gebhart/patrepeval huggingface dataset:
Targeted Cancer Therapies in the Twenty-First Century: Lessons From Imatinib (2010)

An increased understanding of the molecular etiology of cancer has enabled the development of novel therapies that are collectively referred to as molecular targeted agents. Unlike the drugs used in conventional chemotherapy, these agents are designed to specifically interfere with key molecular events that are responsible for the malignant phenotype. They hold great promise for widening the therapeutic window, which would provide more effective treatment options as compared with cytotoxic therapies. In addition, the targeted approach that is characteristic of these drugs provides unique opportunities for combination therapies with other anticancer agents that have non-overlapping toxicities. Targeted agents are therefore primed to become invaluable therapeutic tools in the multimodal treatment of cancer. The challenges associated with these novel targeted therapies are distinct from those faced in conventional chemotherapy. These unique challenges include the need to select appropriate pharmacodynamic markers to guide dose and schedule and to identify biomarkers that enable selection of patient populations that are most likely to benefit from the treatment. In addition, although the emergence of resistance to targeted therapies is a problem frequently faced in the clinic, the molecular characterization of resistance mechanisms provides the opportunity to design second-generation therapies or combination therapies aimed at preventing resistance or restoring response. The development of the tyrosine kinase inhibitor imatinib has revolutionized the treatment of chronic myeloid leukemia (CML). In this article, we discuss the lessons learned from the application of imatinib and other targeted agents in clinical practice and discuss how these insights may guide the development of novel targeted therapies.
P3‐065: Blood‐based microcirculation markers in Alzheimer's disease: Diagnostic value of CT‐proET‐1 in patients with amnestic mild cognitive impairment (2009)

There is an urgent need for blood-based biological markers of Alzheimer's disease (AD), particularly in its pre-dementia stage of mild cognitive impairment (MCI). Cardiovascular risk factors and circulatory dysfunction are associated with AD pathogenesis. The pro-hormone fragments C-terminal endothelin-1 precursor fragment (CT-proET-1), midregional pro-adrenomedullin (MR-proADM), and midregional pro-atrial natriuretic peptide (MR-proANP), are novel blood-based biological markers for circulatory function and an alteration has recently been shown in AD (Buerger K et al., Biol. Psychiatry, in press). We investigated these blood-based (micro-) circulation markers in the diagnosis of the high risk group of amnestic MCI. We prospectively recruited a volunteer cohort of 51 patients with amnestic MCI and 61 healthy age-matched controls (HC) (mean age 71.2 years). CT-proET-1, MR-proADM, and MR-proANP were analysed in plasma using sandwich luminescence immunoassays. Concentrations of the plasma markers were compared between the two groups by use of analysis of variance (ANOVA). In amnestic MCI patients, plasma concentrations of CT-proET-1 were significantly decreased (p<0.0001) compared to HC subjects. MR-proADM and MR-proANP levels were not significantly altered in amnestic MCI. Amnestic MCI patients could be discriminated from HC with a specificity of 90.2% and a sensitivity of 46.9% based on cut-off values of 47 pmol/L for CT-proET-1. At a cut-off of 53.6 pmol/L, specificity was 82.0% and sensitivity was 57.8%. These findings extend our recent data that report altered expression of (micro-) circulation parameters in AD. We show here alterations even in amnestic MCI, a high-risk group of AD. CT-proET-1, the pro-hormone of Endothelin-1, which acts as a vasoconstrictor on the vasculature, yielded the highest diagnostic accuracy. These study results support the hypothesis of a disturbed (micro-) vascular homeostasis even in the early, pre-dementia MCI stage of AD. MCI patients will be followed for further evaluation of the biomarker, particularly in terms of prediction of AD in amnestic MCI subjects.
Cover Picture: Formation of the Solid Electrolyte Interphase at Constant Potentials: A Model Study on Highly Oriented Pyrolytic Graphite (Batteries & Supercaps 3/2018) (2018)

