gebhart/patrepeval huggingface dataset:
RET Aberrations in Diverse Cancers: Next-Generation Sequencing of 4,871 Patients (2016)

<b>Purpose:</b> Aberrations in genetic sequences encoding the tyrosine kinase receptor RET lead to oncogenic signaling that is targetable with anti-RET multikinase inhibitors. Understanding the comprehensive genomic landscape of <i>RET</i> aberrations across multiple cancers may facilitate clinical trial development targeting <i>RET</i><b>Experimental Design:</b> We interrogated the molecular portfolio of 4,871 patients with diverse malignancies for the presence of <i>RET</i> aberrations using Clinical Laboratory Improvement Amendments-certified targeted next-generation sequencing of 182 or 236 gene panels.<b>Results:</b> Among diverse cancers, <i>RET</i> aberrations were identified in 88 cases [1.8% (88/4, 871)], with mutations being the most common alteration [38.6% (34/88)], followed by fusions [30.7% (27/88), including a novel <i>SQSTM1-RET</i>] and amplifications [25% (22/88)]. Most patients had coexisting aberrations in addition to <i>RET</i> anomalies [81.8% (72/88)], with the most common being in <i>TP53</i>-associated genes [59.1% (52/88)], cell cycle-associated genes [39.8% (35/88)], the PI3K signaling pathway [30.7% (27/88)], MAPK effectors [22.7% (20/88)], or other tyrosine kinase families [21.6% (19/88)]. <i>RET</i> fusions were mutually exclusive with MAPK signaling pathway alterations. All 72 patients harboring coaberrations had distinct genomic portfolios, and most [98.6% (71/72)] had potentially targetable coaberrations with either an FDA-approved or an investigational agent. Two cases with lung (<i>KIF5B-RET</i>) and medullary thyroid carcinoma (<i>RET</i> M918T) that responded to a vandetanib (multikinase RET inhibitor)-containing regimen are shown.<b>Conclusions:</b><i>RET</i> aberrations were seen in 1.8% of diverse cancers, with most cases harboring actionable, albeit distinct, coexisting alterations. The current report suggests that optimal targeting of patients with <i>RET</i> anomalies will require customized combination strategies. <i>Clin Cancer Res; 23(8); 1988-97. ©2016 AACR</i>.
Rheological evaluation of the physical properties of hyaluronic acid dermal fillers. (2011)

This rheologic evaluation demonstrates that differences exist among the HA products tested including gel elasticity, viscosity, and the range and distribution of gel particle sizes. Understanding the distinct physical characteristics of different HA dermal fillers and how these characteristics may predict their clinical behavior can assist clinicians in achieving the desired results in patients seeking facial rejuvenation.
Magnetic nanoparticle biosensors (2010)

One of the major challenges in medicine is the rapid and accurate measurement of protein biomarkers, cells, and pathogens in biological samples. A number of new diagnostic platforms have recently been developed to measure biomolecules and cells with high sensitivity that could enable early disease detection or provide valuable insights into biology at the systems level. Most biological samples exhibit negligible magnetic susceptibility; therefore, magnetic nanoparticles have been used for diverse applications including biosensing, magnetic separation, and thermal ablation therapy. This review focuses on the use of magnetic nanoparticles for detection of biomolecules and cells based on magnetic resonance effects using a general detection platform termed diagnostic magnetic resonance (DMR). DMR technology encompasses numerous assay configurations and sensing principles, and to date magnetic nanoparticle biosensors have been designed to detect a wide range of targets including DNA/mRNA, proteins, enzymes, drugs, pathogens, and tumor cells. The core principle behind DMR is the use of magnetic nanoparticles as proximity sensors that modulate the spin-spin relaxation time of neighboring water molecules, which can be quantified using clinical MRI scanners or benchtop nuclear magnetic resonance (NMR) relaxometers. Recently, the capabilities of DMR technology were advanced considerably with the development of miniaturized, chip-based NMR (microNMR) detector systems that are capable of performing highly sensitive measurements on microliter sample volumes and in multiplexed format. With these and future advances in mind, DMR biosensor technology holds considerable promise to provide a high-throughput, low-cost, and portable platform for large scale molecular and cellular screening in clinical and point-of-care settings.
Synthesis and Mode of Action of125I- and3H-Labeled Thieno[2,3-c]pyridine Antagonists of Cell Adhesion Molecule Expression (2002)

