gebhart/patrepeval huggingface dataset:
Progression of tumors arising from large ACF is associated with the MUC5AC expression during rat colon MNNG carcinogenis (2006)

Aberrant crypt foci (ACF) are microscopic lesions which have been postulated to precede the development of adenomas, precursors of colon cancer. The gastric M1/MUC5AC mucin has also been described as an early marker of colon carcinogenesis in the human and in the rat. To study changes in mucin expression associated with the genesis of tumors, Wistar rats were treated by intrarectal instillations of MNNG, twice a week for 2 weeks, and were sacrificed 10 (n = 20), 14 (n = 20), 22 (n = 20), 30 (n = 10) and 66 (n = 16) weeks after the beginning of the treatment. In the treated rats, the MUC5AC mucin was mainly expressed in ACF compared with the histologically normal mucosae, which showed few isolated MUC5AC-positive normal crypts. During carcinogenesis, the percentage of large ACF [> or =10 aberrant crypts] increased and the number of MUC5AC-positive (NCs) decreased. At Week 30, small tumors were observed arising from large ACF, both types of lesions expressing MUC5AC. At Week 66, large tumors showed remnants of MUC5AC-positive ACF in their adjacent mucosae. This observation suggests that the expression of MUC5AC is associated with the ACF/adenoma sequence and supports the notion of large ACF as precursors of adenomas/adenocarcinomas. Moreover, the expression of MUC5AC in the transitional mucosa adjacent to both rat and human colon tumors suggests that some human tumors could arise from large ACF, and reinforces the concept of the premalignant potential of these lesions.
Rapid Nanodroplet-Based Real-time PCR System with Laser Heating (2008)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text H. Kim, S. Dixit, A. Cherif, and G. W. Faris, "Rapid Nanodroplet-Based Real-time PCR System with Laser Heating," in Frontiers in Optics 2008/Laser Science XXIV/Plasmonics and Metamaterials/Optical Fabrication and Testing, OSA Technical Digest (CD) (Optica Publishing Group, 2008), paper FML1. Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Video rate spectral imaging using a coded aperture snapshot spectral imager (2009)

We have previously reported on coded aperture snapshot spectral imagers (CASSI) that can capture a full frame spectral image in a snapshot. Here we describe the use of CASSI for spectral imaging of a dynamic scene at video rate. We describe significant advances in the design of the optical system, system calibration procedures and reconstruction method. The new optical system uses a double Amici prism to achieve an in-line, direct view configuration, resulting in a substantial improvement in image quality. We describe NeAREst, an algorithm for estimating the instantaneous three-dimensional spatio-spectral data cube from CASSI's two-dimensional array of encoded and compressed measurements. We utilize CASSI's snapshot ability to demonstrate a spectral image video of multi-colored candles with live flames captured at 30 frames per second.
FLOCOR™: a new anti-adhesive, rheologic agent (1998)

FLOCOR (purified poloxamer 188) is a surfactant molecule that represents a new class of pharmacological agent. FLOCOR is different in that its activity does not depend on high affinity receptor binding but rather on altering the way cells and molecules interact with water. Extensive preclinical studies in models of vascular occlusive disorders, including circulatory shock, acute stroke, and myocardial infarction (MI), suggest that iv. administration of poloxamer 188 improves microvascular blood flow in ischaemic tissues by inhibiting adhesive interactions, lowering blood viscosity and reducing friction along the vessel wall. In clinical studies, poloxamer 188 demonstrated statistically significant benefits in patients with acute myocardial infarction (AMI) and acute vaso-occlusive crisis of sickle cell disease. However, these studies were conducted with commercial grades of poloxamer 188 that contained nephrotoxic impurities, and elevated creatinine was observed in a small percentage of patients. A new highly purified version of poloxamer 188 free from impurities has been developed. Highly purified poloxamer 188 (trade name FLOCOR) is better tolerated in models of renal failure and is anticipated to have a significantly improved therapeutic index compared to commercial grade poloxamer 188. Clinical studies are now in progress in order to confirm the therapeutic benefits of FLOCOR (purified poloxamer 188).
Induction of fetal hemoglobin production in subjects with sickle cell anemia by oral sodium phenylbutyrate (1994)

