gebhart/patrepeval huggingface dataset:
Novel angiotensin peptides regulate blood pressure, endothelial function, and natriuresis. (1998)

Accumulating evidence suggests that angiotensin-(1-7) is an important component of the renin-angiotensin system, having actions that are either identical to or opposite that of angiotensin II. Angiotensin I can be directly converted to angiotensin-(1-7), bypassing formation of angiotensin II. This pathway is under the control of three enzymes: neutral endopeptidases 24.11 (neprilysin) and 24.15 and prolyl-endopeptidase 24.26. Two of the three angiotensin-forming enzymes (neprilysin and endopeptidase 24.15) also contribute to the breakdown of bradykinin and the atrial natriuretic peptide. Furthermore, angiotensin-(1-7) is a major substrate for angiotensin-converting enzyme. These observations suggest that the process of biotransformation between the various Ang peptides of the renin-angiotensin system and other vasodepressor peptides are intertwined through this enzymatic pathway. Substantial evidence suggests that angiotensin-(1-7) stimulates the synthesis and release of vasodilator prostaglandins, and nitric oxide, while also augmenting the metabolic actions of bradykinin. In addition, angiotensin-(1-7) alters tubular sodium and bicarbonate reabsorption, decreases Na+-K+-ATPase activity, induces diuresis, and exerts a vasodilator effect. These physiologic effects of angiotensin-(1-7) favor a blood pressure-lowering effect. The majority of the data currently available suggest that angiotensin-(1-7) mediates its effects through a novel non-AT1/AT2 receptor subtype.
A Neoplastic Epithelial Duct Cell Line Established From An Irradiated Human Salivary Gland (1981)

Transformed epithelial cells were isolated by using tissue culture techniques from an irradiated human submandibular salivary gland which showed no neoplastic lesion. These cells, carrying colony-forming ability in semisolid agar, formed a semiconfluent monolayer with occasional tubular arrangement. All transformed clones were demonstrated by electron microscopic examination to be only one type of cells having fine structure similar to intercalated duct cells. Of six clones isolated, one clone with stable growth was cultured within the sponge matrix, resulting in formation of duct-like structure with mucinous eosinophilic substance. Moreover, inoculation of the cloned cells into nude mice resulted in a production of adenocarcinoma with solid and trabecular pattern. These findings indicate that a human intercalated duct cell line carrying tumorigenicity is established from a human submandibular salivary gland with an exposure to irradiation.
Hemolytic-Uremic Syndrome after Shigellosis (1978)

To investigate three possible causes of the acute hemolysis in the hemolytic-uremic syndrome, we studied prospectively 207 children and 34 adults with shigellosis in Bangladesh. Nineteen children showed acute hemolytic anemia, a leukemoid reaction, thrombocytopenia and oliguria; nine other had, in addition, a serum urea nitrogen level of over 100 mg per diciliter. Eight of the nine had pseudomembranous colitis, and six of the nine died. The frequency of bacteremia was similar in all grades of shigellosis. Circulating immune complexes were found in 10 of 20 patients with uncomplicated shigellosis and in four of six with severe hemolytic-uremic syndrome. Limulus assay for endotoxemia was positive in nine of 18 patients with hemolysis (50 per cent) and three of 61 with uncomplicated shigellosis (5 per cent) (P less than 0.001). These data support the hypothesis that severe colitis in shigellosis is associated with circulating endotoxin from the colon producing coagulopathy, renal microangiopathy and hemolytic anemia.
Synthesis of (R)‐1,2,11‐trihydroxy‐, (R)‐2,11‐, and (R)‐2,10‐dihydroxyaporphines — non naturally occurring aporphine alkaloids from pukateine and thebaine (1991)

