gebhart/patrepeval huggingface dataset:
Recombinant adenylate cyclase toxin of Bordetella pertussis induces cytotoxic T lymphocyte responses against HLA*0201-restricted melanoma epitopes (2003)

The adenylate cyclase (CyaA) of Bordetella pertussis is able to deliver CD8(+) T cell epitopes into the cytosol of CD11b(+) dendritic cells (DC) following its specific interaction with the alpha(M)beta(2) integrin (CD11b/CD18). This delivery results in intracellular processing and presentation by MHC class I molecules of the CD8(+) T cell epitopes inserted into CyaA. Indeed, we previously showed that CyaA toxins carrying a single cytotoxic T lymphocyte (CTL) epitope can induce efficient protective and therapeutic antitumor immunity in mice. With a view to elaborating cancer immunotherapy in humans using CyaA, we constructed two recombinant CyaA carrying HLA*0201-restricted melanoma epitopes. Here we show that these recombinant CyaA induce strong anti-melanoma CTL responses in HLA*0201 transgenic mice, even after a single i.v. immunization without adjuvant. These responses are long lasting, since they were also detected 5 months after the last injection. Finally, human DC treated with the recombinant CyaA were shown to process and present efficiently the melanoma epitopes to human CTL clones. Altogether, our results demonstrate that tumoral epitopes inserted into CyaA are efficiently processed and presented in association with human MHC molecules. These observations suggest that CyaA is capable of activating antitumoral CTL in humans and highlight the potential of CyaA for use in cancer immunotherapy.
Comparison of Binax Legionella Urinary Antigen EIA kit with Binax RIA Urinary Antigen kit for detection of Legionella pneumophila serogroup 1 antigen (1996)

The Legionella Urinary Antigen EIA kit (Binax, Portland, Maine) was compared with the EQUATE RIA Legionella Urinary Antigen kit (Binax) for its ability to detect the presence of urinary antigens to Legionella pneumophila serogroup 1. Urine specimens from patients without Legionnaires' disease (n = 33) were negative by both methods (specificity, 100%). Twenty (77%) of 26 urine specimens from patients with Legionnaires' disease positive by the radioimmunoassay kit were also positive by the enzyme immunoassay (EIA) kit. If the cutoff for a positive EIA result were lowered to a ration of > or = 2.5, 23 of 26 (88%) urine specimens would have been positive by EIA and the specificity would remain 100%. Use of the EIA kit is an acceptable method for detecting L. pneumophila serogroup 1 urinary antigens by laboratories that do not want to handle radioactive materials.
Steiner tree problems (1992)

Abstract We give a survey up to 1989 on the Steiner tree problems which include the four important cases of euclidean, rectilinear, graphic, phylogenetic and some of their generalizations. We also provide a rather comprehensive and up‐to‐date bibliography which covers more than three hundred items.
A fibronectin scaffold approach to bispecific inhibitors of epidermal growth factor receptor and insulin-like growth factor-I receptor (2011)

Engineered domains of human fibronectin (Adnectins™) were used to generate a bispecific Adnectin targeting epidermal growth factor receptor (EGFR) and insulin-like growth factor-I receptor (IGF-IR), two transmembrane receptors that mediate proliferative and survival cell signaling in cancer. Single-domain Adnectins that specifically bind EGFR or IGF-IR were generated using mRNA display with a library containing as many as 10 ( 13) Adnectin variants. mRNA display was also used to optimize lead Adnectin affinities, resulting in clones that inhibited EGFR phosphorylation at 7 to 38 nM compared to 2.6 μM for the parental clone. Individual, optimized, Adnectins specific for blocking either EGFR or IGF-IR signaling were engineered into a single protein (EI-Tandem Adnectin). The EI-Tandems inhibited phosphorylation of EGFR and IGF-IR, induced receptor degradation, and inhibited down-stream cell signaling and proliferation of human cancer cell lines (A431, H292, BxPC3 and RH41) with IC 50 values ranging from 0.1 to 113 nM. Although Adnectins bound to EGFR at a site distinct from those of anti-EGFR antibodies cetuximab, panitumumab and nimotuzumab, like the antibodies, the anti-EGFR Adnectins blocked the binding of EGF to EGFR. PEGylated EI-Tandem inhibited the growth of both EGFR and IGF-IR driven human tumor xenografts, induced degradation of EGFR, and reduced EGFR phosphorylation in tumors. These results demonstrate efficient engineering of bispecific Adnectins with high potency and desired specificity. The bispecificity may improve biological activity compared to monospecific biologics as tumor growth is driven by multiple growth factors. Our results illustrate a technological advancement for constructing multi-specific biologics in cancer therapy.
Efficacy And Tolerability Of The Neuraminidase Inhibitor Zanamivir (2001)

