gebhart/patrepeval huggingface dataset:
Randomized Placebo-Controlled Phase II Trial of Perifosine Plus Capecitabine As Second- or Third-Line Therapy in Patients With Metastatic Colorectal Cancer (2011)

P-CAP showed promising clinical activity compared with CAP in previously treated patients with mCRC. A phase III trial is underway comparing P-CAP with CAP in patients with refractory mCRC.
The neurokinin-2 receptor antagonist ibodutant improves overall symptoms, abdominal pain and stool pattern in female patients in a phase II study of diarrhoea-predominant IBS (2016)

Background Tachykinins have been implicated in the pathophysiology of IBS with diarrhoea (IBS-D). Our aim was to study the efficacy and safety of ibodutant, a selective neurokinin-2 (NK2) receptor antagonist, in patients with IBS-D. Methods This multinational double-blind, placebo-controlled study recruited 559 patients with IBS-D according to Rome III criteria. After a 2-week treatment-free run-in, patients were randomised to ibodutant 1 mg, 3 mg, 10 mg or placebo once daily for eight consecutive weeks. Responders were those with a combined response of satisfactory relief (weekly binary question yes/no) of overall IBS symptoms and abdominal pain/discomfort on ≥75% weeks (primary end point). Secondary end points included abdominal pain and stool pattern. Data were also analysed according to US Food and Drug Administration (FDA)-approved interim end points (improvement of pain and stool consistency). Safety was assessed by monitoring adverse events and laboratory tests. Prespecified statistical analysis involved the whole group as well as gender subgroups. Results Demographics and baseline characteristics were comparable for all treatment arms. In the overall population, responsiveness tended to increase with escalating ibodutant doses. In the prespecified analysis by gender, ibodutant 10 mg demonstrated significant superiority over placebo in females (p=0.003), while no significant effect occurred in males. This was confirmed for secondary end points and for the responder analysis according to FDA-approved end points. The tolerability and safety of ibodutant was excellent at all doses. Conclusions Ibodutant showed dose-dependent efficacy response in IBS-D, reaching statistical significance at the 10 mg dose in female patients. The safety and tolerability profile of ibodutant was similar to placebo. Trial registration number NCT01303224.
Increased Height of Fused Segments Contributes to Early-Phase Strut Subsidence after Anterior Cervical Corpectomy with Fusion for Multilevel Ossification of the Posterior Longitudinal Ligament (2020)

A postoperative increase in FSH may affect graft stability and lead to early implant migration.
Impact of ASR Performance on Free Speaking Language Assessment (2018)

In free speaking tests candidates respond in spontaneous speech to prompts. This form of test allows the spoken language proficiency of a non-native speaker of English to be assessed more fully than read aloud tests. As the candidate's responses are unscripted, transcription by automatic speech recognition (ASR) is essential for automated assessment. ASR will never be 100% accurate so any assessment system must seek to minimise and mitigate ASR errors. This paper considers the impact of ASR errors on the performance of free speaking test auto-marking systems. Firstly rich linguistically related features, based on part-of-speech tags from statistical parse trees, are investigated for assessment. Then, the impact of ASR errors on how well the system can detect whether a learner's answer is relevant to the question asked is evaluated. Finally, the impact that these errors may have on the ability of the system to provide detailed feedback to the learner is analysed. In particular, pronunciation and grammatical errors are considered as these are important in helping a learner to make progress. As feedback resulting from an ASR error would be highly confusing, an approach to mitigate this problem using confidence scores is also analysed.
A prototype instrument for single pinhole small animal adaptive SPECT imaging (2008)

