gebhart/patrepeval huggingface dataset:
Epratuzumab with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated diffuse large B-cell lymphoma (2011)

Approximately 60% of patients with diffuse large B-cell non-Hodgkin lymphoma (DLBCL) are curable with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemoimmunotherapy. Epratuzumab (E) is an unlabeled anti-CD22 monoclonal antibody with efficacy in relapsed DLBCL. This phase 2 trial tested the safety and efficacy of combining E with R-CHOP (ER-CHOP) in untreated DLBCL. A secondary aim was to assess the efficacy of interim positron emission tomography (PET) to predict outcome in DLBCL. Standard R-CHOP with the addition of E 360 mg/m(2) intravenously was administered for 6 cycles. A total of 107 patients were enrolled in the study. Toxicity was similar to standard R-CHOP. Overall response rate in the 81 eligible patients was 96% (74% CR/CRu) by computed tomography scan and 88% by PET. By intention to treat analysis, at a median follow-up of 43 months, the event-free survival (EFS) and overall survival (OS) at 3 years in all 107 patients were 70% and 80%, respectively. Interim PET was not associated with EFS or OS. Comparison with a cohort of 215 patients who were treated with R-CHOP showed an improved EFS in the ER-CHOP patients. ER-CHOP is well tolerated and results appear promising as a combination therapy. This study was registered at www.clinicaltrials.gov as #NCT00301821.
Synthesis of Enantiomerically Pure N-tert-Butanesulfinyl Imines (tert-Butanesulfinimines) by the Direct Condensation of tert-Butanesulfinamide with Aldehydes and Ketones (1999)

Experimental details for the first general methods for the one-step preparation of N-tert-butanesulfinyl imines (tert-butanesulfinimines) (2) from aldehydes and ketones is described. To effect the condensations of tert-butanesulfinamide (1) with aldehydes, the Lewis acidic dehydrating agents MgSO4, CuSO4, or Ti(OEt)4 are employed. Aldehyde condensations mediated by MgSO4 proceed in high yields (84−96%) when an excess of aldehyde is used. In contrast, only a slight excess of aldehyde (1.1 equiv) relative to tert-butanesulfinamide provides sulfinimines in high yields when the more Lewis acidic dehydrating agent CuSO4 is used. The CuSO4-mediated procedure is effective for a wide range of aldehydes, including sterically demanding aldehydes, such as isobutyraldehyde (90%), and electron-rich aldehydes, such as p-anisaldehyde (81%). The still more Lewis acidic Ti(OEt)4 and Ti(O-i-Pr)4 also afford N-tert-butanesulfinyl aldimines from especially unreactive aldehydes, such as pivaldehyde (82%). In addition, Ti(OEt)4 is effective for the condensation of 1 with ketones to afford a wide range of N-tert-butanesulfinyl ketimines in good yields (77−91%). For sulfinyl ketimines derived from methyl or n-alkyl phenyl ketones and methyl or n-alkyl isopropyl ketones, only the E isomer is detected by 1H and 13C NMR in CDCl3. For those cases where the difference in steric demand about the imine is very small, such as for 2-hexanone, high E/Z ratios are still observed (5:1).
Vitiligo autoantibodies are effective against melanoma (1993)

The results of this study point to the presence of anti-melanoma autoantibodies in the sera of patients with localized and diffuse vitiligo. These antibodies have a destructive effect on melanoma cells in vitro and in vivo.
MicroRNA-210 Regulates Cancer Cell Proliferation through Targeting Fibroblast Growth Factor Receptor-like 1 (FGFRL1) (2010)

The importance of microRNAs (miRNAs) in human malignancies has been well recognized. Here, we report that the expression of microRNA-210 (miR-210) is down-regulated in human esophageal squamous cell carcinoma and derived cell lines. Marked decreases in the level of miR-210 were observed especially in poorly differentiated carcinomas. We found that miR-210 inhibits cancer cell survival and proliferation by inducing cell death and cell cycle arrest in G(1)/G(0) and G(2)/M. Finally, we identified fibroblast growth factor receptor-like 1 (FGFRL1) as a target of miR-210 in esophageal squamous cell carcinoma and demonstrated that FGFRL1 accelerates cancer cell proliferation by preventing cell cycle arrest in G(1)/G(0). Taken together, our findings show an important role for miR-210 as a tumor-suppressive microRNA with effects on cancer cell proliferation.
Image guidance of breast cancer surgery using 3-D ultrasound images and augmented reality visualization (1998)

