gebhart/patrepeval huggingface dataset:
Histone Deacetylase Inhibitors in Clinical Studies as Templates for New Anticancer Agents (2015)

Histone dacetylases (HDACs) are a group of enzymes that remove acetyl groups from histones and regulate expression of tumor suppressor genes. They are implicated in many human diseases, especially cancer, making them a promising therapeutic target for treatment of the latter by developing a wide variety of inhibitors. HDAC inhibitors interfere with HDAC activity and regulate biological events, such as cell cycle, differentiation and apoptosis in cancer cells. As a result, HDAC inhibitor-based therapies have gained much attention for cancer treatment. To date, the FDA has approved three HDAC inhibitors for cutaneous/peripheral T-cell lymphoma and many more HDAC inhibitors are in different stages of clinical development for the treatment of hematological malignancies as well as solid tumors. In the intensifying efforts to discover new, hopefully more therapeutically efficacious HDAC inhibitors, molecular modeling-based rational drug design has played an important role in identifying potential inhibitors that vary in molecular structures and properties. In this review, we summarize four major structural classes of HDAC inhibitors that are in clinical trials and different computer modeling tools available for their structural modifications as a guide to discover additional HDAC inhibitors with greater therapeutic utility.
Synthetic riboregulators - an alternative means to control gene expression (2005)

Summary During the last years, the important role RNA plays for regulating gene expression in all organisms has become obvious. Consequently, several recent approaches aim to utilize the outstanding chemical properties of RNA in developing artificial RNA regulators for conditional gene expression systems. Rational design, in vitro selection and in vivo screening systems have been combined to create a versatile set of RNA based molecular switches. These tools rely on diverse mechanisms and exhibit activity in several organisms. In this review, we summarize recent developments in the application of synthetic riboswitches for gene regulation in vivo.
Anti‐müllerian hormone as a marker of ovarian reserve* (2005)

Plasma AMH assessments are superior to FSH in identifying women with reduced ovarian reserve. Anti-mullerian hormone assessment should be considered as a useful adjunct to FSH/oestradiol levels and antral follicle count when estimating ovarian reserve.
Improvement of water use efficiency in rice by expression of HARDY , an Arabidopsis drought and salt tolerance gene (2007)

Freshwater is a limited and dwindling global resource; therefore, efficient water use is required for food crops that have high water demands, such as rice, or for the production of sustainable energy biomass. We show here that expression of the Arabidopsis HARDY (HRD) gene in rice improves water use efficiency, the ratio of biomass produced to the water used, by enhancing photosynthetic assimilation and reducing transpiration. These drought-tolerant, low-water-consuming rice plants exhibit increased shoot biomass under well irrigated conditions and an adaptive increase in root biomass under drought stress. The HRD gene, an AP2/ERF-like transcription factor, identified by a gain-of-function Arabidopsis mutant hrd-D having roots with enhanced strength, branching, and cortical cells, exhibits drought resistance and salt tolerance, accompanied by an enhancement in the expression of abiotic stress associated genes. HRD overexpression in Arabidopsis produces thicker leaves with more chloroplast-bearing mesophyll cells, and in rice, there is an increase in leaf biomass and bundle sheath cells that probably contributes to the enhanced photosynthesis assimilation and efficiency. The results exemplify application of a gene identified from the model plant Arabidopsis for the improvement of water use efficiency coincident with drought resistance in the crop plant rice.
The Fast m-Transform: A Fast Computation of Cross-Correlations with Binary m-Sequences (1991)

An algorithm is presented for the fast computation of the m-transform, a Hadamard transform intimately related to cross-correlation of analog signals with binary m-sequences. It is shown that m-transforms are in the same Hadamard equivalence class as Walsh–Hadamard transforms and can, thus, becomputed by means of the Fast Walsh Transform (FWT) algorithm, preceded and followed by a permutation. The FWT is performed in place in the original data array, while the permutations are executed during loading and reading of this array. Real-time generation of the array addresses for loading and reading adds little to execution time of the FWT. The implementation described here lends itself particularly well to applications in linear and nonlinear systems analysis.
Growth and Properties of Semiconductor Core/Shell Nanocrystals with InAs Cores (2000)

