gebhart/patrepeval huggingface dataset:
Update on a phase (ph) 2 study of bortezomib in patients (pts) with relapsed or refractory indolent or aggressive non-Hodgkin's lymphomas (NHL) (2004)

6581 Background: Proteasome inhibition disrupts many cell cycle checkpoints and pathways that lead to apoptosis. Preclinical and ph 1 studies suggested the proteasome inhibitor bortezomib (VELCADE™, Vc) was active in lymphoma. Methods: The primary objective of this ph 2 study was to document the response rate (RR) and toxicity of Vc in pts with relapsed or refractory NHL. Pts ≥ 16 yr, with relapsed or refractory mantle cell (MCL, gp A) or other B cell lymphomas (gp B) were eligible. Pts received Vc 1.5 mg/m2 IV on d1, 4, 8 and 11 q21d, were restaged q2 cycles, and treated for up to 6 cycles unless removed from study. Results:45 pts: 32 males, 13 females, median age 60 yr (range 45–81), were enrolled. There were 25 pts in gp A and 20 pts in gp B, including 10 diffuse large cell lymphoma (DLCL), 4 follicular lymphoma (FL), 3 transformed (t) FL, 2 small lymphocytic lymphoma (SLL), 1 Waldenström's macroglobulinemia (WM). Gp A had 3 median prior therapies (range 1–6); gp B had 4 (range 1–12). In gp A, of 21 evaluable (ev) pts, there were 11 responders: 3 CR, 1 CRu (unconfirmed CR), and 7 PR (RR = 52.3%), 2 MR, 2 no change (NC), 6 POD (progression of disease). Mean DOR (duration of response) was 5.7 mo (1.2–15 mo). In gp B, there were 8 ev DLCL with 1 PR (DOR 4 mo), 1 NC, 6 POD; 4 ev FL with 2 MR, 1 NC, 1 POD; 1 ev tFL with POD; 2 ev SLL with 1 NC, 1 POD; 1 WM pt had PR. Grade 3/4 toxicities were GI (5 pts), hypotension/fatigue (6 pts), neuropathy (1 pt with prior vinca/taxanes), and pneumonia (2 pts); hematologic toxicities were neutropenia (8) (only 1 pt with ANC <500) and thrombocytopenia (14 pt) (only 1 pt with platelets <10; most entered with platelets <30–50). 2 patients died: 1 had Cryptococcus meningitis, 1 had generalized zoster with encephalitis. Conclusions: This study showed remarkable activity of Vc in MCL and encouraging results in other B cell lymphomas. Future studies will include combinations of Vc with other chemotherapy and/or biological agents. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Millennium Pharmaceuticals, Inc. Millennium Pharmaceuticals, Inc. Millennium Pharmaceuticals, Inc.
Prognostic value of<i>ERBB</i>family mRNA expression in breast carcinomas (2003)

The ErbB-driven autocrine growth pathway has been implicated in the development and progression of most common human epithelial malignancies; its blockade is therefore a promising therapeutic strategy, and several candidate drugs are currently undergoing clinical trials. Paradoxically, little is known of the expression pattern of these 4 genes in human tumors, and the clinical significance of the 2 most recently discovered ERBB genes, ERBB3 and ERBB4, is unclear. We used a real-time quantitative RT-PCR assay to quantify ERBB family mRNA copy numbers in a large series of breast tumors from patients with known long-term outcome. ERBB gene expression varied widely, by more than 2 orders of magnitude for ERBB1 and ERBB3, more than 3 orders for ERBB2 and more than 4 orders for ERBB4. We found a positive correlation between ERBB3 and ERBB4 mRNA levels, and a negative correlation between the expression of these 2 latter genes and that of ERBB1. Compared to normal breast tissue, ERBB1 was underexpressed (82.3% of tumors), ERBB2 (16.9%) and ERBB3 (46.2%) were overexpressed and ERBB4 was both underexpressed (24.6%) and overexpressed (29.2%). Links were also found between ERBB status on the one hand and Scarff-Bloom-Richardson (SBR) histopathological grade and estrogen receptor alpha (ERa) status on the other hand. Relapse-free survival (RFS) was shorter among patients with ERBB3-overexpressing tumors (p=0.0092) and longer among those with ERBB4-underexpressing tumors (p=0.0085) relative to patients with normal expression of the respective genes; in contrast, RFS was not significantly influenced by ERBB1 or ERBB2 mRNA status. Only ERBB4 status retained prognostic significance in Cox multivariate regression analysis (p=0.015). Our results point to the involvement of several ErbB-specific ligands (amphiregulin and neuregulin 1) and enzymes or adaptor molecules (PI3K, Src, Shc and Grb7) in the ErbB pathway dysregulation associated with breast cancer. These findings reveal a complex expression pattern of ERBB gene family members in breast tumors and suggest that it is this pattern of expression, rather than the expression of individual family members, that should be taken into account when evaluating antitumoral drugs designed to target these receptors.
Interoperability of Wi-Fi hotspots and cellular networks (2004)

