gebhart/patrepeval huggingface dataset:
Curcumin Downregulates NF-kB and Related Genes in Patients with Multiple Myeloma: Results of a Phase I/II Study. (2007)

Abstract Although the role of NF-kB and STAT3 pathways in proliferation/metastasis of various tumor cells is well established, no agent has been described which could downregulate the activation of these transcription factors in cancer patients (pts). Curcumin has been shown to potently suppress the activation of these transcription factors in cultured cells. Based on these observations, we initiated a clinical trial of curcumin alone (administered orally at 2, 4, 6, 8, or 12 grams/day in 2 divided doses) or in combination with Bioperine (10 mg in 2 divided doses) for 12 weeks in multiple myeloma (MM) pts. The objectives of this study were to evaluate the clinical safety and biologic effects in MM pts who had asymptomatic, relapsed/refractory, or plateau phase disease. Blood was collected for PK/PD and PBMCs were examined (baseline and during treatment) for evaluating the effect of treatment on expression of NF-kB (p65), COX-2 and phospho-STAT3 as surrogate biomarkers. NF-kB activation status was also measured by electrophoretic mobility shift assay. At least 6 pts are enrolled at each dose level; 3 on the curcumin arm and 3 on the curcumin + bioperine arm. Pts with at least stable disease were allowed to continue treatment up to one year. Treatment with curcumin and bioperine has been well tolerated, with no significant adverse events. At the 12 grams dose level, 2 of the 5 pts had difficulty swallowing the large number of capsules. Of the 29 evaluable pts treated so far, no objective responses have been seen. Twelve pts continued treatment for more than 12 weeks and 5 (1 patient at 4 grams, 2 pts at 6 grams, and 2 pts at 8 grams dose levels) completed one year of treatment with stable disease. With few exceptions, little if any free drug was found in the plasma. Total curcumin levels (mostly conjugated drug) were dependent on both dose and the duration of administration. PBMCs from 28 MM pts examined showed constitutively active NF-kB (mean ± STD, 74.2% ± 14.0 positive cells), COX2 (66% ± 15.4), and STAT3 (52.8% ± 19.2). Oral administration of curcumin significantly downregulated the constitutive activation of NF-kB (at 3 months a median reduction of 77%, p<0.0001) and STAT3 (69%, p<0.001), and suppressed COX2 (66%, p<0.0001) expression in most of the pts at each of the monthly time points. Conclusions: This is the first report to indicate that curcumin, a highly safe agent, is bioavailable and can downregulate NF-kB, STAT3 and COX2 in MM pts. These findings suggest a potential therapeutic role for curcumin that can be further investigated either alone or as a modulator of chemo-resistance in combination with other active agents.
A New Class of Orthosteric uPAR·uPA Small-Molecule Antagonists Are Allosteric Inhibitors of the uPAR·Vitronectin Interaction (2015)

The urokinase receptor (uPAR) is a GPI-anchored cell surface receptor that is at the center of an intricate network of protein-protein interactions. Its immediate binding partners are the serine proteinase urokinase (uPA), and vitronectin (VTN), a component of the extracellular matrix. uPA and VTN bind at distinct sites on uPAR to promote extracellular matrix degradation and integrin signaling, respectively. Here, we report the discovery of a new class of pyrrolone small-molecule inhibitors of the tight ∼1 nM uPAR·uPA protein-protein interaction. These compounds were designed to bind to the uPA pocket on uPAR. The highest affinity compound, namely 7, displaced a fluorescently labeled α-helical peptide (AE147-FAM) with an inhibition constant Ki of 0.7 μM and inhibited the tight uPAR·uPAATF interaction with an IC50 of 18 μM. Biophysical studies with surface plasmon resonance showed that VTN binding is highly dependent on uPA. This cooperative binding was confirmed as 7, which binds at the uPAR·uPA interface, also inhibited the distal VTN·uPAR interaction. In cell culture, 7 blocked the uPAR·uPA interaction in uPAR-expressing human embryonic kidney (HEK-293) cells and impaired cell adhesion to VTN, a process that is mediated by integrins. As a result, 7 inhibited integrin signaling in MDA-MB-231 cancer cells as evidenced by a decrease in focal adhesion kinase (FAK) phosphorylation and Rac1 GTPase activation. Consistent with these results, 7 blocked breast MDA-MB-231 cancer cell invasion with IC50 values similar to those observed in ELISA and surface plasmon resonance competition studies. Explicit-solvent molecular dynamics simulations show that the cooperativity between uPA and VTN is attributed to stabilization of uPAR motion by uPA. In addition, free energy calculations revealed that uPA stabilizes the VTNSMB·uPAR interaction through more favorable electrostatics and entropy. Disruption of the uPAR·VTNSMB interaction by 7 is consistent with the cooperative binding to uPAR by uPA and VTN. Interestingly, the VTNSMB·uPAR interaction was less favorable in the VTNSMB·uPAR·7 complex suggesting potential cooperativity between 7 and VTN. Compound 7 provides an excellent starting point for the development of more potent derivatives to explore uPAR biology.
F-sin(theta) lens system and applications (2001)

