gebhart/patrepeval huggingface dataset:
Activation of p38 Mitogen-Activated Protein Kinase Is Required for Death Receptor–Independent Caspase-8 Activation and Cell Death in Response to Sphingosine (2009)

Sphingosine induces activation of multiple signaling pathways that play critical roles in controlling cell death. However, the precise molecular mechanism of cell death induced by sphingosine remains to be clarified. In this study, we show that sphingosine induces death receptor-independent caspase-8 activation and apoptotic cell death via p38 mitogen-activated protein kinase (MAPK) activation and that suppression of the MAPK/extracellular signal-regulated kinase (ERK) kinase/ERK pathway by protein phosphatase 2A (PP2A) is required for p38 MAPK activation. Treatment of cells with sphingosine induced suppression of ERK and activation of p38 MAPK. Inhibition of p38 MAPK led to the marked suppression of death receptor-independent caspase-8 activation and subsequent cell death induced by sphingosine. Interestingly, pretreatment with phorbol 12-myristate 13-acetate or transfection of MAPK/ERK kinase/ERK resulting in ERK activation completely attenuated sphingosine-induced p38 MAPK activation. PP2A activity was additionally elevated on sphingosine treatment. Small interfering RNA targeting of PP2A effectively attenuated sphingosine-induced p38 MAPK activation through restoration of ERK activity, suggesting PP2A-mediated opposing regulation of ERK and p38 MAPK. Our findings clearly imply that activation of p38 MAPK promotes death receptor-independent activation of caspase-8 and apoptotic cell death pathways, thus providing a novel cellular mechanism for the anticancer activity of sphingolipid metabolites.
Asymmetric Epoxidation of Enones With Oxygen in the Presence of Diethylzinc and (R,R)‐N‐Methylpseudoephedrine (1996)

An efficient method for the asymmetric epoxidation of α,β-unsaturated ketones 1 is embodied in their reaction with oxygen in the presence of diethylzinc and (R,R)-N-methyl-pseudoephedrine. It affords epoxides 2 in excellent yields, with complete diastereoselectivity, and with enantiomeric excesses of up to 92% ee. The enantiomerically pure amino alcohol employed can be recovered virtually quantitatively with unchanged optical purity.
AnatomyNet: Deep 3D Squeeze-and-excitation U-Nets for fast and fully automated whole-volume anatomical segmentation (2018)

Purpose Radiation therapy (RT) is a common treatment for head and neck (HaN) cancer where therapists are often required to manually delineate boundaries of the organs-at-risks (OARs). The radiation therapy planning is time-consuming as each computed tomography (CT) volumetric data set typically consists of hundreds to thousands of slices and needs to be individually inspected. Automated head and neck anatomical segmentation provides a way to speed up and improve the reproducibility of radiation therapy planning. Previous work on anatomical segmentation is primarily based on atlas registrations, which takes up to hours for one patient and requires sophisticated atlas creation. In this work, we propose the AnatomyNet, an end-to-end and atlas-free three dimensional squeeze-and-excitation U-Net (3D SE U-Net), for fast and fully automated whole-volume HaN anatomical segmentation. Methods There are two main challenges for fully automated HaN OARs segmentation: 1) challenge in segmenting small anatomies (i.e., optic chiasm and optic nerves) occupying only a few slices, and 2) training model with inconsistent data annotations with missing ground truth for some anatomical structures because of different RT planning. We propose the AnatomyNet that has one down-sampling layer with the trade-off between GPU memory and feature representation capacity, and 3D SE residual blocks for effective feature learning to alleviate these challenges. Moreover, we design a hybrid loss function with the Dice loss and the focal loss. The Dice loss is a class level distribution loss that depends less on the number of voxels in the anatomy, and the focal loss is designed to deal with highly unbalanced segmentation. For missing annotations, we propose masked loss and weighted loss for accurate and balanced weights updating in the learning of the AnatomyNet. Results We collect 261 HaN CT images to train the AnatomyNet, and use MICCAI Head and Neck Auto Segmentation Challenge 2015 as the benchmark dataset to evaluate the performance of the AnatomyNet. The objective is to segment nine anatomies: brain stem, chiasm, mandible, optic nerve left, optic nerve right, parotid gland left, parotid gland right, submandibular gland left, and submandibular gland right. Compared to previous state-of-the-art methods for each anatomy from the MICCAI 2015 competition, the AnatomyNet increases Dice similarity coefficient (DSC) by 3.3% on average. The proposed AnatomyNet takes only 0.12 seconds on average to segment a whole-volume HaN CT image of an average dimension of 178 × 302 × 225. All the data and code will be available a . Conclusion1 We propose an end-to-end, fast and fully automated deep convolutional network, AnatomyNet, for accurate and whole-volume HaN anatomical segmentation. The proposed Anato-myNet outperforms previous state-of-the-art methods on the benchmark dataset. Extensive experiments demonstrate the effectiveness and good generalization ability of the components in the AnatomyNet.
Subxiphoid Access to Normal Pericardium with Micropuncture Set: Technical Feasibility Study in Pigs (2006)

