gebhart/patrepeval huggingface dataset:
DCLK1 Regulates Pluripotency and Angiogenic Factors via microRNA-Dependent Mechanisms in Pancreatic Cancer (2013)

Stem cell pluripotency, angiogenesis and epithelial-mesenchymal transition (EMT) have been shown to be significantly upregulated in pancreatic ductal adenocarcinoma (PDAC) and many other aggressive cancers. The dysregulation of these processes is believed to play key roles in tumor initiation, progression, and metastasis, and is contributory to PDAC being the fourth leading cause of cancer-related deaths in the US. The tumor suppressor miRNA miR-145 downregulates critical pluripotency factors and oncogenes and results in repressed metastatic potential in PDAC. Additionally, the miR-200 family regulates several angiogenic factors which have been linked to metastasis in many solid tumors. We have previously demonstrated that downregulation of DCLK1 can upregulate critical miRNAs in both in vitro and in vivo cancer models and results in downregulation of c-MYC, KRAS, NOTCH1 and EMT-related transcription factors. A recent report has also shown that Dclk1 can distinguish between normal and tumor stem cells in Apc min/+ mice and that ablation of Dclk1 + cells resulted in regression of intestinal polyps without affecting homeostasis. Here we demonstrate that the knockdown of DCLK1 using poly(lactide-co-glycolide)encapsulated-DCLK1-siRNA results in AsPC1 tumor growth arrest. Examination of xenograft tumors revealed, (a) increased miR-145 which results in decreased pluripotency maintenance factors OCT4, SOX2, NANOG, KLF4 as well as KRAS and RREB1; (b) increased let-7a which results in decreased pluripotency factor LIN28B; and (c) increased miR-200 which results in decreased VEGFR1, VEGFR2 and EMT-related transcription factors ZEB1, ZEB2, SNAIL and SLUG. Specificity of DCLK1 post-transcriptional regulation of the downstream targets of miR-145, miR-200 and let-7a was accomplished utilizing a luciferase-based reporter assay. We conclude that DCLK1 plays a significant master regulatory role in pancreatic tumorigenesis through the regulation of multiple tumor suppressor miRNAs and their downstream pro-tumorigenic pathways. This novel concept of targeting DCLK1 alone has several advantages over targeting single pathway or miRNA-based therapies for PDAC.
Self-Aligned Contacting of Carbon Nanotubes (2003)

An important prerequisite for the implementation of carbon nanotubes (CNTs) in microelectronic circuits is the evaluation of their electronic properties. For this, the generation of low‐ohmic electrical contacts between CNTs and metallic circuit lines is crucial. We describe a parallel process which does not rely on e‐beam lithography and yields self‐aligned, low‐ohmic contacts on wafer scale. CNTs that are spray deposited on metallic test structures created by optical lithography are subsequently embedded by electroless metallization and annealed. With this method we are able to simultaneously lower the contact resistance of an unlimited number of CNTs. The reduction of the contact resistance depends on the metals involved and the annealing process. This new method enables the statistical evaluation of the CNT quality dependence on synthesis conditions.
Isolation of Proteins and Protein Complexes by Immunoprecipitation (2008)

Immunoprecipitation (IP) uses the specificity of antibodies to isolate target proteins (antigens) out of complex sample mixtures. Three different approaches for performing IP will be discussed; traditional (classical) method, oriented affinity method and direct affinity method. The traditional method of incubating the IP antibody with the sample and sequentially binding to Protein A or G agarose beads (resin) facilitates the most efficient target antigen recovery. However, this approach results in the target protein becoming contaminated with the IP antibody that can interfere with downstream analyses. The orientated affinity method uses Protein A or G beads to serve as an anchor to which the IP antibody is crosslinked thereby preventing the antibody from co-eluting with the target protein. Similarly, the direct affinity method also immobilizes the IP antibody except in this case it is directly attached to a chemically activated support. Both methods prevent co-elution of the IP antibody enabling reuse of the immunomatrix. All three approaches have unique advantages and can also be used for co-immunoprecipitation to study protein:protein interactions and investigate the functional proteome.
Analysis of the oxidation state and oxidation number by ab initio molecular orbital calculations: chlorine and sulfur compounds (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAnalysis of the oxidation state and oxidation number by ab initio molecular orbital calculations: chlorine and sulfur compoundsKeiko Takano, Haruo Hosoya, and Suehiro IwataCite this: J. Am. Chem. Soc. 1982, 104, 14, 3998–4005Publication Date (Print):July 1, 1982Publication History Published online1 May 2002Published inissue 1 July 1982https://pubs.acs.org/doi/10.1021/ja00378a037https://doi.org/10.1021/ja00378a037research-articleACS PublicationsRequest reuse permissionsArticle Views127Altmetric-Citations16LEARN 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
Targeted deep sequencing of mucinous ovarian tumors reveals multiple overlapping RAS-pathway activating mutations in borderline and cancerous neoplasms (2015)

