gebhart/patrepeval huggingface dataset:
IκBβ is an essential co-activator for LPS-induced IL-1β transcription in vivo (2010)

Inhibitor of κB (IκB) β (IκBβ) represents one of the major primary regulators of NF-κB in mammals. In contrast to the defined regulatory interplay between NF-κB and IκBα, much less is known about the biological function of IκBβ. To elucidate the physiological role of IκBβ in NF-κB signaling in vivo, we generated IκBβ-deficient mice. These animals proved to be highly refractory to LPS-induced lethality, accompanied by a strong reduction in sepsis-associated cytokine production. In response to LPS, IκBβ is recruited to the IL-1β promoter forming a complex with the NF-κB subunits RelA/c-Rel required for IL-1β transcription. Further transcriptome analysis of LPS-stimulated wild-type and IκBβ-deficient BM-derived macrophages revealed several other genes with known regulatory functions in innate immunity arguing that a subset of NF-κB target genes is under control of IκBβ. Collectively, these findings provide an essential proinflammatory role for IκBβ in vivo, and establish a critical function for IκBβ as a transcriptional coactivator under inflammatory conditions.
Decomposed symbolic forward traversals of large finite state machines (1996)

BDD-based symbolic traversals are the state-of-the-art technique for reachability analysis of finite state machines. They are currently limited to medium-small circuits for two reasons: BDD peak size during image computation and BDD explosion for state space representation. Starting from these limits, this paper presents a technique that decomposes the search space decreasing the BDD peak size and the number of page faults during image computation. Results of intermediate computations and large BDDs are efficiently stored in the secondary memory. A decomposed traversal that allows exact explorations of state spaces is obtained. Experimental results show that this approach is particularly effective on the larger MCNC, ISCAS'89, and ISCAS'89-addendum circuits.
A NEW CONTINUOUS MEASURING METHOD OF WHEEL/RAIL CONTACT FORCES (1994)

Wheel load fluctuation of considerable amplitude is almost always observed on Shinkansen vehicles running at high speed. From the acceleration measured on the axlebox, the frquency of this fluctuation is estimated to be approximately 50 to 70 Hz. As continuous outputs of wheel load can not be obtained by the conventional measuring method, it is difficult to investigate such a high frequency phenomenon exactly. A new method of continuous measuring the forces and derailment quotients up to about 100 Hz has been developed, using the strain of a wheel. In the running test on Shinkansen, it was confirmed by using this method that the wheel load fluctuation was related to the axlebox acceleration generated through small irregularity on the rail surface.
Beyond Nondiscrimination: AT&T Mobility LLC v. Concepcion and the Further Federalization of U.S. Arbitration Law (2012)

The article presents information on the court case of AT&T Mobility LLC v. Concepcion that was decided by the U.S. Supreme Court and which questioned the preemption of state law and the Federal Arbitration Act related to the enforcement of arbitration agreement. The unconscionability doctrine, the case law related to arbitration and the contract law is discussed. The interpretation of arbitration law is also discussed.
Caries and periodontal disease of the elderly in Pomerania, Germany: results of the Study of Health in Pomerania (2004)

It seems therefore that in this population, the major oral health concern is related to caries and the small number of teeth retained among the dentate subjects.
Evolution from point to extended defects in ion implanted silicon (1997)

