gebhart/patrepeval huggingface dataset:
Phenotypic classification of mutants: a tool for understanding ligand binding and activation of muscarinic acetylcholine receptors (2007)

GPCRs (G-protein-coupled receptors) such as the M(1) muscarinic receptor have so far proved recalcitrant to direct structure determination. Nevertheless systematic mutagenesis, particularly alanine scanning, has advanced our understanding of their structure-function relationships. GPCRs exhibit multiple conformational states with different affinities for and abilities to activate their cognate G-proteins. Ligand binding alters these conformational equilibria, thus promoting or inhibiting signalling. Alanine-scanning mutagenesis probes the relative contributions of a particular amino acid side chain to the stability of the ground and activated states of the receptor and its complexes. These determine the phenotype of the mutant receptor. Classification of the phenotypes suggests functional roles for particular amino acid side chains, allowing us to group them accordingly. From a rhodopsin-based homology model of the M(1) mAChR, a coherent view emerges of how these clusters of residues function in ligand anchoring, transduction of binding energy, global structural stabilization and selective stabilization of the ground state or the activated state of the receptor. We can identify differences in ligand-binding modes, and suggest inter- and intra-molecular interactions that are weakened or broken, or formed or intensified during acetylcholine-induced activation. In due course, we may be able to extend these insights to activation by unconventional agonists.
INTERRATER RELIABILITY OF CARIES DIAGNOSIS BY LASER FLUORESCENCE (2001)

The purpose of study was to measure the interrater reliability of the caries diagnostic instrument, Diagnodent(KaVo, Germany), using a new laser fluorescence technique. Occlusal surfaces and smooth surfaces of one hundred extracted human premolars and molars were examined by four dentists. Pearson correlation coeffcients were 0703 to 0.870 for occlusal surfaces and 0.764 to 0.932 for smooth surfaces (P
Effects of rapid changes of external Na+ concentration at different moments during the action potential in guinea‐pig myocytes. (1994)

1. A rapid solution-changing system using a solenoid was set up. The half-time for changing the external solution surrounding a ventricular cardiac cell was 7.2 +/- 1.4 ms, whereas the time needed to change 90% of this solution was 48.5 +/- 7.9 ms. This rapid switching system was used to reduce the external sodium concentration at different moments during the action potential (recorded using the whole-cell method) to 50% of its original value. This was performed in order to investigate the effect on the shape and duration of the action potential of modifying the activity of the sodium-calcium exchanger. 2. A diminution of the action potential duration was seen irrespective of the substitute used for reducing the NaCl concentration from 140 to 70 mM. The magnitude of this diminution depended on the presence or absence of EGTA (5 mM) in the pipette solution and also on the moment during the action potential at which the NaCl substitution occurred. 3. Some differences were observed depending on whether the NaCl substitute used was lithium chloride or choline chloride. When choline chloride or N-methyl-D-glucamine was used as the NaCl substitute, the amplitude of the action potential was slightly reduced (by 2-5 mV) when the solution was changed 40 ms before the action potential was triggered. This reduction was never observed when LiCl was used as the NaCl substitute. 4. The effects on the shape of the action potential of changing from a solution containing 140 mM NaCl to one containing 70 mM NaCl and 70 mM LiCl were much more rapid when these changes occurred at a later stage during the action potential. The rate of repolarization was more than doubled when the change occurred at a late stage of the action potential but was hardly changed at the beginning of the plateau. 5. These experiments confirm the role of the sodium-calcium exchange current in determining the duration of the mammalian ventricular action potential. However, it is also possible that the sodium background current plays a significant role in determining the shape of the action potential.
Implementation of Variable-Delay Random PWM for Automotive Applications (2007)

