gebhart/patrepeval huggingface dataset:
Involvement ofgacSandrpoSin enhancement of the plant growth-promoting capabilities ofEnterobacter cloacaeCAL2 and UW4 (2001)

The plant growth-promoting bacteria Enterobacter cloacae CAL2 and UW4 were genetically transformed with a multicopy plasmid containing an rpoS or gacS gene from Pseudomonas fluorescens. The transformed strains were compared with the nontransformed strains for growth, indoleacetic acid (IAA) production, antibiotic production, 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase activity, siderophore production, cell morphology, and the ability to promote canola root elongation. All transformed strains had a longer lag phase, were slower in reaching stationary phase, and attained a higher cell density than the nontransformed strains. Transformation resulted in cells that were significantly shorter than the nontransformed cells. The transformed strains also produced significantly more IAA than the nontransformed strains. Introduction of rpoS or gacS from Pseudomonas fluorescens was associated with a reduction in the production of both antibiotics, 2,4-diacetylphloroglucinol and mono-acetylphloroglucinol, produced by Enterobacter cloacae CAL2. With Enterobacter cloacae CAL2, plasmid-borne rpoS, but not gacS, increased the level of ACC deaminase activity, while introduction of rpoS in Enterobacter cloacae UW4 caused a decrease in ACC deaminase activity. Neither gacS nor rpoS significantly affected the level of siderophores synthesized by either bacterial strain. Overproduction of either GacA or RpoS in Enterobacter cloacae CAL2 resulted in a significant increase in the root lengths of canola seedlings when seeds were treated with the bacteria, and overproduction of RpoS caused an increase in canola shoot as well as root lengths.
Comparison of real-time virtual and fiberoptic bronchoscopy in patients with bronchial carcinoma: opportunities and limitations. (1997)

Virtual bronchoscopy represents a new noninvasive method for evaluating helical CT findings. In comparison with fiberoptic bronchoscopy, virtual bronchoscopy offers the advantage of being able to visualize areas beyond even high-grade stenoses. In addition to the limited view of fiberoptic bronchoscopy, extraluminal causes of lumen compressions can be analyzed in the cross-sectional images and evaluated together with the virtual representation. However, it was not possible to detect small infiltrations with virtual bronchoscopy. This new representation of helical CT data might be helpful for postoperative follow-up examinations, such as after stent implantation, and can be carried out without additional risk to the patient. Radiologists do need special fiberoptic bronchoscopy knowledge and experience with three-dimensional-reconstructions to differentiate between real stenoses and artificial stenoses that might be caused by pulsation artifacts.
Novel Potent BRAF Inhibitors: Toward 1 nM Compounds through Optimization of the Central Phenyl Ring (2009)

BRAF, a serine/threonine specific protein kinase that is part of the MAPK pathway and acts as a downstream effector of RAS, is a potential therapeutic target in melanoma. We have developed a series of small-molecule BRAF inhibitors based on a 1H-imidazo[4,5-b]pyridine-2(3H)-one scaffold (ring A) as the hinge binding moiety and a number of substituted phenyl rings C that interact with the allosteric binding site. The introduction of various groups on the central phenyl ring B combined with appropriate A- and C-ring modifications afford very potent compounds that inhibit (V600E)BRAF kinase activity in vitro and oncogenic BRAF signaling in melanoma cells. Substitution on the central phenyl ring of a 3-fluoro, a naphthyl, or a 3-thiomethyl group improves activity to yield compounds with an IC(50) of 1 nM for purified (V600E)BRAF and nanomolar activity in cells.
A new adenoviral helper–dependent vector results in long-term therapeutic levels of human coagulation factor IX at low doses in vivo (2002)

