gebhart/patrepeval huggingface dataset:
"Anergy" of TH0 helper T lymphocytes induces downregulation of TH1 characteristics and a transition to a TH2-like phenotype. (1994)

Mature CD4+ helper T lymphocytes have been categorized into two major functional phenotypes, TH1 and TH2, which produce distinct arrays of lymphokines and which are thought to arise from a pluripotential precursor cell termed TH0. Clonal anergy can be induced in TH1 clones by stimulating via the T cell receptor (TCR) complex in the absence of a costimulator molecule; however, anergy has been difficult to demonstrate in TH2 clones. We show here that treatment of cloned TH0 lines with anergizing stimuli results in the selective loss of TH1 characteristics and retention of a TH2 phenotype. Treated cells exhibit a substantial reduction in interleukin 2 (IL-2) production and antigen-specific cytolytic activity, but retain comparable IL-4 and IL-5 production in response to restimulation via the TCR complex. TH0 clones exposed to anergizing stimuli also increase in size, thus morphologically resembling TH2 cells. The signaling characteristics of these cells also are altered, in that they exhibit an elevated basal level of intracellular free calcium which fails to increase significantly with subsequent restimulation, reminiscent of the signaling characteristics of TH2 cells. "Anergized" TH0 clones thus share several functional, morphologic, and physiologic properties with cells of the TH2 phenotype, suggesting that TH2 cells may arise when TH0 cells are stimulated via the TCR complex in the absence of a putative costimulator molecule.
Insulin receptor substrate 1 is phosphorylated by the serine kinase activity of phosphatidylinositol 3-kinase (1994)

Insulin receptor substrate (IRS) 1, which is tyrosine phosphorylated in response to insulin, presents multiple serine/threonine phosphorylation sites. To search for a serine kinase activity towards IRS 1, immunoprecipitates from basal or stimulated 3T3-L1 adipocytes were used in an in vitro kinase assay. When IRS 1 was isolated from insulin-treated cells, serine phosphorylation of IRS 1 occurred, which we attribute to the kinase activity of the phosphatidylinositol 3-kinase (PI3-kinase). Importantly, in an in vitro reconstitution assay, an excess of the PI3-kinase subunit prevents this phosphorylation. Together, our results suggest that following insulin stimulation, PI3-kinase associates with IRS 1, allowing for its serine phosphorylation. This phosphorylation event could play a role in the modulation of insulin signalling.
Protein engineering of improved prolyl endopeptidases for celiac sprue therapy (2008)

Due to their unique ability to cleave immunotoxic gluten peptides endoproteolytically, prolyl endopeptidases (PEPs) are attractive oral therapeutic candidates for protecting celiac sprue patients from the toxic effects of dietary gluten. Enhancing the activity and stability of PEPs under gastric conditions (low pH, high pepsin concentration) is a challenge for protein engineers. Using a combination of sequence- and structure-based approaches together with machine learning algorithms, we have identified improved variants of the Sphingomonas capsulata PEP, a target of clinical relevance. Through two rounds of iterative mutagenesis and analysis, variants with as much as 20% enhanced specific activity at pH 4.5 and 200-fold greater resistance to pepsin were identified. Our results vividly reinforce the concept that conservative changes in proteins, especially in hydrophobic residues within tightly packed regions, can profoundly influence protein structure and function in ways that are difficult to predict entirely from first principles and must therefore be optimized through iterative design and analytical cycles. Incubation with whole wheat bread under simulated gastric conditions also suggests that some variants have pharmacologically significant improvements in gluten detoxification activity.
“Fast excitation” CID in a quadrupole ion trap mass spectrometer (2003)

