gebhart/patrepeval huggingface dataset:
Stem cell-associated heterogeneity in Glioblastoma results from intrinsic tumor plasticity shaped by the microenvironment (2019)

The identity and unique capacity of cancer stem cells (CSC) to drive tumor growth and resistance have been challenged in brain tumors. Here we report that cells expressing CSC-associated cell membrane markers in Glioblastoma (GBM) do not represent a clonal entity defined by distinct functional properties and transcriptomic profiles, but rather a plastic state that most cancer cells can adopt. We show that phenotypic heterogeneity arises from non-hierarchical, reversible state transitions, instructed by the microenvironment and is predictable by mathematical modeling. Although functional stem cell properties were similar in vitro, accelerated reconstitution of heterogeneity provides a growth advantage in vivo, suggesting that tumorigenic potential is linked to intrinsic plasticity rather than CSC multipotency. The capacity of any given cancer cell to reconstitute tumor heterogeneity cautions against therapies targeting CSC-associated membrane epitopes. Instead inherent cancer cell plasticity emerges as a novel relevant target for treatment.
Hormonal regulation of the growth hormone gene. Relationship of the rate of transcription to the level of nuclear thyroid hormone-receptor complexes. (1984)

Using cultured GH1 cells, we reported that stimulation (3- to 5-fold) of growth hormone synthesis and mRNA levels by thyroid hormone is mediated by a chromatin-associated receptor. Thyroid hormone also elicits a rapid reduction of homologous receptor in GH1 cells primarily by decreasing the synthetic rate of receptor ( Raaka , B. M., and Samuels , H. H. (1981) J. Biol. Chem. 256, 6883-6889). Without 3,5,3'-triiodo-L-thyronine (L-T3), glucocorticoid agonists induced a limited and delayed effect while L-T3 + glucocorticoid synergistically stimulated the response an additional 2- to 4-fold compared to L-T3. In this study, we utilized GC cells, a related cell line, to compare the abundance of L-T3-receptor complexes to the rate of growth hormone mRNA synthesis and gene transcription. Gene transcription was assessed by in vitro labeling of nuclei with [alpha-32P]UTP which were derived from cells incubated with hormone(s), while mRNA synthesis was determined in intact cells by [3H]uridine labeling. Labeled growth hormone mRNA and gene transcripts were quantitated by filter hybridization to plasmid containing growth hormone cDNA. L-T3 rapidly decreased receptor levels in GC cells with kinetics similar to that in GH1 cells. Both the L-T3 and the synergistic L-T3 + glucocorticoid stimulation of growth hormone mRNA synthesis changed in parallel with the level of L-T3-receptor complexes. Glucocorticoid hormones alone elicited a variable response which resulted in minimal stimulation or inhibition of growth hormone mRNA synthesis or gene transcription rates. No apparent lag was identified between the kinetics of L-T3 binding to receptor and stimulation of growth hormone gene transcription. L-T3 stimulated growth hormone gene transcription rates maximally in 1 h which then progressively decreased in parallel with L-T3-receptor levels. Using [3H]uridine pulse-chase, growth hormone mRNA was found to have a half-life of approximately 50 h in agreement with the decay curve of growth hormone production of deinduced cells. Our studies suggest that regulation of the growth hormone response is predominantly determined by positive control of growth hormone gene transcription which is proportional to the concentration of thyroid hormone-receptor complexes.
Label-free optical detection of action potential in mammalian neurons (2017)

We describe an optical technique for label-free detection of the action potential in cultured mammalian neurons. Induced morphological changes due to action potential propagation in neurons are optically interrogated with a phase sensitive interferometric technique. Optical recordings composed of signal pulses mirror the electrical spike train activity of individual neurons in a network. The optical pulses are transient nanoscale oscillatory changes in the optical path length of varying peak magnitude and temporal width. Exogenous application of glutamate to cortical neuronal cultures produced coincident increase in the electrical and optical activity; both were blocked by application of a Na-channel blocker, Tetrodotoxin. The observed transient change in optical path length in a single optical pulse is primarily due to physical fluctuations of the neuronal cell membrane mediated by a yet unknown electromechanical transduction phenomenon. Our analysis suggests a traveling surface wave in the neuronal cell membrane is responsible for the measured optical signal pulses.
Neuroinflammation and Peripheral Immune Infiltration in Parkinson's Disease: An Autoimmune Hypothesis (2008)