We have developed a new helper-dependent (HD) adenoviral vector FTC that contains 3 cis-acting sequences as stuffer DNA: a human fragment of alphoid repeat DNA, matrix-attachment regions (MARs), and the hepatocyte control region enhancer. To determine the most robust human coagulation factor IX (hFIX) expression cassette in an adenovirus, we first tested different hFIX expression sequences with or without flanking MARs in first-generation adenoviral vectors. After intravenous infusion of the vector, serum levels of up to 100 000 ng/mL hFIX (normal level, 5000 ng/mL) were obtained at nontoxic doses. In order to make a direct comparison, a first-generation and a gene-deleted vector with identical hFIX expression cassettes were constructed. Both first-generation and HD adenovirus-treated animals demonstrated a threshold effect in a dose-response study. With the administration of 2 x 10(9) transducing particles of either vector, supraphysiological serum levels of hFIX were obtained, with the highest expression (41 000 ng/mL) occurring during the first 2 months after injection. The serum factor IX concentrations, while remaining in the therapeutic range, slowly declined by 95% over a period of 1 year. At this dose, interleukin-6 and tumor necrosis factor-alpha serum concentrations were elevated in animals that received the first-generation but not the HD vector. This study compares the properties of a gene-deleted and first-generation adenovirus with equivalent expression cassettes and suggests that the cis-DNA elements contained in the vector and expression cassette have important effects on gene expression in vivo.
Early gut colonizers shape parasite susceptibility and microbiota composition in honey bee workers (2016)

Microbial symbionts living within animal guts are largely composed of resident bacterial species, forming communities that often provide benefits to the host. Gut microbiomes of adult honey bees (Apis mellifera) include core residents such as the betaproteobacterium Snodgrassella alvi, alongside transient parasites such as the protozoan Lotmaria passim To test how these species affect microbiome composition and host physiology, we administered S alvi and/or L passim inocula to newly emerged worker bees from four genetic backgrounds (GH) and reared them in normal (within hives) or stressed (protein-deficient, asocial) conditions. Microbiota acquired by normal bees were abundant but quantitatively differed across treatments, indicating treatment-associated dysbiosis. Pretreatment with S. alvi made normal bees more susceptible to L. passim and altered developmental and detoxification gene expression. Stressed bees were more susceptible to L. passim and were depauperate in core microbiota, yet supplementation with S. alvi did not alter this susceptibility. Microbiomes were generally more variable by GH in stressed bees, which also showed opposing and comparatively reduced modulation of gene expression responses to treatments compared with normal bees. These data provide experimental support for a link between altered gut microbiota and increased parasite and pathogen prevalence, as observed from honey bee colony collapse disorder.
Mpl: from an acute myeloproliferative virus to the isolation of the long sought thrombopoietin. (1998)

Mpl, the receptor for thrombopoietin (TPO), was isolated as a cellular sequence transduced by a new acute myeloproliferative virus. Human and murine c-mpl were subsequently cloned and Mpl was identified as a member of the growth factor receptor superfamily. For a time, Mpl remained an orphan receptor. Engineering of cell lines expressing c-mpl provided a sensitive tool for detecting the ligand of Mpl, and led to the molecular cloning of TPO, the long sought proliferation and differentiation factor for the megakaryocytic lineage. Afterwards, signal transduction by Mpl was studied, and the functional elements of the cytoplasmic domain responsible for cell proliferation and differentiation were identified. When studied in various human hematologic malignancies, Mpl expression was shown to be increased in 50% of the patients with acute myeloblastic leukemia (AML). In vitro treatment of AML cells by TPO led to proliferation, suggesting that TPO could contribute, at least in part, to abnormal growth of AML cells. A tremendous number of studies have followed the isolation of TPO, and have shown that TPO is the primary regulator of physiological platelet production. However, roles for Mpl and TPO in other lineages, especially in erythroid and immature hematopoietic progenitors, have also emerged from these studies.
Methods in Yeast Genetics: A Laboratory Course Manual (1990)

An intensive course in yeast genetics has been held at Cold Spring Harbor Laboratory for some years, and the course manual reflects its content and scope.
Cullin 1 Functions as a Centrosomal Suppressor of Centriole Multiplication by Regulating Polo-like Kinase 4 Protein Levels (2009)

