gebhart/patrepeval huggingface dataset:
Levodopa delivery systems: advancements in delivery of the gold standard (2010)

Despite the fact that Parkinson's disease (PD) was discovered almost 200 years ago, its treatment and management remain immense challenges because progressive loss of dopaminergic nigral neurons, motor complications experienced by the patients as the disease progresses and drawbacks of pharmacotherapeutic management still persist. Various therapeutic agents have been used in the management of PD, including levodopa (l-DOPA), selegiline, amantadine, bromocriptine, entacapone, pramipexole dihydrochloride and more recently istradefylline and rasagiline. Of all agents, l-DOPA although the oldest, remains the most effective. l-DOPA is easier to administer, better tolerated, less expensive and is required by almost all PD patients. However, l-DOPA's efficacy in advanced PD is significantly reduced due to metabolism, subsequent low bioavailability and irregular fluctuations in its plasma levels. Significant strides have been made to improve the delivery of l-DOPA in order to enhance its bioavailability and reduce plasma fluctuations as well as motor complications experienced by patients purportedly resulting from pulsatile stimulation of the striatal dopamine receptors.Drug delivery systems that have been instituted for the delivery of l-DOPA include immediate release formulations, liquid formulations, dispersible tablets, controlled release formulations, dual-release formulations, microspheres, infusion and transdermal delivery, among others. In this review, the l-DOPA-loaded drug delivery systems developed over the past three decades are elaborated.The ultimate aim was to assess critically the attempts made thus far directed at improving l-DOPA absorption, bioavailability and maintenance of constant plasma concentrations, including the drug delivery technologies implicated.This review highlights the fact that neuropharmaceutics is at a precipice, which is expected to spur investigators to take that leap to enable the generation of innovative delivery systems for the effective management of PD.
UWB Modem with Low Power Options (2009)

For UWB to be a competitive solution in mobile devices, power consumption of the modem has to be optimized. The focus of this paper is to decrease the power consumption of the modem at physical layer by trading frequency diversity when operating at data rates up to 200 Mbps and by changing the constraint length of convolutional code and using QPSK when operating at data rates 320 Mbps and up. We show more than 50% and 25% gains in power consumption at physical layer with additional 1 dB and 3 dB received SNR at data rates 53.3 Mbps and 480 Mbps, respectively.
Neoadjuvant Chemotherapy and Immunotherapy in Luminal B-like Breast Cancer: Results of the Phase II GIADA Trial (2021)

Luminal B-like breast cancers with a Basal molecular subtype and/or a state of immune activation may respond to sequential anthracyclines and anti-PD-1. Our data generate hypotheses that, if validated, could guide immunotherapy development in this context.
Aspects of NMR reciprocity and applications in highly conductive media (2018)

Abstract In the context of NMR spectroscopy and MRI, the principle of reciprocity provides a convenient method for determining the reception sensitivity from the transmitted rf field pattern. The reciprocity principle for NMR was originally described by Hoult et al ( J Magn Reson . 1976; 24 :71) and is related to the broader Lorentz reciprocity principle and similar theorems from antenna theory. One frequent application of the reciprocity principle is that for a single coil used for both transmission and detection, the transmit and receive fields can be assumed to be equal. This aspect is also where some of the conceptual difficulty of applying the theorem may be encountered. For example, the questions of whether one should use the complex conjugate field for detection or whether one should apply the theorem in the rotating frame or in the laboratory frame may give rise to considerable confusion. We attempt here to provide a helpful discussion of the application of the reciprocity principle in such a way as to clarify some of the confounding questions. In particular, we avoid the use of the “negatively rotating frame,” which is frequently mentioned in this context, since we consider it to unnecessarily complicate the matter. In addition, we also discuss the implications of the theorem for magnetic resonance experiments on conducting samples, and metals, in particular.
Nanocrystalline TiO2-Catalyzed Solid-State Polymerization of Diacetylene in the Visible Region (2007)