Collision-induced dissociation (CID) in a quadrupole ion trap mass spectrometer is usually performed by applying a small amplitude excitation voltage at the same secular frequency as the ion of interest. Here we disclose studies examining the use of large amplitude voltage excitations (applied for short periods of time) to cause fragmentation of the ions of interest. This process has been examined using leucine enkephalin as the model compound and the motion of the ions within the ion trap simulated using ITSIM. The resulting fragmentation information obtained is identical with that observed by conventional resonance excitation CID. "Fast excitation" CID deposits (as determined by the intensity ratio of the a(4)/b(4) ion of leucine enkephalin) approximately the same amount of internal energy into an ion as conventional resonance excitation CID where the excitation signal is applied for much longer periods of time. The major difference between the two excitation techniques is the higher rate of excitation (gain in kinetic energy) between successive collisions with helium atoms with "fast excitation" CID as opposed to the conventional resonance excitation CID. With conventional resonance excitation CID ions fragment while the excitation voltage is still being applied whereas for "fast excitation" CID a higher proportion of the ions fragment in the ion cooling time following the excitation pulse. The fragmentation of the (M + 17H)(17+) of horse heart myoglobin is also shown to illustrate the application of "fast excitation" CID to proteins.
Nurbs curve and surface fitting and interpolation (1995)

In patients with a long cross-clamping period, using an oral CSA single dose before conducting CABG surgery, the risk of PMI could be decreased. Also, oral CsA has protective effect for CABG in diabetic patients with hypertension.
Retroviral Vectors for Gene Therapy (2010)

Since their first clinical trial 20 years ago, retroviral (gretroviral and lentiviral) vectors have now been used in more than 350 gene-therapy studies. Retroviral vectors are particularly suited for gene-correction of cells due to long-term and stable expression of the transferred transgene(s), and also because little effort is required for their cloning and production. Several monogenic inherited diseases, mostly immunodeficiencies, can now be successfully treated. The occurrence of insertional mutagenesis in some studies allowed extensive analysis of integration profiles of retroviral vectors, as well as the design of lentiviral vectors with increased safety properties. These new-generation vectors will enable us to continue the successful story of gene therapy, and treat more patients and even more complex diseases.
ILAE Official Report: A practical clinical definition of epilepsy (2014)

Epilepsy was defined conceptually in 2005 as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. This definition is usually practically applied as having two unprovoked seizures >24 h apart. The International League Against Epilepsy (ILAE) accepted recommendations of a task force altering the practical definition for special circumstances that do not meet the two unprovoked seizures criteria. The task force proposed that epilepsy be considered to be a disease of the brain defined by any of the following conditions: (1) At least two unprovoked (or reflex) seizures occurring >24 h apart; (2) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years; (3) diagnosis of an epilepsy syndrome. Epilepsy is considered to be resolved for individuals who either had an age-dependent epilepsy syndrome but are now past the applicable age or who have remained seizure-free for the last 10 years and off antiseizure medicines for at least the last 5 years. "Resolved" is not necessarily identical to the conventional view of "remission or "cure." Different practical definitions may be formed and used for various specific purposes. This revised definition of epilepsy brings the term in concordance with common use. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
An SDMA protocol for wireless multimedia networks (2002)

Efficient exploitation of spatial diversity is fundamentally important to resource critical wireless applications. A medium access protocol (MAC) for space division multiple access (SDMA) packet networks is proposed. The new protocol performs scheduling based on users' spatial characteristics and quality-of-service (QoS) requirements to achieve throughput multiplication and reduction of packet delays. The system's performance is evaluated under mixed audio and data traffic patterns and the results show that the new protocol can lead to a significant improvement in network performance.
Analysis of jitter due to power-supply noise in phase-locked loops (2002)

Phase-locked loops (PLL) in RF and mixed signal VLSI circuits experience supply noise which translates to a timing jitter. In this paper an analysis of the timing jitter due to the noise on the power supply rails is presented. Stochastic models of the power supply noise in VLSI circuits for different values of on-chip decoupling capacitances are presented first. This is followed by calculation of the phase noise of the voltage-controlled oscillator (VCO) in terms of the statistical properties of supply noise. Finally the timing jitter of the PLL is predicted in response to the VCO phase noise. A PLL circuit has been designed in 0.35 /spl mu/m CMOS process, and our mathematical model was applied to determine the timing jitter. Experimental results prove the accuracy of the predicted model.
Sterol mutants ofSaccharomyces cerevisiae: Chromatographic analyses (1977)

