gebhart/patrepeval huggingface dataset:
Non-Cardiomyocytes Influence the Electrophysiological Maturation of Human Embryonic Stem Cell-Derived Cardiomyocytes During Differentiation (2009)

Various types of cardiomyocytes undergo changes in automaticity and electrical properties during fetal heart development. Human embryonic stem cell-derived cardiomyocytes (hESC-CMs), like fetal cardiomyocytes, are electrophysiologically immature and exhibit automaticity. We used hESC-CMs to investigate developmental changes in mechanisms of automaticity and to determine whether electrophysiological maturation is driven by an intrinsic developmental clock and/or is regulated by interactions with non-cardiomyocytes in embryoid bodies (EBs). We isolated pure populations of hESC-CMs from EBs by lentivirus-engineered Puromycin resistance at various stages of differentiation. Using pharmacological agents, calcium (Ca(2+)) imaging, and intracellular recording techniques, we found that intracellular Ca(2+)-cycling mechanisms developed early and contributed to dominant automaticity throughout hESC-CM differentiation. Sarcolemmal ion channels evolved later upon further differentiation within EBs and played an increasing role in controlling automaticity and electrophysiological properties of hESC-CMs. In contrast to the development of intracellular Ca(2+)-handling proteins, ion channel development and electrophysiological maturation of hESC-CMs did not occur when hESC-CMs were isolated from EBs early and maintained in culture without further interaction with non-cardiomyocytes. Adding back non-cardiomyocytes to early-isolated hESC-CMs rescued the arrest of electrophysiological maturation, indicating that non-cardiomyocytes in EBs drive electrophysiological maturation of early hESC-CMs. Non-cardiomyocytes in EBs contain most cell types present in the embryonic heart that are known to influence early cardiac development. Our study is the first to demonstrate that non-cardiomyocytes influence electrophysiological maturation of early hESC-CMs in cultures. Defining the nature of these extrinsic signals will aid in the directed maturation of immature hESC-CMs to mitigate arrhythmogenic risks of cell-based therapies.
A Legal Basis for Domain Name Allocation (1997)

The purpose of this memo is to focus discussion on the particular
problems with the exhaustion of the top level domain space in the
Internet and the possible conflicts that can occur when multiple
organisations are vying for the same name. This memo provides
information for the Internet community. It does not specify an
Internet standard of any kind.
Pain and Neuropathy in Cancer Survivors (2006)

In Brief The research on pain and neuropathy conducted on cancer survivors is of varying quality.
The Intermediate in the Uridine Diphosphate Galactose 4-Epimerase Reaction (1973)

Abstract Incubation of UDP-galactose with substrate amounts of UDP-galactose 4-epimerase (EC 5.1.3.2) from Escherichia coli for different times between 2 and 120 min, followed by reduction with NaB3H4 invariably yields a mixture of labeled UDP-glucose and UDP-galactose. Chemical degradation of tritiated hexoses, isolated after NaB3H4 reduction of 2-min incubation mixtures, shows all of the tritium associated with carbon 4, in agreement with the results presented earlier using longer incubation times (Maitra, U. S., and Ankel, H. (1972) Proc. Nat. Acad. Sci. U. S. A. 68, 2660). The total amount of label introduced after 2 min of incubation, when enzyme activity is practically unchanged, is considerably less than that after 120 min of incubation, when enzyme activity is reduced to about 50%. The excess of labeled UDP-hexoses after 120 min of incubation can be quantitatively related to the amount of inactive enzyme formed, assuming that during inactivation additional UDP-4-ketohexose is produced in amounts equivalent to the amounts of inactive enzyme.
Multifunction device security awareness (2008)

This document will discuss the vulnerabilities and threats associated with modern copier/print/fax/e-mail devices commonly known as "document centers." This project will increase awareness of the potential loss of an organization's data. More specifically, this discussion will include published vulnerabilities (regarding certain models), previous discussion and the author's perspective regarding the potential threat. Lastly, this paper will demonstrate the technical anatomy of two different attack vectors against an organization's document center. Research was conducted within a small business office environment, outside operational hours under special permission and agreement, which by necessity limited the scope to single-device experimentation.
Forced Mitotic Entry of S-Phase Cells as a Therapeutic Strategy Induced by Inhibition of WEE1 (2012)

