gebhart/patrepeval huggingface dataset:
Activation of H-ras oncogenes in preneoplastic mouse mammary tissues. (1990)

The mammary hyperplastic outgrowth (HOG) line C4, resulted from serial transplantation of a hyperplastic alveolar nodule which arose in a dimethylbenz(a)anthracene (DMBA) treated mouse. The immortalized C4 outgrowth line, on transplantation into syngeneic mice, develops as preneoplastic, hyperplastic outgrowths and subsequently into malignant carcinomas after a long latent period (greater than 6 months). Treatment of mice carrying C4 HOG transplants with DMBA resulted in a reduced latent period for tumor development (less than 3 months) and an increased tumor incidence. DNA's from C4 HOGs and mammary carcinomas of untreated as well as DMBA-treated mice were analyzed for the presence of oncogenes by the NIH3T3 focus forming assay. Transforming H-ras genes were detected in two of 6 preneoplastic HOGs and 10 of 12 carcinomas from DMBA-treated mice. DNAs from neither the HOGs nor the tumors from untreated mice were positive in this assay. The H-ras locus was then directly examined in the 61st codon by in vitro amplification of each of the tissue DNAs using PCR. The location of the activating mutation was determined by hybridization of amplified DNA to mixed sequence oligonucleotide probes. The specific nature of the mutation was defined by RFLPs using XbaI, TaqI and Sau96I restriction enzymes. Six of the H-ras oncogenes in DMBA-promoted tumors were activated by commonly observed A to T transversions at the 61st codon, while five (including an additional tumor with H-ras oncogene revealed by PCR analysis) contained novel A to G transitions. The H-ras oncogene in one DMBA-treated HOG sample was activated by A to T while the second contained an A to G mutations, representative of both modes of mutational activation involved in this model of mammary tumorigenesis. In summary, DMBA-induced point mutated H-ras oncogenes appear to potentiate the progression of hyperplastic outgrowths (HOG) to mammary carcinomas.
Bcr and Abr Cooperate in Negatively Regulating Acute Inflammatory Responses (2009)

Bcr and Abr are GTPase-activating proteins for the small GTPase Rac. Both proteins are expressed in cells of the innate immune system, including neutrophils and macrophages. The function of Bcr has been linked to the negative regulation of neutrophil reactive oxygen species (ROS) production, but the function of Abr in the innate immune system was unknown. Here, we report that mice lacking both proteins are severely affected in two models of experimental endotoxemia, including exposure to Escherichia coli lipopolysaccharide and polymicrobial sepsis, with extensive microvascular leakage, resulting in severe pulmonary edema and hemorrhage. Additionally, in vivo-activated neutrophils of abr and bcr null mutant mice produced excessive tissue-damaging myeloperoxidase (MPO), elastase, and ROS. Moreover, the secretion of the tissue metalloproteinase MMP9 by monocytes and ROS by elicited macrophages was abnormally high. In comparison, ROS production from bone marrow monocytes was not significantly different from that of controls, and the exocytosis of neutrophil secondary and tertiary granule products, including lactoferrin, was normal. These data show that Abr and Bcr normally curb very specific functions of mature tissue innate immune cells, and that each protein has distinct as well as partly overlapping functions in the downregulation of inflammatory processes.
Diagnosis and treatment of diabetic neuropathy. (1999)

糖尿病性神経障害は,比較的早期より発症し,頻度も高く,突然死の一因として最近注目されている.死に至らないまでも,患者に与える苦痛は計り知れず,他の合併症に及ぼす影響も大きいのが糖尿病性神経障害である.しかし,その早期診断と適切な管理・治療は必ずしも確立された訳ではない.診断的には,自律神経障害が比較的早期から診断可能な報告が散見され,種々のアプローチがなされている.一方,管理・治療としては糖尿病性神経障害の危険因子の可能な限りの排除が大切で,最近高血圧が注目され,血糖コントロール同様に血圧コントロールの重要性が唱えられている.治療薬として,新しいAR阻害薬の開発が世界的に進行中であり, PKCβ阻害薬の有効性が動物実験的に確かめられ臨床治験が欧米を中心にはじまろうとしている.ここでは,新しい成績を混じえて,糖尿病性神経障害の診断と治療の現状を述べてみたい.
Genomic Insights into Marine Microalgae (2008)