This study was performed with approval from the ethics committee for animal research of the local government. The purpose of the study was to evaluate the technical feasibility of a technique for subxiphoid access to the normal pericardial space with a micropuncture set in 10 large white pigs. With fluoroscopic guidance, a fine needle was inserted through a subxiphoid approach into the anterior mediastinal space to puncture the pericardium, and a micropuncture set was placed in the pericardial space successfully in all animals without complications. Necropsy at 24 hours did not reveal hemomediastinum, hemopericardium, or laceration of the pericardium. Results of the experiments in animals indicated that the technique was feasible and safe.
Identification of Residues Lining the Anthrax Protective Antigen Channel (1998)

In its activated 63 kDa form, the protective antigen (PA) component of anthrax toxin forms a heptameric prepore, which converts to a pore (channel) in endosomal membranes at low pH and mediates translocation of the toxin's enzymic moieties to the cytosol. It has been proposed that the prepore-to-pore conversion involves a conformational rearrangement of a disordered amphipathic loop (D2L2; residues 302-325), in which loops from the 7 protomers combine to form a transmembrane 14-stranded beta barrel. To test this model, we generated Cys substitutions in 24 consecutive residues of the D2L2 loop, formed channels in artificial bilayers with each mutant, and examined changes in channel conductance after adding the thiol-reactive, bilayer-impermeant reagent methanethiosulfonate ethyltrimethylammonium (MTS-ET) to the trans compartment. The rationale for these experiments is that reaction of MTS-ET with a Cys residue adds a positively charged group and therefore would likely reduce channel conductance if the residue were in the ion-conducting pathway. We found alternating reduction and absence of reduction of conductance in consecutive residues over two stretches (residues 302-311 and 316-325). This pattern is consistent with alternating polar and apolar residues of the two stretches projecting into the pore lumen and into the bilayer, respectively. Residues connecting these two stretches (residues 312-315) were responsive to MTS-ET, consistent with their being in a turn region. Single channels formed by selected mutants (H304C and N306C) showed multiple conductance step changes in response to MTS-ET, consistent with an oligomeric pore. We also found that the binding site for the channel-blocking tetraalkylammonium ions is located cis relative to the inserted D2L2 loops. These findings constitute strong evidence in favor of the model of conversion of the prepore to a 14-stranded beta barrel pore and solidify the foundation for studies to understand the mechanism of translocation by anthrax toxin.
Microfilament reorganization is associated with functional activation of alpha M beta 2 on monocytic cells. (1994)

Selected agonists convert the leukocyte integrin alpha M beta 2 on monocytes from a low to a high affinity state competent to bind factor X and fibrinogen. Conformational changes of alpha M beta 2 re hypothesized to account for this functional transition. Here we report that cytochalasins known to interfere with actin filaments induce the alpha M beta 2 functional transition. Upon exposure to cytochalasin B, isolated human blood monocytes and cells of the monocytic cell line THP-1 bound 125I-factor X (X) or 125I-fibrinogen (Fg) in a Ca(2+)-dependent, saturable manner. Monoclonal antibodies (mAbs) to the alpha M subunit and the common beta 2 subunit of leukocyte integrins inhibited X and Fg binding, whereas mAbs to the alpha chains of the other leukocyte integrins had no effect. Anti-alpha M mAb immunoprecipitated 125I-X that had been chemically cross-linked to its cognate receptor. Specific binding was not associated with an increased surface density of beta 2 integrins consistent with conformational remodeling of the receptor. Simultaneous analysis of actin forms in viable monocytes indicated a dynamic redistribution of cellular actin. The transient increase in G actin concurrent with an agonist action such as cytochalasin or ADP was reversed by an increase in F actin coincident with X/Ca2+ binding. A potential role of actin redistribution in alpha M beta 2 functional transition is supported by the finding that cells in which cellular actin is restricted to G rather than F form bound X and initiated a rapid coagulant response. We propose that a transient disassembly of actin filaments may relieve constraints on alpha M beta 2 via the cytoplasmic domains, permitting the conformational dynamics required for recognition of ligands.
Utilizing genetically engineered bacteria to produce plant‐specific glucosides (2001)