Introducing the desired amount of distortion in an optical system is possible and relatively straight forward for optical designer. Known f-theta lenses used in laser scanner system is one of the most popular lenses of this type. With the development of DWDM system, compact spectrometer and various grating based devices, the interest in solving optical problems with innovative optical design has been a revival. On the other hand, it is possible to simplify considerably the task of the software by designing more sophisticated optical element. The F-sin(theta) lens is such a device which can be used in various grating based devices to improve the performance. This optical device is intended to provide a new lens or lens group which can be used with a diffraction grating to provide a linear output plane with the wavelength (lambda), but also with the order of diffraction (m), or with the grating spatial frequency, or with the inverse of the index of refraction (1/n). Based on theoretical consideration, we calculated which amount of distortion is desired to get linear output plane for a grating based device. We present singlet, achromatic doublet and mirror having this characteristic. These F-sin(theta) lenses present satisfactory distortion characteristic and have an improved correction for the curvature of image plane. F-sin(theta) lens will be also name F-lambda lens.
Genetic Variations Associated With Recurrent Venous Thrombosis (2014)

Multiple genetic SNP analysis is useful in the prediction of recurrent thrombosis, even more so when combining this model with clinical risk factors.
A new resonant gate drive circuit with efficient energy recovery and low conduction loss (2005)

In this paper, a new resonant gate drive circuit is proposed. The proposed circuit consists of four control switches and a small resonant inductance. The current through the resonant inductance is discontinuous in order to minimize circulating current conduction loss present in other methods. The proposed circuit also achieves quick turn-on and turn-off transition times to reduce switching loss and conduction loss in power MOSFETS. An analysis, design procedure and simulation results are presented for the proposed circuit
Influence of the -doping sheet and setback layer on the performance of an InGaP/GaAs heterojunction bipolar transistor (1998)

In this paper, we demonstrate the qualitative influence of a -doping sheet and setback layer on the performance of an InGaP/GaAs heterojunction bipolar transistor (HBT). The results of a theoretical simulation show that the potential spike is reduced by the simultaneous employment of an appropriate setback layer and -doping sheet. Due to the reduction in the potential spike, a high current gain, even at a small collector current regime, and small offset voltage can be attained. Experimentally, an offset voltage as small as 55 mV and current gain of 11 at collector current of A are obtained without a passivation structure.
Erratum: “High efficiency semimetal/semiconductor nanocomposite thermoelectric materials” [J. Appl. Phys. 108, 123702 (2010)] (2011)

First Page
Self-Assembly of Uniform Nanoporous Silica Fibers (2005)

Self-assembly of nanoporous silica shapes is of great interest for modern nanotechnology because of uniform pore size, simplicity, and low cost of production. However, there are two major problems that prevent broad use of the self-assembly process. First, the process brings too broad a variety of the assembled shapes. Secondly, the yield of the desired shapes is far from 100%. Here, we describe a process of acidic self-assembly of silica shapes that is free of both of these problems. The process described results in virtually a 100% of very uniform fibers. Each fiber has a hexagonal cross section of approximately 2 /spl mu/m and a length of approximately 5 /spl mu/m. The highly uniform pores with periodicity of 3.8 nm are unidirectional along the fiber. These new fibers can be used in chromatography, drug delivery, manufacturing nanowires, nanoreactors for "one-dimensional" chemistry, etc.
Urinary Protein Biomarker Panel for the Detection of Recurrent Bladder Cancer (2014)

