gebhart/patrepeval huggingface dataset:
Mucus Hypersecretion in Chronic Obstructive Pulmonary Disease (2000)

Most patients with chronic obstructive pulmonary disease (COPD) exhibit characteristics of airway mucus hypersecretion, namely sputum production, increased luminal mucus, submucosal gland hypertrophy and goblet cell hyperplasia. The clinical consequences of hypersecretion are impaired gas exchange and compromised mucociliary clearance, which encourages bacterial colonization and associated exacerbations. However, the extent of the contribution of mucus to pathophysiology of COPD is controversial. Early epidemiological studies found little evidence for the involvement of mucus in the age-related decline in lung function and mortality associated with COPD and concluded that chronic airflow obstruction and mucus hypersecretion were independent processes. Later studies found positive associations between phlegm production and decline in lung function, hospitalization and death. Thus, although not diagnostic for the condition, mucus hypersecretion contributes to morbidity and mortality in certain groups of patients with COPD. This suggests that it is important to develop drugs that inhibit mucus hypersecretion in these patients. Unfortunately, ambiguity in clinical studies of mucoactive drugs means that mucolytics are not recommended in clinical management. Future research should determine whether there is an intrinsic abnormality in mucus in COPD, which will determine development of appropriate inhibitors, which in turn can be used in 'proof of concept' and in treatment.
Peroxiredoxin Tsa1 Is the Key Peroxidase Suppressing Genome Instability and Protecting against Cell Death in Saccharomyces cerevisiae (2009)

Peroxiredoxins (Prxs) constitute a family of thiol-specific peroxidases that utilize cysteine (Cys) as the primary site of oxidation during the reduction of peroxides. To gain more insight into the physiological role of the five Prxs in budding yeast Saccharomyces cerevisiae, we performed a comparative study and found that Tsa1 was distinguished from the other Prxs in that by itself it played a key role in maintaining genome stability and in sustaining aerobic viability of rad51 mutants that are deficient in recombinational repair. Tsa2 and Dot5 played minor but distinct roles in suppressing the accumulation of mutations in cooperation with Tsa1. Tsa2 was capable of largely complementing the absence of Tsa1 when expressed under the control of the Tsa1 promoter. The presence of peroxidatic cysteine (Cys(47)) was essential for Tsa1 activity, while Tsa1(C170S) lacking the resolving Cys was partially functional. In the absence of Tsa1 activity (tsa1 or tsa1(CCS) lacking the peroxidatic and resolving Cys) and recombinational repair (rad51), dying cells displayed irregular cell size/shape, abnormal cell cycle progression, and significant increase of phosphatidylserine externalization, an early marker of apoptosis-like cell death. The tsa1(CCS) rad51- or tsa1 rad51-induced cell death did not depend on the caspase Yca1 and Ste20 kinase, while the absence of the checkpoint protein Rad9 accelerated the cell death processes. These results indicate that the peroxiredoxin Tsa1, in cooperation with appropriate DNA repair and checkpoint mechanisms, acts to protect S. cerevisiae cells against toxic levels of DNA damage that occur during aerobic growth.
VLSI implementation for one-dimensional multilevel lifting-based wavelet transform (2004)

The lifting scheme has been developed as a flexible tool suitable for constructing biorthogonal wavelets recently. We present an efficient VLSI architecture for the implementation of 1D lifting discrete wavelet transform. The architecture folds the computations of all resolution levels into the same low-pass and high-pass units to achieve higher hardware utilization. Because of its modular, regular, and flexible structure, the design is scalable for different resolution levels. In addition, its area is independent of the length of the 1D input sequence and its latency is independent of the number of resolution levels. Since the architecture has a similar topology to a scan chain, we can modify it easily to become a testable scan-based design by adding very few hardware resources. For the computations of N-sample 1D k-level analysis (5, 3) lifting wavelet transform, the design takes N+1 clock cycles, and requires two multipliers, four adders, and (3 + 2.25 /spl times/ 2/sup k/) registers. In the simulation, it works with a clock period of 10 ns and achieves a processing rate of about 100 /spl times/ 10/sup 6/ samples/sec for k-level lifting wavelet transform.
Synthetic Lethality through the Lens of Medicinal Chemistry (2020)

