gebhart/patrepeval huggingface dataset:
EK2 Derivatives of Bacteriophage Lambda Useful in the Cloning of DNA from Higher Organisms: The λgt WES System (1977)

A derivative of bacteriophage lambda has been modified and tested together with an appropriate host system to meet the criteria of EK2 biologic containment for cloning DNA from higher organisms. In this report certain of the safety features are summarized and some of the tests carried out to confirm the containment properties of the vector are described. The cloning efficiency of this system, together with available gene purification and hybrid screening technology, indicate that it can be used to clone DNA fragments carrying specific, unique mammalian genes.
Gene Expression Profile of Aging and Its Retardation by Caloric Restriction (1999)

The gene expression profile of the aging process was analyzed in skeletal muscle of mice. Use of high-density oligonucleotide arrays representing 6347 genes revealed that aging resulted in a differential gene expression pattern indicative of a marked stress response and lower expression of metabolic and biosynthetic genes. Most alterations were either completely or partially prevented by caloric restriction, the only intervention known to retard aging in mammals. Transcriptional patterns of calorie-restricted animals suggest that caloric restriction retards the aging process by causing a metabolic shift toward increased protein turnover and decreased macromolecular damage.
Analysis of β‐glucans and chitin in a Saccharomyces cerevisiae cell wall mutant using high‐performance liquid chromatography (1994)

We have previously shown that mutations in the yeast KNR4 gene resulted in pleiotropic cell wall defects, including resistance to killer 9 toxin, elevated osmotic sensitivity to SDS and increased resistance to zymolyase, a (1-->3)-beta-glucanase. In this report, we further demonstrated that knr4 mutant cells were more permeable to a chromogenic substrate, X-GAL, suggesting that the mutant cell walls were leakier to certain non-permeable molecules. To determine if these defects resulted from structural changes in the cell walls, we analysed the alkali-insoluble cell wall components using HPLC assays developed for this purpose. Comparative analysis using four isogenic strains from a 'knr4 disrupted' tetrad demonstrated that mutant cell walls contained much less (1-->3)-beta-glucan and (1-->6)-beta-glucan; however, the level of chitin, a minor cell wall component, was found to be five times higher in the mutant strains compared to the wild-type strains. The data suggested that the knr4 mutant cell walls were dramatically weakened, which may explain the pleiotropic cell wall defects.
The role of the membrane‐bound tumour antigen, melanotransferrin (p97), in iron uptake by the human malignant melanoma cell (2000)

Melanotransferrin (MTf) is a membrane-bound transferrin (Tf) homologue with several characteristics in common with serum Tf. MTf is found at high levels in melanoma cells and previous studies have shown that MTf can bind Fe. In addition, Chinese hamster ovary cells transfected with MTf transport Fe from 59Fe-citrate at greater rates than control cells. However, the role of MTf in the Fe uptake process of human melanoma cells remains unknown. In the present study we have characterized the role of MTf in Fe uptake by SK-Mel-28 melanoma cells in order to understand its function. Initial studies examined whether modulation of intracellular Fe levels using the Fe chelator desferrioxamine (DFO) or the Fe donor ferric ammonium citrate (FAC) could change MTf mRNA levels. In contrast to transferrin receptor (TfR) mRNA that increased after exposure to DFO and decreased after incubation with FAC, there was no change in MTf mRNA levels. In addition, compared to control cells, there was no alteration of 125I-labelled anti-MTf mAb-binding in cells exposed to DFO or FAC, suggesting no change in the number of MTf sites. Further studies examined the ability of DFO and FAC to modulate Fe uptake from 59Fe-citrate which is bound by MTf. In contrast to the effect of DFO or FAC at increasing and decreasing Fe uptake from 59Fe-Tf, respectively, DFO had no influence on 59Fe-citrate uptake, whereas FAC markedly increased it. Collectively, these studies suggest that MTf is not regulated in a manner similar to the TfR in response to cellular Fe levels. MTf can be removed from the membrane by phosphatidylinositol-specific phospholipase C (PtdIns-PLC). Preincubation of melanoma cells with PtdIns-PLC reduced anti-MTf mAb binding to 3% of the control, while PtdIns-PLC only slightly reduced 59Fe uptake from 59Fe-citrate. These results suggest that MTf played only a minor role in Fe uptake from 59Fe-citrate by these cells. The expression of MTf mRNA (poly A+) was also examined in 50 human tissues and found to be markedly different to Tf mRNA or TfR mRNA. Surprisingly, MTf mRNA expression was widespread in normal tissues, and was observed at its highest levels in the salivary gland. In contrast to expectations, MTf mRNA expression was generally greater in adult than fetal tissues.
Mechanisms of stenosis after arterial injury. (1983)