Inhibition of the protein kinase WEE1 synergizes with chemotherapy in preclinical models and WEE1 inhibitors are being explored as potential cancer therapies. Here, we investigate the mechanism that underlies this synergy. We show that WEE1 inhibition forces S-phase-arrested cells directly into mitosis without completing DNA synthesis, resulting in highly abnormal mitoses characterized by dispersed chromosomes and disorganized bipolar spindles, ultimately resulting in mitotic exit with gross micronuclei formation and apoptosis. This mechanism of cell death is shared by CHK1 inhibitors, and combined WEE1 and CHK1 inhibition forces mitotic entry from S-phase in the absence of chemotherapy. We show that p53/p21 inactivation combined with high expression of mitotic cyclins and EZH2 predispose to mitotic entry during S-phase with cells reliant on WEE1 to prevent premature cyclin-dependent kinase (CDK)1 activation. These features are characteristic of aggressive breast, and other, cancers for which WEE1 inhibitor combinations represent a promising targeted therapy.
Heparin Inhibits Ligand Binding to the Leukocyte Integrin Mac-1 (CD11b/CD18) (1999)

We describe a pharmacologically relevant property of heparin that may contribute to its benefits in clinical use. The binding of heparin to Mac-1 and the resulting inhibition in binding of Mac-1 ligands may directly modulate coagulation, inflammation, and cell proliferation.
Effects of 25-OHD3 on renal function in pediatric patients with chronic renal failure. (1984)

19 nondialyzed pediatric patients with chronic renal failure and renal osteodystrophy participated in a 4- year prospective trial of the effects of 25-hydroxycholecalciferol (25-OHD3) in the treatment and prevention of clinical symptoms of renal osteodystrophy. Controversy over the possible deleterious effects of other vitamin D metabolites, namely 1,25-dihydroxycholecalciferol and 1, alpha-hydroxyvitamin D3, led to an examination of the rate of decline in renal function both before and during treatment with 25-OHD3. Serum creatinine and glomerular filtration rates were stable in the patients who completed 2, 3, and 4 years of treatment with 25-OHD3. There was no acceleration in the deterioration of renal function during treatment with 25-OHD3 beyond that which would be expected without vitamin D therapy of any kind. There was an increase in mean serum creatinine after 1 year of treatment because 5 children who entered the study were already in the terminal (accelerated) phase of renal function deterioration. These children completed 1 year of therapy with 25-OHD3.
Fluticasone propionate: an effective alternative treatment for seasonal allergic rhinitis in adults and adolescents. (1994)

Fluticasone aqueous nasal spray was effective in relieving nasal symptoms in adolescents and adults with seasonal allergic rhinitis. Fluticasone administered once or twice daily was superior to beclomethasone administered twice daily in relieving nasal obstruction and rhinorrhea and in reducing nasal symptoms more quickly.
Restriction of major surface protein 2 (MSP2) variants during tick transmission of the ehrlichiaAnaplasma marginale (1999)

Anaplasma marginale is an ehrlichial pathogen of cattle that establishes lifelong persistent infection. Persistence is characterized by rickettsemic cycles in which new A. marginale variant types, defined by the sequence of the expressed msp2 transcripts, emerge. The polymorphic msp2 transcripts encode structurally distinct MSP2 proteins and result in an antigenically diverse and continually changing A. marginale population within the blood. In this manuscript, we used sequence analysis of msp2 transcripts to show that a restricted repertoire of variant types, designated SGV1 and SGV2, is expressed within the tick salivary gland. The same SGV1 and SGV2 variant types were expressed in ticks regardless of the variant types expressed in the blood of infected cattle at the time of acquisition feeding by the ticks. Importantly, subsequent tick transmission to susceptible cattle resulted in acute rickettsemia composed of organisms expressing only the same SGV1 and SGV2 variant types. This indicates that the msp2 expressed by organisms within the tick salivary gland predicts the variant type responsible for acute rickettsemia and disease. This restriction of transmitted A. marginale variant types, in contrast to the marked diversity within persistently infected cattle, supports development of MSP2 vaccines to prevent acute rickettsemia in tick-transmitted infections.
Preoperative Determination of Several Serum Tumor Markers in Patients with Primary Epithelial Ovarian Carcinoma (1999)