This paper presents the implementation of variable-delay random pulsewidth modulation (VD-RPWM) for an automotive traction drive inverter. RPWM is desirable as a means of reducing electromagnetic emissions from the inverter and minimizing electromagnetic-compatibility filtering requirements. It can also serve in reducing acoustic noise generated by the drive. The algorithm is implemented on a power-PC-based microprocessor. Experimental results are presented to verify the operation of the algorithm and its compatibility with basic motor-control functions. Spectrum plots of the phase current and voltage demonstrate the effectiveness of the technique in mitigating electromagnetic interference. The effects on torque ripple and acoustic noise are also investigated
A Practical Approach to T-Cell Receptor Cloning and Expression (2011)

Although cloning and expression of T-cell Receptors (TcRs) has been performed for almost two decades, these procedures are still challenging. For example, the use of T-cell clones that have undergone limited expansion as starting material to limit the loss of interesting TcRs, must be weighed against the introduction of mutations by excess PCR cycles. The recent interest in using specific TcRs for cancer immunotherapy has, however, increased the demand for practical and robust methods to rapidly clone and express TcRs. Two main technologies for TcR cloning have emerged; the use of a set of primers specifically annealing to all known TcR variable domains, and 5'-RACE amplification. We here present an improved 5'-RACE protocol that represents a fast and reliable way to identify a TcR from 10(5) cells only, making TcR cloning feasible without a priori knowledge of the variable domain sequence. We further present a detailed procedure for the subcloning of TcRα and β chains into an expression system. We show that a recombination-based cloning protocol facilitates simple and rapid transfer of the TcR transgene into different expression systems. The presented comprehensive method can be performed in any laboratory with standard equipment and with a limited amount of starting material. We finally exemplify the straightforwardness and reliability of our procedure by cloning and expressing several MART-1-specific TcRs and demonstrating their functionality.
Bone marrow transplantation in chronic GvHD and autoimmune diseases. (1996)

The same ex vivo marrow's treatment that we used in mismatched BMT (incubation with vincristine and methylprednisolone) was used in two patients with chronic GVHD and in one patient with PRCA. The conditioning regimen with cyclophosphamide and ALG was aimed to kill only the patient's lymphocytes, and did not cause a deep myeloid aplasia. The patients achieved a clear improvement of their symptoms.
Buffer overflows: attacks and defenses for the vulnerability of the decade (2002)

Buffer overflows have been the most common form of security vulnerability for the last ten years. Moreover, buffer overflow vulnerabilities dominate the area of remote network penetration vulnerabilities, where an anonymous Internet user seeks to gain partial or total control of a host. If buffer overflow vulnerabilities could be effectively eliminated, a very large portion of the most serious security threats would also be eliminated. We survey the various types of buffer overflow vulnerabilities and attacks and survey the various defensive measures that mitigate buffer overflow vulnerabilities, including our own StackGuard method. We then consider which combinations of techniques can eliminate the problem of buffer overflow vulnerabilities, while preserving the functionality and performance of existing systems.
Synthetic Signal Propagation Through Direct Cell-Cell Interaction (2012)

Contact-dependent cell communication has the potential to generate elaborate cell patterns, and this occurs in vivo. We used the Delta-Notch signaling system, consisting of the ligand Delta and the receptor Notch, to construct a positive feedback loop between adjacent cells to generate a propagating signal in cultured cells. To amplify the responses of Notch to Delta, we created a cell-cell positive feedback loop using an engineered transcriptional cascade and a Notch positive regulator, Lunatic fringe. We used mathematical modeling to determine the appropriate amount of amplification to enable the induction of Delta to propagate from one cell to its neighboring cells, which generated bistability within the local cell populations and resulted in discrete groups of cells that were either positive or negative for Delta. These results demonstrate the sufficiency of the cell-cell positive feedback loop to generate signal propagation and cell population-level bistability. This study represents a step in engineering more elaborate cell patterns in mammalian cells.
Improving TCP performance in IP networks with wireless links (2003)