Marine eukaryotic photosynthesis is dominated by a diverse group of unicellular organisms collectively called microalgae. Microalgae include cells derived from a primary endosymbiotic event (similar to land plants) and cells derived from subsequent secondary and/or tertiary endosymbiotic events. These latter cells are chimeras of several genomes and dominate primary production in the marine environment. Two consequences of multiple endosymbiotic events include complex targeting mechanisms to allow nuclear-encoded proteins to be imported into the plastid and coordination of enzymes, potentially from disparate originator cells, to form complete metabolic pathways. In this review, we discuss the forces that shaped the genomes of marine microalgae and then discuss some of the metabolic consequences of such a complex evolutionary history. We focus our metabolic discussion on carbon, nitrogen, and iron. We then discuss biomineralization and new evidence for programmed cell death in microalgae. We conclude with a short summary on advances in genetic manipulation of microalgae and thoughts on the future directions of marine algal genomics.
3D electromagnetic inversion using conjugate gradients (2002)

In large scale 3D EM inverse problems it may not be possible to directly invert a full least-squares system matrix involving model sensitivity elements. Thus iterative methods must be employed. For the inverse problem, the authors favor either a linear or nonlinear (NL) CG scheme, depending on the application. In a NL CG scheme, the gradient of the objective function is required at each relaxation step along with a univariate line search needed to determine the optimum model update. Solution examples based on both approaches are presented.
Crystal Structure of Pentalenene Synthase: Mechanistic Insights on Terpenoid Cyclization Reactions in Biology (1997)

The crystal structure of pentalenene synthase at 2.6 angstrom resolution reveals critical active site features responsible for the cyclization of farnesyl diphosphate into the tricyclic hydrocarbon pentalenene. Metal-triggered substrate ionization initiates catalysis, and the alpha-barrel active site serves as a template to channel and stabilize the conformations of reactive carbocation intermediates through a complex cyclization cascade. The core active site structure of the enzyme may be preserved among the greater family of terpenoid synthases, possibly implying divergence from a common ancestral synthase to satisfy biological requirements for increasingly diverse natural products.
Fluorescent Protein Voltage Probes Derived from ArcLight that Respond to Membrane Voltage Changes with Fast Kinetics (2013)

We previously reported the discovery of a fluorescent protein voltage probe, ArcLight, and its derivatives that exhibit large changes in fluorescence intensity in response to changes of plasma membrane voltage. ArcLight allows the reliable detection of single action potentials and sub-threshold activities in individual neurons and dendrites. The response kinetics of ArcLight (τ1-on ~10 ms, τ2-on ~ 50 ms) are comparable with most published genetically-encoded voltage probes. However, probes using voltage-sensing domains other than that from the Ciona intestinalis voltage sensitive phosphatase exhibit faster kinetics. Here we report new versions of ArcLight, in which the Ciona voltage-sensing domain was replaced with those from chicken, zebrafish, frog, mouse or human. We found that the chicken and zebrafish-based ArcLight exhibit faster kinetics, with a time constant (τ) less than 6 ms for a 100 mV depolarization. Although the response amplitude of these two probes (8-9%) is not as large as the Ciona-based ArcLight (~35%), they are better at reporting action potentials from cultured neurons at higher frequency. In contrast, probes based on frog, mouse and human voltage sensing domains were either slower than the Ciona-based ArcLight or had very small signals.
Diagnostic and prognostic importance of T-cell receptor gene analysis in patients with S�zary syndrome (2001)

TCR gene analysis defines a distinct clinicopathologic group of patients with SS. Clonal patients have a poor prognosis and are likely to die from leukemia/lymphoma, whereas nonclonal patients may have a reactive, inflammatory T-cell disorder. The authors suggest that the definitive diagnostic criteria for patients with SS should include the presence of a clonal TCR gene rearrangement.
Microarray analysis of the Bacillus subtilis K‐state: genome‐wide expression changes dependent on ComK (2002)

In Bacillus subtilis, the competence transcription factor ComK activates its own transcription as well as the transcription of genes that encode DNA transport proteins. ComK is expressed in about 10% of the cells in a culture grown to competence. Using DNA microarrays representing approximately 95% of the protein-coding open reading frames in B. subtilis, we compared the expression profiles of wild-type and comK strains, as well as of a mecA mutant (which produces active ComK in all the cells of the population) and a comK mecA double mutant. In these comparisons, we identified at least 165 genes that are upregulated by ComK and relatively few that are downregulated. The use of reporter fusions has confirmed these results for several genes. Many of the ComK-regulated genes are organized in clusters or operons, and 23 of these clusters are preceded by apparent ComK-box promoter motifs. In addition to those required for DNA uptake, other genes that are upregulated in the presence of ComK are probably involved in DNA repair and in the uptake and utilization of nutritional sources. From this and previous work, we conclude that the ComK regulon defines a growth-arrested state, distinct from sporulation, of which competence for genetic transformation is but one notable feature. We suggest that this is a unique adaptation to stress and that it be termed the 'K-state'.
Gene transfer of glutamic acid decarboxylase reduces neuropathic pain (2005)

