gebhart/patrepeval huggingface dataset:
The secretome of apoptotic human peripheral blood mononuclear cells attenuates secondary damage following spinal cord injury in rats (2015)

After spinal cord injury (SCI), secondary damage caused by oxidative stress, inflammation, and ischemia leads to neurological deterioration. In recent years, therapeutic approaches to trauma have focused on modulating this secondary cascade. There is increasing evidence that the success of cell-based SCI therapy is due mainly to secreted factors rather than to cell implantation per se. This study investigated peripheral blood mononuclear cells as a source of factors for secretome- (MNC-secretome-) based therapy. Specifically, we investigated whether MNC-secretome had therapeutic effects in a rat SCI contusion model and its possible underlying mechanisms. Rats treated with MNC-secretome showed substantially improved functional recovery, attenuated cavity formation, and reduced acute axonal injury compared to control animals. Histological evaluation revealed higher vascular density in the spinal cords of treated animals. Immunohistochemistry showed that MNC-secretome treatment increased the recruitment of CD68(+) cells with concomitant reduction of oxidative stress as reflected by lower expression of inducible nitric oxide synthase. Notably, MNC-secretome showed angiogenic properties ex vivo in aortic rings and spinal cord tissue, and experiments showed that the angiogenic potential of MNC-secretome may be regulated by CXCL-1 upregulation in vivo. Moreover, systemic application of MNC-secretome activated the ERK1/2 pathway in the spinal cord. Taken together, these results indicate that factors in MNC-secretome can mitigate the pathophysiological processes of secondary damage after SCI and improve functional outcomes in rats.
THE SEATTLE VIRUS WATCH (1977)

The following findings were made from observations of adenovirus (AV) infections in Seattle VW families, 1965-1969, which extended the 1961-1965 New York VW studies: That infections are predominantly enteric, may be abortive or invasive and followed by persistent intermittent excretion was confirmed. That such excretion is most characteristic of types 1, 2, 3 and 5 viruses may explain why these types were usually endemic. However, since observed duration of excretion was not increased despite a longer average observation period, persistent excretion appears not to continue indefinitely and generation-to-generation transmission now seems improbable. Unilike New York, alternate cycling of types 1 and 2 viruses was not seen. Among homotypic susceptibles, infection rates for the endemic types were highest in infants (greater than 90% for types 1 and 2), decreased with age in older children but increased in parents, perhaps because of closer contact with infants. Development of serum neutralizing antibody was most frequent (about 90%) after types 1 and 2 infection; in all cases, titers decayed over time. While delayed virus spread related to persistent intermittent excretion did occur, spread closely following new or renewed (after larger than or equal to 3 months) excretion was more important. Sibling introducers were more effective spreaders than infants, and duration of excretion was more important than mode. These data indicate that homotypic immunity is 85% protective against infection. A protective effect of heterotypic immunity could not be shown. Illness (chiefly respiratory and often febrile) was associated with 49% of infections in susceptibles and with 65% when respiratory shedding occurred. The contribution of AV to all infectious illness, based on virus-positive infections only, was 5% in infants and 3% in the 2-4-year age group; for febrile illness, the corresponding contributions were about 10% and 5%. Inclusion of infections discovered only be serology (49% of all infections) would greatly increase the contribution of AV to illness.
Disparities in HbA1c Levels Between African-American and Non-Hispanic White Adults With Diabetes (2006)

The higher A1C observed in this meta-analysis among African Americans compared with non-Hispanic whites may contribute to disparity in diabetes morbidity and mortality in this population.
Kv1.3 potassium channel blockade as an approach to insulin resistance (2005)

Diabetes mellitus is a devastating metabolic disease caused by either insulin deficiency or resistance and characterised by abnormal glucose, protein and lipid metabolism. It affects > 150 million people worldwide, 14 million in the US alone (90% Type II and 10% Type I) where it accounts for approximately 15% of healthcare expenditure. Insulin resistance is a cardinal feature of Type II diabetes. The molecular mechanisms that mediate insulin resistance are under intense scrutiny, and a major goal of this effort is to uncover potential therapeutic targets. Recent data indicate that the voltage-gated potassium channel, Kv1.3, is an important regulator of peripheral insulin sensitivity and glucose metabolism. Indeed, Kv1.3 channel inhibition increases insulin sensitivity by decreasing inflammatory cytokines and by facilitating the translocation of GLUT4 to the plasma membrane. In light of these novel findings, the author believes that Kv1.3 is a promising target for the development of drugs useful in the management of insulin resistance and diabetes.
Crystal Structures of the Soluble Methane Monooxygenase Hydroxylase from Methylococcus capsulatus (Bath) Demonstrating Geometrical Variability at the Dinuclear Iron Active Site (2001)

