gebhart/patrepeval huggingface dataset:
Further evidence that one of the earliest alterations in colorectal carcinogenesis involves APC. (1994)

Colorectal cancer is hypothesized to arise after the accumulation of multiple mutations in critical oncogenes or tumor suppressor genes. The relative timing of each mutation is unknown because the exact number and types of mutations differ between tumors. However, for every mutation except the first, tumor heterogeneity must exist until clonal dominance is reestablished. This principle was applied to mutant APC genes in eight colorectal adenomas. The APC mutations were homogeneously present throughout the adenomas, including those less than 1 cm in size, but absent from the normal polyp stalks. In one adenoma with APC and c-K-ras mutations, both mutations were simultaneously present in only a small discrete portion, suggesting that the c-K-ras mutation was acquired after the APC mutation. These findings suggest that when mutations in APC occur, they are usually one of the first events in colorectal carcinogenesis or provide such a strong selective advantage that intratumor heterogeneity is seldom observed.
BIRC6 Protein, an Inhibitor of Apoptosis: Role in Survival of Human Prostate Cancer Cells (2013)

The data suggest a role for BIRC6 in prostate cancer progression and treatment resistance, and indicate for the first time that the BIRC6 gene and its product are potentially valuable targets for treatment of prostate cancers.
Acetyl‐CoA Carboxylase Inhibitors (2011)

This chapter contains sections titled: Introduction Biochemistry Chemistry of ACCase Inhibitors Structure–Activity Relationships Pinoxaden Summary and Outlook Acknowledgments References
Characterization of a unique variant of bat rabies virus responsible for newly emerging human cases in North America. (1996)

The silver-haired bat variant of rabies virus (SHBRV) has been identified as the etiological agent of a number of recent human rabies cases in the United States that are unusual in not having been associated with any known history of conventional exposure. Comparison of the different biological and biochemical properties of isolates of this virus with those of a coyote street rabies virus (COSRV) revealed that there are unique features associated with SHBRV. In vitro studies showed that, while the susceptibility of neuroblastoma cells to infection by both viruses was similar, the infectivity of SHBRV was much higher than that of COSRV in fibroblasts (BHK-21) and epithelial cells (MA-104), particularly when these cells were kept at 34 degrees C. At this temperature, low pH-dependent fusion and cell-to-cell spread of virus is seen in BHK-21 cells infected with SHBRV but not with COSRV. It appears that SHBRV may possess an unique cellular tropism and the ability to replicate at lower temperature, allowing a more effective local replication in the dermis. This hypothesis is supported by in vivo results which showed that while SHBRV is less neurovirulent than COSRV when administered via the intramuscular or intranasal routes, both viruses are equally neuroinvasive if injected intracranially or intradermally. Consistent with the above findings, the amino acid sequences of the glycoproteins of SHBRV and COSRV were found to have substantial differences, particularly in the region that contains the putative toxic loop, which are reflected in marked differences in their antigenic composition. Nevertheless, an experimental rabies vaccine based on the Pittman Moore vaccine strain protected mice equally well from lethal doses of SHBRV and COSRV, suggesting that currently used vaccines should be effective in the postexposure prophylaxis of rabies due to SHBRV.
Ultra Low Voltage Operations in Bulk CMOS Logic Circuits with Dopant Segregated Schottky Source/Drain Transistors (2006)

Ultra low power circuit operation is demonstrated with dopant segregated Schottky (DSS) source/drain transistors for the first time. DSS greatly improves propagation delay in multiple fan-in NAND gates at constant standby current. The delay is enhanced to 21% at 0.8V for 3-input NAND gates. Energy delay product (EDP) is improved by more than 50% with DSS at 0.8V
The LIR motif – crucial for selective autophagy (2013)