This paper presents an enhancement of the congestion control algorithm of the transmission control protocol (TCP) and evaluates the performance of the proposed Fast-TCP in a mobile and wireless environment. The base stations in mobile and wireless networks face congestion which degrades the performance of TCP significantly. Initially to relieve the congestion an acknowledgment (ACK) delay proposal, called Fast-TCP, has recently been proposed to be used for more accurate control of the TCP transmission rate and better TCP traffic shaping by Nokia Research Center. This paper shows the simulation results of the performance of Fast-TCP in wireless environments. Compared with plain TCP, Fast-TCP provides better throughput and fairness.
Fractional Flow Reserve–Guided PCI versus Medical Therapy in Stable Coronary Disease (2012)

In patients with stable coronary artery disease and functionally significant stenoses, FFR-guided PCI plus the best available medical therapy, as compared with the best available medical therapy alone, decreased the need for urgent revascularization. In patients without ischemia, the outcome appeared to be favorable with the best available medical therapy alone. (Funded by St. Jude Medical; ClinicalTrials.gov number, NCT01132495.).
A Study of Texture Classification Using Spectral Features (1982)

Abstract : Prior spectral feature study was not successful because of inaccuracy in 2-D spectral estimation. In this report, a generalization of Lim-Malik method is used to accurately estimate the ring and wedge spectral features for classification of textural images with a typical performance of over 80 percent correct classification for six texture classes. The results compare favorably with other texture features but require less computation using iterative algorithm. (Author)
Effect of In Vitro and In Vivo Anakinra on Cytokines Production in Schnitzler Syndrome (2013)

IL-1 receptor antagonist anakinra is usually highly efficient in Schnitzler syndrome (SS), a rare inflammatory condition associating urticaria, fever, and IgM monoclonal gammopathy. In this study, we aimed to assess lipopolysaccharide (LPS)-induced production of inflammatory cytokines by peripheral blood mononuclear cells (PBMCs) before and after 1 month of anakinra in patients with SS. LPS-induced production of IL-1β, IL-6 and TNFα was assessed by enzyme-linked immunosorbent assay with and without anakinra in vitro, and before and after 1 month (in vivo condition) of treatment in 2 patients with SS. Spontaneous production of IL-1β, IL-6 and TNF-α by PBMCs was similar in the patients and the healthy controls and was almost undetectable. Stimulation with LPS caused a higher release of cytokines from the patients than from the healthy controls. Before in vivo anakinra start, in vitro adjunction of anakinra reduced the high LPS-induced production of IL-1β and TNFα in both patients and of IL-6 in one patient. After 1 month of treatment with anakinra, while the patients had dramatically improved, there was also a marked reduction in LPS-induced cytokines production, which was almost normalized in one patient. This study shows an abnormal LPS-induced inflammatory cytokines production in SS, which can be decreased or even normalized by in vitro and in vivo anakinra.
Diagnosis of hepatitis C (1997)

Currently, the second- and third-generation enzyme immunoassays (EIA-2 and EIA-3) for hepatitis C virus antibody (anti-HCV) are the most practical screening tests for the diagnosis of HCV infection. The need for and the choice of supplementary or confirmatory tests depend on the clinical setting and the likelihood of a true-positive EIA result. Detection of HCV RNA in serum by polymerase chain reaction (PCR) assay is the gold standard for the diagnosis of HCV infection. However, the lack of uniformity in current PCR assays has tarnished this standard. Confirmatory tests for the diagnosis of HCV infection are in general unnecessary in anti-HCV-positive patients who present with chronic liver disease. When indicated, the most appropriate test in this setting is a qualitative PCR assay for HCV RNA. Confirmatory tests should always be performed in anti-HCV-positive blood donors and individuals with normal aminotransferase levels. The most appropriate approach is to retest for anti-HCV using recombinant immunoblot assay (RIBA) and then test for HCV RNA using PCR assay in those who are RIBA positive or indeterminate. Liver histology is the gold standard in assessing severity of liver disease. Quantitative tests for serum HCV RNA levels do not help to determine the severity of liver disease. At the moment, HCV genotyping should be considered a research tool and not a part of the diagnostic work-up in clinical practice. The goals of treatment for chronic hepatitis C are sustained biochemical and virological response. Viral clearance should be determined by qualitative PCR assay. Quantifying serum HCV RNA level can help in predicting response to interferon treatment, but further studies using more standardized assays are needed to determine if these values can be used to select patients for treatment.
DeepChain: Auditable and Privacy-Preserving Deep Learning with Blockchain-based Incentive (2019)

