gebhart/patrepeval huggingface dataset:
Seamless Integration of Handwriting Recognition into Pen-Enabled Displays for Fast User Interaction (2012)

This paper proposes a framework for the integration of handwriting recognition into natural user interfaces. As more and more pen-enabled touch displays are available, we make use of the distinction between touch actions and pen actions. Furthermore, we apply a recently introduced mode detection approach to distinguish between handwritten strokes and graphics drawn with the pen. These ideas are implemented in the Touch & Write SDK which can be used for various applications. In order to evaluate the effectiveness of our approach, we have conducted experiments for an annotation scenario. We asked several users to mark and label several objects in videos. We have measured the labeling time when using our novel user interaction system and compared it to the time needed when using common labeling tools. Furthermore, we compare our handwritten input paradigm to other existing systems. It turns out that the annotation is performed much faster when using our method and the user experience is also much better.
Influence of solid support, solvent and coupling reagent on the head-to-tail cyclization of resin-bound peptides. (1995)

Head-to-tail cyclization of peptides attached to insoluble supports by means of the side chains of aspartic acid or glutamic acid allows the rapid synthesis of cyclic peptides of widely varied amino acid sequence. However, two side reactions dramatically reduce the yield of the desired compound; these are (1) interpeptide condensation that creates dimers, trimers and higher-order oligomers and (2) racemization of the C-terminal residue. A comparison was made between benzotriazoyloxy-tris-(dimethyl-amino)phosphonium hexafluorophosphate (BOP) and diisopropylcarbodiimide (DIPCDI) as cyclization reagents on kieselguhr-supported polydimethylacrylamide, chloromethyl-PolyHipe, and two commercially available polystyrene supports using DMF, CH2Cl2 and THF as cyclization solvents. Both of the side reactions are dependent on the amino acid sequence, the reagent used to couple the ends of the peptide and the solid support.
Antiinflammatory effects of 5‐HT3receptor antagonists in lipopolysaccharide‐stimulated primary human monocytes (2004)

There is evidence from both human and animal research that 5-hydroxytryptamine (5-HT)3 receptor antagonists, particularly tropisetron, exert analgesic and antiinflammatory effects. However, the underlying mechanisms of these effects have not yet been investigated in detail. Therefore, the antiinflammatory effects of tropisetron and ondansetron were investigated in human monocytes. In human monocytes, both lipopolysaccharide (LPS)-stimulated tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta secretion were dose-dependently inhibited by tropisetron starting at a concentration of 5 microg/mL and reaching maximal levels at 25 microg/mL (IC50: 32 microg/mL and 12 microg/mL, respectively). LPS-induced IL-6 and PGE2 release was only slightly inhibited at high doses, whereas LPS-induced release of IL-8 and matrix metalloprotease (MMP)-9 was not affected. In conclusion, our data show that the binding of tropisetron to 5-HT3 receptors results in antiinflammatory effects through inhibition of TNF-alpha/IL-1beta, which might explain the antiphlogistic effects of 5-HT3 antagonists.
Cloning and functional characterization of a cocaine‐sensitive dopamine transporter (1991)

We report the cloning of a rat cDNA encoding a functional dopamine transporter. This cDNA, derived from an intron-containing gene, encodes a protein of 620 amino acids. Hydropathicity analysis of the protein sequence suggests the presence of 12 putative transmembrane domains. The protein displays considerable identity with transporters for noradrenaline and GABA (64 and 30%, respectively). Transient expression of the cDNA in COS7 cells directs the expression of dopamine uptake activity with appropriate pharmacology and in a sodium-dependent fashion. In situ hybridization reveals that the mRNA for this transporter is expressed in the substantia nigra and ventral tegmental area, regions that contain dopaminergic cell bodies.
The role of eIF4 in cell proliferation. (1996)

Translational control has a key role in regulating cell growth. The mRNA binding translation factors (eIF4s) selectively modulate the translation of different mRNAs based on their differing properties, especially the extent of inhibitory secondary structure in their 5' untranslated regions. The mRNA 5' cap is recognized by eIF4E, which can then recruit other translation factors including the helicase cIF4A. Overexpression of eIF4E leads to cell transformation or disordered growth. It also enhances the translation of certain mRNAs, including that for cyclin D1. Decreased expression of eIF4E leads to reduced rates of cell growth. Transformed cells express elevated levels of eIF4E. eIF4E is subject to phosphorylation, which is increased by agents that stimulate translation. However, the role of eIF4E phosphorylation and the signalling pathways through which it is controlled remain to be elucidated. Oncogenic ras leads to increased phosphorylation of eIF4E, and the ability of ras to transform cells is diminished when eIF4E expression is decreased, implying that eIF4E is a key mediator of ras mediated transformation. The recent discovery of inhibitors of eIF4E (eIF4E binding proteins, 4EBP1/2) adds another regulatory component to the system. Although a role for 4EBP1 in cell transformation (or rather in impeding it) has yet to be established, this is an exciting and likely possibility. It should also be noted that 4EBP1 seems to be under the control of the p70S6K pathway, which has a role in cell cycle progression.
Biological and Pharmacological Activities of Carvacrol and Carvacrol Bearing Essential Oils (2008)

