gebhart/patrepeval huggingface dataset:
Probing the β2 Adrenoceptor Binding Site with Catechol Reveals Differences in Binding and Activation by Agonists and Partial Agonists (2005)

The beta(2) adrenergic receptor (beta(2)AR) is a prototypical family A G protein-coupled receptor (GPCR) and an excellent model system for studying the mechanism of GPCR activation. The beta(2)AR agonist binding site is well characterized, and there is a wealth of structurally related ligands with functionally diverse properties. In the present study, we use catechol (1,2-benzenediol, a structural component of catecholamine agonists) as a molecular probe to identify mechanistic differences between beta(2)AR activation by catecholamine agonists, such as isoproterenol, and by the structurally related non-catechol partial agonist salbutamol. Using biophysical and pharmacologic approaches, we show that the aromatic ring of salbutamol binds to a different site on the beta(2)AR than the aromatic ring of catecholamines. This difference is important in receptor activation as it has been hypothesized that the aromatic ring of catecholamines plays a role in triggering receptor activation through interactions with a conserved cluster of aromatic residues in the sixth transmembrane segment by a rotamer toggle switch mechanism. Our experiments indicate that the aromatic ring of salbutamol does not activate this mechanism either directly or indirectly. Moreover, the non-catechol ring of partial agonists does not interact optimally with serine residues in the fifth transmembrane helix that have been shown to play an important role in activation by catecholamines. These results demonstrate unexpected differences in binding and activation by structurally similar agonists and partial agonists. Moreover, they provide evidence that activation of a GPCR is a multistep process that can be dissected into its component parts using agonist fragments.
Potentiation of growth factor activity by exogenous c-myc expression. (1986)

The c-myc oncogene has been implicated in deregulation of cell growth in neoplastic cells and response to "competence-inducing" growth factors in normal cells. In the latter case, expression of c-myc has been shown to be associated with the transition from the G0 to the G1 phase of the cell cycle induced by platelet-derived growth factor (PDGF). In the work reported here, we have introduced the c-myc coding region, in a retroviral vector, into mouse and rat cells. We show that under conditions of anchorage-independent growth, constitutive c-myc expression increases the response of rodent cells to PDGF, as well as to other growth factors of both the competence-inducing and "progression" classes. These effects of the myc product are observed whether or not an exogenous ras gene has also been introduced into the same cells. Possible models for the influence of myc on growth responses are discussed.
The ICSI Meeting Corpus (2003)

We have collected a corpus of data from natural meetings that occurred at the International Computer Science Institute (ICSI) in Berkeley, California over the last three years. The corpus contains audio recorded simultaneously from head-worn and table-top microphones, word-level transcripts of meetings, and various metadata on participants, meetings, and hardware. Such a corpus supports work in automatic speech recognition, noise robustness, dialog modeling, prosody, rich transcription, information retrieval, and more. We present details on the contents of the corpus, as well as rationales for the decisions that led to its configuration. The corpus were delivered to the Linguistic Data Consortium (LDC).
Application of 18F-FDG PET/CT in Nasopharyngeal Carcinoma (2007)

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy occurring worldwide, with particularly high frequencies in Southern China, Hong Kong, Singapore and Taiwan. Imaging is vital for detection, staging, and treatment. 2-[Fluorine-18] fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) has been shown to be a valuable imaging tool in patients for initial staging and restaging diagnosis of NPC. Dual-modality positron emission tomography/computed tomography (PET/CT) provides the technical basis for intrinsically aligned functional and morphologic data sets. The false-negative and false-positive rate may be decreased by using combined FDG-PET/CT. FDG-PET/CT may be as a standard clinical imaging modality in the staging of NPC and in the detection of recurrent disease after radiotherapy. It could provide valuable information in localizing primary tumor in patients with neck nodal metastases from an unknown primary tumor.
Shape tensors for efficient and learnable indexing (2002)