A series of thieno[2,3-c]pyridine antagonists of cell adhesion molecule (CAM) expression, such as A-205804 (1) and A-249377 (2), selectively suppressed the induced expression of E-selectin and ICAM-1 over VCAM-1. In an effort to explore the biological mechanism of action of these inhibitors, we synthesized (125)I- and (3)H-labeled thieno[2,3-c]pyridines 5 and 6. An isolated diazonium tetrafluoroborate salt efficiently trapped Na(125)I on very small scale (7.5 microg of Na(125)I), providing the corresponding (125)I-labeled thieno[2,3-c]pyridine in modest yield. Preliminary mechanistic investigations using these radiolabeled compounds revealed that, upon incubation with human umbilical vein endothelial cells (HUVECs), these inhibitors of CAM expression translocated to the cell nucleus and were noncovalently associated with macromolecules of molecular weight greater than 650 kDa.
Groundwater Quality of Aligarh District of Uttar Pradesh (2000)

Groundwater samples from eight irrigation wells, five domestic wells (depth 4 to 36 m) and two canals (both rural and urban) used for irrigation and drinking purposes were analysed for nutrients, heavy metals and pesticides during the period 1996–97. The results indicate that pH, alkalinity, NO3, F, PO4 and CI−, Zn, Al, Cu, Fe and Pb were within the tolerance limits, while Cr and Cd were at threshold level. The concentration of heavy metals was higher in domestic wells than in irrigation wells and concentration of heavy metals decreased with increase in the depth of well. Concentration of pesticides, viz. HCH, 2,4-D, malathion, parathion, aldrin/dieldrin were within the recommended limits, while DDT was beyond the limit.
Differential expression pattern of membrane‐type matrix metalloproteinases in rheumatoid arthritis (2000)

Our results indicate a role for MT1-MMP not only in the matrix degradation by fibroblasts, but also in osteoclast-mediated bone resorption in RA. Given the ability of MT1-MMP to activate MMP-2 and MMP-13, the findings also point to a cooperation between fibroblasts and macrophages in degrading cartilage and bone. While MT3-MMP is also intensely expressed in RA synovium, MT2- and MT4-MMP appear not to be involved in rheumatoid joint destruction.
First immunotherapeutic CAR-T cells against the immune checkpoint protein HLA-G (2021)

We report for the first time that HLA-G, which is both a TSA and an ICP, constitutes a valid target for CAR-T cell therapy to specifically target and eliminate both tumor cells and HLA-G<sup>+</sup> suppressive cells.
Hot-Air Treatment Device for Quarantine Research (1991)

Journal Article Hot-Air Treatment Device for Quarantine Research Get access Jennifer L. Sharp, Jennifer L. Sharp Subtropical Horticulture Research Station, USDA-ARS, Miami, Florida 33158 Search for other works by this author on: Oxford Academic PubMed Google Scholar Jerome J. Gaffney, Jerome J. Gaffney Subtropical Horticulture Research Station, USDA-ARS, Miami, Florida 33158 Search for other works by this author on: Oxford Academic PubMed Google Scholar James Moss, I., James Moss, I. Subtropical Horticulture Research Station, USDA-ARS, Miami, Florida 33158 Search for other works by this author on: Oxford Academic PubMed Google Scholar Walter P. Gould Walter P. Gould Subtropical Horticulture Research Station, USDA-ARS, Miami, Florida 33158 Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Economic Entomology, Volume 84, Issue 2, 1 April 1991, Pages 520–527, https://doi.org/10.1093/jee/84.2.520 Published: 01 April 1991 Article history Received: 20 June 1990 Accepted: 18 September 1990 Published: 01 April 1991
Use of an on-press acoustic sensor to monitor coldset offset printing of newspaper (2006)

