gebhart/patrepeval huggingface dataset:
Immunotherapy for Alzheimer‘s Disease: From Anti-β-Amyloid to Tau-Based Immunization Strategies (2012)

The exact mechanisms leading to Alzheimer's disease (AD) are largely unknown, limiting the identification of effective disease-modifying therapies. The two principal neuropathological hallmarks of AD are extracellular β-amyloid (Aβ), peptide deposition (senile plaques) and intracellular neurofibrillary tangles containing hyperphosphorylated tau protein. During the last decade, most of the efforts of the pharmaceutical industry were directed against the production and accumulation of Aβ. The most innovative of the pharmacological approaches was the stimulation of Aβ clearance from the brain of AD patients via the administration of Aβ antigens (active vaccination) or anti-Aβ antibodies (passive vaccination). Several active and passive anti-Aβ vaccines are under clinical investigation. Unfortunately, the first active vaccine (AN1792, consisting of preaggregate Aβ and an immune adjuvant, QS-21) was abandoned because it caused meningoencephalitis in approximately 6% of treated patients. Anti-Aβ monoclonal antibodies (bapineuzumab and solanezumab) are now being developed. The clinical results of the initial studies with bapineuzumab were equivocal in terms of cognitive benefit. The occurrence of vasogenic edema after bapineuzumab, and more rarely brain microhemorrhages (especially in Apo E ε4 carriers), has raised concerns on the safety of these antibodies directed against the N-terminus of the Aβ peptide. Solanezumab, a humanized anti-Aβ monoclonal antibody directed against the midregion of the Aβ peptide, was shown to neutralize soluble Aβ species. Phase II studies showed a good safety profile of solanezumab, while studies on cerebrospinal and plasma biomarkers documented good signals of pharmacodynamic activity. Although some studies suggested that active immunization may be effective against tau in animal models of AD, very few studies regarding passive immunization against tau protein are currently available. The results of the large, ongoing Phase III trials with bapineuzumab and solanezumab will tell us if monoclonal anti-Aβ antibodies may slow down the rate of deterioration of AD. Based on the new diagnostic criteria of AD and on recent major failures of anti-Aβ drugs in mild-to-moderate AD patients, one could argue that clinical trials on potential disease-modifying drugs, including immunological approaches, should be performed in the early stages of AD.
Some correlations between specificity and sequence of the first complementarity-determining segments of human kappa light chains. (1976)

Examination of the sequences of the first complementarity-determining segments of the light chains of two IgM cold agglutinins agains blood group I, four monoclonal IgM antibodies against IgG proteins, and of three Bence Jones proteins provides clues for predicting which residues contribute to antibody specificity and indicates that these predictions may be tested by evaluating recovery of antibody activity and specificity when various light chains are recombined with homologous and heterologous heavy chains.
Pathogenesis of CerebralCryptococcus neoformansInfection after Fungemia (2002)

The pathogenesis of cerebral infection after Cryptococcus neoformans fungemia in outbred mice was investigated. Confocal microscopy and cultures on ficoll-hypaque gradient-separated blood cells were used to detect yeasts in the cytoplasms of monocytes. In semithin brain sections, poorly capsulated yeasts were seen in macrophages in the leptomeningeal space, in monocytes circulating in leptomeningeal capillaries, or in the endothelial cells themselves, strengthening the hypothesis that monocytes and endothelial cells play key roles in the pathogenesis of cryptococcal meningitis. Similar fungal loads and cellular reactions were seen in mice and in 1 patient with acquired immune deficiency syndrome (AIDS), all with acute cryptococcal meningoencephalitis, and in mice and in 1 patient with AIDS, all with cured cryptococcal infection. Immunostaining revealed both the presence of cryptococcal polysaccharide in various brain cells and antigenic variability both from yeast cell to yeast cell and over time. Thus, our data established the relevance and interest that this experimental model has for investigation of the pathogenesis of human cryptococcal meningitis.
Clinical characteristics of infant acute leukemia with or without 11q23 translocations. (1988)

