gebhart/patrepeval huggingface dataset:
RESILIENT part I, an open-label, safety run-in of liposomal irinotecan in adults with small cell lung cancer (SCLC) who have progressed with platinum-based first-line (1L) therapy: Subgroup analyses by platinum sensitivity. (2020)

9069 Background: Most patients with extensive SCLC develop drug resistance to platinum-based 1L therapy or discontinue for other reasons, and second-line (2L) therapies are limited. RESILIENT (NCT03088813) is a two-part phase 2/3 study assessing the safety, tolerability and efficacy of 2L liposomal irinotecan monotherapy in adults with SCLC who progressed with platinum-based 1L therapy. Preliminary data from RESILIENT part 1 (cut-off May 8 2019; ≥ 12 weeks follow-up) showed that liposomal irinotecan 70 mg/m 2 free base every 2 weeks was generally well tolerated and had encouraging antitumor activity (Paz-Ares et al. WCLC 2019 OA03.03). Objective response rate (ORR; secondary endpoint) was 44% (11/25). Here we report efficacy analyses in post hoc subgroups by platinum sensitivity. Methods: RESILIENT part 1 was an open-label, single-arm study comprising dose-finding and dose-expansion phases. Eligible patients were aged ≥ 18 y, with an ECOG performance status score of 0/1 and adequate organ function; a single line of prior immunotherapy was allowed. Participants received liposomal irinotecan 70 mg/m 2 or 85 mg/m 2 free base every 2 weeks, with tumor assessments every 6 weeks (RECIST v1.1). Analyses were undertaken for the dose-finding phase recommended dose (RD) in subgroups of platinum-resistant/sensitive patients (with/without progression within 90 days from completion of 1L therapy). Results: During dose finding, 5 patients received liposomal irinotecan 85 mg/m 2 (deemed not tolerable; dose-limiting toxicity) and 12 received 70 mg/m 2 (deemed tolerable; RD for dose-expansion phase in which 13 more patients were included). Analyses included all 25 patients receiving the RD (mean exposure, 13.95 weeks [median 14.86; SD 7.222]). In the platinum-sensitive subgroup (33.3% men; median age 62.0 y) ORR was 53.3% (8/15) and 12-week disease control rate (DCR12wks) was 60% (9/15); in the platinum-resistant subgroup (50% men, median age 58.0 y) both ORR and DCR12wks were 30% (3/10). Overall and progression-free survival (secondary endpoints) are not yet mature. Conclusions: ORR and DCR12wks were numerically higher in platinum-sensitive than in platinum-resistant patients with SCLC who had progressed with platinum-based 1L therapy before receiving 2L liposomal irinotecan 70 mg/m 2 in this phase 2 study. RESILIENT part 2, an ongoing, phase 3, randomized controlled trial vs topotecan, will provide further data. Clinical trial information: NCT03088813.
High-Throughput Analysis of Genome-Wide Receptor Tyrosine Kinase Expression in Human Cancers Identifies Potential Novel Drug Targets (2004)

Novel high-throughput analyses in molecular biology allow sensitive and rapid identification of disease-related genes and drug targets. We have used quantitative real-time reverse transcription-PCR reactions (n = 23000) to analyze expression of all human receptor tyrosine kinases (n = 56) in malignant tumors (n = 313) of different origins and normal control samples (n = 58). The different tumor types expressed very different numbers of receptor tyrosine kinases: whereas brain tumors and testicular cancer expressed 50 receptor tyrosine kinases, acute myeloid leukemia (AML) samples expressed only 20 different ones. Specimens of similar tumor origin exhibited characteristic receptor tyrosine kinase expression patterns and were grouped together in hierarchical cluster analyses. When we focused on specific tumor entities, receptor tyrosine kinases were identified that were disease and/or stage specific. Leukemic blasts from AML bone marrow samples differed significantly in receptor tyrosine kinase expression compared with normal bone marrow and purified CD34+ cells. Among the differentially expressed receptor tyrosine kinases, we found FLT3, c-kit, CSF1 receptor, EPHB6, leukocyte tyrosine kinase, and ptk7 to be highly overexpressed in AML samples. Whereas expression changes of some of these were associated with altered differentiation patterns (e.g., CSF1 receptor), others, such as FLT3, were genuinely overexpressed in leukemic blasts. These data and the associated database (http://medweb.uni-muenster.de/institute/meda/research/) provide a comprehensive view of receptor tyrosine kinase expression in human cancer. This information can assist in the definition of novel drug targets.
A Pharmacologic Approach to Acquired Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction in Smoking Related Lung Disease (2012)

