gebhart/patrepeval huggingface dataset:
Abstract #3233: Targeted therapy of human colonic, lung, and pancreatic cancer xenografts, growing in nude mice, with potent antibody conjugates of SN-38 (2009)

SN-38 is a potent topoisomerase I inhibitor and the active drug form of the clinically used cancer therapeutic, CPT-11. To increase bioavailability and reduce toxicity, antibody (MAb)-targeted SN-38 chemotherapy was evaluated in preclinical models of human colonic, lung, and pancreatic carcinomas. Two improved bifunctional SN-38 derivatives, \#8220;CL2-SN-38\#8221; (maleimido-[x]-Phe-Lys-PABOCO-20-O-SN-38, where PAB is p-aminobenzyl and \#8216;x\#8217; comprises a PEG group for solubility) and its ethyl carbonate variant, \#8220;CL2-SN-38(Et)\#8221;, were conjugated to mildly reduced humanized MAbs, hPAM4 (anti-MUC-1), hMN-14 (anti-CEACAM5), hRS7 (anti-EGP-1), and an isotype-matched control, hLL2 (anti-CD22). SN-38/MAb molar substitutions in the conjugates were in the range of 6-7, and the conjugates\#8217; cytotoxicities were similar to that of SN-38. Female athymic nude mice with human tumor xenografts were treated i.p.with specific or non-targeting MAb-SN38 conjugates or an equidose mixture of specific MAb and SN-38 as follows: 0.46 mg conjugated SN-38/kg, q4d×8 (protocol-1) or q4d×4 (protocol-2); or 0.23 mg conjugated SN-38/kg, q4d×8 (protocol-3). In some experiments, CPT-11 was also used as a control. A lung metastatic model of GW-39 human colonic carcinoma and s.c. models of LS174T human colonic, Calu-3 human lung, and human CaPan1 pancreatic carcinomas were treated. In the lung metastatic model of human colon carcinoma, therapy with hMN-14-CL2-SN-38 conjugate (protocol-3; n = 8-10) increased median survival 1.7-3-fold to 147 days vs. controls. In the s.c. LS174T colon cancer model (protocol-1, n = 8), survival due to treatment with hMN-14-CL2-SN-38(Et) was significantly better than that due to all controls including treatment with the maximum tolerated dose (MTD; 40 mg/kg, q2d×5) of CPT-11 (log rank test, P 600% on day 28. Therapy data for ongoing pilot experiments in 2 additional colon cancer xenograft models as well as expanded study in the CaPan1 model will also be reported. These results show selective and significant therapeutic efficacies due to treatments with MAb-SN-38 conjugates in preclinical models of solid human tumors. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3233.
Pannexin-1 Is Required for ATP Release during Apoptosis but Not for Inflammasome Activation (2011)

Apoptotic cell death is important for embryonic development, immune cell homeostasis, and pathogen elimination. Innate immune cells also undergo a very rapid form of cell death termed pyroptosis after activating the protease caspase-1. The hemichannel pannexin-1 has been implicated in both processes. In this study, we describe the characterization of pannexin-1-deficient mice. LPS-primed bone marrow-derived macrophages lacking pannexin-1 activated caspase-1 and secreted its substrates IL-1β and IL-18 normally after stimulation with ATP, nigericin, alum, silica, flagellin, or cytoplasmic DNA, indicating that pannexin-1 is dispensable for assembly of caspase-1-activating inflammasome complexes. Instead, thymocytes lacking pannexin-1, but not the P2X7R purinergic receptor, were defective in their uptake of the nucleic acid dye YO-PRO-1 during early apoptosis. Cell death was not delayed but, unlike their wild-type counterparts, Panx1(-/-) thymocytes failed to recruit wild-type peritoneal macrophages in a Transwell migration assay. These data are consistent with pannexin-1 liberating ATP and other yet to be defined "find me" signals necessary for macrophage recruitment to apoptotic cells.
Technology Transfer and Scale Up of a Potential Cancer‐Preventive Plant Dynamic Extraction of Glucoraphanin (2005)