The widespread deployment of Wi-Fi hotspots and wide area cellular networks opens up the exciting possibility of interoperability between these types of networks. Interoperability allows a mobile device to dynamically use the multiple net-work interfaces available to it so as to maximize user satisfaction and system performance. In this paper, we define three basic user profiles for the network users and demonstrate through simulation studies that dynamic switching on the basis of the user profiles of the mobile devices leads to higher network performance and increased user satisfaction. Careful design of pricing, billing and revenue sharing schemes is necessary to ensure the commercial viability of the multiple service providers involved in an inter-operable network setting. Different pricing and revenue sharing schemes are introduced and analyzed using simulation studies. We also demonstrate how load balancing can improve network performance in an inter-operable network.
Dynamic breast MRI with spiral trajectories: 3D versus 2D (2000)

A three-dimensional (3)D spiral sequence was developed for dynamic breast magnetic resonance (MR) imaging with much improved image quality. Partial Z phase encoding was applied to obtain thinner slices for a coverage of the whole breast. Comparison between the 3D and a previously developed multi-slice 2D spiral sequences was performed on ten healthy volunteers without contrast and five breast patients with gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA). The 3D spiral images had significantly less off-resonance blurring and spiral artifacts. With a small compromise on temporal resolution (7.7 seconds in 2D and 10.6 seconds in 3D), we obtained 32 interpolated 3-5 mm slices (with 20 Z phase encodes) for a full coverage of 10-16 cm breast with the same 1 x 1 mm2 in-plane resolution as the 2D sequence, which had 12 8-13 mm slices. Contrast between glandular and soft tissue in normal breasts was increased by about 25%. The reduced repetition time in the 3D spiral acquisition led to an increased Gd-enhanced signal. The difference between the enhancement of malignant and benign lesions increased by sevenfold. We expect that this new development could lead to improved specificity in characterizing breast lesions using MR imaging.
Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weapons-related radiocarbon. (1991)

Normal structure and function of the lung parenchyma depend upon elastic fibers. Amorphous elastin is biochemically stable in vitro, and may provide a metabolically stable structural framework for the lung parenchyma. To test the metabolic stability of elastin in the normal human lung parenchyma, we have (a) estimated the time elapsed since the synthesis of the protein through measurement of aspartic acid racemization and (b) modeled the elastin turnover through measurement of the prevalence of nuclear weapons-related 14C. Elastin purified by a new technique from normal lung parenchyma was hydrolyzed; then the prevalences of D-aspartate and 14C were measured by gas chromatography and accelerator-mass spectrometry, respectively. D-aspartate increased linearly with age; Kasp (1.76 x 10(-3) yr(-1) was similar to that previously found for extraordinarily stable human tissues, indicating that the age of lung parenchymal elastin corresponded with the age of the subject. Radiocarbon prevalence data also were consistent with extraordinary metabolic stability of elastin; the calculated mean carbon residence time in elastin was 74 yr (95% confidence limits, 40-174 yr). These results indicate that airspace enlargement characteristic of "aging lung" is not associated with appreciable new synthesis of lung parenchymal elastin. The present study provides the first tissue-specific evaluation of turnover of an extracellular matrix component in humans and underscores the potential importance of elastin for maintenance of normal lung structure. Most importantly, the present work provides a foundation for strategies to directly evaluate extracellular matrix injury and repair in diseases of lung (especially pulmonary emphysema), vascular tissue, and skin.
Clinical quantitative pupillometry: The latency of pupillary constriction as measured with the IRIS system (preliminary results) (1988)