Oregano essential oils obtained from the genera Origanum, Thymus, Coridothymus, Thymbra, Satureja and Lippia are rich in carvacrol, a monoterpenic phenol isomeric with thymol. Turkey is the biggest exporter of oregano herb and oil to the world markets. Oregano is mainly used in food, spice and pharmaceutical industries. Carvacrol is responsible for the biological activities of oregano. Many diverse activities of carvacrol such as antimicrobial, antitumor, antimutagenic, antigenotoxic, analgesic, antispasmodic, antiinflammatory, angiogenic, antiparasitic, antiplatelet, AChe inhibitory, antielastase, insecticidal, antihepatotoxic and hepatoprotective activities and uses such as feed additive, in honeybee breeding and in gastrointestinal ailments have been shown. This paper highlights these activities and attempts to explain the possible in vivo mechanism of action of carvacrol.
Chemosensitivity profiles of human cancers assessed by the 6‐day SRC assay on serially xenografted tumors (1986)

To assess the potential value of the 6-day subrenal capsule (SRC) assay in preclinical evaluation of new drugs using serially xenografted human tumors as source of tumor tissue, we studied the response of 31 human tumor lines (8 malignant melanomas, 12 sarcomas, 9 lung carcinomas and 2 colon carcinomas) to relevant standard drugs and to a new imidazotetrazine, Mitozolomide. Mitozolomide was found to be the most active drug tested in 50% of the lung carcinomas and as active as CCNU in melanomas. The activity of the standard anticancer drugs against subrenal grafts closely resembled the patterns seen with the same tumors in the clinic. In further attempts to validate the procedure, sensitivity profiles of some tumors were concurrently determined in the subcutaneous (s.c.) nude mouse model. In 11 out of the 12 tumors, the two assays selected the same drug as being the most active and in most of these tumors the two procedures gave the same ranking for the different drugs. Also, when the relative sensitivities of a series of melanoma xenografts to each of two drugs (DTIC and CCNU) were tested, the two assays gave the same ranking of the xenografts for each drug. The concordance between the two assays and the fact that the s.c. nude mouse assay reflects the chemosensitivity of the parent tumor in patients, suggest that the application of the 6-day SRC assay to xenografted tumors is a valid and useful procedure permitting rapid preclinical evaluation of new drugs to be carried out at relatively low cost.
Development and status of the SNS ion source (2004)

The ion source for the Spallation Neutron Source (SNS) is a radio-frequency, multicusp source designed to deliver 45 mA of H with a normalized rms emittance of less than 0.2 π mm mrad to the SNS accelerator. The ion source— designed, constructed, and commissioned at Lawrence Berkeley National Laboratory (LBNL)—satisfies the basic requirements of commissioning and early operation of the SNS accelerator. To improve reliability of the ion source and consequently the availability of the SNS accelerator, we are undertaking a comprehensive ion source development program at Oak Ridge National Laboratory (ORNL). To date, this program has focused on design and development of internal and external ion source antennas having long operational lifetimes, development and characterization of efficient RF matching networks, simulation and measurement of the extracted ion beam and, optimization of the beam extraction and Cs systems. This report will outline progress made in some of these areas as well as summarize the current state of the SNS ion source discussing specifically source performance during front end re-commissioning at ORNL.
Bovine factor VII. Its purification and complete amino acid sequence. (1988)