Abstract Glucosinolates are anionic, hydrophilic β‐thioglucoside N‐hydroxysulfates, which are abundant plant secondary metabolites found in cruciferous plants and are of particular interest for their chemoprotective, antioxidant and antibiotic activities. The purification of gluoraphanin (GR), the predominant glucosinolate in broccoli, was achieved using high‐speed countercurrent chromatography (HSCCC) with a high salt, highly polar phase system of 1‐propanol‐acetonitrile‐saturated ammonium sulphate‐water (1∶0.5∶1.2∶1) on a preparative scale (850 mL capacity) Pharma‐Tech HSCCC instrument at ca 700 mg glucosinolates per run in about 3 hours. To scale up the production of glucosinolates the technology was transferred from Johns Hopkins to Brunel Institute for Bioengineering (BIB). Within three days a 50×scale up was achieved with comparable target compound recovery and purity using a MIDI‐dynamic extraction centrifuge (928 mL capacity) with run times of 30 min and processing loads of 30 mL of ca 50% w/w viscous solutions (15 g injected). The 34 runs processed 589 g of extract producing a total of 52.6 g of 98% pure GR.
A prototype RF dosimeter for independent measurement of the average specific absorption rate (SAR) during MRI (2007)

This dosimeter provides a simple portable means of measuring the power deposited in a body-equivalent sample load, independent of the scanner. Further work will develop SAR dosimetry for the torso and for higher fields.
The Epidermal Growth Factor Receptor Engages Receptor Interacting Protein and Nuclear Factor-κB (NF-κB)-inducing Kinase to Activate NF-κB (2001)

The transcription factor nuclear factor-kappaB (NF-kappaB) is activated by a diverse number of stimuli including tumor necrosis factor-alpha, interleukin-1, UV irradiation, viruses, as well as receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR). NF-kappaB activation by the tumor necrosis factor receptor (TNFR) involves the formation of a multiprotein complex termed a signalosome. Although previous studies have shown that the activated EGFR can induce NF-kappaB, the mechanism of this activation remains unknown. In this study, we identify components of the signalosome formed by the activated EGFR required to activate NF-kappaB and show that, although the activated EGFR uses mechanisms similar to the TNFR, it recruits a distinct signalosome. We show the EGFR forms a complex with a TNFR-interacting protein (RIP), which plays a key role in TNFR-induced NF-kappaB activation, but not with TRADD, an adaptor protein which serves to recruit RIP to the TNFR. Furthermore, we show that the EGFR associates with NF-kappaB-inducing kinase (NIK) and provide evidence suggesting multiprotein complex formation between the EGFR, RIP, and NIK. Using a dominant negative NIK mutant, we show that NIK activation is required for EGFR-mediated NF-kappaB induction. We also show that a S32/36 IkappaBalpha mutant blocks EGFR-induced NF-kappaB activation. Our studies also suggest that a high level of EGFR expression, a frequent occurrence in human tumors, is optimal for epidermal growth factor-induced NF-kappaB activation. Finally, although protein kinase B/Akt has been implicated in tumor necrosis factor and PDGF-induced NF-kappaB activation, our studies do not support a role for this protein in EGFR-induced NF-kappaB activation.
Flexible flow for 3D nonrigid tracking and shape recovery (2005)

We introduce linear methods for model-based tracking of nonrigid 3D objects and for acquiring such models from video. 3D motions and flexions are calculated directly from image intensities without information-lossy intermediate results. Measurement uncertainty is quantified and fully propagated through the inverse model to yield posterior mean (PM) and/or mode (MAP) pose estimates. A Bayesian framework manages uncertainty, accommodates priors, and gives confidence measures. We obtain highly accurate and robust closed-form estimators by minimizing information loss from non-reversible (inner-product and least-squares) operations, and, when unavoidable, performing such operations with the appropriate error norm. For model acquisition, we show how to refine a crude or generic model to fit the video subject. We demonstrate with tracking, model refinement, and super-resolution texture lifting from low-quality low-resolution video.
Social approach in genetically engineered mouse lines relevant to autism (2008)

Profound impairment in social interaction is a core symptom of autism, a severe neurodevelopmental disorder. Deficits can include a lack of interest in social contact and low levels of approach and proximity to other children. In this study, a three-chambered choice task was used to evaluate sociability and social novelty preference in five lines of mice with mutations in genes implicated in autism spectrum disorders. Fmr1(tm1Cgr/Y)(Fmr1(-/y)) mice represent a model for fragile X, a mental retardation syndrome that is partially comorbid with autism. We tested Fmr1(-/y)mice on two genetic backgrounds, C57BL/6J and FVB/N-129/OlaHsd (FVB/129). Targeted disruption of Fmr1 resulted in low sociability on one measure, but only when the mutation was expressed on FVB/129. Autism has been associated with altered serotonin levels and polymorphisms in SLC6A4 (SERT), the serotonin transporter gene. Male mice with targeted disruption of Slc6a4 displayed significantly less sociability than wild-type controls. Mice with conditional overexpression of Igf-1 (insulin-like growth factor-1) offered a model for brain overgrowth associated with autism. Igf-1 transgenic mice engaged in levels of social approach similar to wild-type controls. Targeted disruption in other genes of interest, En2 (engrailed-2) and Dhcr7, was carried on genetic backgrounds that showed low levels of exploration in the choice task, precluding meaningful interpretations of social behavior scores. Overall, results show that loss of Fmr1 or Slc6a4 gene function can lead to deficits in sociability. Findings from the fragile X model suggest that the FVB/129 background confers enhanced susceptibility to consequences of Fmr1 mutation on social approach.
EXTRACTION OF CIRCULATING TUMOR CELLS FROM BLOOD USING ACOUSTOPHORESIS (2010)