We present a quantitative study of the evolution of point defects into clusters and extended defects in ion-implanted Si. Deep level transient spectroscopy (DLTS) measurements are used to identify and count the electrically active defects in the damaged region produced by Si ion implantation at energies of 145 keV–2 MeV, and fluences from 1×108 to 5×1013 Si/cm2. Analyses of silicon annealed in the temperature range 100–680 °C allow us to monitor the transition from simple point defects to defect clusters and extended defects that occur upon increasing the ion fluence and the annealing temperature. At low doses, &lt;1010 Si/cm2, only about 2% of the Frenkel pairs generated by the ion beam escape recombination and are stored into an equal number of interstitial and vacancy-type point defects. Thermal treatments produce a concomitant annealing of interstitial and vacancy-type defects until, at temperatures above 350 °C, only two to three interstitial-type defects per ion are left, and the DLTS spectra contain signatures of second-order point defects. Interstitial clusters at Ev+0.29 and Ev+0.48 eV are found to dominate the residual damage of silicon implanted at higher fluences, 1×1012–7×1013 Si/cm2, and at annealing temperatures, T⩾600 °C. These interstitial clusters have point defect capture kinetics and are not observable in transmission electron microscopy (TEM), suggesting that they are smaller than ≈50 Å. Finally, for silicon implanted at higher Si doses, ⩾5×1013 Si/cm2, thermal treatments at 680 °C result in a strong decrease in the concentration of the interstitial cluster signatures and in the introduction of a different DLTS signal, Ev+0.50 eV, which exhibits logarithmic rather than exponential carrier capture kinetics, a feature typical of an extended defect. Comparison of the formation and dissolution of this extended defect signature with TEM analyses indicates that this level is a signature of the rodlike {311} defects that are known to store the interstitials responsible for transient enhanced diffusion. These results suggest that the small interstitial clusters are either the precursors of the {311} defects or that they compete with {311} defects as sinks for self-interstitials.
Time-Decaying Bloom Filters for Data Streams with Skewed Distributions (2005)

Bloom Filters are space-efficient data structures for membership queries over sets. To enable queries for multiplicities of multi-sets, the bitmap in a Bloom Filter is replaced by an array of counters whose values increment on each occurrence. In a data stream model, however, data items arrive at varying rates and recent occurrences are often regarded as more significant than past ones. In most data stream applications, it is critical to handle this "time-sensitivity". Furthermore, data streams with skewed distributions are common in many emerging applications, e.g., traffic engineering and billing, intrusion detection, trading surveillance and outlier detection. For such applications, it is inefficient to allocate counters of uniform size to all buckets. In this paper, we present Time-decaying Bloom Filters (TBF), a Bloom Filter that maintains the frequency count for each item in a data stream, and the value of each counter decays with time. For data streams with highly skewed distributions, we proposed further optimization by allowing dynamically allocating free counters to the "large" items. We performed preliminary experiments to verify the optimization.
A soybean trypsin inhibitor. Crystallization and x-ray crystallographic study. (1977)

Five trypsin and alpha-chymotrypsin inhibitors which have low molecular weights (ranging from 6800 to 8600) and are present in soybean seeds of the Tracy variety have been isolated and purified, and single crystals which give x-ray diffraction data beyond 3-A spacings have been obtained from one of them. The trypsin inhibitor crystallizes in a monoclinic unit cell of symmetry P2(1) and dimensions a = 25.919(7) A, b = 43.23(1) A, c = 19.905(5) A, and beta = 103.63(2) degrees. The assymmetric unit contains 1 molecule of molecular weight 6800. The crystal, which has been found to be unusually stable to x-radiation, has solvent content of approximately 26% by volume.
New Hemolysin (γ) Produced by <i>Escherichia coli</i> (1969)

A new hemolysin (gamma) of Escherichia coli, active in the absence of viable bacteria, has been recognized in mutants resistant to nalidixic acid. Nalidixic acid affects either the production or release of the hemolysin.
Synaptic synthesis of the fragile X protein: Possible involvement in synapse maturation and elimination (1999)

Fragile X mental retardation syndrome results from the absence of or a defect in the protein (FMRP) encoded by the FMR1 gene. FMRP is found in dendrites and synapses as well as in the neuronal cell soma and nucleus, and although it is known to bind to RNA, the function of the protein in neurons is not known. We have studied activity-dependent changes in postsynaptically localized protein translation in central nervous system neurons. We find that FMRP is one of the proteins produced at synapses following stimulation of metabotropic glutamate receptors. We have also observed that Fragile X knockout mice, like human Fragile X patients, have excess numbers of long, thin, immature-appearing dendritic processes. Together, these findings suggest that FMRP plays a role in the process whereby synaptic activity during development results in structural and functional maturation of the synapse. We hypothesize that synaptic synthesis of FMRP may be essential for activity-based synapse maturation and elimination, a key process in normal brain development.
Classical and Quantum Information Channels in Protein Chain (2006)