Until recently, management options for influenza were limited to vaccination and use of the M2 inhibitors amantadine or rimantadine. Increased insight into the mechanisms of influenza virus replication combined with advances in the science of rational drug design have resulted in the development of the neuraminidase inhibitors, a new class of medicines that promise significantly to impact the management of influenza. The neuraminidase inhibitor zanamivir is the first antiviral specifically developed to combat both influenza A and influenza B viruses. The efficacy and tolerability of zanamivir have been established in an extensive program of double-blind, placebo-controlled trials conducted at study sites throughout the world. Zanamivir rapidly and effectively alleviated influenza symptoms regardless of patients' age or clinical characteristics. In clinical trials involving more than 4000 patients and in usual clinical practice involving tens of thousands more to date, no zanamivir-resistant viruses have been isolated. Adverse event data collected during Phase II and Phase III clinical trials of zanamivir in the treatment of influenza show that it has favorable tolerability, a feature that distinguishes it from other antiviral therapies for influenza. An important tool for the management of influenza, zanamivir will help health care practitioners to reduce the clinical, economic, and humanistic impacts of this disease.
Isolation and Characterization of the Diatom Phaeodactylum Δ5-Elongase Gene for Transgenic LC-PUFA Production in Pichia pastoris (2014)

The diatom Phaeodactylum tricornutum can accumulate eicosapentaenoic acid (EPA) up to 30% of the total fatty acids. This species has been targeted for isolating gene encoding desaturases and elongases for long-chain polyunsaturated fatty acid (LC-PUFA) metabolic engineering. Here we first report the cloning and characterization of Δ5-elongase gene in P. tricornutum. A full-length cDNA sequence, designated PhtELO5, was shown to contain a 1110 bp open reading frame encoding a 369 amino acid polypeptide. The putative protein contains seven transmembrane regions and two elongase characteristic motifs of FLHXYHH and MYSYY, the latter being typical for microalgal Δ5-elongases. Phylogenetic analysis indicated that PhtELO5 belongs to the ELO5 group, tightly clustered with the counterpart of Thalassiosira pseudonana. Heterologous expression of PhtELO5 in Pichia pastoris confirmed that it encodes a specific Δ5-elongase capable of elongating arachidonic acid and eicosapentaenoic acid. Co-expression of PhtELO5 and IsFAD4 (a ∆4-desaturase from Isochrysis sphaerica) demonstrated that the high-efficiency biosynthetic pathway of docosahexaenoic acid was assembled in the transgenic yeast. Substrate competition revealed that PhtELO5 exhibited higher activity towards n-3 PUFA than n-6 PUFA. It is hypothesized that Phaeodactylum ELO5 may preferentially participate in biosynthesis of transgenic LC-PUFA via a n-3 pathway in the yeast host.
Group (III) Nitrides M[Mg2Al2N4] (M = Ca, Sr, Ba, Eu) and Ba[Mg2Ga2N4]—Structural Relation and Nontypical Luminescence Properties of Eu2+ Doped Samples (2014)

The isotypic nitridomagnesoaluminates M[Mg2Al2N4] (M = Ca,Sr, Ba,Eu) as well as a novel nitridomagnesogallate Ba[Mg2Ga2N4] have been synthesized by high-temperature reactions in arc-welded tantalum ampules. The crystal structures were solved and refined using single-crystal X-ray diffraction or powder X-ray diffraction data, respectively. All compounds crystallize in the UCr4C4-structure type (space group I4/m (no. 87), Z = 2, Ca[Mg2Al2N4]: a = 8.0655(11), c = 3.2857(7) Å, wR2 = 0.085 Sr[Mg2Al2N4]: a = 8.1008(11), c = 3.3269(7) Å, wR2 = 0.084; Eu[Mg2Al2N4]: a = 8.1539(12), c = 3.3430(7) Å, wR2 = 0.033; Ba[Mg2Al2N4]: a = 8.2602(9), c = 3.43198(19) Å, wRp = 0.031; Ba[Mg2Ga2N4]: a = 8.3654(12), c = 3.4411(7) Å, wR2 = 0.031) forming highly condensed anionic networks of disordered (Al/Mg)N4 and (Ga/Mg)N4 units, connected to each other by common edges and corners. The M2+ site is centered in vierer ring channels along [001] and coordinated in a cuboidal surrounding by N. Eu2+ doped samples of M[Mg2Al2N4] (M = Ca,Sr,Ba) exhibit nontypical luminescence properties including trapped exciton emission in the red spectral region. These compounds widen the group of novel red-emitting materials such as Ca[LiAl3N4]:Eu2+, Sr[LiAl3N4]:Eu2+, or Sr[Mg3SiN4]:Eu2+. Therefore, deep discussion of the observed anomalous luminescence is essential to understand the correlations between all these materials, which are fundamental to design narrow band luminescence of Eu2+ systems.
A 490uW fully MICS compatible FSK transceiver for implantable devices (2009)