An amphiphilic diacetylene, 10,12-pentacosadiynoic acid, was in-situ topochemically polymerized within a TiO2 nanostructure under visible light irradiation. The red shift of the wavelength at which the polymerization occurs can be attributed to the photocatalytic effect of TiO2 upon absorption of irradiation. Since visible light can be transmitted through the entire nanoporous TiO2 film, it is possible to obtain complete polymerization of the diacetylene monomers inside the TiO2 nanopores so as to provide an approach toward fabrication of the polydiacetylene/TiO2 nanocomposite structure and further development of optoelectronic devices.
Resource Efficient Gesture Sensing Based on FMCW Radar using Spiking Neural Networks (2021)

Gesture recognition is a natural and intuitive human computer-interface compared to traditional interfaces such as mouse and keyboards. Radar forms a promising modality for portable gesture recognition systems, where minute finger motions can be easily sensed and processed to extract meaningful information presenting the user's intention. Compared to several conventional deep learning approaches that have been proposed in the literature, in this paper we present a novel spiking neural network (SNNs) for gesture recognition using a 60-GHz frequency modulated continuous wave radar (FMCW) chipset. SNNs are more hardware friendly and energy-efficient than their deep learning counterparts making them attractive for portable devices. We have demonstrated in measurement the application of SNN for the processing of radar data.
Amigo2-upregulation in Tumour Cells Facilitates Their Attachment to Liver Endothelial Cells Resulting in Liver Metastases (2017)

Since liver metastasis is the main cause of death in cancer patients, we attempted to identify the driver gene involved. QRsP-11 fibrosarcoma cells were injected into the spleens of syngeneic mice to isolate tumour sub-populations that colonize the liver. Cells from liver metastatic nodules were established and subsequently injected intrasplenically for selection. After 12 cycles, the cell subline LV12 was obtained. Intravenous injection of LV12 cells produced more liver metastases than QRsP-11 cells, whereas the incidence of lung metastases was similar to that of QRsP-11 cells. LV12 cells adhered to liver-derived but not to lung-derived endothelial cells. DNA chip analysis showed that amphoterin-induced gene and open reading frame 2 (Amigo2) was overexpressed in LV12 cells. siRNA-mediated knockdown of Amigo2 expression in LV12 cells attenuated liver endothelial cell adhesion. Ex vivo imaging showed that suppression of Amigo2 in luciferase-expressing LV12 cells reduced attachment/metastasis to liver to the same level as that observed with QRsP-11 cells. Forced expression of Amigo2 in QRsP-11 cells increased liver endothelial cell adhesion and liver metastasis. Additionally, Amigo2 expression in human cancers was higher in liver metastatic lesions than in primary lesions. Thus, Amigo2 regulated tumour cell adhesion to liver endothelial cells and formation of liver metastases.
Practical Concerns for Scalable Synchronization (2005)

With the advent of multi-core chips and simultaneous multithreading technologies, high degrees of parallelism will soon become the norm for both small- and large-scale systems. Operating systems for such highly parallel environments require efficient synchronization. Unfortunately, the everincreasing overhead of synchronization instructions on modern CPUs has made such efficiency difficult to achieve. This paper evaluates the performance of synchronization strategies on modern CPU architectures. We show that synchronization instructions can be a thousand times more expensive than normal instructions and that formerly scalable synchronization strategies now perform very poorly. We then evaluate several state-of-the-art solutions that combine copy-based update and deferred reclamation to allow lock-free concurrent reading. These solutions exhibit different update management and reclamation strategies, each of which performs well, but offers a unique trade-off between performance, memory consumption, and complexity. We present an experimental evaluation of these strategies, focusing primarily on the read-mostly scenarios common in operatingsystem kernels, and discuss the impact of potential future changes in CPU architecture.
Plasmonic paper: an emerging analytical platform for highly sensitive biosensors(Conference Presentation) (2016)