Personalized medicine and therapies represent the goal of modern medicine, as drug discovery strives to move away from one-cure-for-all and makes use of the various targets and biomarkers within differing disease areas. This approach, especially in oncology, is often undermined when the cells make use of alternative survival pathways. As such, acquired resistance is unfortunately common. In order to combat this phenomenon, synthetic lethality is being investigated, making use of existing genetic fragilities within the cancer cell. This Perspective highlights exciting targets within synthetic lethality, (PARP, ATR, ATM, DNA-PKcs, WEE1, CDK12, RAD51, RAD52, and PD-1) and discusses the medicinal chemistry programs being used to interrogate them, the challenges these programs face, and what the future holds for this promising field.
Empirical Bayes and Resampling Based Multiple Testing Procedure Controlling Tail Probability of the Proportion of False Positives. (2005)

Simultaneously testing a collection of null hypotheses about a data generating distribution based on a sample of independent and identically distributed observations is a fundamental and important statistical problem involving many applications. In this article we propose a new re-sampling based multiple testing procedure asymptotically controlling the probability that the proportion of false positives among the set of rejections exceeds q at level alpha, where q and alpha are user supplied numbers. The procedure involves 1) specifying a conditional distribution for a guessed set of true null hypotheses, given the data, which asymptotically is degenerate at the true set of null hypotheses, and 2) specifying a generally valid null distribution for the vector of test-statistics proposed in Pollard & van der Laan (2003), and generalized in our subsequent article Dudoit, van der Laan, & Pollard (2004), van der Laan, Dudoit, & Pollard (2004), and van der Laan, Dudoit, & Pollard (2004b). Ingredient 1) is established by fitting the empirical Bayes two component mixture model (Efron (2001b)) to the data to obtain an upper bound for marginal posterior probabilities of the null being true, given the data. We establish the finite sample rational behind our proposal, and prove that this new multiple testing procedure asymptotically controls the wished tail probability for the proportion of false positives under general data generating distributions. In addition, we provide simulation studies establishing that this method is generally more powerful in finite samples than our previously proposed augmentation multiple testing procedure (van der Laan, Dudoit, & Pollard (2004b)) and competing procedures from the literature. Finally, we illustrate our methodology with a data analysis.
A Quantitative Study of the Homologous Flares on 2000 November 24 (2004)

We present an examination of multiwavelength observations of three X-class homologous flares that occurred on 2000 November 24. By investigating the behavior of the two-ribbon flares in Hα and the ultraviolet (1600 Å), we found that the temporal variation of the distance between the two ribbons shows a good correlation with the soft X-ray light curve. From this finding we can derive the relation dISXR(t)/dt ∝ Vrib(t), where ISXR(t) is the soft X-ray intensity and Vrib(t) is the separation velocity of the two ribbons. This relation is similar to the well-known empirical law, the Neupert effect. We also measured the rise time, velocity of the plasmoid/filament ejection, and separation velocity of the two ribbons for each of these homologous flares. Since the magnetic reconnection model predicts that each of these physical parameters has a dependence on the coronal magnetic field strength Bc, we derived the relative Bc between the three flares from each of the parameters. We compared the relative Bc values, which are derived from those parameters, and found that they are roughly equal. Our results successfully support the magnetic reconnection model. Moreover, the relative hard X-ray maximum intensity in each flare is consistent with the relative Bc derived above, if we assume that the hard X-ray intensity is proportional to the energy release rate as implied by the Neupert effect.
MAb 18D3 Triggering of Integrin β1 Will Prevent but Not Terminate Proliferation of Human T Cells (1994)

