gebhart/patrepeval huggingface dataset:
Discovery of the Hemifumarate and (α-l-Alanyloxy)methyl Ether as Prodrugs of an Antirheumatic Oxindole:  Prodrugs for the Enolic OH Group (1996)

Ether, ester, and carbonate derivatives of the antirheumatic oxindole 1 were prepared and screened as potential prodrugs of 1. This effort led to the discovery of the (α-l-alanyloxy)methyl ether and hemifumarate derivatives of 1 which deliver the drug efficiently into the circulation of test animals, are stable in the solid state, and possess good stability in solution at low pH as required to ensure gastric stability. Success in achieving acceptable bioavailabilties of 1 across species (rats, dogs, and monkeys) followed the inclusion of ionizable functionality within the promoiety to compensate for masking the polar enolic OH group of the free drug. However, the introduction of ionizable functionality was often associated with decreased stability, as demonstrated by the hemisuccinate, hemiadipate, hemisuberate, and α-amino ester derivatives of 1 which could not be isolated. A clear exception was the hemifumarate derivative of 1 which was not only isolable but actually more stable at neutral pH than the nonionizable ester analogues. The solution and solid state stability of the hemifumarate, together with its activity as a prodrug of 1, suggests that hemifumarate be considered as an alternative to hemisuccinate as a prodrug derivative for alcohols, particularly in situations where solution state stability is an issue.
Conformational variants of class II MHC/peptide complexes induced by N- and C-terminal extensions of minimal peptide epitopes (1999)

Class II MHC molecules are known to exist in conformational variants. "Floppy" and "compact" forms of murine MHC molecules, for example, are discriminated by their migration behavior on SDS/PAGE and represent empty and ligand-loaded forms. Here we show that formation of distinctly faster-migrating ligand complexes (F-forms) rather than the normal compact (C-) forms of HLA-DR1 or -DR4 results from extensions of minimal peptide epitopes (such as HA306-318 or IC106-120) by approximately 10 amino acids at either the N or the C terminus. Two similar but distinct F-forms (FI and FII) were detected, depending on the site of the extension. Both F-forms were characterized by increased surface hydrophobicity and reduced SDS-stability. Native gel separations and size exclusion chromatography indicated that the F-forms had increased hydrodynamic radii compared with the C-form and an apparent size similar to that of empty MHC molecules. The regions on the ligand overhangs responsible for the effect began at a distance of approximately 5 amino acids on either side of the epitopes, comprised 4-8 amino acids (i.e., a total overhang of 9-14), and did not have a particular sequence preference. The possible functional significance of these forms is discussed.
Inflammasome activation and IL-1β target IL-1α for secretion as opposed to surface expression (2011)

Interleukin-1α (IL-1α) and -β both bind to the same IL-1 receptor (IL-1R) and are potent proinflammatory cytokines. Production of proinflammatory (pro)-IL-1α and pro-IL-1β is induced by Toll-like receptor (TLR)-mediated NF-κB activation. Additional stimulus involving activation of the inflammasome and caspase-1 is required for proteolytic cleavage and secretion of mature IL-1β. The regulation of IL-1α maturation and secretion, however, remains elusive. IL-1α exists as a cell surface-associated form and as a mature secreted form. Here we show that both forms of IL-1α, the surface and secreted form, are differentially regulated. Surface IL-1α requires NF-κB activation only, whereas secretion of mature IL-1α requires additional activation of the inflammasome and caspase-1. Surprisingly, secretion of IL-1α also required the presence of IL-1β, as demonstrated in IL-1β-deficient mice. We further demonstrate that IL-1β directly binds IL-1α, thus identifying IL-1β as a shuttle for another proinflammatory cytokine. These results have direct impact on selective treatment modalities of inflammatory diseases.
Inhibition of Breast Cancer Cell Growth In vitro and In vivo : Effect of Restoration of Wwox Expression (2007)