Deep learning can achieve higher accuracy than traditional machine learning algorithms in a variety of machine learning tasks. Recently, privacy-preserving deep learning has drawn tremendous attention from information security community, in which neither training data nor the training model is expected to be exposed. Federated learning is a popular learning mechanism, where multiple parties upload local gradients to a server and the server updates model parameters with the collected gradients. However, there are many security problems neglected in federated learning, for example, the participants may behave incorrectly in gradient collecting or parameter updating, and the server may be malicious as well. In this article, we present a distributed, secure, and fair deep learning framework named DeepChain to solve these problems. DeepChain provides a value-driven incentive mechanism based on Blockchain to force the participants to behave correctly. Meanwhile, DeepChain guarantees data privacy for each participant and provides auditability for the whole training process. We implement a prototype of DeepChain and conduct experiments on a real dataset for different settings, and the results show that our DeepChain is promising.
Overlapping and CpG methylation-sensitive protein-DNA interactions at the histone H4 transcriptional cell cycle domain: distinctions between two human H4 gene promoters. (1992)

Transcriptional regulation of vertebrate histone genes during the cell cycle is mediated by several factors interacting with a series of cis-acting elements located in the 5' regions of these genes. The arrangement of these promoter elements is different for each gene. However, most histone H4 gene promoters contain a highly conserved sequence immediately upstream of the TATA box (H4 subtype consensus sequence), and this region in the human H4 gene FO108 is involved in cell cycle control. The sequence-specific interaction of nuclear factor HiNF-D with this key proximal promoter element of the H4-FO108 gene is cell cycle regulated in normal diploid cells (J. Holthuis, T.A. Owen, A.J. van Wijnen, K.L. Wright, A. Ramsey-Ewing, M.B. Kennedy, R. Carter, S.C. Cosenza, K.J. Soprano, J.B. Lian, J.L. Stein, and G.S. Stein, Science, 247:1454-1457, 1990). Here, we show that this region of the H4-FO108 gene represents a composite protein-DNA interaction domain for several distinct sequence-specific DNA-binding activities, including HiNF-D, HiNF-M, and HiNF-P. Factor HiNF-P is similar to H4TF-2, a DNA-binding activity that is not cell cycle regulated and that interacts with the analogous region of the H4 gene H4.A (F. LaBella and N. Heintz, Mol. Cell. Biol. 11:5825-5831, 1991). The H4.A gene fails to interact with factors HiNF-M and HiNF-D owing to two independent sets of specific nucleotide variants, indicating differences in protein-DNA interactions between these H4 genes. Cytosine methylation of a highly conserved CpG dinucleotide interferes with binding of HiNF-P/H4TF-2 to both the H4-FO108 and H4.A promoters, but no effect is observed for either HiNF-M or HiNF-D binding to the H4-FO108 gene. Thus, strong evolutionary conservation of the H4 consensus sequence may be related to combinatorial interactions involving overlapping and interdigitated recognition nucleotides for several proteins, whose activities are regulated independently. Our results also suggest molecular complexity in the transcriptional regulation of distinct human H4 genes.
Neurotensin receptor 1 gene activation by the Tcf/β-catenin pathway is an early event in human colonic adenomas (2005)

