gebhart/patrepeval huggingface dataset:
Sputum matrix metalloproteinase-9 is associated with emphysema on computed tomography in COPD (2013)

Background Matrix-metalloproteinase (MMP)-9 has been implicated in the pathogenesis of COPD. The relationship between disease severity and sputum MMP-9 concentrations and activity is not known. The purpose of the study was to examine the relationship between disease severity assessed by lung function and computed tomography (CT) and sputum MMP-9 concentrations and activity in patients with COPD. Methods In 53 COPD subjects, smokers and ex-smokers; mild, moderate and severe; 46 healthy controls, smokers and never smokers, we measured sputum MMP-9 concentrations (ELISA) and enzyme activity (FRET), induced sputum cell counts, diffusing capacity for carbon monoxide (DLco) and CT assessment of emphysema (% low attenuation areas below-950 Hounsfield units). Results In COPD sputum MMP-9 concentrations are higher than in healthy non-smokers (p=0.007), and similar to healthy smokers (p=0.340). Ex-smokers with COPD had higher concentrations and activity of sputum MMP-9 than current smokers with COPD (P=0.002 and P&lt;0.001 respectively). MMP-9 in sputum correlated with induced sputum neutrophil% [correlation coefficient 0.724 (0.536, 0.846)]. In COPD, disease severity when assessed by the CT measure of emphysema, but not by spirometry or DLco values, is directly associated with sputum MMP-9 concentrations (0.439 (0.175, 0.651). Conclusions Sputum MMP-9 concentrations in COPD is directly associated with the degree of emphysema measured by CT. This finding supports a role for MMP-9 in the pathogenesis of emphysema.
Data from Cyst Fluid Telomerase Activity Predicts the Histologic Grade of Cystic Neoplasms of the Pancreas (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Pancreatic cysts frequently pose clinical dilemmas. On one hand, cysts with high-grade dysplasia offer opportunities for cure, on the other hand, those with low-grade dysplasia are easily over treated. Cyst fluid markers have the potential to improve the evaluation of these cysts. Because telomerase activity is commonly activated in malignant cells, we evaluated the diagnostic performance of cyst fluid telomerase activity measurements for predicting histologic grade.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; Telomerase activity was measured using telomerase repeat amplification with digital-droplet PCR in surgically aspirated cyst fluid samples from 219 patients who underwent pancreatic resection for a cystic lesion (184 discovery, 35 validation) and 36 patients who underwent endoscopic ultrasound fine-needle aspiration. Methodologic and clinical factors associated with telomerase activity were examined.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Telomerase activity was reduced in samples that had undergone prior thawing. Among 119 samples not previously thawed, surgical cyst fluids from cystic neoplasms with high-grade dysplasia ± associated invasive cancer had higher telomerase activity [median (interquartile range), 1,158 (295.9–13,033)] copies/μL of cyst fluid than those without [19.74 (2.58–233.6) copies/μL; &lt;i&gt;P&lt;/i&gt; &lt; 0.001)]. Elevated cyst fluid telomerase activity had a diagnostic accuracy for invasive cancer/high-grade dysplasia of 88.1% (discovery), 88.6% (validation), and 88.2% (merged). Among cysts classified preoperatively as having “worrisome features,” cyst fluid telomerase activity had high diagnostic performance (sensitivity 73.7%, specificity 90.6%, accuracy, 86.1%). In multivariate analysis, telomerase activity independently predicted the presence of invasive cancer/high-grade dysplasia.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Cyst fluid telomerase activity can be a useful predictor of the neoplastic grade of pancreatic cysts. &lt;i&gt;Clin Cancer Res; 22(20); 5141–51. ©2016 AACR&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;&lt;i&gt;See related commentary by Allen et al., p. 4966&lt;/i&gt;&lt;/p&gt;&lt;/div&gt;
ChemInform Abstract: Synthesis of Optically Active Thiadecalins and Thiahydrindans by a Proline‐Catalyzed Intramolecular Michael Reaction. (1989)

