gebhart/patrepeval huggingface dataset:
Abstract ES2-3: The Clonal and Mutational Composition of Triple Negative Breast Cancers (2012)

Abstract The notion that cancers are mosaics, composed of clones of cells has been fundamental to cancer biology for several decades. Clonal evolution may underpin clinical features of cancer, such as emergence of treatment resistance, the heterogeneous responses of metastatic disease within individual patients and divergence between primary and metastatic disease. Spatial and temporal variation in clonal composition poses significant challenges for diagnostic sampling and disease monitoring. We have recently developed next generation sequencing approaches to these questions and applied them to the understanding of mutational and clonal composition of primary triple negative breast cancers (TNBC). The notion that triple negative breast cancers form a distinct disease entity is already strongly challenged by expression analysis and small scale mutational analysis. Our results show that both the mutational composition and clonal structure of primary triple negative breast cancers is in fact a complete spectrum, exploding the notion of TNBC (currently defined), as a distinct disease. Clonal analysis suggests a means by which the genetic complexity might be reduced by following patient evolution over time and space. I will discuss the specific implications of the mutational and transcriptome landscapes of TNBC in relation to possible disease biologies. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr ES2-3.
Electrogates for stop-and-go control of liquid flow in microfluidics (2018)

Diagnostics based on microfluidic devices necessitate specific reagents, flow conditions, and kinetics for optimal performance. Such an optimization is often achieved using assay-specific microfluidic chip designs or systems with external liquid pumps. Here, we present “electrogates” for stop-and-go control of flow of liquids in capillary-driven microfluidic chips by combining liquid pinning and electrowetting. Electrogates are simple to fabricate and efficient: a sample pipetted to a microfluidic chip flows autonomously in 15-μm-deep hydrophilic channels until the liquid meniscus is pinned at the edge of a 1.5-μm-deep trench patterned at the bottom of a rectangular microchannel. The flow can then be resumed by applying a DC voltage between the liquid and the trench via integrated electrodes. Using a trench geometry with a semicircular shape, we show that retention times longer than 30 min are achieved for various aqueous solutions such as biological buffers, artificial urine, and human serum. We studied the activation voltage and activation delay of electrogates using a chip architecture having 6 independent flow paths and experimentally showed that the flow can be resumed in less than 1 s for voltages smaller than 10 V, making this technique compatible with low-power and portable microfluidic systems. Electrogates therefore can make capillary-driven microfluidic chips very versatile by adding flow control in microfluidic channels in a flexible manner.
DNA binding activity of the Arabidopsis G-box binding factor GBF1 is stimulated by phosphorylation by casein kinase II from broccoli. (1992)

To study the phosphorylation of one of the G-box binding factors from Arabidopsis (GBF1), we have obtained large amounts of this protein by expression in Escherichia coli. Bacterial GBF1 was shown to be phosphorylated very efficiently by nuclear extracts from broccoli. The phosphorylation activity was partially purified by chromatography on heparin-Sepharose and DEAE-cellulose and was characterized. It showed the essential features of casein kinase II activity: utilization of GTP in addition to ATP as a phosphate donor, strong inhibition by heparin, preference for acidic protein substrates, salt-induced binding to phosphocellulose, and salt-dependent deaggregation. The very low Km value for GBF1 (220 nM compared to approximately 10 microM for casein) was in the range observed for identified physiological substrates of casein kinase II. Phosphorylation of GBF1 resulted in stimulation of the G-box binding activity and formation of a slower migrating protein-DNA complex. The conditions of this stimulatory reaction fully corresponded to the properties of casein kinase II, in particular its dependence on the known phosphate donors. The DNA binding activity of the endogenous plant GBF was shown to be reduced by treatment with calf alkaline phosphatase; this reduction was diminished by addition of fluoride and phosphate or incubation in the presence of casein kinase II and ATP.
Stationary Detection of the Pedestrian?s Intention at Intersections (2013)