Multi-point geometry: The geometry of 1 point in N images under perspective projection has been thoroughly investigated, identifying bilinear, trilinear, and quadrilinear relations between the projections of 1 point in 2, 3 and 4 frames respectively. The dual problem-the geometry of N points in 1 image-has been studied mostly in the context of object recognition, often assuming weak perspective or affine projection. We provide here a complete description of this problem. We employ a formalism in which multiframe and multi-point geometries appear in symmetry. Points and projections are interchangeable. We then derive bilinear equations for 6 points (dual to 3-frame geometry), trilinear equations for 7 points (dual to 3-frame geometry), and quadrilinear equations for 8 points (dual to the epipolar geometry). We show that the quadrilinear equations are dependent on the the bilinear and trilinear equations, and we show that adding more points will not generate any new equation. The new equations are used to design new algorithms for the reconstruction of shape from many frames, and for learning invariant relations for indexing into a database.
Opioid-induced respiratory depression is associated with increased tidal volume variability (2003)

Background and objective: μ-agonistic opioids cause concentration-dependent hypoventilation and increased irregularity of breathing. The aim was to quantify opioid-induced irregularity of breathing and to investigate its time-course during and after an opioid infusion, and its ability to predict the severity of respiratory depression. Methods: Twenty-three patients breathing spontaneously via a continuous positive airway pressure (CPAP) mask received an intravenous (i.v.) infusion of alfentanil (2.3 μg kg−1 min−1, 14 patients) or pirinitramide (piritramide) (17.9 μg kg−1 min−1, nine patients) until either a cumulative dose of 70 μg kg−1 for alfentanil or 500 μg kg−1 for pirinitramide had been achieved or the infusion had to be stopped for safety reasons. Tidal volumes (VT) and minute ventilation were measured with an anaesthesia workstation. For every 20 breaths, the quartile coefficient was calculated (Qeff20VT). Results: Both the decrease of minute volume and the increase of Qeff20VT during and after opioid infusion were highly significant (P < 0.001, ANOVA). Patients in which the alfentanil infusion had to be terminated prematurely had lower minute volumes (P = 0.002, t-test) and higher Qeff20VT (P = 0.034, t-test) than those who received the complete dose. Changes in the regularity of breathing measured as Qeff20VT parallel those of minute ventilation during and after opioid infusion. Conclusions: Opioids cause a more complicated disturbance of the control of respiration than a mere resetting to higher PCO2. Furthermore, Qeff20VT appears to predict the severity of opioid-induced respiratory depression.
FastEstimator: A Deep Learning Library for Fast Prototyping and Productization (2019)

As the complexity of state-of-the-art deep learning models increases by the month, implementation, interpretation, and traceability become ever-more-burdensome challenges for AI practitioners around the world. Several AI frameworks have risen in an effort to stem this tide, but the steady advance of the field has begun to test the bounds of their flexibility, expressiveness, and ease of use. To address these concerns, we introduce a radically flexible high-level open source deep learning framework for both research and industry. We introduce FastEstimator.
IBM Streams Processing Language: Analyzing Big Data in motion (2013)

The IBM Streams Processing Language (SPL) is the programming language for IBM InfoSphere® Streams, a platform for analyzing Big Data in motion. By “Big Data in motion,” we mean continuous data streams at high data-transfer rates. InfoSphere Streams processes such data with both high throughput and short response times. To meet these performance demands, it deploys each application on a cluster of commodity servers. SPL abstracts away the complexity of the distributed system, instead exposing a simple graph-of-operators view to the user. SPL has several innovations relative to prior streaming languages. For performance and code reuse, SPL provides a code-generation interface to C++ and Java®. To facilitate writing well-structured and concise applications, SPL provides higher-order composite operators that modularize stream sub-graphs. Finally, to enable static checking while exposing optimization opportunities, SPL provides a strong type system and user-defined operator models. This paper provides a language overview, describes the implementation including optimizations such as fusion, and explains the rationale behind the language design.
Sliding mode observer for wide-speed sensorless control of PMSM drives (2004)