A modified method for purification of blood clotting factor VII from bovine plasma was developed, and its complete amino acid sequence was established. The isolated factor VII was activated with factor XIIa, and the resulting two-chain factor VII (factor VIIa) was reduced and S-pyridylethylated or S-aminoethylated. The amino acid sequences of the S-alkylated heavy and light chains were determined by sequencing the fragments obtained from enzymatic and chemical cleavages. Fast atom bombardment mass spectrometry was also used to establish the COOH-terminal sequence of the heavy chain. The light chain consists of 152 residues with one carbohydrate chain at Asn145, and 11 gamma-carboxyglutamic acid residues are found within the NH2-terminal 35 residues. The light chain contains 0.2-0.3 mol of beta-hydroxyaspartic acid/mol of protein, indicating that an aspartic acid residue in bovine factor VII is incompletely hydroxylated. Moreover, a pentapeptide, Ala-Ser*-Ser-Pro-Cys (positions 51-55), isolated from an enzymatic digest of the light chain, contained an unknown serine derivative, but its structure is still unclear. On the other hand, the heavy chain is composed of 255 residues and one asparagine-linked carbohydrate chain at Asn203. Bovine factor VII, with a total of 407 residues, has 71% sequence identity with the human molecule (406 residues) predicted from the cDNA sequence (Hagen, F. S., Gray, C. L., O'Hara, P., Grant, F. J., Saari, G. C., Woodbury, R. G., Hart, C. E., Insley, M., Kisiel, W., Kurachi, K., and Davie, E. W. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 2412-2416).
What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases (2019)

Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human's gut microbiota are shaped in early life as their composition depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual. However, a healthy host⁻microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurological disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions.
Microchip technology in drug delivery (2000)

The realization that the therapeutic efficacy of certain drugs can be affected dramatically by the way in which they are delivered has created immense interest in controlled drug delivery systems. Much previous work in drug delivery focused on achieving sustained drug release rates over time, while a more recent trend is to make devices that allow the release rate to be varied over time. Advances in microfabrication technology have made an entirely new type of drug delivery device possible. Proof-of-principle experiments have shown that silicon microchips have the ability to store and release multiple chemicals on demand. Future integration of active control electronics, such as microprocessors, remote control units, or biosensors, could lead to the development of a 'pharmacy on a chip,' ie 'smart' microchip implants or tablets that release drugs into the body automatically when needed.
Identification of Residues of the Epidermal Growth Factor Receptor Proximal to Residue 45 of Bound Epidermal Growth Factor (1996)

A triple mutant of murine epidermal growth factor (mEGF), N1Q/H22Y/R45K-mEGF, was constructed by site-directed mutagenesis, expressed, purified, and characterized for use in an affinity cross-linking study to identify aminoacyl residues of the EGF receptor adjacent to a residue in the carboxyl-terminal domain of bound EGF thought to be important in distinguishing between EGF and transforming growth factor-alpha in their recognition by the receptor. Cyclization of Gln1 to form pyroglutamate (pE) limited the site of cross-linking in the mutant to Lys45, permitting identification of receptor residues that are proximal to this residue of bound EGF. The resulting N1pE/H22Y/R45K-mEGF was shown to be comparable to wild-type mEGF in receptor binding and stimulation of receptor autophosphorylation. 125I-Labeled N1pE/H22Y/R45K-mEGF was reacted with the heterobifunctional cross-linking reagent sulfo-N-succinimidyl-4-(fluorosulfonyl)benzoate, and the resulting modified EGF was incubated with A431 membrane vesicles bearing EGF receptors. Incubation resulted in specific cross-linking of the labeled N1pE/H22Y/R45K-mEGF to EGF receptors. The resulting cross-linked complex was then partially purified, denatured, reduced, and carboxyamidomethylated. Digestion with endoprotease LysC resulted in a unique radiolabeled peptide that could be immunoprecipitated using antibodies to mEGF. This immunoprecipitated fragment was purified by gel electrophoresis and subjected to microsequencing. The resulting sequence was matched to that of a LysC fragment of the receptor, which begins with Thr464 and is near the interface of receptor subdomains III and IV. Loss of signal at cycle 2 suggests that the point of attachment of cross-linked N1pE/H22Y/R45K is Lys465 of the receptor.
Spatial-scanning hyperspectral imaging probe for bio-imaging applications (2016)

The three common methods to perform hyperspectral imaging are the spatial-scanning, spectral-scanning, and snapshot methods. However, only the spectral-scanning and snapshot methods have been configured to a hyperspectral imaging probe as of today. This paper presents a spatial-scanning (pushbroom) hyperspectral imaging probe, which is realized by integrating a pushbroom hyperspectral imager with an imaging probe. The proposed hyperspectral imaging probe can also function as an endoscopic probe by integrating a custom fabricated image fiber bundle unit. The imaging probe is configured by incorporating a gradient-index lens at the end face of an image fiber bundle that consists of about 50,000 individual fiberlets. The necessary simulations, methodology, and detailed instrumentation aspects that are carried out are explained followed by assessing the developed probe's performance. Resolution test targets such as United States Air Force chart as well as bio-samples such as chicken breast tissue with blood clot are used as test samples for resolution analysis and for performance validation. This system is built on a pushbroom hyperspectral imaging system with a video camera and has the advantage of acquiring information from a large number of spectral bands with selectable region of interest. The advantages of this spatial-scanning hyperspectral imaging probe can be extended to test samples or tissues residing in regions that are difficult to access with potential diagnostic bio-imaging applications.
High-Throughput Genomic Profiling of Adult Solid Tumors Reveals Novel Insights into Cancer Pathogenesis (2017)