Abstract The synthesis of ( R )‐2,10‐dihydroxyaporphine ( 3a ), ( R )‐2,10‐dihydroxy‐ N‐n ‐propylnoraporphine ( 3b ) from thebaine and ( R )‐2,11‐dihydroxyaporphine (7), and 1,2,11‐trihydroxyaporphine ( 9 ), from pukateine is reported. The rearrangement of thebaine and northebaine with methanesulfonic acid to 1a and 1b with subsequent N ‐propylation gave 1b . Tetrazolyation of 1a, 1b and hydrogenolysis of 2a and 2b on Pd/C in acetic acid with subsequent O‐demethylation with hydrobromic acid (48%) led to 3a and 3b . R (‐)‐2,11‐Dihydroxyaporphine ( 7 ) was prepared by lithium/ammonia reduction of pukateine. ( R )‐1,2,11‐Trihydroxyaporphine ( 9 ) was synthesized by reaction of pukateine with boron tribromide in dichloromethane.
Syntheses of Chiral Homoazacalix[4]arenes Incorporating Amino Acid Residues:  Molecular Recognition for Racemic Quaternary Ammonium Ions (2002)

Chiral calixarene analogues incorporating amino acid residues into the macrocyclic rings were prepared from the cyclization reactions of bis(chloromethyl)phenol-formaldehyde tetramer with amino acid methyl ester in moderate yields. The macrocycles form a chiral concavity, which is induced by the chiral transmission from the point chirality of the amino acid residues to the phenol-formaldehyde tetramer unit. The macrocycles have the cavity pi-basic enough to include the quaternary ammonium ion due to the cation-pi interaction and can serve as a shift reagent for racemic ammonium ions during 1H NMR analysis.
HLA-A1 and HLA-A3 T cell epitopes derived from influenza virus proteins predicted from peptide binding motifs. (1993)

The potential value of peptide binding motifs of HLA class I molecules for the prediction of viral epitopes presented to T cells has been analyzed for two common HLA alleles. CTL generated against type A influenza virus recognize peptide epitopes derived from the nucleoprotein (NP) and basic polymerase 1 presented by HLA-A1, and epitopes derived from NP presented by HLA-A3. Distinct peptide binding motifs with characteristic anchor residues were previously identified for each of these class I molecules based on the sequences of endogenous peptides: for HLA-A1, position 3 = Asp or Glu and position 9 = Tyr; for HLA-A3, position 2 = Leu and position 9 = Lys or Tyr. Six peptides containing the HLA-A1 binding motif were identified within the sequences of the NP and basic polymerase 1 proteins, and one peptide containing the HLA-A3 motif was identified in the NP molecule. Three of the six HLA-A1 peptides and the one HLA-A3 NP peptide could bind to HLA-A1 or HLA-A3, respectively, in an in vitro peptide binding assay. Two of the HLA-A1-binding peptides could sensitize target cells for lysis by influenza virus-immune CTL populations restricted by HLA-A1 (NP 44-52 CTELKLSDY and PB1 591-599 VSDGGPNLY), and the one HLA-A3 NP peptide (NP 265-273 ILRGSVAHK) could sensitize target cells for lysis by HLA-A3-restricted influenza-immune CTL. Each peptide was also shown to be able to induce peptide-specific class I-restricted CTL in vitro, and the CTL generated against two of these peptides could specifically recognize virus-infected targets. Thus, these peptide binding motifs can be used to construct immunogenic synthetic epitopes which are capable of inducing antiviral T cell-mediated immune responses.
In Vivo Proof of Concept of Activity and Safety of UCART19, an Allogeneic “Off-the-Shelf” Adoptive T-Cell Immunotherapy Against CD19+ B-Cell Leukemias (2014)