Alterations in the Wnt/APC (adenomatous polyposis coli) signalling pathway, resulting in beta-catenin/T cell factor (Tcf)-dependent transcriptional gene activation, are frequently detected in familial and sporadic colon cancers. The neuropeptide neurotensin (NT) is widely distributed in the gastrointestinal tract. Its proliferative and survival effects are mediated by a G-protein coupled receptor, the NT1 receptor. NT1 receptor is not expressed in normal colon epithelial cells, but is over expressed in a number of cancer cells and tissues suggesting a link to the outgrowth of human colon cancer. Our results demonstrate that the upregulation of NT1 receptor occurring in colon cancer is the result of Wnt/APC signalling pathway activation. We first established the functionality of the Tcf response element within the NT1 receptor promoter. Consequently, we observed the activation of NT1 receptor gene by agents causing beta-catenin cytosolic accumulation, as well as a strong decline of endogenous receptor when wt-APC was restored. At the cellular level, the re-establishment of wt-APC phenotype resulted in the impaired functionality of NT1 receptor, like the breakdown in NT-induced intracellular calcium mobilization and the loss of NT pro-invasive effect. We corroborated the Wnt/APC signalling pathway on the NT1 receptor promoter activation with human colon carcinogenesis, and showed that NT1 receptor gene activation was perfectly correlated with nuclear or cytoplasmic beta-catenin localization while NT1 receptor was absent when beta-catenin was localized at the cell-cell junction in early adenomas of patients with familial adenomatous polyposis, hereditary non-polyposis colorectal cancer and loss of heterozygosity tumours. In this report we establish a novel link in vitro between the Tcf/beta-catenin pathway and NT1 receptor promoter activation.
Multitouch Radial Menu Integrating Command Selection and Control of Arguments with up to 4 Degrees of Freedom (2016)

We design and evaluate a multitouch radial menu for large screens with two desirable properties. First, it allows a single gesture to select a command and then continuously control arguments for that command with unbroken kinesthetic tension. Second, arguments are controlled with 1 or 2 fingers for up to 4 degrees of freedom (DoF). For example, the user may select one command for 4 DoF direct manipulation (translation + scaling + rotation), or another command for 3 DoF camera operations (pan + zoom), using the same two-finger pinch gesture, but with different initial orientations of the gesture to disambiguate. We present a taxonomy to classify previous menuing techniques sharing the first property, and discuss how very few techniques have both of these properties. Our work also extends previous work by Banovic et al. in the following ways: our menu supports submenus and a fast default command, and we experimentally evaluate the effect of varying the number of rings in the menu, the symmetry of the menu, and the use of one hand vs. two hands vs. a stylus and hand.
β‐Site APP cleaving enzyme up‐regulation induced by 4‐hydroxynonenal is mediated by stress‐activated protein kinases pathways (2005)

4-Hydroxynonenal (HNE), an aldehydic product of lipid peroxidation, up-regulates expression of the beta-site APP cleaving enzyme (BACE-1), an aspartyl protease responsible for the beta-secretase cleavage of amyloid precursor protein (AbetaPP), and results in increased levels of amyloid beta (Abeta) peptide. The mechanisms underlying this remain unclear but are of fundamental importance because prevention of BACE-1 up-regulation is viewed as an important therapeutic strategy. In this study, we exposed NT(2) neurons to a range of HNE concentrations (0.5-5 microm) that elicited an up-regulation of BACE-1 expression, a significant increase in intracellular and secreted levels of Abeta peptides as well as apoptosis involving poly-ADP ribose polymerase cleavage and activation of caspase 3. To delineate the molecular events involved in HNE-mediated BACE-1 activation, we investigated the involvement of stress-activated protein kinases (SAPK), signal transducers and activators of transcription (STAT) and serine-threonine kinase B/phosphatidylinositol phosphate 3 kinase (Akt/PtdIns3K). Using specific pharmacological inhibitors, our results show that activation of c-Jun N-terminal kinases and p38(MAPK.), but not STAT or Akt/PtdIns3K, pathways mediate the HNE-dependent up-regulation of BACE-1 expression. Therefore, HNE, an oxidative stress mediator detected in vivo in the brains of Alzheimer's disease patients, may play a pathogenetic role in Alzheimer's disease by selectively activating SAPK pathways and BACE-1 that regulate the proteolytic processing of AbetaPP.