gebhart/patrepeval huggingface dataset:
A phase I study of pharmacokinetic (PK)-driven sequential dosing of rucaparib (RUB) with irinotecan liposome (nal-IRI) and fluorouracil (5FU) in metastatic gastrointestinal (mGI) and pancreas (PANC) cancers. (2022)

563 Background: RUB is an oral PARP1,2,3 inhibitor that demonstrated efficacy in patients (pts) with ovarian and prostate cancers harboring deleterious BRCA mutations. RUB exerts synergistic anti-tumor effect with IRI preclinically though the combination has overlapping toxicities. We previously published on the population PK of nal-IRI (Adiwijaya, Ma et al, Clin Pharm Ther 2017). We conducted a phase I study to evaluate a novel sequential dosing of RUB with nal-IRI/5FU in mGI cancer pts. Methods: Eligible pts had incurable mGI cancer previously received > 1 line of therapy (rx), ECOG PS 0-1, had RECIST measurable disease, adequate organ reserves and not received IRI for metastatic disease. Previous PARPi rx was excluded. The endpoints included dose limiting toxicity (DLT), maximum tolerated dose (MTD) and toxicity profile. The dose escalation utilized the 3+3 design. RUB was given oral bid on Day 4 to 13 and 18 to 27 with nal-IRI i.v. and 5FU i.v. 2400 mg/m2 over 46 hr on Day 1 and 15, every 28 day. Planned dose levels were RUB 400 mg/nal-IRI 50 mg/m2 (DL1), 400 mg/70 mg/m2 (DL2) and 600 mg/70 mg/m2 (DL3). Adverse events (AEs) were scored per CTCAE v4.03. Molecular profile was evaluated by CLIA-certified NGS testing. Results: Eighteen pts including 11 colorectal (CRC), 6 PANC, 1 gastroesophageal (GE) were enrolled and 12 were evaluable for DLTs. DL2 was not tolerable (DLT: G3 diarrhea, nausea and vomiting) and DL2A was added (RUB 600 mg/nal-IRI 50 mg/m2). DL2A enrolled 6 pts with no DLT and was determined as the MTD. Of DLT-evaluable pts, G3 and worse treatment-related AEs from all cycles were diarrhea (33%), fatigue (25%), leukopenia (25%), neutropenia (25%), anemia (8%) and nausea (8%). Four of 12 response evaluable pts had partial response: 2 CRC (1 had ATM mut), 1 PANC ( ATM mut), 1 GE ( BRCA2 mut) whilst 3 responders previously had platinum (PLA). Five pts had stable disease beyond 16 weeks (range 18.9 to 100.7 weeks), and all had prior PLA. Conclusions: The study successfully determined the MTD of RUB in combination with nal-IRI and 5FU. Encouraging efficacy was observed in PLA-treated mGI cancers including responses in those harboring ATM and BRCA alterations. The study is proceeding to evaluate the efficacy of the combination in metastatic pancreas cancer pts with and without BRCA1/2 or PALB2 alterations. Clinical trial information: NCT03337087.
The Wnt/β‐catenin pathway determines the predisposition and efficiency of liver‐to‐pancreas reprogramming (2018)

Liver-to-pancreas TD occurs in defined predisposed cells. These cells' predisposition is maintained by Wnt signaling that endows the cells with the plasticity needed to alter their transcriptional program and developmental fate when triggered by ectopic pTFs. These results may have clinical implications by drastically increasing the efficacy of TD in future clinical uses. (Hepatology 2018).
Strain-level typing and identification of bacteria – a novel approach for SERS active plasmonic nanostructures (2018)