Using the IRIS pupillometer described by Reulen et at. (1988), a group of 46 patients suffering from optic neuritis was investigated. The latency of the pupil constriction was determined and shown to be prolonged when the affected eye was stimulated with visible light, prolonged with respect to stimulation of the healthy fellow eye. In a small group of nine myotonic dystrophy patients also the latency of the peak constriction was measured. In the latter group only the interval between onset of constriction and peak velocity was prolonged. This interval could not be proven to be prolonged in the group of optic neuritis patients. This may indicate that the constriction latency is a reliable parameter for detecting nervous dysfunction, while the difference between moment of onset and peak velocity can be used to determine muscle dysfunction.
A Combination of Leucine, Metformin, and Sildenafil Treats Nonalcoholic Fatty Liver Disease and Steatohepatitis in Mice (2016)

Sirt1, AMPK, and eNOS modulate hepatic energy metabolism and inflammation and are key players in the development of NASH. L-leucine, an allosteric Sirt1 activator, synergizes with low doses of metformin or sildenafil on the AMPK-eNOS-Sirt1 pathway to reverse mild NAFLD in preclinical mouse models. Here we tested a possible multicomponent synergy to yield greater therapeutic efficacy in NAFLD/NASH. Liver cells and macrophages or an atherogenic diet induced NASH mouse model was treated with two-way and three-way combinations. The three-way combination Sild-Met-Leu increased hepatic fatty acid oxidation and reduced lipogenic gene expression and inflammatory marker <i>in vitro</i>. In mice, Sild-Met-Leu reduced the diet induced increases of ALT, TGF<i>β</i>, PAI-1, IL1<i>β</i>, and TNF<i>α</i>, hepatic collagen expression, and nearly completely reversed hepatocyte ballooning and triglyceride accumulation, while all two-way combinations had only modest effects. Therefore, these data provide preclinical evidence for therapeutic efficacy of Sild-Met-Leu in the treatment of NAFLD and NASH.
Analysis of a hybrid genetic simulated annealing strategy applied in multi-objective optimization of orbital maneuvers (2017)

Over the several last decades, evolutionary algorithms have been widely used for parameter optimization in different engineering tasks. Engineering optimization has been widely involved in aerospace sciences because of its practicality in obtaining optimal solutions to different challenging problems including dynamics and control of nonlinear systems. Such fields contain different aspects of aerospace engineering including missile systems, unmanned aerial vehicles [8], and hypersonic aircrafts [9]. One of the problems specific to aerospace engineering is the optimization of orbital maneuvers for satellites and spacecraft [10], [11]. This problem requires heuristic search techniques in finding the optimal transfer strategy that minimizes some specific criteria like control effort [12] or fuel mass [13].
Evaluation of Steel Fiber Reinforcement for Punching Shear Resistance in Slab-Column Connections - Part I: Monotonically Increased Load (2010)

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Biology of<i>Pseudomonas stutzeri</i> (2006)

Pseudomonas stutzeri is a nonfluorescent denitrifying bacterium widely distributed in the environment, and it has also been isolated as an opportunistic pathogen from humans. Over the past 15 years, much progress has been made in elucidating the taxonomy of this diverse taxonomical group, demonstrating the clonality of its populations. The species has received much attention because of its particular metabolic properties: it has been proposed as a model organism for denitrification studies; many strains have natural transformation properties, making it relevant for study of the transfer of genes in the environment; several strains are able to fix dinitrogen; and others participate in the degradation of pollutants or interact with toxic metals. This review considers the history of the discovery, nomenclatural changes, and early studies, together with the relevant biological and ecological properties, of P. stutzeri.
Human Bone Marrow Mesenchymal Stem Cells Accelerate Recovery of Acute Renal Injury and Prolong Survival in Mice (2008)

