gebhart/patrepeval huggingface dataset:
Molecular Pathways: Clinical Applications and Future Direction of Insulin-like Growth Factor-1 Receptor Pathway Blockade (2015)

The IGF1R signaling pathway is a complex and tightly regulated network that is critical for cell proliferation, growth, and survival. IGF1R is a potential therapeutic target for patients with many different malignancies. This brief review summarizes the results of clinical trials targeting the IGF1R pathway in patients with breast cancer, sarcoma, and non-small cell lung cancer (NSCLC). Therapeutic agents discussed include both monoclonal antibodies to IGF1R (dalotuzumab, figitumumab, cixutumumab, ganitumab, R1507, AVE1642) and newer IGF1R pathway targeting strategies, including monoclonal antibodies to IGF1 and IGF2 (MEDI-573 and BI 836845) and a small-molecule tyrosine kinase inhibitor of IGF1R (linsitinib). The pullback of trials in patients with breast cancer and NSCLC based on several large negative trials is noted and contrasted with the sustained success of IGF1R inhibitor monotherapy in a subset of patients with sarcoma. Several different biomarkers have been examined in these trials with varying levels of success, including tumor expression of IGF1R and its pathway components, serum IGF ligand levels, alternate pathway activation, and specific molecular signatures of IGF1R pathway dependence. However, there remains a critical need to define predictive biomarkers in order to identify patients who may benefit from IGF1R-directed therapies. Ongoing research focuses on uncovering such biomarkers and elucidating mechanisms of resistance, as this therapeutic target is currently being analyzed from the bedside to bench.
A Simplified Ordering Scheme Minimizing Average BER for MIMO Systems with Adaptive Modulation (2005)

This paper proposes a new detection ordering scheme, which minimizes average error rate of the MIMO system with per antenna rate control. This paper shows an optimal scheme minimizing average error rate expressed by the Q function, and simplifies the optimal scheme by using the minimum equivalent SINR scaled by modulation indices, based on approximated error rate. In spite of reduced complexity, the simplified scheme demonstrates the almost same performance as the optimal scheme. Owing to the diversity of detection ordering, the proposed scheme has over 2 dB higher SNR gain at the BER of 10 -3 than the existing ordering schemes in balanced array size systems.
An evolutionary adaptive neuro-fuzzy inference system for estimating field penetration index of tunnel boring machine in rock mass (2021)

Field penetration index (FPI) is one of the representative key parameters to examine the tunnel boring machine (TBM) performance. Lack of accurate FPI prediction can be responsible for numerous disastrous incidents associated with rock mechanics and engineering. This study aims to predict TBM performance (i.e. FPI) by an efficient and improved adaptive neuro-fuzzy inference system (ANFIS) model. This was done using an evolutionary algorithm, i.e. artificial bee colony (ABC) algorithm mixed with the ANFIS model. The role of ABC algorithm in this system is to find the optimum membership functions (MFs) of ANFIS model to achieve a higher degree of accuracy. The procedure and modeling were conducted on a tunnelling database comprising of more than 150 data samples where brittleness index (BI), fracture spacing, α angle between the plane of weakness and the TBM driven direction, and field single cutter load were assigned as model inputs to approximate FPI values. According to the results obtained by performance indices, the proposed ANFIS_ABC model was able to receive the highest accuracy level in predicting FPI values compared with ANFIS model. In terms of coefficient of determination (R2), the values of 0.951 and 0.901 were obtained for training and testing stages of the proposed ANFIS_ABC model, respectively, which confirm its power and capability in solving TBM performance problem. The proposed model can be used in the other areas of rock mechanics and underground space technologies with similar conditions.
Extradural Compression of Sensorimotor Cortex: A Useful Model for Studies on Ischemic Brain Damage and Neuroprotection (2002)

