gebhart/patrepeval huggingface dataset:
Sensitivity to pertuzumab (2C4) in ovarian cancer models: cross-talk with estrogen receptor signaling (2007)

Pertuzumab (Omnitarg, rhuMab 2C4) is a humanized monoclonal antibody, which inhibits HER2 dimerization. Because it has shown some clinical activity in ovarian cancer, this study sought to identify predictors of response to this agent in a model of ovarian cancer. A panel of 13 ovarian cancer cell lines was treated with heregulin beta1 (HRGbeta1) or transforming growth factor-alpha, and cell proliferation was assessed. Both agents increased cell number in the majority of cell lines studied, the response to both being similar (r = 0.83; P = 0.0004, Pearson test). HRGbeta1 stimulation could be partially reversed by pertuzumab in 6 of 13 cell lines, with complete reversal in PE04 and PE06 cells. Addition of pertuzumab to transforming growth factor-alpha-stimulated cells produced growth inhibition in 3 of 13 cell lines (PE01, PE04, and PE06). The magnitude of HRGbeta1-driven growth stimulation correlated significantly with an increase in extracellular signal-regulated kinase 2 (P = 0.037) but not Akt (P = 0.99) phosphorylation. Such HRGbeta1-driven phosphorylation of extracellular signal-regulated kinase 1/2 and Akt could be reduced with pertuzumab, accompanied by changes in cell cycle distribution. In cell lines responsive to pertuzumab, HRGbeta1-enhanced phosphorylation of HER2 (Tyr(877)) was reduced. Estrogen-stimulated changes in growth, cell cycle distribution, and signaling were reversed by pertuzumab, indicating cross-talk between HER2 and estrogen signaling. These data indicate that there is a subset of ovarian cancer cell lines sensitive to pertuzumab and suggest possible predictors of response to identify patients who could benefit from this therapy. Furthermore, we have identified an interaction between HER2 and estrogen signaling in this disease.
Hippocampal theta rhythm: A tag for short‐term memory (2005)

The theta rhythm is the largest extracellular synchronous signal that can be recorded from the mammalian brain, and has been strongly implicated in mnemonic functions of the hippocampus. We advance the proposal that the theta rhythm represents a "tag" for short-term memory processing in the hippocampus. We propose that the hippocampus receives two main types of input, theta from ascending brainstem-diencephalo-septal systems and "information bearing" mainly from thalamocortical and cortical systems. The temporal convergence of activity of these two systems results in the encoding of information in the hippocampus, primarily reaching it via cortical routes. By analogy to processes associated with long-term potentiation (LTP), we suggest that theta represents a strong depolarizing influence on NMDA receptor-containing cells of the hippocampus. The temporal coupling of a theta-induced depolarization and the release of glutamate to these cells from intra- and extrahippocampal sources activates them. This, in turn, initiates processes leading to a (short-term) strengthening of connections between presynaptic ("information bearing") and postsynaptic neurons of the hippocampus. Theta is selectively present in the rat during active exploratory movements. During exploration, a rat continually gathers and updates information about its environment. If this information is temporally coupled to theta (as with the case of locomotion), it becomes temporarily stored in the hippocampus by mechanisms similar to the early phase of LTP (E-LTP). If the exploratory behavior of the rat goes unreinforced, these relatively short-lasting traces (1-3 h) gradually weaken and eventually fade-to be reupdated. On the other hand, if the explorations of the rat lead to rewards (or punishments), additional modulatory inputs to the hippocampus become activated and convert the short-term, theta-dependent memory, into long-term stores.
Current strategies for microRNA research (2012)

The short ribonucleic acid molecules (20-24 nucleotides) known as microRNAs (miRNAs) are non-coding RNAs that disrupt translation or degrade target mRNAs posttranscriptionally in a sequence-specific manner, and the miRNA may not be completely complementary to its targets. This class of RNAs is thought to be functionally important because many individual miRNAs are evolutionally conserved across widely diverse phyla. Further, miRNAs are associated with diverse biological phenomena, such as cell growth, apoptosis, development, differentiation, cancer, and arthritis. MicroRNA research is one of a number of rapidly evolving fields of basic and biomedical science, with many new techniques being developed. However, miRNA experiments require modifications of preexisting molecular techniques or specialized methods, given the difficulties stemming from their small size. In this review, we summarize current in-silico and biochemical strategies for miRNA research to outline the current status of the research techniques now being employed to find a new direction in the field.
Synovial T cell hyporesponsiveness to myeloid dendritic cells is reversed by preventing PD-1/PD-L1 interactions (2014)