We tested whether transfer of the gene coding for glutamic acid decarboxylase to dorsal root ganglion using a herpes simplex virus vector to achieve release of GABA in dorsal horn would attenuate nociception in this condition. Subcutaneous inoculation of a replication-defective herpes simplex virus vector expressing glutamic acid decarboxylase (vector QHGAD67) 7 days after selective L5 spinal nerve ligation reversed mechanical allodynia and thermal hyperalgesia; the antiallodynic effect lasted 6 weeks and was reestablished by reinoculation. QHGAD67 inoculation also suppressed induction of c-Fos and phosphorylated extracellular signal-regulated kinase 1 and 2 in the spinal cord.
APSK Constellation with Gray Mapping (2011)

Amplitude phase shift keying (APSK) constellation is superior to its quadrature amplitude modulation (QAM) counterpart from the mutual information point of view. However, due to the lack of Gray mapping, it introduces high independent demapping loss. In this letter, a special kind of APSK constellations with Gray mapping (Gray-APSK) is proposed, which provides considerable shaping gain compared with the QAM constellations with Gray mapping (Gray-QAM) in both independent and iterative demapping scenarios, as verified by average mutual information analysis and bit error rate simulations.
Clinical toxicity of interferons in cancer patients: a review. (1986)

All major types of human interferons (IFNs) have been purified and clinically administered as antitumor agents. We summarize here experience to date with toxicity of IFNs in cancer patients. The acute syndrome consists of fever, chills, myalgias, arthralgias, and headache, with some variation according to type of IFN, route of administration, schedule, and dose. Fatigue, perhaps reflecting CNS toxicity, is the most prevalent nonacute symptom. At high doses, IFNs are neurotoxic; the abnormalities seen by EEG resemble those in diffuse encephalitis. Hematologic toxicity consists mainly of leukopenia, but anemia and thrombocytopenia occur in some patients. Nausea, vomiting, and diarrhea are the main gastrointestinal symptoms. Elevation of serum transaminases seems to reflect liver toxicity. Renal function is well preserved, except for rare instances of acute renal failure. Cardiac toxicity remains questionable, although heart failure and arrhythmias have been associated with the administration of IFNs. Most, if not all, of these effects are reversible or can be ameliorated. With IFN alpha, the type most widely used in clinical studies, doses of 1 million to 9 million units (MU) are generally well tolerated, but doses greater than or equal to 18 MU yield moderate to severe toxicity. Doses greater than or equal to 36 MU can induce severe toxicity and significantly alter the performance status of the patient.
Bronchioloalveolar lung CTCs retain cytomorphologic features of primary tumor type (2008)

19118 Background: Circulating tumor cell (CTC) detection and enumeration could provide a valuable tool for identifying patients at a lower risk of recurrence, determining prognosis, and aiding clinicians with individualized treatment strategies. Detailed morphologic review of CTCs and comparison with cells from the primary tumor are conducted on a case of progressive bronchoalveolar carcinoma. Methods: 10cc of blood was drawn from a non-smoking 47 year old female initially diagnosed with stage IIIB NSCL cancer in 2003. She was initially treated with concurrent chemoradiation followed by consolidative Taxotere, but recurred locally in Jan 2005. She subsequently received multiple agents secondary to progression. In an Oct 07 sample, 67 CTCs were identified by means of an immunoflorescence staining protocol and fiber-optic array scanning technology. CTC verification involved cytokeratin and DAPI positivity and CD45 negativity as criteria. Fluorescent images were taken before a Wright-Giemsa stain was applied to visualize cytologic details of each CTC. Results: This patient’s CTCs are larger than surrounding WBCs, with low-to-moderate nuclear/cytoplasmic ratios and a generous cytoplasmic domain. The cells often appear as doublets and clusters. In comparison to the cells of the patient’s original lung biopsy by FNA, which revealed a well-differentiated bronchoalveolar type carcinoma, the CTCs retain the morphologic features of very large size in comparison to WBCs and low N/C ratio generated by a voluminous cytoplasmic domain. Conclusions: The striking cytomorphologic difference between the CTCs in this patient with a progressive but well-differentiated adenocarcinoma, versus previously studied patients with less well-differentiated tumors of breast and colon, suggests that cytomorphologic features of tumors are retained when cells enter the bloodstream. The comparison images demonstrate the differences between CTCs of a breast cancer (cuboidal cells in tissue, round high N/C ratio cells in circulation), a colon cancer (columnar cells in tissue, elongated cells with eccentric cytoplasm in circulation), and this well-differentiated lung cancer (moderate to low N/C ratio cells in tissue, moderate to low N/C ratios in circulation). No significant financial relationships to disclose.
Quantitative real time PCR for the measurement of white spot syndrome virus in shrimp (2002)

