gebhart/patrepeval huggingface dataset:
An outbreak of listeriosis suspected to have been caused by rainbow trout (1997)

An outbreak of listeriosis in Sweden, consisting of nine cases, was investigated by means of molecular typing of strains from patients and strains isolated from suspected foodstuffs, together with interviews of the patients. Listeria monocytogenes was isolated from six of the patients, and all isolates were of the same clonal type. This clonal type was also isolated from a "gravad" rainbow trout, made by producer Y, found in the refrigerator of one of the patients. Unopened packages obtained from producer Y were also found to contain the same clonal type of L. monocytogenes. Based on the interview results and the bacteriological typing, we suspect that at least six of the nine cases were caused by gravad or cold-smoked rainbow trout made by producer Y. To our knowledge, this is the first rainbow trout-borne outbreak of listeriosis ever reported.
Bronchoalveolar lavage in allergic asthmatics. (1987)

Introduction A n estimated 4% of Americans suffer from (1), and expenditures for the medical care of asthmatics, plus losses engendered by nonattendance at work and school, are estimated at more than 1 billion dollars annually (2). Despite the importance of this disorder, a great deal remains to be understood about each of the asthma syndromes. The asthma syndrome that has been best defined is extrinsic (allergic) asthma. A significant amount of information regarding this disorder is currently available from physiologic studies, aerosol challenge studies, in vitro studies of isolated lung fragments, and various animal models. Until recently, little information was available regarding the local immediate and delayed responses to allergen in patients with allergic asthma. This review will focus on the study of these events, especially as they relate to the use of bronchoalveolar lavage (BAL).
GPR124, an orphan G protein-coupled receptor, is required for CNS-specific vascularization and establishment of the blood–brain barrier (2011)

Every organ in the body requires blood vessels for efficient delivery of oxygen and nutrients, but independent vascular beds are highly specialized to meet the individual needs of specific organs. The vasculature of the brain is tightly sealed, with blood-brain barrier (BBB) properties developing coincident with neural vascularization. G protein-coupled receptor 124 (GPR124) (tumor endothelial marker 5, TEM5), an orphan member of the adhesion family of G protein-coupled receptors, was previously identified on the basis of its overexpression in tumor vasculature. Here, we show that global deletion or endothelial-specific deletion of GPR124 in mice results in embryonic lethality associated with abnormal angiogenesis of the forebrain and spinal cord. Expression of GPR124 was found to be required for invasion and migration of blood vessels into neuroepithelium, establishment of BBB properties, and expansion of the cerebral cortex. Thus, GPR124 is an important regulator of neurovasculature development and a potential drug target for cerebrovascular diseases.
Clinical usefulness of D-dimer testing in cancer patients with suspected pulmonary embolism (2006)

Limited data are available about the diagnostic value of D-dimer testing in cancer patients with clinically suspected pulmonary embolism (PE). Therefore, we evaluated i) the safety and clinical usefulness of an ELISA D-dimer test to rule out PE in cancer patients compared with non-cancer patients and ii) whether adopting a higher D-dimer cut-off value might increase the usefulness of D-dimer in cancer patients. We analysed data from two outcome studies which enrolled 1,721 consecutive patients presenting in the emergency department with clinically suspected PE. Presence of an active malignancy was abstracted from the database. All patients underwent a sequential diagnostic work-up including an ELISA D-dimer test and a 3-month followup. Sensitivity and predictive value (NPV) were 100% in both cancer and non-cancer patients. PE was ruled out by a negative D-dimer test in 494/1,554 (32%) patients without cancer, and in 18/164 (11%) patients with a malignancy. At cut-off values varying from 500 to 900 microg/l, the sensitivity was unchanged (100%, 95% CI: 93% to 100%) and the specificity increased from 16% (95% CI: 11% to 24%) to 30% (95% CI: 22% to 39%). The 3-month thromboembolic risk was 0% (95% CI: 0% to 18%) in cancer patients with a negative D-dimer test. ELISA D-dimer appears safe to rule out pulmonary embolism in cancer patients but it is negative in only one of ten patients at the usual cut-off value. Increasing the cut-off value of D-dimer in cancer patients might increase the test's clinical usefulness.
Characterization of a Glycoprotein of TTP4000 – A Soluble Decoy RAGE Antagonist (2013)

