gebhart/patrepeval huggingface dataset:
Improvement in the symptoms of smooth muscle dystonia during eculizumab therapy in paroxysmal nocturnal hemoglobinuria. (2005)

Aberrant smooth muscle dystonia during hemolytic episodes in paroxysmal nocturnal hemoglobinuria (PNH) is implicated in the symptoms of abdominal pain, dysphagia and erectile dysfunction. Here we report two PNH patients treated with the complement inhibitor, eculizumab. Complement inhibition has been sustained for over 2 years and results in resolution of intravascular hemolysis and amelioration of symptoms associated with smooth muscle contractions.
Fidelity of phi29 DNA polymerase. Comparison between protein-primed initiation (1992)

Peer reviewed
Applications of Synthetic Peptides (1985)

Abstract Peptide chemists are increasingly concerned with the synthesis of polypeptides of biological and medical interest. This article describes several important applications of synthetic peptides in biochemistry, molecular biology, immunology, and medicine. Synthetic peptides may be useful in structure‐function studies of polypeptides, as peptide hormones and hormone analogues, in the preparation of cross‐reacting antibodies, and in the design of novel enzymes. Peptide chemists can actively contribute to progress in these fields if they are aware of the current problems in the life sciences.
Abstract 4470: Elucidating the role of drug-linker hydrophobicity in the disposition of antibody-drug conjugates (2014)

Abstract The in vitro potency of antibody-drug conjugates (ADCs) is generally proportional to the level of drug loading, with higher drug per antibody levels producing more potent ADCs. However, this intuitive relationship often fails to translate in vivo, presumably because plasma clearance of the ADC also increases with drug loading, resulting in substantially reduced exposure to highly loaded ADCs (Hamblett, KJ et al, Clin. Cancer Res. 2004, 10: 7063-7070). We postulated that this accelerated clearance effect is not purely a function of the number of drugs per antibody, but also of the intrinsic hydrophobicity of each drug-linker. Collectively, drug-linker hydrophobicity and number of drugs per antibody determine the overall hydrophobicity of the ADC. To test this hypothesis, we designed and prepared a series of drug-linkers within the auristatin class that varied in hydrophobicity, and used them to produce a corresponding series of homogeneous 8-loaded ADCs. The pharmacokinetic profiles of these ADCs were determined and found to correlate well with their relative retention times by hydrophobic interaction chromatography. We further postulated that hydrophobicity-driven clearance is likely to be mediated by cells of the mononuclear phagocytic system (MPS). To identify the specific cell populations responsible for accelerated ADC clearance, we performed an immunohistochemistry-based biodistribution study which has provided clear evidence for the cellular sites of hydrophobic ADC clearance which are not operative on native antibodies or hydrophilic ADCs. Using the information gained from these studies, we have successfully prepared a hydrophilic auristatin drug-linker which enables the preparation of ADCs uniformly loaded with 8 drugs per antibody at defined cysteine sites. These ADCs evade clearance by the MPS, maintain native antibody pharmacokinetics, and translate their high in vitro potency into the in vivo setting. Citation Format: Svetlana O. Doronina, Jocelyn R. Setter, Tim D. Bovee, Martha E. Anderson, Mechtild Jonas, Steven Daniho, Heather Kostner, Peter D. Senter, Robert P. Lyon. Elucidating the role of drug-linker hydrophobicity in the disposition of antibody-drug conjugates. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4470. doi:10.1158/1538-7445.AM2014-4470
Prostaglandin E2 induces vascular endothelial growth factor secretion in prostate cancer cells through EP2 receptor‐mediated cAMP pathway (2007)