Abstract Intravenous arginine butyrate has been shown to increase fetal hemoglobin (HbF) in sickle cell and thalassemia patients. Recently, we observed that sodium 4-phenylbutyrate, a drug administered orally to treat urea cycle disorders, increases HbF production in nonanemic children and adults. We treated six subjects with sickle cell disease over a period of 14 to 179 days. All subjects received their initial therapy of 9 to 13 g/m2/day as 0.5-g tablets of sodium 4-phenylbutyrate as inpatients. All subjects showed a rapid increase in the percentage of F-reticulocytes (pretreatment, 1% to 20%; posttreatment, 10% to 44%). Four subjects were treated only 11 to 25 days as inpatients. Two of these four subjects failed to respond to the outpatient component because of their inability to maintain an intake of 30 to 40 tablets per day. One subject (C) developed a rash at day 10 and discontinued treatment at day 14. Another subject (B) was transfused for a painful crisis on day 25. Subject A, treated for 179 days, has an increased percentage of F cells, from 54% to 77%, and increased HbF levels, from 10.6% to 18%. Subject F, treated for 154 days, has an increased percentage of F cells, from 59% to 73%, and an increased percentage of HbF, from 10.4% to 16%. All subjects showed some increase in weight. Subject A developed mild transient ankle edema. Myelotoxicity was not seen in any treated patient. Oral administration of sodium 4- phenylbutyrate rapidly increases F-cell production in sickle cell disease.
Development of Pyrrolo[2,1‐c][1,4]benzodiazepine β‐Galactoside Prodrugs for Selective Therapy of Cancer by ADEPT and PMT (2008)

The pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) are a class of well-studied DNA-interactive agents with a potential for use in the treatment of cancer. The clinical utility of these molecules is limited because of the lack of selectivity for tumor tissues, high reactivity of the pharmacophoric imine functionality, low water solubility, and stability. To address the shortcomings, especially the lack of selectivity, associated with the molecules, two new beta-galactoside prodrugs of PBDs have been synthesized and evaluated for their potential use in selective therapy of solid tumors by ADEPT and PMT protocols. The preliminary studies reveal the prodrugs to be much less toxic compared to the parent moieties. These prodrugs are activated by E. coli beta-galactosidase (EC 3.2.1.23) to form the active cytotoxic moiety signifying their utility in ADEPT of cancer. One of the significant outcomes of the present study is the toxification of the prodrug 1 a by the endogenous beta-galactosidase of human liver cancer cells (Hep G2) to form the cytotoxic moiety, enabling selective therapy of hepatocellular carcinoma. Another important property of these molecules is their enhanced water solubility and stability, which are essential for a molecule to be an effective drug.
Molecular cloning and characterization of human WNT3 (2001)

Mouse Wnt-3 is a proto-oncogene, which is activated by mouse mammary tumor virus (MMTV). Human WNT3 cDNA fragment, previously isolated by another group, corresponds to a partial coding sequence. WNT3 cDNA, spanning the complete coding sequence, was isolated in this study. WNT3 encoded 355-amino-acid polypeptide with the N-terminal signal peptide and two N-linked glycosylation sites. WNT3 was most homologous to WNT3A (84.2% total amino-acid identity) among human WNTs. The WNT3 gene on the human chromosome 17q21 region consisted of five exons. WNT3 mRNAs were detected in fetal brain, adult brain, and testis by Northern blot analyses. WNT3 mRNA was relatively highly expressed in A549 cells (lung cancer) and MKN45 cells (gastric cancer) among 37 human cancer cell lines. WNT3 was significantly up-regulated in a case of primary breast cancer and in a case of primary rectal cancer among various types of human primary cancers. These results strongly suggest that WNT3 might play a key role in some cases of human breast, rectal, lung, and gastric cancer through activation of the WNT - beta-catenin - TCF signaling pathway, similar to mouse Wnt-3.
Relational inductive biases, deep learning, and graph networks (2018)