The development of luminal narrowing in relationship to intimal thickening was investigated in rat common carotid artery denuded of endothelium. After denudation with a balloon embolectomy catheter endothelium was observed to regenerate from the ends of the denuded segment but not to cover the central third of the artery by 12 weeks. Cross-sections of denuded (Evans blue stained) and reendothelialized (white) areas showed that intimal thickening in the blue, but not the white, region progressively increased with time and was maximal between 4 and 12 weeks. Luminal narrowing was most pronounced at 2 weeks (75%) and less at 12 weeks (35%). The apparent discrepancy in these results was resolved by demonstrating that the vessel circumference in the blue region at the level of the internal elastic lamina was reduced at 2 weeks and the same as controls at 12 weeks; intravenous infusion of papaverine abolished this vasoconstriction of the left carotids at 2 weeks after injury. These results demonstrate that luminal narrowing early after injury is in large part due to smooth muscle contraction of the vessel and late due only to intimal thickening. During the period between 2 and 12 weeks the fraction of the intima occupied by smooth muscle cells decreased markedly, but the total volume due to smooth muscle cells remained relatively constant. Previous studies have demonstrated by DNA measurements that arterial wall cell number is the same at 2 and 12 weeks; these results taken together indicate that continued intimal thickening at late time points is due to synthesis and accumulation of connective tissue without further increase in smooth muscle cell number.
DNA polymerase III of Mycoplasma pulmonis: isolation and characterization of the enzyme and its structural gene, polC (1994)

Mycoplasmas have originated from Gram-positive bacteria via rapid degenerative evolution. The results of previous investigations of mycoplasmal DNA polymerases suggest that the process of evolution has wrought a major simplification of the typical Gram-positive bacterial DNA polymerase profile, reducing it from three exonuclease (exo)-positive enzymes to a single exo-negative species. The objective of this work was to rigorously investigate this suggestion, focusing on the evolutionary fate of DNA polymerase III (Pol III), the enzyme which Gram-positive bacteria specifically require for replicative DNA synthesis. The approach used Mycoplasma pulmonis as the model organism and exploited structural gene cloning, enzymology, and Pol III-specific inhibitors of the HPUra class as investigative tools. Our results indicate that M. pulmonis has strongly conserved a single copy of a structural gene homologous to polC, the Gram-positive bacterial gene encoding Pol III. M. pulmonis was found to possess a DNA polymerase that displays the size, primary structure, exonuclease activity, and level of HPUra sensitivity expected of a prototypical Gram-positive Pol III. The high level of sensitivity of M. pulmonis growth to Gram-positive Pol III-selective inhibitors of the HPUra type strongly suggests that Mycoplasma has conserved not only the basic structure of Pol III, but also its essential replicative function. Evidence for a second, HPUra-resistant polymerase activity in M. pulmonis is also described, indicating that the DNA polymerase composition of Mycoplasma is complex and closer to that of Gram-positive bacteria than previously thought.
Delayed Primary Closure Using Silastic Vessel Loops and Skin Staples: Description of the Technique and Case Reports (1999)

The use of Silastic vessel loops and skin staples for closure of surgical wounds, with or without tissue loss, is a relatively simple technique that can be done at the patient's bedside or in an office setting, using local anesthesia. The vessel loops are tightened or additional staples are placed, as required, until the skin edges are approximated. In a variety of wounds, use of Silastic vessel loops eliminates the need for skin grafting or secondary wound closure and minimizes the morbidity associated with these procedures.
An N-glucosylated peptide detecting disease-specific autoantibodies, biomarkers of multiple sclerosis (2005)