This study was designed to evaluate the clinical significance of the use of preoperative serum tumor markers in primary epithelial ovarian cancer. Subjects comprised 111 patients with primary epithelial ovarian cancer. Lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBDH), carcinoembryonic antigen (CEA), CA19-9, tissue polypeptide antigen (TPA), CA125 and sialyl TN (STN) serum levels were measured within 7 days before surgery. The tumor marker values were compared with the histopathologic diagnosis. The overall agreement between the test results and the actual outcome was calculated using Student's t test and analysis of variance (ANOVA). Survival curves were constructed according to the Kaplan-Meier method, and differences in survival were assessed with the log-rank test. The prognostic significance of tumor markers for survival was assessed in a multivariate analysis with the Cox proportional hazards model. Of the tumor markers examined in this study, CA125 showed the highest positive rate (77.6%), followed by 63.2% for STN and 55.9% for CA19-9. When the positive rate was compared according to histologic types, serous cystadenocarcinoma, mucinous cystadenocarcinoma, endometrioid adenocarcinoma and clear cell carcinoma showed the highest positive rates for CA125 (94.1%), CA19-9 (76.9%), CA125 (91.7%) and STN (75.0%), respectively. Regarding the distribution of tumor marker levels according to the FIGO stage, LDH, HBDH, TPA and CA125 were correlated with the clinical stage while CEA, CA19-9 and STN did not show any correlation. From analyses of tumor marker levels according to histologic types, all patients with a ratio of CA125 to CEA of >1, 000 had serous cystadenocarcinoma and a ratio of CA125 to CA19-9 of >50 showed serous cystadenocarcinoma or endometrioid adenocarcinoma. On the other hand, all patients with a ratio of LDH or HBDH to CA19-9 of <1.0 had mucinous cystadenocarcinoma or clear cell carcinoma. From univariate analysis, the survival time of patients with elevated CA125, TPA or STN was significantly shorter than that of patients with normal CA125, TPA or STN levels. When the Cox's proportional hazard model was used, we identified age, clinical stage, clear cell carcinoma and serum STN as independent prognostic factors. Serum CA125, TPA or STN may give significant prognostic information in epithelial ovarian carcinoma. It is noteworthy that STN has been identified as an independent prognostic factor and has a high rate of positivity in clear cell carcinoma.
THE LIPOPHOSPHOGLYCAN OF LEISHMANIA PARASITES (1992)

Protozoan parasites of the genus Leishmania have the remarkable ability to avoid destruction in the hostile environments they encounter throughout their life cycle. The molecular details of how these pathogens persevere with impunity under harsh conditions are beginning to be understood. The fact that Leishmania parasites have adapted to not only survive, but to proliferate probably is due to the protection conferred by specialized molecules on the parasite's cell surface. One such macromolecule is a novel glycoconjugate called lipophosphoglycan. This heterogeneous, lipid-containing polysaccharide is the major surface molecule of the parasite and has been implicated in a surprisingly large number of functions that may contribute the the parasite's pathogenesis. This review emphasizes the structural aspects of lipophosphoglycan and its possible functions and biosynthesis.
Noninvasive two-photon imaging reveals retinyl ester storage structures in the eye (2004)

Visual sensation in vertebrates is triggered when light strikes retinal photoreceptor cells causing photoisomerization of the rhodopsin chromophore 11-cis-retinal to all-trans-retinal. The regeneration of preillumination conditions of the photoreceptor cells requires formation of 11-cis-retinal in the adjacent retinal pigment epithelium (RPE). Using the intrinsic fluorescence of all-trans-retinyl esters, noninvasive two-photon microscopy revealed previously uncharacterized structures (6.9 +/- 1.1 microm in length and 0.8 +/- 0.2 microm in diameter) distinct from other cellular organelles, termed the retinyl ester storage particles (RESTs), or retinosomes. These structures form autonomous all-trans-retinyl ester-rich intracellular compartments distinct from other organelles and colocalize with adipose differentiation-related protein. As demonstrated by in vivo experiments using wild-type mice, the RESTs participate in 11-cis-retinal formation. RESTs accumulate in Rpe65-/- mice incapable of carrying out the enzymatic isomerization, and correspondingly, are absent in the eyes of Lrat-/- mice deficient in retinyl ester synthesis. These results indicate that RESTs located close to the RPE plasma membrane are essential components in 11-cis-retinal production.
Isolation and characterization of the normal crossreacting antigen: homology of its NH2-terminal amino acid sequence with that of carcinoembryonic antigen. (1978)