(Macro)autophagy is a fundamental degradation process for macromolecules and organelles of vital importance for cell and tissue homeostasis. Autophagy research has gained a strong momentum in recent years because of its relevance to cancer, neurodegenerative diseases, muscular dystrophy, lipid storage disorders, development, ageing and innate immunity. Autophagy has traditionally been thought of as a bulk degradation process that is mobilized upon nutritional starvation to replenish the cell with building blocks and keep up with the energy demand. This view has recently changed dramatically following an array of papers describing various forms of selective autophagy. A main driving force has been the discovery of specific autophagy receptors that sequester cargo into forming autophagosomes (phagophores). At the heart of this selectivity lies the LC3-interacting region (LIR) motif, which ensures the targeting of autophagy receptors to LC3 (or other ATG8 family proteins) anchored in the phagophore membrane. LIR-containing proteins include cargo receptors, members of the basal autophagy apparatus, proteins associated with vesicles and of their transport, Rab GTPase-activating proteins (GAPs) and specific signaling proteins that are degraded by selective autophagy. Here, we comment on these new insights and focus on the interactions of LIR-containing proteins with members of the ATG8 protein family.
Fluorescence near interfaces: The role of photonic mode density (1998)

Abstract A review of fluorescence near interfaces is presented. Recent work that examines the role of photonic mode density in this process is surveyed and the underlying concepts discussed. The review includes an examination of the role of surface and waveguide modes, as well as non-radiative decay. The importance of textured surfaces in providing large changes in photonic mode density and in coupling non-radiative modes to radiation is highlighted. Indications are given for future areas of research and on how photonic mode density may influence optical processes other than fluorescence.
Filamins Regulate Cell Spreading and Initiation of Cell Migration (2009)

Mammalian filamins (FLNs) are a family of three large actin-binding proteins. FLNa, the founding member of the family, was implicated in migration by cell biological analyses and the identification of FLNA mutations in the neuronal migration disorder periventricular heterotopia. However, recent knockout studies have questioned the relevance of FLNa to cell migration. Here we have used shRNA-mediated knockdown of FLNa, FLNb or FLNa and FLNb, or, alternatively, acute proteasomal degradation of all three FLNs, to generate FLN-deficient cells and assess their ability to migrate. We report that loss of FLNa or FLNb has little effect on migration but that knockdown of FLNa and FLNb, or proteolysis of all three FLNs, impairs migration. The observed defect is primarily a deficiency in initiation of motility rather than a problem with maintenance of locomotion speed. FLN-deficient cells are also impaired in spreading. Re-expression of full length FLNa, but not re-expression of a mutated FLNa lacking immunoglobulin domains 19 to 21, reverts both the spreading and the inhibition of initiation of migration.Our results establish a role for FLNs in cell migration and spreading and suggest that compensation by other FLNs may mask phenotypes in single knockout or knockdown cells. We propose that interactions between FLNs and transmembrane or signalling proteins, mediated at least in part by immunoglobulin domains 19 to 21 are important for both cell spreading and initiation of migration.
Immunization with viruslike particles induces long-term protection of rabbits against challenge with cottontail rabbit papillomavirus (1996)

Rabbits were immunized with recombinant baculovirus-produced virus-like particles (VLPs) of cottontail rabbit papillomavirus (CRPV) to determine whether these antigens could induce long-term protection against experimental challenge with CRPV. Infectious CRPV and human papillomavirus type 11 L1 VLPs were used as positive and negative control immunogens, respectively. Three groups of immunized animals were challenged with 10-fold serial dilutions of infectious CRPV at 2 weeks, 6 months, and 12 months after immunizations. Antibody titers in serum reached 1:10,000 immediately after the final booster immunization and then decayed to 1:150 at 6 months and 1:100 at 12 months in unchallenged rabbits. Serum neutralization titers followed similar kinetics. Papillomas grew on control-immunized rabbits at sites challenged with 10(-1) (100% of sites), 10(-2) (96% of sites), 10(-3) (63% of sites), and 10(-4) (13% of sites) dilutions of virus. At 2 weeks after CRPV L1 VLP immunizations, the rabbits were completely protected against virus challenge. At both 6 and 12 months after CRPV L1 VLP immunizations, strong protection was also observed. In the last two groups, three of seven rabbits were completely protected and only 4 of 14 or 29% of sites challenged with 10(-1 dilution of virus grew papillomas. Papillomas growing at these four sites were also reduced in size (3.5 +/- 0.7 mm) at 50 days postchallenge compared with sites challenged with 10(-1) dilution on control-immunized rabbits (13.2 +/- 4.2 mm). The results demonstrate that strong and long-lasting protection against experimental challenge with papillomaviruses can be achieved with VLP immunogens.
Glial and Neuronal Tau Pathology in Tauopathies (2013)