Investigation of the properties of peptide plane in protein chain from both classical and quantum approach is presented. We calculated interatomic force constants for peptide plane and hydrogen bonds between peptide planes in protein chain. On the basis of force constants, displacements of each atom in peptide plane, and time of action we found that the value of the peptide plane action is close to the Planck constant. This indicates that peptide plane from the energy viewpoint possesses synergetic classical/quantum properties. Consideration of peptide planes in protein chain from information viewpoint also shows that protein chain possesses classical and quantum properties. So, it appears that protein chain behaves as a triple dual system: (1) structural - amino acids and peptide planes, (2) energy - classical and quantum state, and (3) information - classical and quantum coding. Based on experimental facts of protein chain, we proposed from the structure-energy-information viewpoint its synergetic code system.
Development of a High-Throughput Assay for Screening of γ-Secretase Inhibitor with Endogenous Human, Mouse or Drosophila γ-Secretase (2009)

Selective lowering of amyloid-beta levels with small-molecule gamma-secretase inhibitors is a promising therapeutic approach for Alzheimer's disease. In this work, we developed a high throughput assay for screening of gamma-secretase inhibitors with endogenous gamma-secretase and a fluorogenic substrate. The IC(50) values of known gamma-secretase inhibitors generated with this method were comparable with reported values obtained by other methods. The assay was optimized and applied to a small-scale screening of 1,280 compounds. The discovery of several new inhibitors warrants further investigation. This assay was also proven to be easily adopted to test compounds for drosophila and mouse gamma-secretase, which could be very useful to assess compounds activity against gamma-secretase from different species before the in vivo test in animal models.
DC-20 GHz MMIC multi-bit digital attenuators with on-chip TTL control (2002)

Broadband digital attenuators (DC to 20 GHz) featuring on-chip translators for direct TTL control have been designed and fabricated with the ITT multifunction self-aligned gate process for MMIC (monolithic microwave integrated circuit) insertion into advanced EW (electronic warfare) systems. The MMIC digital attenuators provide exceptional performance, with through-state insertion losses of less than 5 dB for a 4-b attenuator, 4 dB for a 2-b attenuator, 2 dB for a switched attenuator, and normalized mean attenuation accuracies within 0.5 dB from DC to 20 GHz for each attenuator. When cascaded, this set of digital attenuators provides the high-dynamic range (>75 dB) required for advanced EW system applications.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Biologically active γ-lactams: synthesis and natural sources (2016)

The γ-lactam moiety is present in a large number of natural and non-natural biologically active compounds. The range of biological activities covered by these compounds is very broad. Functionalized γ-lactams are thus of high interest and have great potential in medicinal chemistry. This review provides a description of the title compounds by focusing on their synthesis, natural sources and biological activities.
Human recombinant tissue transglutaminase ELISA: an innovative diagnostic assay for celiac disease (2000)

OBJECTIVE: Tissue transglutaminase is the autoantigen recognized by the sera of celiac patients. An enzyme-linked immunosorbent assay (ELISA) based on guinea-pig tissue transglutaminase was recently used to measure serum tissue transglutaminase antibodies for the diagnosis of celiac disease. We determine the sensitivity and specificity of an ELISA test based on the use of human recombinant transglutaminase, compared with the guinea pig transglutaminase ELISA and IgA antiendomysium antibodies. METHODS: Serum samples were tested from 65 patients with intestinal biopsy proven celiac disease, from 10 patients with Crohn's disease, and from 150 healthy blood donors. RESULTS: Human transglutaminase ELISA identified 64 of 65 celiac patients, whereas the guinea pig transglutaminase ELISA and IgA antiendomysium antibodies identified 58 of 65 and 60 of 65 subjects, respectively. The three tests showed comparable specificity. CONCLUSIONS: These results proved that the human tissue transglutaminase-based ELISA represents a cost-effective strategy for identifying both symptomatic and atypical forms of celiac disease and could mean that intestinal biopsy need no longer be the gold standard for diagnosing this clinical condition. Furthermore, early identification and treatment of patients with celiac disease in an outpatient setting could have significant implications for reducing long-term morbidity and can produce major savings in future health care costs.
New Metrics for Evaluating Viral Respiratory Pathogenesis (2020)

Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was used to directly measure changes in pulmonary function during two respiratory viral infections. This methodology closely tracked with traditional pathogenesis metrics, distinguished both virusand dose-specific responses, and identified long-term respiratory changes following both SARS-CoV and Influenza A Virus infection. Together, the work highlights the utility of examining respiratory function following infection in order to fully understand viral pathogenesis.
Structure and biological activity of a 1,3-beta-D-glucan-binding protein in crustacean blood. (1994)

The prophenoloxidase activating system, an enzyme cascade present in arthropod blood, has been shown to be involved in defense and recognition reactions. This system is converted to its active form by fungal 1,3-beta-D-glucans through binding to a plasma protein, a 1,3-beta-D-glucan-binding protein. Here the molecular cloning and carbohydrate composition of the 1,3-beta-D-glucan-binding protein from the freshwater crayfish Pacifastacus leniusculus are reported. It is also demonstrated that this protein can act as an opsonin, stimulating phagocytic uptake of yeast particles by isolated blood cells. The deduced amino acid sequence of 1,339 residues shows no significant similarity to proteins with similar functions in other animals such as the mannan-binding and lipopolysaccharide-binding proteins present in mammals. However, a short sequence motif with similarity to the active site of microbial 1,3-1,4-beta-D-glucan 4-glucanohydrolases was found to occur twice in the 1,3-beta-D-glucan-binding protein.
Biodefense Hampered by Inadequate Tests (2001)

ANTHRAXProdded by the unnerving events of the past 4 weeks, government and industry labs are stepping up efforts to develop tests that can detect the presence of anthrax and tell whether a person is infected. Experts predict a tremendous push to develop many new tools in the coming years. Indeed, companies at the forefront of pathogen detection find themselves among the few that are doing very well since 11 September.
Two Regions within the Amino-Terminal Half of APOBEC3G Cooperate To Determine Cytoplasmic Localization (2008)

APOBEC3G limits the replication of human immunodeficiency virus type 1, other retroviruses, and retrotransposons. It localizes predominantly to the cytoplasm of cells, which is consistent with a model wherein cytosolic APOBEC3G packages into assembling virions, where it exerts its antiviral effect by deaminating viral cDNA cytosines during reverse transcription. To define the domains of APOBEC3G that determine cytoplasmic localization, comparisons were made with APOBEC3B, which is predominantly nuclear. APOBEC3G/APOBEC3B chimeric proteins mapped a primary subcellular localization determinant to a region within the first 60 residues of each protein. A panel of 25 APOBEC3G mutants, each with a residue replaced by the corresponding amino acid of APOBEC3B, revealed that several positions within this region were particularly important, with Y19D showing the largest effect. The mislocalization phenotype of these mutants was only apparent in the context of the amino-terminal half of APOBEC3G and not the full-length protein, suggesting the existence of an additional localization determinant. Indeed, a panel of five single amino acid substitutions within the region from amino acids 113 to 128 had little effect by themselves but, in combination with Y19D, two substitutions-F126S and W127A-caused full-length APOBEC3G to redistribute throughout the cell. The critical localization-determining residues were predicted to cluster on a common solvent-exposed surface, suggesting a model in which these two regions of APOBEC3G combine to mediate an intermolecular interaction that controls subcellular localization.
Expression of the tumor necrosis factor receptor—associated factors 1 and 2 and regulation of the nuclear factor—kB antiapoptotic activity in human gliomas (2005)

Data in this study confirm the upregulation of NF-kappaB in gliomas and reveal a correlation between levels of this transcription factor and tumor grade. A constitutive expression of TRAF1, TRAF2, and TANK/I-TRAF in human gliomas was documented. These proteins are involved in the intracellular signal transduction of the TNFR superfamily and in the control of NF-kappaB expression and its antiapoptotic activity.
Age differences in health care spending, fiscal year 1976. (1977)