The normal antigen, NCA, which crossreacts with the carcinoembryonic antigen, CEA, was purified from normal spleen tissue by an immunochemical purification method using insolubilized antibodies to either CEA or NCA. The highly purified NCA obtained was extensively characterized by immunological tests. The molecular weight of NCA determined by chromatography on Sephadex G-200 was approximately 100,000. The total amount of carbohydrate in NCA was 30%, compared to 60% in CEA. NCA and CEA also differed in sugar composition. The amino acid composition of NCA was nearly identical to that of CEA, except for the apparent presence of methionine in NCA but not in CEA. The sequence of the first 26 NH2-terminal amino acids in NCA was identical to that of CEA except at position 21, where alanine was found in NCA instead of valine in CEA.
Wave-plate polarizing beam splitter based on a form-birefringent multilayer grating (1998)

We have fabricated a novel device that acts as a quarter-wave plate at normal incidence and as a polarizing beam splitter at an angle of incidence of ~40 deg . The device is made from a multilayer (SiO(2) /Si(3)N(4)) surface-relief zeroth-order one-dimensional grating with a period of 0.3 mum . The device is designed for an operating wavelength of 632.8 nm. We designed the device by using rigorous coupled-wave analysis and fabricated it by direct-write electron-beam lithography and reactive ion etching. Measurements confirmed the performance of the device as a wave plate and as a polarizing beam splitter.
COMMERCIAL CODE Bank Deposits and Collections: Provide Regulations Relating to Funds Transfers Between Banks (1992)

The Act amends Georgia's Commercial Code to add a new Article 4A, designed to provide a uniform set of rules to govern funds transfers between financial institutions. The addition of Article 4A to Georgia's Commercial Code follows the 1989 completion of the new Article 4A of the Uniform Commercial Code.
Physical implementation of 3D integrated solenoids within silicon substrate for hybrid IC applications (2009)

This paper presents an original concept of a 3D solenoid realized in a 300μm depth High Resistivity Silicon (HRS) substrate using the Through Silicon Via (TSV) interconnection technology. Electrical performances deduced from two-ports S-parameters are reported. A comparison is performed considering first conventional O-shaped planar BiCMOS (Al Back-end) inductor, then a CMOS (45nm node, Cu Back-end) O-shaped inductor respect to area occupation together with electrical performances. A predictive electrical model is proposed and compared to measurement results. Correlations between simulation and measurements are found satisfactory.
Euler Vector for Search and Retrieval of Gray-Tone Images (2005)

A new combinatorial characterization of a gray-tone image called Euler Vector is proposed. The Euler number of a binary image is a well-known topological feature, which remains invariant under translation, rotation, scaling, and rubber-sheet transformation of the image. The Euler vector comprises a 4-tuple, where each element is an integer representing the Euler number of the partial binary image formed by the gray-code representation of the four most significant bit planes of the gray-tone image. Computation of Euler vector requires only integer and Boolean operations. The Euler vector is experimentally observed to be robust against noise and compression. For efficient image indexing, storage and retrieval from an image database using this vector, a bucket searching technique based on a simple modification of Kd-tree, is employed successfully. The Euler vector can also be used to perform an efficient four-dimensional range query. The set of retrieved images are finally ranked on the basis of Mahalanobis distance measure. Experiments are performed on the COIL database and results are reported. The retrieval success can be improved significantly by augmentiong the Euler vector by a few additional simple shape features. Since Euler vector can be computed very fast, the proposed technique is likely to find many applications to content-based image retrieval.
The epidermal growth factor receptor as a target for cancer therapy. (2001)

