gebhart/patrepeval huggingface dataset:
Novel Potent Pharmacological Cyclin-Dependent Kinase Inhibitors (2009)

Progression of the cell cycle is controlled by various activating and inhibiting cellular factors. The subtle balance between these counteracting regulators in normal cells ensures proper cell cycle progression and facilitates cellular responses to a variety of stress stimuli. Key activators include cyclin-dependent kinases (CDKs) and, consequently, loss or inactivation of CDK inhibitors contributes to the escape of cancer cells from cell cycle control and hyperactivation of CDKs occurs in various neurodegenerative disorders. However, these adverse effects may be compensated by pharmacological counterparts. Inhibitors of CDKs representing various classes of compounds with diverse CDK inhibitory patterns have been developed, but inhibitors that have high selectivity and offer highly targeted activity against both cell cycle and transcriptional CDKs are of particular interest. This review focuses on pharmacological CDK inhibitors that have entered clinical trials and some compounds that have been evaluated preclinically. Recent discoveries in cell cycle regulation have provided rationales for clinical applications of CDK inhibitors in both monotherapeutic and combined therapeutic regimens.
Data from Engineered Thio-Trastuzumab-DM1 Conjugate with an Improved Therapeutic Index to Target Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Antibody drug conjugates (ADCs) combine the ideal properties of both antibodies and cytotoxic drugs by targeting potent drugs to the antigen-expressing tumor cells, thereby enhancing their antitumor activity. Successful ADC development for a given target antigen depends on optimization of antibody selection, linker stability, cytotoxic drug potency, and mode of linker-drug conjugation to the antibody. Here, we systematically examined the &lt;i&gt;in vitro&lt;/i&gt; potency as well as &lt;i&gt;in vivo&lt;/i&gt; preclinical efficacy and safety profiles of a heterogeneous preparation of conventional trastuzumab-mcc-DM1 (TMAb-mcc-DM1) ADC with that of a homogeneous engineered thio-trastuzumab-mpeo-DM1 (thioTMAb-mpeo-DM1) conjugate.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design and Results:&lt;/b&gt; To generate thioTMAb-mpeo-DM1, one drug maytansinoid 1 (DM1) molecule was conjugated to an engineered cysteine residue at Ala114 (Kabat numbering) on each trastuzumab-heavy chain, resulting in two DM1 molecules per antibody. ThioTMAb-mpeo-DM1 retained similar &lt;i&gt;in vitro&lt;/i&gt; anti–cell proliferation activity and human epidermal growth factor receptor 2 (HER2) binding properties to that of the conventional ADC. Furthermore, it showed improved efficacy over the conventional ADC at DM1-equivalent doses (μg/m&lt;sup&gt;2&lt;/sup&gt;) and retained efficacy at equivalent antibody doses (mg/kg). An improved safety profile of &gt;2-fold was observed in a short-term target-independent rat safety study. In cynomolgus monkey safety studies, thioTMAb-mpeo-DM1 was tolerated at higher antibody doses (up to 48 mg/kg or 6,000 μg DM1/m&lt;sup&gt;2&lt;/sup&gt;) compared with the conventional ADC that had dose-limiting toxicity at 30 mg/kg (6,000 μg DM1/m&lt;sup&gt;2&lt;/sup&gt;).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; The engineered thioTMAb-mpeo-DM1 with broadened therapeutic index represents a promising antibody drug conjugate for future clinical development of HER2-positive targeted breast cancer therapies. Clin Cancer Res; 16(19); 4769–78. ©2010 AACR.&lt;/p&gt;&lt;/div&gt;
CAMEL Phase 2 (2006)

This chapter contains sections titled: Introduction Architecture Feature Description Subscription Data Basic Call State Model CAMEL Phase 2 Relationship Interaction with GSM Supplementary Services
ChemInform Abstract: Stereocontrolled Syntheses of Fluorinated Carbohydrates (2000)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
10-Watt, single-mode, single-frequency, 1.03 &#x03BC;m Yb<sup>3+</sup>-doped phosphate fiber amplifier (2008)

We describe the first 10-W single-mode, single-frequency Yb <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3+</sup> -doped phosphate fiber amplifier. The fiber is doped with 12 wt% Yb <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> O <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> and only 47.5-cm long. A 25-W phosphate fiber laser with 52.7% slope efficiency is also reported.
Ambulante Diagnostik und Therapie der Gonarthrose (2000)