The oxidation of methane to methanol is performed at carboxylate-bridged dinuclear iron centers in the soluble methane monooxygenase hydroxylase (MMOH). Previous structural studies of MMOH, and the related R2 subunit of ribonucleotide reductase, have demonstrated the occurrence of carboxylate shifts involving glutamate residues that ligate the catalytic iron atoms. These shifts are thought to have important mechanistic implications. Recent kinetic and theoretical studies have also emphasized the importance of hydrogen bonding and pH effects at the active site. We report here crystal structures of MMOH from Methylococcus capsulatus (Bath) in the diiron(II), diiron(III), and mixed-valent Fe(II)Fe(III) oxidation states, and at pH values of 6.2, 7.0, and 8.5. These structures were investigated in an effort to delineate the range of possible motions at the MMOH active site and to identify hydrogen-bonding interactions that may be important in understanding catalysis by the enzyme. Our results present the first view of the diiron center in the mixed-valent state, and they indicate an increased lability for ferrous ions in the enzyme. Alternate conformations of Asn214 near the active site according to redox state and a distortion in one of the alpha-helices adjacent to the metal center in the diiron(II) state have also been identified. These changes alter the surface of the protein in the vicinity of the catalytic core and may have implications for small-molecule accessibility to the active site and for protein component interactions in the methane monooxygenase system. Collectively, these results help to explain previous spectroscopic observations and provide new insight into catalysis by the enzyme.
Design and Synthesis of Dipeptide Nitriles as Reversible and Potent Cathepsin S Inhibitors (2002)

The specificity of the immune response relies on processing of foreign proteins and presentation of antigenic peptides at the cell surface. Inhibition of antigen presentation, and the subsequent activation of T-cells, should, in theory, modulate the immune response. The cysteine protease Cathepsin S performs a fundamental step in antigen presentation and therefore represents an attractive target for inhibition. Herein, we report a series of potent and reversible Cathepsin S inhibitors based on dipeptide nitriles. These inhibitors show nanomolar inhibition of the target enzyme as well as cellular potency in a human B cell line. The first X-ray crystal structure of a reversible inhibitor cocrystallized with Cathepsin S is also reported.
Antiretroviral Prophylaxis for HIV Prevention in Heterosexual Men and Women (2012)

Oral TDF and TDF-FTC both protect against HIV-1 infection in heterosexual men and women. (Funded by the Bill and Melinda Gates Foundation; Partners PrEP ClinicalTrials.gov number, NCT00557245.).
Recent Advances in Design of Immunogenic and Effective Naked DNA Vaccines Against Cancer (2013)

A variety of clinical trials for vaccines against cancer have provided evidence that DNA vaccines are well tolerated and have an excellent safety profile. DNA vaccines require much improvement to make them sufficiently effective against cancer in the clinic. Nowadays, it is clear that an increased antigen expression correlates with improved immunogenicity and it is critical to vaccine performance in large animals and humans. Similarly, additional strategies are required to activate effective immunity against poorly immunogenic tumour antigens. This review discusses very recent scientific references focused on the development of sophisticated DNA vaccines against cancer. We report a selection of novel and relevant patents employed to improve their immunogenicity through several strategies such as the use of tissue-specific transcriptional elements, nuclear localisation signalling, codon-optimisation and by targeting antigenic proteins to secretory pathway. Recent patents validating portions or splice variants of tumour antigens as candidates for cancer DNA vaccines with improved specificity, such as mesothelin and hTERT, are also discussed. Lastly, we review novel patents on the use of genetic immunomodulators, such as "universal" T helper epitopes derived from tetanus toxin, E. coli heat labile enterotoxin and vegetable proteins, as well as cytokines, chemokines or costimulatory molecules such as IL-6, IL-15, IL- 21 to amplify immunity against cancer.
High-efficiency retroviral-mediated gene transfer into human and nonhuman primate peripheral blood lymphocytes. (1995)