Of 34 infants less than 1 year of age with acute leukemia, 20 had an 11q23 translocation (group I), 8 had t(4;11), 5 had t(11;19), 3 had t(1;11), 2 had t(10;11), 1 had t(9;11), and the other had an 11q+ chromosome. Nine had other chromosome changes (group II), including t(1;19), t(8;14), 5q- chromosome, or +8 in one each, and a translocation involving 7p22 in two. The other five had normal diploidy in their leukemic cells (group III). Thus, the 11q23 translocation was seen in 50% of the leukemic infants, and in as high as 75% of the infants less than 6 months old. While the 7p22 translocations were both seen in those less than 6 months, the four chromosome abnormalities without 11q23 translocation mentioned above and normal diploidy were found only in those 6 months old or more. The group I patients had higher leukocyte counts than the group II (p less than 0.05) or group III (p less than 0.01) patients. Of the 20 group I patients, 16 were classified as having ALL, and 4 were classified as having ANLL. Eleven of 15 ALLs with the 11q23 translocation showed an Ia+, CALLA-, and B4+ (8 of 9 examined) immunophenotype. Coexpression of lymphoid and myeloid Ags was seen in four ALLs and two ANLLs with the 11q23 translocation. The survival of group II patients (median, 9 months) was significantly shorter than that of group I (median, 19 months) (p less than 0.05) or group III (median, 44 months) (p less than 0.01) patients; the difference in the survival between group I and group III patients was not significant. It is noteworthy that 5 of the 20 group I patients have survived 20 months or more without relapsing.
A digital to time converter with fully digital calibration scheme for ultra-low power ADPLL in 40 nm CMOS (2015)

In this paper, a digital-to-time converter (DTC) assisting a time-to-digital converter (TDC) as a fractional phase error detector in an ultra-low power ADPLL is proposed and demonstrated in 40nm CMOS. A phase prediction algorithm via the assistance of the DTC reduces the required TDC range, thus saving substantial power. Additionally, a fully digital calibration algorithm is presented and proved to validate the whole ADPLL system and improve the DTC linearity. At 1 V supply voltage, the measured time resolution of the DTC is 22 ps. The TDC resolution is also indirectly measured with a closed-loop 2.4 GHz ADPLL, where -95.3 dBc/Hz in-band phase noise corresponds to a worst-case TDC resolution of 22 ps.
Dynamic view expansion for minimally invasive surgery using simultaneous localization and mapping (2009)

Navigation during Minimally Invasive Surgery (MIS) has recognized difficulties due to limited field-of-view, off-axis visualization and loss of direct 3D vision. This can cause visual-spatial disorientation when exploring complex in vivo structures. In this paper, we present an approach to dynamic view expansion which builds a 3D textured model of the MIS environment to facilitate in vivo navigation. With the proposed technique, no prior knowledge of the environment is required and the model is built sequentially while the laparoscope is moved. The method is validated on simulated data with known ground truth. Its potential clinical value is also demonstrated with in vivo experiments.
EnrichNet: network-based gene set enrichment analysis (2012)

Supplementary data are available at Bioinformatics Online.
Differential inhibition of fracture healing by non‐selective and cyclooxygenase‐2 selective non‐steroidal anti‐inflammatory drugs (2003)