Tauopathies are degenerative diseases characterized by the accumulation of phosphorylated tau in neurons and glial cells. With some exceptions, tau deposits in neurons are mainly manifested as pretangles and tangles unrelated to the tauopathy. It is thought that abnormal tau deposition in neurons occurs following specific steps, but little is known about the progression of tau pathology in glial cells in tauopathies. We compared tau pathology in different astrocyte phenotypes and oligodendroglial inclusions with that in neurons in a large series of tauopathies, including progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease, Pick disease, frontotemporal lobar degenerations (FTLD) associated with mutations in the tau gene, globular glial tauopathy (GGT), and tauopathy in the elderly. Our findings indicate that disease-specific astroglial phenotypes depend on i) the primary amino acid sequence of tau (mutated tau, 3Rtau, and 4Rtau); ii) phospho-specific sites of tau phosphorylation, tau conformation, tau truncation, and ubiquitination in that order (which parallel tau modifications related to pretangle and tangle stages in neurons); and iii) modifications of the astroglial cytoskeleton. In contrast to astrocytes, coiled bodies in oligodendrocytes have similar characteristics whatever the tauopathy, except glial globular inclusions in GGT, and coiled bodies and globular oligodendroglial inclusions in FTLD-tau/K317M. These observations indicate that tau pathology in glial cells largely parallels, but is not identical to, that in neurons in many tauopathies.
Cosegregation of chromosomes containing immortal DNA strands in cells that cycle with asymmetric stem cell kinetics. (2002)

A long-standing intriguing hypothesis in cancer biology is that adult stem cells avoid mutations from DNA replication errors by a unique pattern of chromosome segregation. At each asymmetric cell division, adult stem cells have been postulated to selectively retain a set of chromosomes that contain old template DNA strands (i.e., "immortal DNA strands"). Using cultured cells that cycle with asymmetric cell kinetics, we confirmed both the existence of immortal DNA strands and the cosegregation of chromosomes that bear them. Our findings also lead us to propose a role for immortal DNA strands in tissue aging as well as cancer.
The Kinase Mirk/Dyrk1B Mediates Cell Survival in Pancreatic Ductal Adenocarcinoma (2006)

Ductal adenocarcinoma of the pancreas is almost uniformly lethal as this cancer is invariably detected at an advanced stage and is resistant to treatment. The serine/threonine kinase Mirk/Dyrk1B has been shown to be antiapoptotic in rhabdomyosarcomas. We have now investigated whether Mirk might mediate survival in another cancer in which Mirk is widely expressed, pancreatic ductal adenocarcinoma. Mirk was an active kinase in each pancreatic cancer cell line where it was detected. Mirk knockdown by RNA interference (RNAi) reduced the clonogenicity of Panc1 pancreatic cancer cells 4-fold and decreased tumor cell number, showing that Mirk mediates survival in these cells. Mirk knockdown by synthetic duplex RNAis in Panc1, AsPc1, and SU86.86 pancreatic cancer cells induced apoptosis and enhanced the apoptosis induced by gemcitibine. Mirk knockdown did not increase the abundance or activation of Akt. However, four of five pancreatic carcinoma cell lines exhibited either elevated Mirk activity or elevated Akt activity, suggesting that pancreatic cancer cells primarily rely on Mirk or Akt for survival signaling. Mirk protein was detected by immunohistochemistry in 25 of 28 cases (89%) of pancreatic ductal adenocarcinoma, with elevated expression in 11 cases (39%). Increased expression of Mirk was seen in pancreatic carcinomas compared with primary cultures of normal ductal epithelium by serial analysis of gene expression and by immunohistochemistry. Thus, Mirk is a survival factor for pancreatic ductal adenocarcinoma. Because knockout of Mirk does not cause embryonic lethality, Mirk is not essential for normal cell growth and may represent a novel therapeutic target.
Flexible Nerve Stimulation Electrode With Iridium Oxide Sputtered on Liquid Crystal Polymer (2009)