Despite decades of research and the development of a large group of animal models, our understanding of the mechanisms responsible for the progressive loss of dopamine neurons in Parkinson's disease (PD) is unknown. So-called neuroprotective studies demonstrate that a vast group of molecules readily attenuate the dopamine (DA) neuron loss produced by DA neurotoxin insult. Despite these successes, these neuroprotective strategies have been surprisingly ineffective in patients. This may reflect the fact that the initial pathogenic event and the subsequent disease progression is a consequence of different mechanisms. As we began to think about this disconnect, we discovered that animals exposed to DA neurotoxins exhibited blood-brain barrier (BBB) dysfunction. If the BBB in PD patients is disrupted, then the barrier that normally segregates peripheral vascular factors from brain parenchyma is no longer present. Immune cells could then enter brain and produce a self-perpetuating (progressive) degenerative process. In this review, we propose that peripheral immunity contributes to the degenerative process of PD and may be responsible for the progressive nature of the disease. This hypothesis is supported by a broad and diverse literature that is just beginning to come together to suggest that PD is, in part, an autoimmune disease. In order to understand this hypothesis, the reader must question the conventional wisdom that the BBB is intact in PD, the brain is an immune privileged area, and that pathogenic insult and disease progression may reflect different mechanisms.
Hyperoxia Improves Oxygen Consumption in the Detached Feline Retina (2007)

Hyperoxia has been shown to improve photoreceptor survival in the detached retina. The present work suggests that hyperoxia is protective because it allowed increased photoreceptor oxygen consumption. Whereas normal Po(2)s were maintained at the inner and outer border of the avascular region during hyperoxia, Q(av) was not restored to normal, suggesting that other factors are involved in photoreceptor dysfunction during detachment in addition to insufficient oxygen delivery.
Named entity recognition in query (2009)

This paper addresses the problem of Named Entity Recognition in Query (NERQ), which involves detection of the named entity in a given query and classification of the named entity into predefined classes. NERQ is potentially useful in many applications in web search. The paper proposes taking a probabilistic approach to the task using query log data and Latent Dirichlet Allocation. We consider contexts of a named entity (i.e., the remainders of the named entity in queries) as words of a document, and classes of the named entity as topics. The topic model is constructed by a novel and general learning method referred to as WS-LDA (Weakly Supervised Latent Dirichlet Allocation), which employs weakly supervised learning (rather than unsupervised learning) using partially labeled seed entities. Experimental results show that the proposed method based on WS-LDA can accurately perform NERQ, and outperform the baseline methods.
Surface Characterization of a Silicon-Chip-Based DNA Microarray (2001)