The identification of a reliable urine-based surveillance and detection assay would be of benefit to both patients and the healthcare system.
A Breath Fungal Secondary Metabolite Signature to Diagnose Invasive Aspergillosis (2014)

In patients with suspected fungal pneumonia, an Aspergillus secondary metabolite signature in breath can identify individuals with IA. These results provide proof-of-concept that direct detection of exogenous fungal metabolites in breath can be used as a novel, noninvasive, pathogen-specific approach to identifying the precise microbial cause of pneumonia.
Underwater Sound Generation Using Carbon Nanotube Projectors (2010)

The application of solid-state fabricated carbon nanotube sheets as thermoacoustic projectors is extended from air to underwater applications, thereby providing surprising results. While the acoustic generation efficiency of a liquid immersed nanotube sheet is profoundly degraded by nanotube wetting, the hydrophobicity of the nanotube sheets in water results in an air envelope about the nanotubes that increases pressure generation efficiency a hundred-fold over that obtained by immersion in wetting alcohols. Due to nonresonant sound generation, the emission spectrum of a liquid-immersed nanotube sheet varies smoothly over a wide frequency range, 1-10(5) Hz. The sound projection efficiency of nanotube sheets substantially exceeds that of much heavier and thicker ferroelectric acoustic projectors in the important region below about 4 kHz, and this performance advantage increases with decreasing frequency. While increasing thickness by stacking sheets eventually degrades performance due to decreased ability to rapidly transform thermal energy to acoustic pulses, use of tandem stacking of separated nanotube sheets (that are addressed with phase delay) eliminates this problem. Encapsulating the nanotube sheet projectors in argon provided attractive performance at needed low frequencies, as well as a realized energy conversion efficiency in air of 0.2%, which can be enhanced by increasing the modulation of temperature.
Design of Patterned Magnetic Recording Media for Tera-Bit Recording (2006)

Specifications of patterned magnetic recording media for tera-bit recording were designed as an extension of perpendicular magnetic recording. Effective thermal stability of the magnetic dots with perpendicular anisotropy was estimated using the magnetic field where magnetization reversal begins in the magnetic dot array by the applied perpendicular field. The estimated magnetic properties of the media with an areal density of 1 Tbit/in2 were expected to be realized with known hard magnetic materials such as Co-Pt and FePt alloys. Effects of the size and shape of dots and the spacing between dots on the magnetic reversal properties were investigated using a micromagnetic simulation. It was found that the spacing between dots would impose strong restriction on the achievable recording density. Recording simulation on a designed patterned medium indicated possibility of realization of 1 Tbit/in2 recording.
Inductive and capacitive array imaging of buried objects (2006)

Despite ongoing research and development efforts, landmine and unexploded ordnance infestation continues to be a problem. Remediation efforts typically utilise inexpensive hand-held metal detectors that rely on the principle of electromagnetic induction. While these devices often detect all relevant metal objects, they generally cannot discriminate between harmful objects and harmless clutter. False indications continue to far outnumber verified detections. One promising method for improving the discrimination between harmful and harmless objects is the use of sensor arrays that provide images of hidden objects and complementary information about the buried object from a variety of angles. This paper will review the progress of high-resolution inductive and capacitive sensing array development for buried object detection. These sensor arrays use unique designs incorporating a single drive with multiple sense elements. The drive creates a shaped magnetic or electric field pattern that concentrates the field energy into longer wavelength spatial modes with 'focused' penetration into the ground. Images obtained from scans over buried objects provide a basis for spatial filtering and signal processing while multiple sensor arrays placed at different positions within the drive provide different 'views' of buried objects and clutter. Model-based grid measurement methods will also be reviewed as a real-time method for multiple property measurements, and real-time data analysis/image generation.
A report of Streptococcus pneumoniae serotype 6D in Europe (2011)