Abstract Chimeric antigen receptor (CAR)-redirected T-cells have given rise to long-term durable remissions and remarkable objective response rates in patients with refractory leukemia, raising hopes that a wider application of CAR technology may lead to a new paradigm in cancer treatment. A limitation of the current autologous approach is that CAR T-cells must be manufactured on a "per patient basis". We have developed a standardized platform for manufacturing T-cells from third-party healthy donors to generate allogeneic "off-the-shelf" engineered CD19-CAR+ T-cell–based frozen products. Our platform involves the use of transcription activator-like effector nucleases (TALEN™), which mediate the simultaneous inactivation of two genes through genome editing. The knockout of the TCR alpha gene eliminates TCR expression and is intended to abrogate the donor T-cell’s potential for graft-versus-host disease (GvHD), while knocking out the CD52 gene makes donor T-cells resistant to the lymphodepleting agent alemtuzumab. In addition, our T-cells are engineered to coexpress the RQR8 gene as a safety feature, with the aim of rendering them sensitive to the monoclonal antibody rituximab. We previously provided proof-of-concept for the application of this approach by manufacturing TCR/CD52-deficient RQR8+ and CD19-CAR+ T-cells (UCART19) using a good manufacturing practice–compatible process, and we also demonstrated that the resulting UCART19 cells were functional using in vitro assays. Here we report the ability of UCART19 cells to engraft into an orthotopic human CD19+ lymphoma xenograft immunodeficient mouse model. UCART19 cells exhibited antitumor activity equivalent to that of standard CD19 CAR T-cells. We also demonstrated that UCART19 cells did not mediate alloreactivity in a xeno-GvHD mouse model. Furthermore, the effectiveness of the rituximab-induced depletion mechanism of RQR8+ cells was shown in an immunocompetent mouse model. In conclusion, our work significantly enlarges upon previous results by showing in vivo that (1) concomitant inactivation of a second gene has no deleterious effects on T-cells, (2) the antitumor potency of manufactured TCR/CD52-deficient CD19–CAR+ T-cells is similar to that of standard CD19-CAR+ T-cells, (3) TCR gene inactivation is efficient at preventing potential graft-versus-host reaction, and (4) allogeneic T-cells can be depleted by the use of rituximab. This valuable dataset supports the development of allogeneic CAR T-cells, and UCART19 will be investigated in an exploratory, first-in-human, clinical trial where refractory/relapsed CD19+ B-cell leukemia patients are to be enrolled. Disclosures Gouble: Cellectis SA: Employment. Poirot:Cellectis SA: Employment. Schiffer-Mannioui:Cellectis SA: Employment. Galetto:Cellectis SA: Employment. Derniame:Cellectis SA: Employment. Arnould:Cellectis SA: Employment. Desseaux:Cellectis SA: Employment. Smith:Cellectis SA: Employment.
Combined Adenovirus-Mediated Nitroreductase Gene Delivery and CB1954 Treatment: A Well-Tolerated Therapy for Established Solid Tumors (2001)

Gene-directed enzyme prodrug therapy (GDEPT) is a refinement of cancer chemotherapy that generates a potent cell-killing drug specifically in tumor cells by enzymatic activation of an inert prodrug. We describe in vivo studies that evaluate the efficacy and safety of intratumoral (i.t.) injection of an adenovirus vector (CTL102) expressing Escherichia coli nitroreductase (NTR) combined with systemic prodrug (CB1954) treatment. A single i.t. injection of CTL102 (7.5 x 10(9) to -2 x 10(10) particles) followed by CB1954 treatment produced clear anti-tumor effects in subcutaneous (s.c.) xenograft models of four cancers that are likely candidates for GDEPT (i.e., primary liver, head and neck, colorectal and prostate). Virus dose-response studies (s.c. liver model) revealed a steep increase and subsequent rapid plateauing of both NTR gene delivery and anti-tumor efficacy. Evidence of minor virus spread (toxicity) was observed in a s.c. head and neck xenograft model. This was eliminated by passive immunization with neutralizing anti-Ad5 antibodies prior to virus injection without reducing the magnitude of the anti-tumor effect. Preexisting anti-Ad5 neutralizing antibodies may therefore be an advantage rather than an issue in the clinical use of this new therapy.
Investigation of smart inspection of critical layer reticles using additional designer data to determine defect significance (2003)