Transplantation of bone marrow mesenchymal stem cells (BM-MSC) or stromal cells from rodents has been identified as a strategy for renal repair in experimental models of acute kidney injury (AKI), a highly life-threatening clinical setting. The therapeutic potential of BM-MSC of human origin has not been reported so far. Here, we investigated whether human BM-MSC treatment could prevent AKI induced by cisplatin and prolong survival in an immunodeficient mouse model. Results showed that human BM-MSC infusion decreased proximal tubular epithelial cell injury and ameliorated the deficit in renal function, resulting in reduced recipient mortality. Infused BM-MSC became localized predominantly in peritubular areas and acted to reduce renal cell apoptosis and to increase proliferation. BM-MSC also induced protection against AKI-related peritubular capillary changes consisting of endothelial cell abnormalities, leukocyte infiltration, and low endothelial cell and lumen volume density as assessed by morphometric analysis. These findings indicate that human MSC of bone marrow origin hold potential to prolong survival in AKI and should be considered for testing in a clinical trial. Disclosure of potential conflicts of interest is found at the end of this article.
Temporal reasoning in sequence graphs (1992)

Temporal reasoning is widely used in AI, especially for natural language processing. Existing methods for temporal reasoning are extremely expensive in time and space, because complete graphs are used. We present an approach of temporal reasoning for expert systems in technical applications that reduces the amount of time and space by using sequence graphs. A sequence graph consists of one or more sequence chains and other intervals that are connected only loosely with these chains. Sequence chains are based on the observation that in technical applications many events occur sequentially. The uninterrupted execution of technical processes for a long time is characteristic for technical applications. To relate the first intervals in the application with the last ones makes no sense. In sequence graphs only these relations are stored that are needed for further propagation. In contrast to other algorithms which use incomplete graphs, no information is lost and the reduction of complexity is significant. Additionally, the representation is more transparent, because the &quot;flow&quot; of time is modelled.
RNA Interference as a Plausible Anticancer Therapeutic Tool (2012)

RNA interference has created a breakthrough in gene silencing technology and there is now much debate on the successful usage of RNAi based methods in treating a number of debilitating diseases. Cancer is often regarded as a result of mutations in genomic DNA resulting in faulty gene expression. The occurrence of cancer can also be influenced by epigenetic irregularities in the chromatin structure which leads to alterations and mutations in DNA resulting in cancer cell formation. A number of therapeutic approaches have been put forth to treat cancer. Anti cancer therapy often involves chemotherapy targeting all the cells in common, whereby both cancer cells as well as normal cells get affected. Hence RNAi technology has potential to be a better therapeutic agent as it is possible to deactivate molecular targets like specific mutant genes. This review highlights the successful use of RNAi inducers against different types of cancer, thereby paving the way for specific therapeutic medicines.
Extracting Renewable Energy from a Salinity Difference Using a Capacitor (2009)

Completely renewable energy can be produced by using water solutions of different salinity, like river water and sea water. Many different methods are already known, but development is still at prototype stage. Here I report a novel method, based on electric double-layer capacitor technology. Two porous electrodes, immersed in the salt solution, constitute a capacitor. It is first charged, then the salt solution is brought into contact with fresh water. The electrostatic energy increases as the salt concentration of the solution is reduced due to diffusion. This device can be used to turn sources of salinity difference into completely renewable sources of energy. An experimental demonstration is given, and performances and possible improvements are discussed.
ChemInform Abstract: A Formal Total Synthesis of (.+‐.)‐Anatoxin‐a by an Intramolecular Pd‐Catalyzed Aminocarbonylation Reaction. (1998)

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.
MediaBroker: an architecture for pervasive computing (2004)