Abstract The thiahydrindanes (IV) and (V) and the thiadecaline (VIII) are prepared from the enones (I) and (VI) via epoxidation, regioselective oxirane cleavage with mercaptoacetone (II), dehydration, and subsequent cyclization in the presence of L‐proline.
ChemInform Abstract: A New Labdane Diterpene from the Flowers of Solidago canadensis. (2008)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Transducer Placement for Broadband Active Vibration Control Using a Novel Multidimensional QR Factorization (1998)

This paper advances the state of the art in the selection of minimal configurations of sensors and actuators for active vibration control with smart structures. The method extends previous transducer selection work by (1) presenting a unified treatment of the selection and placement of large numbers of both sensors and actuators in a smart structure, (2) developing computationally efficient techniques to select the best sensor-actuator pairs for multiple unknown force disturbances exciting the structure, (3) selecting the best sensors and actuators over multiple frequencies, and (4) providing bounds on the performance of the transducer selection algorithms. The approach is based on a novel, multidimensional extension of the Householder QR factorization algorithm applied to the frequency response matrices that define the vibration control problem. The key features of the algorithm are its very low computational complexity, and a computable bound that can be used to predict whether the transducer selection algorithm will yield an optimal configuration before completing the search. Optimal configurations will result from the selection method when the bound is tight, which is the case for many practical vibration control problems. This paper presents the development of the method, as well as its application in active vibration control of a plate.
Structure and topology of monomeric phospholamban in lipid membranes determined by a hybrid solution and solid-state NMR approach (2009)

Phospholamban (PLN) is an essential regulator of cardiac muscle contractility. The homopentameric assembly of PLN is the reservoir for active monomers that, upon deoligomerization form 1:1 complexes with the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), thus modulating the rate of calcium uptake. In lipid bilayers and micelles, monomeric PLN exists in equilibrium between a bent (or resting) T state and a more dynamic (or active) R state. Here, we report the high-resolution structure and topology of the T state of a monomeric PLN mutant in lipid bilayers, using a hybrid of solution and solid-state NMR restraints together with molecular dynamics simulations in explicit lipid environments. Unlike the previous structural ensemble determined in micelles, this approach gives a complete picture of the PLN monomer structure in a lipid bilayer. This hybrid ensemble exemplifies the tilt, rotation, and depth of membrane insertion, revealing the interaction with the lipids for all protein domains. The N-terminal amphipathic helical domain Ia (residues 1-16) rests on the surface of the lipid membrane with the hydrophobic face of domain Ia embedded in the membrane bilayer interior. The helix comprised of domain Ib (residues 23-30) and transmembrane domain II (residues 31-52) traverses the bilayer with a tilt angle of approximately 24 degrees . The specific interactions between PLN and lipid membranes may represent an additional regulatory element of its inhibitory function. We propose this hybrid method for the simultaneous determination of structure and topology for membrane proteins with compact folds or proteins whose spatial arrangement is dictated by their specific interactions with lipid bilayers.
The bradykinin B1 receptor and the central regulation of blood pressure in spontaneously hypertensive rats (1999)

1. We evaluated if the brain bradykinin (BK) B1 receptor is involved in the regulation of blood pressure (BP) in conscious rats. 2. Basal mean BP and HR were 115 +/- 2 and 165 +/- 3 mmHg and 345 +/- 10 and 410 +/- 14 beats min in Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR), respectively. Intracerebroventricular (i.c.v.) injection of 1 nmol B1 receptor agonist Lys-desArg9-BK significantly increased the BP of WKY and SHR by 7+/-1 and 19+/-2 mmHg, respectively. One nmol Sar[D-Phe8]-desArg9-BK, a kininase-resistant B1 agonist, increased the BP of WKY and SHR by 19+/-2 and 17+/-2 mmHg, respectively and reduced HR in both strains. 3. I.c.v. injection of 0.01 nmol B1 antagonists, LysLeu8-desArg9-BK or AcLys[D-betaNal7,Ile8]-desArg9-BK (R715), significantly decreased mean BP in SHR (by 9+/-2 mmHg the former and 14+/-3 mmHg the latter compound), but not in WKY. In SHR, the BP response to R715 was associated to tachycardia. 4. I.c.v. Captopril, a kininase inhibitor, increased the BP of SHR, this response being partially prevented by i.c.v. R715 and reversed into a vasodepressor effect by R715 in combination with the B2 antagonist Icatibant. 5. I.c.v. antisense oligodeoxynucleotides (ODNs) targeted to the B1 receptor mRNA decreased BP in SHR, but not in WKY. HR was not altered in either strain. Distribution of fluorescein-conjugated ODNs was detected in brain areas surrounding cerebral ventricles. 6. Our results indicate that the brain B1 receptor participates in the regulation of BP. Activation of the B1 receptor by kinin metabolites could participate in the pathogenesis of hypertension in SHR.
Is it time to start with device-based prognosticators? (2009)