Behavioral and morphological changes were examined for up to 9 days after moderate cerebral ischemia caused by slow compression of a specific brain area in the sensorimotor cortex of Sprague-Dawley rats. Functional deficits after the cerebral ischemia were assessed by daily beam-walking tests, whereas morphological changes were verified using Nissl staining on day 1, 2, 3, 5, and 9, respectively. Rats exposed to cerebral ischemia displayed impaired beam walking performance. Mild hypothermia prevented both the compression-produced functional deficits and the brain damage. Younger (5 weeks) animals showed less neurological deficits than older (9 weeks) animals. Histological examination revealed a pronounced increase in the number of injured pyramidal neurons from day 1 to day 3 in the primarily damaged brain region. Between day 3 and day 5, the number of injured cells remained constant, whereafter there was a slow decline of thionin-positive neurons as examined on day 9. The noncompetitive NMDA receptor antagonist, dizocilpine (MK-801; 3 mg/kg, i.p.), did not alter the neurological impairment on day 1, but improved thereafter the rate of functional recovery and reduced the number of damaged cells. The AMPA receptor antagonist, LY326325 (15 or 30 mg/kg; i.p.), dose-dependently diminished the neurological deficits on day 1, enhanced the rate of recovery, and reduced the number of injured neurons over time. Our data suggest that short-lasting extradural compression of a well-defined brain area in the sensorimotor cortex is a highly reproducible model with a high success rate for the study of functional and morphological consequences after cerebral ischemia as well as for the evaluation of the therapeutic potential of novel, neuroprotective pharmacological agents.
Adaptive Responses as Mechanisms of Resistance to BRAF Inhibitors in Melanoma (2019)

<b>:</b> The introduction of v-raf murine sarcoma viral oncogene homolog B (BRAF) inhibitors in melanoma patients with BRAF (V600E) mutations has demonstrated significant clinical benefits. However, rarely do tumours regress completely. Frequently, the reason for this is that therapies targeting specific oncogenic mutations induce a number of intrinsic compensatory mechanisms, also known as adaptive responses or feedback loops, that enhance the pro-survival and pro-proliferative capacity of a proportion of the original tumour population, thereby resulting in tumour progression. In this review we will summarize the known adaptive responses that limit BRAF mutant therapy and discuss potential novel combinatorial therapies to overcome resistance.
Inhibition of separated forms of cyclic nucleotide phosphodiesterase from pig coronary arteries by 1,3-disubstituted and 1,3,8-trisubstituted xanthines (1981)

A series of xanthines with varied substituents in the 1, 3, and 8 positions were prepared in an attempt to understand the structure--activity relationship for alkylxanthines as inhibitors of two different forms of cyclic nucleotide phosphodiesterase. Polar substituents on the 1 or 3 position of the xanthine reduced the potency of the xanthines to inhibit both the calmodulin-sensitive and the "cyclic AMP specific" forms of phosphodiesterase. Polar substituents on the 8 position of the xanthine, other than a carboxylic acid, increased the potency to inhibit the calmodulin-sensitive form of phosphodiesterase, if they were capable of donating electrons to the xanthine nucleus. On the other hand, any substituent in the 8 position larger than H reduced the potency of the xanthines to inhibit the cyclic AMP specific form of phosphodiesterase. Topographical maps of the active sites of the two forms of phosphodiesterase are presented in summary.
High performance silver ohmic contacts to YBa2Cu3O6+<i>x</i> superconductors (1988)

Silver-YBa2Cu3O6+x superconductor ohmic contacts with specific contact resistance on the order of 10−8 Ω cm2 have been demonstrated. Alloying the contacts in O2 at 500 °C enhances the contact conductivity by two orders of magnitude.
Thioredoxin Ameliorates Cutaneous Inflammation by Regulating the Epithelial Production and Release of Pro-Inflammatory Cytokines (2013)