Triggering of integrins can deliver signals that will regulate T cell activation and proliferation when coupled with TCR/CD3 signaling. While co-activation stimuli can be achieved either with immobilized natural ligands or immobilized monoclonal antibodies specific for various integrin subunits, counterposing effects can be delivered by ligation of the integrin beta 1 chain (CD29) resulting in the downregulation of T cell proliferation. Thus, integrins may play a pivotal role in cell activation and are involved in both positive and negative regulatory pathways. In this report, anti-beta 1 mAb 18D3 was used to investigate the role of beta 1 in the negative regulation of T cell proliferation. T lymphocytes were stimulated to proliferate when activated with immobilized mAb to CD3 in conjunction with all of a panel of immobilized mAb to different alpha 4 (CD49d) and beta 1 epitopes, except the anti-beta 1.1 mAb 18D3. In soluble form, mAb 18D3 inhibited the induction of DNA synthesis dependent on costimulation of CD3 and the integrin alpha 4 subunit by a mechanism independent of anti-adhesive properties. In kinetic experiments, the addition of mAb 18D3 effectively inhibited the ultimate induction of DNA synthesis at all time points until the time coinciding with the onset of T cell proliferation, indicating that triggering the beta 1.1 epitope may only act to quench activation events prior to cellular commitment to synthesize DNA. MAb 18D3 did not induce cell death nor render cells incompetent for restimulation, but appeared to selectively inhibit IL-2 synthesis with little effect on the induction of IL-2 receptor expression.
Development and Biocompatibility Characterization of a BioMEMS Sensor for Monitoring the Progression of Fracture Healing (2009)

Orthopaedic extremity injuries present a large medical and financial burden to the United States and world-wide communities [1]. Approximately six million long bone fractures are reported annually in the United States and approximately 10% of these fractures do not heal properly. Though the exact mechanism of impaired healing is poorly understood, many of these non-unions result when there is a communited condition that does not proceed through a stabilized healing pathway [2]. Currently, clinicians may monitor healing visually by radiographs, or via manual manipulation of the bone at the fracture [3]. Unfortunately, the course of aberrant fracture healing is not easily diagnosed in the early period when standard radiographic information of the fracture is not capable of discriminating the healing pathway. Manual assessment of fracture healing is also an inadequate diagnostic tool in the early stages of healing [4].
A Novel Density Functional Study of the Ground State Properties of a Localized Trinuclear Copper(II,II,III) Mixed-Valence System (2002)

Herein we report the analysis of a mixed-valence localized trinuclear copper(II,II,III) cluster by density functional theory. We focused on two peculiar aspects of this system. First we investigated the triplet ground state potential energy surface on a model system. To this end we computed, on the [E multiply sign in circle e] adiabatic potential energy surface, the potential energy profile along the e mode and constructed ab initio the full potential energy surface (the so called Mexican hat), by a fitting procedure. Next, we analyzed the magnetooptical properties of the minimum energy structures. In particular, we applied the single determinant method to compute the full manifold of states arising from the highest occupied molecular orbitals (magnetic orbitals). This procedure yielded results in agreement with previous calculations and with the available experimental data when using a model closer to the X-ray structure or when directly dealing with the complete structure of the system.
Comment on ‘‘Instability of the electron-hole plasma in silicon’’ (1986)

A Comment on the Letter by M. Combescot and J. Bok, Phys. Rev. Lett. 48, 1413 (1982).Received 21 January 1985DOI:https://doi.org/10.1103/PhysRevLett.56.205©1986 American Physical Society
The application of response surface methodology to sterilization process development and validation of a water cascade autoclave. (2000)

The application of Response Surface Methodology (RSM) to the performance validation of a water cascade sterilizer is described. The methodology was successfully used to 1) identify the cold and hot zones within maximum load configurations through three dimensional thermal mapping, 2) demonstrate the consistency of consecutive sterilization cycles in companion sterilizers, and 3) set target sterilizing values (F0) to achieve a high statistical assurance that any location will be above a minimum F0 (sterility assurance) and below a maximum F0 (for stability considerations).
Increased analytical sensitivity of RT‐PCR of PSA mRNA decreases diagnostic specificity of detection of prostatic cells in blood (1997)