The results confirm that overexpression of exogenous Wwox inhibits breast cancer cell growth in vitro and in vivo and, perhaps more importantly, shows that restoration of endogenous Wwox expression, and likely other proteins, by treatment with a de novo methyltransferase inhibitor, also inhibits breast cancer cell growth and reverses breast cancer xenograft growth.
Identification of Epidermal Growth Factor Receptor and c-erbB2 Pathway Inhibitors by Correlation With Gene Expression Patterns (1997)

Novel EGF receptor or c-erbB2 pathway inhibitors can be identified in the NCI drug screen by correlation of cytotoxicity patterns with EGF receptor or c-erbB2 mRNA expression levels.
Acute and Long-Term Effects of Full-Power Electroporation Ablation Directly on the Porcine Esophagus (2017)

Esophageal architecture remains unaffected 2 months after irreversible electroporation, purposely targeting the adventitia. Irreversible electroporation seems to be a safe modality for catheter ablation near the esophagus.
Expression Profiles Provide Insights into Early Malignant Potential and Skeletal Abnormalities in Multiple Endocrine Neoplasia Type 2B Syndrome Tumors (2004)

Identifying the molecular basis for genotype-phenotype correlations in human diseases has direct implications for understanding the disease process and hence for the identification of potential therapeutic targets. To this end, we performed microarray expression analysis on benign (pheochromocytomas) and malignant (medullary thyroid carcinomas, MTCs) tumors from patients with multiple endocrine neoplasia (MEN) type 2A or 2B, related syndromes that result from distinctive mutations in the RET receptor tyrosine kinase. Comparisons of MEN 2B and MEN 2A MTCs revealed that genes involved in the process of epithelial to mesenchymal transition, many associated with the tumor growth factor beta pathway, were up-regulated in MEN 2B MTCs. This MEN 2B MTC profile may explain the early onset of malignancy in MEN 2B compared with MEN 2A patients. Furthermore, chondromodulin-1, a known regulator of cartilage and bone growth, was expressed at high levels specifically in MEN 2B MTCs. Chondromodulin-1 mRNA and protein expression was localized to the malignant C cells, and its high expression was directly associated with the presence of skeletal abnormalities in MEN 2B patients. These findings provide molecular evidence that associate the previously unexplained skeletal abnormalities and early malignancy in MEN 2B compared with MEN 2A syndrome.
Identification of Cyclic ADP-ribose-dependent Mechanisms in Pancreatic Muscarinic Ca2+ Signaling Using CD38 Knockout Mice (2001)

We showed that muscarinic acetylcholine (ACh)-stimulation increased the cellular content of cADPR in the pancreatic acinar cells from normal mice but not in those from CD38 knockout mice. By monitoring ACh-evoked increases in the cytosolic Ca(2+) concentration ([Ca(2+)](i)) using fura-2 microfluorimetry, we distinguished and characterized the Ca(2+) release mechanisms responsive to cADPR. The Ca(2+) response from the cells of the knockout mice (KO cells) lacked two components of the muscarinic Ca(2+) release present in wild mice. The first component inducible by the low concentration of ACh contributed to regenerative Ca(2+) spikes. This component was abolished by ryanodine treatment in the normal cells and was severely impaired in KO cells, indicating that the low ACh-induced regenerative spike responses were caused by cADPR-dependent Ca(2+) release from a pool regulated by a class of ryanodine receptors. The second component inducible by the high concentration of ACh was involved in the phasic Ca(2+) response, and it was not abolished by ryanodine treatment. Overall, we conclude that muscarinic Ca(2+) signaling in pancreatic acinar cells involves a CD38-dependent pathway responsible for two cADPR-dependent Ca(2+) release mechanisms in which the one sensitive to ryanodine plays a crucial role for the generation of repetitive Ca(2+) spikes.
High Density n-Si/n-TiO2Core/Shell Nanowire Arrays with Enhanced Photoactivity (2008)