Overall, the prevalence of RAS-alteration and striking co-occurrence of pathway "double-hits" supports a critical role for tumor progression in this ovarian malignancy. Given the spectrum of RAS-activating mutations, it is clear that targeting this pathway may be a viable therapeutic option for patients with recurrent or advanced stage mucinous ovarian carcinoma, however caution should be exercised in selecting one or more personalized therapeutics given the frequency of non-redundant RAS-activating alterations.
Conservation of the 17-Kilodalton Antigen Gene within the Genus <i>Bartonella</i> (2000)

The 17-kDa antigen of Bartonella henselae has previously been shown to elicit a strong humoral immune response in patients with cat scratch disease (CSD) and to be useful in screening human serum samples for CSD. In this study, PCR amplification of genes homologous to the 17-kDa antigen gene of B. henselae was performed using genomic DNAs from several species of Bartonella, including the currently recognized human pathogens. Amplicons of similar size were demonstrated using the following chromosomal DNA templates: B. henselae (two strains), B. quintana (two strains), B. elizabethae, B. clarridgeiae, B. vinsonii subsp. vinsonii, and B. vinsonii subsp. berkhoffii. No evidence of a B. bacilliformis homolog of the 17-kDa antigen gene was obtained using multiple primer pairs. DNA sequencing revealed open reading frames capable of coding for proteins with sizes similar to that of the 17-kDa antigen of B. henselae in all of the amplicons; however, extensive sequence divergence across the genus was noted. Cloning of the amplified products into pUC19 resulted in recombinants that directed synthesis of homologs of the 17-kDa protein. Immunoblot analysis using human sera from CSD cases demonstrated very little cross-reactivity among different species for this protein. In contrast, immunoblots using rabbit serum raised to the recombinant B. henselae antigen showed extensive cross-reactivity with the proteins of other Bartonella species. The data suggest that the use of the 17-kDa antigen as a serologic reagent may allow the development of more specific diagnostic assays. Furthermore, the nucleotide sequences from the various versions of the 17-kDa antigen gene should be useful for rapid identification of Bartonella at the species level.
Silver nanoparticles within vertically aligned multi-wall carbon nanotubes with open tips for antibacterial purposes (2010)

Vertically aligned multi-wall carbon nanotube (CNT) arrays were fabricated in tip-growth mode on Ni/Si substrates using plasma enhanced chemical vapor deposition. In a purification process including hydrogenation and acid washing of the Ni/CNTs, the oxygen-containing functional groups were substantially reduced and a wide hollow core at the tip of the CNTs was formed by removing the Ni seeds. Sol–gel silver nanoparticles were deposited on the surface of the unpurified Ni/CNTs, while they could also be embedded within the hollow core of the Ni-removed CNTs. The persistency of the silver ions in the Ni-removed Ag–CNTs in comparison to the release of the silver ions from the Ag–Ni/CNTs in a dilute HNO3 solution confirmed the effective embedding of the Ag nanoparticles within the hollow core of the Ni-removed CNTs. The Ni-removed Ag–CNTs showed a strong antibacterial activity against Escherichia coli bacteria in the dark (inactivation of 99.8 ± 0.1% of the bacteria as compared to the Ni-removed CNTs and the Ag–Ni/CNTs with 62 ± 11 and 47 ± 18% inactivation in 120 min), while the bacteria even exhibited some proliferation on the surface of the unpurified Ni/CNT arrays. In the context of cell membrane rupture of the bacteria through a direct contact mechanism, it was proposed that the Ni seeds acted as obstacles for an effective contact between the bacteria and the tips of the CNT arrays.
Reduced T2* Values in Soleus Muscle of Patients with Type 2 Diabetes Mellitus (2012)