The sterols accumulated by ergosterol deficient mutants of the genes erg6, erg2, erg3, and erg5 (formerly po11, po12, po13, and po15) have been analyzed by gas liquid chromatography. Together with pure sterols obtained from the mutants, they were characterized on SE-30, OV-17, and OV-225. The effects of molecular structure on the retention characteristics of a range of C28 ergostane sterols have been studied. The double mutants obtained by crossing the single mutants were also analyzed and their sterols identified where possible. The effects of the erg mutations on the control of sterol biosynthesis in yeast are discussed.
<title>Analysis of the viewing zone of multiview autostereoscopic displays</title> (2002)

The viewing zone of a multi-view autostereoscopic display can be shown to be completely determined by four parameters: the width of the screen, the optimal distance of the viewer from the screen, the width over which an image can be seen across the whole screen at this optimal distance (the eye box width), and the number of views. A multi-view display's viewing zone can thus be completely described without reference to the internal implementation of the device. These results can be used to determine what can be seen from any position in front of the display. This paper presents a summary of the equations derived in an earlier paper. These equations allow us to analyze an autostereoscopic display, as specified by the above parameters. We build on this work by using the derived equations to analyze the configurations of the extant models of the Cambridge autostereoscopic display: 10' 8- and 16-view, 25' 28-view, 50' 15-view displays and an experimental 25' 7-view display.
A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model (2004)

Alzheimer disease (AD) is characterized by excessive deposition of amyloid beta-peptides (A beta peptides) in the brain. In the nonamyloidogenic pathway, the amyloid precursor protein (APP) is cleaved by the alpha-secretase within the A beta peptide sequence. Proteinases of the ADAM family (adisintegrin and metalloproteinase) are the main candidates as physiologically relevant alpha-secretases, but early lethality of knockout animals prevented a detailed analysis in neuronal cells. To overcome this restriction, we have generated transgenic mice that overexpress either ADAM10 or a catalytically inactive ADAM10 mutant. In this report we show that a moderate neuronal overexpression of ADAM10 in mice transgenic for human APP([V717I]) increased the secretion of the neurotrophic soluble alpha-secretase-released N-terminal APP domain (APPs alpha), reduced the formation of A beta peptides, and prevented their deposition in plaques. Functionally, impaired long-term potentiation and cognitive deficits were alleviated. Expression of mutant catalytically inactive ADAM10 led to an enhancement of the number and size of amyloid plaques in the brains of double-transgenic mice. The results provide the first in vivo evidence for a proteinase of the ADAM family as an alpha-secretase of APP, reveal activation of ADAM10 as a promising therapeutic target, and support the hypothesis that a decrease in alpha-secretase activity contributes to the development of AD.
Bringing Crystal Structures to Reality by Three-Dimensional Printing (2014)

The process of converting structural models derived from single-crystal X-ray diffraction experiments into physical models for the purposes of visualization/communication and collaboration by the use of three-dimensional (3D) printing techniques is described. Digital information regarding the relative positioning of atoms in a crystal structure is translated, using a suite of computer programs, into a 3D computer model of a solid form, corresponding to that information which can then be saved in a file format for 3D printing. These files are then used to produce to-scale physical models of the structural information using two different 3D printing methodologies.
DNA Hypermethylation Profiles in Squamous Cell Carcinoma of the Vulva (2008)