Multiple sclerosis (MS) is a complex disease that seems to depend on several pathophysiological processes. Because of its varied clinical presentation, natural history, and response to therapeutic interventions, MS can be considered to be a group of diseases that have not been yet characterized, thus resulting in difficult evaluation of prognosis. In the last few years, the role of autoAbs in MS has been reevaluated, and, therefore, their identification as specific biomarkers became a relevant target. In this paper, we demonstrate that an aberrant N-glucosylation is a fundamental determinant of autoAb recognition in MS. Thus, we developed CSF114(Glc), an antigenic probe accurately measuring IgM autoAbs in the sera of a patient population, as disease biomarker. The relevance of CSF114(Glc) is demonstrated by its clinical application and correlation with disease activity and prognosis. In fact, CSF114(Glc), a structure-based designed glycopeptide, is able to recognize, by ELISA, the presence of specific IgM autoAbs in the sera of a MS patient population but not in blood donors and other autoimmune conditions. AutoAbs specific for CSF114(Glc) isolated from MS patients recognized myelin and oligodendrocyte antigens by immunohistochemistry but not other nonrelevant tissues. We demonstrate that CSF114(Glc) is a reliable, specific probe in a longitudinal study of untreated MS patients. Development of IgG/IgM anti-CSF114(Glc) Abs paralleled clinical activity and brain lesions positive to MRI. Therefore, a CSF114(Glc)-based immunoassay on sera may have important prognostic value in monitoring MS disease progression guiding optimal therapeutic treatment.
Renal sympathetic activity in spontaneously hypertensive rats and normotensive controls, as studied by three different methods (1984)

Recordings of sympathetic activity from multifibre preparations of renal nerves have produced conflicting results concerning the presence or absence of an increased sympathetic discharge in spontaneously hypertensive rat (SHR) compared to normotensive Wistar-Kyoto rats (WKY). Therefore, recordings of single fibre activity to the kidney were performed in anesthetized SHR and WKY in comparison with multifibre recordings in conscious, undisturbed rats. A new method of estimating sympathetic discharge by analyzing the variability of "cycle activity" in multifibre nerve recordings was also used. The average nerve activity in a great number of cardiac cycles was then expressed in relation (in per cent) to the nerve activity in a small number of cardiac cycles with the highest and lowest nerve activity in each rat. Single fibre recordings showed a significantly higher sympathetic activity to the kidneys in SHR (3.8 +/- 0.3 Hz) than in WKY (1.7 +/- 0.2 Hz; p less than 0.001). Also average "cycle activity" was significantly higher in conscious SHR (34 +/- 1%) than in WKY (26 +/- 2%, p less than 0.01). This was due to the larger number of cardiac cycles in SHR with high sympathetic activity while WKY showed more of "silent" cardiac cycles which lacked nerve impulses. Further, the recordings of rectified multifibre renal nerve activity also showed an elevated sympathetic activity in conscious SHR rats. The increased renal sympathetic activity appears to reflect the "primary" central nervous "hyperreactivity" characterizing SHR hypertension. It is suggested that the increased renal sympathetic activity may be of particular importance for the development of primary hypertension in SHR and perhaps also in man.
Unifying Identification and Context Learning for Person Recognition (2018)

Despite the great success of face recognition techniques, recognizing persons under unconstrained settings remains challenging. Issues like profile views, unfavorable lighting, and occlusions can cause substantial difficulties. Previous works have attempted to tackle this problem by exploiting the context, e.g. clothes and social relations. While showing promising improvement, they are usually limited in two important aspects, relying on simple heuristics to combine different cues and separating the construction of context from people identities. In this work, we aim to move beyond such limitations and propose a new framework to leverage context for person recognition. In particular, we propose a Region Attention Network, which is learned to adaptively combine visual cues with instance-dependent weights. We also develop a unified formulation, where the social contexts are learned along with the reasoning of people identities. These models substantially improve the robustness when working with the complex contextual relations in unconstrained environments. On two large datasets, PIPA and Cast In Movies (CIM), a new dataset proposed in this work, our method consistently achieves state-of-the-art performance under multiple evaluation policies.
Brain-derived neurotrophic factor mechanisms and function in adult synaptic plasticity: new insights and implications for therapy. (2006)