Peripheral blood lymphocytes (PBLs) are primary targets for gene therapy of inherited and acquired disorders of the immune system. We describe the development of an optimized transduction system that provides for high-efficiency retrovirus-mediated gene transfer into primary PBLs. This optimized transduction protocol combines centrifugation of the lymphocytes (1000 x g) at the inception of transduction with phosphate depletion, low-temperature incubation (32 degrees C), and the use of the packaging cell line PG13. Gene marking studies of human and primate PBLs using these optimized transduction conditions demonstrated that the transduction efficiency exceeded 50% of the total lymphocyte population. The optimized transduction efficiency of PBLs with amphotropic retroviral vectors was in excess of 25%. The transduction procedure does not alter phenotype, viability, or expansion of the transduced cells. Our data indicate that this optimized transduction system leads to high-efficiency gene transfer into primary human lymphocytes, which obviates the requirement for selection of transduced cells prior to gene-therapy procedures. Thus, large quantities of healthy retrovirally transduced lymphocytes containing a broad immunological repertoire can be generated for use in clinical protocols. Our results represent a significant improvement in the methodology for the transduction of lymphocytes for gene therapy.
Fabrication of ohmic contact based on platinum to p-type compositionally graded AlGaAs layers (2009)

Novel metallization scheme was proposed for ohmic contact formation to compositionally graded p-type AlGaAs. A metal multilayers of Ti/Pt/Au, Pt/Ti/Pt/Au and Pt/Ti/Ni/Au were deposited by thermal evaporation using electron gun and resistance heater. The contacts were sequentially annealed by rapid thermall annealing system in N2 atmosphere at various temperatures (in the range from 350°C to 550°C). The duration of annealing step was 2 minutes. The as-deposited Pt/Ti/Pt/Au and Pt/Ti/Ni/Au multilayer metallizations had resistivities of 1.4·10-5 Ω·cm2 which have been gradually deteriorated after each subsequent annealing. The current-voltage characteristics of the ohmic contacts to compositionally graded p-type AlGaAs epitaxial layers were studied and discussed.
Gene expression profile in mouse myocardium after ischemia (2000)

This study was designed to elaborate a molecular profile of expressed genes during ischemic injury to the mouse heart after surgical constriction of the left coronary artery without reperfusion. A mouse cDNA array containing 588 known genes was used to compare gene expression in heart RNA after 24-h ischemia with control tissue. Alterations in gene expression on the array were supported by relative reverse transcription-polymerase chain reaction analysis after timed periods of ischemia. Decreased levels of the cell cycle regulator p18ink4 and the oxidative responsive gene glutathione S-transferase were accompanied by an upregulation of the genes associated with cardiac muscle development, alpha-myosin heavy chain and fetal myosin alkali light chain. Other stress responses elicited by cardiac injury included an induction of Egr-1 and Egr-3 transcription factors, as well as the apoptotic regulator Bax. Altogether, these findings indicate that expression of genes associated with a fetal transcription program may be involved with the post ischemic remodeling process in heart ventricles.
PICan: An integromics framework for dynamic cancer biomarker discovery (2015)

Modern cancer research on prognostic and predictive biomarkers demands the integration of established and emerging high-throughput technologies. However, these data are meaningless unless carefully integrated with patient clinical outcome and epidemiological information. Integrated datasets hold the key to discovering new biomarkers and therapeutic targets in cancer. We have developed a novel approach and set of methods for integrating and interrogating phenomic, genomic and clinical data sets to facilitate cancer biomarker discovery and patient stratification. Applied to a known paradigm, the biological and clinical relevance of TP53, PICan was able to recapitulate the known biomarker status and prognostic significance at a DNA, RNA and protein levels.
PARP-1 is involved in autophagy induced by DNA damage (2009)