Cigarette smoking reduces CFTR activity and is causally related to reduced mucus transport in smokers due to inhibition of CFTR dependent fluid transport. These effects are reversible by the CFTR potentiator ivacaftor, representing a potential therapeutic strategy to augment mucociliary clearance in patients with smoking related lung disease.
Enriched Environment Increases Neural Stem/Progenitor Cell Proliferation and Neurogenesis in the Subventricular Zone of Stroke-Lesioned Adult Rats (2005)

Enriched environment increased the neural stem/progenitor cell pool and neurogenesis in the adult subventricular zone 5 weeks after a cortical stroke. This might be of potential importance for tissue regeneration.
Serum-free culturing of mammalian cells - adaptation to and cryopreservation in fully defined media (2007)

Long term storage of living cells is a central issue in cell biology and medicine. In addition to the cryoprotectant dimethyl sulphoxide (DMSO), foetal bovine serum (FBS) is often added to the freezing medium for the cryoconservation of serum dependent cell lines. FBS, with its high protein content, protects cells against shear forces and gives the medium a desirable osmotic environment with a physiological viscosity. However, the harvesting of FBS is painful for the foetus and should be avoided for ethical reasons. In this work we describe the adaptation of several commonly used cell lines to serum- and protein-free media; however, such cell lines should not be frozen in a conservation medium containing serum. We tested the synthetic surfactant ''Pluronic F68'', known to protect mammalian cells grown in serum-free bioreactors (Papoutsakis, 1991), as an active cryoprotectant. In samples containing 0.1 to 1% Pluronic F68, we found a significant increase in viable cells after thawing. Values up to 115% of starting cell number indicate that the cells proliferate within the first 24 hours after thawing, a property which was not observed in cryoconservation media without Pluronic F68.
Characteristic gene expression profiles in the progression from normal gastric epithelial cells to moderate gastric epithelial dysplasia and to gastric cancer. (2012)

The results of this study provided global gene expression profiles during the development and progression from normal gastric epithelial cells to mGED to gastric cancer. These data may provide new insights into the molecular pathology of gastric cancer which may be useful for the detection, diagnosis, and treatment.
Revascularization Determines Volume Retention and Gene Expression by Fat Grafts in Mice (2005)

Autologous fat transplantation is a popular and useful technique in plastic and reconstructive surgery. The efficiency and survival of such grafts is predictable in many cases, but there are still issues to be resolved, such as how to improve graft volume retention. To address the issue of volume retention, we studied the effect of revascularization from the recipient on the size and function of adipocytes in fat grafts. Treatment of mice with TNP-470, an angiogenesis inhibitor, reduced blood flow from the recipient into the graft after subcutaneous transplantation of epididymal fat. The weight of transplanted tissues and the size of adipocytes in the grafts were significantly lower in mice treated with TNP-470 (TNP mice) than in control mice. Expression of genes for enzymes related to lipid accumulation was decreased in the grafts of TNP mice compared with control mice. Moreover, the expression of adipocyte-derived angiogenic peptides, VEGF and leptin, was significantly lower in the grafts of TNP mice than in grafts from control animals. The expression of VEGF and leptin by cultured human adipocytes was increased in the presence of conditioned medium from cultured vascular endothelial cells. These results show that the inhibition of the revascularization of fat grafts after transplantation reduces graft volume retention and cellular function. Early and adequate revascularization may be important for both the supply of nutrients and vasoactive interactions between vascular endothelial cells and adipocytes in graft.
Structured highlight inspection of specular surfaces (1988)