The front cover artwork is provided by the BMW Group and Lancaster University. The image illustrates the evolution of the solid electrolyte interphase (SEI) on lithium-ion battery anodes during its formation and the probing of its electrochemical properties via the ferrocene outer–sphere reaction. More information can be found in the article by B. Antonopoulos et al. (DOI: 10.1002/batt.201800029
Converting Enzyme Inhibitors and Their Effects on the Renin-Angiotensin System of the Blood Vessel Wall (1989)

A local vascular tissue renin-angiotensin system (RAS) may contribute to blood pressure control and the maintenance of high blood pressure in some forms of hypertension, independently of the plasma RAS. Vascular converting enzyme (CE), present mainly in the endothelial layer of arteries and veins, can be altered in hypertension. Locally generated vascular angiotensin II (ANG II) may exert a number of actions on vascular tone and function, including directly and sympathetically mediated vasoconstriction, changes in vascular compliance in larger vessels, influence on vascular reactions to inflammation and injury, and alterations in vascular texture. Orally administered CE inhibitors have been shown to block not only the plasma RAS but also CE in the vasculature, leading to decreased vascular ANG II concentrations and possibly to an accumulation of locally generated vasodilator peptides and prostaglandins in the vascular wall. In spontaneously hypertensive rats, the slow recovery of CE activity in the vasculature on drug withdrawal was more closely associated with the slow return of blood pressure to hypertensive levels than the fast recovery of the plasma RAS. These and other experimental data discussed in this article favor the hypothesis that local CE inhibition in the vascular wall of resistance vessels, large arteries and veins contributes to the beneficial therapeutic effects of CE inhibitors in cardiovascular disorders such as hypertension and congestive heart failure.
Detectability comparison of simulated objects within a dense breast phantom using high energy x-ray phase sensitive and conventional imaging systems (2017)

The objective of this study was to compare the detectability of simulated objects within a dense breast phantom using high energy x-rays for phase sensitive breast imaging in comparison with a conventional imaging system. A 5 cm thick phantom was used which represented a compressed breast consisting of 70% glandular and 30% adipose tissue ratio in non-uniform background. The phantom had a 6 &times; 6 matrix of holes with milled depths ranging from 1 to 0.1 mm and diameters ranging from 4.25 to 0.25 mm representing simulated tumors. The in-line phase sensitive prototype was equipped with a micro-focus x-ray source and a flat panel detector with a 50 &mu;m pixel pitch, both mounted on an optical rail. Phase contrast image of the phantom was acquired at 120 kVp, 4.5 mAs at source to object distance (SOD) of 68 cm and source to image detector distance (SIDD) of 170 cm with a geometric magnification (M) of 2.5. A 2.5 mm aluminum (Al) filter was used for beam hardening. The conventional image was acquired using the same porotype with the phantom in contact with the detector at 40 kVp, 12.5 mAs under SID = 68 cm. The mean glandular dose (D<sub>g</sub>) for both the acquisitions was 1.3 mGy. The observer study and CNR analyses indicated that the phase contrast image had higher disk detectability as compared to the conventional image. The edge enhancement provided by the phase sensitive images warrants in identifying boundaries of malignant tissues and in providing optimal results in phase retrieval process. The potential demonstrated by this study for imaging a dense breast with a high energy phase sensitive x-ray imaging to improve tumor detection in warrants further investigation of this technique.
Electronic Health Record–Embedded Decision Support Platform for Morphine Precision Dosing in Neonates (2019)

Morphine is the opioid most commonly used for neonatal pain management. In intravenous form, it is administered as continuous infusions and intermittent injections, mostly based on empirically established protocols. Inadequate pain control in neonates can cause long-term adverse consequences; however, providing appropriate individualized morphine dosing is particularly challenging due to the interplay of rapid natural physiological changes and multiple life-sustaining procedures in patients who cannot describe their symptoms. At most institutions, morphine dosing in neonates is largely carried out as an iterative process using a wide range of starting doses and then titrating to effect based on clinical response and side effects using pain scores and levels of sedation. Our background data show that neonates exhibit large variability in morphine clearance resulting in a wide range of exposures, which are poorly predicted by dose alone. Here, we describe the development and implementation of an electronic health record-integrated, model-informed decision support platform for the precision dosing of morphine in the management of neonatal pain. The platform supports pharmacokinetic model-informed dosing guidance and has functionality to incorporate real-time drug concentration information. The feedback is inserted directly into prescribers' workflows so that they can make data-informed decisions. The expected outcomes are better clinical efficacy and safety with fewer side effects in the neonatal population.
Influence of Topology on the Long-Range Electron-Transfer Phenomenon (2001)