Plant-derived glucosides have attracted much attention due to their widespread applications. This class of products is difficult to isolate or to synthesize in pure form because of the resulting low yields. Thus, simple approaches for the generation of such glucosides would be highly beneficial. We purified and characterized a novel glucosyltransferase from plant cell suspension cultures of Rauvolfia serpentina, which showed rather low substrate specificity. We obtained its cDNA and expressed the active recombinant protein in bacteria (Escherichia coli) with excellent plant-specific glucosylation efficiencies. Compared with the plant system, the bacteria delivered the new enzyme, which was in the form of a soluble or matrix-bound enzyme, approximately 1800 times more efficiently for the synthesis of a wide range of glucosides. More importantly, the engineered E. coli strain allowed for in vivo glucosylation and release of the product into the culture medium, as shown by the formation of arbutin, which is a potent inhibitor of human melanin biosynthesis with commercial value.
A Study on Breath Acetone in Diabetic Patients Using a Cavity Ringdown Breath Analyzer: Exploring Correlations of Breath Acetone With Blood Glucose and Glycohemoglobin A1C (2009)

Acetone is qualitatively known as a biomarker of diabetes; however, the quantitative information on acetone concentration in diabetic breath is incomplete, and the knowledge of correlations of breath acetone with diabetic diagnostic parameters, namely, blood glucose (BG) and glycohemoglobin A1C (A1C), are unknown. We utilized a pilot-scale breath acetone analyzer based on the cavity ringdown spectroscopy (CRDS) technique to conduct breath tests with 34 Type 1 diabetic (T1D), ten Type 2 diabetic (T2D) patients, and 15 apparently healthy individuals. Relations between breath acetone and BG, A1C, and several other bio indices, such as the type of diabetes, onset-time, gender, age, and weight were investigated. Our observations show that a linear correlation between the mean group acetone and the mean group BG level does exist (R = 0.98, P < 0.02) when all the T1D subjects tested are grouped by different BG levels, 40-100, 101-150, 151-200, and 201-419 mg/dL. Similarly, among the T1D subjects studied, when their A1C's are grouped by < 7, 7-9.9, and 10-13, a linear correlation between the mean group A1C and the mean group acetone concentration is observed (R = 0.98, P < 0.02). No strong correlations are observed when the BG and A1C numbers are not grouped. The mean breath acetone concentration in the T1D subjects studied in this work is determined to be 2.19 ppmv (parts per million by volume), which is higher than the mean breath acetone concentration, 0.48 ppmv, in the 15 healthy people tested.
Induced refolding of a temperature denatured llama heavy‐chain antibody fragment by its antigen (2005)

In a previous study we have shown that llama VHH antibody fragments are able to bind their antigen after a heat shock of 90 degrees C, in contrast to the murine monoclonal antibodies. However, the molecular mechanism by which antibody:antigen interaction occurs under these extreme conditions remains unclear. To examine in more detail the structural and thermodynamic aspects of the binding mechanism, an extensive CD, ITC, and NMR study was initiated. In this study the interaction between the llama VHH -R2 fragment and its antigen, the dye Reactive Red-6 (RR6) has been explored. The data show clearly that most of the VHH-R2 population at 80 degrees C is in an unfolded conformation. In contrast, CD spectra representing the complex between VHH-R2 and the dye remained the same up to 80 degrees C. Interestingly, addition of the dye to the denatured VHH-R2 at 80 degrees C yielded the spectrum of the native complex. These results suggest an induced refolding of denatured VHH-R2 by its antigen under these extreme conditions. This induced refolding showed some similarities with the well established "induced fit" mechanism of antibody-antigen interactions at ambient temperature. However, the main difference with the "induced fit" mechanism is that at the start of the addition of the antigen most of the VHH molecules are in an unfolded conformation. The refolding capability under these extreme conditions and the stable complex formation make VHHs useful in a wide variety of applications.
Use of N-terminal modified poly(L-lysine)-antibody conjugate as a carrier for targeted gene delivery in mouse lung endothelial cells (1992)