Do we really need to look into device-based prognostic indicators of mortality of heart failure patients? After all, numerous studies demonstrated the predictive importance of a large number of parameters including natriuretic peptides, inflammatory markers, and electrocardiographic parameters, not to mention innumerable demographic and readily available blood tests. Thus, one could view the excellent study by Singh et al. 1 in this issue of the journal as an academic exercise in prognostication of the outcome of heart failure patients. Indeed, we already have models and scores aiming at a better prognostic performance across the heart failure spectrum, i.e. the Heart Failure Survival Score, the Seattle Heart Failure Model, the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure predictive schemes, the Acute Decompensated Heart Failure National Registry regression tree discrimination, just to mention some of them. However, the study by Singh et al. 1 provides more reasons to care about prognostic indicators in general and, in this case, based on device diagnostics. Indeed, currently available models and scores are imperfect for predicting major events, such as implantation of left ventricular assist device, heart transplantation, and mortality. The authors used a rather simple dynamic predictive model based on device diagnostic data in risk stratification of out-patient heart failure patients treated with cardiac resynchronization therapy (CRT). They showed, e.g., that higher heart rate variability measured by Standard Deviation of the averages of intrinsic R-R intervals (SDANN) at two points in time (2 weeks and 3 months after CRT implantation), and relative large increase from 2 weeks value to 3 months value were associated with a decreased risk of death.

Although the … 

*Corresponding author. Tel: +41 91 805 3340, Fax: +41 91 805 3167, Email: angelo.auricchio{at}cardiocentro.org
ChemInform Abstract: PALLADIUM CATALYZED FRAGMENTATION REACTION AS AN APPROACH TO VITAMIN A ESTER (1982)

Abstract Aus dem Polyen‐aldehydcarbonsäureester (I) entsteht mit dem Dianion (II) der Isobuttersäure die Hydroxycarbonsäure (IIIa), die zu (IIIb) acetyliert und durch Fragmentierung in den Polyenester (IV) übergeführt wird.
MANAGEMENT SUPERVISION PLAN RECEIVED POSITIVELY. AN EVALUATION OF THREE YEARS OF EXPERIENCE (2001)

An increasing number of projects in the civil engineering sector are being implemented under quality assurance. This means not only that the contractor works with a quality plan, but also that the management supervises execution using a management supervision plan. Grontmij has been using a supervision plan for the past three years, and the experiences are positive. This article includes the reactions of those involved to the work, quality and supervision plans, and an overview of the improvement points resulting from the evaluation.
P2‐037: Development and analytical validation of a novel assay for measurement of total tau in human CSF (2012)