Artificial intelligence (AI) has undergone a renaissance recently, making major progress in key domains such as vision, language, control, and decision-making. This has been due, in part, to cheap data and cheap compute resources, which have fit the natural strengths of deep learning. However, many defining characteristics of human intelligence, which developed under much different pressures, remain out of reach for current approaches. In particular, generalizing beyond one's experiences--a hallmark of human intelligence from infancy--remains a formidable challenge for modern AI. The following is part position paper, part review, and part unification. We argue that combinatorial generalization must be a top priority for AI to achieve human-like abilities, and that structured representations and computations are key to realizing this objective. Just as biology uses nature and nurture cooperatively, we reject the false choice between "hand-engineering" and "end-to-end" learning, and instead advocate for an approach which benefits from their complementary strengths. We explore how using relational inductive biases within deep learning architectures can facilitate learning about entities, relations, and rules for composing them. We present a new building block for the AI toolkit with a strong relational inductive bias--the graph network--which generalizes and extends various approaches for neural networks that operate on graphs, and provides a straightforward interface for manipulating structured knowledge and producing structured behaviors. We discuss how graph networks can support relational reasoning and combinatorial generalization, laying the foundation for more sophisticated, interpretable, and flexible patterns of reasoning. As a companion to this paper, we have released an open-source software library for building graph networks, with demonstrations of how to use them in practice.
Monomeric structure of the cardioprotective chemokine SDF‐1/CXCL12 (2009)

The chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) directs leukocyte migration, stem cell homing, and cancer metastasis through activation of CXCR4, which is also a coreceptor for T-tropic HIV-1. Recently, SDF-1 was shown to play a protective role after myocardial infarction, and the protein is a candidate for development of new anti-ischemic compounds. SDF-1 is monomeric at nanomolar concentrations but binding partners promote self-association at higher concentrations to form a typical CXC chemokine homodimer. Two NMR structures have been reported for the SDF-1 monomer, but only one matches the conformation observed in a series of dimeric crystal structures. In the other model, the C-terminal helix is tilted at an angle incompatible with SDF-1 dimerization. Using a rat heart explant model for ischemia/reperfusion injury, we found that dimeric SDF-1 exerts no cardioprotective effect, suggesting that the active species is monomeric. To resolve the discrepancy between existing models, we solved the NMR structure of the SDF-1 monomer in different solution conditions. Irrespective of pH and buffer composition, the C-terminal helix remains tilted at an angle with no evidence for the perpendicular arrangement. Furthermore, we find that phospholipid bicelles promote dimerization that necessarily shifts the helix to the perpendicular orientation, yielding dipolar couplings that are incompatible with the NOE distance constraints. We conclude that interactions with the alignment medium biased the previous structure, masking flexibility in the helix position that may be essential for the distinct functional properties of the SDF-1 monomer.
Zinc Deficiency and the Development of Esophageal and Forestomach Tumors in Sprague-Dawley Rats Fed Precursors of <italic>N</italic>-Nitroso-<italic>N</italic>-benzylmethylamine<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref> (1984)

Nine-week-old zinc-sufficient (100 mg zinc/kg feed) and zinc-deficient (7 mg zinc/kg feed) noninbred male Sprague-Dawley rats were given free access 5 days a week to deionized drinking water containing low (0.05%) or high (0.25%) quantities of benzylmethylamine (BMA) and concurrently 0.5% NaNO2. In contrast to the action of the preformed carcinogen N-nitroso-N-benzylmethylamine, which almost invariably produced esophageal tumors, oral administration of its precursors, BMA and NaNO2, resulted in forestomach tumors as well. In both the high- and low-BMA groups given precursors for 16 weeks, the incidence of papillomas in both the esophagus and forestomach was significantly higher in the zinc-deficient than in the zinc-sufficient rats, but zinc deficiency did not significantly increase the yield of forestomach carcinomas. However, when combined high BMA and NaNO2 administration was prolonged to 37 weeks, the yield of forestomach carcinomas was significantly greater in the zinc-deficient than in the zinc-sufficient animals. Because endogenous synthesis of N-nitrosamines from ingested precursors is an important source of human exposure to these carcinogenic compounds and because dietary zinc deficiency might be operating in some areas with a high incidence of esophageal cancer, our data are of more than routine significance.
Low-cost non-intrusive debugging strategies for distributed parallel programs (2003)