The authors have designed and constructed a small-animal adaptive SPECT imaging system as a prototype for quantifying the potential benefit of adaptive SPECT imaging over the traditional fixed geometry approach. The optical design of the system is based on filling the detector with the region of interest for each viewing angle, maximizing the sensitivity, and optimizing the resolution in the projection images. Additional feedback rules for determining the optimal geometry of the system can be easily added to the existing control software. Preliminary data have been taken of a phantom with a small, hot, offset lesion in a flat background in both adaptive and fixed geometry modes. Comparison of the predicted system behavior with the actual system behavior is presented, along with recommendations for system improvements.
Data from Development of ASG-15ME, a Novel Antibody–Drug Conjugate Targeting <i>SLITRK6</i>, a New Urothelial Cancer Biomarker (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;i&gt;SLITRK6&lt;/i&gt; is a member of the SLITRK family of neuronal transmembrane proteins that was discovered as a bladder tumor antigen using suppressive subtractive hybridization. Extensive immunohistochemistry showed SLITRK6 to be expressed in multiple epithelial tumors, including bladder, lung, and breast cancer as well as in glioblastoma. To explore the possibility of using SLITRK6 as a target for an antibody–drug conjugate (ADC), we generated a panel of fully human mAbs specific for SLITRK6. ADCs showed potent &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt; cytotoxic activity after conjugation to Monomethyl Auristatin E or Monomethyl Auristatin F. The most potent ADC, ASG-15ME, was selected as the development candidate and given the product name AGS15E. ASG-15ME is currently in phase I clinical trials for the treatment of metastatic urothelial cancer. This is the first report that SLITRK6 is a novel antigen in bladder cancer and also the first report of the development of ASG-15ME for the treatment of metastatic bladder cancer. &lt;i&gt;Mol Cancer Ther; 15(6); 1301–10. ©2016 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Use of a “Catalytic” Cosolvent, N,N‐Dimethyl Octanamide, Allows the Flow Synthesis of Imatinib with no Solvent Switch (2016)

A general, efficient method for C-N cross-coupling has been developed using N,N-dimethyloctanamide as a catalytic cosolvent for biphasic continuous-flow applications. The described method was used to generate a variety of biarylamines and was integrated into a two-step sequence which converted phenols into biarylamines via either triflates or tosylates. Additionally, the method was applied to a three-step synthesis of imatinib, the API of Gleevec, in good yield without the need of solvent switches.
Computer-Guided Design, Synthesis, and Protein Kinase C Affinity of a New Salicylate-Based Class of Bryostatin Analogs (2014)

Bryostatin 1 is in clinical trials for the treatment of cancer and Alzheimer's disease and is a candidate for a first-in-class approach to HIV/AIDS eradication. It is neither readily available nor optimally suited for clinical use. Using a function oriented synthesis strategy, a new class of bryostatin-inspired analogs was designed with a simplified salicylate-derived subunit, enabling step-economical synthesis (23 total steps) of agents exhibiting bryostatin-like affinity to protein kinase C (PKC).
Reduced Peptide Bond Pseudopeptide Analogues of Substance P (1989)