Synaptic plasticity, the fiundamental ability of synapses to undergo experience-dependent changes in synaptic strength, is thought to underlie a range of long-term adaptive responses of the central nervous system. The inability to generate or maintain appropriate changes in synaptic connectivity and neuronal circuitry is likely to impair cognitive futnction associated with many neurological and psychiatric disorders. The success of intervening therapeutic approaches will depend on the ability to target key component mechanisms in the complex process of synaptic plasticity. Brain-derived neurotrophic factor (BDNF) has emerged as a major regulator of synaptic plasticity and a key target in disorders such as major depression and Alzheimner's disease. This review discusses findings that link BDNF mechanisms in synaptic plasticity to disease mechanisms and possible future therapies.
Identification of Novel Receptors on Myeloma Cells and Monocytes That Contribute to Myeloma Tumor Proliferation and Angiogenesis. (2005)

Abstract Hyper-activation of multiple cell signaling pathways, including Akt, IRS-1, JAK/ STAT3, NF-kB, Wnt and MAPK, contribute to myeloma cell survival and/or proliferation, and myeloma tumor vascularization. We discovered the novel expression of two cell surface receptors that are able to activate these cell signals but were not previously known to be expressed by hematopoietic cells or to be involved in hematological malignancies. We analyzed bone marrow (BM) and peripheral blood (PB) mononuclear cells (MCs) from multiple myeloma (MM) patients and normal donors for the expression of new surface receptors by flow cytometry. We found that the malignant cells from myeloma patients (N = 10) and the MM cell lines RPMI 8226 and U266 express the receptor protein tyrosine phosphatase b/z (RPTPb/z). RPTPb/z contributes to the growth of solid tumors, including glioblastoma, neuroblastoma and melanoma by aberrant accumulation of b-catenin, leading to activation of Wnt, NF-kB and Akt-mediated cell signals. We interfered with RPTPb/z stimulation by its ligand, pleiotrophin (PTN), using specific anti-PTN antibody and showed significant inhibition of MM proliferation in vitro by MTT assay. Importantly, when this antibody was administered to MM tumor-bearing mice in vivo a significant decrease in tumor volume was detected. We have also discovered that peripheral blood monocytes from MM patients (N = 9) and normal donors (N = 7), and a monocytic cell line (THP-1), display untranslocated anaplastic lymphoma kinase (ALK) on the cell surface. Dysregulated ALK expression on a variety of solid tumors is associated with tumor growth, vascularization and metastasis. ALK+ monocytes and THP-1 cells, but not ALK− peripheral B or T lymphocytes or the ALK− monocytic cell line U937, respond to ALK stimulation by modulating hematopoietic genes and inducing the expression of endothelial genes as well as exhibiting changes in morphology typical of early vascular endothelial cells (Chen et al, 2004, Blood104: 1472). ALK cross-linking leads to activation of the signaling intermediates IRS-1, PI3′K/Akt, STAT3 and MAPK, that are known to play key roles in angiogenesis. Thus RPTPb/z and ALK, or their downstream signal mediators, could be important new molecular targets for anti-myeloma (RPTPb/z) or anti-angiogenic (ALK) therapy. We are defining the signaling pathway(s) leading from RPTPb/z stimulation to MM cellular proliferation and survival, and from ALK to tumor vascularization via monocytic transdifferentiation. These studies provide potential new targets that should lead to new therapeutic strategies for treating MM.
Candida albicans allergen immunotherapy in recurrent vaginal candidiasis. (2001)