Non-steroidal anti-inflammatory drugs (NSAIDs) specifically inhibit cyclooxygenase (COX) activity and are widely used as anti-arthritics, post-surgical analgesics, and for the relief of acute musculoskeletal pain. Recent studies suggest that non-specific NSAIDs, which inhibit both COX-1 and COX-2 isoforms, delay bone healing. The objectives of this study were 2-fold; first, to measure the relative changes in the normal expression of COX-1 and COX-2 mRNAs over a 42 day period of fracture healing and second, to compare the effects of a commonly used non-specific NSAID, ketorolac, with a COX-2 specific NSAID, Parecoxib (a pro-drug of valdecoxib), on this process. Simple, closed, transverse fractures were generated in femora of male Sprague-Dawley rats weighing approximately 450 g each. Total RNA was prepared from the calluses obtained prior to fracture and at 1, 3, 5, 7, 10, 14, 21, 35 and 42 days post-fracture and levels of COX-1 and COX-2 mRNA were measured using real time PCR. While the relative levels of COX-1 mRNA remained constant over a 21-day period, COX-2 mRNA levels showed peak expression during the first 14 days of healing and returned to basal levels by day 21. Mechanical properties of the calluses were then assessed at 21 and 35 days post-fracture in untreated animals and animals treated with either ketorolac or high or low dose parecoxib. At both 21 and 35 days after fracture, calluses in the group treated with the ketorolac showed a significant reduction in mechanical strength and stiffness when compared with controls (p<0.05). At the 21-day time point, calluses of the parecoxib treated animals showed a lower mean mechanical strength than controls, but the inhibition was not statistically significant. Based on physical analysis of the bones, 3 of 12 (25%) of the ketorolac-treated and 1 of 12 (8%) of the high dose parecoxib-treated animals showed failure to unite their fractures by 21 days, while all fractures in both groups showed union by 35 days. Histological analysis at 21 days showed that the calluses in the ketorolac-treated group contained substantial amounts of residual cartilage while neither the control nor the parecoxib-treated animals showed comparable amounts of cartilage at this stage. These results demonstrate that ketorolac and parecoxib delay fracture healing in this model, but in this study daily administration of ketorolac, a non-selective COX inhibitor had a greater affect on this process. They further demonstrate that a COX-2 selective NSAID, such as parecoxib (valdecoxib), has only a small effect on delaying fracture healing even at doses that are known to fully inhibit prostaglandin production.
Intrinsic Self-DNA Triggers Inflammatory Disease Dependent on STING (2014)

Inflammatory diseases such as Aicardi-Goutières syndrome and severe systemic lupus erythematosus are generally lethal disorders that have been traced to defects in the exonuclease TREX1 (DNase III). Mice lacking TREX1 similarly die at an early age through comparable symptoms, including inflammatory myocarditis, through chronic activation of the stimulator of IFN genes (STING) pathway. In this study, we demonstrate that phagocytes rather than myocytes are predominantly responsible for causing inflammation, an outcome that could be alleviated following adoptive transfer of normal bone marrow into TREX1(-/-) mice. TREX1(-/-) macrophages did not exhibit significant augmented ability to produce proinflammatory cytokines compared with normal macrophages following exposure to STING-dependent activators, but rather appeared chronically stimulated by genomic DNA. These results shed molecular insight into inflammation and provide concepts for the design of new therapies.
A Review of Image Denoising Algorithms, with a New One (2005)

International audience
Trap States in Lead Iodide Perovskites (2015)

Recent discoveries of highly efficient solar cells based on lead iodide perovskites have led to a surge in research activity on understanding photo carrier generation in these materials, but little is known about trap states that may be detrimental to solar cell performance. Here we provide direct evidence for hole traps on the surfaces of three-dimensional (3D) CH3NH3PbI3 perovskite thin films and excitonic traps below the optical gaps in these materials. The excitonic traps possess weak optical transition strengths, can be populated from the relaxation of above gap excitations, and become more significant as dimensionality decreases from 3D CH3NH3PbI3 to two-dimensional (2D) (C4H9NH3I)2(CH3NH3I)(n-1)(PbI2)(n) (n = 1, 2, 3) perovskites and, within the 2D family, as n decreases from 3 to 1. We also show that the density of excitonic traps in CH3NH3PbI3 perovskite thin films grown in the presence of chloride is at least one-order of magnitude lower than that grown in the absence of chloride, thus explaining a widely known mystery on the much better solar cell performance of the former. The trap states are likely caused by electron-phonon coupling and are enhanced at surfaces/interfaces where the perovskite crystal structure is most susceptible to deformation.
Bladder inhibition by intermittent pudendal nerve stimulation in cat using transdermal amplitude‐modulated signal (TAMS) (2012)