Measurement of Alzheimer's disease (AD) biomarkers in clinical cerebrospinal fluid (CSF) samples has been challenging with existing assays due to inter-lot variability, matrix interferences, and inconsistent quantitation. Here we describe the development and analytical validation of an assay to measure Total Tau in human CSF using Fit-for-Purpose and CLSI principles. Elements of assay development and performance are presented as well as results of multi-lot validation. Monoclonal antibodies were evaluated and selected based on sensitivity, specificity, affinity, and performance characteristics in human CSF. Critical reagents were subjected to biochemical and functional characterization to verify purity, integrity, and lot-to-lot consistency. The assay was developed with MSD's MULTI-ARRAY® technology and optimized to minimize CSF matrix effects and interferences. Analytical validation was assessed across three independent kit lots to verify performance including sensitivity, accuracy, and precision using matrix-based validation samples. Tests were conducted by multiple analysts over multiple runs and days. Dilution linearity and spike recovery were measured using well-curated normal and AD CSF samples. The assay demonstrated good sensitivity, performance, and inter-lot reproducibility and differentiated between normal and AD CSF samples. The average LLOD determined from 54 runs over three independent kit lots was 10 pg/mL with a quantitative range of 30 to 8000 pg/mL. The precision, accuracy, and total error were determined from matrix-based controls with typical precision of <10% CV (inter-plate) and <5% CV (intra-plate). Dilution linearity and spike recovery testing demonstrated quantitation of Tau protein over the range of the assay and minimal interference from human CSF matrix. Furthermore, the assay detected 6 isoforms of human Tau and was tolerant of significant CSF contamination with hemolyzed blood. Data also showed that the assay measured elevated levels of Tau in AD samples compared to healthy samples. A new assay was developed and analytically validated to measure Tau in human CSF. The result is an assay with good analytical performance characteristics and lot to lot reproducibility with the ability to distinguish Tau levels between healthy and AD CSF samples. This assay will support ongoing efforts to standardize testing of biomarkers for AD and other tauopathies.
Generative co-design for microfluidics-accelerated 3D printing (2022)

Increasing the speed of 3D printing is critical for its widespread adoption as a manufacturing technique. A recently-introduced multi-material 3D printing process called injection CLIP has been shown to accelerate printing by nearly an order of magnitude using computationally-designed microfluidic networks. However, automated design tools for 3D microfluidics have lagged far behind increasing fabrication capabilities and needs. Here, to facilitate the study and application of this novel printing process, we present a fluid dynamics-informed generative design tool for microfluidic networks based on native CAD geometries.
KRAS G12C mutation and risk of disease recurrence in stage I surgically resected lung adenocarcinoma (2023)

KRAS G12C mutations are found in about 12-13% of LUAD samples and it is unclear whether they are associated with worse survival outcomes in resected, stage I LUAD. We assessed whether KRAS-G12C mutated tumours had worse DFS when compared to KRAS-nonG12C mutated tumours and to KRAS wild-type tumours in a cohort of resected, stage I LUAD (IRE cohort). We then leveraged on publicly available datasets (TCGA-LUAD, MSK-LUAD<sup>604</sup>) to further test the hypothesis in external cohorts. In the stage I IRE cohort we found a significant association between the KRAS-G12C mutation and worse DFS in multivariable analysis (HR: 2.47). In the TCGA-LUAD stage I cohort we did not find statistically significant associations between the KRAS-G12C mutation and DFS. In the MSK-LUAD<sup>604</sup> stage I cohort we found that KRAS-G12C mutated tumours had worse RFS when compared to KRAS-nonG12C mutated tumours in univariable analysis (HR 3.5). In the pooled stage I cohort we found that KRAS-G12C mutated tumours had worse DFS when compared to KRAS-nonG12C mutated tumours (HR 2.6), to KRAS wild-type tumours (HR 1.6) and to any other tumours (HR 1.8); in multivariable analysis, the KRAS-G12C mutation was associated with worse DFS (HR 1.61). Our results suggest that patients with resected, stage I LUAD with a KRAS-G12C mutation may have inferior survival outcomes..
Proxy signatures for delegating signing operation (1996)

In this paper a new type of digital proxy signature is proposed. The proxy signature allows a designated person, called a proxy signer, to sign on behalf of an original signer. Classification of the proxy signatures is shown from the point of view of the degree of delegation, and conditions of a proposed proxy signature for partial delegation are clarified. The proposed proxy signature scheme is based on the discrete logarithm problem. Compared to the consecutive execution of the ordinary digital signature schemes, it has a direct form, and a verifier does not need a public key of a user other than the original signer in the verification stage. Moreover, it requires less amount of computational work than the consecutive execution of the signature schemes. Due to this efficiency together with the delegation property, an organization, e.g. a software company, can very efficiently create many signatures of its own by delegating its signing operations to multiple employees. Another attractive feature of the proposed schemes is their highapplicability to other ordinary signature schemes based on the discrete logarithm problem. For instance, designated confirmer proxy signatures can be constructed. Furthermore, using a proposed on-line proxy updating protocol, the original signer can revoke proxies of dishonest proxy signers.
Automation of a Quantitative Immunochemical Microanalysis of Human Serum Transferrin: A Model System (1970)