Recurrent vaginal candidiasis is a worldwide problem affecting millions of women. Candida albicans is a potent allergen in some situations and it has been suggested that local hypersensitivity to this yeast can be a factor in the prolongation of the disease. A small number of studies show some benefits of allergen immunotherapy in these patients. We evaluated the efficacy of C. albicans allergen immunotherapy in women with immediate skin test positive for this fungus. We conducted a prospective cohort study of women with recurrent vaginal candidiasis referred by gynecologists to an allergist. All patients had established positive C. albicans in vaginal cultures and were unresponsive to other modes of treatment. None had diabetes or AIDS. In their allergy evaluation, they had an immediate (prick or intradermal) skin test positive to C. albicans. These women were offered the option of C. albicans allergen immunotherapy for a period of 24 months. The efficacy of therapy was evaluated by comparison of the mean incidence of episodes per year before and after immunotherapy Over a period of 33 months, 34 women were enrolled (mean age 33.5 years; range 18-57). They were treated with weekly injections of C. albicans allergenic extract over a mean (+/- SD) period of 17.4+/-7.2 months (4-24 months). Twenty-two of the women had improvement in symptoms. There were complete responses, i.e., absence of acute episodes for 2 years, in nine patients (26%) and partial responses, i.e., decrease in the number and intensity of episodes, in 13 patients (38%). Overall there was a 64% improvement in these patients (95% CI: 46.5-79.9). Eleven patients showed no improvement and one worsened. The effects were evident after 2-12 months of therapy (mean 3.5 months). The mean incidence of episodes of vaginitis per year decreased from a mean (+/- SD) of 8.5+/-2.6 to 3.6+/-4.3 (p = 0.000). The study also showed that the majority of patients were atopic (70%), had allergic rhinitis (67%) and familial history of allergy (70%). Our results suggest that in a subgroup of patients with recurrent vaginal candidiasis, C. albicans allergen immunotherapy lowers the number and intensity of episodes.
Adipose Tissue‐Derived Mesenchymal Stem Cells Improve Revascularization Outcomes to Restore Renal Function in Swine Atherosclerotic Renal Artery Stenosis (2012)

Reno-protective strategies are needed to improve renal outcomes in patients with atherosclerotic renal artery stenosis (ARAS). Adipose tissue-derived mesenchymal stem cells (MSCs) can promote renal regeneration, but their potential for attenuating cellular injury and restoring kidney repair in ARAS has not been explored. We hypothesized that replenishment of MSC as an adjunct to percutaneous transluminal renal angioplasty (PTRA) would restore renal cellular integrity and improve renal function in ARAS pigs. Four groups of pigs (n = 7 each) were studied after 16 weeks of ARAS, ARAS 4 weeks after PTRA and stenting with or without adjunct intrarenal delivery of MSC (10 × 10(6) cells), and controls. Stenotic kidney blood flow (renal blood flow [RBF]) and glomerular filtration rate (GFR) were measured using multidetector computer tomography (CT). Renal microvascular architecture (micro-CT), fibrosis, inflammation, and oxidative stress were evaluated ex vivo. Four weeks after successful PTRA, mean arterial pressure fell to a similar level in all revascularized groups. Stenotic kidney GFR and RBF remained decreased in ARAS (p = .01 and p = .02) and ARAS + PTRA (p = .02 and p = .03) compared with normal but rose to normal levels in ARAS + PTRA + MSC (p = .34 and p = .46 vs. normal). Interstitial fibrosis, inflammation, microvascular rarefaction, and oxidative stress were attenuated only in PTRA + MSC-treated pigs. A single intrarenal delivery of MSC in conjunction with renal revascularization restored renal hemodynamics and function and decreased inflammation, apoptosis, oxidative stress, microvascular loss, and fibrosis. This study suggests a unique and novel therapeutic potential for MSC in restoring renal function when combined with PTRA in chronic experimental renovascular disease.
Free radicals in inflammatory bowel diseases pathophysiology and therapeutic implications. (1994)

Inflammatory bowel diseases are characterized by the accumulation of granulocytes and monocytes/macrophages at the site of inflammation. Activation of these cells leads to the release of degradative enzymes, e.g., proteinases and glycosidases, and the production of reactive oxygen metabolites. This has been shown both in animal models of experimental intestinal injury, and in human inflammatory bowel disease. Scavenging of oxygen radicals protected tissue from damage in experimental inflammation models. Human studies with specific oxygen radical scavengers are rare, preliminary results appear promising. The fact that the aminosalicylates used in the treatment of inflammatory bowel disease are potent antioxidants underscores the important role of reactive oxygen metabolites in this setting.