Prostaglandin E2 (PGE2) has been shown to induce expression of vascular endothelial growth factor (VEGF) and other signaling molecules in several cancers. PGE2 elicits its functions though four G-protein coupled membrane receptors (EP1-4). In this study, we investigated the role of EP receptors in PGE2-induced molecular events in prostate cancer cells. qRT-PCR analysis revealed that PC-3 cells express a substantially higher level of EP2 and moderately higher EP4 than DU145 and LNCaP cells. LNCaP cells had virtually no detectable EP2 mRNA. EP1 and EP3 mRNAs were not detected in these cells. Treatment of prostate cancer cells with PGE2 (1 nM-10 microM) increased both VEGF secretion and cyclic adenosine monophosphate (cAMP) production. Levels of induction in PC-3 cells were greater than in DU145 and LNCaP cells. The selective EP2 agonist CAY10399 also significantly increased VEGF secretion and cAMP production in PC-3 cells, but not in DU145 and LNCaP cells. Moreover, PGE2 and CAY10399 increased mitogen activated protein kinase/extracellular signal regulated kinase (MAPK/Erk) and Akt phosphorylation in PC-3 and DU145 cells, but not in LNCaP cells. However, neither the MAPK/Erk inhibitor U0126 nor the PI3K/Akt inhibitor LY294002 abolished PGE2-induced VEGF secretion in PC-3 cells. We further demonstrated that the adenylate cyclase activator forskolin and the cAMP anologue 8-bromo-cAMP mimicked the effects of PGE2 on VEGF secretion in PC-3 cells. Meanwhile, the adenylate cyclase inhibitor 2'5'-dideoxyadenosine, at concentrations that inhibited PGE2-induced cAMP, significantly blocked PGE2-induced VEGF secretion in PC-3 cells. We conclude that PGE2-induced VEGF secretion in prostate cancer cells is mediated through EP2-, and possibly EP4-, dependent cAMP signaling pathways.
Coupling of Gab1 to C-Met, Grb2, and Shp2 Mediates Biological Responses (2000)

Gab1 is a substrate of the receptor tyrosine kinase c-Met and involved in c-Met-specific branching morphogenesis. It associates directly with c-Met via the c-Met-binding domain, which is not related to known phosphotyrosine-binding domains. In addition, Gab1 is engaged in a constitutive complex with the adaptor protein Grb2. We have now mapped the c-Met and Grb2 interaction sites using reverse yeast two-hybrid technology. The c-Met-binding site is localized to a 13-amino acid region unique to Gab1. Insertion of this site into the Gab1-related protein p97/Gab2 was sufficient to confer c-Met-binding activity. Association with Grb2 was mapped to two sites: a classical SH3-binding site (PXXP) and a novel Grb2 SH3 consensus-binding motif (PX(V/I)(D/N)RXXKP). To detect phosphorylation-dependent interactions of Gab1 with downstream substrates, we developed a modified yeast two-hybrid assay and identified PI(3)K, Shc, Shp2, and CRKL as interaction partners of Gab1. In a trk-met-Gab1-specific branching morphogenesis assay, association of Gab1 with Shp2, but not PI(3)K, CRKL, or Shc was essential to induce a biological response in MDCK cells. Overexpression of a Gab1 mutant deficient in Shp2 interaction could also block HGF/SF-induced activation of the MAPK pathway, suggesting that Shp2 is critical for c-Met/Gab1-specific signaling.
Diffractive properties of highly birefringent volume gratings: investigation (2002)

We have performed a detailed comparison of the predictions of coupled-wave theories of isotropic and anisotropic volume gratings. It is shown that material birefringence can dramatically modify the diffractive properties of volume gratings. The predictions of the coupled-wave theories have also been compared with the diffractive properties of volume gratings fabricated with polymer-dispersed liquid crystals. It is shown that a coupled-wave theory that includes the effects of the birefringence of the liquid crystal must be used to explain the diffraction properties of these highly anisotropic gratings. Information can be obtained about the alignment of the liquid crystal within the composite gratings from comparisons of theory and experiment.
Mode analysis and stabilization of a spatial power combining array with strongly coupled oscillators (1993)

In order to attain stabilized power-combining operation of a strongly coupled active antenna array, a mode analysis for the multimoding array problem is presented, and an effective method for exciting only the in-phase power-combining mode is proposed. In a one-dimensional array of active antennas coupled mutually through microstrip lines, the frequencies and the voltage distributions of the normal modes are obtained. Stable modes of the array are identified using the averaged potential theory. Time evolutions of the mode amplitudes are also calculated. In order for only the desired power-combining mode to oscillate, appropriate resistors are introduced at the midpoints of the coupling lines between the active antennas. An experiment for arrays with up to eight active antennas has been carried using Gunn diodes. It has been confirmed that the introduction of the resistors is effective for stable excitation of the in-phase power-combining mode.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
EEG Recordings Following Intrathecal Iohexol Administration (1990)