There are currently great needs to develop low-cost inorganic materials that can efficiently perform solar water splitting as photoelectrolysis of water into hydrogen and oxygen has significant potential to provide clean energy. We investigate the Si/TiO(2) nanowire heterostructures to determine their potential for the photooxidation of water. We observed that highly dense Si/TiO(2) core/shell nanowire arrays enhanced the photocurrent by 2.5 times compared to planar Si/TiO(2) structure due to their low reflectance and high surface area. We also showed that n-Si/n-TiO(2) nanowire arrays exhibited a larger photocurrent and open circuit voltage than p-Si/n-TiO(2) nanowires due to a barrier at the heterojunction.
Approved Drugs Containing Thiols as Inhibitors of Metallo-β-lactamases: Strategy To Combat Multidrug-Resistant Bacteria (2015)

Resistance to β-lactam antibiotics can be mediated by metallo-β-lactamase enzymes (MBLs). An MBL inhibitor could restore the effectiveness of β-lactams. We report on the evaluation of approved thiol-containing drugs as inhibitors of NDM-1, VIM-1, and IMP-7. Drugs were assessed by a novel assay using a purchasable fluorescent substrate and thermal shift. Best compounds were tested in antimicrobial susceptibility assay. Using these orthogonal screening methods, we identified drugs that restored the activity of imipenem.
The Epidermal Growth Factor Receptor Responsive miR-125a Represses Mesenchymal Morphology in Ovarian Cancer Cells (2009)

The epithelial-to-mesenchymal transition (EMT) that occurs during embryonic development is recapitulated during tumor metastasis. Important regulators of this process include growth factors, transcription factors, and adhesion molecules. New evidence suggests that microRNA (miRNA) activity contributes to metastatic progression and EMT; however, the mechanisms leading to altered miRNA expression during cancer progression remain poorly understood. Importantly, overexpression of the epidermal growth factor receptor (EGFR) in ovarian cancer correlates with poor disease outcome and induces EMT in ovarian cancer cells. We report that EGFR signaling leads to transcriptional repression of the miRNA miR-125a through the ETS family transcription factor PEA3. Overexpression of miR-125a induces conversion of highly invasive ovarian cancer cells from a mesenchymal to an epithelial morphology, suggesting miR-125a is a negative regulator of EMT. We identify AT-rich interactive domain 3B (ARID3B) as a target of miR-125a and demonstrate that ARID3B is overexpressed in human ovarian cancer. Repression of miR-125a through growth factor signaling represents a novel mechanism for regulating ovarian cancer invasive behavior.
Antibiofouling Polymer-Coated Superparamagnetic Iron Oxide Nanoparticles as Potential Magnetic Resonance Contrast Agents for in Vivo Cancer Imaging (2006)

We report the fabrication and characterization of antifouling polymer-coated magnetic nanoparticles as nanoprobes for magnetic resonance (MR) contrast agents. Magnetite superparamagnetic iron oxide nanoparticles (SPION) were coated with the protein- or cell-resistant polymer, poly(TMSMA-r-PEGMA), to generate stable, protein-resistant MR probes. Coated magnetic nanoparticles synthesized using two different preparation methods (in situ and stepwise, respectively) were both well dispersed in PBS buffer at a variety of pH conditions (pH 1-10). In addition, dynamic light scattering data revealed that their sizes were not altered even after 24 h of incubation in 10% serum containing cell culture medium, indicative of a lack of protein adsorption on their surfaces. When the antibiofouling polymer-coated SPION were incubated with macrophage cells, uptake was significantly lower in comparison to that of the popular contrast agent, Feridex I.V., suggesting that the polymer-coated SPION can be long-circulated in plasma by escaping from uptake by the reticular endothelial system (RES) such as macrophages. Indeed, when the coated SPION were administered to tumor xenograft mice by intravenous injection, the tumor could be detected in T2-weighted MR images within 1 h as a result of the accumulation of the nanomagnets within the tumor site. Although the poly(TMSMA-r-PEGMA)-coated SPION do not have any targeting ligands on their surface, they are potentially useful for cancer diagnosis in vivo.
Chitosan: Properties, preparations and application to microparticulate systems (1997)