Many of the estimation techniques developed to achieve speed or position sensorless, motor drives suffer from the variation of motor parameters such as the stator resistance, stator inductance or torque constant. In particular, conventional linear estimators are not adaptive to variations of the operating point. The sliding mode technique has shown promising results when estimating or controlling nonlinear systems. This paper presents a sliding mode observer (SMO) for estimating the position and speed of a permanent magnet synchronous motor (PMSM) to achieve sensorless drive system. The technique can be generalized to other motor drives and motion control systems. The effects of the variation of motor parameters such as stator resistance and stator inductance on the position and/or speed estimations, over a wide speed range, have been studied. Compared to other methods, the observer is more robust to parameter detuning. Simulations results are presented.
The Gut–Lung Axis in Respiratory Disease (2015)

Host-microorganism interactions shape local cell functionality, immune responses, and can influence disease development. Evidence indicates that the impact of host-microbe interactions reaches far beyond the local environment, thus influencing responses in peripheral tissues. There is a vital cross-talk between the mucosal tissues of our body, as exemplified by intestinal complications during respiratory disease and vice versa. Although, mechanistically, this phenomenon remains poorly defined, the existence of the gut-lung axis and its implications in both health and disease could be profoundly important for both disease etiology and treatment. In this review, we highlight how changes in the intestinal microenvironment, with a particular focus on the intestinal microbiota, impact upon respiratory disease.
Comparison of the Host Responses to Wild-Type andcpsBMutantKlebsiella pneumoniaeInfections (2006)

Previously, we established an intranasal mouse model of Klebsiella pneumoniae infection and validated its utility using a highly virulent wild-type strain and an avirulent capsular polysaccharide mutant. In the present study we compare the host responses to both infections by examining cytokine production, cellular infiltration, pulmonary histology, and intranasal immunization.
Strengthened Lazy Heaps: Surpassing the Lower Bounds for Binary Heaps (2014)

Let $n$ denote the number of elements currently in a data structure. An in-place heap is stored in the first $n$ locations of an array, uses $O(1)$ extra space, and supports the operations: minimum, insert, and extract-min. We introduce an in-place heap, for which minimum and insert take $O(1)$ worst-case time, and extract-min takes $O(\lg{} n)$ worst-case time and involves at most $\lg{} n + O(1)$ element comparisons. The achieved bounds are optimal to within additive constant terms for the number of element comparisons. In particular, these bounds for both insert and extract-min -and the time bound for insert- surpass the corresponding lower bounds known for binary heaps, though our data structure is similar. In a binary heap, when viewed as a nearly complete binary tree, every node other than the root obeys the heap property, i.e. the element at a node is not smaller than that at its parent. To surpass the lower bound for extract-min, we reinforce a stronger property at the bottom levels of the heap that the element at any right child is not smaller than that at its left sibling. To surpass the lower bound for insert, we buffer insertions and allow $O(\lg^2{} n)$ nodes to violate heap order in relation to their parents.
Current Status and Future of Light Emitting Polymer Display driven by Poly‐Si TFT (1999)

Abstract The combination of Light Emitting Polymer (LEP) with Poly‐Si TFT has great potential to realize an ideal type of the flat panel display. High‐resolution monochrome LEP display driven by p‐Si TFT with integrated driver has been already developed. That demonstrated its high potential. The current status of the technologies will be introduced, with some comment for further developmental work.
Cloning and expression of a chimeric antibody directed against the human transferrin receptor. (1990)

The cloning, construction and expression of chimeric Ig genes, encoding a mAb directed against the human transferrin receptor, is described. From a mouse hybridoma cell line, secreting an antitransferrin receptor antibody, mRNA was prepared and converted into cDNA using Ig-specific oligonucleotides. H and L chain encoding cDNA fragments were isolated and sequenced. Chimeric genes were constructed by linking the murine V region cDNA fragments to human C region exons. After sequential transfection of nonproducing mouse hybridoma cells with the expression vectors containing the chimeric H and L chain genes, antibody secreting transfectomas were obtained. ELISA and immunoblot analysis clearly demonstrate the secretion of human kappa- and gamma-1 chain. Flow microfluorimetry analysis of the chimeric antibody shows that the Ag-binding capacity has been retained. The chimeric antibody most likely will be less immunogenic then the original mouse antibody when used in human cancer therapy.
Cardiomyopathy in transgenic mice with cardiac-specific overexpression of serum response factor (2001)

