gebhart/patrepeval huggingface dataset:
Reverse time migration of internal multiples (2015)

Summary Internal multiple reflections have different propagation paths compared with primary reflections and surface-related multiples, thus can complement illuminations where other waves are unavailable. We propose a novel approach to image structures with internal multiples. With this method, internal multiples are separated and used as data for reverse time migration. Instead of applying image condition directly to the source and receiver waves, we decompose both source and receiver waves extrapolated into up- and down-going waves. Then apply the image condition to up-going source and receiver waves to form an up-up image, and apply to down-going source and receiver waves to form a down-down image. The image from the true reflector and the artifact show different features in the down-down and up-up images. We use a similarity analysis to compare the up-up and down-down images, and separate true images from artifacts. Numerical examples with simple velocity models are used to demonstrate how to construct up-up and down-down image conditions and eliminate migration artifacts. Finally, we test the 2D SMAART JV model with salt structures for migration using internal multiples.
Assessment of Plasma DNA Levels, Allelic Imbalance, and CA 125 as Diagnostic Tests for Cancer (2002)

Plasma DNA concentration may not be sensitive or specific enough for cancer screening or diagnosis, even when combined with CA 125. AI was detected with high specificity in plasma DNA from patients with ovarian cancer and should be studied further as a screening tool.
Motility is critical for effective distribution and accumulation of bacteria in tumor tissue (2011)

Motile bacteria can overcome the penetration limitations of cancer chemotherapeutics because they can actively migrate into solid tumors. Although several genera of bacteria have been shown to accumulate preferentially in tumors, the spatiotemporal dynamics of bacterial tumor colonization and their dependence on bacterial motility are not clear. For effective tumor regression, bacteria must penetrate and distribute uniformly throughout tumors. To measure these dynamics, we used an in vitro model of continuously perfused tumor tissue to mimic the delivery and systemic clearance of Salmonella typhimurium strains SL1344 and VNP20009, and Escherichia coli strains K12 and DH5α. Tissues were treated for 1 hour with 10(5) or 10(7) CFU ml(-1) suspensions of each strain and the location and extent of bacterial accumulation were observed for 30 hours. Salmonella had 14.5 times greater average swimming speed than E. coli and colonized tissues at 100 times lower doses than E. coli. Bacterial motility strongly correlated (R(2) = 99.3%) with the extent of tissue accumulation. When inoculated at 10(5) CFU ml(-1), motile Salmonella formed colonies denser than 10(10) CFU/(g-tissue) and less motile E. coli showed no detectable colonization. Based on spatiotemporal profiles and a mathematical model of motility and growth, bacterial dispersion was found to be necessary for deep penetration into tissue. Bacterial colonization caused apoptosis in tumors and apoptosis levels correlated (R(2) = 98.6%) with colonization density. These results show that motility is critical for effective distribution of bacteria in tumors and is essential for designing cancer therapies that can overcome the barrier of limited tumor penetration.
Pathophysiology and management of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (2020)

Background: &nbsp;Epidermal necrolysis (EN) is an acute mucocutaneous reaction syndrome characterized by extensive necrosis and epidermal exfoliation and can cause death. The initial lesion is in the form of erythematous macules, then progressively grow to sagging blister lesion and subsequent epidermal peeling. The causes of SJS and TEN may vary such as infections, vaccinations, drugs, systemic diseases, and food. However, the main cause is the drug as found in many cases.&nbsp; Methods: &nbsp;The pathophysiology of the EN is still unclear. Pathologically, tissue damage in the form of epidermal necrolysis is a picture of mass keratinocyte cell death through apoptosis. The stimuli that can induce apoptosis include cellular stress, DNA damage and intracellular cytokines. It may as a result of the role of cytotoxic T cells against keratinocytes, through perforin-granzyme B or Fas-FasL interactions and granulysin. Another theory of SJS-TEN pathophysiology is the slow acetylation (drug metabolic disorder) and the theory of genetic susceptibility. Result: &nbsp;Finally, we include a comprehensive review of well-established widely available therapies&nbsp;in SJS-TEN patients.&nbsp; Discussion:&nbsp; It requires rapid diagnosis, suspension of suspected drug as soon as possible, supportive therapy and specific therapy Conclusion:&nbsp; An understanding of the pathophysiology and current management of SJS and TEN is expected to assist in the prevention of disease and early diagnosis and can provide more effective therapy for SJS-TEN treatment &nbsp; Keywords:&nbsp; Epidermal necrolysis, SJS-TEN, perforin-granzyme B, Fas-FasL interactions, granulysin
Cerebral Atherosclerosis Is Associated With Cystic Infarcts and Microinfarcts but Not Alzheimer Pathologic Changes (2013)