Genomic profiling is widely predicted to become a standard of care in clinical oncology, but more effective data sharing to accelerate progress in precision medicine will be required. Here, we describe cancer-associated genomic profiles from 18,004 unique adult cancers. The dataset was composed of 162 tumor subtypes including multiple rare and uncommon tumors. Comparison of alteration frequencies to The Cancer Genome Atlas identified some differences and suggested an enrichment of treatment-refractory samples in breast and lung cancer cohorts. To illustrate novelty within the dataset, we surveyed the genomic landscape of rare diseases and identified an increased frequency of <i>NOTCH1</i> alterations in adenoid cystic carcinomas compared with previous studies. Analysis of tumor suppressor gene patterns revealed disease specificity for certain genes but broad inactivation of others. We identified multiple potentially druggable, novel and known kinase fusions in diseases beyond those in which they are currently recognized. Analysis of variants of unknown significance identified an enrichment of <i>SMAD4</i> alterations in colon cancer and other rare alterations predicted to have functional impact. Analysis of established, clinically relevant alterations highlighted the spectrum of molecular changes for which testing is currently recommended, as well as opportunities for expansion of indications for use of approved targeted therapies. Overall, this dataset presents a new resource with which to investigate rare alterations and diseases, validate clinical relevance, and identify novel therapeutic targets. <i>Cancer Res; 77(9); 2464-75. ©2017 AACR</i>.
A Biomimetic Approach to Asymmetric Acyl Transfer Catalysis (1999)

Small peptide catalysts containing modified histidine residues are reported that effect enantioselective acylation reactions. The catalysts described include octapeptide β-hairpins (e.g., 11) that exhibit high selectivities (up to krel = 51), tetrapeptide β-turns (e.g., 7) that afford moderate selectivities (up to krel = 28), and several simple derivatives of the modified histidine amino acid that do not exhibit appreciable enantioselectivity. Supporting structural studies (1H NMR and X-ray) are presented which lead to the proposal of a model in which catalyst rigidity and structural complexity contribute to higher degrees of enantioselection. A covalently rigidified octapeptide (20) is prepared through solid-phase Ru-catalyzed ring-closing metathesis; kinetic evaluation of this peptide reveals that substituents along the peptide backbone may be more important than covalent stabilization of a structural motif. Detailed kinetics studies on the most selective peptide catalysts are presented that suggest the reactions are first order in catalyst and substrate. Additional kinetic studies indicate unambiguously that enantioselectivities are due to specific acceleration of reaction for one substrate enantiomer, rather than the deceleration of the reaction for the other. The results are presented in the context of a possible enantiomer-specific hydrogen-bonding interaction in the stereochemistry-determining step for these processes.
Arginase I Production in the Tumor Microenvironment by Mature Myeloid Cells Inhibits T-Cell Receptor Expression and Antigen-Specific T-Cell Responses (2004)

T cells infiltrating tumors have a decreased expression of signal transduction proteins, a diminished ability to proliferate, and a decreased production of cytokines. The mechanisms causing these changes have remained unclear. We demonstrated recently that peritoneal macrophages stimulated with interleukin 4 + interleukin 13 produce arginase I, which decreases the expression of the T-cell receptor CD3zeta chain and impairs T-cell responses. Using a 3LL murine lung carcinoma model we tested whether arginase I was produced in the tumor microenvironment and could decrease CD3zeta expression and impair T-cell function. The results show that a subpopulation of mature tumor-associated myeloid cells express high levels of arginase I, whereas tumor cells and infiltrating lymphocytes do not. Arginase I expression in the tumor was seen on day 7 after tumor injection. Tumor-associated myeloid cells also expressed high levels of cationic amino acid transporter 2B, which allowed them to rapidly incorporate L-Arginine (L-Arg) and deplete extracellular L-Arg in vitro. L-Arg depletion by tumor-associated myeloid cells blocked the re-expression of CD3zeta in stimulated T cells and inhibited antigen-specific proliferation of OT-1 and OT-2 cells. The injection of the arginase inhibitor N-hydroxy-nor-L-Arg blocked growth of s.c. 3LL lung carcinoma in mice. High levels of arginase I were also found in tumor samples of patients with non-small cell carcinoma. Therefore, arginase I production by mature myeloid cells in the tumor microenvironment may be a central mechanism for tumor evasion and may represent a target for new therapies.