Tissue water transverse relaxation times (T2) are highly sensitive to fluid and lipid accumulations in skeletal muscles whereas the related T2* is sensitive to changes in tissue oxygenation in addition to factors affecting T2. Diabetes mellitus (DM) affects muscles of lower extremities progressively by impairing blood flow at the macrovascular and microvascular levels. This study is to investigate whether T2 and T2* are sensitive enough to detect abnormalities in skeletal muscles of diabetic patients in the resting state. T2 and T2* values in calf muscle of 18 patients with type 2 DM (T2DM), 22 young healthy controls (YHC), and 7 age-matched older healthy controls (OHC) were measured at 3T using multi-TE spin echo and gradient echo sequences. Regional lipid levels of the soleus muscle were also measured using the Dixon method in a subset of the subjects. Correlations between T2, T2*, lipid levels, glycated hemoglobin (HbA1c) and presence of diabetes were evaluated. We found that T2 values were significantly higher in calf muscles of T2DM subjects, as were T2* values in anterior tibialis, and gastrocnemius muscles of T2DM participants. However, soleus T2* values of the T2DM subjects were significantly lower than those of the older, age-matched HC cohort (22.9±0.5 vs 26.7±0.4 ms, p<0.01). The soleus T2* values in the T2DM cohort were inversely correlated with the presence of diabetes (t = -3.46, p<0.001) and with an increase in HbA1c, but not with body mass index or regional lipid levels. Although multiple factors may contribute to changes in T2* values, the lowered T2* value observed in the T2DM soleus muscle is most consistent with a combination of high oxygen consumption and poor regional perfusion. This finding is consistent with results of previous perfusion studies and suggests that the soleus in individuals with T2DM is likely under tissue oxygenation stress.
Phosphorylation regulates association of PDE3A isoforms with distinct interactomes (1013.23) (2014)

Inhibitors of cyclic nucleotide phosphodiesterase PDE3A have inotropic actions in human myocardium, but their long‐term use increases mortality in patients with heart failure. We previously showed that two isoforms in cardiac myocytes, PDE3A1 and PDE3A2 ‐ whose amino‐acid sequences are identical except for a unique N‐terminal extension in PDE3A1 ‐ are selectively phosphorylated in response to the activation of different signaling pathways: PDE3A1 is phosphorylated at S312 by PKA and PDE3A2 is phosphorylated at S428 by PKC. Here we examined the effects of phosphorylation on protein‐protein interactions. Exposure of PDE3A1‐transfected HEK293 cells to isoproterenol (to activate PKA) and of PDE3A2‐transfected HEK293 cells to PMA (to activate PKC) led to shifts in their elution on gel‐filtration chromatography consistent with an increase in their interactions with other proteins. Two‐dimensional electrophoresis of co‐immunoprecipitated proteins indicates that the two isoforms bind to unique sets of proteins. These differences in the interactomes of PDE3A1 and PDE3A2 suggest that the two isoforms, which are indistinguishable with respect to catalytic activity and inhibitor sensitivity, may be selectively targeted by small molecules capable of disrupting their protein‐protein interactions and thereby blocking their recruitment to specific intracellular signaling complexes, with the possibility of eliciting inotropic actions without increasing mortality.
A Systemic Network for <i>Chlamydia pneumoniae</i> Entry into Human Cells (2010)

Bacterial entry is a multistep process triggering a complex network, yet the molecular complexity of this network remains largely unsolved. By employing a systems biology approach, we reveal a systemic bacterial-entry network initiated by Chlamydia pneumoniae, a widespread opportunistic pathogen. The network consists of nine functional modules (i.e., groups of proteins) associated with various cellular functions, including receptor systems, cell adhesion, transcription, and endocytosis. The peak levels of gene expression for these modules change rapidly during C. pneumoniae entry, with cell adhesion occurring at 5 min postinfection, receptor and actin activity at 25 min, and endocytosis at 2 h. A total of six membrane proteins (chemokine C-X-C motif receptor 7 [CXCR7], integrin beta 2 [ITGB2], platelet-derived growth factor beta polypeptide [PDGFB], vascular endothelial growth factor [VEGF], vascular cell adhesion molecule 1 [VCAM1], and GTP binding protein overexpressed in skeletal muscle [GEM]) play a key role during C. pneumoniae entry, but none alone is essential to prevent entry. The combination knockdown of three genes (coding for CXCR7, ITGB2, and PDGFB) significantly inhibits C. pneumoniae entry, but the entire network is resistant to the six-gene depletion, indicating a resilient network. Our results reveal a complex network for C. pneumoniae entry involving at least six key proteins.
BAX UTR G (-248) A Polymorphism Has No Impact on Survival in Patients with Multiple Myeloma. (2006)