Each of the last 6 peptide bonds in the COOH terminus of [Leu11]substance P [( Leu11]SP) and [Nle11]spantide were replaced with [CH2NH], and each analogue was tested for SP agonist or antagonist activity by determining its ability to interact with SP receptors on dispersed acini from guinea pig pancreas. Each of the 6 spantide and 5 of the 6 SP analogues had no agonist activity, whereas [psi 9-10]SP was an agonist. For the spantide pseudopeptides, the psi 10-11 analogue (Ki,2.8 microM) was equipotent as an antagonist to spantide itself, whereas the psi 9-10, psi 8-9, psi 7-8, and psi 6-7 analogues were 2.5, 7, 5, and 3 times less potent. For the SP pseudopeptides, the psi 10-11 analogue was the most potent antagonist (Ki, 6.2 microM), whereas the psi 8-9, psi 7-8, and psi 6-7 analogues were 7-, 36-, and 39-fold less potent. There was a close correlation between the ability of each pseudopeptide to inhibit binding of 125I-Bolton-Hunter-SP and to affect amylase secretion. [psi 10-11]SP inhibited SP-stimulated amylase release in a competitive manner, and its inhibitory ability was specific for the SP receptor. Despite [psi 10-11]SP, spantide, and [psi 10-11]spantide having similar affinities for the SP receptor (Ki, 2-6 microM), for inhibition of binding of 125I-[Tyr4]bombesin, the analogues differed with [psi 10-11]SP having a 50-fold lower affinity than for the SP receptor, whereas [psi 10-11]spantide had a 4-fold lower affinity and spantide a 1.5-fold lower affinity for the SP receptor. These results demonstrate that SP pseudopeptides represent a new class of SP receptor antagonists and, in contrast to the currently described SP receptor antagonists, are more specific for SP receptors.
ChemInform Abstract: Analysis of the Conformational Nature, Resolvability, and Thermal Racemization of Hetero 2,3‐Dispiro Cyclohexanones. The Weighting of Carbonyl/C‐X Stabilization Relative to the Electronic Interaction Between the Vicinal Electronegative Substituents (1994)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Oxygenation of [tris(2-pyridyl)amine](trifluoromethanesulfonato)copper(I) in nonaqueous solvents. Synthesis and structural characterization of the cubane-like cluster [Cu4(OH)4(SO3CF3)2[N(C5H4N)3]4][SO3CF3]2.C3H6O (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOxygenation of [tris(2-pyridyl)amine](trifluoromethanesulfonato)copper(I) in nonaqueous solvents. Synthesis and structural characterization of the cubane-like cluster [Cu4(OH)4(SO3CF3)2[N(C5H4N)3]4][SO3CF3]2.C3H6OPatricia L. Dedert, Theophilus Sorrell, Tobin J. Marks, and James A. IbersCite this: Inorg. Chem. 1982, 21, 9, 3506–3517Publication Date (Print):September 1, 1982Publication History Published online1 May 2002Published inissue 1 September 1982https://pubs.acs.org/doi/10.1021/ic00139a047https://doi.org/10.1021/ic00139a047research-articleACS PublicationsRequest reuse permissionsArticle Views320Altmetric-Citations58LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
ERC-20R and ERC-721R: Reversible Transactions on Ethereum (2022)

Blockchains are meant to be persistent: posted transactions are immutable and cannot be changed. When a theft takes place, there are limited options for reversing the disputed transaction, and this has led to significant losses in the blockchain ecosystem. In this paper we propose reversible versions of ERC-20 and ERC-721, the most widely used token standards. With these new standards, a transaction is eligible for reversal for a short period of time after it has been posted on chain. After the dispute period has elapsed, the transaction can no longer be reversed. Within the short dispute period, a sender can request to reverse a transaction by convincing a decentralized set of judges to first freeze the disputed assets, and then later convincing them to reverse the transaction. Supporting reversibility in the context of ERC-20 and ERC-721 raises many interesting technical challenges. This paper explores these challenges and proposes a design for our ERC-20R and ERC-721R standards, the reversible versions of ERC-20 and ERC-721. We also provide a prototype implementation. Our goal is to initiate a deeper conversation about reversibility in the hope of reducing some of the losses in the blockchain ecosystem.
A Rapid and Simple Nonradioactive Method for In Vitro Testing of Ribozyme Activity (2002)

Ribozymes that target specific messenger RNA transcripts are powerful tools in the emerging fields of functional genomics, proteomics, and metabolomics. We have found that successful in vitro testing greatly increases the likelihood of producing ribozymes with good efficacy in living cells. A rapid and simple nonradioactive method for systematic in vitro testing of ribozyme-cleaving activity is reported. Ribozymes are synthesized enzymatically from double-stranded DNA (dsDNA) oligonucleotides without vector cloning. Substrate target DNA template is cloned into a vector flanked with SP6 and T7 promoters at multiple cloning sites that permit colorimetric screening and ampicillin selection, enhancing the efficiency of the cloning procedure. Ribozyme cleavage products are satisfactorily resolved on 2.0% NuSieve 3:1 agarose (FMC Products, Rockland, ME)/formaldehyde gels by electrophoresis. This method avoids the preparation of polyacrylamide gels. Using this procedure, the ribozyme, target substrate RNA, and ribozyme cleavage products are all easily detected by ethidium bromide staining. Resolution and detection are fast and simple, eliminating the need for either polyacrylamide gel analysis or radiolabeling. The use of RNase inhibitors in the assays is also assessed and discussed.
Synthesis and biological activity of a new class of insecticides: the N‐(5‐aryl‐1,3,4‐thiadiazol‐2‐yl)amides (2016)