Microbiology Society journals contain high-quality research papers and topical review articles. We are a not-for-profit publisher and we support and invest in the microbiology community, to the benefit of everyone. This supports our principal goal to develop, expand and strengthen the networks available to our members so that they can generate new knowledge about microbes and ensure that it is shared with other communities.
Reversible Inhibitors of the Gastric (H+/K+)-ATPase. 4. Identification of an Inhibitor with an Intermediate Duration of Action (1995)

3-Acyl-4-(arylamino)quinolines were previously identified as gastric (H+/K+)-ATPase inhibitors, and clinical efficacy has been demonstrated for compound 3 (SK&F 96067). In the present study the further structure-activity relationship of this series is developed. Only a limited range of substituents are tolerated on the N-aryl ring or the 6- and 7-positions of the quinoline, and although hydroxylated derivatives were identified possessing markedly greater affinity for the enzyme, none of these proved to have adequate potency after oral dosing. In contrast, the 8-position of the quinoline ring proved suitable for a wide variety of substituents, allowing modification of physicochemical properties while retaining primary activity. This led to the identification of compound 4 (SK&F 97574), which combines good oral potency with a somewhat longer duration of action than 3 (though much shorter than covalent inhibitors such as omeprazole). This compound was selected for further development and evaluation in man.
Differential super-orthogonal space-time trellis coded modulation (2005)

In this paper, first, we extend the design of super-orthogonal space-time trellis codes to improve their performance. Then, we present a differential space-time trellis coded modulation scheme based on these extended super-orthogonal codes when the channel state information is not available at the transmitter and the receiver. We compare our differential modulation scheme with the trellis coded differential unitary space-time modulation scheme and note that not only does the proposed differential trellis coded modulation scheme achieve full diversity, but also it provides identical or higher coding gain and much lower decoding complexity for a given transmission rate. Simulation results demonstrate the good performance of our proposed scheme.
Inductively coupled microfluidic pressure meter for<i>in vivo</i>monitoring of cerebrospinal fluid shunt function (2012)

A microfluidic pressure sensor with inductively coupled, wireless readout capability has been developed for integration into cerebrospinal fluid shunt valve implants. The sensor consists of a deformable PDMS film that is bonded over a microfluidic reservoir, forming a fluidic capacitor. Deflection of the capacitor membrane is detected remotely through a shift in the resonance frequency of a micro-fabricated LC circuit. Sensors were fabricated by a combination of conventional MEMS technologies and rapid soft lithography. A direct pattern transfer technique was used to pattern the deformable PDMS film with a metal coating for the capacitive readout. The mechanical response of the fluidic capacitor was characterized by measuring the deflection of the PDMS film using an extrinsic Fabry-Perot interferometer (EFPI), and wireless sensing was demonstrated by the shift in resonance frequency of the sensor via an inductively coupled antenna. The sensor transduces pressure into a change in resonant frequency with sensitivity > 3.4 ppm Pa⁻¹ and responsivity 4.6 kHz Pa⁻¹, over a dynamic range of 0~3 kPa.
Coencapsulation of ISCs and MSCs Enhances Viability and Function of both Cell Types for Improved Wound Healing (2019)

Combining MSCs with ISCs results in a more robust healing response than singly delivered cells, warranting further investigation of coencapsulation for MSC therapies.
LED lights with hidden intensity-modulated blue channels for enhanced subconscious visual responses (2017)

An LED light suitable for general illumination is proposed to enhance subconscious visual responses, which are essential to our well-being. Using the silent substitution technique, a melanopsin-selective flicker was added into white light. A linear optimization algorithm suppresses perceivable fluctuations of colors of illuminated objects.
Fabrication, testing, and performance of a variable-focus x-ray compound lens (2002)

Design, fabrication, testing, and performance of an x-ray lens assembly are described. The assembly consists of a number of precisely stacked and aligned parts, each of which is a section of an extruded aluminum piece having 16 parabolic cavities. The wall thickness between adjacent cavities is 0.2 mm. By stacking a number of long, extruded parts and cutting the assembly diagonally, a variable-focus lens system is derived. Moving the lens horizontally allows the incident beam to pass through fewer or more cavities focusing the emerging beam at any desired distance from the lens. The variable focus aluminum lens has been used at the Advanced Photon Source to collimate a monochromatic, 8 keV undulator beam. Results indicate collimation consistent with theoretical expectations.
The Pressure Dependence of Permeability as a Function of Stiff and Compliant Porosities (2013)