The immobilization of DNA (deoxyribonucleic acid) on solid supports is a crucial step for any application in the field of DNA microarrays. It determines the efficacy of the hybridization and influences the signal strength for the detection. We used solid supports made from silicon wafers as an alternative substrate to the commonly used microscope glass slides. The covalent immobilization of thiol-terminated DNA oligonucleotides on self-assembled layers of (3-mercaptopropyl)trimethoxysilane (MPTS) by disulfide bond formation was investigated. Contact angle measurement, variable angle spectral ellipsometry (VASE), X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM) were used to characterize the changing properties of the surface during the DNA array fabrication. During wafer processing the contact angle changed from 3° for the hydroxylated surface to 48.5° after deposition of MPTS. XPS data demonstrated that all sulfur in the MPTS layer was present in the form of reduced SH or S−S groups. VASE measurements indicated a layer thickness of 57.8 Å for the immobilized 16 base oligonucleotides including a 18 carbon atom spacer located between the disulfide bond and the oligomer. AFM was used to characterize the DNA layer before and after hybridization to a complementary target. The data recorded after hybridization revealed a sharp increase in particle size from 89 nm2 to a mean value of 363 nm2. Fluorescence microscopy was used to monitor the hybridization of a fluorescently labeled DNA target to the immobilized probe. The heat stable disulfide-linkage formed during the oligonucleotide immobilization allowed the stripping of complementary DNA targets as well as rehybridization. These data show the advantages and applicability of silicon wafers that have been processed with CMOS (complementary metal oxide semiconductor) compatible processes as solid support in DNA technology. This approach offers the possibility of integration with other silicon-based components such as PCR microreactors and capillary electrophoresis units into a “lab-on-a-chip”.
Encoding and decoding hydrogen-bond patterns of organic compounds (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleEncoding and decoding hydrogen-bond patterns of organic compoundsMargaret C. EtterCite this: Acc. Chem. Res. 1990, 23, 4, 120–126Publication Date (Print):April 1, 1990Publication History Published online1 May 2002Published inissue 1 April 1990https://pubs.acs.org/doi/10.1021/ar00172a005https://doi.org/10.1021/ar00172a005research-articleACS PublicationsRequest reuse permissionsArticle Views10399Altmetric-Citations3648LEARN 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 Get e-Alerts
CEA radioimmunotherapy with 131I-labetuzumab improves survival post salvage resection of colorectal cancer metastases in the liver (2005)

3627 Background: Although complete (R0) resection of liver metastases (LM) remains the treatment of choice for colorectal cancer (CRC) patients amenable to curative therapy, only about one-third survive 5 years. The objective of this study was to evaluate the safety and efficacy of radioimmunotherapy (RAIT) post salvage resection of LM. Methods: Twenty-three patients who underwent surgery for LM of CRC received a dose of 40–60 mCi/m2 131I-labetuzumab, a humanized monoclonal antibody against carcinoembryonic antigen (CEA). Safety (n=23), disease-free survival (DFS) and overall survival (OS) (n=19) were determined, and efficacy then compared retrospectively to similar control patients treated at the same institution and during a similar timeframe, but without RAIT. Results: With a median follow-up of 64 months, median OS from the first liver resection for RAIT patients was 68.0 months (95% CI: 46.0 months, infinity) vs. 31.0 months (95% CI: 24.0, 59.0 months) for the control group (p=0.004). DFS for RAIT patients had a median of 18.0 months (95% CI: 11.0, 31.0 months) vs. 12.0 months (95% CI: 6.5, 21.5 months) for the controls (p=0.284). Five-year survival was 51.3% and 7.4% for RAIT and control groups, respectively. Also, RAIT benefited patients independently of bilobar involvement, the size and number of LM, or the resection margins. The major side effect was a transient myelosuppression, resulting mostly in a grade =< 3 neutropenia and/or thrombocytopenia. Conclusion: Since both median OS and the 5-year survival rate appear to be improved with adjuvant RAIT post complete LM resection in CRC, these results justify further evaluation in a multicenter, randomized trial. No significant financial relationships to disclose.
von Hippel-Lindau Disease (2006)

von Hippel-Lindau disease, which is characterized by an increased risk of hemangioblastomas, clear cell renal carcinomas, and pheochromocytomas, is caused by inactivating mutations of the VHL tumor suppressor gene. The VHL gene product, pVHL, has multiple functions, but the best documented, and the one most clearly linked to tumor development, relates to its role as the substrate recognition module of a ubiquitin ligase complex that targets hypoxia-inducible factor (HIF) for destruction. pVHL function is often compromised in sporadic kidney cancers, and inhibitors of the HIF-responsive growth factor (vascular endothelial growth factor) are active against this disease. pVHL, by inhibiting atypical protein kinase C and hence JunB, also affects neuronal survival, as do the products of the other genes linked to familial pheochromocytoma or paraganglioma (NF1, RET, SDHB, SDHC, and SDHD). It is hypothesized that tumor-associated alleles of these genes allow primitive sympathoadrenal precursors to escape developmental culling, and that such cells are at increased risk of forming tumors.
Low-Intensity Laser Therapy: A Review (2000)