Core/shell semiconductor nanocrystals with InAs cores were synthesized and characterized. III−V semiconductor shells (InP and GaAs), and II−VI semiconductor shells (CdSe, ZnSe, and ZnS) were overgrown on InAs cores with various radii using a two step synthesis. In the first step cores were prepared, and in the second step the shells were grown using high-temperature pyrolysis of organometallic precursors in a coordinating solvent. Core/shell growth was monitored by absorption and photoluminescence spectroscopy. The band gap shifts to the red upon growth of InP or CdSe shells, while for ZnSe and ZnS shells that have larger band offsets with respect to InAs, the band gap energy is maintained. This behavior is reproduced by band gap energy calculations using a particle within a spherical box model. The photoluminescence quantum yield is quenched in InAs/InP core/shells but increases substantially up to 20% for InAs/CdSe and InAs/ZnSe core/shells. For InAs/ZnS core/shells the enhancement of the photoluminescence quantum yields is smaller, up to 8%. The core/shell nanocrystals were characterized using transmission electron microscopy, X-ray photoelectron spectroscopy, and powder X-ray diffraction. X-ray photoelectron spectroscopy provides evidence for shell growth. The X-ray diffraction peaks shift and narrow upon shell growth, providing evidence for an epitaxial growth mode. Simulations of the X-ray diffraction patterns reproduce both effects, and show that there is one stacking fault present for every four to five layers in the core and core/shell nanocrystals. The stability of InAs/CdSe and InAs/ZnSe core/shells against oxidation is substantially improved compared with the cores, and the photostability is significantly better compared with a typical near-IR laser dye IR140. Core/shell nanocrystals with InAs cores are suggested as a novel type of fluorophores covering the near-IR spectral range, with high emission quantum yields and improved stability compared with traditional near-IR laser dyes.
Cloning of genes involved in carbazole degradation of Pseudomonas sp. strain CA10: nucleotide sequences of genes and characterization of meta-cleavage enzymes and hydrolase (1997)

The DNA fragment encoding meta-cleavage enzymes and the meta-cleavage compound hydrolase, involved in carbazole degradation, was cloned from the carbazole-utilizing bacterium Pseudomonas sp. strain CA10. DNA sequence analysis of this 2.6-kb SmaI-SphI fragment revealed that there were three open reading frames (ORF1, ORF2, and ORF3, in this gene order). ORF1 and ORF2 were indispensable for meta-cleavage activity for 2'-aminobiphenyl-2,3-diol and its easily available analog, 2,3-dihydroxybiphenyl, and were designated carBa and carBb, respectively. The alignment of CarBb with other meta-cleavage enzymes indicated that CarBb may have a non-heme iron cofactor coordinating site. On the basis of the phylogenetic tree, CarBb was classified as a member of the protocatechuate 4,5-dioxygenase family. This unique extradiol dioxygenase, CarB, had significantly higher affinity and about 20-times-higher meta-cleavage activity for 2,3-dihydroxybiphenyl than for catechol derivatives. The putative polypeptide encoded by ORF3 was homologous with meta-cleavage compound hydrolases in other bacteria, and ORF3 was designated carC. The hydrolase activity of CarC for 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid, the meta-cleavage compound of 2,3-dihydroxybiphenyl, was 40 times higher than that for 2-hydroxy-6-oxohepta-2,4-dienoic acid, the meta-cleavage compound of 3-methylcatechol. Alignment analysis and the phylogenetic tree indicate that CarC has greatest homologies with hydrolases involved in the monoaromatic compound degradation pathway. These results suggest the possibility that CarC is a novel type of hydrolase.
Overview of Affinity Tags for Protein Purification (2004)

Addition of an affinity tag is a useful method for differentiating recombinant proteins expressed in bacterial and eukaryotic expression systems from the background of total cellular proteins, and for detecting protein-protein interactions. This overview describes the historical basis for the development of affinity tags, affinity tags that are commonly used today, how to choose an appropriate affinity tag for a particular purpose, and several recently developed affinity tag technologies that may prove useful in the near future.
MET/HGF pathway activation as a paradigm of resistance to targeted therapies (2017)