RAGE is a member of the Ig supergene family that binds amyloid beta with nanomolar affinity. Amyloid beta is implicated in the pathology of neurodegenerative Alzheimer's disease. We have developed TTP4000, a novel fusion protein that has similar ligand binding characteristics as sRAGE but a superior pharmacokinetic profile. TTP4000 was shown to significantly reduce soluble, brain Aβ levels in a mouse model of Alzheimers disease which correlates with a decrease in plaque load, reduction in inflammatory cytokine levels and improved measures of behavior. In this study we investigated the role of glycosylation on TTP4000 ligand binding activity. Incubation of wildtype TTP4000 with PNGase F and endoglycosidases to remove glycans results in improved ligand binding activity. Treatment of cells with 2‐deoxy‐D‐glucose results in reduced glycosylation and a slight increase in Aβ binding activity. We also show a relationship between reduction of TTP4000 glycosylation and increased ligand binding activity following mutation of N‐linked glycan sites that prevent glycosylation of TTP4000 at asparagines 2, 58, and 288. The N2Q‐R198A mutant showed 48 fold greater affinity in the Aβ binding assay when compared to wildtype. We also observed reduced expression levels of TTP4000 mutants when too much glycan was removed. The data herein demonstrate the importance of glycosylation for both stability and ligand binding activity in the design of a RAGE peptide antagonist.
The effects of deformation, ischemia, and reperfusion on the development of muscle damage during prolonged loading (2011)

Deep tissue injury (DTI) is a severe form of pressure ulcer where tissue damage starts in deep tissues underneath intact skin. In the present study, the contributions of deformation, ischemia, and reperfusion to skeletal muscle damage development were examined in a rat model during a 6-h period. Magnetic resonance imaging (MRI) was used to study perfusion (contrast-enhanced MRI) and tissue integrity (T2-weighted MRI). The levels of tissue deformation were estimated using finite element models. Complete ischemia caused a gradual homogeneous increase in T2 (∼20% during the 6-h period). The effect of reperfusion on T2 was highly variable, depending on the anatomical location. In experiments involving deformation, inevitably associated with partial ischemia, a variable T2 increase (17-66% during the 6-h period) was observed reflecting the significant variation in deformation (with two-dimensional strain energies of 0.60-1.51 J/mm) and ischemia (50.8-99.8% of the leg) between experiments. These results imply that deformation, ischemia, and reperfusion all contribute to the damage process during prolonged loading, although their importance varies with time. The critical deformation threshold and period of ischemia that cause muscle damage will certainly vary between individuals. These variations are related to intrinsic factors, such as pathological state, which partly explain the individual susceptibility to the development of DTI and highlight the need for regular assessments of individual subjects.
A 20 Mb/s Phase Modulator Based on a 3.6 GHz Digital PLL With −36 dB EVM at 5 mW Power (2012)

This paper presents a low-power high-bit-rate phase modulator based on a digital PLL with single-bit TDC and two-point injection scheme. At high bit rates, this scheme requires a controlled oscillator with wide tuning range and becomes critically sensitive to the delay spread between the two injection paths, considerably degrading the achievable error-vector magnitude and causing significant spectral regrowth. A multi-capacitor-bank oscillator topology with an automatic background regulation of the gains of the banks and a digital adaptive filter for the delay-spread correction are introduced. The phase modulator fabricated in a 65-nm CMOS process synthesizes carriers in the 2.9-to-4.0-GHz range from a 40-MHz crystal reference and it is able to produce a phase change up to ±π with 10-bit resolution in a single reference cycle. Measured EVM at 3.6 GHz is -36 dB for a 10-Mb/s GMSK and a 20-Mb/s QPSK modulation. Power dissipation is 5 mW from a 1.2-V voltage supply, leading to a total energy consumption of 0.25 nJ/bit.
Crystal Structure of Cas9 in Complex with Guide RNA and Target DNA (2014)