We show how five low-cost and nonintrusive techniques that work using free commodity tools such as GDB can be used to improve the debugging process of multi-threaded and/or distributed parallel programs. These techniques have been used in the development of major software middleware - DataCutter and MQO - and have proven their value by lowering the time necessary to detect and correct bugs.
Ovarian Cancer-associated Mutations Disable Catalytic Activity of CDK12, a Kinase That Promotes Homologous Recombination Repair and Resistance to Cisplatin and Poly(ADP-ribose) Polymerase Inhibitors (2014)

Mutations in the tumor suppressors BRCA1 and BRCA2, which encode proteins that are key participants in homologous recombination (HR) repair, occur in ∼20% of high grade serous ovarian cancers. Although only 20% of these tumors have mutations in BRCA1 and BRCA2, nearly 50% of these tumors have defects in HR. Notably, however, the underlying genetic defects that give rise to HR defects in the absence of BRCA1 and BRCA2 mutations have not been fully elucidated. Here we show that the recurrent somatic CDK12 mutations identified in ovarian cancers impair the catalytic activity of this kinase, which is involved in the transcription of a subset of genes, including BRCA1 and other DNA repair genes. Furthermore, we show that disabling CDK12 function in ovarian cancer cells reduces BRCA1 levels, disrupts HR repair, and sensitizes these cells to the cross-linking agents melphalan and cisplatin and to the poly(ADP-ribose) polymerase (PARP) inhibitor veliparib (ABT-888). Taken together, these findings suggest that many CDK12 mutations are an unrecognized cause of HR defects in ovarian cancers.
Synergistic effects of (--)-epigallocatechin gallate with (--)-epicatechin, sulindac, or tamoxifen on cancer-preventive activity in the human lung cancer cell line PC-9. (1999)

The study on incorporation of [3H](-)-epigallocatechin gallate (EGCG) into human lung cancer cell line PC-9 indicated that the [3H]EGCG incorporation was significantly enhanced by (-)-epicatechin, an inert tea polyphenol without a galloyl moiety. (-)-Epicatechin enhanced apoptosis, growth inhibition of PC-9 cells, and inhibition of tumor necrosis factor-alpha release from BALB/c-3T3 cells by EGCG and other tea polyphenols with a galloyl moiety in a dose-dependent manner. Moreover, the effects of EGCG on induction of apoptosis were also synergistically enhanced by other cancer-preventive agents, such as sulindac and tamoxifen. This paper reports significant evidence that whole green tea is a more reasonable mixture of tea polyphenols for cancer prevention in humans than EGCG alone and that it is even more effective when it is used in combination with other cancer preventives.
Adoptive immunotherapy of cancer using monocyte-derived macrophages: rationale, current status, and perspectives (1998)

Adoptive transfer of host defense cells may be able to correct an otherwise defective generation of competent immune cells in patients with cancer. Ex vivo-grown cytotoxic macrophages (MAC) able to recognize and destroy tumor cells but not normal cells are effective in murine models of metastasizing tumors. After the development of large-scale technology to generate MAC in vitro from blood monocytes (MO), clinical trials in cancer patients have proven the feasibility and safety of infusing >3 x 10(9) autologous MO-derived MAC activated by interferon-gamma or lipopolysaccharide. Various modalities of adoptive immunotherapy with human MAC have been realized: routes of application used were intravenous, intraperitoneal, intrapleural, and through selective hepatic artery perfusion. In addition, MAC have been generated from MO collected after granulyte-macrophage colony-stimulating factor treatment in vivo. Biodistribution studies using 111indium-labeled cells have revealed localization of MAC to sites of bulk tumor growth on regional infusion as well as to liver metastases on systemic application. Malignant ascites disappeared in about 50% of patients after intraperitoneal treatment, yet no other evidence of therapeutic efficacy of MAC could be demonstrated. Further advances of adoptive transfer of MO-derived cells are developed with emphasis on the generation of antigen-presenting cells primed in vitro with tumor cells or specific peptides.
A novel approach for sequential assignment of proton, carbon-13, and nitrogen-15 spectra of larger proteins: heteronuclear triple-resonance three-dimensional NMR spectroscopy. Application to calmodulin (1990)