Effective treatment of knee osteoarthritis must be based on available recommendations and guidelines.
Persistent One-Dimensional Face-to-Face π-Stacks within Organic Cocrystals (2006)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTPersistent One-Dimensional Face-to-Face π-Stacks within Organic CocrystalsAnatoliy N. Sokolov, Tomislav Friščić, Steven Blais, John A. Ripmeester, and Leonard R. MacGillivrayView Author Information Department of Chemistry, University of Iowa, Iowa City, Iowa 52242-1294, and Steacie Institute for Molecular Science, National Research Council of Canada, Ottawa, Ontario, Canada K1A 0R6 Cite this: Crystal Growth & Design 2006, 6, 11, 2427–2428Publication Date (Web):August 12, 2006Publication History Received31 July 2006Published online12 August 2006Published inissue 1 November 2006https://pubs.acs.org/doi/10.1021/cg0605133https://doi.org/10.1021/cg0605133rapid-communicationACS PublicationsCopyright © 2006 American Chemical SocietyRequest reuse permissionsArticle Views653Altmetric-Citations47LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Aromatic compounds,Bipyridine,Layers,Noncovalent interactions,Supramolecular structures and assemblies Get e-Alerts
Osmoregulation Requires Brain Expression of the Renal Na-K-2Cl Cotransporter NKCC2 (2015)

The Na-K-2Cl cotransporter 2 (NKCC2) was thought to be kidney specific. Here we show expression in the brain hypothalamo-neurohypophyseal system (HNS), wherein upregulation follows osmotic stress. The HNS controls osmotic stability through the synthesis and release of the neuropeptide hormone, arginine vasopressin (AVP). AVP travels through the bloodstream to the kidney, where it promotes water conservation. Knockdown of HNS NKCC2 elicited profound effects on fluid balance following ingestion of a high-salt solution-rats produced significantly more urine, concomitant with increases in fluid intake and plasma osmolality. Since NKCC2 is the molecular target of the loop diuretics bumetanide and furosemide, we asked about their effects on HNS function following disturbed water balance. Dehydration-evoked GABA-mediated excitation of AVP neurons was reversed by bumetanide, and furosemide blocked AVP release, both in vivo and in hypothalamic explants. Thus, NKCC2-dependent brain mechanisms that regulate osmotic stability are disrupted by loop diuretics in rats.
Substitution of the Side-Chain-Constrained Amino Acids β-Methyl-2‘,6‘-Dimethyl-4‘-Methoxytyrosine in Position 2 of a Bicyclic Oxytocin Analogue Provides Unique Insights into the Bioactive Topography of Oxytocin Antagonists (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTSubstitution of the Side-Chain-Constrained Amino Acids β-Methyl-2',6'-Dimethyl-4'-Methoxytyrosine in Position 2 of a Bicyclic Oxytocin Analogue Provides Unique Insights into the Bioactive Topography of Oxytocin AntagonistsSubo Liao, Mark D. Shenderovich, Zhigang Zhang, Lenka Maletinska, Jirina Slaninova, and Victor J. HrubyView Author Information Department of Chemistry, the University of Arizona Tucson, Arizona 85721 Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences, Prague, Czech Republic Cite this: J. Am. Chem. Soc. 1998, 120, 29, 7393–7394Publication Date (Web):July 11, 1998Publication History Received16 March 1998Published online11 July 1998Published inissue 1 July 1998https://pubs.acs.org/doi/10.1021/ja980848bhttps://doi.org/10.1021/ja980848brapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views136Altmetric-Citations22LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Antagonists,Conformation,Monomers,Peptides and proteins,Receptors Get e-Alerts
Optimal nuclear magnetic resonance excitation schemes for the central transition of a spin 3/2 in the presence of residual quadrupolar coupling (2008)

Optimal control theory is applied for enhancing the intensity of the central peak of a spin 3/2 signal in the presence of a residual quadrupolar coupling. While a maximum enhancement is always possible in the regime omega(rf) << omega(Q) via the use of modulated and shaped pulses, the intermediate rf-power regime omega(rf)-omega(Q) does not admit simple solutions based on intuition. In this work we present optimized shaped pulses that have been derived using an optimization algorithm based on optimal control and test these with (23)Na NMR in this regime. In addition to enhancing the intensity of the central transition signal, the satellite peaks can be effectively suppressed, which is a useful feature for the implementation in (23)Na imaging sequences.
Prolonged Duration Local Anesthesia Using Liposomal Bupivacaine Combined With Liposomal Dexamethasone and Dexmedetomidine (2017)

Codelivery of Lipo-DexP and Lipo-DMED enhanced the efficacy of Lipo-Bup. This benefit was also seen with codelivery of both adjuvant molecules in the unencapsulated state, but with marked systemic toxicity.
ChemInform Abstract: Alkene Chemoselectivity in Ring‐Closing Metathesis: A Formal Synthesis of (‐)‐Periplanone‐B. (1999)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
General purpose logic gate using ballistic nanotransistors (2011)