Resistance to targeted therapeutics is a key issue limiting the long-term utility of these medications in the management of molecularly selected subsets of cancer patients, including patients with non-small cell lung cancer harboring oncogenic alterations affecting <i>EGFR</i>, <i>ALK</i> and other genes. Bypass resistance mediated by activation of MET kinase has emerged as a frequent, validated and pivotal resistance mechanism in multiple types of cancers. Biochemical understanding is accumulating to explain the unique role of MET in such bypass pathways, providing alternate downstream activation opportunities and intricate interactions during epithelial-mesenchymal transitions. Multiple diagnostic testing platforms have become available for selecting appropriate patients for MET targeting in a variety of settings. Importantly, in light of the failures of several earlier clinical studies of MET targeting agents, a large array of recent and current MET-focused trials are incorporating stricter patient selection and more robust predictive biomarkers providing hope for validation of MET targeting as a clinically impactful strategy.
Relaxin Activates Multiple cAMP Signaling Pathway Profiles in Different Target Cells (2009)

Although RXFP1-cAMP signaling in HEK293T cell systems is now relatively well-defined, the signaling pathways activated by relaxin in its target cells and tissues are still unclear. This study aimed to examine the cAMP signaling of RXFP1 in cells that endogenously express the receptor. Seven cell types derived from various backgrounds were screened for receptor expression. Only in THP-1 cells and rat cardiac fibroblasts was there activation of the Galpha(i3)-Gbetagamma-phosphatidylinositol 3-kinase-protein kinase Czeta pathway, leading to cAMP accumulation. In all other cells there was activation of a combination of the initial pathways to affect cAMP. T-47D cells could activate only Galpha(s), whereas Colo 16 and rat renal fibroblasts from obstructed kidney could activate both Galpha(s) and Galpha(oB) pathways. Thus, the signaling pathways activated by relaxin are highly dependent upon the cell type under investigation, and this may help to explain the varied physiological responses exerted by relaxin in its different target tissues.
Hadamard Transform Time‐of‐Flight Mass Spectrometry: More Signal, More of the Time (2003)

Hadamard transform time-of-flight mass spectrometry (HT-TOF MS) is a type of mass analysis that was developed to couple continuous ion sources to the inherently pulsed nature of time-of-flight measurements. Unlike conventional TOF MS, the Hadamard transform method offers a duty cycle of 50%, with the possibility of extending it to 100%. Because it is a multiplexing technique, the attainable signal-to-noise ratio (SNR) is also significantly higher than that of conventional TOF MS. This review covers the basic principles behind HT-TOF MS. We illustrate, through examples, the source of the high-duty cycle and the increase in SNR. These features translate to a mass spectral storage rate that is the fastest among similar instruments, which enables its use as a detector for high-speed separations.
A murine model of mucopolysaccharidosis VII. Gross and microscopic findings in beta-glucuronidase-deficient mice. (1990)

This report describes the clinical and pathologic alterations found in mice that have a recessively inherited, essentially complete deficiency of the lysosomal enzyme beta-glucuronidase. Affected animals have a shortened life span and are dysmorphic and dwarfed. Abnormal gait and decreased joint mobility correlate with glycosaminoglycan accumulation in articular tissue and cartilaginous and bony lesions result in extensive skeletal deformation. In these enzyme-deficient animals, lysosomes, distended by fine fibrillar and granular storage material, are particularly prominent in the macrophage system but also occur in other tissues including the skeletal and central nervous systems. The clinical and pathologic abnormalities in these mutant mice closely parallel those identified in humans with mucopolysaccharidoses (MPS). Therefore, these mice provide a well-defined genetic system for the analysis of the pathophysiology of mucopolysaccharidosis type VII, which has many features in common with the other MPS. The mutant mice provide an attractive animal model to test potential therapies for lysosomal storage disease.
Heterogeneous Transfer Learning for Image Classification (2011)