One of the potential applications of surface-enhanced Raman spectroscopy (SERS) is the detection of biological compounds and microorganisms. Here we demonstrate that SERS coupled with principal component analysis (PCA) serves as a perfect method for determining the taxonomic affiliation of bacteria at the strain level. We demonstrate for the first time that it is possible to distinguish different genoserogroups within a single species, Listeria monocytogenes, which is one of the most virulent foodborne pathogens and in some cases contact with which may be fatal. We also postulate that it is possible to detect additional proteins in the L. monocytogenes cell envelope, which provide resistance to benzalkonium chloride and cadmium. A better understanding of this infectious agent could help in selecting the appropriate pharmaceutical product for enhanced treatment. Graphical abstract ᅟ.
Efficient and Stereoselective Synthesis of β-Trifluoromethyl α,β-Unsaturated Esters via Iron(III) Porphyrin-Catalyzed Olefination of Ketones (2003)

beta-Trifluoromethyl alpha,beta-unsaturated esters were efficiently prepared by reactions of fluorine-containing ketones with diazo compounds via metalloporphyrin-catalyzed olefination in the presence of triphenylphosphine. The commercially available Fe(III)(TPP)Cl (TPP: tetraphenylporphyrin) is effective for catalyzing the olefination of a variety of trifluoromethyl ketones with different diazoacetate esters under mild conditions. The reactions proceeded with high yields (up to 95% isolated yield) and high stereoselectivity (up to 99% (E)-selectivity).
Cochannel FM interference suppression using adaptive notch filters (1994)

In this paper, a method of reducing cochannel FM interference with adaptive tracking notch filters, first proposed by E. Baghdady (1959), is refined and extended. Analytical descriptions and computer simulations of a novel adaptive notch filter are presented. The new form of adaptive notch filter is useful for suppressing strong cochannel FM and CW signals and allows simple, practical realizations of very high and adaptive notch filters in either analog or digital technologies. The analysis demonstrates that when the instantaneous frequency of the stronger interfering FM carrier signal is known precisely, the stronger signal can be completely eliminated. In some cases, placing an additional adaptive notch filter in front of the stronger signal demodulator to suppress the weaker desired cochannel signal improves the estimate of the stronger signal.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Applications of Diethoxymethane as a Versatile Process Solvent and Unique Reagent in Organic Synthesis (2001)

Diethoxymethane (DEM) has recently become available in commercial quantities. It has unique properties and is useful in a variety of applications in organic synthesis. It is low boiling (88 °C), azeotropes with water, and has a very low affinity for water. It is stable under basic conditions and as manufactured does not require drying for use as a solvent, even for organometallic reactions. DEM is useful as a process solvent especially for sodium hydride reactions, organolithium chemistry, copper-catalyzed conjugate additions, and phase-transfer reactions. As such, DEM is a potential replacement for tetrahydrofuran (THF), dichloromethane (CH2Cl2), glyme (1,2-dimethoxyethane), and methylal (1,1-dimethoxymethane). DEM is also useful as an ethoxymethylating agent, a formaldehyde equivalent, and a carbonylation substrate. Due to these unique properties and applications, DEM has exciting potential for widespread use both as a reagent and especially as a preferred solvent.
An improved uep based on the importance of MacroBlock (2011)

In this paper, an improved Unequal Error Protection (UEP) scheme based on importance of the MacroBlock (MB) is proposed. At first, the importance level matrix of the MB is established to present the movement of the object. Then based on a variation of H.264/AVC dispersed FMO mode, the MBs with the same importance level are assigned to a Slice Group (SG) with k-means clustering algorithm. At last, the improved UEP scheme is proposed to provide different SGs with different degrees of protection. Compared to the competing approaches, the simulation results indicate that a significant performance improvement can be achieved under various packet loss probabilities. In addition, the complexity is reduced.
<i>Staphylococcus aureus</i> Resists Human Defensins by Production of Staphylokinase, a Novel Bacterial Evasion Mechanism (2004)