Abstract Multiple myeloma is a malignant tumour of plasma cells that remains incurable for the vast majority of patients with a median survival of 2–3 years. The bax protein is a member of the Bcl-2 family and is an important pro-apoptotic protein. Low BAX expression has been shown to be associated with prolonged survival in patients with myeloma(1). A novel polymorphism, G(-248)A in the BAX promoter in patients with Chronic lymphocytic leukaemia (CLL) has shown to be associated with reduced Bax protein expression, progressive disease and treatment failure(2, 3). We report here the impact of this polymorphism on survival in 304 (M: 168; F: 136) patients with myeloma Materials and Methods This study included 158 (M: 89; F: 69) patients from MRC Myeloma VII trial and 146 (M: 79; F: 67) under our care from January 1992 and February 2006. DNA was extracted from myeloma patients and healthy volunteer’s peripheral blood using a standard salting out method. Analysis of the 5-UTR polymorphism was undertaken using method already published by our centre(3). Patients received either intensive or non intensive antimyeloma therapy as per standard practice. Statistical analysis was carried out using SAS software. Results The frequency of GG and GA/AA genotypes was 81.6% and 18.4% in myeloma patients as compared to 85.2% and 14.8% in normal controls. Median age at diagnosis was 58 yr (range 34–87 yrs). (GA/AA Group: 58 yrs (42–85); GG Group: 58 yr (34–87)). There were no significant differences in the sex distribution, β2 microglobulin, haemoglobin, bone lesions, calcium and age between the GA/AA &amp; GG groups with p values 0.72, 0.46, 0.95, 0.61, 0.49 and 0.46 respectively. Abnormal creatinine levels were significantly few in GA/AA group (p value: 0.002). Median survival for the AA/GA group was 48 months (95% CI 36 – 61 months) compared with 54 months in the GG group (95% CI 46 – 63 months)[p=0.5 log-rank test] with a median follow up of 62 months (range 1 to 141). Conclusions Our results show that the GA/AA polymorphism has no impact on the overall survival in patients with myeloma. Further work is ongoing in order to assess the impact of this polymorphism on response in various treatment groups.
Intracellular Chloride Channels Regulate Endothelial Metabolic Reprogramming in Pulmonary Arterial Hypertension (2022)

Mitochondrial fission and a metabolic switch from oxidative phosphorylation to glycolysis are key features of vascular pathology in pulmonary arterial hypertension (PAH) and are associated with exuberant endothelial proliferation and apoptosis. The underlying mechanisms are poorly understood. We describe the contribution of two intracellular chloride channel proteins, CLIC1 and CLIC4, both highly expressed in PAH and cancer, to mitochondrial dysfunction and energy metabolism in PAH endothelium. Pathological overexpression of CLIC proteins induces mitochondrial fragmentation, inhibits mitochondrial cristae formation, and induces metabolic shift toward glycolysis in human pulmonary artery endothelial cells, consistent with changes observed in patient-derived cells. Interactions of CLIC proteins with structural components of the inner mitochondrial membrane offer mechanistic insights. Endothelial CLIC4 excision and mitofusin 2 supplementation have protective effects in human PAH cells and preclinical PAH. This study is the first to demonstrate the key role of endothelial intracellular chloride channels in the regulation of mitochondrial structure, biogenesis, and metabolic reprogramming in expression of the PAH phenotype.
A Spherical Active Coded Aperture for $4\pi $ Gamma-Ray Imaging (2017)