Transfer learning as a new machine learning paradigm has gained increasing attention lately. In situations where the training data in a target domain are not sufficient to learn predictive models effectively, transfer learning leverages auxiliary source data from other related source domains for learning. While most of the existing works in this area only focused on using the source data with the same structure as the target data, in this paper, we push this boundary further by proposing a heterogeneous transfer learning framework for knowledge transfer between text and images. We observe that for a target-domain classification problem, some annotated images can be found on many social Web sites, which can serve as a bridge to transfer knowledge from the abundant text documents available over the Web. A key question is how to effectively transfer the knowledge in the source data even though the text can be arbitrarily found. Our solution is to enrich the representation of the target images with semantic concepts extracted from the auxiliary source data through a novel matrix factorization method. By using the latent semantic features generated by the auxiliary data, we are able to build a better integrated image classifier. We empirically demonstrate the effectiveness of our algorithm on the Caltech-256 image dataset.
Reversible Expression of CD34 by Murine Hematopoietic Stem Cells (1999)

We used a mouse transplantation model to address the recent controversy about CD34 expression by hematopoietic stem cells. Cells from Ly-5.1 C57BL/6 mice were used as donor cells and Ly-5.2 mice were the recipients. The test cells were transplanted together with compromised marrow cells of Ly-5.2 mice. First, we confirmed that the majority of the stem cells with long-term engraftment capabilities of normal adult mice are CD34(-). We then observed that, after the injection of 150 mg/kg 5-fluorouracil (5-FU), stem cells may be found in both CD34(-) and CD34(+) cell populations. These results indicated that activated stem cells express CD34. We tested this hypothesis also by using in vitro expansion with interleukin-11 and steel factor of lineage(-) c-kit(+) Sca-1(+) CD34(-) bone marrow cells of normal mice. When the cells expanded for 1 week were separated into CD34(-) and CD34(+) cell populations and tested for their engraftment capabilities, only CD34(+) cells were capable of 2 to 5 months of engraftment. Finally, we tested reversion of CD34(+) stem cells to CD34(-) state. We transplanted Ly-5.1 CD34(+) post-5-FU marrow cells into Ly-5.2 primary recipients and, after the marrow achieved steady state, tested the Ly-5.1 cells of the primary recipients for their engraftment capabilities in Ly-5.2 secondary recipients. The majority of the Ly-5.1 stem cells with long-term engraftment capability were in the CD34(-) cell fraction, indicating the reversion of CD34(+) to CD34(-) stem cells. These observations clearly demonstrated that CD34 expression reflects the activation state of hematopoietic stem cells and that this is reversible.
The mutA mistranslator tRNA‐induced mutator phenotype requires recA and recB genes, but not the derepression of lexA‐regulated functions (1999)

The mapping of mutA and mutC mutator alleles to the glyV and glyW glycine tRNA genes, respectively, and the subsequent discovery that the mutA phenotype is abolished in a DeltarecA strain raise the possibility that asp --> gly misinsertion may induce a novel mutagenic pathway. The recA requirement suggests three possibilities: (i) the SOS mutagenesis pathway is activated in mutA cells; (ii) loss of recA function interferes with mutA-promoted asp --> gly misinsertion; or (iii) a hitherto unrecognized recA-dependent mutagenic pathway is activated by translational stress. By assaying the expression levels of a reporter plasmid bearing a umuC :lacZ fusion, we show that the SOS regulon is not in a derepressed state in mutA cells. Neither overexpression of the lexA gene through a multicopy plasmid nor replacement of the wild-type lexA allele with the lexA1[Ind-] allele interferes with the expression of the mutA phenotype. The mutA phenotype is unaffected in cells defective for dinB, as shown here, and is unaffected in cells defective for umuD and umuC genes, as shown previously. We show that mutA-promoted asp --> gly misinsertion occurs in recA- cells and, therefore, the requirement for recA is 'downstream' of mistranslation. Finally, we show that the mutA phenotype is abolished in cells deficient for recB, suggesting that cellular recombination functions may be required for the expression of the mutator phenotype. We propose that translational stress induces a previously unrecognized mutagenic pathway in Escherichia coli.
Use of Graphite as a Highly Reversible Electrode with Superior Cycle Life for Sodium‐Ion Batteries by Making Use of Co‐Intercalation Phenomena (2014)