Of the $120.4 billion spent by the Nation for personal health care in fiscal year 1976, 29% was spent for those aged 65 or older, 15% for those under age 19, and the remaining 56% for those aged 19-64. The average health bill reached $1,521 for the aged, $547 for the intermediate age group, and $249 for the young. Public funds financed 68% of the health expenses of the aged with Medicare and Medicaid together accounting for 59%. Private sources paid 74% of the health expenses of the young and 70% of the expenses of those aged 19-64. Third-party payments met 65% of the health expenditures of all those under age 65.
Sequential Phosphorylation of Smoothened Transduces Graded Hedgehog Signaling (2011)

The correct interpretation of a gradient of the morphogen Hedgehog (Hh) during development requires phosphorylation of the Hh signaling activator Smoothened (Smo); however, the molecular mechanism by which Smo transduces graded Hh signaling is not well understood. We show that regulation of the phosphorylation status of Smo by distinct phosphatases at specific phosphorylated residues creates differential thresholds of Hh signaling. Phosphorylation of Smo was initiated by adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase (PKA) and further enhanced by casein kinase I (CKI). We found that protein phosphatase 1 (PP1) directly dephosphorylated PKA-phosphorylated Smo to reduce signaling mediated by intermediate concentrations of Hh, whereas PP2A specifically dephosphorylated PKA-primed, CKI-phosphorylated Smo to restrict signaling by high concentrations of Hh. We also established a functional link between sequentially phosphorylated Smo species and graded Hh activity. Thus, we propose a sequential phosphorylation model in which precise interpretation of morphogen concentration can be achieved upon versatile phosphatase-mediated regulation of the phosphorylation status of an essential activator in developmental signaling.
WINTHER: An international study to select rational therapeutics based on the analysis of matched tumor and normal biopsies in subjects with advanced malignancies. (2017)

TPS11625 Background: Today, personalized cancer medicine implies matching the patient’s tumor genomic characteristics with molecularly and immune targeted agents. Although there are an increasing number of DNA aberrations that can now be matched to a cognate therapy, some patients do not display such druggable oncogene drivers. Methods: WINTHER is an open non-randomized study involving 6 cancer centers in France, Spain, Israel, Canada and USA applying genomic and also transcriptomic assays to guide treatment decisions. The novelty of the WINTHER approach lies in the use of tumor and matched normal tissue biopsies together and an algorithm for predicting efficacy of therapies. The aim is to provide a rational therapeutic choice for all of the patients enrolled in the study whether or not they harbor actionable DNA alterations. The study endpoint is the comparison of the progression-free-survival (PFS) under the WINTHER selected therapy to the PFS of the last therapeutic line. Patients included have refractory metastatic cancer of any histological type, with at least one prior therapeutic regimen and performance status of 0 to 1. Patients who have received a matched treatment based on a molecular anomaly as their immediate prior therapy were excluded. After consent, patients undergo a tumor and histologically-matched normal tissue biopsy. Extracted DNA and RNA of both tumor and normal from frozen tissues at the local center under common standard operating procedures are sent to centralized laboratories for omics investigations. DNA is investigated at Foundation Medicine Inc. and RNA at Gustave Roussy using Agilent technology. For RNA, the WINTHER algorithm is applied on the differential RNA expression data between tumor and normal tissues and establishes the list of drugs with the presumed higher score of efficacy for each patient. Patients with actionable genomic events enter in ARM A, and patients without any druggable anomaly of the DNA enter in ARM B and are treated using the WINTHER algorithm RNA-based treatment decision tool. To date, the trial has recruited 303 patients. Clinical trial information: NCT01856296.
Fracture toughness and crack-resistance curve behavior in metallic glass-matrix composites (2009)

Nonlinear-elastic fracture mechanics methods are used to assess the fracture toughness of bulk metallic glass (BMG) composites; results are compared with similar measurements for other monolithic and composite BMG alloys. Mechanistically, plastic shielding gives rise to characteristic resistance-curve behavior where the fracture resistance increases with crack extension. Specifically, confinement of damage by second-phase dendrites is shown to result in enhancement of the toughness by nearly an order of magnitude relative to unreinforced glass.