers of radical-induced damage in biological tissues and fluids and other biomarkers of antioxidant status.
Molecular mechanisms responsible for aberrant splicing of SERCA1 in myotonic dystrophy type 1 (2007)

Myotonic dystrophy type 1 (DM1) is an autosomal dominant neuromuscular disorder associated with an expansion of CTG trinucleotide repeats in the 3'-untranslated region of the myotonic dystrophy protein kinase (DMPK) gene. The RNA gain-of-function hypothesis proposes that mutant DMPK mRNA alters the function and localization of alternative splicing regulators, which are critical for normal RNA processing. Previously, we found alternative splicing variants of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase 1 (SERCA1), which excluded exon 22, in skeletal muscle of DM1 patients. In the present study, we analyzed the molecular mechanisms responsible for the splicing dysregulation of SERCA1. Five 'YGCU(U/G)Y' motifs that could potentially serve as Muscleblind-like 1, (MBNL1)-binding motifs, are included downstream from the SERCA1 exon 22. Exon trapping experiments showed that MBNL1 acts on the 'YGCU(U/G)Y' motif, and positively regulates exon 22 splicing. Of the five MBNL1 motifs in intron 22, the second and third sites were important for regulation of exon 22 splicing, but the other three binding sites were not required. Overexpression of the CUG repeat expansion of DMPK mRNA resulted in exclusion of exon 22 of SERCA1. These results suggest that sequestration of MBNL1 into the CUG repeat expansion of DMPK mRNA could cause the exclusion of SERCA1 exon 22, and the expression of this aberrant splicing form of SERCA1 could affect the regulation of Ca(2+) concentration of sarcoplasmic reticulum in DM patients.
Long-Lasting Immune Responses 4 Years after GAD-Alum Treatment in Children with Type 1 Diabetes (2011)

A phase II clinical trial with glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) has shown efficacy in preserving residual insulin secretion in children and adolescents with recent-onset type 1 diabetes (T1D). We have performed a 4-year follow-up study of 59 of the original 70 patients to investigate long-term cellular and humoral immune responses after GAD-alum-treatment. Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with GAD(65). Frequencies of naïve, central and effector memory CD4+ and CD8+ T cells were measured, together with cytokine secretion, proliferation, gene expression and serum GAD(65) autoantibody (GADA) levels. We here show that GAD-alum-treated patients display increased memory T-cell frequencies and prompt T-cell activation upon in vitro stimulation with GAD(65), but not with control antigens, compared with placebo subjects. GAD(65)-induced T-cell activation was accompanied by secretion of T helper (Th) 1, Th2 and T regulatory cytokines and by induction of T-cell inhibitory pathways. Moreover, post-treatment serum GADA titres remained persistently increased in the GAD-alum arm, but did not inhibit GAD(65) enzymatic activity. In conclusion, memory T- and B-cell responses persist 4 years after GAD-alum-treatment. In parallel to a GAD(65)-induced T-cell activation, our results show induction of T-cell inhibitory pathways important for regulating the GAD(65) immunity.
Clozapine-Induced Hypersalivation (2000)

It is unclear whether clozapine increases salivation through its muscarinic M4 receptor activation and/or blockade of alpha2-adrenoceptors, or by causing a distortion in swallowing reflex. Treatment options include chewing gum, reducing the dosage of clozapine, or prescribing pharmacologic agents such as anticholinergics or alpha2-adrenoceptor agonists.
Intracellular Infection by the Human Granulocytic Ehrlichiosis Agent Inhibits Human Neutrophil Apoptosis (2000)

In patients with human granulocytic ehrlichiosis (HGE), the HGE agent has been seen only in the peripheral blood granulocytes, which have a life span too short for ehrlichial proliferation. To determine if the HGE agent delays the apoptosis of human peripheral blood neutrophils for its advantage, peripheral blood granulocytes consisting mostly of neutrophils were incubated with freshly freed host cell-free HGE agent in vitro. The HGE agent induced a significant delay in morphological apoptosis and the cytoplasmic appearance of histone-associated DNA fragments in the granulocytes. This antiapoptotic effect was dose dependent. Although much weaker than the HGE agent freshly freed from the host cells, noninfectious purified HGE agent stored frozen and thawed also had antiapoptotic effect, which was lost with proteinase K treatment but not with periodate treatment. Treatment of neutrophils with a transglutaminase inhibitor, monodansylcadaverine, blocked the antiapoptotic effect of the HGE agent. Addition of oxytetracycline, however, did not prevent or reverse the antiapoptotic effect of the HGE agent. These results suggest that binding of a protein component(s) of the HGE agent to neutrophils and subsequent cross-linking and/or internalization of the receptor and ehrlichiae are required for antiapoptotic signaling, but ehrlichial protein synthesis and/or proliferation is not required. MG-132, a proteasome inhibitor, and cycloheximide accelerated the apoptosis of neutrophils and overrode the antiapoptotic effect of the HGE agent. Studies with specific inhibitors suggest that protein kinase A, NF-kappaB, and interleukin 1beta are not involved in the antiapoptotic mechanism of the HGE agent.
Advances in Applied Biotechnology (2012)

ISBN: 978-953-307-820-5
Basement Membrane Collagen: Degradation by Migrating Endothelial Cells (1983)

One of the first steps in neovascularization is dissolution of the basement membrane at the point of endothelial outgrowth. An assay was developed to determine whether basement membrane collagens (types IV and V) are degraded by endothelial cells migrating toward a chemotactic stimulus. Fetal bovine endothelial cells were placed on one side of a filter containing the collagen substrate, and a chemoattractant derived from retinal extracts was placed on the opposite side. Degradation of both type IV and type V collagens was observed when the retinal factor was placed on the side of the filter opposite the endothelial cells. Metalloproteinases that cleaved type IV and type V collagens could be extracted from the endothelial cells with detergents. Such endothelial cell-associated (possibly membrane-bound) proteinases may locally disrupt the basement membrane and facilitate the outgrowth of capillary sprouts toward the angiogenic stimulus.
A Very Efficient Algorithm For Correction Of Skewed Documents (2000)

Publication in the conference proceedings of EUSIPCO, Tampere, Finland, 2000
HIV Acquires Functional Adhesion Receptors from Host Cells (1995)

CD4 is known to serve as the principal cellular receptor for HIV. However, several observations suggest that other molecules may be involved in infection of cells by HIV. Cell adhesion molecules and their ligands expressed on HIV-susceptible cells have been implicated in the biology of HIV in a number of studies. We have recently reported that HIV and SIV acquire cell adhesion molecules from host cells. We now report that a specific cell adhesion molecule, CD44, that is acquired by HIV retains its biological activity when expressed on the virus. We tested CEMx174 cells, which are CD4-positive and HIV-susceptible for phorbol ester-inducible binding to hyaluronic acid through CD44. Phorbol ester-stimulated but not unstimulated CEMx174 cells bound hyaluronic acid. Likewise, HIV from stimulated cells but not from unstimulated cells bound hyaluronic acid through acquired CD44 molecules. This is the first demonstration that adhesion molecules acquired by HIV are functional and the results imply that HIV may have the capacity to bind to any cell or substrate that its host cell binds to. The demonstration of functional adhesion receptors on HIV has important implications with respect to the tropism, infectivity, and dissemination of HIV.