We present, for the first time, separation of three different prostate cancer cell lines from leukocyte fractions by means of continuous flow acoustophoresis. This flow-through separation approach, which utilize acoustophoretic forces to extract CTCs from blood has a significant advantage over affinity based methods in the sense that it comprises a non-contact and label free separation of CTCs from blood.
Photobiological fundamentals of low-power laser therapy (1987)

Quantitative studies of the action of low-power visible monochromatic light on various cells (E. coli, yeasts, HeLa) were performed to find irradiation conditions (wavelength, dose, intensity) conducive to vital activity stimulation. The action spectra of visible light on DNA and RNA synthesis in HeLa cells have maxima near 404, 620, 680, 760, and 830 nm. Growth simulation of E. coli is at a maximum when irradiated at 404, 454, 570, 620, and 750 nm, and biomass accumulation stimulation in yeasts has a maxima at 404, 570, 620, 680, and 760 nm. Absorption of quanta is only a trigger for the rearrangement of cellular metabolism, with photosignal transduction being effected by standard cellular means such as changes in the cAMP level. Respiratory chain components are discussed as primary photoacceptors. It is concluded that "laser biostimulation" is of a photobiological nature, and low-power laser effects can be related to well-known photobiological phenomena.
Absence of Pyridoxine-5‘-Phosphate Oxidase (PNPO) Activity in Neoplastic Cells:  Isolation, Characterization, and Expression of PNPO cDNA (1998)

Major differences in the metabolism of vitamin B6 in various cancers compared to their normal cellular counterparts have been documented. In particular, pyridoxine- 5'-phosphate oxidase (PNPO), the rate-limiting enzyme in pyridoxal 5'-phosphate (PLP) biosynthesis, is absent in liver and neurally-derived tumors. We show that the expression of PNPO is developmentally regulated not only in liver but also in brain. Specifically, PNPO activity in fetal brain tissue is 7.5-fold lower than that found in adult brain tissue. Furthermore, the isolation and characterization of a PNPO cDNA are described. The isolated cDNA was verified to be the authentic PNPO cDNA on the basis of two criteria. First, the translated product from the PNPO cDNA is immunologically reactive to a polyclonal PNPO antibody. Second, PNPO negative hepatoma cell lines stably transfected with the PNPO cDNA express enzymatically active PNPO protein. The availability of these biological reagents will not only facilitate in depth investigations of the reasons for the absence of PNPO in liver and brain malignancies but also aid in an understanding of the biochemical regulation of B6 metabolism in development.
Experimental and clinical investigations of human insoluble bone matrix gelatin. A report of 24 cases. (1993)

Human bone matrix gelatin (hBMG) was implanted into the quadriceps muscles of mice to determine its osteoinductive activity and immune responses. The host mouse muscle assay reacted positively to the hBMG, providing an experimental basis for clinical application. At two weeks after implantation, cartilage was produced in the mouse muscle, and new bone and bone marrow were formed at three to four weeks after implantation. Human bone matrix gelatin, which was thus shown to have osteoinductive activity, was subsequently implanted in 24 patients. Generally, the bone defects were filled with new bone tissue with increased density within two to four months after operation. Nonunion and delayed unions were healed at two to six months after surgery.
Structural characterization of natural human urinary and recombinant DNA-derived erythropoietin. Identification of des-arginine 166 erythropoietin. (1987)