Abnormal centrosome and centriole numbers are frequently detected in tumor cells where they can contribute to mitotic aberrations that cause chromosome missegregation and aneuploidy. The molecular mechanisms of centriole overduplication in malignant cells, however, are poorly characterized. Here, we show that the core SKP1-cullin-F-box component cullin 1 (CUL1) localizes to maternal centrioles and that CUL1 is critical for suppressing centriole overduplication through multiplication, a recently discovered mechanism whereby multiple daughter centrioles form concurrently at single maternal centrioles. We found that this activity of CUL1 involves the degradation of Polo-like kinase 4 (PLK4) at maternal centrioles. PLK4 is required for centriole duplication and strongly stimulates centriole multiplication when aberrantly expressed. We found that CUL1 is critical for the degradation of active PLK4 following deregulation of cyclin E/cyclin-dependent kinase 2 activity, as is frequently observed in human cancer cells, as well as for baseline PLK4 protein stability. Collectively, our results suggest that CUL1 may function as a tumor suppressor by regulating PLK4 protein levels and thereby restraining excessive daughter centriole formation at maternal centrioles.
High‐Temperature/Field Alternating‐Current Behavior of ZnO‐Based Varistors (1988)

The ac electrical response of the grain boundary in the ZnO–Bi 2 O 3 ‐based varistor system (in the frequency range 10 −2 ≤f≤10 7 Hz) has been analyzed using complex plane analysis techniques as a function of temperature (90°≤T≤150°C) and electric field (E 60%lmA/cm2 ≤E≤E lmA/cm2 ). The high‐temperature/field data were best represented in the impedance plane. The lumped parameter equivalent circuit representation, containing a voltage variable resistive element associated with the grain boundary, was in agreement with a model previously reported in the literature. The resulting equivalent circuit representation of the grain‐boundary response consisting of a resistance and a capacitance are interpreted in terms of various phenomena occurring at the electrical thickness of the grain boundary.
Marathon evaluation of optical materials for 157-nm lithography<xref ref-type="fn" rid="FN1">*</xref> (2003)

We present the methodology and recent results on the long-term evaluation of optical materials for 157-nm lithographic applications. We review the unique metrology capabilities that have been developed for accurately assessing optical properties of samples both online and offline, utilizing VUV spectrophotometry with in situ lamp-based cleaning. We describe ultraclean marathon testing chambers that have been designed to decouple effects of intrinsic material degradation from extrinsic ambient effects. We review our experience with lithography-grade 157-nm lasers and detector durability. We review the current status of bulk materials for lenses, such as CaF2 and BaF2, and durability results of antireflectance coatings. Finally, we discuss the current state of laser durability of organic pellicles.
Characterization of Influenza Virus NS1 Protein by Using a Novel Helper-Virus-Free Reverse Genetic System (2000)

ABSTRACT We have developed a novel helper-virus-free reverse genetic system to genetically manipulate influenza A viruses. The RNPs, which were purified from the influenza A/WSN/33 (WSN) virus, were treated with RNase H in the presence of NS (nonstructural) cDNA fragments. This specifically digested the NS RNP. The NS-digested RNPs thus obtained were transfected into cells together with the in vitro-reconstituted NS RNP. The NS-digested RNPs alone did not rescue viruses; however, cotransfection with the NS RNP did. This protocol was also used to rescue the NP transfectant. We obtained two NS1 mutants, dl 12 and N110, using this protocol. The dl 12 NS gene contains a deletion of 12 amino acids at positions 66 to 77 near the N terminus. This virus was temperature sensitive in Madin-Darby bovine kidney (MDBK) cells as well as in Vero cells. The translation of all viral proteins as well as cellular proteins was significantly disrupted during a later time of infection at the nonpermissive temperature of 39°C. The N110 mutant consists of 110 amino acids which are the N-terminal 48% of the WSN virus NS1 protein. Growth of this virus was significantly reduced at any temperature. In the virus-infected cells, translation of the M1 protein was reduced to 10 to 20% of that of the wild-type virus; however, the translation of neither the nucleoprotein nor NS1 was significantly interfered with, indicating the important role of NS1 in translational stimulation of the M1 protein.
Staging of lymph nodes with FDG dual-headed PET in patients with non-small-cell lung cancer (1999)