A DNA targeted delivery and expression system has been designed based on an N-terminal modified poly(L-lysine) (NPLL)-antibody conjugate, which readily forms a complex with plasmid DNA. Monoclonal antibodies against the cell-surface thrombomodulin conjugated with NPLL were used for targeted delivery of foreign plasmid DNA to an antigen-expressing mouse lung endothelial cell line in vitro and to mouse lungs in vivo. In both cases significant amounts of DNA can be specifically bound to the target cells or tissues. Specific gene expression was observed in the treated mouse lung endothelial cells.
Caspase-3 Contributes to ZO-1 and Cl-5 Tight-Junction Disruption in Rapid Anoxic Neurovascular Unit Damage (2011)

Our data provide evidence that caspase-3 is rapidly activated during acute cerebral ischemia predominantly without triggering DNA-fragmentation in BEC. Further we detected fast TJ protein disruptions which could be partly blocked by caspase-3 inhibition with Z-DEVD-fmk. We suggest that the basis for clinically relevant BBB breakdown in form of TJ disruptions is initiated within minutes during ischemia and that caspase-3 contributes to this process.
Swallows, oesophageal and gastric motility in normal subjects and in patients with gastro‐oesophageal reflux disease: a 24‐h pH‐manometric study (1998)

GORD patients showed an increase in swallows with altered post-deglutitive oesophageal motility and a reduced amplitude of gastric MMC. Moreover small contractions of gastric antrum are present before acid refluxes, suggesting a multifactorial pathogenesis of the disease.
Dendritic location of neural BC1 RNA. (1991)

In nerve cells, a specialized protein synthetic machinery is thought to operate in local compartments of dendrites, in particular beneath synaptic junctions, and thereby to facilitate swift adjustments of the postsynaptic protein repertoire in situ. This notion has been supported by the identification of polyribosomes and selected mRNAs in those compartments. In this study, we report the discovery of a specific RNA polymerase III transcript in dendrites. This RNA, a noncoding, 152-nucleotide-long, single-gene transcript known as BC1 RNA, is expressed almost exclusively in the nervous system. In adult rats as well as in immature rats in late developmental stages, BC1 RNA has been located in the dendrites and somata of a subset of neurons in the central and peripheral nervous system. The colocalization of BC1 RNA with dendritic mRNAs and polyribosomes may indicate a role--possibly within the functional unit of a high molecular mass ribonucleoprotein particle--in specific pre- or posttranslational processes in postsynaptic compartments of neurons.
Two-dimensional endfire array with increased gain and side lobe reduction (2005)

Endfire arrays such as Yagi antennas can be analyzed in terms of the phase and amplitude distribution in a "virtual aperture" plane transverse to the axis of the array. A method for controlling the amplitude and phase across the virtual aperture is given. It is shown, in particular, that the virtual aperture area can be increased through the use of parasitic side arrays, and that at the same time control of the illumination function can be retained. Thus, it is possible to increase gain and reduce side lobes simultaneously without supergaining. Measured patterns are shown for three different array types. Type I is a Yagi antenna 6 wavelengths long, tuned for maximum gain by using a modified Hansen-Woodyard condition reported elsewhere. Types II and III are two-dimensional endfire arrays, also 6 wavelengths long. Type II was tuned for very low side lobe level (30 db), and Type III for maximum gain obtainable with a more moderate side lobe level (17 db). The gain of Type II was 30% above that of Type I, while the gain of Type III was 60% above Type I. The method presented demonstrates that controlled excitation of a two-dimensional parasitic array with a single feed (rather than a line source) is feasible.
Cathode Performance as a Factor in Electricity Generation in Microbial Fuel Cells (2004)