A low power fully MICS compatible FSK transceiver for implantable devices is implemented in 0.18um CMOS technology with 0.7V supply. The Q-enhancement LNA attenuates image and adjacent channels more than 30 and 13dB, respectively, eliminating the necessity of I/Q LO generation and poly-phase filter. The DCO replaces the frequency synthesizer to reduce the power consumption and to eliminate the XO. The 1mm2 fabricated transceiver consumes 490uW with a data rate of 250kb/s, corresponding to energy consumption of 1.96nJ/b.
Isolation of a peptide for targeted drug delivery into human head and neck solid tumors. (2000)

Lack of tumor specificity remains a major problem with chemotherapies in that side effects prevent the delivery of dosages of drugs that are required to eliminate tumors. In this report, we describe the isolation of a 12-mer peptide (HN-1), with approximately 1% of the mass of typical antibodies, that meets several criteria for targeted drug delivery into a solid tumor. First, internalization of HN-1 by human head and neck squamous cell cancer (HNSCC) cells suggests that HN-1 is capable of translocating drugs across cell membranes. Second, HN-1 appears to be HNSCC-specific, given its reduced uptake by nonmalignant human oral keratinocytes and other types of human cells, its preferential binding to primary HNSCC, and its localization to HNSCC-derived xenografts. Third, the presence of HN-1 within HNSCC xenografts suggests that it is capable of penetrating tumor tissues. Our results establish the utility of tumor-specific peptides for targeted drug delivery into solid tumors.
Concurrent collapse of keratin filaments, aggregation of organelles, and inhibition of protein synthesis during the heat shock response in mammary epithelial cells. (1989)

The sequence of heat shock-induced perturbations in protein synthesis and cytoskeletal organization was investigated in primary cultures of mouse mammary epithelial cells (MMEC). Exposure of the cells to 45 degrees C for 15 min caused a marked inhibition of protein synthesis through 2 h after heart. Resumption of protein synthesis began by 4 h, was complete by 8 h, and was accompanied by induction of four major heat shock proteins (HSPs) of 68, 70, 89, and 110 kD. Fluorescent cytochemistry studies indicated that heat shock elicited a reversible change in the organization of keratin filaments (KFs) and actin filaments but had a negligible effect on microtubules. Changes in the organization of KFs progressed gradually with maximal retraction and collapse into the perinuclear zone occurring at 1-2 h after heat followed by restoration to the fully extended state at 8 h. In contrast, actin filaments disappeared immediately after heat treatment and then rapidly returned within 30-60 min to their original appearance. The translocation of many organelles first into and then away from the juxtanuclear area along with the disruption and reformation of polyribosomes were concurrent with the sequential changes in distribution of KFs. The recovery of the arrangement of KFs coincided with but was independent of the resumption of protein synthesis and induction of HSPs. Thermotolerance could be induced in protein synthesis and KFs, but not in actin filaments, by a conditioning heat treatment. Neither protein synthesis nor induction of HSPs was necessary for the acquisition of thermotolerance in the KFs. The results are compatible with the possibility that protein synthesis may depend on the integrity of the KF network in MMEC. Heat shock thus can efficiently disarrange the KF system in a large population of epithelial cells, thereby facilitating studies on the functions of this cytoskeletal component.
Transactivation by AP-1 Is a Molecular Target of T Cell Clonal Anergy (1992)