Autophagy is a lysosome-dependent degradative pathway frequently activated in tumor cells treated with chemotherapy or radiation. PARP-1 has been implicated in different pathways leading to cell death and its inhibition potentiates chemotherapy-induced cell death. Whether PARP-1 participates in the cell's decision to commit to autophagy following DNA damage is still not known. To address this issue PARP-1 wild-type and deficient cells have been treated with a dose of doxorubicin that induces autophagy. Electron microscopy examination and GFP-LC3 transfection revealed autophagic vesicles and increased expression of genes involved in autophagy (bnip-3, cathepsin b and l and beclin-1) in wild-type cells treated with doxo but not in parp-1(-/-) cells or cells treated with a PARP inhibitor. Mechanistically the lack of autophagic features in PARP-1 deficient/PARP inhibited cells is attributed to prevention of ATP and NAD(+) depletion and to the activation of the key autophagy regulator mTOR. Pharmacological or genetical inhibition of autophagy results in increased cell death, suggesting a protective role of autophagy induced by doxorubicin. These results suggest that autophagy might be cytoprotective during the response to DNA damage and suggest that PARP-1 activation is involved in the cell's decision to undergo autophagy.
The distribution of sterols in algae (1971)

Abstract Available analytical techniques are now sufficient for the separation and identification of sterols from complex mixtures in plants. Gas and thin layer chromatography and mass spectroscopy in particular, have been used to resolve some of the confusion concerning the sterol composition of algae. Red algae (Rhodophyta) contain primarily cholesterol, although several species contain large amounts of desmosterol, and one species contains primarily 22‐dehydrocholesterol. Only a few Rhodophyta contain traces of C‐28 and C‐29 sterols. Fucosterol is the dominant sterol of brown algae (Phaeophyta), apparently the major sterol of every species examined. Most Phaeophyta also contain traces of cholesterol and biosynthetic precursors of fucosterol. The sterols of green algae (Chlorophyta) are much more varied and complex than those of other groups of algae. Whereas the Phaeophyta and Rhodophyta contain one primary sterol, many of the Chlorophyta contain a complex mixture of sterols such as occurs in higher plants. The Chlorophyta contain such sterols as chondrillasterol, poriferasterol, 28‐isofucosterol, ergosterol, cholesterol and others. Sterol composition may be of value in the systematics of plants such as the Chlorophyta. Recently (for the first time) complex mixtures of sterols have been isolated in very small amounts in the blue‐green algae (Cyanophyta). Available data on the sterols of other groups of algae are insufficient for making useful comparisons.
PATHOLOGIC CONFORMATIONS OF PRION PROTEINS (1998)

While many aspects of prion disease biology are unorthodox, perhaps the most fundamental paradox is posed by the coexistence of inherited, sporadic, and infectious forms of these diseases. Sensible molecular mechanisms for prion propagation must explain all three forms of prion diseases in a manner that is compatible with the formidable array of experimental data derived from histopathological, biochemical, biophysical, human genetic, and transgenetic studies. In this review, we explore prion disease pathogenesis initially from the perspective of an autosomal dominant inherited disease. Subsequently, we examine how an intrinsically inherited disease could present in sporadic and infectious forms. Finally, we explore the phenomenologic constraints on models of prion replication with a specific emphasis on biophysical studies of prion protein structures.
Patterned epitaxial vapor-liquid-solid growth of silicon nanowires on Si(111) using silane (2008)

We have carried out a detailed study on the vapour-liquid-solid growth of silicon nanowires (SiNWs) on (111)-oriented Si substrates using Au as catalytic seed material. Arrays of individual seeds were patterned by electron-beam lithography, followed by Au evaporation and lift-off. SiNWs were grown using diluted silane as precursor gas in a low-pressure chemical vapor deposition system. The silane partial pressure, substrate temperature, and seed diameter were systematically varied to obtain the growth rate of the NWs and the rate of sidewall deposition. Activation energies of 19kcal∕mol for the axial SiNW growth and 29kcal∕mol for the radial deposition on the SiNW surface are derived from the data. SiNW growth at elevated temperatures is accompanied by significant Au surface diffusion, leading to a loss of Au from the tips of the SiNWs that depends on the layout and density of the Au seeds patterned. In contrast to NWs grown from a thin-film-nucleated substrate, the deterministic patterning of identical Au seeds of varying diameters allows accurate measurements of the nucleation yield of the SiNW, which is close to 100%, and analysis of the epitaxial relationship with the substrate. In addition to the vertical and the three 70.5°-inclined ⟨111⟩ epitaxial growth directions, we observe three additional 70.5°-inclined directions, which are rotated by 60°. The 60° rotation is explained by the occurrence of stacking faults in the SiNWs. The overall yield of vertically grown ⟨111⟩ NWs depends sensitively on the partial pressure of the silane and, to a lesser extent, on the growth temperature. At 80mTorr partial pressure and 470°C, up to 60% of the SiNWs grow in the vertical ⟨111⟩ direction. In situ doping of SiNWs using arsine resulted in a significant reduction of nucleation and wire growth, whereas doping with trimethylboron and phosphine exhibited no difference in growth and epitaxy compared with undoped samples.
Detection of Chlamydia pneumoniae TWAR in Human Coronary Atherectomy Tissues (1995)