An approach to illumination and imaging of specular surfaces that yields three-dimensional shape information is described. The structured highlight approach uses a scanned array of point sources and images of the resulting reflected highlights to compute local surface height and orientation. A prototype structured highlight inspection system, called SHINY, has been implemented. SHINY demonstrates the determination of surface shape for several test objects including solder joints. The current SHINY system makes the distant-source assumption and requires only one camera. A stereo structured highlight system using two cameras is proposed to determine surface-element orientation for objects in a much larger field of view. Analysis and description of the algorithms are included. The proposed structured highlight techniques are promising for many industrial tasks.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
In Vitro Cell Selectivity of Reversible and Irreversible (2021)

[Figure: see text].
Development of a medical fiber-optic pH sensor based on optical absorption (1992)

A new fiber-optic pH sensor system has been developed. The sensor uses an absorbtive indicator compound with a long wave-length absorption peak near 625 nm; change in absorption over the pH range 6.8 to 7.8 is reasonably linear. The sensor is interrogated by a pulsed, red LED. Return light signal is split into short and long wave-length components with a dichroic mirror; the respective signals are detected by photodiodes, and their photocurrents are used to form a ratiometric output signal. In laboratory tests, the sensor system provided resolution of 0.01 pH, accuracy of +/- 0.01 pH, and response time of 30-40 s. Following gamma sterilization, laboratory sensor testing with heparinized human blood yielded excellent agreement (e.g., r = 0.992 for n = 42) with a clinical blood gas analyzer. Excellent sensor performance and low cost, solid-state instrumentation are hallmarks of this sensor-system design.
Genetically Engineered Mice Handbook (2010)

While mice have always been highly popular laboratory subjects, their suitability for genetic engineering has solidified their position as today's lab animal model of choice. However, their increased use in genetic studies has created a demand for input on phenotyping that is not always easily met. To improve the flow of information on the
DNA/RNA heteroduplex oligonucleotide for highly efficient gene silencing (2015)

Antisense oligonucleotides (ASOs) are recognized therapeutic agents for the modulation of specific genes at the post-transcriptional level. Similar to any medical drugs, there are opportunities to improve their efficacy and safety. Here we develop a short DNA/RNA heteroduplex oligonucleotide (HDO) with a structure different from double-stranded RNA used for short interfering RNA and single-stranded DNA used for ASO. A DNA/locked nucleotide acid gapmer duplex with an α-tocopherol-conjugated complementary RNA (Toc-HDO) is significantly more potent at reducing the expression of the targeted mRNA in liver compared with the parent single-stranded gapmer ASO. Toc-HDO also improves the phenotype in disease models more effectively. In addition, the high potency of Toc-HDO results in a reduction of liver dysfunction observed in the parent ASO at a similar silencing effect. HDO technology offers a novel concept of therapeutic oligonucleotides, and the development of this molecular design opens a new therapeutic field.
Immuno-gene therapy of established prostate tumors using chimeric receptor-redirected human lymphocytes. (2003)

Targeted adoptive immunotherapy is an attractive option for prostate cancer given its accessible primary location, the presence of specific tissue and tumor antigens, and the acceptability of collateral destruction of healthy prostrate tissue. The "T-body" approach, which uses genetically programmed, patient-derived lymphocytes transfected with chimeric receptor genes, combines the effector functions of T lymphocytes and natural killer cells with the ability of antibodies to recognize predefined surface antigens with high specificity and in a non-MHC restricted manner. We evaluated the therapeutic efficacy of anti-erbB2 chimeric receptor-bearing human lymphocytes on human prostate cancer xenografts in a SCID mouse model. Local delivery of erbB2-specific T bodies to well-established s.c. and orthotopic tumors, together with systemic administration of interleukin-2, resulted in retardation of both tumor growth and prostate-specific antigen secretion, prolongation of survival, and complete tumor elimination in a significant number of mice. These preclinical studies demonstrate the therapeutic potential of the T-body approach for locally advanced or recurrent prostate cancer as an adjunct to, or after, conventional therapy.
Pollution Bio- indicators In Al-Diwania River A1- (^a?lisia Province / Iraq (2004)