Gene silencing through promoter hypermethylation is a growing concept in the development of human cancers. In this study, we examined the contribution of aberrant methylation of promoter regions in methylation-prone tumor suppressors to the pathogenesis of vulvar cancer. Thirteen cell lines from 12 patients with squamous cell carcinoma of the vulva were evaluated for aberrant methylation status and gene copy number alterations, concomitantly, using the methylation-specific multiplex ligation-dependent probe amplification assay. Of the 22 tumor suppressor genes examined, aberrant methylation was observed for 9 genes: tumor protein p73 (TP73), fragile histidine triad (FHIT), von Hippel-Lindau (VHL), adenomatosis polyposis coli (APC), estrogen receptor 1 (ESR1), cyclin-dependent kinase inhibitor 2B (CDKN2B), death-associated protein kinase 1 (DAPK1), glutathione S-transferase pi (GSTP1), and immunoglobin superfamily, member 4 (IGSF4). The most frequently methylated genes included TP73 in 9 of 13 cell lines, and IGSF4, DAPK1, and FHIT in 3 of 13 cell lines. Methylation-specific polymerase chain reaction was performed for TP73 and FHIT to confirm aberrant methylation by methylation-specific multiplex ligation-dependent probe amplification. In the context of gene copy number and methylation status, both copies of the TP73 gene were hypermethylated. Loss or decreased mRNA expression of TP73 and IGSF4 by reverse transcription polymerase chain reaction confirmed aberrant methylation. Frequent genetic alterations of loss and gain of gene copy number included gain of GSTP1 and multiple endocrine neoplasia type 1 (MEN1), and loss of malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) and IGSF4 in over 50% of the squamous cell carcinoma of the vulva cell lines. These findings underscore the contribution of both genetic and epigenetic events to the underlying pathogenesis of squamous cell carcinoma of the vulva.
Hardware for dynamic quantum computing (2017)

We describe the hardware, gateware, and software developed at Raytheon BBN Technologies for dynamic quantum information processing experiments on superconducting qubits. In dynamic experiments, real-time qubit state information is fed back or fed forward within a fraction of the qubits' coherence time to dynamically change the implemented sequence. The hardware presented here covers both control and readout of superconducting qubits. For readout, we created a custom signal processing gateware and software stack on commercial hardware to convert pulses in a heterodyne receiver into qubit state assignments with minimal latency, alongside data taking capability. For control, we developed custom hardware with gateware and software for pulse sequencing and steering information distribution that is capable of arbitrary control flow in a fraction of superconducting qubit coherence times. Both readout and control platforms make extensive use of field programmable gate arrays to enable tailored qubit control systems in a reconfigurable fabric suitable for iterative development.
&#945;7 Nicotinic Receptor Agonists as Potential Therapeutic Drugs for Schizophrenia (2005)

Deficient inhibitory processing of the P50 auditory evoked potential is a measurable marker observed in schizophrenia. Several lines of evidence suggest that α7 nicotinic receptors (α7 nAChRs) play a critical role in P50 auditory sensory gating in the human brain. Similar to schizophrenic patients, DBA/2 mice spontaneously exhibit a deficit in inhibitory processing of the P20-N40 auditory evoked potential, which is a rodent analogue of the human P50 auditory evoked potential. Agonists at α7 nAChRs improve deficient inhibitory processing of the P20-N40 auditory gating potential in DBA/2 mice. In this article, we review the role of α7 nAChRs in the pathophysiology of schizophrenia, and α7 nAChR agonists and indirect agonists (5-hydroxytryptamine-3 (5-HT3) receptor antagonists, positive allosteric modulators (galantamine, 5-hydroxyindole, PNU-120596), FK960, FR236924) at α7 nAChRs as potential therapeutic drugs for the treatment of schizophrenia. In addition, we also discuss the role of kynurenic acid as an endogenous antagonist of α7 nAChRs in brain. Keywords: a nicotinic receptors, auditory gating, sensory gating, cognition, schizophrenia
Immunotherapy of Human Melanoma with Gene-Modified Tumor Cell Vaccines (1995)

The incidence of melanoma in the United States is increasing at a faster rate than that of any other cancer. The prognosis for metastatic disease is poor, and more effective treatments for disseminated disease are needed. Since melanoma is one of the more immunogenic tumors, strategies have focussed on immune recognition. In vitro studies suggest that potent tumor-specific cytotoxic T cells can be induced against human melanoma. Melanoma specific T-cell activation depends on appropriate presentation to the immune system of recently defined melanoma-associated antigens presented in the context of self-HLA gene products. Full T-cell activation requires the co- stimulation by B7-CD28 interactions at the T-cell surface and the elaboration of immune cytokines to promote T-cell growth. Data from animal models of tumor-specific immunization with tumor cells engineered to express immune cytokines or the B7 co-stimulatory molecule suggest that gene therapy for human melanoma may be an effective means to treat disseminated disease.
Design and development process of a humanoid robot upper body through experimentation (2005)