With expected implementation of low k1 lithography on 193nm scanners for 65nm node wafer production, high resolution defect inspection will be needed to insure reticle quality and reticle manufacture process monitoring. Reticle cost and reticle defectivity are both increasing with each shrink to the next node. Simultaneously, system on chip (SoC) designs are increasing in which a large area of the exposure field typically contains dummy patterns and other features which are not electrically active. Knowing which defects will electrically impact device yield and performance can improve reticle manufacturing yield and cycle time -- resulting in lower reticle costs. This investigation examines the feasibility of using additional design data layers for die-to-database reticle inspection to determine in real time the relevance of a reticle defect by its location in the device (Smart InspectionTM). The impact to data preparation and inspection throughput is evaluated. The current prototype algorithm is built on the XPA and XPE die-to-database algorithms for chrome-on-glass and EPSM reticles, respectively. The algorithms implement variable sensitivity based on the additional design data regions. During defect review the defects are intelligently binned into the different predetermined design regions. Tests show the new Smart Inspection algorithm provides the capability of using higher than normal sensitivity in critical regions while reducing sensitivity in less critical regions to filter total defect counts and allow for the review of just defects that matter. Performance characterization of a variable sensitivity Smart Inspection algorithm is discussed in addition to the filtering of the total defect count during review to show the defects that matter to device performance. Using seven critical layer production reticles from a system on chip device we examine the applications of Smart Inspection by layer including active, poly, contact, metal and via layers. Data volume for additional data layers show little impact to inspection data prep time. The total area of the reticle where defects do not matter is as high as 70% on some layers. Review capabilities will be examined for various applications such as reviewing defects in the various regions such as SRAM, dummy pattern, and redundant contact/via specified regions. Lastly, the economics of Smart Inspection will be modeled using the collected knowledge of the applications from the production reticle characterized in this investigation.
Lipoprotein-bound LPS induces cytokine tolerance in hepatocytes (2003)

Bacterial endotoxin (LPS) elicits dramatic responses in the host including elevated plasma lipid levels due to the increased synthesis and secretion of triglyceride (TG)-rich lipoproteins by the liver. We postulate that this cytokine-induced hyperlipoproteinemia, clinically termed the 'lipemia of sepsis', represents an innate, non-adaptive host immune response to infection. Data in support of this hypothesis include the capacity of TG-rich lipoproteins (VLDL and chylomicrons, CM) to bind and neutralize LPS. Herein, we present evidence that CM-bound LPS attenuates the hepatocellular response to pro-inflammatory cytokines. Primary rodent hepatocytes pretreated with CM-LPS complexes for 2 h demonstrated a near 70% reduction in cytokine-induced NO production as compared to non-pretreated control cells (P > or = 0.04). Whereas hepatocytes were maximally tolerant to cytokine stimulation 6 h after CM-LPS pretreatment, the cells spontaneously regained cytokine responsiveness within 40 h. The induction of cytokine tolerance in hepatocytes follows the internalization of CM-LPS complexes and is a process regulated by the LDL receptor. CM-LPS complexes failed to induce cytokine tolerance in hepatocytes wherein lipoprotein receptor activity was inhibited with high dose receptor associated protein (30 microg/ml). Similarly, CM-bound LPS did not induce tolerance in hepatocytes from ldlr(-/-) mice. Thus, the biochemical or genetic inhibition of LDL receptor activity effectively prevented the CM-mediated induction of the cytokine tolerant phenotype. In conclusion, the lipemia of sepsis likely represents a mechanism by which the host combats sporadic, non-life-threatening episodes of endotoxemia. Also, it may indicate a negative regulatory mechanism for the hepatic response to sepsis, serving to effectively down-regulate the acute phase response. A better understanding of how TG-rich lipoproteins modulate the host response to LPS could yield novel biological insights with important clinical implications, including the development of lipid-based therapies for bacterial infections.
Single‐Molecule Determination of the Face‐Specific Adsorption of Amelogenin’s C‐Terminus on Hydroxyapatite (2011)

On the face of it: An atomic force microscopy tip, functionalized with Amelogenin protein (Amel), is used to directly determine the single-molecule, face-specific free energy of Amel binding to crystalline hydroxyapatite (see picture). The experimental values compare well with those from molecular dynamics simulations and enable the key interactions controlling face-specific binding to be identified. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
High aerobic glycolysis of rat hepatoma cells in culture: Role of mitochondrial hexokinase (1977)