Although being the standard anode material in lithium-ion batteries (LIBs), graphite so far is considered to fail application in sodium-ion batteries (NIBs) because the Na-C system lacks suitable binary intercalation compounds. Here we show that this limitation can be circumvented by using co-intercalation phenomena in a diglyme-based electrolyte. The resulting compound is a stage-I ternary intercalation compound with an estimated stoichiometry of Na(diglyme)2C20. Highlights of the electrode reaction are its high energy efficiency, the small irreversible loss during the first cycle, and a superior cycle life with capacities close to 100 mAh g(-1) for 1000 cycles and coulomb efficiencies >99.87%. A one-to-one comparison with the analogue lithium-based cell shows that the sodium-based system performs better and also withstands higher currents.
Vascular endothelial growth factor is an autocrine growth factor in human malignant mesothelioma (2001)

Vascular endothelial growth factor (VEGF), a potent mitogen for vascular endothelium, is expressed in malignant pleural mesothelioma (MM). The present report examines the effect of VEGF on MM growth. Four MM cell lines produced significantly higher VEGF levels than normal mesothelial cells (1946+/-14 pg/ml vs. 180+/-17 pg/ml; p<0.001). In addition, MM cells expressed the tyrosine kinase-related VEGF receptors Flt-1 and KDR. Recombinant human VEGF phosphorylated both Flt-1 and KDR and increased proliferation of all four MM cell lines in a dose-dependent fashion. Neutralizing antibodies against either VEGF, Flt-1 or KDR significantly reduced MM cellular proliferation. In addition, expression of VEGF, Flt-1, and KDR was observed in MM biopsies. Moreover, higher VEGF levels were found in the pleural effusions of MM patients than in the effusions of patients with non-malignant pleural disease (1885.7+/-894.9 pg/ml vs. 266.9+/-180.5 pg/ml; p<0.001). Linear regression analysis showed a significant inverse correlation between serum VEGF levels and MM patient survival (r=0.72; p<0.01). No correlation was found between tumour vessel density and either serum (r=0.26; p=0.42) or pleural effusion (r=0.35; p=0.26) VEGF levels. These results indicate that VEGF, via activation of its tyrosine kinase receptors, may be a key regulator of MM growth. In addition, VEGF production could have an impact on patient survival, not only by promoting tumour angiogenesis but also by directly stimulating tumour growth.
Analysis by matrix assisted laser desorption/ ionisation-time of flight mass spectrometry of the post-translational modifications of α1-antitrypsin isoforms separated by two- dimensional polyacrylamide gel electrophoresis (2001)

The state of protein glycosylation in terms of occupation of potential N-linked glycosylation sites (macroheterogeneity) and type of glycosylation at that site (microheterogeneity) is important when investigating the consequences of aberrant glycosylation in the pathophysiology of disease. Protocols have been developed to permit characterisation of the site-specific glycosylation of individual isoforms of glycoproteins after separation by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and analysis of the peptide mixture by peptide mass fingerprinting using matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI-TOF). High resolution of the individual isoforms of α1- antitrypsin was achieved by using narrow range (4.5–5.5) pI strips. The individual isoforms were then subjected to sequential digestion with a recombinant N-glycanase followed by a protease. Using this strategy it was possible not only to increase the coverage of the amino acid sequence but also to monitor the occupancy of all three putative N-linked glycosylation sites. Glycans were enzymatically released from α1-antitrypsin which had been separated in gels formed with a low percentage of bis-acrylamide cross-linker and analysed. Profiles of the N-linked glycans of the individual isoforms of α1-antitrypsin were obtained by MALDI-TOF.
Discovery of EGFR Selective 4,6-Disubstituted Pyrimidines from a Combinatorial Kinase-Directed Heterocycle Library (2006)

The epidermal growth factor receptor (EGFR) tyrosine kinase was one of the first receptor tyrosine kinases to be targeted for drug development by the pharmaceutical industry due to its ubiquitous overexpression in a variety of tumors. Despite the validation of several quinazoline-based scaffolds in the clinic, there is a dearth of alternative chemical structure classes that are capable of inhibiting EGFR kinase activity selectively. Here we describe the discovery of potent and highly selective 4,6-disubstituted pyrimidine inhibitors of enzymatic and cellular EGFR activity and provide an explanation for their exceptional degree of kinase selectivity.