Epidermal growth factor (EGF) receptors are expressed at high levels in about one third of epithelial cancers, and autocrine activation of EGF receptors appears to be critical for the growth of many tumors. We hypothesized that blockade of the binding sites for EGF and transforming growth factor-alpha on EGF receptors with an antireceptor monoclonal antibody (mAb) might be an effective anti-cancer therapy. We produced murine mAb 225 against EGF receptors and demonstrated blockade of receptor function, as well as inhibition of cell growth in cultures and in nude mouse xenografts. mAb C225 is the human:murine chimeric version of mAb 225. Cell cycle inhibition occurred in G(1) phase, and was due to upregulation of p27(Kip1), resulting in inhibition of cyclin E/cyclin dependent kinase-2 activity and hypophosphorylation of Rb. In addition, the amount and/or activities of a number of proapoptotic molecules were enhanced. The antitumor activity in vivo against xenografts was at least partly attributable to reduced vascularization, resulting from decreased vascular endothelial growth factor and basic fibroblast growth factor production by the tumor cells. Metastasis of xenografts was curtailed with mAB C225 treatment, accompanied by a decrease in tumor production of MMP-9. Further studies showed that mAbs 225 and C225 enhanced the cytotoxicity of chemotherapy against xenografts of a variety of human cancer cell lines. Well established xenografts resistant to either mAb or drug treatment alone were eradicated by the combination therapy. Drugs for which this has been demonstrated include doxorubicin, paclitaxel, cisplatin, and topotecan. Antibody treatment also potentiated the responsiveness of human tumor xenografts to radiation therapy. These findings led to clinical trials of human:murine chimeric mAb C225 in combination with chemotherapy or radiotherapy. Results from phase I and II trials involving more than 500 patients are quite promising, in particular in advanced head and neck cancer treated with C225 plus cisplatin or radiation, in advanced colon cancer treated with C225 plus CPT-11, and in advanced pancreatic cancer treated with C225 plus gemcitabine. Phase III trials are now underway.
Liver Fibrosis: From Pathogenesis to Novel Therapies (2016)

Chronic liver injury is accompanied by a dysbalanced scarring process, termed fibrosis. This process is mainly driven by chronic inflammation and an altered activity of a multitude of different chemokines and cytokines, resulting in the infiltration by immune cells (especially macrophages) and increase of matrix-expressing cell types. These processes might lead to cirrhosis representing the end-stage of fibrosis. Recent clinical studies comprising patients successfully treated for viral hepatitis showed that liver fibrogenesis and even cirrhosis may be reverted. The hepatic capacity to remodel scar tissue and to revert into a normal liver follows specific mechanistic principles that include the termination of chronic tissue damage, shifting the cellular bias from inflammation to resolution, initiation of myofibroblast apoptosis or senescence and, finally, fibrinolysis of excess scar tissue. The plurality of molecular and cellular triggers involved in initiation, progression and resolution of hepatic fibrogenesis offers an infinite number of therapeutic possibilities. For instance, inflammatory macrophages can be targeted via inhibition of chemokine CCL2 or its receptor CCR2 (e.g., by cenicriviroc) as well as by transfer of restorative macrophage subsets. Another target is galectin-3 that acts at various stages along the continuum from acute to chronic inflammation. Profibrogenic cytokines (e.g., transforming growth factor-β), matricellular proteins (e.g., CCN1/CYR61) or signaling pathways involved in fibrogenesis offer further possible targets. Other options are the application of therapeutic antibodies directed against components involved in biogenesis or remodeling of connective tissue such as lysyl oxidase-like-2 or synthetic bile acids like obeticholic acid that activate the farnesoid X receptor and was antifibrotic in a phase 2 study (FLINT trial). Factors affecting the gut barrier function or the intestinal microbiome further expanded the repertoire of drug targets. In this review, we discuss novel concepts in resolution of hepatic fibrosis and focus on drug targets that might be suitable to trigger resolution of fibrosis.
Regulation of human immunodeficiency virus 1 transcription by nef microRNA (2005)

MicroRNAs (miRNAs) are approximately 21-25 nt long and interact with mRNAs to lead to either translational repression or RNA cleavage through RNA interference. A previous study showed that human immunodeficiency virus 1 (HIV-1) nef dsRNA from AIDS patients who are long-term non-progressors inhibited HIV-1 transcription. In the study reported here, nef-derived miRNAs in HIV-1-infected and nef transduced cells were identified, and showed that HIV-1 transcription was suppressed by nef-expressing miRNA, miR-N367, in human T cells. The miR-N367 could reduce HIV-1 LTR promoter activity through the negative responsive element of the U3 region in the 5'-LTR. Therefore, nef miRNA produced in HIV-1-infected cells may downregulate HIV-1 transcription through both a post-transcriptional pathway and a transcriptional neo-pathway.