SF T cell hyporesponsiveness upon (TSLP-primed) mDC stimulation in RA joints is partially dependent on PD-1/PD-L1 interactions, as PD-1 and PD-L1 are both highly expressed on SF T cells and mDCs, respectively, and inhibiting PD-1 availability restores T cell proliferation. The potential of IL-7 to robustly reverse this hyporesponsiveness suggests that such proinflammatory cytokines in RA joints strongly contribute to memory T cell activation.
Enhanced Antiviral Benefit of Combination Therapy with Lamivudine and Alpha Interferon against WHV Replication in Chronic Carrier Woodchucks (2000)

Cell culture studies in our laboratory previously demonstrated synergistic antiviral activity for the combinations of lamivudine and a novel recombinant hybrid human alpha B/D interferon (rHu alpha B/D IFN) against hepatitis B virus (HBV) replication. Based on these results, a study was designed to determine if an enhanced antiviral effect with this drug combination could be demonstrated in vivo using the woodchuck hepatitis virus (WHV)/woodchuck experimental model of chronic HBV infection. Both antiviral agents have been shown to be effective against WHV replication in WHV chronic carriers during previous studies by our laboratories. Two combination treatment regimens were compared to matched monotherapies in a placebo-controlled trial. The first used simultaneous administration of rHu alpha B/D IFN and lamivudine for 24 weeks. The other combination treatment regimen used a staggered dosing schedule of 12 weeks of administration of lamivudine alone, followed by 12 weeks of simultaneous dosing with both drugs, followed by 12 weeks of therapy with rHu alpha B/D IFN alone. Both treatment regimens with combinations of lamivudine and rHu alpha B/D IFN were more effective at reducing WHV replication in chronically infected wood-chucks than the corresponding monotherapies. Both combination treatments produced antiviral effects that were at least equal to that expected for additive activity based on estimations generated by Bliss Independence calculations. The staggered treatment regimen reduced viraemia and intrahepatic WHV replication significantly more than that expected for additive interactions, indicating synergistic antiviral effects. These studies demonstrate that combination therapy of chronic WHV infection has enhanced antiviral benefit over corresponding monotherapies and indicate that combination treatment of chronic HBV infection can be superior to therapies using a single antiviral agent.
Model-aided coding of multi-viewpoint image data (2000)

The paper presents a new coding technique for images taken from arbitrary recording positions around a static scene, based on the reconstructed object geometry. Such data structures occur in image-based rendering applications where many hundreds to thousands of images need to be stored and transmitted. Approximate scene geometry enables disparity compensation as well as occlusion detection, leading to improved image prediction. Images are coded in hierarchical order to ensure efficient exploitation of inter-image similarities. The 3-D geometry model allows rendering new views by warping recorded images. The presented algorithm is validated using real-world image data sets, achieving better than 1000:1 compression at acceptable reconstruction quality.
Molecular characterization of one of the maize polygalacturonase gene family members which are expressed during late pollen development (1993)

A gene exhibiting homology to the polygalacturonases of several species, including tomato and Oenothera, has been shown by RNA dot-blot analysis and in situ hybridization experiments to be expressed post-first microspore mitosis in maize. A 2.87 kbp section of the promoter fused to E. coli beta-glucuronidase (uidA) coding sequence conferred the correct spatial and temporal expression in transgenic tobacco plants. However, low levels of expression were detected in other tissues, and in particular in the tissues surrounding the vascular branch points of leaf nodes. The maize polygalacturonase gene is one member of a highly conserved gene family. The lack of detectable expression in sporophytic tissues and the isolation of a number of related cDNAs from maize suggests that all expressed members of this family show the same spatial and temporal regulation.
Escherichia coli periplasmic chaperone FaeE is a homodimer and the chaperone‐K88 subunit complex is a heterotrimer (1994)