Recombinant human erythropoietin (rhEPO) has been purified to apparent homogeneity from a Chinese hamster ovary cell line expressing a cDNA clone of the human gene. NH2-terminal sequencing of the recombinant hormone indicates that the 27-residue leader peptide is correctly and consistently cleaved during secretion of the recombinant protein into conditioned medium, yielding the mature NH2 terminus (Ala-Pro-Pro-Arg...). Analysis of the COOH terminus of rhEPO by peptide mapping and fast atom bombardment mass spectrometry (FABMS) demonstrates that the arginyl residue predicted to be at the COOH terminus (based on confirmation of both genomic and cDNA sequences) is completely missing from the purified protein. The truncated form of the recombinant hormone, designated des-Arg166 rhEPO, displays an in vivo specific activity of greater than 200,000 units/mg protein. Structural characterization of natural human urinary EPO (uEPO) by peptide mapping and FABMS reveals that the urinary hormone is also missing the COOH-terminal Arg166 amino acid residue, a modification that remained undetected until now. There is no evidence of further proteolytic processing at the COOH terminus beyond specific removal of the Arg166 amino acid residue in either rhEPO or uEPO. On the basis of the FABMS data, we propose that the physiologically active form of the hormone circulating in plasma and interacting with target cells in vivo is des-Arg166 EPO.
Nonlinear optics and solid-state lasers: 2000 (2000)

Progress in solid-state laser sources and the nonlinear frequency conversion of lasers has been impressive over the first forty years of their development. The paper reviews the progress with an emphasis on the interactions of the scientists and engineers involved in the work and the motivation for the research. This account, is highly personal and necessarily incomplete. The references cited point to the key results and to reviews of progress in nonlinear optics and solid-state laser sources and should assist those seeking to learn about the field as it developed.
Diastereoselective Synthesis of Bridged Polycyclic Alkaloids via Tandem Acylation/Intramolecular Diels–Alder Reaction (2013)

A mild and efficient stereoselective synthesis of hexacyclic indole alkaloids with a tetrahydro-β-carboline motif has been developed by utilizing the Pictet-Spengler reaction and tandem N-acylation followed by intramolecular Diels-Alder cyclization. Initially, a diene unit was installed in the tetrahedron β-carboline skeleton through Pictet-Spengler cyclization of the corresponding aldehyde with tryptophan ester. The dienophile moiety was introduced by N-acylation of tetrahydro-β-carboline. Successive, in situ, [4 + 2] intramolecular Diels-Alder cycloaddition of the activated dienophile and conjugated diene containing intermediate furnished bridged polycyclic heterocycles with high diastereoselectivity. Formation of four new rings, five new covalent bonds, and five new chiral centers with excellent stereoselectivity is the key feature of this strategy. The diastereoselective formation of product was attributed to intramolecular chirality transfer through a chiral amino acid. The stereoselective outcome of this tandem reaction was confirmed by X-ray crystallographic studies. The developed synthetic strategy was also explored on a soluble polymer support to incorporate the advantage of rapid synthesis and a high-throughput workup process toward the development of a green synthetic protocol for polycyclic alkaloids.
Effect of controlled zinc release on bone mineral density from injectable Zn‐containing β‐tricalcium phosphate suspension in zinc‐deficient diseased rats (2004)

The purpose of this study was to evaluate the efficacy of zinc (Zn)-containing beta-tricalcium phosphate (Zn-TCP) in correcting the bone mineral deficiency noted in osteoporosis using ovariectomized rat model. Four rats were used for each of the four experimental groups: D0, D10, D20, and N10. The rats in D0, D10, and D20 groups were ovariectomized, and fed a vitamin D-, Ca-, and Zn-deficient diet, and induced Zn-deficient osteoporoses for 9 weeks. In contrast, the N10 group was the normal rats fed normal healthy diet for 9 weeks. D0 group was injected with pure beta-TCP suspension, D10 and D20 groups were injected with suspensions containing 10 mg of 10 mol % (6.17 wt % Zn) and 20 mol % (12.05 wt % Zn) Zn-TCP, respectively, and the healthy group, N10 were injected with 10 mol %. Zn-TCP suspensions. Injections were administered intramuscularly in the left thigh once a week in all rats, and fed a vitamin D- and Zn-deficient diet for 9 weeks. The plasma calcium (Ca) and Zn levels, plasma alkaline phosphatase activity (ALP) and bone mineral density (BMD) of the lumbar vertebra and femora were measured. The plasma Zn levels in all the rats were between 1.1 and 2.8 microg/mL. The areas under the curves for the Ca, Zn, and ALP (Ca-AUC, Zn-AUC, and ALP-AUC) levels between 0 and 63 days were calculated. Results for the AUCs were as follows: (1) the Zn-AUCs were in the order of N10 = D20 > D10 > D0; (2) the Ca-AUCs for D0, D10 groups were significantly lower than that for the N10 group; (3) the ALP-AUCs for the D10 and D20 groups were significantly higher than that for the N10 group, and that of the D0 group was in between those. The body weight of D10 and D20 groups significantly increased with time, that of the D0 group increased slightly, and that of the N10 group remained unchanged for the entire experimental period. The BMD of the lumbar vertebrae of the D10 and D20 groups (about 100 mg/cm(2)) was significantly higher than that of the D0 group but lower than that of the N10 group. The BMD of the left femur increased more than that of the right femur with the increase in the amount of Zn in the suspension. The results of this study suggest that the local effect on BMD was more pronounced than the effect on the whole body.
Multiplexed Analysis of Proteins in Tissue Using Multispectral Fluorescence Imaging (2010)