Low-intensity laser radiation is characterized by its ability to induce athermic, nondestructive photobiological processes. Although it has been in use for more than 30 years, this phototherapy is still not an established therapeutic modality. We have summarized the main arguments being brought up against the use of this therapy and have reviewed the literature addressing both its in vitro and in vivo effects. We conclude that low-intensity laser irradiations might be of benefit in selected indications if the existing preliminary data can be confirmed by more prospective and well-controlled studies.
Genomic Structure ofPEX13,a Candidate Peroxisome Biogenesis Disorder Gene (1998)

The peroxisome biogenesis disorders (PBDs) are a set of lethal genetic diseases characterized by peroxisomal metabolic deficiencies, multisystem abnormalities, mental retardation, and premature death. These disorders are genetically heterogeneous and are caused by mutations in genes, termed PEX genes, required for import of proteins into the peroxisomal matrix. We have previously reported the identification of human PEX13, the gene encoding the docking factor for the PTS1 receptor, or PEX5 protein. As such, mutations in PEX13 would be expected to abrogate peroxisomal protein import and result in PBD phenotypes. We report here the structure of the human PEX13 gene. PEX13 spans approximately 11 kb on chromosome 2 and contains four exons, one more than previously thought. The corrected PEX13 cDNA is predicted to encode a protein product with a molecular mass of 44,312 Da. We examined the ability of PEX13 expression to rescue the peroxisomal protein import defects of fibroblast cells representing all known PBD complementation groups. No complementation was observed, suggesting that this gene is not mutated in any set of existing patients. However, given that complementation group assignments have been determined for only a subset of PBD patients, it is possible that PEX13-deficient patients may exist at a low frequency within our existing PBD patient population or within ethnic groups underrepresented in our patient pool.
Specific ER quality control components required for biogenesis of the plant innate immune receptor EFR (2009)

Plant innate immunity depends in part on recognition of pathogen-associated molecular patterns (PAMPs), such as bacterial flagellin, EF-Tu, and fungal chitin. Recognition is mediated by pattern-recognition receptors (PRRs) and results in PAMP-triggered immunity. EF-Tu and flagellin, and the derived peptides elf18 and flg22, are recognized in Arabidopsis by the leucine-rich repeat receptor kinases (LRR-RK), EFR and FLS2, respectively. To gain insights into the molecular mechanisms underlying PTI, we investigated EFR-mediated PTI using genetics. A forward-genetic screen for Arabidopsis elf18-insensitive (elfin) mutants revealed multiple alleles of calreticulin3 (CRT3), UDP-glucose glycoprotein glucosyl transferase (UGGT), and an HDEL receptor family member (ERD2b), potentially involved in endoplasmic reticulum quality control (ER-QC). Strikingly, FLS2-mediated responses were not impaired in crt3, uggt, and erd2b null mutants, revealing that the identified mutations are specific to EFR. A crt3 null mutant did not accumulate EFR protein, suggesting that EFR is a substrate for CRT3. Interestingly, Erd2b did not accumulate CRT3 protein, although they accumulate wild-type levels of other ER proteins. ERD2B seems therefore to be a specific HDEL receptor for CRT3 that allows its retro-translocation from the Golgi to the ER. These data reveal a previously unsuspected role of a specific subset of ER-QC machinery components for PRR accumulation in plant innate immunity.
Regulated cell death pathways: New twists in modulation of BCL2 family function (2009)

A number of cell death pathways have been recognized. Though apoptosis and autophagy have been well characterized, programmed necrosis has recently received attention and may provide clinical alternatives to suppress resistant tumors. Necrosis is primarily characterized by large-scale permeabilization, swelling, and rupture of cell membranes and the release of pro-inflammatory cytokines. Traditionally, necrosis in cancer cells has been indicative of poor prognoses, as chronic inflammation was found to encourage tumor growth. Yet, many antitumor effects associated with necrosis have been discovered in certain settings, such as the formation of an effective antitumor immune response. In this way, finding ways to attenuate the pro-tumor effects of necrosis while engaging the antitumor pathways via drugs, radiation, and sensitization may prove valuable as a clinical focus for the future. We hypothesize that the use of Bcl-2 inhibitors may enhance necrotic death characterized by inflammation and antitumor immunity. In this article, we briefly review apoptosis and autophagy and reason how necrosis may be a suitable alternative therapeutic endpoint. We then highlight novel inhibitors of Bcl-2 that may provide clinical application of our hypothesis in the future.
Mathematical Epidemiology of Infectious Diseases: Model Building, Analysis and Interpretation (2000)