The interaction of FaeE, a periplasmic chaperone involved in K88 biosynthesis, and the major fimbrial subunit FaeG was investigated. The genes encoding the two proteins were subcloned together in the expression vector pINIIIA1. Cells expressing the subcloned genes accumulated in their periplasm a complex of FaeE and FaeG. This complex was purified by isoelectric focusing and anion-exchange fast-protein liquid chromatography. SDS-PAGE, native gel electrophoresis, immunoblotting and determination of the N-terminal amino acid sequences and the molar ratio of the N-terminal amino acid residues revealed that the complex is a heterotrimer consisting of two molecules of FaeE and one molecule of FaeG. The periplasmic chaperone FaeE was purified from the periplasm of cells expressing only the subcloned faeE gene. Gel filtration, protein cross-linking analysis and a biophysical approach in which the rotation diffusion coefficient of the purified FaeE was determined led to the conclusion that the native FaeE chaperone is a homodimer.
Increased Sensitivity to Angiotensin II Is Present Postpartum in Women With a History of Hypertensive Pregnancy (2010)

Pregnancies complicated by new-onset hypertension are associated with increased sensitivity to angiotensin II, but it is unclear whether this sensitivity persists postpartum. We studied pressor response to infused angiotensin II in 25 normotensive postpartum women in both high- and low-sodium balance. Ten women had a history of hypertensive pregnancy (5 with preeclampsia; 5 with transient hypertension of pregnancy), and 15 women had a history of uncomplicated, normotensive pregnancy. Systolic and diastolic blood pressures, aldosterone, and soluble fms-like tyrosine kinase 1 levels were measured before and after angiotensin II infusion in both dietary phases. In high sodium balance, women with a history of hypertensive pregnancy were normotensive but had significantly higher systolic and diastolic blood pressures than controls (115 versus 104 mm Hg and 73 versus 65 mm Hg, respectively; P<0.05). Women with a history of hypertensive pregnancy had a pressor response to salt loading, demonstrated by an increase in systolic blood pressure on a high-salt diet. They also had greater systolic pressor response (10 versus 2 mm Hg; P=0.03), greater increase in aldosterone (56.8 versus 30.8 ng/dL; P=0.03), and increase in soluble fms-like tyrosine kinase 1 levels (11.0 versus -18.9 pg/mL; P=0.02) after infusion of angiotensin II in low-sodium balance compared with controls. Thus, women with a history of hypertensive pregnancy demonstrated salt sensitivity of blood pressure and had increased pressor, adrenal, and soluble fms-like tyrosine kinase 1 responses to infused angiotensin II in low-sodium balance. Increased sensitivity to angiotensin II observed during pregnancy in women with hypertensive pregnancy is present postpartum; this feature may contribute to future cardiovascular risk in these women.
Mutational Analysis of a ras Catalytic Domain (1986)

We used linker insertion-deletion mutagenesis to study the catalytic domain of the Harvey murine sarcoma virus v-rasH transforming protein, which is closely related to the cellular rasH protein. The mutants displayed a wide range of in vitro biological activity, from those that induced focal transformation of NIH 3T3 cells with approximately the same efficiency as the wild-type v-rasH gene to those that failed to induce any detectable morphologic changes. Correlation of transforming activity with the location of the mutations enabled us to identify three nonoverlapping segments within the catalytic domain that were dispensable for transformation and six other segments that were required for transformation. Segments that were necessary for guanosine nucleotide (GDP) binding corresponded to three of the segments that were essential for transformation; two of the three segments share strong sequence homology with other purine nucleotide-binding proteins. Loss of GDP binding was associated with apparent instability of the protein. Lesions in two of the three other required regions significantly reduced GDP binding, while small lesions in the last required region did not impair GDP binding or membrane localization. We speculate that this latter region interacts with the putative cellular target of ras. The results suggest that transforming ras proteins require membrane localization, guanosine nucleotide binding, and an additional undefined function that may represent interaction with their target.
Custom Patellofemoral Arthroplasty of the Knee (2006)

Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.
Structure and alternative splicing of the gene encoding α1G, a human brain T calcium channel α1 subunit (1999)