Quantitative real time PCR, recently developed in molecular biology, is applied in this paper to quantify the white spot syndrome virus (WSSV) in infected shrimp tissue. The WSSV content in moribund shrimp of all species tested ( Penaeus stylirostris, P. monodon, P. vannamei ) ranged from 2.0 × 10 4 to 9.0 × 10 10 WSSV copies μg –1 of total DNA ( n =26). In whole moribund post‐larvae, 4.3 × 10 9 WSSV copies μg –1 of DNA were detected which is equivalent to 5.7 × 10 10 WSSV copies g –1 of post‐larvae. The comparison of WSSV content between different tissues showed that muscle and hepatopancreas tissues contained 10 times less virus than gills, pleopods and haemolymph. With inocula of known virus content, bioassays by immersion challenge showed that a minimum of five logs of WSSV copies was necessary to establish disease in the challenged shrimp. In contrast, five logs of WSSV copies injected into shrimp muscle produced a LT‐50 of 52 h. This real time polymerase chain reaction (PCR) technique is sensitive (four copies), specific (negative with DNA from shrimp baculoviruses and parvoviruses), dynamic (seven logs) and easy to perform (96 tests in &lt;4 h).
Estradiol Administration Improves Splanchnic Perfusion Following Trauma-Hemorrhage and Sepsis (2002)

The increase in gut perfusion could represent a potential mechanism for the salutary effects of 17beta-estradiol following trauma-hemorrhage. Because 17beta-estradiol improves systemic and intestinal perfusion after trauma-hemorrhage and induction of subsequent sepsis, this agent appears to be a promising adjunct for the treatment of trauma victims.
A MUC1 tandem repeat reporter protein produced in CHO-K1 cells has sialylated core 1 O-glycans and becomes more densely glycosylated if coexpressed with polypeptide-GalNAc-T4 transferase (2004)

A recombinant mucin O-glycosylation reporter protein, containing 1.7 tandem repeats (TRs) from the transmembrane mucin MUC1, was constructed. The reporter protein, MUC1(1.7TR)-IgG2a, was produced in CHO-K1 cells to study the glycosylation of the MUC1 TR and the in vivo role of polypeptide-GalNAc-T4 glycosyltransferase. N-terminal sequencing of MUC1(1.7TR)-IgG2a showed that all five potential O-glycosylation sites within the TR were used, with an average density of 4.5 glycans per repeat. The least occupied site was Thr in the PDTR motif, where 75% of the molecules were glycosylated, compared to 88-97% at the other sites. This glycan density was confirmed by an alternative liquid chromatography-mass spectrometry (LC-MS) based approach. The O-linked oligosaccharides were released from MUC1(1.7TR)-IgG2a and analyzed by nano-LC-MS and LC-MS/MS. Four oligosaccharides were present, NeuAcalpha2-3Galbeta1-3GalNAcol, NeuAcalpha2-3Galbeta1-3(NeuAcalpha2-6)GalNAcol, Galbeta1-3(NeuAcalpha2-6)GalNAcol, and Galbeta1-3GalNAcol, the two first being most abundant. Coexpression of the human polypeptide-GalNAc-T4 transferase with MUC1(1.7TR)-IgG2a increased the glycan occupancy at Thr in PDTR, Ser in VTSA, and Ser in GSTA, supporting the function of GalNAc-T4 proposed from previous in vitro studies. The expression of GalNAc-T4 with a mutation in the first lectin domain (alpha) had no glycosylation effect on PDTR and GSTA but surprisingly gave a dominant negative effect with a decreased glycosylation to around 50% at the Ser in VTSA. The results show that introduction of glycosyltransferases can specifically alter the sites for O-glycosylation in vivo.
A novel lateral bipolar transistor with 67 GHz f/sub max/ on thin-film SOI for RF analog applications (2000)