Plasmonic biosensors hold enormous potential for the development of low-cost, label-free, point-of-care biodiagnostics. However, two major challenges need to be overcome to reap the benefits of this class of biosensors: (i) state-of-the-art plasmonic biosensors either offer limited sensitivity or are impractical for real-world applications due to their poor stability and excessive cost; (ii) these biosensors rely on natural antibodies, which are high-cost and impose severe limitations in handling, storage and device integration. We demonstrate that a common filter paper can be transformed into a plasmonic sensing platform for highly sensitive and selective detection of trace levels of chemical and biological analytes. We also demonstrate that short peptides as biorecognition elements compared to larger antibodies as target capture agents offer several advantages. Using a bioplasmonic paper device, we demonstrate the selective and sensitive detection of the cardiac biomarker troponin I. The smaller sized peptide provides higher sensitivity and a lower detection limit using a bioplasmonic paper device. Furthermore, the excellent shelf-life and thermal stability of peptide-based plasmonic biosensors, which precludes the need for special storage conditions, makes it ideal for use in resource-limited settings. We also demonstrate plasmonic biosensors based on artificial antibodies by molecularly imprinting the plasmonic nanotransducers. Apart from significantly lowering the cost, these developments are critical for translating plasmonic sensors to point-of-care and resource-limited settings.
Nanoscale Scanning Probe Thermometry of TaOe-based selector devices (2018)

Crosspoint memory arrays suffer from the sneak path problem, which may cause read failures and increase power consumption [1]. The high nonlinearity of threshold switching devices makes them an ideal candidate for selector device to suppress the leakage current in the one selector/one resistor architecture. However, the mechanism of threshold switching, in particular Negative Differential Resistance (NDR) behavior in oxide materials such as TaOx and NlrO; is still under debate. A leading hypothesis is Joule-heating-induced thermal runaway [2] producing NDR due to spontaneous current localization within the device region. So far, there is no experimental data on the size of the constriction and the temperature within it. We demonstrate the first use of scanning thermal microscopy (SThM) and scanning joule heating expansion microscopy (SJEM), two AFM-based high spatial resolution in-situ characterization methods to directly measure the temperature distribution up to the NDR region in TaOx-based selector devices. These experimental results are essential information for developing accurate numerical modeling of threshold switching devices.
Comparison of RNA-seq and microarray platforms for splice event detection using a cross-platform algorithm (2018)

Our results suggest, therefore, that exon-junction arrays are a viable alternative to RNA-seq for detection of alternative splicing events when focusing on well-described transcriptional regions.
IP-centric control and management of optical transport networks (2000)

Previous techniques for the management and control of optical transport networks are proving inadequate in today's rapidly evolving multivendor environments. This article examines the issues and challenges involved in developing a standardized optical network control plane. The control of optical transport networks is decomposed into provisioning models, a circuit provisioning process based on signaling, a neighbor and service discovery process, and a topology and resource discovery process. Unique properties and challenges of optical transport networks are explained in the context of these functions.
P3‐288: Gamma‐secretase inhibitors have intrinsically different potencies against Aβ production and Notch signaling (2010)

Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly and currently only symptomatic treatments are available. The underlying biochemistry of the disease appears to involve accumulation of the toxic amyloid-β peptide (Aβ) in the brain. Aβ is formed through proteolytic cleavage of the amyloid precursor protein (APP) by the proteases BACE and γ-secretase making development of inhibitors to both enzymes attractive therapeutic approaches for Alzheimer's disease. In addition to APP, γ-secretase cleaves other proteins thereby complicating the development of γ-secretase inhibitors. Of particular concern are the Notch-family of proteins which require γ-secretase cleavage to control cell fate decisions in several tissues, including the gastrointestinal tract and spleen. Here we describe γ-secretase inhibitors possessing intrinsically different inhibitory potencies for Aβ production and Notch signaling, observing a 500-fold range in the Notch/Aβ IC50 ratios among the set of inhibitors studied. To explore the biological relevance of these findings, a cellular model for differentiation of intestinal goblet cells was developed using the HT29 colon cancer cell line. Using this assay, we found that induction of goblet cell-like differentiation could be induced by γ-secretase inhibitors at potencies similar to those measured for inhibition of Notch signaling and that Notch signaling was required for this induction. Taken together, these findings demonstrate that inhibition of Aβ formation and Notch signaling can be partially separated in cultured cells and raise the possibility that Aβ can be inhibited without Notch toxicity in vivo leading to an increased therapeutic index with select γ-secretase inhibitors.
Inhibition of Rat Brain Protein and Nucleic Acid Synthesis by Cannabinoids In Vitro (1972)