The structure of CACNA1G, the gene encoding α1G, a human brain T Ca2+ channel α1 subunit, was determined by comparison of polymerase chain reaction-amplified brain cDNA and genomic sequences. The gene consists of at least 38 exons, two of them newly-identified, spanning at least 66 490 basepairs of chromosome 17q22. Alternative splicing of the RNA occurs at six sites: cassette exons 14, 26, 34 and 35, an internal donor in exon 25 and protein-coding intron 38B. Additionally, the RNA can be polyadenylated at either of two sites. Alternative splicing of CACNA1G RNA may lead to expression of as many as 24 distinct protein products, ranging from 2171 to 2377 amino-acids residues.
Angiogenesis inhibitors for the treatment of small cell lung cancer (SCLC) (2017)

Adding angiogenesis inhibitors to chemotherapy did not improve PFS, OS, ORR, 1-year survival rate, 2-year survival rate or 1-year progression-free survival rate for SCLC. However, subgroup analysis revealed that bevacizumab enhanced PFS. Angiogenesis inhibitors also had a high incidence of constipation and embolism.
Three-dimensional space optimization for near-field ptychography (2019)

A multiple slices approach in ptychography, termed 3ePIE algorithm, solves the multiple scattering problems of thick samples, which is crucial to biomedical imaging and in situ studies. However, it is unclear how many slices need to be separated and what the distance is between each layer respectively, while these two parameters are sensitive and crucial to the recovery of thick samples. The traditional method is to separate the sample with the same interval for convenience and to test the number of sections for the best reconstructions, which is reasonable for continuous samples and has achieved great results. But this kind of segmentation approach may not be scientific enough for those discrete samples with an uneven spatial distribution. The two inaccurate parameters may yield the algorithm to diverge or generate artifacts, and the empty slices may decrease the reconstruction quality and increase computation time. In addition, repeatedly testing the number of slices is tedious work even for a continuous sample. To this end, a genetic algorithm-based 3ePIE approach, termed the GA-3ePIE method, is proposed to retrieve both the interval between each layer and the number of slices. The performance is verified by both simulations and experiments. The maximum number of sections that can be resolved is also investigated in numerical analysis, which is associated with the sampling and overlap rate in a spatial domain. Our method can be also promoted to image thick samples with coherent X-rays and in the electron regime. The limitations of our method are also discussed.
Blocking heat shock protein-90 inhibits the invasive properties and hepatic growth of human colon cancer cells and improves the efficacy of oxaliplatin in p53-deficient colon cancer tumors in vivo (2007)

We recently showed that inhibition of heat shock protein 90 (Hsp90) decreases tumor growth and angiogenesis in gastric cancer through interference with oncogenic signaling pathways. However, controversy still exists about the antimetastatic potential of Hsp90 inhibitors. Moreover, in vitro studies suggested that blocking Hsp90 could overcome p53-mediated resistance of cancer cells to oxaliplatin. We therefore hypothesized that blocking oncogenic signaling with a Hsp90 inhibitor would impair metastatic behavior of colon cancer cells and also improve the efficacy of oxaliplatin in vivo. Human colon cancer cells (HCT116, HT29, and SW620) and the Hsp90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG) were used for experiments. In vitro, 17-DMAG substantially inhibited phosphorylation of epidermal growth factor receptor, c-Met, and focal adhesion kinase, overall resulting in a significant decrease in cancer cell invasiveness. Importantly, 17-DMAG led to an up-regulation of the transcription factor activating transcription factor-3, a tumor suppressor and antimetastatic factor, on mRNA and protein levels. In a cell death ELISA, 17-DMAG markedly induced apoptosis in both p53-wt and p53-deficient cells. In vivo, 17-DMAG significantly reduced tumor growth and vascularization. Furthermore, blocking Hsp90 reduced hepatic tumor burden and metastatic nodules in an experimental model of hepatic colon cancer growth. Importantly, combining oxaliplatin with 17-DMAG in vivo significantly improved growth inhibitory and proapoptotic effects on p53-deficient cells, compared with either substance alone. In conclusion, inhibition of Hsp90 abrogates the invasive properties of colon cancer cells and modulates the expression of the antimetastatic factor activating transcription factor-3. Hence, targeting Hsp90 could prove valuable for treatment of advanced colorectal cancer by effectively inhibiting colon cancer growth and hepatic metastasis and improving the efficacy of oxaliplatin.
Population genetics and molecular epidemiology of Neisseria meningitidis. (1998)