Microinfarcts, which have been correlated with severity of cognitive impairment, were most strongly associated with atherosclerosis. Possible pathogenetic mechanisms include artery-to-artery emboli, especially microemboli that may include atheroemboli or platelet-fibrin emboli. Arteriolosclerosis was positively, whereas cerebral amyloid angiopathy was negatively correlated with lacunar infarcts, which might prove helpful in clinical differentiation of arteriolosclerotic from cerebral amyloid angiopathy-related vascular brain injury.
A high‐affinity competitive inhibitor of type A botulinum neurotoxin protease activity (2002)

The peptide N-acetyl-CRATKML-amide is an effective inhibitor of type A botulinum neurotoxin (BoNT A) protease activity [Schmidt et al., FEBS Lett. 435 (1998) 61-64]. To improve inhibitor binding, the peptide was modified by replacing cysteine with other sulfhydryl-containing compounds. Ten peptides were synthesized. One peptide adapted the structure of captopril to the binding requirements of BoNT A, but it was a weak inhibitor, suggesting that angiotensin-converting enzyme is not a good model for BoNT A inhibitor development. However, replacing cysteine with 2-mercapto-3-phenylpropionyl yielded a peptide with K(i) of 330 nM, the best inhibitor of BoNT A protease activity reported to date. Additional modifications of the inhibitor revealed structural elements important for binding and supported our earlier findings that, with the exception of P1' arginine, subsites on BoNT A are not highly specific for particular amino acid side chains.
In vitro mesenchymal stem cell differentiation after mechanical stimulation (2010)

These experiments confirmed that MSC cell fate choice depends on minute, cell-derived forces. Applied force could assist in commercial manufacture of cultured bio-engineered prostheses for regenerative medicine as it mimics tissue stresses and constitutes a good model for development of tissue substitutes.
Maximal-entropy random walks in complex networks with limited information (2011)

Maximization of the entropy rate is an important issue to design diffusion processes aiming at a well-mixed state. We demonstrate that it is possible to construct maximal-entropy random walks with only local information on the graph structure. In particular, we show that an almost maximal-entropy random walk is obtained when the step probabilities are proportional to a power of the degree of the target node, with an exponent α that depends on the degree-degree correlations and is equal to 1 in uncorrelated graphs.
Regulation of the ETS Transcription Factor ER81 by the 90-kDa Ribosomal S6 Kinase 1 and Protein Kinase A (2002)

The ETS transcription factor ER81 is activated in response to many signals via mitogen-activated protein kinases (MAPKs). However, ER81 is not only phosphorylated on MAPK sites but also at other sites that impact on its transactivation potential. Here we describe that the 90-kDa ribosomal S6 kinase 1 (RSK1), a protein kinase downstream of the extracellular signal-regulated kinase (ERK) subclass of MAPKs, binds to ER81, phosphorylates it, and enhances ER81-dependent transcription. Two in vivo RSK1 phosphorylation sites within ER81, Ser(191) and Ser(216), were identified, whose mutation to alanine reduces ER81 activity upon ERK-MAPK stimulation. Furthermore, RSK1 activates the ER81 cofactor CREB-binding protein and may thereby augment ER81-dependent transcription. Similar to RSK1, the cAMP-dependent protein kinase A (PKA) phosphorylates ER81 on Ser(191)/Ser(216). Additionally, PKA targets ER81 on Ser(334) in vivo. Surprisingly, phosphorylation of Ser(334) severely reduces the DNA-binding ability of ER81 but also enhances the transactivation potential of ER81. These counteractive effects of PKA phosphorylation on ER81-dependent transcription may cause the selective up-regulation of promoters with high but not low affinity for ER81. Collectively, we have identified mechanisms for how two distinct signaling pathways with different effector protein kinases, RSK1 and PKA, converge on ER81, which may regulate ER81 function during development and tumorigenesis.
Design, Parallel Synthesis, and Crystal Structures of Pyrazinone Antithrombotics as Selective Inhibitors of the Tissue Factor VIIa Complex (2003)