This paper presents a new type of logic gate and associated circuit concepts for a recently proposed device, the ballistic deflection transistor (BDT). The BDT is a planar structure based on InGaAs/InAlAs etched into a two-dimensional electron gas (2DEG), and exhibits ballistic transport behavior at room temperature. We propose a general purpose gate (GPG) configuration and present measured results from a fabricated GPG using BDTs, as well as a simulation model for examining other GPG configurations. Using this scheme, any 2-input logic function and its compliment can be realized by selectively connecting the four GPG output terminals.
ChemInform Abstract: Oxidations by Copper Metalloenzymes and Some Biomimetic Approaches (1998)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Structure of the Nitrogen-Centered Radical Formed during Inactivation ofE. coliRibonucleotide Reductase by 2‘-Azido-2‘-deoxyuridine-5‘-diphosphate:  Trapping of the 3‘-Ketonucleotide (2005)

Ribonucleotide reductases (RNRs) catalyze the conversion of nucleotides to deoxynucleotides providing the monomeric precursors required for DNA replication and repair. The class I RNRs are composed of two homodimeric subunits: R1 and R2. R1 has the active site where nucleotide reduction occurs, and R2 contains the diiron tyrosyl radical (Y*) cofactor essential for radical initiation on R1. Mechanism-based inhibitors, such as 2'-azido-2'-deoxyuridine-5'-diphosphate (N(3)UDP), have provided much insight into the reduction mechanism. N(3)UDP is a stoichiometric inactivator that, upon interaction with RNR, results in loss of the Y* in R2 and formation of a nitrogen-centered radical (N*) covalently attached to C225 (R-S-N*-X) in the active site of R1. N(2) is lost prior to N* formation, and after its formation, stoichiometric amounts of 2-methylene-3-furanone, pyrophosphate, and uracil are also generated. On the basis of the hyperfine interactions associated with N*, it was proposed that N* is also covalently attached to the nucleotide through either the oxygen of the 3'-OH (R-S-N*-O-R') or the 3'-C (R-S-N*-C-OH). To distinguish between the proposed structures, the inactivation was carried out with 3'-[(17)O]-N(3)UDP and N* was examined by 9 and 140 GHz EPR spectroscopy. Broadening of the N* signal was detected and the spectrum simulated to obtain the [(17)O] hyperfine tensor. DFT calculations were employed to determine which structures are in best agreement with the simulated hyperfine tensor and our previous ESEEM data. The results are most consistent with the R-S-N*-C-OH structure and provide evidence for the trapping of a 3'-ketonucleotide in the reduction process.
Distinct fusion properties of synaptotagmin-1 and synaptotagmin-7 bearing dense core granules (2014)

Adrenal chromaffin cells release hormones and neuropeptides that are essential for physiological homeostasis. During this process, secretory granules fuse with the plasma membrane and deliver their cargo to the extracellular space. It was once believed that fusion was the final regulated step in exocytosis, resulting in uniform and total release of granule cargo. Recent evidence argues for nonuniform outcomes after fusion, in which cargo is released with variable kinetics and selectivity. The goal of this study was to identify factors that contribute to the different outcomes, with a focus on the Ca(2+)-sensing synaptotagmin (Syt) proteins. Two Syt isoforms are expressed in chromaffin cells: Syt-1 and Syt-7. We find that overexpressed and endogenous Syt isoforms are usually sorted to separate secretory granules and are differentially activated by depolarizing stimuli. In addition, overexpressed Syt-1 and Syt-7 impose distinct effects on fusion pore expansion and granule cargo release. Syt-7 pores usually fail to expand (or reseal), slowing the dispersal of lumenal cargo proteins and granule membrane proteins. On the other hand, Syt-1 diffuses from fusion sites and promotes the release of lumenal cargo proteins. These findings suggest one way in which chromaffin cells may regulate cargo release is via differential activation of synaptotagmin isoforms.
Capacitance–Voltage and Current–Voltage Measurements of Nitride Light-Emitting Diodes (2007)

Capacitance-voltage (C-V ) and current-voltage (I-V) characteristics of nitride light-emitting diodes were measured. The apparent carrier distributions obtained from the C-V curves yielded much information about the samples, including information about the presence of acceptor-like defects in the active layer and the problem of electron overflow. The inconsistency between the experimental and simulated I-V curves also supported the presence of the defects. After compensating the acceptor-like defects by Si dopants and adjusting the overlap between the depletion region and the light-emitting structure, device performance was improved.
Demonstration of lithography patterns using reflective e-beam direct write (2011)