Human thioredoxin-1 (TRX) is a 12-kDa protein with redox-active dithiol in the active site -Cys-Gly-Pro-Cys-. It has been demonstrated that systemic administration and transgenic overexpression of TRX ameliorate inflammation in various animal models, but its anti-inflammatory mechanism is not well characterized. We investigated the anti-inflammatory effects of topically applied recombinant human TRX (rhTRX) in a murine irritant contact dermatitis (ICD) induced by croton oil. Topically applied rhTRX was distributed only in the skin tissues under both non-inflammatory and inflammatory conditions, and significantly suppressed the inflammatory response by inhibiting the production of cytokines and chemokines, such as TNF-α, Il-1β, IL-6, CXCL-1, and MCP-1. In an in vitro study, rhTRX also significantly inhibited the formation of cytokines and chemokines produced by keratinocytes after exposure to croton oil and phorbol 12-myristate 13-acetate. These results indicate that TRX prevents skin inflammation via the inhibition of local formation of inflammatory cytokines and chemokines. As a promising new approach, local application of TRX may be useful for the treatment of various skin and mucosal inflammatory disorders.
Chemical and microbiological solubilization of silicates (1991)

Abstract The solubilization of silicates was investigated using kaolin and quartz sand as model substances. The mineral solubilization was studied in the concentration of solubilized Si and Al. The chemical leaching of the silicates was carried out using inorganic and organic acids as well as sodium hydroxide. The process was more effective in the alkine than in the acid pH range. In the acid medium, oxalic acid showed maximum acidity and a tendency to form complex structures, especially with aluminium, and was most effective in leaching. The microbiological influence on solubilization reactions was tested using a number of microorganisms among them acid, alkali and slime‐forming species. The highest leaching activity was observed in the case of Thiobacillus thiooxidans , whereas the heterotrophic microorganisms (among them Bacillus mucilaginosus ) did not exercise a sollubilizing effect on the silicates. X‐ray phase analysis of leached kaolin samples did not show any differences from the non‐leached mineral.
Do Formulation Differences Alter Abuse Liability of Methylphenidate? (2007)

The primary objective of this study was to determine if the abuse liability of methylphenidate is governed by formulation differences that affect rates of drug delivery. In this double-blind, placebo-controlled, randomized, crossover study, subjects with a history of recreational drug use received single oral doses of placebo, 60 mg of immediate-release methylphenidate (IR) and 108 mg of extended-release methylphenidate (osmotic release oral system [OROS]). Over 24 hours after dosing, blood was collected to determine plasma concentrations of methylphenidate, and subjects completed subjective assessments of abuse liability (Addiction Research Center Inventory, Drug Rating Questionnaire-Subject, and Subjective Drug Value). The abuse-related subjective effects of IR and OROS methylphenidate were statistically significantly different from placebo, confirming the overall validity of the study. Although a higher dose of OROS methylphenidate was used compared with IR methylphenidate (108 mg vs 60 mg), subjective effects were consistently lower for OROS compared with IR methylphenidate (statistically significant for 3 of 6 measures of positive effects), particularly at early time points. In general, pharmacokinetic-pharmacodynamic parameters were correlated from a poor to modest degree, with greater correlations observed for IR methylphenidate. In addition, a post hoc "qualification" method was developed, which demonstrated that pharmacological qualification might improve the assessment of subjective effects. Although requiring epidemiological confirmation, the results suggest that OROS methylphenidate, with its characteristic slow ascending plasma concentration profile, may have lower abuse potential. This conclusion is reflected by lower subjective responses during early hours as compared with the IR formulation with its rapid drug delivery and accompanying greater subjective effects.
Fundamental electro-optic limitations of thin-film lithium niobate microring modulators (2020)

We investigate the impact of waveguide curvature on the electro-optic efficiency of microring resonators in thin-film X-cut or Y-cut lithium niobate (in-plane extraordinary axis) and derive explicit relations on the response. It is shown that such microring modulators have a fundamental upper bound on their electro-optic performance (∼50% filling factor) which corresponds to a specific arrangement of metal electrodes surrounding the microring and yields nearly identical results for X-cut and Y-cut designs. We further show that this limitation does not exist (i.e., 100% filling factor is possible) with Z-cut microring modulators or can be circumvented (i.e., ∼100% filling factor is possible) in X-cut and Y-cut modulators that use a race-track configuration with segmented electrodes. Comparison of our analytical results with multiphysics simulations and measured electro-optic efficiencies of microring resonators in the literature demonstrates the validity and accuracy of our approach.
A uniform integration of higher-order reasoning and external evaluations in answer-set programming (2005)