The CRISPR-associated endonuclease Cas9 can be targeted to specific genomic loci by single guide RNAs (sgRNAs). Here, we report the crystal structure of Streptococcus pyogenes Cas9 in complex with sgRNA and its target DNA at 2.5&amp;nbsp;Å resolution. The structure revealed a bilobed architecture composed of target recognition and nuclease lobes, accommodating the sgRNA:DNA heteroduplex in a positively charged groove at their interface. Whereas the recognition lobe is essential for binding sgRNA and DNA, the nuclease lobe contains the HNH and RuvC nuclease domains, which are properly positioned for cleavage of the complementary and noncomplementary strands of the target DNA, respectively. The nuclease lobe also contains a carboxyl-terminal domain responsible for the interaction with the protospacer adjacent motif (PAM). This high-resolution structure and accompanying functional analyses have revealed the molecular mechanism of RNA-guided DNA targeting by Cas9, thus paving the way for the rational design of new, versatile genome-editing technologies.
Aromatic Dicarboxylic Acids as Building Blocks of Extended Hydrogen-bonded Architectures (1998)

Abstract An examination of the crystal structures of four compounds, 5-amino iso-phthalic acid hemihydrate (monoclinic, P21/n, a = 8.142 (2), b = 17.444 (3), c = 11.140 (2) Å, β=94.19 (3)°, Dc =1.601 g cm−3, Z=8, Rw 2 = 0.106 for 1401 unique reflections), piperazinium(2+) 5-amino iso-phthalate (monoclinic, P21/c, a = 11.820 (2), b = 9.516 (2), c = 12.618 (3) Å, β = 116.70 (3)°, Dc = 1.400 g cm−3, Z = 4, Rw 2, = 0.104 for 2222 unique reflections), 2-chloro-benzylammonium 2-carboxylate-6-carboxylic pyridine (monoclinic, P21/c, a = 22.391 (2), b = 9.322 (3), c=13.274 (2) Å, β=92.567 (11), Dc =1.482 g cm−3, Z=8, Rw 2 = 0.113 for 3610 unique reflections), and 3-fluoro-benzylammonium 2-carboxylate-6-carboxylic pyridine hydrate (monoclinic, P21/c, a = 9.862 (2), b = 13.246 (3), c = 21.153 (4) Å, β = 98.00 (3), Dc =1.463 g cm−3, Z = 8, Rw 2 = 0.154 for 2552 unique reflections), has identified a robust hydrogen-bonded, ribbon-like motif, generated by the geometric fit and hydrogenbond complementarity of the [— COO]− and the [— COOH] functionalities. This preferred interaction between neighbouring anions results in infinite 1-D anionic architectures that are held together by short and near-linear O—H…O hydrogen bonds. In 1 and 2, the amino functionality acts as a crosslink (through N—H…O interactions) between adjacent sheets, thereby generating extended 2-D architectures. 5-Amino iso-phthalic acid exists as a zwitterion in the solid state, an observation which was also indicated by vibrational spectroscopic data. The crystal packing in both 3 and 4 consists of 2-D domains of anions and cations, stacked in an ⋅⋅AABBAABB⋅⋅ manner where the anionic sheets are constructed around the carboxylic-carboxylate supramolecular connector.
The Arabidopsis thaliana gametophytic mutation gemini pollen1 disrupts microspore polarity, division asymmetry and pollen cell fate (1998)

Pollen development and male gametogenesis are critically dependent upon cell polarization leading to a highly asymmetric cell division termed pollen mitosis I. A mutational approach was adopted in Arabidopsis thaliana to identify genes involved these processes. Four independent gemini pollen mutants were isolated which produce divided or twin-celled pollen. The gemini pollen1 mutant was characterized in detail and shown to act gametophytically resulting in reduced transmission through both sexes. gemini pollen1 showed an incompletely penetrant phenotype resulting in equal, unequal and partial divisions at pollen mitosis I. The division planes in gemini pollen1 were shown to be aligned with the polar axis (as in wild type) and evidence was obtained for incomplete nuclear migration, which could account for altered division symmetry. gemini pollen1 also showed division phenotypes consistent with spatial uncoupling of karyokinesis and cytokinesis suggesting that GEMINI POLLEN1 may be required for the localization of phragmoplast activity. Cell fate studies showed that in both equal and unequal divisions a vegetative cell marker gene was activated in both daughter cells. Daughter cells with a range of intermediate or hybrid vegetative/generative cell fates suggests that cell fate is quantitatively related to cell size. The potential mode of action of GEMINI POLLEN1 and its effects on cell fate are discussed in relation to proposed models of microspore polarity and cell fate determination.
DCD —disk caching disk (1996)