This paper describes augmented reality visualization for the guidance of breast-conservative cancer surgery using ultrasonic images acquired in the operating room just before surgical resection. By combining an optical three-dimensional (3-D) position sensor, the position and orientation of each ultrasonic cross section are precisely measured to reconstruct geometrically accurate 3-D tumor models from the acquired ultrasonic images. Similarly, the 3-D position and orientation of a video camera are obtained to integrate video and ultrasonic images in a geometrically accurate manner. Superimposing the 3-D tumor models onto live video images of the patient's breast enables the surgeon to perceive the exact 3-D position of the tumor, including irregular cancer invasions which cannot be perceived by touch, as if it were visible through the breast skin. Using the resultant visualization, the surgeon can determine the region for surgical resection in a more objective and accurate manner, thereby minimizing the risk of a relapse and maximizing breast conservation. The system was shown to be effective in experiments using phantom and clinical data.
Chemopreventive Effects of Bovine Lactoferrin on N‐Butyl‐N‐(4‐ hydroxybutyl)nitrosamine‐induced Rat Bladder Carcinogenesis (2000)

Chemopreventive effects of bovine lactoferrin (bLF), which is found at high concentrations in colostrum, on rat bladder carcinogenesis were investigated using a rat bladder medium-term bioassay. In experiment 1, a total of 80 F344 male rats, 6 weeks old, were divided into 5 groups. Groups 1 and 2 were treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in the drinking water for 8 weeks and after a 1-week interval, received dietary supplementation with 2% and 0.2% bLF, respectively. Group 3 received 0.05% BBN for 8 weeks and then no treatment. Group 4 was administered 2% bLF alone from week 9, without prior carcinogen exposure. Group 5 was maintained without any treatment throughout the experiment. All rats were killed at the end of week 36. Group 1 demonstrated a significantly decreased multiplicity of the bladder tumors (carcinomas and papillomas) as compared with group 3. Maximum cut surface areas of bladder tumors were also significantly decreased in groups 1 and 2 compared with group 3. No bladder tumors were observed in groups 4 or 5. In experiment 2, a total of 60 rats were divided into two groups (30 rats each); both were treated with 0.05% BBN for 4 weeks and after a 1-week interval, one received 2% bLF (group 1) and the other, basal diet (group 2) for 4 weeks. Group 1 demonstrated a tendency for decrease of the 5-bromo-2'-deoxyuridine (BrdU) labeling index. bLF was detected in the urine of rats fed bLF by ELISA as well as western blot analysis. The findings indicate that 2% bLF can inhibit BBN-induced rat bladder carcinogenesis, and that this may be due to bLF in the urine.
Ontogenesis of the MiteVarroa Jacobsoniin Worker and Drone Honeybee Brood Cells (1983)

SummaryOntogenesis of the mite Varroa jacobsoni Oudemans (1904) was observed at 4 h intervals in brood cells of the honeybee Apis mellifera cecropia. Between July and November 1981, in the region of Thessaloniki, 241 worker and 107 drone cells infested with fertile mites were examined in the post-capping period. A macroscopic distinction between the sexes was recorded photographically as early as the first mobile phase of mite ontogenesis. In cells containing either worker or drone brood, egg-laying by the mite began about 60 h after the cell was capped and one egg was laid every 30 min. Normally the offspring included only one male, which developed from an egg laid about 96 h after capping. Ontogenesis lasted 7·5 days in the female Varroa and 5·5 days in the male. The mite can lay at most 7 eggs in a drone cell and 6 in a worker cell.
Effects of Ionic and Nonionic Contrast Media on Clot Structure, Platelet Function and Thrombolysis Mediated by Tissue Plasminogen Activator in Plasma Clots (1995)