Alpha-defensins are peptides secreted by polymorphonuclear cells and provide antimicrobial protection mediated by disruption of the integrity of bacterial cell walls. Staphylokinase is an exoprotein produced by Staphylococcus aureus, which activates host plasminogen. In this study, we analyzed the impact of interaction between alpha-defensins and staphylokinase on staphylococcal growth. We observed that staphylokinase induced extracellular release of alpha-defensins from polymorphonuclear cells. Moreover, a direct binding between alpha-defensins and staphylokinase was shown to result in a complex formation. The biological consequence of this interaction was an almost complete inhibition of the bactericidal effect of alpha-defensins. Notably, staphylokinase with blocked plasminogen binding site still retained its ability to neutralize the bactericidal effect of alpha-defensins. In contrast, a single mutation of a staphylokinase molecule at position 74, substituting lysine for alanine, resulted in a 50% reduction of its alpha-defensin-neutralizing properties. The bactericidal properties of alpha-defensins were tested in 19 S. aureus strains in vitro and in a murine model of S. aureus arthritis. Staphylococcal strains producing staphylokinase were protected against the bactericidal effect of alpha-defensins. When staphylokinase was added to staphylokinase-negative S. aureus cultures, it almost totally abrogated the effect of alpha-defensins. Finally, human neutrophil peptide 2 injected intra-articularly along with bacteria alleviated joint destruction. In this study, we report a new property of staphylokinase, its ability to induce secretion of defensins, to complex bind them and to neutralize their bactericidal effect. Staphylokinase production may therefore be responsible in vivo for defensin resistance during S. aureus infections.
Preparation of potential biofuel 5-ethoxymethylfurfural and other 5-alkoxymethylfurfurals in the presence of oil shale ash (2013)

5-Ethoxymethylfurfural (EMF) can be prepared from the corresponding halomethylfurfural and absolute ethanol in good yield. The use of significantly more affordable 96% ethanol results in formation of levulinic acid or its ester in considerable amount (up to 16%), which is difficult to separate from the desired EMF. In the present study we report that the addition of oil shale ash prevents the hydrolysis of the furan ring and enables the use of 96% ethanol with great success. The developed procedure is applicable to a wide range of aqueous alcohols, is operationally simple and utilizes an inexpensive basic ash, which is deposited in millions of tons per year. Notably, the basicity of the ash is decreased during the process, making its deposits less hazardous to the environment.
Laser machining wood composites (1989)

Etude experimentale de la decoupe par un faisceau laser au CO 2 de panneaux composites formes d'une âme en panneau de particules, de bandes transversales en resine melanine haute densite et de placages de noyer
Participating Publics: Implications for Production Practices at the BBC (2013)

The BBC, one of the largest public service broadcasters in the world, often acts as a model for other public service media enterprises. It is therefore likely to be useful to examine how the BBC has been adapting to emerging participatory practices. The corporation has been particularly reassessing its relationship with the public since the launch of its website, www.bbc.co.uk, in 1997, and the subsequent launch of a suite of ‘online communities’ services (from 1998 onwards). Two production and audience studies (fi rstly located in the BBC New Media and secondly in the BBC Children’s department), Participatory Public Service Media: Presenters and Hosts in BBC New Media (Jackson, 2009) and Children in Virtual Worlds-‘Adventure Rock’ Users and Producers Study (Jackson, Gauntlett, and Steemers, 2009), argue that a reorientation towards a creative, innovative, and interactive public is necessary in order to maintain currency in the present mediascape. Findings from both studies show the increasing importance of both reciprocity and reifi cation in the participatory media; a level of responsiveness from all stakeholders in the media enterprise, and the making of meaning from what might otherwise be a cacophony of diverse media and communication sources.
New Analogues of the Potent Cytotoxic Saponin OSW-1 (2007)

Saponin OSW-1 (5e-G2; 3 beta,16 beta,17 alpha-trihydroxycholest-5-en-22-one 16-O-{O-[2-O-(4-methoxybenzoyl)-beta-D-xylopyranosyl]-(1-->3)-2-O-acetyl-alpha-arabinopyranoside}) analogues: with modified side chain (5a/d-G2), 22-deoxo-23,24,25,26,27-pentanor- (14), 22-deoxo-23-oxa- (17), glycosylated with various monosaccharides (5e-G4/G6/G8), and OSW-1 structural isomer (10) were obtained. The analogues were synthesized using a previously published method for the synthesis of OSW-1. The structures of analogues were fully confirmed by spectroscopic methods, and the S-chirality at C-22 of the structural isomer was established by conformational analysis combined with the NMR spectrometry. The cytotoxicity of the analogues toward several types of malignant tumor cells was examined and compared with that of OSW-1. The results suggest that modification of the steroidal aglycone may lead to compounds with high cytotoxicity.
Impaired Effector Function of Hepatitis C Virus-Specific CD8+ T Cells in Chronic Hepatitis C Virus Infection (2002)