Structure-based drug design (SBDD) and polymer-assisted solution-phase (PASP) library synthesis were used to develop a series of pyrazinone inhibitors of the Tissue Factor/Factor VIIa (TF/VIIa) complex. The crystal structure of a tripeptide-alpha-ketothiazole complexed with TF/VIIa was utilized in a docking experiment to identify the pyrazinone core as a starting scaffold. The pyrazinone core could orient the substituents in the correct spatial arrangement to probe the S1, S2, and S3 pockets of the enzyme. A multistep PASP library synthesis was designed to prepare the substituted pyrazinones varying the P1, P2, and P3 moieties. Hundreds of pyrazinone TF/VIIa inhibitors were prepared and tested in several serine protease enzyme assays involved in the coagulation cascade. The inhibitors exhibited modest activity on TF/VIIa with excellent selectivity over thrombin (IIa) and Factor Xa. The structure-activity relationship of the pyrazinone inhibitors will be discussed and X-ray crystal structures of selected compounds complexed with the TF/VIIa enzyme will be described. This study ultimately led to the synthesis of compound 34, which exhibited 16 nM (IC50) activity on TF/VIIa with >6250 x selectivity vs Factor Xa and thrombin. This potent and highly selective inhibitor of TF/VIIa was chosen for preclinical, intravenous proof-of-concept studies to demonstrate the separation between antithrombotic efficacy and bleeding side effects in a nonhuman primate model of electrolytic-induced arterial thrombosis.
Gene Expression as a Predictive Marker of Outcome in Stage IIB-IIIA-IIIB Non-Small Cell Lung Cancer After Induction Gemcitabine-Based Chemotherapy Followed By Resectional Surgery (2004)

Patients with RRM1 levels in the bottom quartile benefited significantly from gemcitabine/cisplatin neoadjuvant chemotherapy, leading us to conclude that RRM1 mRNA levels should be additionally validated to proceed with tailored chemotherapy.
A model of oncogenic rearrangements: differences between chromosomal translocation mechanisms and simple double-strand break repair (2005)

Recurrent reciprocal translocations are present in many hematologic and mesenchymal malignancies. Because significant sequence homology is absent from translocation breakpoint junctions, non-homologous end-joining (NHEJ) pathways of DNA repair are presumed to catalyze their formation. We developed translocation reporters for use in mammalian cells from which NHEJ events can be selected after precise chromosomal breakage. Translocations were efficiently recovered with these reporters using mouse cells, and their breakpoint junctions recapitulated findings from oncogenic translocations. Small deletions and microhomology were present in most junctions; insertions and more complex events also were observed. Thus, our reporters model features of oncogenic rearrangements in human cancer cells. A homologous sequence at a distance from the break site affected the translocation junction without substantially altering translocation frequency. Interestingly, in a direct comparison, the spectrum of translocation breakpoint junctions differed from junctions derived from repair at a single chromosomal break, providing mechanistic insight into translocation formation.
Impact of Channel Geometry on Two-Phase Flow Heat Transfer Characteristics of Refrigerants in Microchannel Heat Exchangers (1998)