Benthic invertebrates were used as bio- indicators to evaluate the pollution in -Diwania River . Five stations were selected for this purpose , extending from A1 -?? rtream to A1- Sadeer District downstream . The percentage of?ct uP?str?^ ? ?, oligochaeta to total benthic invertebrates were calculated . The population density of evaluation. 'I'he results Were ??? Tubificid worms without hair ehaetae was ©iso used IOBS(01igochaete Index of Sediment Bioindicati©n ), TUSP ? presented as indices Io (Tubificidae Species Percentage ) &amp; degree of pollution Eo . IT was noticed that the 0 in??37.17 percentage of ©lig©chaeta to the total benthic invertebrates ranged between to 60.685 in station 3 , while the percentage ©f Tubificid w©rms t© ©ther ? stati©n oligochaeta ranged from 32% in station 2 to 74.17% in station 3.Io values ranged between 21.3 in station 3 to 22.3 in station I , while lobs index showed a higher value 7.62 in station 3 and lawer value 2.43 in station 3 .the higher value of TUSP index was 32,5 in stati©n 5 and the lawer valus was 15.9 in station 1 . Pollution degree F 1 ( percentage ©f Tubificidae without hair M/gg&amp; ? was rec©rded in stati©n 5-96 respectively ) and degree E in station 3,4&amp;5 (percentage of Tubificidae &amp; ?4-? without hair ehaetae was 15.95 , 15.95 &amp; 16.16 respectively ). According to these results, stati©n 1 &amp; 2 may be regarded as free fr©m p©lluti©n , while the other stations . were considered as slightly p©lluted
Intracerebral Hemorrhage Models in Rat: Comparing Collagenase to Blood Infusion (2007)

Many therapies have shown promise in preclinical stroke studies, but few benefit patients. A greater understanding of stroke pathophysiology is needed to successfully develop therapies, and this depends on appropriate animal models. The collagenase and blood infusion models of intracerebral hemorrhage (ICH) are widely used; yet, investigators often prefer using one model for a variety of reasons. Thus, we directly compared these to highlight advantages and limitations of each as well as the assessment approach. An ICH was created by infusing blood or bacterial collagenase into the rats' striatum. We matched initial hematoma volume in each model (Experiment 1) and assessed the time course of bleeding (Experiment 2). Functional deficits and the progression of injury were tracked over 6 weeks using behavior, magnetic resonance imaging, and histology (Experiment 3). Despite similar initial hematoma volumes, collagenase-induced ICH resulted in a greater blood-brain barrier breakdown and more damage to the striatum, substantia nigra, white matter, and cortex. Magnetic resonance imaging revealed faster hematoma resolution in the blood model, and little increase in the volume of tissue lost from 1 to 6 weeks. In contrast, tissue loss continued over 4 weeks in the collagenase model. Finally, functional deficits recovered more quickly and completely in the blood model. This study highlights key differences between these models and that neither closely replicates the human condition. Thus, both should be used whenever possible taking into account the significant differences between these models and their limitations. Furthermore, this work illustrates significant weaknesses with several outcome measures.
Loads as a Resource: Frequency Responsive Demand (2015)

Current power grid operation predominantly relies on scheduling and regulating generation resources to supply loads and balance load changes. Due to the inherent intermittency of renewable energy, more flexible and fast ramping capacity is required to compensate for the uncertainty and variability introduced by renewable energy resources. With the advancement of information technologies, power system end-use loads are becoming more agile and can participate in provision of balancing energy and other grid services. The use of demand response can greatly reduce the required generation reserve in a clean and environmentally friendly way. In this report, a new frequency responsive load (FRL) controller was proposed based on the GFA controller, which can respond to both over and under-frequency events. A supervisory control was introduced to coordinate the autonomous response from FRLs in order to overcome the issues of excessive system response due to high penetration of FRLs. The effectiveness of the proposed FRL controller was demonstrated by large-scale simulation studies on the WECC system. Specifically, the FRLs were deployed in the WECC system at different penetration levels to analyze the performance of the proposed strategy both with and without supervisory level control. While both methods have their own advantages, the case without supervisory control could lead to system-wide instability depending on the size of the contingency and the number of FRLs deployed in the system. In addition, the voltage impacts of this controller on distribution system were also carefully investigated. Finally, a preliminary measurement and verification approach was also developed.
Hydrogenation of Aldehydes, Esters, Imines, and Ketones Catalyzed by a Ruthenium Complex of a Chiral Tridentate Ligand (2006)