Chitosan, a hydrophilic biopolymer, is obtained industrially by hydrolysing the aminoacetyl groups of chitin. It is a natural, non-toxic, biodegradable polysaccharide available as solution, flake, fine powder, bead and fibre. The sources, biochemical aspects, structure and chemical modification, physico-chemical and functional properties, and applications of chitosan have been investigated extensively in the literature. In this paper, the attractive properties and broad applications of chitosan-based microparticles, their versatile properties, different preparation methods, and pharmaceutical and biopharmaceutical applications are reviewed.
Robotically assisted intraoperative ultrasound with application to ablative therapy of liver cancer (2003)

Management of primary and metastatic tumors of the liver remains a significant challenge to the health care community worldwide. There has been an increasing interest in minimally invasive ablative approaches that typically require precise placement of the tissue ablator within the volumetric center of the tumor, in order to achieve adequate destruction. Standard clinical technique involves manual free hand ultrasonography (US) in conjunction with free hand positioning of the tissue ablator. Several investigational systems exist that simultaneously track a transcutaneous ultrasound (TCUS) probe and an ablator and provide visual overlay of the two on a computer screen, and some of those systems also register the TCUS images with pre-operative CT and/or MRI. Unfortunately, existing TCUS systems suffer from many limitations. TCUS fails to identify nearly half of all treatable liver lesions, whereas intraoperative or laparoscopic US provides excellent tissue differentiation. Furthermore, freehand manipulation of the US probe critically lacks the level of control, accuracy, and stability required for guiding liver ablation. Volumetric reconstruction from sparse and irregular 2D image data is suboptimal. Variable pressure from the sonographer's hand also causes anatomic deformation. Finally, maintaining optimal scanning position with respect to the target lesion is critical, but virtually impossible to achieve with freehand guidance. In response to these limitations, we propose the use of a fully encoded dexterous robotic arm to manipulate the US probe during surgery.
Coiled Tubing and Vessel Motions for Riserless Coiled Tubing Systems (2004)

Abstract Special care must be taken tomaintain the integrity of the coiled tubing when performing subsea well intervention from a lightvessel without the use of a riser. In these cases the coiled tubingwill act as a riser with respect to withstanding the external loads from waves, current andvessel motions. To avoid local buckling of the coiled tubing as it enters the subsea lubricator it is important to keep the vessel positioned such that the bending of the coiled tubingis kept as small as possible. This paper will outline a method for estimating the optimal set pointfor the vessel positionduring riser less coiled tubing operations. The method is based on a combination of measurements and analytical methods for description of the structural behaviour of coiled tubing and the subsea stack. The analytical method developed is compared to simulations using commercial riser analyses software.
The Dissociation Constant of Hypobromous Acid (1950)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Dissociation Constant of Hypobromous AcidLadislas Farkas and Menachem LewinCite this: J. Am. Chem. Soc. 1950, 72, 12, 5766–5767Publication Date (Print):December 1, 1950Publication History Published online1 May 2002Published inissue 1 December 1950https://pubs.acs.org/doi/10.1021/ja01168a522https://doi.org/10.1021/ja01168a522research-articleACS PublicationsRequest reuse permissionsArticle Views107Altmetric-Citations11LEARN 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
The chemistry of thought: neurotransmitters in the brain. (2004)

Inside a neuron, clusters of molecules shuttle toward a cell membrane tightly packaged within vesicles. The vesicles fuse with the cell membrane, expelling the molecules into the extracellular space. As the molecules reach their targets, electrical currents fly, and the brain hums along. Without these chemical and electrical transformations, we would not remember the smell of coffee, recognize our child’s face, or appreciate a delicate melody. The intricate signals and cascades induce thought, behavior, and memory. Analytical chemists are in on the act of understanding the compounds that drive human contemplation, including the reading of this sentence; what will be remembered after reading it; and even what emotions it will evoke. The goal of this article is to provide a general overview of the methods used to characterize neurotransmission in the brain, update recent specialized articles on brain chemistry, and complement articles about imaging MS and new electroanalytical methods that examine the role of dopamine in addiction (1‐3). The brain is composed of nervous system cells, or neurons, which communicate with one another through ports called synapses. Cell‐cell communication, or neurotransmission, is embodied through electrical impulses or chemical messengers. Although electrophysiological signaling is an important facet of brain function, we will focus on chemical signaling in the brain and the analytical methods used to study it.
Real-Time Continuous Pose Recovery of Human Hands Using Convolutional Networks (2014)