Intramolecular electron-transfer phenomena in the radical anions derived from the partial reduction of diradicals (E,E)-p-divinylbenzene-beta,beta'-ylene bis(4-tetradecachlorotriphenylmethyl) diradical (1) and (E,E)-m-divinylbenzene-beta,beta'-ylene bis(4-tetradecachlorotriphenylmethyl) diradical (2) have been studied by optical and ESR spectroscopy. The synthetic methodology used allows for complete control of the geometry of diradicals 1 and 2, which have para and meta topologies, respectively, as well as of their E/Z isomerism. This fact is used to show the influence of the different topologies on the ease of electron transfer, which is larger for the para than for the meta isomer, in which a small or negligible electronic coupling is observed. A related monoradical compound (E)-bis(pentachlorophenyl)[4-(4-bromophenyl-beta-styryl)-2,3,5,6-tetrachlorophenyl]-methyl radical (3), which has only one such redox site, has also been obtained and studied for comparison purposes.
The effect of the pulsatile electromagnetic field in children suffering from bronchial asthma (2003)

From the bibliography it is well known that pulsatile electromagnetic field has an anti-inflammatory and analgesic effect. It causes vasodilatation, myorelaxation, hyper-production of connective tissue and activation of the cell membrane. Therefore our aim was to study the possible therapeutic effect of pulsatile electromagnetic field in asthmatic children. Forty-two children participating in this study were divided in two groups. The 1st group consisting of 21 children (11 females, 10 males, aged 11.8 +/- 0.4 yr) was treated by pulsatile electromagnetic field and pharmacologically. The 2nd group served as control, consisting also of 21 children (11 females, 10 males, aged 11.7 +/- 0.3 yr) and was treated only pharmacologically. Therapeutic effect of the pulsatile electromagnetic field was assessed on the basis of pulmonary tests performed by means of a Spirometer 100 Handi (Germany). The indexes FVC, IVC, ERV, IRV, FEV1, FEV1/FVC%, MEF75,50,25, PEF, PIF and the changes of the flow-volume loop were also registered. The pulsatile electromagnetic field was applied by means of the device MTU 500H, Therapy System (Brno, Czech Republic) for 5 days, two times daily for 30 minutes (magnetic induction: 3 mT, frequency: 4 Hz as recommended by the manufacturer). The results in children of the 1st group showed an improvement of FVC of about 70 ml, IVC of about 110 ml, FEV1 of about 80 ml, MEF75 of about 30 ml, PEF of about 480 ml, PIF of about 550 ml. The increases of ERV, IRV and FEV1/FVC and decreases of MEF25,50 were statistically insignificant. The results in the 2nd group were less clear. The flow-volume loop showed a mild improvement in 14 children. This improvement in the 2nd group was less significant. The clinical status of children and their mood became better. We believe that the pulsatile electro-magnetotherapy in children suffering from asthma is effective. On the basis of our results we can recommend it as a complementary therapy.
Orchestra!: a distributed platform for virtual musical groups and music distance learning over the Internet in Java/sup TM/ technology (2003)

This paper proposes a platform for musical group sessions over the Internet. It has been conceived as an useful instrument for collaborative music developing and enjoying, both at the professional and at the "amateur" level. It has been designed for music distance learning, as well. The system, that we named "Orchestra!", is based on a distributed software architecture and its services are universally accessible through a simple http-client (a browser) and a sound card. Geographical packet-switched network latencies make it impossible to reach a real musical synchronisation among all members of a virtual group. As an alternative, it has been developed a system of progressive and collaborative elaboration of musical audio streams which is insensitive to delays: this idea permits to reproduce "live" performances as well as recording studio activities.
Charge diffusion noise in monocrystalline PbS nanoparticle films (2000)