The effect of Δ 9 -tetrahydrocannabinol (THC), cannabidiol, and cannabigerol on some metabolic processes in infant and adult rat brain cortex slices was studied in vitro. With L-leucine-U- 14 C as the tracer substrate, the incorporation of radioactivity into the protein and nucleic acid fractions was significantly inhibited by THC. The oxygen consumption of the slices, the uptake of L-leucine into the slices, and the evolution of 14 CO 2 were, however, unaffected by THC. Cannabidiol was comparable in activity to THC but cannabigerol was less active. The pattern of inhibition by THC was also observed when the rat brain cortex slices were stimulated by 100 mM K + or 10 μM protoveratrine. THC also brought about a significant decrease in the incorporation of uridine-2- 14 C into the nucleic acid fraction of infant and adult rat brain cortex slices. There was a decreased formation of uridine nucleotides in the presence of THC and an increase in uridine and uracil in the low molecular weight fraction. Experiments with THC-2,4- 14 C established that there was rapid uptake and a concentration of radioactivity in the incubated brain tissue.
Hartmann wave-front measurement at 134 nm with λ_EUV/120 accuracy (2003)

We report, for the first time to our knowledge, experimental demonstration of wave-front analysis via the Hartmann technique in the extreme ultraviolet range. The reference wave front needed to calibrate the sensor was generated by spatially filtering a focused undulator beam with 1.7- and 0.6-microm-diameter pinholes. To fully characterize the sensor, accuracy and sensitivity measurements were performed. The incident beam's wavelength was varied from 7 to 25 nm. Measurements of accuracy better than lambdaEUV/120 (0.11 nm) were obtained at lambdaEUV = 13.4 nm. The aberrations introduced by an additional thin mirror, as well as wave front of the spatially unfiltered incident beam, were also measured.
Nucleotide substitution in the ectodomain of trail receptor DR4 is associated with lung cancer and head and neck cancer. (2001)

Allelic loss of chromosome 8p21-22 occurs frequently in cancer, including lung and head and neck squamous cell cancer. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors, including proapoptotic DR4 and KILLER/DR5, are located on 8p21-22. TRAIL receptors are candidate tumor suppressor genes, because their inactivation would be expected to result in deficient apoptotic signaling. To investigate the involvement of DR4 in human cancer, we have determined the genomic structure of DR4 and screened 31 lung cancer cell lines [14 small cell lung cancer and 17 non-small cell lung cancer (NSCLC)], many with deletions at 8p21-22, and 21 primary NSCLC samples for mutations in DR4. We found two missense alterations in the ectodomain of DR4. One, at nucleotide 626, changes a cytosine to a guanine (C626G) and results in a substitution of an arginine for threonine. The other, at nucleotide 422, changes a guanine to adenine (G422A) and results in a substitution of a histidine for arginine. Using genomic DNA sequencing and RFLP analysis, we show that these two alterations cosegregated in 96% of all of the samples (n = 243) evaluated (tumor and normal). The frequency of being homozygous for both altered alleles was 35% in the lung cancer cell lines but only 13% in age- and race-matched controls, which was a significant increase (chi(2) = 5.2, P = 0.023). The frequency of homozygosity for both alleles was also significantly increased in the primary NSCLC samples (chi(2) = 9.2, P = 0.002) as compared with the age- and race-matched controls. To determine whether the altered alleles are specific for lung cancer, we evaluated 19 head and neck squamous cell cancer and 25 gastric adenocarcinoma samples. Forty-seven % of the former and 44% of the latter were homozygous for both the C626G and G422A alterations, and this was significantly elevated relative to age- and race-matched controls (chi(2) = 8.6, P = 0.003 and chi(2) = 8.2, P = 0.004). These alterations result in amino acid changes in or near the ligand-binding domain of DR4 and, based on the crystal structure of DR5 and its homology with DR4, have the potential to affect TRAIL binding to DR4. Our results suggest that the altered DR4 alleles may be associated with, and should be investigated additionally as potential markers for, predisposition to common malignancies.
Optimizing the Semisynthesis towards glycosylated interferon-β-polypeptide by utilizing bacterial protein expression and chemical modification (2022)