A newly developed acoustic emission on-line monitoring technique (Voltaire J. et al. 2004) provides insight into the dynamic interactions occurring between paper, inkfount emulsion, and rubber blanket in offset printing. The technique uses a microphone placed in the vicinity of the exit of the paper-blanket nip. Through digital signal processing of the measured sound pressure it is possible to distinguish between machinery sound and that caused by the tacky ink splitting. In this study, printing of coldset inks on newsprint was carried out on a two-unit sheet-fed offset press. In line with earlier results, an increase in print density was found to correspond to increased sound pressure at the nip exit for higher frequencies (above 15 kHz). Depending on the status of the press at startup, i.e. ink and fount condition and temperature, an increase or decrease towards a more stable value of the sound pressure was detected during the early running of the press, and in both cases this correlated well with the evolution in print density to its target value. This and related results can prove useful for monitoring, and adjusting by feedback, the initial press equilibration before the print-ready stage. Moreover, the acoustic emission can directly reveal destabilised conditions at longer running times that by other means would not be detected until later.
General and Practical One-Pot Synthesis of Dihydrobenzosiloles from Styrenes (2012)

A one-pot synthesis of dihydrobenzosiloles from styrenes has been developed. The reaction involves the nickel-catalyzed hydrosilylation of styrene with diphenylsilane, followed by the iridium-catalyzed dehydrogenative cyclization. This method is efficient for both electron-rich and -deficient styrenes and exhibits good functional group tolerance, as well as excellent regioselectivity. The forming dihydrobenzosiloles can be efficiently converted into valuable benzosiloles or 2-hydroxyphenethyl alcohols.
Comparative Analysis of Hollow and Filled Polyelectrolyte Microcapsules Templated on Melamine Formaldehyde and Carbonate Cores (2004)

Abstract Summary: A comparative study of polyelectrolyte microcapsules templated on melamine formaldehyde (MF) and manganese carbonate (MnCO 3 ) particles was performed using confocal Raman microscopy, scanning electron microscopy and by force measurements with an atomic force microscope. There is no significant difference between the properties of the shells templated on the MF and completely decomposable carbonate particles. In the case of capsules filled with polystyrene sulfonate (PSS), the MF oligomers formed a network complex with the polymer which resulted in a gel‐like structure in the interior. The existence of such a structure was proved by characteristic MF and PSS bands in Raman spectra, the bulky morphology of the dried capsules and much stiffer resistance to applied force as compared with PSS‐filled capsules templated on carbonate particles. SEM images of PSS‐loaded PAH/PSS capsules assembled on the on the MF template core. magnified image SEM images of PSS‐loaded PAH/PSS capsules assembled on the on the MF template core.
Synthesis of five- and six-coordinate alkylidene complexes of the type Mo(CHR)(NAr)[OCMe(CF3)2]2Sx and their use as living ROMP initiators or Wittig reagents (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of five- and six-coordinate alkylidene complexes of the type Mo(CHR)(NAr)[OCMe(CF3)2]2Sx and their use as living ROMP initiators or Wittig reagentsHarold H. Fox, Jin Kyu Lee, Lee Y. Park, and Richard R. SchrockCite this: Organometallics 1993, 12, 3, 759–768Publication Date (Print):March 1, 1993Publication History Published online1 May 2002Published inissue 1 March 1993https://pubs.acs.org/doi/10.1021/om00027a028https://doi.org/10.1021/om00027a028research-articleACS PublicationsRequest reuse permissionsArticle Views715Altmetric-Citations131LEARN 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
Long-term effects of experimental intracerebral hemorrhage: the role of iron (2006)

An ICH results in an accumulation of iron in the brain that is not cleared within 3 months and that contributes to brain tissue loss and neurological deficits posthemorrhage. Iron chelation may be a useful therapy for patients with ICH.
Circulating microRNAs: emerging biomarkers for diagnosis and prognosis in patients with gastrointestinal cancers (2014)