Current electrode designs require flexible substrates that absorb little moisture and provide large charge injection capability. Sputtered iridium oxide films have superior charge injection capabilities versus noble metals and can adhere to various substrates. Liquid crystal polymers (LCPs) have very little water absorption compared to other flexible substrates. Therefore, the combination of sputtered iridium oxide film on LCP substrate was studied using 50 Hz, 100 micros duration, and 10 mA biphasic current waveforms for 700 h at 67 degrees C in bicarbonate buffer saline. Scanning electron micrograph analysis showed no delamination and approximately 1% of electrode material was lost to the bicarbonate buffer. The charge injection limit and the cathodic charge storage capacity within the water window were 4.6 +/- 1.0 and 31.5 +/-6.6 mC/cm2, respectively. Additional electrochemical analysis revealed significant charge imbalance attributed to oxygen reduction within the water window. These results, along with the flexible, chemically inert, and biocompatible substrate, indicate that sputtered iridium oxide films on LCP could become the method of choice for flexible substrate nerve electrodes.
Can confidence indicators be useful to predict short term manufacturing growth (2002)

In this study we investigate the usefulness of business survey data in forecasting Hungarian manufacturing output growth in the short run. We analyse the individual questions of the business surveys, and use models with different flexibility (factor model, best fitting and recursively best fitting model) to estimate the relationship between the business survey indicators and manufacturing output growth. The models are evaluated according to their forecasting performance. We generally find that although confidence indicators can be useful in forecasting manufacturing output in the short run, their forecasting ability is limited to a one-quarter horizon. For this reason their use in forecasting should mainly be restricted to nowcasting purposes.
Inversionless decoding of both errors and erasures of Reed-Solomon code (1998)

Previously, the authors proposed an inverse-free Berlekamp-Massey (1968, 1969) algorithm to simplify the Reed-Solomon (RS) codes. This modified RS decoding method is the best known technique for finding the error locator polynomial. The inverse-free method is generalized to find both errors and erasures. The basic idea of the new procedure is the replacement of the initial condition of the BM algorithm by the Forney (1965) syndromes. With this improved technique, the complexity of time-domain RS decoders for correcting both errors and erasures is reduced substantially from previous approaches.
Understanding Australian Farmers' Intentions to Change Practices in Response to Calls from Animal Welfare Groups: The Case of Mulesing (2010)

A study was conducted to provide an insight into what motivates farmer intentions for change in cases such as mulesing when such change is pursued by animal welfare groups. The key findings of the study and its implications for the future are highlighted.
Randomized trial of fenretinide (4‐HPR) to prevent recurrences, new localizations and carcinomas in patients operated on for oral leukoplakia: Long‐term results (2005)

We assessed the efficacy of fenretinide at preventing relapses, new lesions and carcinomas after surgical excision of oral leukoplakia. In a controlled multicenter study, 170 patients operated on for oral leukoplakias with benign postoperative histology were randomized to 200 mg fenretinide daily for 1 year vs. no intervention. Preliminary analysis indicated that fenretinide had good tolerability and was effective at preventing relapses and new lesions during treatment. Analysis after 5-year follow-up suggested that fenretinide protected against relapses and new lesions up to 19 months after randomization, with both limits of the 95% hazard ratio CI for fenretinide vs. control below 1 for 7 months after randomization. There was also a protective effect against all first events, including cancer, for 25 months, with both limits of the 95% CI below 1 up to 11 months after randomization. Subsequently, risk ratio estimates were unstable. Fenretinide was well tolerated and effective at preventing relapses and new leukoplakias during treatment and after. The trial had to be stopped prematurely for very low recruitment and had insufficient power to reveal any protective effect against oral carcinoma; nevertheless, continuing studies on this promising chemopreventive are justified.
A new approach for eradication of residual lymphoma cells by host nonreactive anti–third-party central memory CD8 T cells (2013)