Preface, Creed and Apology. What it is All About and What Not. The Top Down Approach. A Workbook. Portrait of the Reader as a Young Person. A Brief Outline of the Book. Acknowledgments. And What About Reality? I: THE BARE BONES: BASIC ISSUES EXPLAINED IN THE SIMPLEST CONTEXT. The Epidemic in a Closed Population. Heterogeneity: The Art of Averaging. Dynamics at the Demographic Time Scale. II: STRUCTURED POPULATIONS. The Concept of State. The Basic Reproduction Ratio. And Everything Else... Age Structure. Spatial Spread. Macroparasites. What is Contact? III: THE HARD PART: ELABORATIONS (ALMOST) ALL EXERCISES. Elaborations for Part I. Elaborations for Part II. Appendix A: Stochastic Basic of the Kermack-McKendrick ODE Model. Appendix B: Bibliographic Skeleton. Index.
Superiority of yeast over bacterial cytosine deaminase for enzyme/prodrug gene therapy in colon cancer xenografts. (1999)

The enzyme/prodrug strategy using bacterial cytosine deaminase (bCD) and 5-fluorocytosine (5-FC) is currently under investigation for cancer gene therapy. A major limitation for the use of bCD is that it is inefficient in the conversion of 5-FC into 5-fluorouracil. In the present study, we show that the K(m) of yeast cytosine deaminase (yCD) for 5-FC was 22-fold lower when compared with that of bCD. HT29 human colon cancer cells transduced with yCD (HT29/yCD) were significantly more sensitive to 5-FC in vitro than HT29 cells transduced with bCD (HT29/bCD). In tumor-bearing nude mice, complete tumor regression was observed in 6 of 13 HT29/yCD tumors in response to 5-FC treatment (500 mg/kg i.p. daily, 5 days a week for 2 weeks), whereas 0 of 10 HT29/bCD tumors were cured. Our study demonstrates an improved efficacy of the CD/5-FC treatment strategy when yCD was used. This enzyme has, therefore, a high potential to increase the therapeutic outcome of the enzyme/prodrug strategy in cancer patients.
Molecular Shot Noise, Burst Size Distribution, and Single-Molecule Detection in Fluid Flow:  Effects of Multiple Occupancy (1998)

We present a new mathematical approach for calculating burst size distributions for the detection of fluorescent molecules introduced into a fluid flow at different rates. The burst size distributions reflect the passage of more than one molecule through the detection volume in close succession. The calculations are based upon a physical model appropriate for the fluorophore phycoerythrin under the conditions of no saturation of excitation, negligible triplet-state dynamics, and negligible detector dead time. The model includes photophysical properties of the fluorophore phycoerythrin (absorption cross section, fluorescence quantum yield, and photostability); diffusion; sample stream hydrodynamics; spatially dependent optical detection efficiency; and excitation laser beam characteristics. Good agreement is found between the mathematical model and experimental results with phycoerythrin.
Atmospheric pressure helium rf plasma source for atomic and molecular mass spectrometry (2000)

A capacitively coupled low power atmospheric pressure rf He plasma established within a thermostated cylindrical steel block serves as a source for the generation of molecular and atomic ions for mass spectral analysis. Volatile analytes separated by gas chromatography are admitted to the source through a coaxial rf-powered center electrode. Variation of the forward power, in the range 5–100 W, and the position of the plasma relative to the differentially pumped extraction orifice of the mass spectrometer, permits control over the relative intensities of parent and daughter ion products of the decomposition of organometallic compounds introduced into the source. Spectral features range from simple response from atomic ions to the detection of the parent molecular compounds and combinations of the two between the extremes of operating conditions. Ferrocene, triethyllead chloride and ethylmercury chloride were used to illustrate the application of the technique.