The cellular immune response contributes to clearance of hepatitis C virus (HCV) and persists for decades after recovery from infection. The immunological basis for the inefficiency of the cellular immune response in chronically infected persons is not known. Here, we used four HLA-A2 tetramers, specific for two HCV core and two HCV NS3 epitopes, to investigate at the single-cell level effector function and phenotype of HCV-specific CD8+ T cells in 20 chronically infected and 12 long-term recovered patients. Overall, HCV-specific, tetramer+ T cells were more frequently found in PBMCs of chronically infected patients than in those of recovered patients. However, when compared with HCV-tetramer+ T cells of recovered patients, they displayed an impaired proliferative capacity. As a result of the impaired proliferative capacity, HCV-specific T cell lines derived from chronically infected patients displayed less peptide-specific cytotoxicity than those from recovered patients. In addition, proliferation and ex vivo IFN-gamma production of HCV-tetramer+ cells, but not influenza-virus-specific T cells, were defective in chronically infected patients and could not be restored by in vitro stimulation with peptide and IL-2. At least three distinct phenotypes of HCV-specific CD8+ T cells were identified and associated with certain functional characteristics. In addition, impairment of proliferative, cytokine, and cytotoxic effector functions of tetramer+ T cells in viremic patients was associated with weak ex vivo HCV-specific CD4+ T cell responses. Thus, the defective functions of HCV-specific CD8+ T cells might contribute to viral persistence in chronically infected patients, and knowledge on their reversibility may facilitate the development of immunotherapeutic vaccines.
Efficient Shadow Detection of Color Aerial Images Based on Successive Thresholding Scheme (2008)

Recently, Tsai presented an efficient algorithm which uses the ratio value of the hue over the intensity to construct the ratio map for detecting shadows of color aerial images. Instead of only using the global thresholding process in Tsai's algorithm, this paper presents a novel successive thresholding scheme (STS) to detect shadows more accurately. In our proposed STS, the modified ratio map, which is obtained by applying the exponential function to the ratio map proposed by Tsai, is presented to stretch the gap between the ratio values of shadow and nonshadow pixels. By performing the global thresholding process on the modified ratio map, a coarse-shadow map is constructed to classify the input color aerial image into the candidate shadow pixels and the nonshadow pixels. In order to detect the true shadow pixels from the candidate shadow pixels, the connected component process is first applied to the candidate shadow pixels for grouping the candidate shadow regions. For each candidate shadow region, the local thresholding process is performed iteratively to extract the true shadow pixels from the candidate shadow region. Finally, for the remaining candidate shadow regions, a fine-shadow determination process is applied to identify whether each remaining candidate shadow pixel is the true shadow pixel or not. Under six testing images, experimental results show that, for the first three testing images, both Tsai's and our proposed algorithms have better detection performance than that of the algorithm of Huang et al., and the shadow detection accuracy of our proposed STS-based algorithm is comparable to Tsai's algorithm. For the other three testing images, which contain some low brightness objects, our proposed algorithm has better shadow detection accuracy when compared with the previous two shadow detection algorithms proposed by Huang et al. and Tsai.
THE TUCSON CHILDREN'S RESPIRATORY STUDY (1989)

Lower respiratory tract illnesses occurring during the first year of life in 1,179 healthy infants enrolled in the Children's Respiratory Study, Tucson, Arizona, are described. The children, who use the pediatricians of a health maintenance organization, were enrolled into the study between May 1980 and January 1984. Data were collected on signs, symptoms, and diagnosis for each illness; nasopharyngeal and throat swabs were collected at the acute visit for viral, chlamydial, and mycoplasmal cultures. The cumulative incidence of illness in the first year of life was 32.88 per 100 children. Of the 348 initial lower respiratory tract illnesses occurring in these infants, 60% were diagnosed as bronchiolitis. At least one infecting agent was identified in 66% of the specimens collected at the time of the first illness. Respiratory syncytial virus was the most common isolate; 12 other agents were also identified. There was a strong (p less than 0.0001) relation between agent identified, symptoms reported, and diagnosis; bronchiolitis was predominantly associated with respiratory syncytial virus and croup with parainfluenza viruses. Sex and ethnicity were unrelated to illness experience or to characteristics of the first illness. Lower respiratory tract illness occurrence in the Children's Respiratory Study appears to be similar to patterns observed elsewhere, suggesting that diagnoses (and infecting agents) have changed little over the past decades.
Origin of Replication, oriC, of the Escherichia coli K12 Chromosome: Genetic Mapping and Minichromosome Replication (1979)