Anergy is a mechanism of T lymphocyte tolerance induced by antigen receptor stimulation in the absence of co-stimulation. Anergic T cells were shown to have a defect in antigen-induced transcription of the interleukin-2 gene. Analysis of the promoter indicated that the transcription factor AP-1 and its corresponding cis element were specifically down-regulated. Exposure of anergic T cells to interleukin-2 restored both antigen responsiveness and activity of the AP-1 element.
High frequency of NPM1 gene mutations in acute myeloid leukemia with prominent nuclear invaginations (“cuplike” nuclei) (2006)

Falini et al[1][1] first reported exon 12 mutations in the nucleophosmin ( NPM1 ) gene in approximately 35% of patients with adult acute myeloid leukemia (AML). These mutations disrupt the nucleolar-localization signal and acquire a nuclear export signal motif at the C-terminus leading to abnormal
The Benefit of Force Feedback in Surgery: Examination of Blunt Dissection (2007)

Force feedback is widely assumed to enhance performance in robotic surgery, but its benefits have not yet been systematically assessed. In this study we examine the effects of force feedback on a blunt dissection task. Twenty subjects used a telerobotic system to expose an artery in a synthetic model while viewing the operative site with a video laparoscope. Subjects were drawn from a range of surgical backgrounds, from inexperienced to attending surgeons. Performance was compared between three force feedback gains: 0% (no force feedback), 37%, and 75%. The absence of force feedback increased the average force magnitude applied to the tissue by at least 50%, and increased the peak force magnitude by at least 100%. The number of errors that damage tissue increased by over a factor of 3. The rate and precision of dissection were not significantly enhanced with force feedback. These results hold across all levels of previous surgical experience. We hypothesize that force feedback is helpful in this blunt dissection task because the artery is stiffer than the surrounding tissue. This mechanical contrast serves to constrain the subject's hand from commanding inappropriate motions that generate large forces.
Competitividad, instituciones y regiones: el impacto del trabajo de los gobiernos estatales en la competitividad regional/estatal (2014)

La competitividad regional es un fenomeno influenciado por multiples factores politicos, economicos, organizacionales, y hasta de indole cultural. Entre estos, los factores institucionales, y en particular el papel del gobierno y sus politicas publicas disenadas para promover el desarrollo de la competitividad, han sido analizados en la literatura desde una perspectiva de mediciones basadas en indices y no desde los resultados de estas politicas. La vasta informacion que recolecta, clasifica y reporta el Instituto Nacional de Estadistica y Geografia (INEGI) representa una oportunidad para evaluar el impacto del gasto publico y las politicas publicas inmersas que se enfocan a intervenir en el proceso productivo de las industrias, empresas e individuos que se desempenan en una particular region. El presente estudio revisa la literatura sobre la competitividad y el crecimiento economico para desarrollar y probar modelos econometricos multinivel para datos longitudinales. El objetivo de este diseno de investigacion es realizar un primer acercamiento cuantitativo utilizando el potencial de las estadisticas ofrecidas por el INEGI para evaluar el impacto en competitividad regional por parte de las politicas publicas y gasto publico de los gobiernos estatales en temas como legislacion, regulacion, desarrollo economico, desarrollo social, imparticion de justicia, seguridad y orden publico, y educacion en sus diferentes niveles. Los resultados revelan la presencia de impactos significativos en los niveles de competitividad con variaciones importantes entre los estados. Entre los impactos mas relevantes, la educacion en algunos niveles, la regulacion, el desarrollo economico y el desarrollo social muestran ser factores criticos para elevar el nivel de competitividad de las empresas y los individuos en las regiones
An integrated approach to mapping the proteome of the human bone marrow stromal cell (2006)

Bone marrow stromal cells, also known as mesenchymal stem or progenitor cells, are thought to play a critical role in hematopoiesis. Because hematopoiesis is dysregulated in leukemic individuals, expression profiling in leukemic stromal cells might yield valuable insights into mechanisms of normal and dysregulated hematopoiesis. Here, proteomics was used to identify expressed proteins in normal and leukemic bone marrow stromal cells. Isobaric tags for relative and absolute quantification (iTRAQ) technology and MS/MS were used to identify and quantify proteins in bone marrow stromal cells from two normal and two leukemic individuals. Approximately 900 distinct proteins were identified with >95% confidence, 73 of which were differentially expressed in leukemic stromal cells. cDNA microarray analysis on Affymetrix oligonucleotide gene chips showed that transcripts correlated with approximately 90% of the expressed proteins. A novel integrated approach for mining and visualization of iTRAQ data is presented. The results provide an initial assessment of the proteome in human bone marrow stromal cells, laying the groundwork for comprehensive analysis of the proteome in these cells, and ultimately, for improved understanding of normal and dysregulated hematopoiesis.
Defective macrophage function in neonates and its impact on unresponsiveness of neonates to polysaccharide antigens (2004)