Electroencephalogram (EEG) recordings were performed before and after intrathecal administration of iohexal (Omnipaque) in 30 patients who underwent cervical myelography or cisternography. Tracings were recorded before, several hours after, and 24 h after iohexol administration. No abnormalities were recorded. It can be concluded that iohexol is a safe contrast medium, having less encephalopathic effects than more commonly used substances such as metrizamide.
Tracheal Macrophages During Regeneration and Repair of Long‐Segment Airway Defects (2021)

NA Laryngoscope, 132:737-746, 2022.
Anti-angiogenic effects of green tea catechin on an experimental endometriosis mouse model (2008)

EGCG significantly inhibits the development of experimental endometriosis through anti-angiogenic effects.
Induction of Th2 cytokines and control of collagen-induced arthritis by nondepleting anti-CD4 Abs (1996)

CD4+ T cells play a key role in the development of cell-mediated autoimmune diseases, and their modulation has been used to prevent autoimmune diseases in animal models. The effect of the nondepleting anti-CD4 mAb (KT6) was investigated in collagen-induced arthritis (CIA) in DBA/1 mice and in adoptive transfer of CIA into SCID mice. KT6 (200 microg/dose/mouse) was administered systematically from the day of collagen type II (CII) immunization and continued by alternate-day injection until day 11. Only 20% of KT6-treated mice developed arthritis compared with 100% of the isotype control treated mice (p < 0.001). KT6 treatment in a similar regimen also abrogated the adoptive transfer of CIA into SCID mice. Serum levels of IgG2a anti-CII Abs in KT6-treated DBA/1 mice were significantly reduced (p < 0.001), while IgG1 anti-CII were not significantly changed (p > 0.05). Lymph node cells of mice treated in vivo with KT6 had a reduced production of IFN-gamma but increased IL-4 upon in vitro challenge with CII. Furthermore, KT6 could also reverse the profile of cytokine release of in vivo primed and pathogenic CII-specific T cells. These results demonstrate that in vivo modulation with nondepleting anti-CD4 Abs prevents CIA, likely by altering the functional profile of Th1 T cells to Th2. Furthermore, we demonstrate that this treatment can not only prevent, but more importantly also control pathogenic T cells by switching their cytokine production from a Th1 to a Th2-like profile. Our results thus provide compelling evidence of how treatment with nondepleting anti-CD4 may control an autoimmune process. They also indicate that this approach not only prevents, but also could control ongoing autoimmune diseases.
Some Tests of Significance, Treated by the Theory of Probability (1935)

It often happens that when two sets of data obtained by observation give slightly different estimates of the true value we wish to know whether the difference is significant. The usual procedure is to say that it is significant if it exceeds a certain rather arbitrary multiple of the standard error; but this is not very satisfactory, and it seems worth while to see whether any precise criterion can be obtained by a thorough application of the theory of probability.
Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, ABI-007, compared with cremophor-based paclitaxel. (2006)

ABI-007, an albumin-bound, 130-nm particle form of paclitaxel, was developed to avoid Cremophor/ethanol-associated toxicities in Cremophor-based paclitaxel (Taxol) and to exploit albumin receptor-mediated endothelial transport. We studied the antitumor activity, intratumoral paclitaxel accumulation, and endothelial transport for ABI-007 and Cremophor-based paclitaxel. Antitumor activity and mortality were assessed in nude mice bearing human tumor xenografts [lung (H522), breast (MX-1), ovarian (SK-OV-3), prostate (PC-3), and colon (HT29)] treated with ABI-007 or Cremophor-based paclitaxel. Intratumoral paclitaxel concentrations (MX-1-tumored mice) were compared for radiolabeled ABI-007 and Cremophor-based paclitaxel. In vitro endothelial transcytosis and Cremophor inhibition of paclitaxel binding to cells and albumin was compared for ABI-007 and Cremophor-based paclitaxel. Both ABI-007 and Cremophor-based paclitaxel caused tumor regression and prolonged survival; the order of sensitivity was lung > breast congruent with ovary > prostate > colon. The LD(50) and maximum tolerated dose for ABI-007 and Cremophor-based paclitaxel were 47 and 30 mg/kg/d and 30 and 13.4 mg/kg/d, respectively. At equitoxic dose, the ABI-007-treated groups showed more complete regressions, longer time to recurrence, longer doubling time, and prolonged survival. At equal dose, tumor paclitaxel area under the curve was 33% higher for ABI-007 versus Cremophor-based paclitaxel, indicating more effective intratumoral accumulation of ABI-007. Endothelial binding and transcytosis of paclitaxel were markedly higher for ABI-007 versus Cremophor-based paclitaxel, and this difference was abrogated by a known inhibitor of endothelial gp60 receptor/caveolar transport. In addition, Cremophor was found to inhibit binding of paclitaxel to endothelial cells and albumin. Enhanced endothelial cell binding and transcytosis for ABI-007 and inhibition by Cremophor in Cremophor-based paclitaxel may account in part for the greater efficacy and intratumor delivery of ABI-007.
Preparation of functionally active cell-permeable peptides by single-step ligation of two peptide modules (1998)