This paper focuses on stat ionary detect ion of the pedestrian's intention to enter the traffic lane at intersections. We use an Interacting Multiple Model Extended Kalman Filter (IMM-EKF) based tracking approach as basic method to recognize this. In addition, we propose a novel Motion Contour image based HOG-like descriptor (MCHOG) in combination with Support Vector Machine (SVM) classification that reaches the decision at an accuracy of 99 % within the initial step at the curb of smart infrastructure. MCHOG implicitly comprises the body language of gait initiation, especially the body bending and the spread of legs. As a result of a case study at laboratory conditions we present Receiver Operating Characteristic (ROC) performance data and an evaluation of the span of time necessary for recognition. While MCHOG in special cases indicates detection of the intention before the whole body moves, on average it allows for detection of gait initiation within 6 frames at a frame rate of 50 Hz and an accuracy of 80%. In addition to a comprehensive evaluation under laboratory conditions we demonstrate feasibility of the methods in a real world intersection scenario and we show the gain which we achieve with MCHOG compared to the IMM-EKF approach.
Solution structure and domain architecture of the divisome protein FtsN (2004)

Summary Prokaryotic cell division occurs through the formation of a septum, which in Escherichia coli requires coordination of the invagination of the inner membrane, biosynthesis of peptidoglycan and constriction of the outer membrane. FtsN is an essential cell division protein and forms part of the divisome, a putative complex of proteins located in the cytoplasmic membrane. Structural analyses of FtsN by nuclear magnetic resonance (NMR) reveals an RNP‐like fold at the C‐terminus (comprising residues 243–319), which has significant sequence homology to a peptidoglycan‐binding domain. Sequential deletion mutagenesis in combination with NMR shows that the remaining of the periplasmic region of FtsN is unfolded, with the exception of three short, only partially formed helices following the trans ‐membrane helix. Based on these findings we propose a model in which FtsN, anchored in the inner membrane, bridges over to the peptidoglycan layer, thereby enabling the coordination of the divisome and the murein‐shaping machinery in the periplasm.
Calcium-dependent affinity chromatography of S-100 and calmodulin on calmodulin antagonist-coupled Sepharose. (1981)

Two different calcium-binding proteins, S-100 and calmodulin, have been isolated from bovine brain by calcium-dependent affinity chromatography on calmodulin antagonist coupled to Sepharose. Calmodulin antagonist N-(6-aminohexyl)-5-chloro-l-napthdenesulfonamide (W-7) has been coupled to epoxy-activated Sepharose 6B or cyanogen bromide-acitivated Sepharose 4B. S-100-like protein bound to W-7 coupled to epoxy-activated Sepharose 6B in the presence of Ca2+ was eluted with the buffer containing 4 m~ ethylene glycol bis(j3-aminoethyl ether)-N,NJ?’,iV-tetraacetic acid (EGTA) instead of Ca2+. This protein did not stimulate cyclic nucleotide phosphodiesterase and was identified as S-100 by demonstrating its cross-reaction with rabbit antisera to bovine 5-100. Amino acid composition together with electrophoretic evidence shows that S-100-like protein is a mixture of S-100a and S100b. Calmodulin-like protein bound to W-7 coupled to cyanogen bromide-activated Sepharose 4B in the presence of Ca2+ was eluted with buffer containing 4 m~ EGTA. This protein could stimulate cyclic nucleotide phosphodiesterase and had an amino acid compostion and electrophoretic mobility very similar to those of calmodulin, indicating that this protein is calmodulin. When N-6-aminohexyl)-l-naphthalene sulfonamide (W5), a chloro-deficient analogue which has lower affinity for calmodulin than W-7, was coupled to epoxy-activated Sepharose 6B, calmodulin instead of S-100 did bind to this Sepharose in the presence of Ca2+ and was eluted with the buffer containing 4 mM EGTA. These results indicate that different immobilized naphthalenesulfonamide derivatives interact differently with S100 and calmodulin in a calcium-dependent manner and provide a rapid purification procedure for S-100 and calmodulin.
Efficient and Accurate Discovery of Patterns in Sequence Data Sets (2011)