We compare the behaviour of permeability and elastic properties of rocks as functions of the tectonic stress and pore pressure. We propose that different parts of the pore and fracture space differently contribute to a control of these two types of physical properties of rocks. The stress dependence of elastic moduli of drained rocks is mainly controlled by deformations (including fractures) of the compliant part of the pore space. This leads to saturating exponential functions expressing load dependences of seismic velocities and of related seismic parameters. On the other hand a temporal evolution of seismicity induced by fluid stimulations (including hydraulic fracturing) of rocks sometimes implies power-law dependences of the permeability on the pore pressure. It seems that in some rocks permeability is controlled by the stiff part of the pore space. This leads to a power-law pressure dependence of the permeability. Sometimes permeability can be controlled by compliant pores (e.g., cracks). Then exponential type of permeability as function of pressure can be observed. Below we propose a permeability model taking these two parts of the porosity into account.
Lasting <i>Gammaproteobacteria</i> profile changes characterized hematological cancer patients who developed oral mucositis following conditioning therapy (2020)

<b>Background:</b> Oral mucositis (OM) is a common side effect of conditioning therapy implemented before hematopoietic stem cell transplantation (HSCT). The role of oral microbiome in OM is not fully elucidated. <b>Objective:</b> To determine oral microbiome profile changes post-conditioning in HSCT patients who developed moderate OM, or mild to no OM. <b>Design:</b> Patient groups were: Muc0-1 with OM-score = 0-1 (43 paired samples) and Muc2 with WHO OM-score = 2 (36 paired samples). Bacterial DNA was isolated from oral samples (saliva, swabs of buccal mucosa, tongue, and supragingival plaque) at pre-conditioning (T <b><sub>0</sub></b> ), post-conditioning mucositis onset (T <b><sub>Muc</sub></b> ), and one-year post-conditioning (T <b><sub>Year</sub></b> ). <i>16S-rRNA</i> gene next-generation sequencing was used to determine the relative abundance (RA) of >700 oral species. <i>Alpha</i>-diversity, <i>beta</i>-diversity and linear discriminant analyses (LDA) were performed Muc2 <i>versus</i> Muc0-1. <b>Results:</b> Muc2 oral microbiome <i>alpha</i>- and <i>beta</i>-diversity differed between T <b><sub>0</sub></b> and T <b><sub>Muc</sub></b> . Muc2 <i>alpha</i>-diversity and Muc0-1 <i>beta-</i>diversity did not differ between T <b><sub>0</sub></b> and T <b><sub>Year</sub></b> . T <b><sub>0</sub></b> to T <b><sub>Muc</sub></b> LDA scores were significant in Muc2 for <i>Gammaproteobacteria</i>. For Muc2 patients, the average RA decreased for <i>Haemophilus parainfluenza</i>, a species known as mucosal surfaces protector, but increased for <i>Escherichia-Shigella</i> genera. <b>Conclusions:</b> Post-conditioning OM might contribute to long-term oral microbiome changes affecting <i>Gammaproteobacteria</i>, in HSCT patients.
ReviewArticle Contributions of Inflammatory Processes to the Development of the Early Stages of Diabetic Retinopathy (2007)

development of diabetic retinopathy. These changes include upregulation of iNOS, COX-2, ICAM-1, caspase 1, VEGF, and NF-κB, increased production of nitric oxide, prostaglandin E2, IL-1β, and cytokines, as well as increased permeability and leukostasis. Using selective pharmacologic inhibitors or genetically modified animals, an increasing number of therapeutic approaches have been identified that significantly inhibit development of at least the early stages of diabetic retinopathy, especially occlusion and degeneration of retinal capillaries. A common feature of a number of these therapies is that they inhibit production of inflammatory mediators. The concept that localized inflammatory processes play a role in the development of diabetic retinopathy is relatively new, but evidence that supports the hypothesis is accumulating rapidly. This new hypothesis offers new insight into the pathogenesis of diabetic retinopathy, and offers novel targets to inhibit the ocular disease.