This pre-clinical study indicated that intermittent stimulation of the pudendal nerve could be as effective as continuous stimulation to inhibit reflex bladder activity. These results are useful for the design and development of new stimulator technology to treat overactive bladder, and are also important for understanding pudendal neuromodulation therapy.
Denervation atrophy is independent from Akt and mTOR activation and is not rescued by myostatin inhibition (2014)

The purpose of our study was to compare two acquired muscle atrophies and the use of myostatin inhibition for their treatment. Myostatin naturally inhibits skeletal muscle growth by binding to ActRIIB, a receptor on the cell surface of myofibers. Because blocking myostatin in an adult wild-type mouse induces profound muscle hypertrophy, we applied a soluble ActRIIB receptor to models of disuse (limb immobilization) and denervation (sciatic nerve resection) atrophy. We found that treatment of immobilized mice with ActRIIB prevented the loss of muscle mass observed in placebo-treated mice. Our results suggest that this protection from disuse atrophy is regulated by serum and glucocorticoid-induced kinase (SGK) rather than by Akt. Denervation atrophy, however, was not protected by ActRIIB treatment, yet resulted in an upregulation of the pro-growth factors Akt, SGK and components of the mTOR pathway. We then treated the denervated mice with the mTOR inhibitor rapamycin and found that, despite a reduction in mTOR activation, there is no alteration of the atrophy phenotype. Additionally, rapamycin prevented the denervation-induced upregulation of the mTORC2 substrates Akt and SGK. Thus, our studies show that denervation atrophy is not only independent from Akt, SGK and mTOR activation but also has a different underlying pathophysiological mechanism than disuse atrophy.
A high performance static magnetic shielded room for detecting biomagnetic nanoparticles (2010)

A three-layer magnetic shielded room (MSR) has been built to house biomagnetic nanoparticles detecting system based on a low temperature Superconducting Quantum Interference Device (SQUID). The MSR with an open type door was designed to match the noise levels of SQUID coupled with one-order gradiometers while minimizing the overall facility cost. The room measures 2 × 2 × 2 m <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> internally and consists of three-layer silicon-steel plate shell instead of the permalloy. The static shielding factor in the room is 25000 at which point the eminent magnetization is 2 nT. This valve matches the measurement of isothermal remanent magnetizations (IRM). We conclude that using cheap materials of silicon-steel plate with relative low permeability can also produce a high performance MSR.
An over 100 W n-GaN/n-AlGaN/GaN MIS-HEMT power amplifier for wireless base station applications (2006)

Novel n-GaN/n-AlGaN/GaN metal-insulator-semiconductor high electron mobility transistors (MIS-HEMTs) with Si <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4 </sub> film were fabricated on a semi-insulating (S.I.) SiC substrate. An n-GaN/n-AlGaN/GaN MIS-HEMT with a breakdown voltage of 400 V was obtained by using SiN/n-GaN cap structure. The single-chip GaN MIS-HEMT amplifier operated at 60 V achieves a high output power of 110 W with a linear gain of 13 dB at 2.14 GHz. This is the first report of an AlGaN/GaN MIS-HEMT with an over 100 W output power. The MIS-HEMT amplifier, combined with a digital pre-distortion (DPD) system, also demonstrates an adjacent channel leakage power ratio (ACLR) of less than -50 dBc for 4-carrier W-CDMA signals
A 4-Hz Fundamental Linewidth on-chip Microlaser (2007)

A compact laser source on a silicon chip with Shawlow-Townes linewidth (i.e., fundamental, quantum limited) down to a few Hertz is demonstrated in this work. The fundamental linewidth is observed to decrease with inverse optical power.
Healthcare Knowledge Acquisition: An Ontology-Based Approach Using the Extensible Markup Language (XML) (2000)