Abstract The quantitative immunochemical determination of human serum transferrin was automated with a 100-µl sample. The estimated standard deviation from the true value was 7.9 mg/100 ml in 21 samples of serum, which had transferrin concentrations of 139-325 mg/100 ml.
Stereoselective HDAC Inhibition from Cysteine‐Derived Zinc‐Binding Groups (2009)

A series of small-molecule histone deacetylase (HDAC) inhibitors, which feature zinc binding groups derived from cysteine, were synthesized. These inhibitors were tested against multiple HDAC isoforms, and the most potent, compound 10, was determined to have IC(50) values below 1 microM. The compounds were also tested in a cellular assay of oxidative stress-induced neurodegeneration. Many of the inhibitors gave near-complete protection against cell death at 10 microM without the neurotoxicity seen with hydroxamic acid-based inhibitors, and were far more neuroprotective than HDAC inhibitors currently in clinical trials. Both enantiomers of cysteine were used in the synthesis of a variety of novel zinc-binding groups (ZBGs). Derivatives of L-cysteine were active in the HDAC inhibition assays, while the derivatives of D-cysteine were inactive. Notably, the finding that both the D- and L-cysteine derivatives were active in the neuroprotection assays suggests that multiple mechanisms are working to protect the neurons from cell death. Molecular modeling was employed to investigate the differences in inhibitory activity between the HDAC inhibitors generated from the two enantiomeric forms of cysteine.
Application of novel calibration scheme based on traceable point-like 22Na sources to various types of PET scanners (2012)

Purpose: We have been developing a practical and reliable calibration scheme based on the use of traceable point-like sources. In using <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">22</sup> Na sources, special care should be taken to avoid the effects of 1.275-MeV γ rays accompanying β <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">+</sup> decays. The purpose of this study is to validate this calibration method with traceable point-like <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">22</sup> Na sources on various types of PET scanners. Method: The traceable point-like <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">22</sup> Na sources with a spherical absorber design used in this study were of the same type as those used in a previous study. The tested PET scanners included one clinical whole-body PET scanner, four types of clinical PET/CT scanners from different manufacturers, and one small-animal PET scanner. The ROI (region of interest) diameter dependence of ROI values were represented with a fitting function, which was assumed to consist of a recovery part due to spatial resolution and a quadratic background part originating from the scattered γ rays. Results: The calibration factors determined using the point-like source were consistent with those by the standard cross-calibration method within ±4%, which was comparable to the uncertainty of the standard cross-calibration method. Conclusion: The novel calibration scheme based on the use of traceable <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">22</sup> Na point-like sources was validated for six types of commercial PET scanners.
Gel Stent Implantation—Recommendations for Preoperative Assessment, Surgical Technique, and Postoperative Management (2018)

The surgical management of glaucoma offers the potential to lower intraocular pressure (IOP) independent of patients’ compliance with their medication regimen. Procedures such as trabeculectomy and tube shunt placement often yield large magnitudes of IOP reduction, but may be associated with short- and long-term complications. Microinvasive glaucoma surgery (MIGS) offers an alternative surgical approach that is inherently less invasive; however, most devices that fit in this category are associated with a lesser degree of IOP-lowering efficacy compared with traditional glaucoma surgeries. A newer MIGS device, a gel stent that facilitates drainage to the subconjunctival space, appears to offer similar IOP reduction to trabeculectomy, but with much less tissue manipulation; better predictability; and less sight-threatening complications, thus making it a potentially safer and more predictable surgical option in appropriate patients. The following proposed protocol, based on evidence-based practices and augmented where necessary by the opinions of experienced surgeons, provides guidance for the pre-, intra-, and postoperative management of patients receiving a gel stent implant. The goal of this protocol is to provide a framework for better patient selection and preparation, surgical pearls, and how best to assess and manage patients in the postoperative period.