This paper presents a novel disk storage architecture called DCD, Disk Caching Disk, for the purpose of optimizing I/O performance. The main idea of the DCD is to use a small log disk, referred to as cache-disk, as a secondary disk cache to optimize write performance. While the cache-disk and the normal data disk have the same physical properties, the access speed of the former differs dramatically from the latter because of different data units and different ways in which data are accessed. Our objective is to exploit this speed difference by using the log disk as a cache to build a reliable and smooth disk hierarchy. A small RAM buffer is used to collect small write requests to form a log which is transferred onto the cache-disk whenever the cache-disk is idle. Because of the temporal locality that exists in office/engineering work-load environments, the DCD system shows write performance close to the same size RAM (i.e. solid-state disk) for the cost of a disk. Moreover, the cache-disk can also be implemented as a logical disk in which case a small portion of the normal data disk is used as the log disk. Trace-driven simulation experiments are carried out to evaluate the performance of the proposed disk architecture. Under the office/engineering work-load environment, the DCD shows superb disk performance for writes as compared to existing disk systems. Performance improvements of up to two orders of magnitude are observed in terms of average response time for write operations. Furthermore, DCD is very reliable and works at the device or device driver level. As a result, it can be applied directly to current file systems without the need of changing the operating system.
Transparent and Photo‐stable ZnO Thin‐film Transistors to Drive an Active Matrix Organic‐Light‐ Emitting‐Diode Display Panel (2008)

Transparent ZnO thin-film transistors (TFTs) with a defect-controlled channel and channel/dielectric interface maintain good photo-stability during device operation. The figure shows a cross-sectional view of a top-gate ZnO-based transparent TFT/storage capacitor cell structure, connected to front-panel organic-light-emitting-diode pixels to operate in bottom emission mode.
Single-port laser-amplifier modulators for local access (1996)

We describe a single-port, reflective, waveguide modulator based on semiconductor laser amplifier technology. The single-port geometry reduces the high packaging cost associated with two-port waveguide modulators, while the internal gain of the amplifier compensates for splitting and coupling losses. A modulator with a bulk active layer showed a reflection-mode chip gain of 17 dB at /spl lambda/=1.56 μm. When driven with pseudorandom digital data at 100 Mb/s, extinction ratios of >12 dB were observed over the broad wavelength range (20 nm) needed for wavelength division multiplexed systems. Bit-error-rate tests confirmed that there was no distortion penalty, compared to a LiNbO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> reference modulator.
Features of apoptotic cells measured by flow cytometry (1992)

The present review describes several methods to characterize and differentiate between two different mechanisms of cell death, apoptosis and necrosis. Most of these methods were applied to studies of apoptosis triggered in the human leukemic HL-60 cell line by DNA topoisomerase I or II inhibitors, and in rat thymocytes by either topoisomerase inhibitors or prednisolone. In most cases, apoptosis was selective to cells in a particular phase of the cell cycle: only S-phase HL-60 cells and G0 thymocytes were mainly affected. Necrosis was induced by excessively high concentrations of these drugs. The following cell features were found useful to characterize the mode of cell death: a) Activation of an endonuclease in apoptocic cells resulted in extraction of the low molecular weight DNA following cell permeabilization, which, in turn, led to their decreased stainability with DNA-specific fluorochromes. Measurements of DNA content made it possible to identify apoptotic cells and to recognize the cell cycle phase specificity of the apoptotic process. b) Plasma membrane integrity, which is lost in necrotic but not apoptotic cells, was probed by the exclusion of propidium iodide (PI). The combination of PI followed by Hoechst 33342 proved to be an excellent probe to distinguish live, necrotic, early- and late-apoptotic cells. c) Mitochondrial transmembrane potential, assayed by retention of rhodamine 123 was preserved in apoptotic but not necrotic cells. d) The ATP-dependent lysosomal proton pump, tested by the supravital uptake of acridine orange (AO) was also preserved in apoptotic but not necrotic cells. e) Bivariate analysis of cells stained for DNA and protein revealed markedly diminished protein content in apoptotic cells, most likely due to activation of endogenous proteases. Necrotic cells, having leaky membranes, had minimal protein content. f) Staining of RNA allowed for the discrimination of G0 from G1 cells and thus made it possible to reveal that apoptosis was selective to G0 thymocytes. g) The decrease in forward light scatter, paralleled either by no change (HL-60 cells) or an increase (thymocytes) of right angle scatter, were early changes during apoptosis. h) The sensitivity of DNA in situ to denaturation, was increased in apoptotic and necrotic cells. This feature, probed by staining with AO at low pH, provided a sensitive and early assay to discriminate between live, apoptotic and necrotic cells, and to evaluate the cell cycle phase specificity of these processes. i) The in situ nick translation assay employing labeled triphosphonucleotides can be used to reveal DNA strand breaks, to detect the very early stages of apoptosis.(ABSTRACT TRUNCATED AT 400 WORDS)
Fiber coupler for mode selection and high-efficiency pump coupling (2013)