Existing sequence mining algorithms mostly focus on mining for subsequences. However, a large class of applications, such as biological DNA and protein motif mining, require efficient mining of “approximate” patterns that are contiguous. The few existing algorithms that can be applied to find such contiguous approximate pattern mining have drawbacks like poor scalability, lack of guarantees in finding the pattern, and difficulty in adapting to other applications. In this paper, we present a new algorithm called FLexible and Accurate Motif DEtector (FLAME). FLAME is a flexible suffix-tree-based algorithm that can be used to find frequent patterns with a variety of definitions of motif (pattern) models. It is also accurate, as it always finds the pattern if it exists. Using both real and synthetic data sets, we demonstrate that FLAME is fast, scalable, and outperforms existing algorithms on a variety of performance metrics. In addition, based on FLAME, we also address a more general problem, named extended structured motif extraction, which allows mining frequent combinations of motifs under relaxed constraints.
Multiple-access performance limits with time hopping and pulse position modulation (2002)

The use of spread spectrum time hopping in combination with pulse position modulation for multiple access communications is studied. The multiple access performance is described in terms of the number of users supported by the system for a given bit error rate and bit transmission rate. Expressions for the maximum number of users and maximum transmission capacity in bits per second are found. Asymptotic values for these quantities are derived.
Controlled Release Biopolymers for Enhancing the Immune Response (2007)

Controlled release of biologically active compounds in the context of drug and vaccine delivery is an important area of research with broad implications in many areas of medicine. In particular, the challenges of oral delivery are of specific interest to reduce the cost and potential health risks related to parenteral administration of pharmaceuticals and vaccine formulations. We discuss the biological activities of two biopolymers, beta-glucans and emulsans, both of which offer significant potential for individual formulations related to drug impact, while in combination offer synergistic opportunities in terms of formulation and delivery. beta-Glucans have been established as potent immunomodulatory and biologically active compounds with application in a wide range of disease systems. The emulsan family of biopolymers also has significant potential in vaccine and drug delivery based on recent studies. Each of these biopolymers offers exciting opportunities to modulate biological responses via control of chemistry and physical properties achieved during biosynthesis or postsynthesis modifications. When combined into a delivery system for controlled release, synergistic outcomes may be achieved that offer new and exciting opportunities as described in the present paper. These outcomes represent the combined improvements of solubility in physiological environments and immunomodulation due to the specific chemistry and structures involved. Overall, this approach provides a new direction in controlled release wherein the biomaterial carrier, in this case emulsan, and the drug, in this case beta-glucan, play an active role both in biological activation as well as in delivery profiles.
On a class of approximate formulas for total ח-electron energy of benzenoid hydrocarbons (2001)

The method for obtaining approximate formulas of the (n, m)-type for the total -electron energy of benzenoid hydrocarbons (communicated in J. Serb. Chem. Soc. 54 (1989) 189) is simplified and extended so as to include arbitrary spectral moments. The accuracy of the formulas thus obtained is very good and these need no additional fitting by means of empirically determined parameters.
Effects of the ion-channel blocker quinine on human sperm volume, kinematics and mucus penetration, and the involvement of potassium channels (2001)