A novel ruthenium complex prepared from a chiral tridentate amine functionalized phosphine has been characterized by X-ray crystallography and been found to be active in the hydrogenation of an unprecedented range of CO and CN double bonds, including the enantioselective hydrogenation and transfer hydrogenation of normally unreactive bulky ketones with up to 90% ee.
Unconventional detection methods for microfluidic devices (2006)

The direction of modern analytical techniques is to push for lower detection limits, improved selectivity and sensitivity, faster analysis time, higher throughput, and more inexpensive analysis systems with ever-decreasing sample volumes. These very ambitious goals are exacerbated by the need to reduce the overall size of the device and the instrumentation - the quest for functional micrototal analysis systems epitomizes this. Microfluidic devices fabricated in glass, and more recently, in a variety of polymers, brings us a step closer to being able to achieve these stringent goals and to realize the economical fabrication of sophisticated instrumentation. However, this places a significant burden on the detection systems associated with microchip-based analysis systems. There is a need for a universal detector that can efficiently detect sample analytes in real time and with minimal sample manipulation steps, such as lengthy labeling protocols. This review highlights the advances in uncommon or less frequently used detection methods associated with microfluidic devices. As a result, the three most common methods - LIF, electrochemical, and mass spectrometric techniques - are omitted in order to focus on the more esoteric detection methods reported in the literature over the last 2 years.
An introduction to data warehousing: what are the implications for the network? (1998)

Data warehousing is an information systems environment, rather than a product. It has emerged as an essential business entity for sophisticated analysis of data. This article presents a clear overview of the implications of data warehousing for business. © 1998 John Wiley & Sons, Ltd.
Nucleotide Sequence of SRV-1, a Type D Simian Acquired Immune Deficiency Syndrome Retrovirus (1986)

Simian acquired immune deficiency syndrome (SAIDS) in the macaque genus of monkeys at the California Primate Research Center is apparently caused by infection by a type D retrovirus. The complete nucleotide sequence (8173 base pairs) of a molecular clone of the prototype SAIDS virus isolate, SRV-1, reveals a typical retrovirus structure with long terminal repeats (346 base pairs) and open reading frames for the gag (663 codons), pol (867 codons), and env (605 codons) genes. SRV-1 also has a separate open reading frame of 314 codons between the gag and pol genes that defines the viral protease gene (prt) and a short open reading frame of unknown significance downstream from the env gene. The SRV-1 protease region shows a high degree of homology to its counterpart in the hamster intracisternal A-type particle genome; both these protease genes are about twice as long as the analogous region of other retroviruses. SRV-1 has no notable similarity in either genetic organization or sequence to the human AIDS retroviruses.
Neurodegeneration in multiple sclerosis: novel treatment strategies (2012)

In recent years it has become clear that the neuronal compartment already plays an important role early in the pathology of multiple sclerosis (MS). Neuronal injury in the course of chronic neuroinflammation is a key factor in determining long-term disability in patients. Viewing MS as both inflammatory and neurodegenerative has major implications for therapy, with CNS protection and repair needed in addition to controlling inflammation. Here, the authors' review recently elucidated molecular insights into inflammatory neuronal/axonal pathology in MS and discuss the resulting options regarding neuroprotective and regenerative treatment strategies.
Proportional-resonant controllers and filters for grid-connected voltage-source converters (2006)

The recently introduced proportional-resonant (PR) controllers and filters, and their suitability for current/voltage control of grid-connected converters, are described. Using the PR controllers, the converter reference tracking performance can be enhanced and previously known shortcomings associated with conventional PI controllers can be alleviated. These shortcomings include steady-state errors in single-phase systems and the need for synchronous d–q transformation in three-phase systems. Based on similar control theory, PR filters can also be used for generating the harmonic command reference precisely in an active power filter, especially for single-phase systems, where d–q transformation theory is not directly applicable. Another advantage associated with the PR controllers and filters is the possibility of implementing selective harmonic compensation without requiring excessive computational resources. Given these advantages and the belief that PR control will find wide-ranging applications in grid-interfaced converters, PR control theory is revised in detail with a number of practical cases that have been implemented previously, described clearly to give a comprehensive reference on PR control and filtering.