Various radiographic contrast agents have anticoagulant or prothrombotic properties. Ionic agents are reported to have greater antithrombotic potential while nonionic agents are considered more thrombogenic. Some agents after fibrin structure and bind to platelets in purified systems. This study compared the effects of iohexol, a nonionic agent, and iothalamate, an ionic agent, on fibrin assembly, clot structure, platelet function and clot dissolution in plasma. Plasma gels containing increasing concentrations of iothalamate were composed of thinner fibers with decreased fiber mass/length ratios (mu) and reduced gel turbidity. Such clots were more rigid and more resistant to fibrinolysis induced by tissue plasminogen activator (tPA). Gel elastic modula increased from 10,000 to 27,000 dyn/cm2 as iothalamate concentration increased from 0 to 20 mM. 50% lysis time increased from 800 to 1,250 s with the addition of 10 mM iothalamate. At 20 mM, iothalamate had no effect on ADP-induced platelet aggregation but prolonged the lag phase seen with collagen-induced aggregation. Platelet force development increased from 15,300 to 20,400 dyn with 20 mM iothalamate. The effect of iohexol were similar. Gel optical density dropped from 0.50 to 0.32, mu fell from 3.3 to 2.2 x 10(13) D/cm, and elastic modulus rose from 11,000 to 24,000 dyn/cm2 as iohexol concentration was increased from 0 to 20 mM. Clots formed in the presence of 60 mM iohexol and tPA did not dissolve in 72 h while control clot 50% lysis time was 450 s. At concentrations > or = 40 mM, iohexol completely blocked collagen-induced platelet aggregation. Platelet force development increased from 7,660 to 19,600 with 40 mM iohexol. Contrast media possess profound fibrin-altering activities in plasma. Fibrin formed in the presence of some agents may be significantly more resistant to fibrinolysis.
Hydrogen Sulfide and Reduced-Sulfur Gases Adversely Affect Neurophysiological Functions (1995)

Hydrogen sulfide (H2S) above 50 parts per million (ppm) causes unconsciousness and death. Lower doses of H2S and related gases have been regarded as innocuous, but the effects of prolonged exposure have not been studied. This study was designed to determine whether people exposed to sulfide gases as a result of working at or living downwind from the processing of "sour" crude oil demonstrate persistent neurobehavioral dysfunction. Thirteen former workers and 22 neighbors of a refinery complained of headaches, nausea, vomiting, depression, personality changes, nosebleeds, and breathing difficulties. Their neurobehavioral functions and a profile of mood states (POMS) were compared to 32 controls, matched for age and educational level. The exposed subjects' mean values were statistically significantly abnormal compared to controls for two-choice reaction time, balance (as speed of sway), color discrimination, digit symbol, trail-making A and B, and immediate recall of a story. Their POMS scores were much higher than those of controls. Visual recall was significantly impaired in neighbors, but not in exworkers. It was concluded that neurophysiological abnormalities were associated with exposure to reduced sulfur gases, including H2S from crude oil desulfurization.
The other side of immunoglobulin G: suppressor of inflammation (2009)

Immunoglobulin G (IgG) molecules can have two completely opposite functions. On one hand, they induce proinflammatory responses and recruit innate immune effector cells during infection with pathogenic microorganisms or autoimmune disease. On the other hand, intravenous infusion of high doses of pooled IgG molecules from thousands of donors [intravenous IG (IVIG) therapy] represents an efficient anti-inflammatory treatment for many autoimmune diseases. Whereas our understanding of the mechanism of the proinflammatory activity of IgG is quite advanced, we are only at the very beginning to comprehend how the anti-inflammatory activity comes about and what cellular and molecular players are involved in this activity. This review will summarize our current knowledge and focus upon the two major models of either IVIG-mediated competition for IgG-triggered effector functions or IVIG-mediated adjustment of cellular activation thresholds used to explain the mechanism of the anti-inflammatory activity.
Implementing optical phased array beam steering with cascaded microlens arrays (2003)

A cascade of microlens arrays that are decentered with respect to each other is one potential method for beam steering; the magnitude of the steering angle depends on the amount of decenter. A simple argument is presented that shows that the output of such a system is analogous to the output of an optical phased array. The periodic nature of the exiting wavefront restricts allowed steering angles to values that are determined by the grating equation and the pitch of the microlens arrays. The efficiency of steering into a desired diffraction order of the phased array is determined by the amount of decenter of the microlens arrays, the coherence of the arrays, and the fill-factor at the output of the array. Maximum fill-factor is desired, which can be achieved through the addition of an intermediate microlens array that acts like a field lens. An experimental implementation of such a triplet cascade of microlens arrays, suitable for steering short wave infrared laser light, is described. The extension of such a cascade to steering broad spectral band light is also discussed.
p107wee1 is a dual-specificity kinase that phosphorylates p34cdc2 on tyrosine 15. (1992)