To identify novel non-invasive biomarkers for improved detection, risk assessment and prognostic evaluation of cancer, expression profiles of circulating microRNAs are currently under evaluation. Circulating microRNAs are highly promising candidates in this context, as they present some key characteristics for cancer biomarkers: they are tissue-specific with reproducible expression and consistency among individuals from the same species, they are potentially derived directly from the tumour and therefore might correlate with tumour progression and recurrence, and they are bound to proteins or contained in subcellular particles, such as microvesicles or exosomes, making them highly stable and resistant to degradation. The present review highlights the origin of circulating microRNAs, their stability in blood samples, and techniques to isolate exosomal microRNAs, and then addresses the current evidence supporting potential clinical applications of circulating miRNAs for diagnostic and prognostic purposes.
Crystal Structures of the Human RNA Demethylase Alkbh5 Reveal Basis for Substrate Recognition (2014)

N(6)-Methylation of adenosine is the most ubiquitous and abundant modification of nucleoside in eukaryotic mRNA and long non-coding RNA. This modification plays an essential role in the regulation of mRNA translation and RNA metabolism. Recently, human AlkB homolog 5 (Alkbh5) and fat mass- and obesity-associated protein (FTO) were shown to erase this methyl modification on mRNA. Here, we report five high resolution crystal structures of the catalytic core of Alkbh5 in complex with different ligands. Compared with other AlkB proteins, Alkbh5 displays several unique structural features on top of the conserved double-stranded β-helix fold typical of this protein family. Among the unique features, a distinct "lid" region of Alkbh5 plays a vital role in substrate recognition and catalysis. An unexpected disulfide bond between Cys-230 and Cys-267 is crucial for the selective binding of Alkbh5 to single-stranded RNA/DNA by bringing a "flipping" motif toward the central β-helix fold. We generated a substrate binding model of Alkbh5 based on a demethylation activity assay of several structure-guided site-directed mutants. Crystallographic and biochemical studies using various analogs of α-ketoglutarate revealed that the active site cavity of Alkbh5 is much smaller than that of FTO and preferentially binds small molecule inhibitors. Taken together, our findings provide a structural basis for understanding the substrate recognition specificity of Alkbh5 and offer a foundation for selective drug design against AlkB members.
In Vitro Methods to Support Transporter Evaluation in Drug Discovery and Development (2013)

This white paper addresses current approaches and knowledge gaps concerning methods to assess the role of transport proteins in drug/metabolite disposition in humans. The discussion focuses on in vitro tools to address key questions in drug development, including vesicle- and cell-based systems. How these methods can be used to assess the liability of compounds for transporter-based drug-drug interactions (DDIs) in vivo is also explored. Existing challenges and approaches to examine the involvement of transporters in drug disposition are discussed.
Methylation of the Epstein-Barr Virus Genome in Normal Lymphocytes (1997)

Epstein-Barr virus (EBV) latent infection in B cells persists over years or decades despite a sustained cytotoxic immune response to viral antigens. We present data that methylated EBV DNA can be detected in the normal lymphocytes of healthy volunteers. Whereas methylation of foreign DNA has been recognized as a potential cellular defense mechanism, methylation of EBV DNA may be an essential part of the virus life cycle in vivo, explaining the persistence of virus-infected B cells in the face of immune surveillance. Methylation of the C promoter helps to prevent expression of the immunodominant antigens expressed from this promoter. First recognized in tumors, methylation-associated evasion of immune surveillance is not an aberration restricted to tumor tissue but is detected in normal EBV-infected lymphocytes. Methylation of the viral genome in latency also provides an explanation for the CpG suppression associated with EBV but not other large DNA viruses.
Effects of prostaglandin E2 on rat skin: inhibition of sterol ester biosynthesis and clearing of scaly lesions in essential fatty acid deficiency (1972)