Generation of T cells endowed with graft-versus-leukemia (GVL) and depleted of graft-versus-host (GVH) activity represents a highly desirable goal in bone marrow transplantation (BMT). Here, we demonstrate that donor anti-third-party CD8 T cells with central memory phenotype (Tcm) exhibit marked GVL reactivity through a unique T-cell receptor-independent mechanism. Thus, in a residual disease mouse model, Tcm therapy following autologous BMT led to significant survival prolongation, with 30% to 40% of the treated mice displaying long-term tumor-free survival. A more impressive finding was that infusion of donor Tcm in an allogeneic model rapidly eliminated residual lymphoma cells and led to long-term survival of 100% in the absence of GVH disease. Collectively, the strong GVL reactivity of anti-third-party Tcm, coupled with their demonstrated enhancement of bone marrow allografting, suggests that the use of Tcm therapy in conjunction with allogeneic T-cell-depleted BMT could be of particular benefit in patients with B-cell malignancies who cannot tolerate intensive myeloablative conditioning.
Covalent Modifiers: An Orthogonal Approach to Drug Design (2009)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTCovalent Modifiers: An Orthogonal Approach to Drug DesignMichele H. Potashman* and Mark E. Duggan*§View Author Information Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, Massachusetts 02139* To whom correspondence should be addressed. For M.H.P.: phone, (617) 444-5010; fax, (617) 577-9288; e-mail, [email protected]. For M.E.D.: phone, (617) 583-1983; e-mail, [email protected]§Current address: Link Medicine Inc., 161 First Street, Cambridge, MA 02142.Cite this: J. Med. Chem. 2009, 52, 5, 1231–1246Publication Date (Web):February 9, 2009Publication History Received11 July 2008Published online9 February 2009Published inissue 12 March 2009https://pubs.acs.org/doi/10.1021/jm8008597https://doi.org/10.1021/jm8008597review-articleACS PublicationsCopyright © 2009 American Chemical SocietyRequest reuse permissionsArticle Views16521Altmetric-Citations288LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Adducts,Inhibition,Inhibitors,Monomers,Peptides and proteins Get e-Alerts
Detection and Characterization of Porcine Endogenous Retrovirus in Porcine Plasma and Porcine Factor VIII (2001)

The pig genome contains porcine endogenous retroviruses (PERVs) capable of infecting human cells. Detection of infectious retrovirus in porcine peripheral blood mononuclear cells and endothelial cells suggested to us that pig plasma is likely to contain PERV. Both PERV env sequences and viral reverse transcriptase (RT) activity were detected in all plasma samples isolated from four NIH minipigs. To detect infectious virus from plasma, we performed a culture assay using three cell lines of feline, swine, and human origin that had previously been shown to be permissive for PERV. Infectious virus was successfully cultured from all four NIH minipig plasmas on the swine cell line ST-IOWA. Using RT-PCR with env-specific primers, we could detect expression of PERV class C envelope in the supernatant of ST-IOWA cells that had been exposed to each pig plasma. We next examined a pig plasma derivative, Hyate:C (porcine factor VIII), and found evidence of PERV particles, since all six lots examined were positive for PERV RNA and RT activity. However, infectious virus could not be detected in clinical lots of Hyate:C, suggesting that the manufacturing process might reduce the load of infectious virus to levels below detectable limits of the assay. Detection of infectious virus in porcine plasma confirms and extends the previous findings that certain porcine cells express PERV when manipulated in vitro and clearly demonstrates that there are porcine cells that express infectious PERV constitutively in vivo.