Charge transport in monocrystalline lead sulfide (PbS) nanoparticle films is investigated by current noise measurements. Monocrystalline and single-sized PbS nanoparticles are synthesized via the gas phase and deposited electrostatically onto semiconducting (GaAs) and on isolating (SiNx) substrates with planar electrode contacts. The particles form inhomogeneous films. Low-frequency current noise of 1-ML-thick films are measured at various voltages, exhibiting diffusion noise characteristics, which indicates a random-walk (diffusion) phenomenon of electrons between the particles.
In vitro clastogenicity of optical isomers of nadifloxacin. (1994)

The potential of optical isomers of the fluoroquinolone antibacterial agent nadifloxacin (NDFX, CAS 124858-35-1) to induce chromosomal aberrations in vitro was investigated in cultured Chinese hamster lung (CHL) cells for 24 h of continuous treatment. S- and R-enantiomers of NDFX showed significant differences in the results of the chromosomal aberration test, but no marked differences in the results of cytotoxicity test, i.e., S-NDFX induced chromosomal aberrations, but R-NDFX did not. These results were equivalent to those obtained with ofloxacin (OFLX, CAS 83380-47-6), which has a chemical structure similar to that of NDFX. Moreover, although neither NDFX nor OFLX induced aberrations, their mixtures, prepared from equal amounts of S- and R-enantiomers, did. This finding suggests that the racemic compound and the mixture of S- and R-enantiomers exist under different conditions within the solution.
Fractional-order sliding-mode stabilization of nonholonomic mobile robots based on dynamic feedback linearization (2016)

This paper considers the stabilization problem of nonholonomic mobile robots with fractional-order sliding-mode control. Two fractional sliding surfaces are designed for the corresponding linear subsystems after using dynamic feedback linearization strategy, then the stabilizing fractional-order controller is proposed. Finally, the simulation results show the efficiency of the control methods.
Semi-solid forming applications: high volume automotive products (2013)

Efforts to improve fuel efficiency by the transportation industry have been directed in recent years toward the use of mass production capable, lowcost, aluminum castings as part of a weight reduction strategy.Die casting and permanent mold methods have been used extensively in the manufacture of light-weight castings to satisfy the need.However, quality limitations imposed by these casting methods such as porosity and the need for impregnation, trapped gas and the ability to heat treat the parts for improved strength, and non-uniform mechanical properties have restricted the range of applications available.In the last six years, a semi-solid forming (SSF) process has developed into a mature, high volume production method for light-weight, aluminum parts.The development of the SSF process depended upon the resolution of a number of critical technical issues: i) a reliable source of feedstock, ii) a robust forming technology capable of producing light-weight products capable of meeting automotive specifications, iii) alloys suitable for the SSF process of rapid cycling/high productivity manufacture, and iv) a joint customer/supplier design for manufacture capability to enable the production of low-cost, functionally innovative products.In this paper, the products and mass production process used for high volume automotive applications will be described.The manufacturing experience described illustrates the benefits of joint supplier/ customer development in the design and manufacture of critical parts.Tailoring of alloy, semi-solid viscosity, tool lubricants, press dynamics, and part design in order to optimize process/product characterize the engineering collaboration that took place.The advantages of the SSF process are described in terms of fundamentals of the forming process and the microstructural characteristics of the product.Robust methodology has been used throughout the development process and is currently being used in broadening SSF technology to include a semi-solid on demand process and a wider range of alloys.
A Micromagnetic Study of the Effect of Spatial Variations in Damping in Perpendicular Recording Heads (2006)

We have used micromagnetic modeling to study the effect of the gyromagnetic damping constant, alpha, on the dynamics of a perpendicular write head. Cases are considered where different regions of the head have different values of alpha, to examine where increased damping might offer benefits in head field rise time. It is found that increasing alpha in the pole region from 0.02 to 0.2 significantly improves both field rise time and amplitude at a drive frequency of 1 Gb/s. Similar increases in the damping of the yoke region and in the soft underlayer (SUL) did not yield nearly as significant improvements in field magnitudes or rise times, but was associated with reduced noise from the SUL. It is also noted for a monopole head design, that a SUL with higher magnetization-thickness product, M <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">S</sub> t, is needed to achieve the desired field amplitude as compared to a shielded pole head. An improvement in the gradient of the field is observed for the shielded head design along with a reduction in the field magnitude
Early Repeated 18F-FDG PET Scans During Neoadjuvant Chemoradiation Fail to Predict Histopathologic Response or Survival Benefit in Adenocarcinoma of the Esophagus (2010)