Serum response factor (SRF), a member of the MCM1, agamous, deficiens, SRF (MADS) family of transcriptional activators, has been implicated in the transcriptional control of a number of cardiac muscle genes, including cardiac alpha-actin, skeletal alpha-actin, alpha-myosin heavy chain (alpha-MHC), and beta-MHC. To better understand the in vivo role of SRF in regulating genes responsible for maintenance of cardiac function, we sought to test the hypothesis that increased cardiac-specific SRF expression might be associated with altered cardiac morphology and function. We generated transgenic mice with cardiac-specific overexpression of the human SRF gene. The transgenic mice developed cardiomyopathy and exhibited increased heart weight-to-body weight ratio, increased heart weight, and four-chamber dilation. Histological examination revealed cardiomyocyte hypertrophy, collagen deposition, and interstitial fibrosis. SRF overexpression altered the expression of SRF-regulated genes and resulted in cardiac muscle dysfunction. Our results demonstrate that sustained overexpression of SRF, in the absence of other stimuli, is sufficient to induce cardiac change and suggest that SRF is likely to be one of the downstream effectors of the signaling pathways involved in mediating cardiac hypertrophy.
Secondary lymphoid organ chemokine reduces pulmonary tumor burden in spontaneous murine bronchoalveolar cell carcinoma. (2001)

The antitumor efficiency of secondary lymphoid organ chemokine (SLC), a CC chemokine that chemoattracts both dendritic cells (DCs) and T lymphocytes,was evaluated in SV40 large T-antigen transgenic mice that develop bilateral multifocal pulmonary adenocarcinomas. Injection of recombinant SLC in the axillary lymph node region led to a marked reduction in tumor burden with extensive lymphocytic and DC infiltration of the tumors and enhanced survival. SLC injection led to significant increases in CD4 and CD8 lymphocytes as well as DC at the tumor sites, lymph nodes, and spleen. The cellular infiltrates were accompanied by the enhanced elaboration of Type 1 cytokines and the antiangiogenic chemokines IFN-gamma inducible protein 10, and monokine induced by IFN-gamma (MIG). In contrast, lymph node and tumor site production of the immunosuppressive cytokine transforming growth factor beta was decreased in response to SLC treatment. In vitro, after stimulation with irradiated autologous tumor, splenocytes from SLC-treated mice secreted significantly more IFN-gamma and granulocyte macrophage colony-stimulating factor, but reduced levels of interleukin 10. Significant reduction in tumor burden in a model in which tumors develop in an organ-specific manner provides a strong rationale for additional evaluation of SLC in regulation of tumor immunity and its use in lung cancer immunotherapy.
Real-Time Quantitative Polymerase Chain Reaction (RQ-PCR) Monitoring of Minimal Residual Disease (MRD) in Core Binding Factor Acute Myeloid Leukaemia (CBF AML). (2006)

Abstract Background: CBF AML, with t(8;21)(q22;q22), inv(16)(p13q22) or t(16;16)(p13;q22) and the associated fusion proteins AML1/ETO or CBFβ/MYH11, has a favourable clinical prognosis although significant numbers of patients still relapse. We examined the prognostic utility of MRD monitoring by RQ-PCR and propose a simple model for prediction of impending haematological relapse. Methods: Patients with CBF AML had samples collected at diagnosis, after induction and consolidation chemotherapy and at routine regular intervals thereafter. RQ-PCR, using the Applied Biosystems 7700 Sequence Detection System, was performed in triplicate and the final result was calculated by averaging 3 values, expressed relative to PGK levels. Stratified Cox regression was used to assess the impact of predictor variables (diagnostic, post-induction, post-consolidation RQ-PCR levels and presence of a 1 log10 increase in sequential RQ-PCR levels) on leukaemia-free survival (LFS). Results: Of 46 patients identified with CBF AML, 29 had diagnostic, regular longitudinal samples and clinical follow up allowing further evaluation; 12 AML1-ETO and 17 CBFβ-MYH11. The median age was 39 years (range 7–68) with 52% male. Median follow up was 34 months (range 1–106) and median sample number was 6 (2–15). Twelve relapses occurred at a median of 11 months (range 4–17) from diagnosis. There were significant differences between transcript levels at diagnosis (median 1.9), post-induction (8.96*10−04), post-consolidation (5.01*10−05), in remission (1*10−06) or relapse (0.15) (p=0.01). Diagnostic, post-induction and post-consolidation RQ-PCR levels did not predict outcome. A log10 rise in a remission bone marrow sample correlated with adverse LFS and imminent risk of haematological relapse (HR 8.6). Relapses occurred a median of 60 days (range 45–272) after a log10 rise. RQ-PCR levels Hazard Ratio (HR) LFS 95% CI P-value Diagnosis 0.22 0.02–2.9 0.25 Post-induction 1.3 0.8–2.1 0.36 Post-consolidation 0.8 0.5–1.2 0.27 1 log10 increase 8.6 1.8–42 0.008 Conclusions: A 1 log10 rise in transcript levels was a highly significant predictor of haematological relapse. Transcript levels at early post-treatment time points did not predict long term outcome, cautioning against de-escalation protocols based on these results. Prospective identification of high risk patients will enable clinical trials to address the efficacy of treatment initiated at molecular progression.
Emerging roles for IL-11 signaling in cancer development and progression: Focus on breast cancer (2015)