Accurate assessment of mediastinal lymph node involvement in patients with non-small-cell lung cancer (NSCLC) is necessary to select patients for direct surgical treatment. The aims of the present study were to assess the feasibility of staging NSCLC with FDG using a dual-headed positron emission tomographic (PET) camera and to compare this non-invasive technique with computed tomography (CT) and lymph node sampling, since both modalities are currently used for staging NSCLC. Thirty-three patients (29 men and 4 women, mean age 60 years) with newly diagnosed NSCLC were studied. In all patients, CT, FDG dual-headed PET and mediastinoscopy were performed within 4 weeks. The results of mediastinoscopy were used to select patients for thoracotomy. For both the assessment of individual lymph node involvement and the patient-based classification, the results of FDG dual-headed PET and CT were compared using the McNemar test. Thirty-one of 187 lymph nodes studied contained tumour metastases. FDG dual-headed PET showed a significantly higher sensitivity (P < 0.001) and specificity (P < 0.001) than CT. FDG dual-headed PET and CT correctly staged 27 and 20 patients, respectively. Due to the significantly higher negative predictive value of FDG dual-headed PET versus CT (P = 0.012), it was a better non-invasive diagnostic tool for selecting patients for surgery. In seven of eight patients, additional intrapulmonary sites of increased uptake were found, which revealed malignancy on histological examination. CT was false-negative in three of these patients. In one patients, increased FDG uptake was caused by an infection. In conclusion, it is possible to stage mediastinal lymph nodes in patients with NSCLC using a dual-headed PET camera. The high negative predictive value of FDG dual-headed PET suggests that mediastinoscopy may be omitted in patients with NSCLC.
Collagen-Related Peptides:  Self-Assembly of Short, Single Strands into a Functional Biomaterial of Micrometer Scale (2007)

We have designed, synthesized, and characterized a short (32-mer; 8-nm), single-stranded, collagen-related peptide (CRP), 1a, which forms triple-helical building blocks that self-assemble into large, composite fibrils by strictly noncovalent means. Computational analysis suggested that the installation of complementary, aromatic π-stacking recognition elements at the N- and C-termini of (Gly-Pro-Hyp)10 would facilitate the head-to-tail assembly of triple-helical subunits. Our CD, 1H NMR, DLS, and TEM results for 1a support the formation of such triple-helical, supramolecular structures. Consistent with self-assembly into micrometer-size, composite fibrils, 1a induced the aggregation of human platelets with nearly the same potency as native Type I collagen. The aromatic−aromatic recognition motif employed in this study provides a straightforward approach to collagen-mimetics and has important implications for the design of triple-helical building blocks that can spontaneously oligomerize into functional fibrillar structures.
Characterization of hemadsorption-negative mutants of Mycoplasma pneumoniae (1981)

Previously isolated mutants of Mycoplasma pneumoniae incapable of hemadsorption were characterized with respect to specific protein content, tracheal ring attachment capability, and virulence for both in vitro and in vivo model systems. Two-dimensional gel electrophoresis revealed both quantitative and qualitative differences between the protein complements of two different mutant strains and that of the virulent parent strain. Studies of mycoplasma attachment to hamster tracheal rings in vitro demonstrated that only one of these mutant strains still possessed the ability to attach to the respiratory epithelium via neuraminidase-sensitive receptors. Measurement of [3H]orotic acid uptake in mycoplasma-infected tracheal rings indicated that infection with the hemadsorption-negative mutants resulted in only slight reductions of ribonucleic acid synthesis, similar to levels observed for tracheal rings infected with an avirulent strain of M. pneumoniae. The virulence potential of the two mutant strains was further investigated by utilizing the hamster model system. Both mutant strains were rapidly cleared from the lungs of infected animals and produced little or no microscopic pneumonia.
Human papillomavirus type 16-immortalized endocervical cells selected for resistance to cisplatin are malignantly transformed and have a multidrug resistance phenotype (2000)