The %ΔSUVmax during the second week of induction chemoradiation did not correlate either with histopathologic response or with survival. Our results show that, in contrast to published reports on neoadjuvant chemotherapy, combined chemoradiotherapy in patients with adenocarcinoma of the esophagus lowers the predictive accuracy of early repeated (18)F-FDG PET in identifying histopathologic responders and those with chances for increased survival below clinically applicable levels.
A New Multi Laterolog Tool with Adaptive Borehole Correction (2008)

Abstract The Dual Laterolog (DLL) is one of the most commonly used resistivity logging devices in environments with highly conductive (salt-saturated) drilling mud and high formation resistivity. However, this device produces only two apparent resistivity logs with different radial depths of investigation, and it has a relatively low vertical resolution. Several array laterologs have been developed during the 1990s to improve both the vertical and radial resolution of measured formation resistivity. Each of these devices provides several depths-of-investigation measurements. However, most of these measurements, especially the shallow ones, are subject to borehole and eccentricity effects in very conductive muds and large boreholes. These effects can be severe. Therefore, conventional borehole corrections based only on borehole size, mud conductivity, and a fixed value of tool eccentricity (typically used for DLL measurements) become ineffective. A newly developed array laterolog device, Multi Laterolog, is based on the Dual Laterolog principle but with four independent focused measurements. This device is effectively shorter in total length than the traditional DLL and provides higher vertical resolution. Four measurements with different depths of investigation yield a detailed radial resistivity profile. A hardware-based feedback loop is employed to ensure the required focusing. To overcome the problems of the borehole and eccentricity effects on shallow measurements, we have developed a model-based adaptive borehole correction (ABC) technique. It is based on a radial 1-D inversion approach that properly corrects laterolog measurements for the borehole effect including determining and accounting for the unknown tool eccentricity. At every logging depth, we determine four earth-model parameters: tool eccentricity (Ecc), formation resistivity (Rt), invasion zone resistivity (Rxo), and invasion length (Lxo). After that, we apply the model-based correction by modifying the tool response in a borehole with mud resistivity Rm to a response in a borehole with virtual mud resistivity equal to Rxo (or to Rt if the formation is not invaded). This approach guarantees that in uninvaded intervals all four laterolog curves are properly "stacked", while in invaded intervals they show a reliable and consistent resistivity profile. The forward modeling used in inversion is based on the five-dimensional interpolation of pre-calculated look-up tables of various eccentered tool responses. Therefore, the inversion is very fast and the new borehole correction algorithm can be applied in real time. As a by-product, we output the length and resistivity of the invaded zone in invaded intervals. Thus, this correction scheme can provide Rt, Rxo and Lxo for thick beds together with borehole- and eccentricity-corrected curves at the wellsite. We illustrate the advantages of the Multi Laterolog and the model-based adaptive borehole corrections on synthetic data and on field data examples.
Chalazia Development in Multiple Myeloma: A New Complication Associated with Bortezomib Therapy (2015)

Multiple myeloma (MM) is a neoplasm of plasma cells within the bone marrow. A major impact on improving survival in MM has been the use of the boronic acid-derived proteasome inhibitor bortezomib, a first-in-class selective inhibitor of the 26S proteasome. Ocular side effects of bortezomib are rare. In this report, we present 2 patients with active MM in whom persistent chalazia became a therapy-interfering complication of treatment with bortezomib. Both patients had relapsed ISS III B kappa light chain myeloma, and they were responding to treatment with bortezomib until chalazia - which caused intolerable discomfort - started. In both patients discontinuation of bortezomib was necessary for chalazia to heal, and restarting of bortezomib was associated with relapse of chalazia.