The development of a humanoid robot within the scope of the collaborative research centre 588 has the objective of creating a machine that closely cooperates with humans. This development area presents a new challenge to designers. In contrast to industrial robots - for which mechanical rigidity, precision and high velocities are primary requirements - the key aspects here are a lightweight construction, prevention of hazards to users, and a motion space that corresponds to that of human beings. In order to meet these requirements, the robot must have manlike appearance, motion spaces and dexterity. Additionally, its kinematics should be familiar to the user, its motions predictable, so as to encourage inexperienced persons to interact with the machine. The design of the body of a mechatronical robot, which is intended to imitate the mechanical and sensory properties of humans, can only be realized in an intense iterative process. This article gives insight into the development processes of exemplary mechanical constructions, presently worked on at the University of Karlsruhe (TH). The design of single body parts and their improvement are presented. Details - why these improvements lead to a higher performance of the complete system - are discussed. This is a status report on current development in this area.
The Oxidation of Thebaine with m‐Chloroperbenzoic Acid. Studies in the (+)‐Morphinan Series. III (1977)

Zur Oxydation von Thebain mit m ‐Chlorperbenzoesäure, III Die Oxydation von Thebain ( 1 ) mit m ‐Chlorperbenzoesäure ist stark abhängig von den gewählten Reaktionsbedingungen. In unserem Fall wird neben 14‐Hydroxy‐codeinon ( 2 ) auch das bekannte, mono‐acetylierte Diol 3 erhalten. Die Rückführung von 3 in 2 und die Verknüpfung mit dem bekannten Ketodiol 5 , über das bisher nicht beschriebene 8, 14‐Dihydroxydihydrothebain ( 4 ) wird gezeigt.
Trends in the Leading Causes of Death in the United States, 1970-2002 (2005)

The absolute number of deaths and age at death continue to increase in the United States. These temporal trends have major implications for health care and health care costs in an aging population.
Conotoxin GI: disulfide bridges, synthesis, and preparation of iodinated derivatives (1984)

The 13 amino acid toxic peptide from the marine snail Conus geographus, conotoxin GI, blocks the acetylcholine receptor at the neuromuscular junction. In this report, we describe a method for analyzing disulfide bonding in nanomole amounts of small cystine-rich peptides. The procedure involves partial reduction and a double-label alkylation of cysteine residues. Using this method, we show that the natural conotoxin GI has a (2-7, 3-13) disulfide configuration. The structure of conotoxin GI has been confirmed by chemical synthesis. The preparation and purification of molecularly homogeneous, iodinated derivatives of this toxin are also described. All derivatives, including the [diiodohistidine,diiodotyrosine]conotoxin GI, retained at least half of the biological activity of unmodified toxin. Since the tetraiodinated toxin, which is greater than 25% by weight iodine, retains considerable toxicity, unmodified histidine and tyrosine residues in conotoxin GI are not crucial for biological activity.
Vaccination with CD47 deficient tumor cells elicits an antitumor immune response in mice (2020)

Cancer cells are poorly immunogenic and have a wide range of mutations, which makes them unsuitable for use in vaccination treatment. Here, we show that elimination of CD47, a ligand for the myeloid cell inhibitory receptor SIRPα, from tumor cells by genetic deletion or antibody blocking, significantly improves the effectiveness of the immune response to tumour cells. In both solid and hematopoietic mouse tumor models, vaccination with tumor cells or tumor antigen-expressing cells, that lack CD47 or were pre-coated with anti-CD47 antibodies, achieved an antitumor immune response. The efficacy of this approach was synergistically enhanced when used in combination with anti-PD-1 antibodies. The induction of antitumor responses depends on SIRPα<sup>+</sup>CD11c<sup>+</sup> DCs, which exhibit rapid expansion following introduction of CD47-deficient tumor cells. Our results indicate that CD47-deficient whole tumor cells can induce antitumor responses.