Neonates do not respond to thymus-independent (TI) antigens (Ag), making them vulnerable to infection with encapsulated bacteria. The antibody (Ab) response of adult and neonatal B cells to TI Ag requires certain cytokines, which are provided by T cells or macrophages (MPhi). Lipopolysaccharide (LPS) failed to induce neonatal MPhi to produce interleukin (IL)-1beta and tumor necrosis factor alpha (TNF-alpha) mRNA and to secrete IL-1beta, IL-12, and TNF-alpha. However, LPS induced neonates to secrete some IL-6 and three- to fivefold more IL-10 than adults. Accordingly, adding adult but not neonatal MPhi could restore the response of purified adult B cells to trinitrophenol (TNP)-LPS, a TI Ag. Increased IL-10 is causally related to decreased IL-1beta and IL-6 production, as IL-10(-/-) neonatal MPhi responded to LPS by secreting more IL-1beta and IL-6 than wild-type (WT) neonatal MPhi. When cultures were supplemented with a neutralizing Ab to IL-10, WT neonatal MPhi secreted increased amounts of IL-6 and allowed neonatal MPhi to promote adult B cells to mount an Ab response against TNP-LPS. Thus, neonates do not respond to TI Ag as a result of the inability of neonatal MPhi to secrete cytokines, such as IL-1beta and IL-6, probably as a result of an excess production of IL-10. This dysregulated cytokine secretion by neonatal MPhi may be a result of a reduction in expression of Toll-like receptor-2 (TLR-2) and TLR-4 and CD14.
DNA-Encoded Chemical Libraries for the Discovery of MMP-3 Inhibitors (2008)

Encoded self-assembling chemical (ESAC) libraries are characterized by the covalent display of chemical moieties at the extremity of self-assembling oligonucleotides carrying a unique DNA sequence for the identification of the corresponding chemical moiety. We have used ESAC library technology in a two-step selection procedure for the identification of novel inhibitors of stromelysin-1 (MMP-3), a matrix metalloproteinase involved in both physiological and pathological tissue remodeling processes, yielding novel inhibitors with micromolar potency.
Molecular cloning of human prostate specific antigen cDNA (1987)

A lambda gt11 clone encoding prostate specific antigen has been isolated from a human prostate cDNA library. The cDNA insert of 1415 nucleotides hybridizes specifically to a prostate mRNA species of 1.5 kb. The nucleotide sequence codes for part of a signal peptide, a short propiece and the mature protein of 237 amino acid residues. The Mr for the non-glycosylated protein was 26,089. One potential site for N-linked carbohydrate attachment was identified. The primary structure shows extensive homology with proteases of the kallikrein family.
Dehydroepiandrosterone in systemic lupus erythematosus (1995)

DHEA may be useful as a therapeutic agent for the treatment of mild to moderate SLE. Further studies of DHEA in the treatment of SLE are warranted.
Class III Homeodomain Leucine-Zipper Proteins Regulate Xylem Cell Differentiation (2005)

Although it has been suggested that class III homeodomain leucine-zipper proteins (HD-Zip III) are involved in vascular development, details of the function of individual HD-Zip III proteins in vascular differentiation have not been resolved. To understand the function of each HD-Zip III protein in vascular differentiation precisely, we analyzed the in vitro transcriptional activity and in vivo function of Zinnia HD-Zip III genes, ZeHB-10, ZeHB-11 and ZeHB-12, which show xylem-related expression. Transgenic Arabidopsis plants harboring cauliflower mosaic virus 35S-driven ZeHB-10 and ZeHB-12 with a mutation in the START domain (mtZeHB-10, mtZeHB-12) showed a higher production of tracheary elements (TEs) and xylem precursor cells, respectively. A systematic analysis with Genechip arrays revealed that overexpression of mtZeHB-12 rapidly induced various genes, including brassinosteroid-signaling pathway-related genes and genes for transcription factors that are expressed specifically in vascular tissues in situ. Furthermore, mtZeHB-12 overexpression did not induce TE-specific genes, including genes related to programmed cell death and lignin polymerization, but did induce lignin monomer synthesis-related genes, which are expressed in xylem parenchyma cells. These results suggest that ZeHB-12 is involved in the differentiation of xylem parenchyma cells, but not of TEs.