MediaBroker is a distributed framework designed to support pervasive computing applications. Specifically, the architecture consists of a transport engine and peripheral clients and addresses issues in scalability, data sharing, data transformation and platform heterogeneity. Key features of MediaBroker are a type-aware data transport that is capable of dynamically transforming data en route from source to sinks; an extensible system for describing types of streaming data; and the interaction between the transformation engine and the type system. Details of the MediaBroker architecture and implementation are presented in this paper. Through experimental study, we show reasonable performance for selected streaming media-intensive applications. For example, relative to baseline TCP performance, MediaBroker incurs under 11% latency overhead and achieves roughly 80% of the TCP throughput when streaming items larger than 100 KB across our infrastructure.
Power control for a spread spectrum cellular mobile radio system (1983)

In two earlier papers (ICC'80 [3] and GLOBECOM'82 [6]) two power control schemes for spread spectrum cellular land mobile radio have been described, one for the upstream (mobile to base) link and one for the downstream link. Here we compare the power control problem for the upstream and the downstream links and show that using simple algebra we can equalize the signal-to-interference ratio for each mobile in a given cell in both links and thereby increase the capacity by 30 to 100% compared with a system with no power control. We also show that the SIR values can be equalized system-wide for both link directions by means of a nontrivial eigenvalue problem, which results in a further capacity improvement of 10 to 15%. Denial statistics are also presented.
Potential induction of quinone reductase activity of natural products in cultured murine Hepa1c1c7 cells (2001)

NAD(P)H:quinone reductase (QR), known as DT-diaphorase, is a kind of detoxifying phase II metabolic enzyme catalyzing hydroquinone formation by two electron reduction pathway from quinone type compounds, and thus facilitating excretion of quinoids from human body. With the usefulness of QR induction activity assay system for the modulation of toxicants, in the course of searching for cancer chemopreventive agents from natural products, the methanolic extracts of approximately two hundreds of oriental medicines were primarily evaluated using the induction potential of quinone reductase (QR) activity in cultured murine Hepa1c1c7 cells. As a result, several extracts including Hordeum vulgare, Momordica cochinchinensis, Strychnos ignatii, Houttuynia cordata, and Polygala japonica were found to significantly induce QR activity. In addition, the methylene chloride fraction of H. vulgare, one major dietary food source, showed potent induction of QR activity . Further study for isolation of active principles from these lead extracts is warranted for the discovery of novel cancer chemopreventive agents.
Identification of hybridomas derived from mouse CD5+ B lymphocytes by fluorescent staining for cytoplasmic CD5 expression. (1994)

The production of hybridomas derived from CD5+ B lymphocytes is important for studying the immunoglobulin gene repertoire and antibody specificity of this B-lymphocyte subpopulation. However, hybridomas derived from these lymphocytes invariably lose surface membrane expression of CD5 following hybridization. This impedes the unequivocal assignment of the generated hybridomas to the CD5+ B-lymphocyte subpopulation from unsorted, or partially sorted, cells. Recent studies have shown that mRNA transcripts of the CD5 gene and the protein product can be detected in the cytoplasm of some mouse hybridomas, indicating that although surface expression has been lost, they may have been generated from CD5+ B lymphocytes. These studies, however, have been unable to discount completely the possibility that aberrant cytoplasmic expression of the CD5 gene occurred as a direct consequence of the hybridization process. To confirm that cytoplasmic CD5 expression in the hybridomas is in fact directly related to the B-lymphocyte origin we have generated hybridomas from FACS-sorted CD5+ and CD5- murine splenic B lymphocytes, and determined their surface and cytoplasmic CD5 expression by fluorescence-activated cell sorting. Our findings reveal that all hybridomas derived from CD5+ B lymphocytes (nine hybridomas) were negative for surface but positive for cytoplasmic CD5 expression, whereas all hybridomas derived from CD5- B lymphocytes (nine hybridomas) were negative for both surface and cytoplasmic CD5 expression. This finding shows that staining for cytoplasmic CD5 expression provides an accurate method of determining the cellular origin of murine B-lymphocyte hybridomas.