Structure-activity relationship (SAR) studies on both the amide tail and the aryl A-ring of novel N-(5-aryl-1,3,4-thiadiazol-2-yl)amides led to a new class of insecticidal molecules active against sap-feeding insect pests. © 2016 Society of Chemical Industry.
Epigenetics Connects the Genome to Its Environment (2014)

Comprehending the reasons for the natural variation and distribution of life-forms in different environments has been a major motivational force for biology since antiquity. With Mendel's discoveries, Darwin's natural selection theories became armed with the concept of genotype. How a genotype is inherited, selected, and how this results in a phenotype have become a spirited debate that has ultimately led to our ideas of genetics and epigenetics. The concept of genetic memory that arose from developmental biology has underpinned the desire to understand the molecular basis of epigenetics. This has finally led to uncovering of many of the molecular building blocks and regulatory pathways of epigenetics. The possibility that the environment through epigenetic regulation may direct trait inheritance has even begun to question some of our fundamental paradigms of the function of the environment in shaping evolution. Some direct role of the environment in heritable phenotype variation cannot be ruled out now. This has blurred our concepts of transgenerational and developmental genetics so much that understanding the connections between these processes has taken an enormously important status in biology. The pace of growth of our knowledge of the biochemical participants in the epigenetic informational system has been truly impressive. Major epigenetic marks involve covalent chemical modifications to DNA and to histones. How these modifications and noncoding RNAs are organized into an epigenetic informational system is being intensively investigated. Understanding the way in which the environment controls the connections and use of epigenetic marks with the DNA sequence code promises to expose a rich new world of biology and new toolboxes that will afford stunning new capabilities in agriculture, medicine, and all practical applications of biology. This chapter discusses the sea change in our understanding of genome–environment interactions.
Tumour suppressor PTEN regulates cell cycle and protein kinase B/Akt pathway in breast cancer cells. (2006)

PTEN function is mediated through the inhibition of the cell cycle and PKB/Akt phosphorylation in breast cancer cells.
Industrial Trent Combustor—Combustion Noise Characteristics (2000)

Thermoacoustic resonance is a difficult technical problem that is experienced by almost all lean-premixed combustors. The Industrial Trent combustor is a novel dry-low-emissions (DLE) combustor design, which incorporates three stages of lean premixed fuel injection in series. The three stages in series allow independent control of two stages—the third stage receives the balance of fuel to maintain the desired power level—at all power conditions. Thus, primary zone and secondary zone temperatures can be independently controlled. This paper examines how the flexibility offered by a 3-stage lean premixed combustion system permits the implementation of a successful combustion noise avoidance strategy at all power conditions and at all ambient conditions. This is because at a given engine condition (power level and day temperature) a characteristic “noise map” can be generated on the engine, independently of the engine running condition. The variable distribution of heat release along the length of the combustor provides an effective mechanism to control the amplitude of longitudinal resonance modes of the combustor. This approach has allowed the Industrial Trent combustion engineers to thoroughly “map out” all longitudinal combustor acoustic modes and design a fuel schedule that can navigate around regions of combustor thermoacoustic resonance. Noise mapping results are presented in detail, together with the development of noise prediction methods (frequency and amplitude) that have allowed the noise characteristics of the engine to be established over the entire operating envelope of the engine. [S0742-4795(00)00802-4]
Using stochastic computing to implement digital image processing algorithms (2011)