Chlamydia pneumoniae TWAR has been associated with coronary heart disease by seroepidemiologic studies and direct detection of the organism in atheromatous lesions of coronary arteries and aorta. In this study, 38 fresh tissue specimens from patients with coronary artery lesions that were treated by directional coronary atherectomy were tested for C. pneumoniae. Twenty-three specimens were from patients with primary lesions and 15 were from patients with restenoses. C. pneumoniae was detected by polymerase chain reaction (PCR), immunocytochemical stain (ICC), or both in 20 of 38 specimens. Using cell identity markers, the organism was localized to macrophages. Ultrastructural evidence of the organism was found in the 2 specimens examined by transmission electron microscopy, which were also positive by both ICC and PCR. C. pneumoniae was found more frequently in tissues from restenoses than in primary lesions (P = .17). There was no relation between the frequency of detection of the organism and C. pneumoniae-specific antibody titers.
DXplain on the Internet. (1998)

DXplain, a computer-based medical education, reference and decision support system has been used by thousands of physicians and medical students on stand-alone systems and over communications networks. For the past two years, we have made DXplain available over the Internet in order to provide DXplain's knowledge and analytical capabilities as a resource to other applications within Massachusetts General Hospital (MGH) and at outside institutions. We describe and provide the user experience with two different protocols through which users can access DXplain through the World Wide Web (WWW). The first allows the user to have direct interaction with all the functionality of DXplain where the MGH server controls the interaction and the mode of presentation. In the second mode, the MGH server provides the DXplain functionality as a series of services, which can be called independently by the user application program.
Methylation and Silencing of the Retinoic Acid Receptor- 2 Gene in Breast Cancer (2000)

Methylation of the RAR-beta2 gene may be an initial step in breast carcinogenesis; treatment of cancer patients with demethylating agents followed by retinoic acid may offer a new therapeutic modality.
N-Glycans in cancer progression (2008)

N-Glycan branching in the medial-Golgi generates ligands for lattice-forming lectins (e.g., galectins) that regulate surface levels of glycoproteins including epidermal growth factor (EGF) and transforming growth factor-beta (TGF-beta) receptors. Moreover, functional classes of glycoproteins differ in N-glycan multiplicities (number of N-glycans/peptide), a genetically encoded feature of glycoproteins that interacts with metabolic flux (UDP-GlcNAc) and N-glycan branching to differentially regulate surface levels. Oncogenesis increases beta1,6-N-acetylglucosaminyltransferase V (encoded by Mgat5) expression, and its high-affinity galectin ligands promote surface retention of growth receptors with a reduced dependence on UDP-GlcNAc. Mgat5(-/-) tumor cells are less metastatic in vivo and less responsive to cytokines in vitro, but undergo secondary changes that support tumor cell proliferation. These include loss of Caveolin-1, a negative regulator of EGF signaling, and increased reactive oxygen species, an inhibitor of phosphotyrosine phosphatases. These studies suggest a systems approach to cancer treatment where the surface distribution of receptors is targeted through metabolism and N-glycan branching to induce growth arrest.
Van de werkvloer (2009)

ZorgSaam Zeeuws-Vlaanderen introduceert organisatiebreed het concept ‘belevingsgericht werken’. Het doel? De zorg beter afstemmen op de wensen van zorgvragers. Om het personeel over de nieuwe aanpak te informeren en te instrueren, ontwikkelde ZorgSaam samen met ROC Westerschelde een elektronische leeromgeving.