Sperm defects in the infertile c-ros knockout mouse model have recently highlighted the importance of volume regulation in sperm function. In this study, washed human spermatozoa were shown to change size and shape, as detected by flow cytometry and light microscopy, in response to the ion-channel blocker quinine (minimum effective doses at 20 and 125 micromol/l respectively). The increase in sperm volume was accompanied by reduced straight-line velocity (VSL) and linearity (LIN) of the swim-path but increased lateral head displacement and curvilinear velocity, while percentage motility was unaffected. Spermatozoa in semen and in artificial cervical mucus were similarly affected at 0.2 and 0.5 mmol/l quinine, resulting in marked reduction of mucus penetration and migration. The effects of quinine on sperm volume and kinematics were reduced or abolished by the K(+)-ionophores valinomycin (1 and 5 micromol/l) and gramicidin (0.5 and 1 micromol/l). In Ca(2+)-free medium; however, the quinine effects largely persisted. The K(+)-channel blocker, 4-aminopyridine (1 and 4 mmol/l), mimicked the quinine effects in the reduction of VSL and LIN, while the K(+)-channel blocker, tetraethylammonium chloride (TEA, 2.5-10 mmol/l), did not affect kinematics. The K(+)-channel (Kv1.3)-specific inhibitor, margatoxin, and the Ca(2+)-dependent K(+)-channel blocker, charybdotoxin, also had no effects. This study suggests that volume regulation in human spermatozoa and the linear trajectory of their motion may rely on quinine-sensitive and TEA-insensitive, largely calcium-independent, potassium channels, and possibly volume-sensitive organic anion channels. These channels could be targets for contraception.
A Medicinal Chemist’s Guide to Molecular Interactions (2010)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTADDITION / CORRECTIONThis article has been corrected. View the notice.A Medicinal Chemist's Guide to Molecular InteractionsCaterina Bissantz, Bernd Kuhn, and Martin Stahl*View Author Information Discovery Chemistry, F. Hoffmann-La Roche AG, CH-4070 Basel, Switzerland*To whom correspondence should be addressed. Phone: +41616888421. Fax: +41616888421. E-mail: [email protected]Cite this: J. Med. Chem. 2010, 53, 14, 5061–5084Publication Date (Web):March 26, 2010Publication History Received27 January 2010Published online26 March 2010Published inissue 22 July 2010https://doi.org/10.1021/jm100112jCopyright © 2010 American Chemical SocietyRIGHTS & PERMISSIONSACS AuthorChoiceArticle Views105668Altmetric-Citations1107LEARN 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 InReddit PDF (6 MB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Aromatic compounds,Group 17 compounds,Ligands,Molecules,Noncovalent interactions Get e-Alerts
Preload-Based Starling-Like Control for Rotary Blood Pumps: Numerical Comparison with Pulsatility Control and Constant Speed Operation (2015)

In this study, we evaluate a preload-based Starling-like controller for implantable rotary blood pumps (IRBPs) using left ventricular end-diastolic pressure (PLVED) as the feedback variable. Simulations are conducted using a validated mathematical model. The controller emulates the response of the natural left ventricle (LV) to changes in PLVED. We report the performance of the preload-based Starling-like controller in comparison with our recently designed pulsatility controller and constant speed operation. In handling the transition from a baseline state to test states, which include vigorous exercise, blood loss and a major reduction in the LV contractility (LVC), the preload controller outperformed pulsatility control and constant speed operation in all three test scenarios. In exercise, preload-control achieved an increase of 54% in mean pump flow ([Formula: see text]) with minimum loading on the LV, while pulsatility control achieved only a 5% increase in flow and a decrease in mean pump speed. In a hemorrhage scenario, the preload control maintained the greatest safety margin against LV suction. PLVED for the preload controller was 4.9 mmHg, compared with 0.4 mmHg for the pulsatility controller and 0.2 mmHg for the constant speed mode. This was associated with an adequate mean arterial pressure (MAP) of 84 mmHg. In transition to low LVC, [Formula: see text] for preload control remained constant at 5.22 L/min with a PLVED of 8.0 mmHg. With regards to pulsatility control, [Formula: see text] fell to the nonviable level of 2.4 L/min with an associated PLVED of 16 mmHg and a MAP of 55 mmHg. Consequently, pulsatility control was deemed inferior to constant speed mode with a PLVED of 11 mmHg and a [Formula: see text] of 5.13 L/min in low LVC scenario. We conclude that pulsatility control imposes a danger to the patient in the severely reduced LVC scenario, which can be overcome by using a preload-based Starling-like control approach.
Continuous subcutaneous octreotide in gastrointestinal cancer patients: pain control and beta-endorphin levels. (2001)