Although microbial fuel cells (MFCs) generate much lower power densities than hydrogen fuel cells, the characteristics of the cathode can also substantially affect electricity generation. Cathodes used for MFCs are often either Pt-coated carbon electrodes immersed in water that use dissolved oxygen as the electron acceptor or they are plain carbon electrodes in a ferricyanide solution. The characteristics and performance of these two cathodes were compared using a two-chambered MFC. Power generation using the Pt-carbon cathode and dissolved oxygen (saturated) reached a maximum of 0.097 mW within 120 h after inoculation (wastewater sludge and 20 mM acetate) when the cathode was equal size to the anode (2.5 x 4.5 cm). Once stable power was generated after replacing the MFC with fresh medium (no sludge), the Coulombic efficiency ranged from 63 to 78%. Power was proportional to the dissolved oxygen concentration in a manner consistent with Monod-type kinetics, with a half saturation constant of K(DO) = 1.74 mg of O2/L. Power increased by 24% when the cathode surface areas were increased from 22.5 to 67.5 cm2 and decreased by 56% when the cathode surface area was reduced to 5.8 cm2. Power was also substantially reduced (by 78% to 0.02 mW) if Pt was not used on the cathode. By using ferricyanide instead of dissolved oxygen, the maximum power increased by 50-80% versus that obtained with dissolved oxygen. This result was primarily due to increased mass transfer efficiencies and the larger cathode potential (332 mV) of ferricyanide than that obtained with dissolved oxygen (268 mV). A cathode potential of 804 mV (NHE basis) is theoretically possible using dissolved oxygen, indicating that further improvements in cathode performance with oxygen as the electron acceptor are possible that could lead to increased power densities in this type of MFC.
Codeletion of CDKN2 and MTAP genes in a subset of non-Hodgkin's lymphoma may be associated with histologic transformation from low-grade to diffuse large-cell lymphoma. (1998)

Identifying the various genetic alterations that contribute to lymphomagenesis is key to our improved understanding of the biological behavior of the disease. Recently, we and others have defined a tumor suppressor region on the short arm of chromosome 9 harboring a cluster of genes, including MTAP, CDKN2A (p16INK4a), and CDKN2B (p15INK4B), which is frequently deleted in a variety of tumor types. To determine whether this region is involved in a particular subset of malignant lymphomas, we have examined 16 cases of diffuse large-cell lymphoma (DLCL) (including three cases that evolved from low-grade non-Hodgkin lymphoma (NHL) (transformed DLCL)), and nine cases of low-grade NHL that had subpopulations of large cells with a diffuse growth pattern (seven follicular NHL, one chronic lymphocytic leukemia, one mycosis fungoides). Interphase fluorescence in situ hybridization was performed on these samples using a 250-kb cosmid contig (COSp16), which encompasses MTAP, CDKN2A, and CDKN2B. Six of the 16 DLCLs and one of nine low-grade NHLs had deletions of COSp16. COSp16 was homozygously deleted in four cases; two cases had hemizygous deletions, and one case had a partial homozygous deletion of the cosmid contig. Three of 13 cases of de novo DLCL, all three transformed DLCLs, and one of nine low-grade NHL had COSp16 deletions. Although the numbers are small, COSp16 deletion was associated with transformed DLCL in contrast to de novo DLCL (P < 0.04, Fisher's exact test) or low-grade NHL (P < 0.02). The COSp16 deletion was mostly submicroscopic and was not observed in association with any specific recurring cytogenetic abnormalities. These results suggest that targeted deletion of the CDKN2A region occurs in a subset of non-Hodgkin's lymphomas, and may be associated with transformed lymphomas.
Ethernet (1976)

Ethernet is a branching broadcast communication system for carrying digital data packets among locally distributed computing stations. The packet transport mechanism provided by Ethernet has been used to build systems which can be viewed as either local computer networks or loosely coupled multiprocessors. An Ethernet's shared communication facility, its Ether, is a passive broadcast medium with no central control. Coordination of access to the Ether for packet broadcasts is distributed among the contending transmitting stations using controlled statistical arbitration. Switching of packets to their destinations on the Ether is distributed among the receiving stations using packet address recognition. Design principles and implementation are described based on experience with an operating Ethernet of 100 nodes along a kilometer of coaxial cable. A model for estimating performance under heavy loads and a packet protocol for error controlled communication are included for completeness.