A novel approach is described for obtaining sequential assignment of the backbone 1H, 13C, and 15N resonances of larger proteins. The approach is demonstrated for the protein calmodulin (16.7 kDa), uniformly (approximately 95%) labeled with 15N and 13C. Sequential assignment of the backbone residues by standard methods was not possible because of the very narrow chemical shift distribution range of both NH and C alpha H protons in this largely alpha-helical protein. We demonstrate that the combined use of four new types of heteronuclear 3D NMR spectra together with the previously described HOHAHA-HMQC 3D experiment [Marion, D., et al. (1989) Biochemistry 28, 6150-6156] can provide unambiguous sequential assignment of protein backbone resonances. Sequential connectivity is derived from one-bond J couplings and the procedure is therefore independent of the backbone conformation. All the new 3D NMR experiments use 1H detection and rely on multiple-step magnetization transfers via well-resolved one-bond J couplings, offering high sensitivity and requiring a total of only 9 days for the recording of all five 3D spectra. Because the combination of 3D spectra offers at least two and often three independent pathways for determining sequential connectivity, the new assignment procedure is easily automated. Complete assignments are reported for the proton, carbon, and nitrogen backbone resonances of calmodulin, complexed with calcium.
Energy efficient battery management (2001)

A challenging aspect of mobile communications consists in exploring ways in which the available run time of terminals can be maximized. We present a detailed electrochemical battery model and a simple stochastic model that captures the fundamental behavior of the battery. The stochastic model is then matched to the electrochemical model and used to investigate battery management techniques that may improve the energy efficiency of radio communication devices. We consider an array of electrochemical cells. Through simple scheduling algorithms, the discharge from each cell is properly shaped to optimize the charge recovery mechanism, without introducing any additional delay in supplying the required power. Then, a battery management scheme, which exploits knowledge of the cells' state of charge, is implemented to achieve a further improvement in the battery performance. In this case, the discharge demand may be delayed. Results indicate that the proposed battery management techniques improve system performance no matter which parameters values are chosen to characterize the cells' behavior.
An oligomer complementary to c-myb-encoded mRNA inhibits proliferation of human myeloid leukemia cell lines. (1989)

To study the role of the protooncogene c-myb in regulating myeloid leukemia cell proliferation and differentiation, we exposed cells of the human leukemia lines HL-60, ML-3, KG-1, and KG-1a to an oligodeoxynucleotide complementary to an 18-base-pair (bp) sequence of c-myb-encoded mRNA. This treatment resulted in a significant decrease in cell proliferation in all of the lines, which was most marked in HL-60 cells. After 5 days in culture, in several separate experiments with different oligomer preparations, 75% growth inhibition was observed in c-myb antisense treated cells in comparison to untreated HL-60 cells. Two c-myb antisense oligomers of identical length with either 2- or 4-bp mismatches had no effect on cell growth nor did an 18-bp c-myb sense or myeloperoxidase antisense oligomer. The effect of a c-myc antisense oligomer (18 bp) on the growth of HL-60, KG-1, and KG-1a cells was also studied. This oligomer had much less inhibitory effect on cell proliferation than did the c-myb antisense sequence. Interestingly, although c-myc antisense treatment induced maturation of HL-60 cells while it inhibited cell proliferation, such an effect was not noted in c-myb antisense treated cells. These studies indicate that the nuclear protein encoded by the c-myb protooncogene is required for maintenance of proliferation in certain leukemia cell lines. In compared to c-myc protein suggest that, at least in HL-60 cells, c-myc amplification or N-ras activation may not be sufficient to maintain the leukemic growth in the absence of c-myb protein. These findings support the hypothesis that development and maintenance of a malignant phenotype requires a multiplicity of interrelated genetic events.