A tumorigenic anchorage-dependent cell line (H-91) was established in culture from an azo-dye-induced rat ascites hepatoma. When grown in a glucose-containing medium the cells exhibit high rates of lactic acid production characteristic of rapidly growing tumor cells. However, when glucose is replaced with galactose the cells grow equally well but exhibit only moderately elevated rates of lactic acid production. The molecular basis for this observation cannot be attributed to differences in permeability because initial rates of glucose and galactose entry into hepatoma cells are identical. Rather, the activity of hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) is found to be high in hepatoma cells, about 20-fold higher than that of control and regenerating rat liver. Moreover, tumor hexokinase activity is not inhibited by low concentrations (<0.6 mM) of the reaction product glucose 6-phosphate. Additionally, 50% of the hexokinase activity of hepatoma cells is found associated with the mitochondrial fraction. This fraction is 3-fold enriched in hexokinase activity relative to the homogenate and 4-fold enriched relative to the nuclear and postmitochondrial fractions. Tumor mitochondrial hexokinase appears to be coupled directly to oxidative phosphorylation, because addition of glucose to respiring hepatoma mitochondria (after a burst of ATP synthesis) results in stimulation of respiration. In contrast, glucose has no effect on the respiration of mitochondria from control and regenerating liver. These results suggest that the high glycolytic capacity of H-91 hepatoma cells is due, at least in part, to an elevated form of hexokinase concentrated in the mitochondrial fraction of the cell.
Five hundred years of bookkeeping: a portrait of Luca Pacioli (1994)

status: Published
Underwater Acoustic Navigation with the WHOI Micro-Modem (2006)

The WHOI Micro-Modem is a compact, low-power acoustic transceiver that can provide both acoustic telemetry and navigation. Its size and versatility make it ideal for integration in autonomous underwater vehicles (AUVs). The modem supports the use of both broadband and narrowband transponders for long baseline navigation systems, has a modem-to-modem ranging capability, and can be configured to provide synchronous oneway ranging, when integrated with a precision clock. This paper gives an overview of the different navigation systems supported by the Micromodem and presents the results from field tests conducted on the SeaBED AUV in deployments in Greece, the Bluefin AUV, and whale localizations in the Stellwagen Bank Marine Sanctuary
Production of interleukin-10 by human bronchogenic carcinoma. (1994)

Interleukin-10 (IL-10) is a recently characterized cytokine with suppressive activity against various aspects of the cellular immune response. Our laboratory has previously demonstrated that another anti-inflammatory cytokine, IL-1 receptor antagonist (IRAP) is produced and secreted by human bronchogenic carcinomas. We speculated that tumor production of IRAP may mitigate host responses and confer increased tumor viability. In this study, we investigated the capacity of human bronchogenic tumors to produce IL-10 as another possible mechanism to attenuate host defenses. We found increased levels of antigenic IL-10 in tissue homogenates of human bronchogenic carcinomas compared with normal lung tissue (13.69 +/- 2.87 versus 5.84 +/- 0.84 ng/mg total protein). Immunohistochemical staining of tumors illustrate primary localization of antigenic IL-10 to individual tumor cells. Analysis of supernatants of several unstimulated human bronchogenic cell lines in vitro demonstrated the ability of tumor cells to constitutively produce IL-10. Functional studies of mononuclear cells, cultured in the presence of conditioned medium from a bronchogenic cell line, demonstrated their increased tumor necrosis factor and IL-6 production with the addition of neutralizing antibodies to IL-10. These findings demonstrate that human bronchogenic carcinomas elaborate functional IL-10, which may significantly impair immune effector cell function and enable the tumor to evade host defenses.
Phase I Study of a Recombinant Adenovirus-Mediated Gene Transfer in Lung Cancer Patients (1996)

This ongoing phase I study has demonstrated that a recombinant adenovirus-mediated marker gene, such as rAd.RSV beta-gal, can be safely introduced into humans and that the gene product is expressed by lung tumor cells of the host.
Minor tobacco alkaloids as biomarkers for tobacco use: comparison of users of cigarettes, smokeless tobacco, cigars, and pipes. (1999)

Anabasine and anatabine, which are present in tobacco but not in nicotine medications, can be used to assess tobacco use in persons undergoing nicotine replacement therapy.