The healthcare enterprise requires a great deal of knowledge to maintain premium efficiency in the delivery of quality healthcare. We employ Knowledge Management based knowledge acquisition strategies to procure 'tacit' healthcare knowledge from experienced healthcare practitioners. Situational, problem-specific Scenarios are proposed as viable knowledge acquisition and representation constructs. We present a healthcare Tacit Knowledge Acquisition Info-structure (TKAI) that allows remote healthcare practitioners to record their tacit knowledge. TKAI employs (a) ontologies for standardisation of tacit knowledge and (b) XML to represent scenario instances for their transfer over the Internet to the server-side Scenario-Base and for the global sharing of acquired tacit healthcare knowledge.
High-Resolution Cardiovascular MRI by Integrating Parallel Imaging With Low-Rank and Sparse Modeling (2013)

Magnetic resonance imaging (MRI) has long been recognized as a powerful tool for cardiovascular imaging because of its unique potential to measure blood flow, cardiac wall motion, and tissue properties jointly. However, many clinical applications of cardiac MRI have been limited by low imaging speed. In this paper, we present a novel method to accelerate cardiovascular MRI through the integration of parallel imaging, low-rank modeling, and sparse modeling. This method consists of a novel image model and specialized data acquisition. Of particular novelty is the proposed low-rank model component, which is specially adapted to the particular low-rank structure of cardiovascular signals. Simulations and in vivo experiments were performed to evaluate the method, as well as an analysis of the low-rank structure of a numerical cardiovascular phantom. Cardiac imaging experiments were carried out on both human and rat subjects without the use of ECG or respiratory gating and without breath holds. The proposed method reconstructed 2-D human cardiac images up to 22 fps and 1.0 mm × 1.0 mm spatial resolution and 3-D rat cardiac images at 67 fps and 0.65 mm × 0.65 mm × 0.31 mm spatial resolution. These capabilities will enhance the practical utility of cardiovascular MRI.
Isolation of Cannabinol, Cannabidiol and Quebrachitol from Red Oil of Minnesota Wild Hemp (1940)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIsolation of Cannabinol, Cannabidiol and Quebrachitol from Red Oil of Minnesota Wild HempRoger Adams, D. C. Pease, and J. H. ClarkCite this: J. Am. Chem. Soc. 1940, 62, 8, 2194–2196Publication Date (Print):August 1, 1940Publication History Published online1 May 2002Published inissue 1 August 1940https://pubs.acs.org/doi/10.1021/ja01865a080https://doi.org/10.1021/ja01865a080research-articleACS PublicationsRequest reuse permissionsArticle Views959Altmetric-Citations61LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
DNA labeling in living cells (2005)

The DNA dye DRAQ5 is well suited for chromatin visualization in living cells and can easily be combined with other fluorophores with blue to orange emission.
The SUGAR-DEPENDENT1 Lipase Limits Triacylglycerol Accumulation in Vegetative Tissues of Arabidopsis (2013)

There has been considerable interest recently in the prospect of engineering crops to produce triacylglycerol (TAG) in their vegetative tissues as a means to achieve a step change in oil yield. Here, we show that disruption of TAG hydrolysis in the Arabidopsis (Arabidopsis thaliana) lipase mutant sugar-dependent1 (sdp1) leads to a substantial accumulation of TAG in roots and stems but comparatively much lower TAG accumulation in leaves. TAG content in sdp1 roots increases with the age of the plant and can reach more than 1% of dry weight at maturity, a 50-fold increase over the wild type. TAG accumulation in sdp1 roots requires both ACYL-COENZYME A:DIACYLGLYCEROL ACYLTRANSFERASE1 (DGAT1) and PHOSPHATIDYLCHOLINE:DIACYLGLYCEROL ACYLTRANSFERASE1 and can also be strongly stimulated by the provision of exogenous sugar. In transgenic plants constitutively coexpressing WRINKLED1 and DGAT1, sdp1 also doubles the accumulation of TAG in roots, stems, and leaves, with levels ranging from 5% to 8% of dry weight. Finally, provision of 3% (w/v) exogenous Suc can further boost root TAG content in these transgenic plants to 17% of dry weight. This level of TAG is similar to seed tissues in many plant species and establishes the efficacy of an engineering strategy to produce oil in vegetative tissues that involves simultaneous manipulation of carbohydrate supply, fatty acid synthesis, TAG synthesis, and also TAG breakdown.