p107wee1 is a protein kinase that functions as a dose-dependent inhibitor of mitosis through its interactions with p34cdc2 in Schizosaccharomyces pombe. To characterize the kinase activity of p107wee1, its carboxyl-terminal catalytic domain was purified to homogeneity from overproducing insect cells. The apparent molecular mass of the purified protein (p37wee1KD) was determined to be approximately 37 kDa by gel filtration, consistent with it being a monomer. Serine and tyrosine kinase activities cofiltered with p37wee1KD, demonstrating that p107wee1 is a dual-specificity kinase. In vitro, p107wee1 phosphorylated p34cdc2 on Tyr-15 only when p34cdc2 was complexed with cyclin. Neither monomeric p34cdc2 nor a peptide containing Tyr-15 was able to substitute for the p34cdc2/cyclin complex in this assay. Furthermore, the phosphorylation of p34cdc2 by p107wee1 in vitro inhibited the histone H1 kinase activity of p34cdc2. These results indicate that p107wee1 functions as a mitotic inhibitor by directly phosphorylating p34cdc2 on Tyr-15 and that the preferred substrate for phosphorylation is the p34cdc2/cyclin complex.
1,3‐Alternate Calix[4]arenecrown‐5 Conformers: New Synthetic Ionophores with Better K+/Na+ Selectivity than Valinomycin (1996)

Abstract New 25,27‐dialkoxycalix‐[4]arenecrown‐5 conformers 8, 10 , and 11 have been synthesized and studied. The compounds 8a and 8b , fixed in 1,3‐ alternate structure, have been obtained in 57 and 40% yield, respectively, by reaction of the corresponding 25,27‐dialkoxycalix[4]arenes 7a–b with tetraethylene glycol di‐ p ‐toluenesulfonate in the presence of Cs 2 CO 3 . The cone 10a and 10b and the partial cone 11 conformers were obtained by selective demethylation of the 25,27 ‐dimethoxycalix[4]arenecrown‐5 ( 6a ) and subsequent dialkylation with NaH/DMF and KO t Bu/THF, respectively. In the solid state (X‐ray), compound 6a adopts a flattened cone conformation, which is also found to be most abundant in CD 3 CN and CD 3 OD solution. Upon complexation with potassium picrate compound 6a was converted quantitatively into the 1,3‐ alternate conformation. All new ligands synthesized were used in the extraction of alkali metal cations from H 2 O into CHCl 3 , and as active components in supported liquid membranes and in chemically modified field effect transistors. Results were compared to those obtained with with the natural antibiotic valinomycin 1 . All ligands showed high selectivity for potassium. Ligand 8a , fixed in the 1,3‐ alternate conformation, is more selective than valinomycin and shows the highest K + /Na + selectivity known so far.
Molecular and Biochemical Characterization of the aaNATl (Dat) Locus in Drosophila melanogaster : Differential Expression of Two Gene Products (1998)

In insects, arylalkylamine N-acetyltransferases (AANATs) have been implicated in several physiological processes, including sclerotization, inactivation of certain neurotransmitters, and, similar to the function in vertebrates, catalysis of the rate-limiting step in melatonin biosynthesis. Here, we report an extensive biochemical and functional analysis of the products of the aaNAT1 gene of Drosophila melanogaster. The aaNAT1 gene generates two transcripts through alternative first-exon usage. These transcripts are under tissue-specific and developmental control and encode proteins which differ in their N-terminus with respect to their starting methionine. The more abundant isoform, AANATlb, is first expressed during late embryogenesis in the brain, the ventral nerve cord, and the midgut; in adults, AANATlb is still detectable in the brain and midgut. The less abundant isoform, AANATla, appears only during late pupal stages and in adults is found predominantly in the brain. We demonstrate that the mutation Dat(lo) represents a hypomorphic allele of aaNAT1b, in which an insertion of two transposable elements, MDG412 and blastopia, has occurred within the first intron of the gene. Using a deficiency which removes the aaNAT1 gene, we provide evidence that aaNAT1 is not essential for the process of sclerotization. Furthermore, neither of the two enzyme isoforms shows circadian regulation of RNA or protein levels. The differing levels of abundance and distinct developmental control of AANAT1a and AANAT1b suggest different in vivo functions for these two enzymes.
Rapid enhancement of protein phosphorylation in A-431 cell membrane preparations by epidermal growth factor. (1979)