Interleukin (IL)-11 is a member of the IL-6 family of cytokines that is defined by the shared use of the GP130 signal transducing receptor subunit. In addition of its long recognized activities as a hemopoietic growth factor, IL-11 has an emerging role in epithelial cancer biology. Through the activation of the GP130-Janus kinase signaling cascade and associated transcription factor STAT3, IL-11 can confer many of the tumor intrinsic 'hallmark' capabilities to neoplastic cells, if they express the ligand-specific IL-11Rα receptor subunit. Accordingly, IL-11 signaling has recently been identified as a rate-limiting step for the growth tumors arising from the mucosa of the gastrointestinal tract. However, there is less appreciation for a potential role of IL-11 to support breast cancer progression, apart from its well documented capacity to facilitate bone metastasis. Here we review evidence that IL-11 expression in breast cancer correlates with poor disease outcome and discuss some of the molecular mechanisms that are likely to underpin these observations. These include the capacity of IL-11 to stimulate survival and proliferation of cancer cells alongside angiogenesis of the primary tumor and of metastatic progenies at distant organs. We review current strategies to interfere with IL-11 signaling and advocate that inhibition of IL-11 signaling may represent an emerging therapeutic opportunity for numerous cancers.
Photophysical Properties of Biologically Compatible CdSe Quantum Dot Structures (2005)

The photophysical properties of CdSe and ZnS(CdSe) semiconductor quantum dots in nonpolar and aqueous solutions were examined with steady-state (absorption and emission) and time-resolved (time-correlated single-photon-counting) spectroscopy. The CdSe structures were prepared from a single CdSe synthesis, a portion of which were ZnS-capped, thus any differences observed in the spectral behavior between the two preparations were due to changes in the molecular shell. Quantum dots in nonpolar solvents were surrounded with a trioctylphosphine oxide (TOPO) coating from the initial synthesis solution. ZnS-capped CdSe were initially brighter than bare uncapped CdSe and had overall faster emission decays. The dynamics did not vary when the solvent was changed from hexane to dichloromethane; however, replacement of the TOPO cap by pyridine affected CdSe but not ZnS(CdSe). CdSe was then solubilized in water with mercapto-acetic acid or dihydrolipoic acid, whereas ZnS(CdSe) could be solubilized only with dihydrolipoic acid. Both solubilization agents quenched the nanocrystal emission, though with CdSe the quenching was nearly complete. Additional quenching of the remaining emission was observed when the redox-active molecule adenine was conjugated to the water-soluble CdSe but was not seen with ZnS(CdSe). The emission of aqueous CdSe could be enhanced under prolonged exposure to room light and resulted in a substantial increase of the emission lifetimes; however, the enhancement occurred concurrently with precipitation of the nanocrystals, which was possibly caused by photocatalytic destruction of the mercaptoacetic acid coating. These results are the first presented on aqueous CdSe quantum dot structures and are presented in the context of designing better, more stable biological probes.