The diagnostic specificity of the detection of disseminated prostatic cells by reverse-transcriptase polymerase chain reaction (RT-PCR) of PSA mRNA was investigated. A sensitive nested PCR was developed. In blood samples from 10 healthy female and 10 healthy male persons examined by RT-PCR, mRNA of PSA was detected 3 times in each group. In the groups of patients suffering from benign prostate hyperplasia and prostate cancer, 6 of 11 and 5 of 12, respectively, gave positive RT-PCR results. With increasing analytical sensitivity of the RT-PCR of PSA mRNA, the diagnostic specificity of the assay is decreased. Further development of this diagnostic method requires the introduction of the quantitative PCR which may make possible discrimination between prostatic and non-prostatic source of PSA mRNA by quantification. © 1997 Wiley-Liss, Inc.
Complete resolution of transplantation-associated thrombotic microangiopathy and hepatic veno-occlusive disease by defibrotide and plasma exchange. (2005)

Transplantation-associated thrombotic microangiopathy has been associated with significantly reduced survival following allogeneic bone marrow transplantation. We describe here the course of Transplantation-associated thrombotic microangiopathy and hepatic veno-occlusive disease, and response to plasma exchange therapy. A 19-year-old male patient underwent hematopoietic stem cell transplantation (HSCT) from his HLA-matched brother for lymphoblastic lymphoma in the first complete remission. Transplantation-associated thrombotic microangiopathy was diagnosed 17 days after transplantation. At that time, neurological abnormalities were not present. Cyclosporin A (CsA) was discontinued. Hematological stabilization was recorded. On day +20, abdominal distention, painful hepatomegaly and ascites complicated the clinical picture. With a high hepatic venous pressure gradient (18mmH20), veno-occlusive disease of the liver was diagnosed and defibrotide was started, which resulted in a dramatic cessation of pain and increase in urinary output. However, transplantation-associated thrombotic microangiopathy-related symptoms progressed and plasma exchange was instituted, which resulted in worsening of veno-occlusive disease symptoms. He was referred to the Intensive Care Unit due to respiratory compromise and was intubated. Plasma exchange was continued in order after hemofiltration. In three days, fever resolved, hemofiltration could be stopped, and ventilator dependence ended. After 19 aphereses, serum LDH level returned to normal and schistocytes were minimal on microscopic examination of the blood film. Platelet count increase was more gradual. Plasma exchange was discontinued. On the 40th day of defibrotide, all symptoms related with veno-occlusive disease were resolved and defibrotide was stopped. We think that our case is important to establish the relation and management strategy of these two small vessel complications of HSCT.
Treatment of aphthous stomatitis with saturated potassium nitrate/dimethyl isosorbide. (2004)

Concentrated potassium nitrate has been used to lessen the pain caused by aphthous stomatitis. The problem with this approach is that it can have difficulty penetrating into the deeper layers of mucosae or skin, and for this reason, its beneficial affects are not routinely predictable. When dimethyl isosorbide is added to potassium nitrate in an aqueous hydroxyethyl cellulose gel, it enhances the capacity of potassium nitrate to more completely permeate these tissues and predictably promote rapid pain control and aphthae healing.
Gene transfer of dominant negative Rho kinase suppresses neointimal formation after balloon injury in pigs (2000)

Restenosis after angioplasty still remains a major problem for which neointimal formation appears to play an important role. Recent studies in vitro suggested that Rho kinase, a target protein of Rho, is important in various cellular functions. We thus examined whether Rho kinase is involved in the restenotic changes after balloon injury. In vivo gene transfer was performed immediately after balloon injury in both sides of the porcine femoral arteries with adenoviral vector encoding either a dominant negative form of Rho kinase (AdDNRhoK) or beta-galactosidase (AdLacZ) as a control. One week after the transfer, immunohistochemistry confirmed the successful gene expression in the vessel wall, whereas 2 wk after the transfer, Western blotting showed the functional upregulation of Rho kinase at the AdLacZ site and its suppression at the AdDNRhoK site. Angiography showed the development of a stenotic lesion at the AdLacZ site where histological neointimal formation was noted, whereas those changes were significantly suppressed at the AdDNRhoK site. These results indicate that Rho kinase is involved in the pathogenesis of neointimal formation after balloon injury in vivo.
5-Mode amplifier with low modal crosstalk for spatial mode multiplexing transmission with low signal processing complexity (2015)

We build a 5-mode amplifier with low modal crosstalk. With this amplifier we demonstrate, for the first time, an amplified transmission of 100Gbits/s signals over 80km of few mode fiber with low signal processing complexity.
An injection-locked 8.5 GHz VCO with decade-wide programmable locking range in SiGe BiCMOS (2015)