The synthesis of a sufficient amount of homogeneous glycoprotein is of great interest because natural glycoproteins show considerable heterogeneity in oligosaccharide structures, making the studies on glycan structure-function relationship difficult. Herein, we report optimized methods that can accelerate the semisynthesis of homogeneous glycoproteins based on recombinant expression and chemical conversion. Peptide thioesters and peptides with Cys residues at their N-terminals are necessary intermediates to perform native chemical ligation. We successfully performed thioesterification for a peptide prepared in <i>E. coli via</i> Cys-cyanylation at its C-terminal followed by hydrazinolysis and acidic thiolysis. These optimized conditions could tolerate an acid labile Thz protected Cys at the N-terminal of a peptide-hydrazide and specific cyanylation of the C-terminal Cys to yield a peptide thioester. To reduce the amount of precious oligosaccharide that is required in the conventional SPPS method, an improved liquid phase glycopeptide coupling was also optimized in a good yield (46% over four steps). Lastly, chemoselective protection of the internal cysteines and activation of the N-terminal cysteine were optimized toward a long peptide prepared in <i>E. coli</i>. By using these strategies, a full-length interferon-β glycosyl polypeptide as a model was successfully obtained.
Miniemulsion Copolymerization of Methyl Methacrylate and Butyl Acrylate by Ultrasonic Initiation (2005)

The ultrasonically initiated batch miniemulsion copolymerizations of methyl methacrylate (MMA) and butyl acrylate (BA) are studied at different MMA:BA ratios (including homopolymerizations), and the physical properties and chemical composition of the polymers formed are investigated. Trends in the evolution of the particle number are rationalized with reference to the mechanical properties of the polymer particles, with the number concentration of the softer, BA-rich particles reducing with continued sonication. Molecular weight data are consistent with high radical fluxes entering the particles, with the radical entry frequency calculated from the peroxide yield in a model system to be ∼1.5 × 10-2 s-1. To within experimental uncertainty, the copolymer composition is found to be consistent with the terminal model for propagation reactions and previously published reactivity ratios; hence, it is concluded that ultrasound has little effect on the propagation step in a free-radical polymerization process. The results obtained also support a miniemulsion polymerization pathway for sonochemically synthesized latex particles.
Narcotweets: Social Media in Wartime (2015)

This paper describes how people living in armed conflict environments use social media as a participatory news platform, in lieu of damaged state and media apparatuses. We investigate this by analyzing the microblogging practices of Mexican citizens whose everyday life is affected by the Drug War. We provide a descriptive analysis of the phenomenon, combining content and quantitative Twitter data analyses. We focus on three interrelated phenomena: general participation patterns of ordinary citizens, the emergence and role of information curators, and the tension between governmental regulation and drug cartel intimidation. This study reveals the complex tensions among citizens, media actors, and the government in light of large scale organized crime.
Tumor growth and angiogenesis induced by a secreted binding protein for fibroblast growth factors. (1994)

Basic fibroblast growth factor (bFGF) is a strong inducer of angiogenesis and thus may play an important role in the growth of solid tumors. However, bFGF is usually found immobilized on the extracellular matrix, and it is only partly understood how it is solubilized to reach and activate its extracellular receptors. We studied the potential contribution to this process by a secreted binding protein (BP) with high affinity for FGFs. An expression vector for BP was transfected into a human cell line (SW-13) that contains constitutively high levels of bFGF. The BP-expressing cells began to grow colonies in soft agar due to their autocrine stimulation by bFGF and released biologically active bFGF into their media. Furthermore, they grew into well vascularized tumors in athymic nude mice. In addition, we found the BP mRNA expressed at high levels in squamous cell carcinoma (SCC) tissues from patients and in SCC cell lines of different origin as well as in immortalized keratinocytes. However, we failed to detect BP mRNA in normal adult tissues or in a number of non-SCC tumor cell lines. Expression of the secreted BP appears to be a mechanism through which immobilized FGF can be activated to support tumor growth and angiogenesis.