Cis-diamminedichloroplatinum (II) (cisplatin, CDDP) is a highly effective chemotherapeutic agent against cervical cancer, but drug resistance is a major obstacle in its clinical application. The mechanism of drug resistance in human cervical cancer is not well understood. Here, we established an in vitro endocervical, cisplatin-resistant cell system that mimics the development of cisplatin resistance in the human cervix. Human papillomavirus (HPV) type 16-immortalized human endocervical cells (HEN-16-2) were treated with cisplatin, and the cisplatin-selected cells (HEN-16-2/CDDP) were resistant to cisplatin, paclitaxel, actinomycin D, doxorubicin, etoposide, and 5-fluorouracil, thus demonstrating a multidrug resistance (MDR) phenotype. Furthermore, compared with a similar passage of drug-sensitive HEN-16-2 cells, HEN-16-2/CDDP cells exhibited the general growth characteristics of cancer cell lines: faster growth in medium containing serum and high calcium levels, higher saturation density, anchorage-independent growth, and formation of tumors in nude mice. These results provided the first in vitro evidence that cisplatin selection can transform HPV-immortalized endocervical cells and cause a phenotype of MDR.
Human Fas ligand: gene structure, chromosomal location and species specificity (1994)

Fas ligand (FasL) is a 40 kDa type II membrane protein belonging to the tumor necrosis factor family, which induces apoptosis by binding to its receptor, Fas. In this report, we isolated the chromosomal gene for human FasL. The human FasL gene consists of approximately 8.0 kb and is split into four exons. The human FasL gene was mapped on chromosome 1q23 by in situ hybridization against human metaphase chromosomes. Human FasL cDNA was isolated by the reverse polymerase chain reaction of mRNA prepared from human activated peripheral blood lymphocytes. Human FasL is a type II membrane protein consisting of 281 amino acids with a calculated M(r) of 31,759. It has an identity of 76.9% at the amino acid sequence level with mouse FasL. Both human and mouse recombinant FasL expressed in COS induced apoptosis in the cells expressing either human Fas or mouse Fas, indicating that FasL fully cross-reacts between human and mouse. A comparison of human and mouse FasL chromosomal genes indicated that a approximately 300 bp sequence upstream of the ATG initiation codon is highly conserved between them. Several transcription cis-regulatory elements such as SP-1, NF-kappa B and IRF-1 were recognized in this region.
Adipose-specific disruption of autotaxin enhances nutritional fattening and reduces plasma lysophosphatidic acid (2011)

Autotaxin (ATX) is a secreted lysophospholipase D that generates the lipid mediator lysophosphatidic acid (LPA). ATX is secreted by adipose tissue and its expression is enhanced in obese/insulin-resistant individuals. Here, we analyzed the specific contribution of adipose-ATX to fat expansion associated with nutritional obesity and its consequences on plasma LPA levels. We established ATX(F/F)/aP2-Cre (FATX-KO) transgenic mice carrying a null ATX allele specifically in adipose tissue. FATX-KO mice and their control littermates were fed either a normal or a high-fat diet (HFD) (45% fat) for 13 weeks. FATX-KO mice showed a strong decrease (up to 90%) in ATX expression in white and brown adipose tissue, but not in other ATX-expressing organs. This was associated with a 38% reduction in plasma LPA levels. When fed an HFD, FATX-KO mice showed a higher fat mass and a higher adipocyte size than control mice although food intake was unchanged. This was associated with increased expression of peroxisome proliferator-activated receptor (PPAR)γ2 and of PPAR-sensitive genes (aP2, adiponectin, leptin, glut-1) in subcutaneous white adipose tissue, as well as in an increased tolerance to glucose. These results show that adipose-ATX is a negative regulator of fat mass expansion in response to an HFD and contributes to plasma LPA levels.
Comparative efficacy of switching to natalizumab in active multiple sclerosis (2015)

Using large, real-world, propensity-matched datasets we demonstrate that after a relapse on IFNβ or GA, switching to natalizumab (rather than between IFNβ and GA) led to superior outcomes for patients in all measures assessed. Results were consistent regardless of the prior treatment identity.
Straight-Forward Versus Anatomic Trajectory Technique of Thoracic Pedicle Screw Fixation: A Biomechanical Analysis (2003)

The straight-forward technique results in a 39% increase in maximum insertional torque and a 27% increase in pullout strength compared to the anatomic technique. The maximum insertional torque at the neurocentral junction resulted in a 36% increase using the straight-forward technique versus the anatomic trajectory. Bone mineral density directly correlates with pullout strength for both techniques.