This paper presents a low-noise subharmonically injection-locked VCO with programmable locking range. A pulse generator with programmable duty cycle converts the external reference signal into a narrow pulse that locks the VCO. Record low phase noise of -115 dBc/Hz at 100 kHz offset is achieved by combining a low-noise CML pulse generator with a cross-coupled VCO. The VCO features programmable locking range from 10 to 500 MHz. Fabricated in a production SiGe BiCMOS technology, the circuit demonstrates record low phase noise, both at close-in and far-out frequency offsets from the carrier.
Microsomal Δ9, Δ6 and Δ5 desaturase activities and liver membrane fatty acid profiles in alcohol‐fed rats (1990)

In experimentally produced alcoholic fatty liver microsomal fatty acid composition was measured using gas chromatography. The results showed an increase in linoleic acid (18:2, n-6) and hexadecaenoic acid (22:6, n-3) and a decrease in arachidonic acid (20:4, n-6) in alcohol-fed rats. Using high performance liquid chromatographic separation of radiolabelled substrate and products, delta 9, delta 6 and delta 5 desaturase enzymes were assayed. The activity of delta 9 and delta 5 desaturase was decreased in alcohol-fed rats and delta 6 desaturase activity was similar in control and alcohol-fed groups. These results indicated there was no causal relationship between desaturase activity and membrane fatty acid changes. Increased amounts of eicosatrienoic acid (20:3, n-9) in rats fed less than 5% fat were observed in both control and alcohol-fed rats. The results indicated that essential fatty acid deficiency was not due to alcohol consumption.
WE‐C‐214‐07: A Global Digital Benchmark and QA Data Center for Radiotherapy Quality Assurance (2011)

Purpose: To establish a centralized database platform for radiotherapy quality assurance (QA). This can be an interactive platform where physicists can download digital benchmark cases from, perform radiotherapy planning and QA measurements with various planning and delivery systems, and upload the results. Data retrieval and analysis functions can then be developed for the quality assessment of the radiation plan and measurement in the context of prior data with similar planning, delivery and measurement technologies. Data mining of the system can in turn generate quantitative guidance for clinical trial QA requirements that have the optimum combination of stringent mandates and realistic accommodations. Methods: Built upon prior experience of Task Group(TG) 119 from IMRT workgroup of AAPM, and digital data phantoms from EORTC, these groups collaborate with clinical trial work group of AAPM and advanced technology consortium (ATC) to establish a virtual QA environment within National Biomedical Imaging Archive (NBIA). Digital phantoms from TG 119 and EORTC dosimetric evaluation with DICOM image, structures, plan and dose were uploaded to the virtual QA environment for the established community to download and perform evaluation of basic dosimetric parameters including, structure volumes, geometric location of structure center, designated points on dose volume histogram (DVH). Nine different treatment planning or related systems with various versions are included in these evaluations. Results: Volume variations among versions of these nine systems are 2.7%, 4.2%, 14.7%, 4.7% for prostate PTV, prostate, rectum and bladder respectively. DVH reading differences are 0.1%, 2.4% and 1.5% for prostate D95, rectum D30 and bladder D30. DVH reading differences for cube 10 are 1%, 86% and 100% for V0, V20 and V30 respectively. Conclusions: A virtual QA environment has been established within NBIA for radiation oncology inter‐system and inter‐institution QA. Initial testing in reading geometric and dosimetric parameters identified significant variations among systems.
Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) robustly detects and distinguishes 11p15 abnormalities associated with overgrowth and growth retardation (2007)

MS-MLPA robustly and sensitively detects and distinguishes epigenetic and copy number abnormalities at 11p15 and is an effective first line investigation of 11p15 in individuals with overgrowth or growth retardation.
Identification and characterization of pseudogenes in the rice gene complement (2009)

These pseudogenes still have a detectable open reading frame and are thus distinct from pseudogenes detected within intergenic regions which typically lack definable open reading frames. Families containing the highest number of pseudogenes are fast-evolving families involved in ubiquitination and secondary metabolism.