Microchannel surfaces, often machined to 20 to 1000 μm in width and depth, are employed in high-heat-flux applications. However, a large number of variables, control the two-phase flow heat transfer coefficient. The pressure, the surface heat flux, and the mass flux significantly affect the thermal transport. Experiments were conducted on a setup that was built for testing microchannel heat exchanges. The parameters considered in the study are power input: 20 to 300 W, volume flow rate: 35 to 300 ml/min, quality: 0 to 0.5, inlet subcooling: 5 to 15°C. The results indicate that the heat transfer coefficient and pressure drop are functions of the flow quality, the mass flux, and, of course, the heat flux and the related surface superheat. The heat transfer coefficient decreases from a value of 12,000 W/m2-K to 9000, W/m2-K at 80°C, when the wall superheat is increased from 10 to 80°C. The coefficient decreases by 30 percent when the exit vapor quality is increased from 0.01 to 0.65.
The Genome of Human Parvovirus B19 Can Replicate in Nonpermissive Cells with the Help of Adenovirus Genes and Produces Infectious Virus (2009)

Human parvovirus B19 (B19V) is a member of the genus Erythrovirus in the family Parvoviridae. In vitro, autonomous B19V replication is limited to human erythroid progenitor cells and in a small number of erythropoietin-dependent human megakaryoblastoid and erythroid leukemic cell lines. Here we report that the failure of B19V DNA replication in nonpermissive 293 cells can be overcome by adenovirus infection. More specifically, the replication of B19V DNA in the 293 cells and the production of infectious progeny virus were made possible by the presence of the adenovirus E2a, E4orf6, and VA RNA genes that emerged during the transfection of the pHelper plasmid. Using this replication system, we identified the terminal resolution site and the nonstructural protein 1 (NS1) binding site on the right terminal palindrome of the viral genome, which is composed of a minimal origin of replication spanning 67 nucleotides. Plasmids or DNA fragments containing an NS1 expression cassette and this minimal origin were able to replicate in both pHelper-transfected 293 cells and B19V-semipermissive UT7/Epo-S1 cells. Our results have important implications for our understanding of native B19V infection.
Laminin receptors and laminin-binding proteins during tumor invasion and metastasis. (1993)

Interactions between cancer cells and laminin, a major component of basement membranes, play a critical role at several steps of the complex process of tumor invasion and metastasis. These interactions are mediated through a large variety of cell surface proteins designated as laminin receptors and/or laminin-binding proteins. The growing number of identified laminin binding proteins and domains of this glycoprotein that are biologically active illustrate the complexity of cellular interactions with laminin. The 67-kD laminin receptor (67 LR) was the first protein identified in 1983 as a high-affinity laminin receptor, and its expression is dramatically increased in a large variety of cancer cells. The 67 LR is the subject of several controversies and confusion generated mainly by two events. First, the identification of several new laminin-binding proteins has raised the difficult task of attributing specific functions to specific receptors in contrast to initial beliefs that all cellular laminin-driven biological activities were mediated through the 67 LR. The second source of controversy is the large molecular-weight discrepancy between the 37-kD polypeptide encoded by the 67 LR cDNA clone and the mature 67 LR. In this manuscript, a critical and extensive review of the data accumulated on the 67 LR is presented regarding both its molecular structure and its role during tumor invasion and metastasis. A hypothetical model of the 67 LR is also proposed. Since the first identification of the 67 LR, at least 14 other cell surface molecules have been reported to be potential laminin receptors or laminin-binding proteins. These include members of the beta-galactoside-binding lectin family, seven members of the integrin family, the galactosyltransferase and some not yet fully characterized cell surface molecules. These laminin receptors and laminin-binding proteins are also described and their functions are also discussed with a particular emphasis on their participation in the constitution of the invasive phenotype.
Antitumor activity and long-term fate of chimeric antigen receptor–positive T cells in patients with neuroblastoma (2011)