Noninvasive cellular import of synthetic peptides can be accomplished by incorporating a hydrophobic, membrane-permeable sequence (MPS). Herein, we describe a facile method that expedites synthesis of biologically active, cell-permeable peptides by site-specific ligation of two free peptide modules: one bearing a functional sequence and the second bearing a MPS. A nonpeptide thiazolidino linkage between the two modules is produced by ligation of the COOH-terminal aldehyde on the MPS and the NH2-terminal 1, 2-amino thiol moiety on the functional sequence. This thiazolidine ligation approach is performed with stoichiometric amounts of fully unprotected MPS and functional peptide in an aqueous buffered solution, eliminating the need for additional chemical manipulation and purification prior to use in bioassays. Two different MPSs were interchangeably combined with two different functional sequences to generate two sets of hybrid peptides. One set of hybrid peptides, carrying the cytoplasmic cell adhesion regulatory domain of the human integrin beta3, inhibited adhesion of human erythroleukemia cells to fibrinogen-coated surfaces. A second set of hybrid peptides, carrying the nuclear localization sequence of the transcription factor NF-kappaB, inhibited nuclear import of transcription factors NF-kappaB, activator protein 1, and nuclear factor of activated T cells in agonist-stimulated Jurkat T lymphocytes. In each assay, these nonamide bond hybrids were found to be functionally comparable to peptides prepared by the conventional method. Cumulatively, this new ligation approach provides an easy and rapid method for engineering of functional, cell-permeable peptides and demonstrates the potential for synthesis of cell-permeable peptide libraries designed to block intracellular protein-protein interactions.
Compositional Matrix-Space Models for Sentiment Analysis (2011)

We present a general learning-based approach for phrase-level sentiment analysis that adopts an ordinal sentiment scale and is explicitly compositional in nature. Thus, we can model the compositional effects required for accurate assignment of phrase-level sentiment. For example, combining an adverb (e.g., “very”) with a positive polar adjective (e.g., “good”) produces a phrase (“very good”) with increased polarity over the adjective alone. Inspired by recent work on distributional approaches to compositionality, we model each word as a matrix and combine words using iterated matrix multiplication, which allows for the modeling of both additive and multiplicative semantic effects. Although the multiplication-based matrix-space framework has been shown to be a theoretically elegant way to model composition (Rudolph and Giesbrecht, 2010), training such models has to be done carefully: the optimization is nonconvex and requires a good initial starting point. This paper presents the first such algorithm for learning a matrix-space model for semantic composition. In the context of the phrase-level sentiment analysis task, our experimental results show statistically significant improvements in performance over a bagof-words model. 1
Development of Chemical Probes for Investigation of Salt-Inducible Kinase Function in Vivo (2016)

Salt-inducible kinases (SIKs) are promising therapeutic targets for modulating cytokine responses during innate immune activation. The study of SIK inhibition in animal models of disease has been limited by the lack of selective small-molecule probes suitable for modulating SIK function in vivo. We used the pan-SIK inhibitor HG-9-91-01 as a starting point to develop improved analogs, yielding a novel probe 5 (YKL-05-099) that displays increased selectivity for SIKs versus other kinases and enhanced pharmacokinetic properties. Well-tolerated doses of YKL-05-099 achieve free serum concentrations above its IC50 for SIK2 inhibition for >16 h and reduce phosphorylation of a known SIK substrate in vivo. While in vivo active doses of YKL-05-099 recapitulate the effects of SIK inhibition on inflammatory cytokine responses, they did not induce metabolic abnormalities observed in Sik2 knockout mice. These results identify YKL-05-099 as a useful probe to investigate SIK function in vivo and further support the development of SIK inhibitors for treatment of inflammatory disorders.
Controlled inflation of voids in cellular polymer ferroelectrets: Optimizing electromechanical transducer properties (2004)