We present a new application of multispectral analysis for subcellular measurement of multiple proteins in formalin-fixed paraffin embedded tissue and cells. Typically, the targets of interest are present in the same or spatially overlapping cellular compartments. Such co-localization can complicate analysis and interpretation of the images obtained using traditional fluorescence, especially when spectrally overlapping labels are present. The spectral properties of currently available fluorescent dyes set an upper limit to the number of molecules that can be detected simultaneously with traditional fluorescence. By exciting a set of fluorophores at the same wavelength and unmixing their emission signals from background autofluorescence, we were able to image three targets in a single channel. This parallel imaging approach provides significant advantages for multiplexed analysis of tissues and cells.
Characterization of a human MHC class III region gene product with S-thioesterase activity (1999)

Palmitoylated proteins contain a 16-carbon saturated fatty acyl group that is post-translationally attached by a labile thioester bond.These modified proteins are mainly membrane-bound ; the lability of the thioester bond allows the process to be reversible, a unique property of this modification.We report here that the gene for G14, located in the class III region of the human MHC, encodes a polypeptide with significant sequence similarity to mammalian palmitoyl protein thioesterase (PPT1), an enzyme that removes palmitate from palmitoylated proteins.The gene for G14, also known as PPT2, is transcribed as at least five different transcripts, which are expressed in different cell lines of the immune system.Immunoprecipitation of these mammalian cells, with an anti-G14 antiserum, showed a specific band of approx.42 kDa in cell extracts and supernatants.Expression of the G14 cDNA in the baculovirus system revealed that it encoded Abbreviations used : Nbs 2 , 5,5h-dithiobis-(2-nitrobenzoic acid) ; FCS, foetal calf serum ; FNIII, fibronectin type III ; h, human ; IFN-γ, interferon γ ; INCL, infantile neuronal ceroid lipofuscinosis ; LPAATα, lysophosphatidic acid acyltransferase α ; LTBP, latent transforming growth-factor-β-binding protein ; PPT, palmitoyl protein thioesterase ; RT-PCR, reverse-transcriptase-mediated PCR.1 Present address : UK HGMP
Eicosapentaenoic and docosahexaenoic acids alter rat spleen leukocyte fatty acid composition and prostaglandin E2 production but have different effects on lymphocyte functions and cell‐mediated immunity (1998)

Weanling rats were fed on high-fat (178 g/kg) diets which contained 4.4 g alpha-linolenic (ALA), gamma-linolenic, arachidonic (ARA), eicosapentaenoic (EPA), or docosahexaenoic acid (DHA)/100 g total fatty acids. The proportions of all other fatty acids, apart from linoleic acid, and the proportion of total polyunsaturated fatty acids (PUFA) (approximately 35 g/100 g total fatty acids) were constant, and the n-6 to n-3 PUFA ratio was maintained as close to 7 as possible. The fatty acid compositions of the serum and of spleen leukocytes were markedly influenced by that of the diet. Prostaglandin E2 production was enhanced from leukocytes from rats fed the ARA-rich diet and was decreased from leukocytes from the EPA- or DHA-fed rats. Replacing dietary ALA with EPA resulted in diminished ex vivo lymphocyte proliferation and natural killer (NK) cell activity and a reduced cell-mediated immune response in vivo. In contrast, replacing ALA with DHA reduced ex vivo lymphocyte proliferation but did not affect ex vivo NK cell activity or the cell-mediated immune response in vivo. Replacement of a proportion of linoleic acid with either gamma-linolenic acid or ARA did not affect lymphocyte proliferation, NK cell activity, or the cell-mediated immune response. Thus, this study shows that different n-3 PUFA exert different immunomodulatory actions, that EPA exerts more widespread and/or stronger immunomodulatory effects than DHA, that a low level of EPA is sufficient to influence the immune response, and that the immunomodulatory effects of fish oil may be mainly due to EPA.