We generated MHC-independent chimeric antigen receptors (CARs) directed to the GD2 antigen expressed by neuroblastoma tumor cells and treated patients with this disease. Two distinguishable forms of this CAR were expressed in EBV-specific cytotoxic T lymphocytes (EBV-CTLs) and activated T cells (ATCs). We have previously shown that EBV-CTLs expressing GD2-CARs (CAR-CTLs) circulated at higher levels than GD2-CAR ATCs (CAR-ATCs) early after infusion, but by 6 weeks, both subsets became low or undetectable. We now report the long-term clinical and immunologic consequences of infusions in 19 patients with high-risk neuroblastoma: 8 in remission at infusion and 11 with active disease. Three of 11 patients with active disease achieved complete remission, and persistence of either CAR-ATCs or CAR-CTLs beyond 6 weeks was associated with superior clinical outcome. We observed persistence for up to 192 weeks for CAR-ATCs and 96 weeks for CAR-CTLs, and duration of persistence was highly concordant with the percentage of CD4(+) cells and central memory cells (CD45RO(+)CD62L(+)) in the infused product. In conclusion, GD2-CAR T cells can induce complete tumor responses in patients with active neuroblastoma; these CAR T cells may have extended, low-level persistence in patients, and such persistence was associated with longer survival. This study is registered at www.clinialtrials.gov as #NCT00085930.
Simple route to sterically pure diketopiperazines (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSimple route to sterically pure diketopiperazinesDanute E. Nitecki, Berthold Halpern, and John W. WestleyCite this: J. Org. Chem. 1968, 33, 2, 864–866Publication Date (Print):February 1, 1968Publication History Published online1 May 2002Published inissue 1 February 1968https://pubs.acs.org/doi/10.1021/jo01266a091https://doi.org/10.1021/jo01266a091research-articleACS PublicationsRequest reuse permissionsArticle Views1103Altmetric-Citations157LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Natural Convection Heat Transfer Studies of Simulated and Actual Electronic Components Using Dielectric Liquids for Immersion Cooling (1992)

Two experimental studies of the natural convection characteristics of heated protrusions immersed in dielectric liquids were conducted. the first study used a three by three array of simulated 20 pin dual-in-line chips which were made from aluminum blocks with full heaters. The second set of experiments used a three by three array of thermal evaluation devices mounted on an alumina substrate. The devices were 8.9 mm square chips which contained resistors and a type of temperature sensing transistor. Both studies used an insulated Plexiglas enclosure with a top mounted heat exchanger maintained at a constant 10 degrees C. Each array was mounted on a Plexiglass substrate, and spacers were used to vary the horizontal distance from the components to the enclosure wall. Five separate enclosure widths were used, with a maximum spacing of 40 mm. The vertically oriented aluminum blocks were tested with FC-71 and power levels ranging from 0.115 W/chip to 2.9 W/chip. The non-dimensional data obtained was used to develop an empirical correlation which predicts Nusselt number as a function of Rayleigh number and enclosure width. The correlation was accurate to within 4% of the array averaged data, and the maximum uncertainty in the Nusselt number was 7.4%. The actual electronic components were tested with FC-71, FC-43 and FC-75. Power levels ranged from 0.34 W/chip to 1.48 W/chip. Again, the data obtained was used to develop a Nusselt number correlation. In this case a better correlation of the data was achieved using Grashof number and enclosure width. The correlation is accurate to within 2% of the array averaged data. The maximum Nusselt number uncertainty was 4.7%
5G New Radio: Unveiling the Essentials of the Next Generation Wireless Access Technology (2019)

The fifth generation (5G) wireless access technology, known as New Radio (NR), will address a variety of usage scenarios from enhanced mobile broadband to ultra-reliable low-latency communications to massive machine type communications. Key technology features include ultra-lean transmission, support for low latency, advanced antenna technologies, and spectrum flexibility including operation in high frequency bands and inter-working between high and low frequency bands. This article provides an overview of the essentials of the state of the art in 5G wireless technology represented by the 3GPP NR technical specifications, with a focus on the physical layer. We describe the fundamental concepts of 5G NR, explain in detail the design of physical channels and reference signals, and share the various design rationales influencing standardization.
Base-specific reactions useful for DNA sequencing: methylene blue – sensitized photooxidation of guanine and osmium tetraoxide modification of thymine (1978)

Exposure of DNA to methylene blue and visible or ultraviolet light causes guanine-specific modification, and subsequent treatment with piperidine leads to chain cleavage at each guanine residue. Treatment of DNA with osmium tetraoxide in dilute pyridine leads to thymidine-specific modification, and subsequent treatment with piperidine leads to chain cleavage at the modified thymidine residues. Both reactions can be used in conjunction with other base specific modifications described by Maxam and Gilbert (1) for the determination of the nucleotide sequence in DNA.