We introduce HEX programs, which are nonmono-tonic logic programs admitting higher-order atoms as well as external atoms, and we extend the well-known answer-set semantics to this class of pro-grams. Higher-order features are widely acknowl-edged as useful for performing meta-reasoning, among other tasks. Furthermore, the possibility to exchange knowledge with external sources in a fully declarative framework such as Answer-Set Programming (ASP) is nowadays important, in par-ticular in view of applications in the Semantic Web area. Through external atoms, HEX programs can model some important extensions to ASP, and are a useful KR tool for expressing various applications. Finally, complexity and implementation issues for a preliminary prototype are discussed. 1
Perpetual Contract NFT as Collateral for DeFi Composability (2022)

Ethereum and its standardized token interface have formed decentralized finance (DeFi), an open financial system based on blockchain smart contracts. The DeFi ecosystem has become richer with the introduction of DeFi composability projects, such as Lido finance and Curve finance. DeFi composability denotes the concatenation of DeFi services in which each DeFi service locks assets as collateral and gives another asset as liquidity of locked assets to providers. Providers use the tokens given for other concatenated DeFi services, such as lending, decentralized exchanges (DEXs), and derivatives. The DeFi ecosystem uses ERC-20 tokens which can represent the value of an asset. ERC-721 non-fungible tokens (NFTs) are not widely adopted in DeFi, since they represent rights to an asset and are not considered appropriate for valuation. In this paper, we propose a new concept, perpetual contract NFT, which exploits perpetual future contracts in the cryptocurrency derivatives market. Unlike futures contracts in a traditional derivatives market, in the cryptocurrency derivatives market, most futures contracts are perpetual. In addition, the value of futures contract is backed by collateral. Therefore, if we mint the rights to perpetual contracts as NFT, we can use the perpetual contract NFT as collateral for DeFi composability. To validate our proposal and its profitability, we experiment with the position NFT of Uniswap v3. Through validation, we show that our concept works in real-world scenarios.
平成15年度論文賞対象論文の概要とその研究背景 (2003)

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Engine Fault Diagnosis Based on ELM and Evidence Theory (2013)

For the diversity and complexity of engine fault,an engine fault diagnosis method based on extreme learning machine(ELM) and D-S evidence theory was proposed by means of information fusion principle.The method conducted local diagnosis by building multi-ELM classification modules.The similarity matrix was acquired by calculating the category inner distance between the actual output and the standard output,the belief function assignment frame of each sensor was built by normalizing the similarity matrix,and finally the final diagnosis result was calculated according to the D-S evidence theory.The example shows that,compared with the diagnosis of single vibration or noise signal,the method improves the diagnosis accuracy and decreases the uncertainty of diagnosis result.The method makes full use of redundant and complementary information among all sensors with fusing the multi-source and multi-feature parameters.
Improved naturalness with a heavy Higgs boson: An alternative road to CERN LHC physics (2006)

The quadratic divergences of the Higgs mass may be cancelled either accidentally or by the exchange of some new particles. Alternatively its impact on naturalness may be weakened by raising the Higgs mass, which requires changing the standard model below its natural cutoff. We show in detail how this can be achieved, while preserving perturbativity and consistency with the electroweak precision tests, by extending the standard model to include a second Higgs doublet that has neither a vev nor couplings to quarks and leptons. This inert doublet model yields a perturbative and completely natural description of electroweak physics at all energies up to 1.5 TeV. The discrete symmetry that yields the inert doublet is unbroken, so that dark matter may be composed of neutral inert Higgs bosons, which may have escaped detection at LEP2. Predictions are given for multilepton events with missing transverse energy at the Large Hadron Collider, and for the direct detection of dark matter.
The Neuroprotective Effect of Pyrroloquinoline Quinone on Traumatic Brain Injury (2011)