Replication of the circular chromosome of Escherichia coli (Cairns 1964) is bidirectional (Masters and Broda 1971; Bird et al. 1972; Prescott and Kuempel 1972). Replication appears to be initiated at a fixed site (Marsh and Worcel 1977) which has been located about 20 megadaltons (MD) counterclockwise of the ilv operon (von Meyenburg et al. 1977) at 82.5 minutes on the genetic map (Bachmann et al. 1976). For this site, the origin of replication of the chromosome, the symbol oriC has been introduced (Hiraga 1976).
Physiologic myometrial thickening: a source of confusion. (1979)

Focal myometrial thickening, thought to represent a focal transient myometrial contraction, was observed to disappear during the course of an ultrasonic examination.
Smart Automation System for Controlling Various Appliances using a Mobile Device (2019)

This paper outlines the methodology of designing and developing a smart control system for controlling light, air conditioning and ceiling fans in a room. This system considers the requirements of the users appropriately and makes a comfort zone for the users. An android application with a user friendly Graphical Interface, which is easy to communicate with the smart control system, has been developed. The application is connected with the control system through Wi-Fi across a cloud network and it can respond quickly. RGB LED panel light system that controls the color, color temperature and luminance was designed by considering the requirements of the instances and lighting conditions. Although there are RGB LED panel lights available, there are no systems defined for the activity based color modes. An IR Remote module controller system was built for controlling inverter type air conditioners by giving commands from a smart phone application. This system considers the mean value of the preferences of many users to control the air conditioning system. The running mode of the air conditioner is chosen from the data given through the application by many users in a same place. Although the inverter type air conditioners continuously regulate the temperatures, the fan does not do it. Because of this problem, a ceiling fan controlling system with two modes, automatic and manual, was designed. Automatic mode utilizes the users skin moisture related hybrid system to set the room temperature. Manual mode works according to the suggestions given by the crowd just as the air conditioning system. This air conditioning and ceiling fan control system that works according to the suggestions of crowd is better than the individual preference system using a conventional remote controller.
Microscopic Imaging and Spectroscopy with Scattered Light (2010)

Optical contrast based on elastic scattering interactions between light and matter can be used to probe cellular structure, cellular dynamics, and image tissue architecture. The quantitative nature and high sensitivity of light scattering signals to subtle alterations in tissue morphology, as well as the ability to visualize unstained tissue in vivo, has recently generated significant interest in optical-scatter-based biosensing and imaging. Here we review the fundamental methodologies used to acquire and interpret optical scatter data. We report on recent findings in this field and present current advances in optical scatter techniques and computational methods. Cellular and tissue data enabled by current advances in optical scatter spectroscopy and imaging stand to impact a variety of biomedical applications including clinical tissue diagnosis, in vivo imaging, drug discovery, and basic cell biology.
Using genetic algorithms to automate system implementation in a novel three-dimensional packaging technology (2002)

Implementing electronic systems in a low-cost, three-dimensional multichip module (MCM) technology provides significantly improved system density over planar packaging technologies. However, the extra dimension necessitates a new approach to design automation. Through experience gained in manually partitioning electronic systems, generic design rules have been formulated and implemented in software. The approach adopted is based on a genetic algorithm which can produce multiple candidate solutions and has the potential to simultaneously optimize multiple design criteria. This paper presents the initial results for the automatic configuration of a variety of systems. The results obtained by the algorithm are compared to known optimal solutions for "test" cases and to the results obtained by manual partitioning for the first heterogeneous MCM-V system.