Traditionally, e-beam direct write lithography has been too slow for most lithography applications. E-beam direct write lithography has been used for mask writing rather than wafer processing since the maximum blur requirements limit column beam current - which drives e-beam throughput. To print small features and a fine pitch with an e-beam tool requires a sacrifice in processing time unless one significantly increases the total number of beams on a single writing tool. Because of the uncertainty with regards to the optical lithography roadmap beyond the 22 nm technology node, the semiconductor equipment industry is in the process of designing and testing e-beam lithography tools with the potential for high volume wafer processing. For this work, we report on the development and current status of a new maskless, direct write e-beam lithography tool which has the potential for high volume lithography at and below the 22 nm technology node. A Reflective Electron Beam Lithography (REBL) tool is being developed for high throughput electron beam direct write maskless lithography. The system is targeting critical patterning steps at the 22 nm node and beyond at a capital cost equivalent to conventional lithography. Reflective Electron Beam Lithography incorporates a number of novel technologies to generate and expose lithographic patterns with a throughput and footprint comparable to current 193 nm immersion lithography systems. A patented, reflective electron optic or Digital Pattern Generator (DPG) enables the unique approach. The Digital Pattern Generator is a CMOS ASIC chip with an array of small, independently controllable lens elements (lenslets), which act as an array of electron mirrors. In this way, the REBL system is capable of generating the pattern to be written using massively parallel exposure by ~1 million beams at extremely high data rates (~ 1Tbps). A rotary stage concept using a rotating platen carrying multiple wafers optimizes the writing strategy of the DPG to achieve the capability of high throughput for sparse pattern wafer levels. The lens elements on the DPG are fabricated at IMEC (Leuven, Belgium) under IMEC's CMORE program. The CMOS fabricated DPG contains ~ 1,000,000 lens elements, allowing for 1,000,000 individually controllable beamlets. A single lens element consists of 5 electrodes, each of which can be set at controlled voltage levels to either absorb or reflect the electron beam. A system using a linear movable stage and the DPG integrated into the electron optics module was used to expose patterns on device representative wafers. Results of these exposure tests are discussed.
<title>Finite differencing of periodic structures</title> (1997)

Finite difference time domain is a powerful numerical method. We review our modeling and design of optical gratings and 2D photonic crystals, aided by the recently developed quartic perfectly matched layer boundary condition. For optical gratings with a quarter wave phase shift, we show that light can be confined in an air bridge micro-cavity. Such devices exhibit sharp transmission resonances in the stop bands. Photonic crystals also demonstrate strong localization of light so waveguides of air can be formed. In addition, even when the bending radius is zero, the transmission exceeds 0.95 percent.
Role of CXCR2 in cigarette smoke-induced lung inflammation (2005)

It has been hypothesized that the destruction of lung tissue observed in smokers with chronic obstructive pulmonary disease and emphysema is mediated by neutrophils recruited to the lungs by smoke exposure. This study investigated the role of the chemokine receptor CXCR2 in mediating neutrophilic inflammation in the lungs of mice acutely exposed to cigarette smoke. Exposure to dilute mainstream cigarette smoke for 1 h, twice per day for 3 days, induced acute inflammation in the lungs of C57BL/6 mice, with increased neutrophils and the neutrophil chemotactic CXC chemokines macrophage inflammatory protein (MIP)-2 and KC. Treatment with SCH-N, an orally active small molecule inhibitor of CXCR2, reduced the influx of neutrophils into the bronchoalveolar lavage (BAL) fluid. Histological changes were seen, with drug treatment reducing perivascular inflammation and the number of tissue neutrophils. beta-Glucuronidase activity was reduced in the BAL fluid of mice treated with SCH-N, indicating that the reduction in neutrophils was associated with a reduction in tissue damaging enzymes. Interestingly, whereas MIP-2 and KC were significantly elevated in the BAL fluid of smoke exposed mice, they were further elevated in mice exposed to smoke and treated with drug. The increase in MIP-2 and KC with drug treatment may be due to the decrease in lung neutrophils that either are not present to bind these chemokines or fail to provide a feedback signal to other cells producing these chemokines. Overall, these results demonstrate that inhibiting CXCR2 reduces neutrophilic inflammation and associated lung tissue damage due to acute cigarette smoke exposure.
ChemInform Abstract: Potential Antiviral Agents. Stereospecific Synthesis of Purines and Pyrimidines Substituted with Chiral Acyclic Chains by Sugar‐Ring Opening of α‐L‐Arabinopyranosyl Nucleosides. (1992)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Dispersion-tolerant 10-gb/s duobinary system employing heterodyne detection and MLSE (2006)

We experimentally demonstrate a 10.7-Gb/s duobinary transmission system operating over a chromatic-dispersion range of /spl sim/12 000 ps/nm. Heterodyne detection and maximum-likelihood sequence estimation are employed to achieve this result.