In this paper, a novel lateral bipolar transistor on thin film silicon-on-insulator (SOI) is presented. With a small emitter size of 0.12/spl times/3.0 /spl mu/m/sup 2/, low base resistance of 270 /spl Omega/ due to a novel Co silicided base electrode and low base-collector parasitic capacitances of 1.4 fF due to SOI material, it achieves the highest f/sub max/ of 67 GHz among SOI bipolar transistors. Also, the low emitter-base capacitance of 1.5 fF and the low collector-substrate capacitance of 2.5 fF are realized. The transistor has a simple structure, which is fabricated with simplified processes without any new sophisticated technologies, excluding trench isolation and epitaxial base used in current bipolar transistors. This can lower the fabrication cost of transistors. We have demonstrated the possibility of lateral bipolar transistor on thin film SOI as next-generation device for RF analog applications.
Novel Potent Orally Active Selective VEGFR-2 Tyrosine Kinase Inhibitors:  Synthesis, Structure−Activity Relationships, and Antitumor Activities of N-Phenyl-N‘-{4-(4-quinolyloxy)phenyl}ureas (2005)

N-Phenyl-N'-{4-(4-quinolyloxy)phenyl}ureas were found to be a novel class of potent inhibitors for the vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase through synthetic modifications of a lead compound and structure-activity relationship studies. A representative compound 6ab, termed Ki8751, inhibited VEGFR-2 phosphorylation at an IC(50) value of 0.90 nM, and also inhibited the PDGFR family members such as PDGFRalpha and c-Kit at 67 nM and 40 nM, respectively. However, 6ab did not have any inhibitory activity against other kinases such as EGFR, HGFR, InsulinR and others even at 10000 nM. 6ab suppressed the growth of the VEGF-stimulated human umbilical vein endothelial cell (HUVEC) on a nanomolar level. 6ab showed significant antitumor activity against five human tumor xenografts such as GL07 (glioma), St-4 (stomach carcinoma), LC6 (lung carcinoma), DLD-1 (colon carcinoma) and A375 (melanoma) in nude mice and also showed complete tumor growth inhibition with the LC-6 xenograft in nude rats following oral administration once a day for 14 days at 5 mg/kg without any body weight loss.
Role of Interleukin-17 and the Neutrophil in Asthma (2001)

Recent clinical evidence shows that acute, severe exacerbations of asthma are associated with recruitment and activation of neutrophils in the airways. There is also experimental evidence from rodents that T-lymphocytes are involved in the recruitment of neutrophils following allergen challenge in sensitised airways. This review addresses the potential role of neutrophils and the cytokine interleukin-17 (IL-17) in severe asthma. IL-17 is produced and released as a free protein from T-lymphocytes of the memory (CD45RO+) subset. Evidence from rats in vivo suggests that IL-17 can recruit and activate neutrophils in the airways; the recruitment is mediated by the rat correlate to the neutrophil chemoattractant interleukin-8 (IL-8) macrophage inflammatory protein-2 (MIP-2). Endogenous peptidases modulate neutrophil recruitment by acting on NK-1 receptors in rat airways in vivo. Human bronchial epithelial cells in vitro respond to stimulation with IL-17 by increasing the production and release of the human neutrophil chemoattractant IL-8. This release of IL-8 is functionally significant; it causes neutrophil chemotaxis in vitro. Furthermore, this IL-8 release is sensitive to a glucocorticoid and is potentiated by the pro-inflammatory cytokine, tumour necrosis factor-alpha (TNF-alpha) in vitro. In addition, IL-17 stimulates human bronchial epithelial cells in vitro to release the neutrophil-activating factor IL-6. This effect of IL-17 on IL-6, and IL-8 is in part mediated via mitogen-activated protein kinases. In conclusion, as indicated in rat airways in vivo and in human bronchial epithelial cells in vitro, IL-17 may constitute a link between the activation of certain T-lymphocytes and mobilisation of neutrophils in the airways, via induced release of C-X-C chemokines and tachykinins. Further studies are required to answer the question whether free, soluble IL-17 protein plays this role in the airways of patients with severe asthma.