A pump/signal fiber coupler with functions of pump light coupling and high-order-mode suppression is reported. This coupler is composed of pump fibers and a double-clad fiber (DCF) with high pump-coupling efficiency. The core of DCF is microdeformed in the coupling region, which serves mode selection. Theoretical analysis and experimental results verify these functions. In the experiment, the pump-coupling and signal-transmitting efficiency of the coupler were ~98% and ~96%, respectively. This coupler can prevent mode distortion with fundamental mode launching, and improve the fiber laser beam quality with high-order-mode launching.
Design, synthesis, and biological evaluation of diketopiperazine based ionizable lipids for the in vivo delivery of messenger RNA (2016)

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2016.
Preparation of teeth for esthetic restorations. (2002)

Preparation details have been described for a porcelain veneer restoration on the most commonly used teeth. With operator knowledge of the preparation, sharp instrumentation, and, most of all, patience, it is possible to place a restoration that may last as long as any others outside of those made of cast or direct gold. It is imperative to remember that this type of conservative "esthetic" dentistry should be performed only on canine-guided occlusions after equilibration (if necessary) (Fig. 13). Even then, it still is possible to fracture a veneer accidentally (Fig. 14). Prior to beginning treatment, it is prudent to inform the patient of the pros and cons of using porcelain veneers, including a warning of possible failure.
microRNAs associated with the different human Argonaute proteins (2012)

MicroRNAs (miRNAs) are small noncoding RNAs that function in literally all cellular processes. miRNAs interact with Argonaute (Ago) proteins and guide them to specific target sites located in the 3'-untranslated region (3'-UTR) of target mRNAs leading to translational repression and deadenylation-induced mRNA degradation. Most miRNAs are processed from hairpin-structured precursors by the consecutive action of the RNase III enzymes Drosha and Dicer. However, processing of miR-451 is Dicer independent and cleavage is mediated by the endonuclease Ago2. Here we have characterized miR-451 sequence and structure requirements for processing as well as sorting of miRNAs into different Ago proteins. Pre-miR-451 appears to be optimized for Ago2 cleavage and changes result in reduced processing. In addition, we show that the mature miR-451 only associates with Ago2 suggesting that mature miRNAs are not exchanged between different members of the Ago protein family. Based on cloning and deep sequencing of endogenous miRNAs associated with Ago1-3, we do not find evidence for miRNA sorting in human cells. However, Ago identity appears to influence the length of some miRNAs, while others remain unaffected.
Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome–positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance (2007)

Nilotinib, an orally bioavailable, selective Bcr-Abl tyrosine kinase inhibitor, is 30-fold more potent than imatinib in pre-clinical models, and overcomes most imatinib resistant BCR-ABL mutations. In this phase 2 open-label study, 400 mg nilotinib was administered orally twice daily to 280 patients with Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia in chronic phase (CML-CP) after imatinib failure or intolerance. Patients had at least 6 months of follow-up and were evaluated for hematologic and cytogenetic responses, as well as for safety and overall survival. At 6 months, the rate of major cytogenetic response (Ph < or = 35%) was 48%: complete (Ph = 0%) in 31%, and partial (Ph = 1%-35%) in 16%. The estimated survival at 12 months was 95%. Nilotinib was effective in patients harboring BCR-ABL mutations associated with imatinib resistance (except T315I), and also in patients with a resistance mechanism independent of BCR-ABL mutations. Adverse events were mostly mild to moderate, and there was minimal cross-intolerance with imatinib. Grades 3 to 4 neutropenia and thrombocytopenia were observed in 29% of patients; pleural or pericardial effusions were observed in 1% (none were severe). In summary, nilotinib is highly active and safe in patients with CML-CP after imatinib failure or intolerance. This clinical trial is registered at http://clinicaltrials.gov as ID no. NCT00109707.