Membranes prepared from A-431 human epidermoid carcinoma cells retained the ability to bind 125I-labeled epidermal growth factor (EGF) in a specific manner. In the presence of [gamma-32P]ATP and Mn2+ or Mg2+, this membrane preparation was capable of phosphorylating endogenous membrane components, including membrane-associated proteins; the major phosphorylated amino acid residue detected in partial acid hydrolysates was phosphothreonine. The binding of EGF to these membranes in vitro resulted in a severalfold stimulation of the phosphorylation reaction; again, the major phosphorylated amino acid residue detected in partial acid hydrolysates was phosphothreonine. Membrane-associated dephosphorylation reactions did not appear to be affected by EGF. The phosphorylation reaction was not stimulated by cyclic AMP or cyclic GMP in the absence or presence of EGF. The phosphorylation system of the membrane was able to utilize [gamma-32P]GTP in both the basal and EGF-stimulated reactions. The enhanced membrane phosphorylation was specific for EGF and its derivatives; a wide variety of other peptide hormones were ineffective. The A-431 membrane preparation also was capable of phosphorylating exogenous proteins, such as histone, phosvitin, and ribonuclease, by a process which was stimulated by EGF. These findings suggest that one of the biochemical consequences of the binding of EGF to membranes is a rapid activation of a cyclic AMP-independent phosphorylating system.
Synthesis of a Novel Esterase-Sensitive Cyclic Prodrug of a Hexapeptide Using an (Acyloxy)alkoxy Promoiety (1997)

Synthetic methodology for preparing novel esterase-sensitive cyclic prodrugs of peptides with increased protease stability and cell membrane permeability compared to linear peptides is described. Cyclic prodrug 1 of the hexapeptide H-Trp-Ala-Gly-Gly-Asp-Ala-OH linked by the N-terminal amino group to the C-terminal carboxyl group via an (acyloxy)alkoxy promoiety was synthesized. A convergent synthetic approach involving Boc[[(alaninyloxy)methyl]carbonyl]-N-tryptophan (2) and H-Ala-Gly-Gly-Asp(OBzl)-OTce (3) was used. The key fragment 2 has the promoiety inserted between the Ala and the Trp residues. Fragment 3 was synthesized by a solution-phase approach using standard Boc-amino acid chemistry. These fragments were coupled to produce the protected linear hexapeptide, which after deprotection was cyclized using standard high-dilution techniques to yield cyclic prodrug 1. In pH 7.4 buffer (HBSS) at 37 °C, cyclic prodrug 1 was shown to degrade quantitatively to the hexapeptide (t1/2 = 206 ± 11 min). The rate of hydrolysis of cyclic prodrug 1 was significantly faster in human blood (t1/2 = 132 ± 4 min) than in HBSS. Paraoxon, a known inhibitor of esterases, slowed this hydrolysis of cyclic prodrug 1 to a value (t1/2 = 198 ± 9 min) comparable to the chemical stability. In human blood, cyclic prodrug 1 was shown to be 25-fold more stable than the linear hexapeptide.
Nitrate Acts as a Signal to Induce Organic Acid Metabolism and Repress Starch Metabolism in Tobacco (1997)

, , Marianne Lauerer, , Michel Caboche, Mark Stitt, Nitrate Acts as a Signal to Induce Organic Acid Metabolism and Repress Starch Metabolism in Tobacco, The Plant Cell, Vol. 9, No. 5 (May, 1997), pp. 783-798
VE‐cadherin‐CreER T2 transgenic mouse: A model for inducible recombination in the endothelium (2006)

To introduce temporal control in genetic experiments targeting the endothelium, we established a mouse line expressing tamoxifen-inducible Cre-recombinase (Cre-ERT2) under the regulation of the vascular endothelial cadherin promoter (VECad). Specificity and efficiency of Cre activity was documented by crossing VECad-Cre-ERT2 with the ROSA26R reporter mouse, in which a floxed-stop cassette has been placed upstream of the beta-galactosidase gene. We found that tamoxifen specifically induced widespread recombination in the endothelium of embryonic, neonatal, and adult tissues. Recombination was also documented in tumor-associated vascular beds and in postnatal angiogenesis assays. Furthermore, injection of tamoxifen in adult animals resulted in negligible excision (lower than 0.4%) in the hematopoietic lineage. The VECad-Cre-ERT2 mouse is likely to be a valuable tool to study the function of genes involved in vascular development, homeostasis, and in complex processes involving neoangiogenesis, such as tumor growth.