Octreotide can be used as an adjuvant analgesic in the management of gastrointestinal cancer pain which is managed by continuous s.c. administration. Although fuither research needs to be done, octreotide's administration seemed to improve hepatic function of these patients, therefore, it could potentially have a positive effect in the patient's quality of life.
Phase I study of DFP-11207, a novel oral fluoropyrimidine with reasonable AUC and low Cmax and improved tolerability, in patients with solid tumors (2020)

5-fluorouracil (5-FU) and 5-FU derivatives, such as capecitabine, UFT, and S-1, are the mainstay of chemotherapy treatment for gastrointestinal cancers, and other solid tumors. Compared with other cytotoxic chemotherapies, these drugs generally have a favorable safety profile, but hematologic and gastrointestinal toxicities remain common. DFP-11207 is a novel oral cytotoxic agent that combines a 5-FU pro-drug with a reversible DPD inhibitor and a potent inhibitor of OPRT, resulting in enhanced pharmacological activity of 5-FU with decreased gastrointestinal and myelosuppressive toxicities. In this Phase I study (NCT02171221), DFP-11207 was administered orally daily, in doses escalating from 40 mg/m<sup>2</sup>/day to 400 mg/m<sup>2</sup>/day in patients with esophageal, colorectal, gastric, pancreatic or gallbladder cancer (n = 23). It was determined that DFP-11207 at the dose of 330 mg/m<sup>2</sup>/day administered every 12 hours was well-tolerated with mild myelosuppressive and gastrointestinal toxicities. The pharmacokinetic analysis determined that the 5-FU levels were in the therapeutic range at this dose. In addition, fasted or fed states had no influence on the 5-FU levels (patients serving as their own controls). Among 21 efficacy evaluable patients, 7 patients had stable disease (33.3%), of which two had prolonged stable disease of >6 months duration. DFP-11207 can be explored as monotherapy or easily substitute 5-FU, capecitabine, or S-1 in combination regimens.
Stability analysis of grid-connected voltage source inverters with LCL-filters using partial state feedback (2007)

This paper addresses the stability of discrete controlled grid connected voltage source inverters with LCL-filter usually found in wind power generation systems. First a theorem that relates the controllability of the discrete dynamic equation with the LCL-filter parameters and the sampling frequency is derived. Then, a robust partial state feedback design on the linear matrix inequalities framework guarantee the stability damping the LCL-filter resonance for a large set of grid conditions without requiring tuning procedures. Finally, an internal model controller is added to ensure asymptotic reference tracking and disturbance rejection, therefore reducing significantly the impact of grid background voltage distortion on the line currents. Simulation and experimental results are presented to support the theoretical analysis carried out and to demonstrate the system performance.
Diffusional Viscosity of a Polycrystalline Solid (1950)

According to a suggestion of Nabarro, any crystal can change its shape by self-diffusion in such way as to yield to an applied shearing stress, and this can cause the macroscopic behavior of a polycrystalline solid to be like that of a viscous fluid. It is possible that this phenomenon is the predominant cause of creep at very high temperatures and very low stresses, though not under more usual conditions. The theory underlying it is developed quantitatively, and calculations of rate of creep, or equivalently of effective viscosity, are given for aggregates of quasi-spherical grains and for wires composed of cylindrical grains. Allowance is made for the effect of tangential stress relaxation at the grain boundaries. It is suggested that mosaic boundaries and boundaries between grains of nearly the same orientation may be unable to serve as sources or sinks of the diffusion currents, in which case the creep rate will depend only on the configuration of grain boundaries having a sizable orientation difference. Numerical comparison of the theory with experiments on the high temperature creep of wires favors this view, but is not entirely satisfactory. Suggestions for further experiments are made.