When exposed to sufficiently high electric fields, polymer-foam electret materials with closed cells exhibit ferroelectric-like behavior and may therefore be called ferroelectrets. In cellular ferroelectrets, the influence of the cell size and shape distributions on the application-relevant properties is not yet understood. Therefore, controlled inflation experiments were carried out on cellular polypropylene films, and the resulting elastical and electromechanical parameters were determined. The elastic modulus in the thickness direction shows a minimum with a corresponding maximum in the electromechanical transducer coefficient. The resonance frequency shifts as a function of the elastic modulus and the relative density of the inflated cellular films. Therefore, the transducer properties of cellular ferroelectrets can be optimized by means of controlled inflation.
Discriminative Video Pattern Search for Efficient Action Detection (2011)

Actions are spatiotemporal patterns. Similar to the sliding window-based object detection, action detection finds the reoccurrences of such spatiotemporal patterns through pattern matching, by handling cluttered and dynamic backgrounds and other types of action variations. We address two critical issues in pattern matching-based action detection: 1) the intrapattern variations in actions, and 2) the computational efficiency in performing action pattern search in cluttered scenes. First, we propose a discriminative pattern matching criterion for action classification, called naive Bayes mutual information maximization (NBMIM). Each action is characterized by a collection of spatiotemporal invariant features and we match it with an action class by measuring the mutual information between them. Based on this matching criterion, action detection is to localize a subvolume in the volumetric video space that has the maximum mutual information toward a specific action class. A novel spatiotemporal branch-and-bound (STBB) search algorithm is designed to efficiently find the optimal solution. Our proposed action detection method does not rely on the results of human detection, tracking, or background subtraction. It can handle action variations such as performing speed and style variations as well as scale changes well. It is also insensitive to dynamic and cluttered backgrounds and even to partial occlusions. The cross-data set experiments on action detection, including KTH, CMU action data sets, and another new MSR action data set, demonstrate the effectiveness and efficiency of the proposed multiclass multiple-instance action detection method.
An adaptive resource partitioning algorithm for SMT processors (2008)

Simultaneous Multithreading (SMT) increases processor throughput by allowing the parallel execution of several threads. However, fully sharing processor resources may cause resource monopolization by a single thread or other misallocations, resulting in overall performance degradation. Static resource partitioning techniques have been suggested, but are not as effective as dynamically controlling the resource usage of each thread since program behavior does change during its execution.
Transcriptional Regulation of the Melanoma Prognostic Marker Melastatin (TRPM1) by MITF in Melanocytes and Melanoma (2004)

Determining the metastatic potential of intermediate thickness lesions remains a major challenge in the management of melanoma. Clinical studies have demonstrated that expression of melastatin/TRPM1 strongly predicts nonmetastatic propensity and correlates with improved outcome, leading to a national cooperative prospective study, which is ongoing currently. Similarly, the melanocytic markers MLANA/MART1 and MITF also have been shown to lose relative expression during melanoma progression. Recent studies have revealed that MITF, an essential transcription factor for melanocyte development, directly regulates expression of MLANA. This prompted examination of whether MITF also might transcriptionally regulate TRPM1 expression. The TRPM1 promoter contains multiple MITF consensus binding elements that were seen by chromatin immunoprecipitation to be occupied by endogenous MITF within melanoma cells. Endogenous TRPM1 expression responded strongly to MITF up- or down-regulation, as did TRPM1 promoter-driven reporters. In addition, MITF and TRPM1 mRNA levels were correlated tightly across a series of human melanoma cell lines. Mice homozygously mutated in MITF showed a dramatic decrease in TRPM1 expression. Finally, the slope of TRPM1 induction by MITF was particularly steep compared with other MITF target genes, suggesting it is a sensitive indicator of MITF expression and correspondingly of melanocytic differentiation. These studies identify MITF as a major transcriptional regulator of TRPM1 and suggest that its prognostic value may be linked to MITF-mediated regulation of cellular differentiation.