Severe scaly lesions in the skin, especially in the feet and tail, of the rat were induced by feeding a diet deficient in essential fatty acids (EFA). Analysis of the fatty acids in skin lipids of these EFA-deficient rats showed a marked increase of monoenoic acids (16:1 and 18:1) and eicosatrienoic acid (20:3), with concomitant decreases of dienoic acid (18:2) and tetraenoic acid (20:4). Topical application of prostaglandin E(2) (PGE(2)) to the scaly lesions resulted in clearance of the lesions, but did not significantly alter the composition of fatty acids in the skin. Intraperitoneal injection of PGE(2) had no observable effect on the skin lesions. Furthermore, incubation of skin specimens from the EFA-deficient rats with (14)C-labeled glucose showed a 4-5-fold increase of incorporation of glucose carbon into lipid fractions, particularly the sterol esters, and a 3-4-fold increase in pentose cycle activity. Addition of PGE(2) to the incubation mixture resulted in approximately 70% inhibition of sterol ester biosynthesis by skin of the EFA-deficient rats. These results suggest that the effects of PGE(2) in clearing the scales may be associated with its inhibitory effect on abnormal sterol esterification in the skin of the EFA-deficient rats.
Clinical differences between idiopathic and scleroderma‐related pulmonary hypertension (2006)

The results confirm that there are significant clinical and survival differences between IPAH and PAH-Scl. The presence of left heart disease, although more common in PAH-Scl, was not predictive of the higher mortality in these patients.
Evaluating Efficiencies of Dual AAV Approaches for Retinal Targeting (2017)

Retinal gene therapy has come a long way in the last few decades and the development and improvement of new gene delivery technologies has been exponential. The recent promising results from the first clinical trials for inherited retinal degeneration due to mutations in <i>RPE65</i> have provided a major breakthrough in the field and have helped cement the use of recombinant adeno-associated viruses (AAV) as the major tool for retinal gene supplementation. One of the key problems of AAV however, is its limited capacity for packaging genomic information to a maximum of around 4.8 kb. Previous studies have demonstrated that homologous recombination and/or inverted terminal repeat (ITR) mediated concatemerization of two overlapping AAV vectors can partially overcome the size limitation and help deliver larger transgenes. The aim of this study was to investigate and compare the use of different AAV dual-vector approaches in the mouse retina using a systematic approach comparing efficiencies <i>in vitro</i> and <i>in vivo</i> using a unique oversized reporter construct. We show that the hybrid approach relying on vector genome concatemerization by highly recombinogenic sequences and ITRs sequence overlap offers the best levels of reconstitution both <i>in vitro</i> and <i>in vivo</i> compared to <i>trans</i>-splicing and overlap strategies. Our data also demonstrate that dose and vector serotype do not affect reconstitution efficiency but a discrepancy between mRNA and protein expression data suggests a bottleneck affecting translation.
The magnitude of interproximal spaces between adjacent teeth. (1993)

Previous studies have shown that the human resting dentition naturally exhibits slight interproximal spacing between 80% to 90% of all adjacent teeth. The purpose of this study was to measure occurrence and dimension of interproximal spacing. Pieces of shim stock of various thicknesses were used to measure the dimension of interproximal spaces between natural or restored approximating tooth surfaces in 40 human subjects. The midline was frequently found to exhibit the largest space, and the dimension of the spacing was found to be greater in anterior teeth than posterior teeth. The canine-premolar spaces were also relatively large. The magnitude of interproximal tooth spacing was not related to gender or age. Results indicate that the position of teeth is naturally adjusted to maintain interproximal spacing. Interproximal spacing may allow for physiological movement to increase tolerance to trauma and improve tactile sensation.
Phase I Study of ch14.18 With Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin-2 in Children With Neuroblastoma After Autologous Bone Marrow Transplantation or Stem-Cell Rescue: A Report From the Children's Oncology Group (2008)

ch14.18 in combination with IL-2 was tolerable in the early post-HDC/SCR period. cis-RA can be administered safely between courses of ch14.18 and cytokines.