gebhart/patrepeval huggingface dataset:
Expression of thrombospondin (TSP1) and its receptors (CD36 and CD51) in normal, hyperplastic, and neoplastic human breast. (1993)

We have previously shown that thrombospondin (TSP) is present in normal breast secretions, and high levels of TSP are observed in malignant breast secretions and cytosols. Three genes encoding for three distinct TSPs (TSP1, TSP2, TSP3) have recently been described. In this study, using both immunohistochemistry and in situ hybridization, we report on the distribution of TSP1 in normal, hyperplastic, and neoplastic human breast. Its immunolocalization was also compared with that of two known cell surface receptors for TSP1: CD36 and CD51. In nonlactating ducts of normal and hyperplastic breast, TSP1 and CD51 are expressed in the basement membrane and in the basal surface of myoepithelial cells, respectively. In lactating adenomas, both TSP1 and CD51 disappear from the myoepithelial-stromal junction of ducts. However, TSP1 becomes selectively expressed at the apices of secretory epithelial cells of lactating ducts together with CD36, suggesting that the distribution of TSP1 and the appearance of its receptors are dependent on the secretory activity of human mammary ducts. In neoplastic human breast, a strong immunostaining for TSP1 is observed in the basement membrane surrounding in situ carcinomas (preinvasive cancer), and excessive TSP1 deposits are also observed in desmoplasia of invasive ductal carcinomas. TSP1 mRNA is localized in myoepithelial cells surrounding in situ carcinomas and in fibroblasts present in desmoplastic areas. On the other hand, few invasive ductal carcinoma cells (10%) express TSP1, while CD51 is moderately expressed by some neoplastic clusters, and no immunoreactivity is observed for CD36. By contrast, TSP1 is codistributed with CD51 in most of the invasive lobular carcinoma cells (40 to 80%) and with CD36 in a subpopulation (30 to 40%) of these invasive tumor cells. As previously observed with lactating adenomas, it is likely that the coexpression of TSP1 and CD36 is related to the secretory activity of invasive lobular carcinoma cells. The different distribution of TSP1 in invasive ductal versus lobular carcinomas may well reflect biological differences between these two main types of breast carcinoma. In this regard, the coexpression of TSP1 and CD36 may, in part at least, account for the variably invasive behavior of lobular carcinoma cells.
Identification of a unique T cell-derived lymphokine that primes macrophages for tumor cytotoxicity. (1989)

Macrophage activation factor (MAF) activity, assessed by the ability to activate macrophages (MO) to lyse RBL--a TNF-resistant, retrovirally transformed, tumor target--was detected in the PHA-stimulated supernatant (Sup) of LBRM, a murine T cell line. LBRM Sup provided a priming signal to MO, but required the subsequent addition of small amounts of LPS for the expression of tumor cytotoxicity. The identity of the lymphokine responsible for this MAF activity was investigated. IFN-gamma, the only previously characterized lymphokine capable of priming MO for tumor cytotoxicity, did have MAF activity in the assay, but IFN-gamma could not be detected by ELISA in LBRM Sup, and LBRM-derived mRNA lacked detectable message for IFN-gamma. Moreover, anti-IFN-gamma failed to inhibit the MAF activity of LBRM Sup, suggesting that the presence of small, undetectable amounts of IFN-gamma were neither responsible nor required for LBRM MAF activity. LBRM MAF activity appeared distinct from the other previously identified lymphokines produced by LBRM, since granulocyte-macrophage-CSF, IL-2, and IL-3 purified from LBRM Sup were unable to activate MO to lyse RBL. IL-4 and TNF, two lymphokines not known to be produced by LBRM but able to activate MO for cytotoxicity of some tumor targets, were also unable to activate MO for RBL cytotoxicity. LBRM MAF lacked antiviral activity in biologic assays, further distinguishing the lymphokine from IFN-gamma, and had an apparent Mr of 30,000 Da using gel filtration chromatography. Thus, the LBRM T cell line produces a previously undescribed lymphokine that primes MO for tumor cytotoxicity.
Deciduous fruit and nut crops: Mild temperatures of 1958–51 winter cause concern to deciduous industry because of light crops in prospect (1951)

Deciduous fruit and nuts crops of northern California probably will be below normal in 1951.
Bioabsorbable composites. I: Fundamental design considerations using free radically crosslinkable matrices (1993)

Abstract Bioabsorbable composites have been fabricated, consisting of poly (glycolic acid) surgical mesh embedded in free radically crosslinked poly (D, Iactide‐ co ‐8‐caprolactone) fumarate‐ or poly(D, Iactide‐ co‐ ‐glycolic acid) fumarate‐based matrices. Styrene and methyl methacrlate were investigated as hydrophobic comonomers and were found to significantly improve the degree of crosslinking, tensile strength and retention of physical properties during the initial stages of degradation particularly styrene. Hydrolytic degradation studies showed that the neat poly(D, L‐lactide‐ co ‐8caprolactone) fumarate matrix dwas excessively hydrophilic, failing after 10 days of immersion; a matrix modified with 25 wt% styrene underwent a steady, nearly linear loss in mass over a period of 35 days without fragmentation. A composite based on neat poly (D, L‐lactide‐ co ‐8‐caprolactone) fumarate displayed a tensile strength of 37 Mpa and modulus of 107 Mpa; addition of 25 wt% styrene yielded tensile strength and modulus of 64 Mpa and 689 Mpa, respectively. A silane coupling agent was shown to dramatically improve the fiber‐matrix interfacial adhesion; tensile strength of a poly(D, L‐lactide‐ co ‐glycolic acid) fumarate compsite was increase from 84 to 92 MPa upon fiber pretreatment. Improved adhesion was also demonstrated using SEM. Bioabsorbable composites are rigid at biological temperatures, but some can be custom formed at elevated temperatures, which might be useful in certain surgical applications.
Phase I study of a new radiosensitizer containing hydrogen peroxide and sodium hyaluronate for topical tumor injection: A new enzyme-targeting radiosensitization treatment, Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II) (2009)