We present a novel method for real-time continuous pose recovery of markerless complex articulable objects from a single depth image. Our method consists of the following stages: a randomized decision forest classifier for image segmentation, a robust method for labeled dataset generation, a convolutional network for dense feature extraction, and finally an inverse kinematics stage for stable real-time pose recovery. As one possible application of this pipeline, we show state-of-the-art results for real-time puppeteering of a skinned hand-model.
Attenuation of rodent neuropathic pain by an orally active peptide, RAP-103, which potently blocks CCR2- and CCR5-mediated monocyte chemotaxis and inflammation (2011)

Chemokine signaling is important in neuropathic pain, with microglial cells expressing CCR2 playing a well-established key role. DAPTA, a HIV gp120-derived CCR5 entry inhibitor, has been shown to inhibit CCR5-mediated monocyte migration and to attenuate neuroinflammation. We report here that as a stabilized analog of DAPTA, the short peptide RAP-103 exhibits potent antagonism for both CCR2 (half maximal inhibitory concentration [IC50] 4.2 pM) and CCR5 (IC50 0.18 pM) in monocyte chemotaxis. Oral administration of RAP-103 (0.05-1 mg/kg) for 7 days fully prevents mechanical allodynia and inhibits the development of thermal hyperalgesia after partial ligation of the sciatic nerve in rats. Administered from days 8 to 12, RAP-103 (0.2-1 mg/kg) reverses already established hypersensitivity. RAP-103 relieves behavioral hypersensitivity, probably through either or both CCR2 and CCR5 blockade, because by using genetically deficient animals, we demonstrated that in addition to CCR2, CCR5 is also required for the development of neuropathic pain. Moreover, RAP-103 is able to reduce spinal microglial activation and monocyte infiltration, and to inhibit inflammatory responses evoked by peripheral nerve injury that cause chronic pain. Our findings suggest that targeting CCR2/CCR5 should provide greater efficacy than targeting CCR2 or CCR5 alone, and that dual CCR2/CCR5 antagonist RAP-103 has the potential for broad clinical use in neuropathic pain treatment.
Characterization of the S-phase-specific transcription regulatory elements in a DNA replication-independent testis-specific H2B (TH2B) histone gene. (1990)

The testis-specific H2B histone (TH2B) gene is expressed in pachytene spermatocytes of meiotic prophase I during rat spermatogenesis. The TH2B RNA and histones are not synthesized in any other tissues, and the synthesis is independent of DNA replication. However, the cloned TH2B gene has two DNA sequence elements which stimulate transcription of the cloned gene in an S-phase-dependent manner when introduced into somatic cells. The factors interacting with the two elements, CCAAT at -127 base pairs and octamer ATTTGCAT at -93 base pairs, interact with each other to bring about a maximum stimulation of S-phase-dependent transcription. The level of CCAAT and octamer-binding proteins is unchanged during the cell cycle, and the S-phase-dependent transcription of TH2B and endogenous mouse H2B genes does not require synthesis of new proteins during the S phase. Cell cycle-specific posttranslational modification of regulatory proteins may be responsible for the S-phase-dependent transcription of H2B histone genes. The biological significance of the presence of S-phase-specific transcription regulatory elements in the DNA replication-independent and tissue-specific TH2B gene is not known.
Copper-Catalyzed Cyclization of Iodo-tryptophans: A Straightforward Synthesis of Pyrroloindoles (2008)

Pyrroloindoles are a key structural motif found in a wide number of biologically active alkaloids. Intramolecular copper-catalyzed coupling of readily accessible 2-iodo-tryptophan derivatives occurs in excellent yield, affording a wide range of polysubstituted, enantioenriched tetrahydropyrrolo[2,3- b]indoles. Diketopiperazines are also suitable substrates for this cyclization reaction, which affords a straightforward entry to tetra- to hepta-polycyclic systems.