Gamma-ray imaging facilitates the efficient detection, characterization, and localization of compact radioactive sources in cluttered environments. Fieldable detector systems employing active planar coded apertures have demonstrated broad energy sensitivity via both coded aperture and Compton imaging modalities. However, planar configurations suffer from a limited field of view, especially in the coded aperture mode. To improve upon this limitation, we introduce a novel design by rearranging the detectors into an active coded spherical configuration, resulting in a 4π isotropic field of view for both coded aperture and Compton imaging. This paper focuses on the low-energy coded aperture modality and the optimization techniques used to determine the optimal number and configuration of 1-cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> CdZnTe coplanar grid detectors on a 14-cm diameter sphere with 192 available detector locations.
Induction of cytotoxic T lymphocytes against the Plasmodium falciparum circumsporozoite protein by immunization with soluble recombinant protein without adjuvant (1993)

Immunization of mice with irradiated malaria sporozoites induces protection that is dependent on CD8+ T cells, and adoptive transfer of CD8+ cytotoxic T lymphocyte (CTL) clones against rodent malaria circumsporozoite (CS) protein and sporozoite surface protein 2 completely protects against sporozoite challenge. Thus, there are now efforts to develop vaccines that induce CTL against the CS protein and sporozoite surface protein 2. Until recently, it was thought that induction of CTL required production of target proteins within cells, breakdown of the proteins to peptides in the cytoplasm, and transport of the peptides to the cell surface in combination with class I major histocompatibility complex molecules. It has now been shown that immunization with peptides in Freund's complete adjuvant and with soluble protein in liposomes can induce CTL. To determine whether we could induce CTL against the Plasmodium falciparum CS protein by immunization with soluble protein, B10.BR mice were immunized intravenously, intraperitoneally, or intramuscularly with a recombinant P. falciparum CS protein called RLF mixed with the adjuvant DETOX (monophosphoryl lipid A, cell wall skeleton of Mycobacteria phlei, and squalane). Two weeks after the last dose, spleen cells from mice immunized intravenously, but not intraperitoneally or intramuscularly, had peptide-specific, major histocompatibility complex-restricted, CD8+ T-cell-dependent cytolytic activity against peptide 368-390 from the 7G8 P. falciparum CS protein. To determine whether the adjuvant was required for induction of the cytolytic activity, mice were immunized with RLF without adjuvant, and similar cytolytic activity was demonstrated. The finding that we could induce CTL by administration of soluble protein without adjuvant markedly broadens the possibilities for vaccinologists working to develop methods of inducing CTL in humans.
Infrared hole-burning spectroscopy of matrix-isolated ReO_4^− molecules (1981)

CO(2)-laser-diode-laser hole-burning spectroscopy has been used to measure the temperature-dependent homogeneous linewidth of the ReO(4)(-) infrared active internal-vibrational mode (nu(3)) in alkali halide lattices. Hole widths as small as 20 MHz (FWHM) have been observed in an inhomogeneously broadened line of width as large as 1 cm(-1). Our measurement of the homogeneous linewidth over 4 orders of magnitude indicates that elastic acoustic phonon scattering is the dominant T(2) relaxation process from 10 to 600 K.
Adult acute leukemia: hand mirror cell variant. (1996)

Two patients with numerous hand mirror cells in the bone marrow were investigated by morphologic, cytochemical, immunohistochemical, flow cytometric, cytogenetic, and gene rearrangement analysis. Both demonstrated a mixed immunophenotype with expression of myeloid and T-lymphoid features. Interestingly, both strongly expressed CD2 (adhesion molecule) and CD7. Review of the literature uncovered additional cases of acute mixed leukemia--hand mirror variant with strong expression of CD2, CD7, and CDIIb, suggesting a unique subset. Under normal physiologic conditions lymphoid cells and monocytes assume a hand mirror configuration when adhesion molecules (i.e., CD2, CDIIb) are triggered by their corresponding ligands. Evidently not all acute leukemias with surface adhesion molecules form hand mirrors, which suggests an additional stimulatory event. The presence of adhesion molecules on these activated cells is important to homing, trafficking, spread of the malignant cells, clinical course, prognosis, and treatment. Therefore all HMC cases require detailed analysis to ensure accurate diagnosis. In-depth evaluation of such cases should give new insights into clinical presentation, prognosis, and treatment of these unusual cases.
RH : A genetic metric for measuring intra-host Plasmodium falciparum relatedness and distinguishing cotransmission from superinfection (2022)

Code and barcode sequences associated with the manuscript "RH: A genetic metric for measuring intra-host Plasmodium falciparum relatedness and distinguishing cotransmission from superinfection" published in PNAS Nexus