Pyrroloquinoline quinone (PQQ) is a water-soluble, anionic, quinonoid substance that has been established as an essential nutrient in animals. Owing to the inherent properties of PQQ as an antioxidant and redox modulator in various systems, PQQ is expected to be used in pharmacological applications in the near future. Although many recent studies have investigated its neuroprotective effects, the effect of PQQ on traumatic brain injury (TBI) has not been examined. In this study we employed Morris water maze (MWM) training, the results of which showed that PQQ led to improved behavioral performance in post-TBI animals. Considering that many experiments have suggested that β-1,4-galactosyltransferase I (β-1,4-GalT-I) and -V play significant roles in inflammation and the nervous system, in the present study we used Western blot analysis to study the effect of PQQ on the expression of β-1,4-GalT-I and -V. We found apparent expression upregulation of β-1,4-GalT-I and -V after PQQ was systemically administered. Lectin-fluorescent staining with RCA-I also revealed that PQQ contributed to expression upregulation of the galactosidase β-1 (Gal β-1), 4-galactosyltransferase N-acylsphingosine (4-GlcNAc) group in microglia and neurons of the cortex and hippocampal CA2 region. In summary, our experiment established that PQQ may play an important role in recovery post-TBI.
The Effects of ML 3000 on Antigen-induced Responses in Sheep (1997)

ML 3000 is a dual inhibitor of cyclooxygenase (COX) and 5-lipoxygenase (5-LO), two enzymes that contribute to the airway inflammation in asthma. When administered as an aerosol at a dose of 100 mg, 0.5 h before antigen challenge in allergic sheep, ML 3000 provided significant inhibition against the early bronchial response (EAR, mean 33% protection, P<0.05), completely blocked the late antigen-induced bronchoconstriction (LAR, mean 81% protection, P<0. 05) and the airway hyperresponsiveness (AHR, P<0.05) to aerosolized carbachol that occurs 24 h after antigen challenge in this model. Consistent with this functional protection was a small but significant reduction in the percentage of neutrophils recovered in bronchoalveolar lavage (BAL) at 8 h and 24 h after challenge. These findings are similar to previous data obtained in this animal model with other 5-LO inhibitors (blockade of the LAR and AHR) and COX inhibitors (blockade of AHR). These results suggest that aerosol administration of a dual inhibitor of COX and 5-LO may have beneficial effects in the treatment of allergic airway disease.
A comprehensive review of the lipid cubic phase or<i>in meso</i>method for crystallizing membrane and soluble proteins and complexes (2014)

The lipid cubic phase or in meso method is a robust approach for crystallizing membrane proteins for structure determination. The uptake of the method is such that it is experiencing what can only be described as explosive growth. This timely, comprehensive and up-to-date review introduces the reader to the practice of in meso crystallogenesis, to the associated challenges and to their solutions. A model of how crystallization comes about mechanistically is presented for a more rational approach to crystallization. The possible involvement of the lamellar and inverted hexagonal phases in crystallogenesis and the application of the method to water-soluble, monotopic and lipid-anchored proteins are addressed. How to set up trials manually and automatically with a robot is introduced with reference to open-access online videos that provide a practical guide to all aspects of the method. These range from protein reconstitution to crystal harvesting from the hosting mesophase, which is noted for its viscosity and stickiness. The sponge phase, as an alternative medium in which to perform crystallization, is described. The compatibility of the method with additive lipids, detergents, precipitant-screen components and materials carried along with the protein such as denaturants and reducing agents is considered. The powerful host and additive lipid-screening strategies are described along with how samples that have low protein concentration and cell-free expressed protein can be used. Assaying the protein reconstituted in the bilayer of the cubic phase for function is an important element of quality control and is detailed. Host lipid design for crystallization at low temperatures and for large proteins and complexes is outlined. Experimental phasing by heavy-atom derivatization, soaking or co-crystallization is routine and the approaches that have been implemented to date are described. An overview and a breakdown by family and function of the close to 200 published structures that have been obtained using in meso-grown crystals are given. Recommendations for conducting the screening process to give a more productive outcome are summarized. The fact that the in meso method also works with soluble proteins should not be overlooked. Recent applications of the method for in situ serial crystallography at X-ray free-electron lasers and synchrotrons are described. The review ends with a view to the future and to the bright prospects for the method, which continues to contribute to our understanding of the molecular mechanisms of some of nature's most valued proteinaceous robots.