Under non-epidemic conditions, Neisseria meningitidis causes disease primarily in children under the age of 5 and the cases are sporadic without any evident relationship between them. Occasionally, localized outbreaks of meningococcal disease occur, and sometimes epidemic waves of disease may spread to several countries or even continents and constitute a pandemic. In the past 10 years or so, population genetic analyses have provided insights into the biology of the bacterium and the epidemiology of meningococcal disease, improving our understanding of the cause of epidemics. Through the application of molecular methods, and especially multilocus enzyme electrophoresis, to N. meningitidis strains of worldwide origin, it has been possible to identify virulent clones and provide a surveillance system to warn of meningococcal epidemics. The characteristics of the predominant clones which are nowadays causing meningococcal disease in the world are summarized here and the importance of population genetics in interpreting the epidemiological data is illustrated.
Superconducting Wires of High Tc Oxides (1987)

Superconducting wires of Y–Ba–Cu–O system have been investigated. Wires were fabricated by powder method. The wires were successfully reduced to a small diameter. Wires of Y 1 Ba 2 Cu 3 O 7 exhibit zero resistance at 90 K.
DNA damage triggers a prolonged p53-dependent G1 arrest and long-term induction of Cip1 in normal human fibroblasts. (1994)

The tumor suppressor p53 is a cell cycle checkpoint protein that contributes to the preservation of genetic stability by mediating either a G1 arrest or apoptosis in response to DNA damage. Recent reports suggest that p53 causes growth arrest through transcriptional activation of the cyclin-dependent kinase (Cdk)-inhibitor Cip1. Here, we characterize the p53-dependent G1 arrest in several normal human diploid fibroblast (NDF) strains and p53-deficient cell lines treated with 0.1-6 Gy gamma radiation. DNA damage and cell cycle progression analyses showed that NDF entered a prolonged arrest state resembling senescence, even at low doses of radiation. This contrasts with the view that p53 ensures genetic stability by inducing a transient arrest to enable repair of DNA damage, as reported for some myeloid leukemia lines. Gamma radiation administered in early to mid-, but not late, G1 induced the arrest, suggesting that the p53 checkpoint is only active in G1 until cells commit to enter S phase at the G1 restriction point. A log-linear plot of the fraction of irradiated G0 cells able to enter S phase as a function of dose is consistent with single-hit kinetics. Cytogenetic analyses combined with radiation dosage data indicate that only one or a small number of unrepaired DNA breaks may be sufficient to cause arrest. The arrest also correlated with long-term elevations of p53 protein, Cip1 mRNA, and Cip1 protein. We propose that p53 helps maintain genetic stability in NDF by mediating a permanent cell cycle arrest through long-term induction of Cip1 when low amounts of unrepaired DNA damage are present in G1 before the restriction point.
Comparison of excessive Balmer α line broadening of glow discharge and microwave hydrogen plasmas with certain catalysts (2002)

From the width of the 656.3 nm Balmer α line emitted from microwave and glow discharge plasmas, it was found that a strontium–hydrogen microwave plasma showed a broadening similar to that observed in the glow discharge cell of 27–33 eV; whereas, in both sources, no broadening was observed for magnesium–hydrogen. Microwave helium–hydrogen and argon–hydrogen plasmas showed extraordinary broadening corresponding to an average hydrogen atom temperature of 180–210 eV and 110–130 eV, respectively. The corresponding results from the glow discharge plasmas were 33–38 eV and 30–35 eV respectively, compared to ≈4 eV for plasmas of pure hydrogen, neon–hydrogen, krypton–hydrogen, and xenon–hydrogen maintained in either source. Similarly, the average electron temperature Te for helium–hydrogen and argon–hydrogen microwave plasmas were high, 30 500±5% K and 13 700±5% K, respectively; compared to 7400±5% K and 5700±5% K for helium and argon alone, respectively. External Stark broadening or acceleration of charged species due to high fields can not explain the microwave results since no high field was present, and the electron density was orders of magnitude too low for the corresponding Stark effect. Rather, a resonant energy transfer mechanism is proposed.