As device scaling continues to nanoscale dimensions, circuit reliability will continue to become an ever greater problem. Stochastic computing, which performs computing with random bits (stochastic bits streams), can be used to enable reliable computation using those unreliable devices. However, one of the major issues of stochastic computing is that applications implemented with this technique are limited by the available computational elements. In this paper, first we will introduce and prove a stochastic absolute value function. Second, we will demonstrate a mathematical analysis of a stochastic tanh function, which is a key component used in a stochastic comparator. Third, we will present a quantitative analysis of a one-parameter linear gain function, and propose a new two-parameter version. The validity of the present stochastic computational elements is demonstrated through four basic digital image processing algorithms: edge detection, frame difference based image segmentation, median filter based noise reduction, and image contrast stretching. Our experimental results show that stochastic implementations tolerate more noise and consume less hardware than their conventional counterparts.
A flatness based approach to trajectory modification of residual motion of highrise elevators (2001)

As high-rise buildings continue to grow, design and control of elevators still remains a challenging problem. An important issue is to transport passengers with minimal residual motion once the elevator has reached its destination floor. A simple and elegant solution of the residual motion control problem can be given using the theory of /spl delta/-flatness. The elevator car is modeled as a rigid body connected by two flexible ropes. Forces are applied at the ends of the ropes using motors. An approach is presented to modify the residual motion of an elevator car through selection of force trajectory applied by the motors. The approach is demonstrated by experiments.
Different Arms of the Adaptive Immune System Induced by a Combination Vaccine Work in Concert to Provide Enhanced Clearance of Influenza (2014)

Current split influenza virus vaccines that induce strain-specific neutralising antibodies provide some degree of protection against influenza infection but there is a clear need to improve their effectiveness. The constant antigenic drift of influenza viruses means that vaccines are often not an exact match to the circulating strain and so levels of relevant antibodies may not be sufficiently high to afford protection. In the situation where the emergent influenza virus is completely novel, as is the case with pandemic strains, existing vaccines may provide no benefit. In this study we tested the concept of a combination vaccine consisting of sub-optimal doses of split influenza virus vaccine mixed with a cross-protective T-cell inducing lipopeptide containing the TLR2 ligand Pam2Cys. Mice immunised with combination vaccines showed superior levels of lung viral clearance after challenge compared to either split virus or lipopeptide alone, mediated through activation of enhanced humoral and/or additional cellular responses. The mechanism of action of these vaccines was dependent on the route of administration, with intranasal administration being superior to subcutaneous and intramuscular routes, potentially through the induction of memory CD8+ T cells in the lungs. This immunisation strategy not only provides a mechanism for minimising the dose of split virus antigen but also, through the induction of cross-protective CD8+ T cells, proves a breadth of immunity to provide potential benefit upon encounter with serologically diverse influenza isolates.
Administration of Recombinant Human Interleukin 12 to Chronically SIV mac -Infected Rhesus Monkeys (1998)

With the demonstration that interleukin 12 can enhance natural killer (NK) cell activity and drive CD4+ lymphocytes toward T helper type 1 (Thl) responses, there is a strong rationale for exploring the use of this cytokine as an immunomodulatory therapy in HIV-1-infected individuals. To assess its potential safety and effects on both immune and virologic aspects of HIV-1 infection, recombinant human IL-12 (rhIL-12) was assessed in rhesus monkeys chronically infected with the simian immunodeficiency virus of macaques (SIVmac). The activity of rhIL-12 on rhesus monkey lymphocytes was confirmed with the demonstration that peripheral blood lymphocyte lysis of the NK-sensitive cell line Colo was enhanced by this recombinant cytokine. Further, rhIL-12 was shown to induce interferon-gamma production by rhesus monkey lymphocytes in vitro. Then, in separate studies, two treatment regimens of rhIL-12 were assessed in SIVmac-infected monkeys: a low-dose regimen (0.1 microg/kg, daily for 4 weeks) and a high-dose regimen (2.5 microg/kg, every 3-4 days, for 3 weeks). Both rhIL-12 treatment regimens were well tolerated by these virus-infected animals. The high-dose regimen of rhIL-12 induced transient decreases in circulating lymphocytes in the SIVmac-infected monkeys. Furthermore, no changes in lymphocyte-associated SIVmac DNA or SIVmac plasma RNA levels were seen in the treated monkeys. These studies indicate that short-term treatment with rhIL-12 is well tolerated and causes no measurable changes in virus load in chronically SIVmac-infected rhesus monkeys.