Using a currently employed linear accelerator, our intent was to inactivate peroxidase/catalase in tumor tissue by the application of hydrogen peroxide, which is degraded to produce oxygen, thus re-oxygenizing the tumor tissue. In this way, we can convert radioresistant tumors into radiosensitive ones. On the basis of this strategy, we previously developed a new enzyme-targeting radiosensitization treatment named KORTUC I, which remarkably enhances the radiotherapeutic effect on various types of superficially exposed and locally advanced malignant neoplasms. Based on our clinical experience using KORTUC I, we also developed a new radiosensitizer containing hydrogen peroxide and sodium hyaluronate for injection into various types of tumors that are not superficially exposed (KORTUC II; described herein). KORTUC II was approved by our local ethics committee for advanced skin cancer, including malignant melanoma, bone/soft tissue malignant neoplasms, breast cancer, and metastatic lymph nodes. A maximum of 6 ml of the agent was injected into tumor tissue one to two times per week under ultrasonographic guidance, just prior to each administration of radiation therapy. Eleven patients, including seven with breast cancer, were enrolled in the KORTUC II trial upon fully informed consent. KORTUC II was well tolerated, with a minimum of adverse effects. Nine of the 11 patients showed a complete response (CR), and no severe complications occurred in any of the 11 patients. This new enzyme-targeting radiosensitization treatment may be indicated for various types of locally advanced neoplasms, including soft tissue neoplasms and breast cancers.
Molecular cloning of mouse tumour necrosis factor cDNA and its eukaryotic expression (1985)

Tumour necrosis factor (TNF), released by induced macrophages, causes tumour necrosis in animals and kills preferentially transformed cells in vitro. mRNA induced in the established mouse monocytic PU 5.1.8 cell line by lipopolysaccharide, was converted into double-stranded cDNA and cloned in the pAT153 vector. Recombinant plasmids were screened by plus-minus hybridization and TNF-specific oligonucleotide probes constructed on the basis of partial amino acid sequences of rabbit TNF. A series of TNF specific clones were identified and confirmed by hybrid selection of mouse TNF-specific mRNA. The sequence codes for a 235 amino acids long polypeptide, of which 156 amino acids presumably correspond to the mature product. It can be concluded that mature mouse TNF is a glycosylated dimer. Biologically active TNF was secreted by both Cos-I and CHO-cells transfected with the chimaeric expression vector pSV2d2-mTNF containing the coding region of the mouse TNF cDNA gene.
BODIPY dyes in photodynamic therapy (2012)

BODIPY dyes tend to be highly fluorescent, but their emissions can be attenuated by adding substituents with appropriate oxidation potentials. Substituents like these have electrons to feed into photoexcited BODIPYs, quenching their fluorescence, thereby generating relatively long-lived triplet states. Singlet oxygen is formed when these triplet states interact with 3O2. In tissues, this causes cell damage in regions that are illuminated, and this is the basis of photodynamic therapy (PDT). The PDT agents that are currently approved for clinical use do not feature BODIPYs, but there are many reasons to believe that this situation will change. This review summarizes the attributes of BODIPY dyes for PDT, and in some related areas.
Escherichia coli gene that controls sensitivity to alkylating agents (1978)

A new type of Escherichia coli mutant which shows increased sensitivity to methyl methane sulfonate but not to UV light or to gamma rays was isolated after mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine. The mutant is unable to reactivate phage lambdavir or double-stranded phiX174 DNA (replicative form) that had been treated with methyl methane sulfonate. The mutant is sensitive to other alkylating agents, such as ethyl methane sulfonate, mitomycin C, and N-methyl-N'-nitro-N-nitrosoguanidine, as well. It grows normally and exhibits almost normal recombination proficiency. The mutant possesses normal levels of DNA polymerase I, exonuclease I, exonuclease V, endonuclease specific for methyl methane sulfonate-treated DNA, and 3-methyladenine-DNA glycosidase activities. The genetic locus responsible has been named alk and is located near his on the chromosome.
Preparation of single- and double-oligonucleotide antibody conjugates and their application for protein analytics (2020)

Oligonucleotide-conjugated antibodies have gained importance for their use in protein diagnostics. The possibility to transfer the readout signal from the protein to the DNA level with an oligonucleotide-conjugated antibody increased the sensitivity of protein assays by orders of magnitude and enabled new multiplexing strategies. A bottleneck in the generation of larger oligonucleotide-conjugated antibody panels is the low conjugation yield between antibodies and oligonucleotides, as well as the lack of product purification methods. In this study, we combined a non-site-directed antibody conjugation technique using copper-free click chemistry with ion-exchange chromatography to obtain purified single and double oligonucleotide-conjugated antibodies. We optimized the click conjugation reaction of antibodies with oligonucleotides by evaluating crosslinker, reaction temperature, duration, oligonucleotide length, and secondary structure. As a result, we were able to achieve conjugation yields of 30% at a starting quantity as low as tens of nanograms of antibody, which makes the approach applicable for a wide variety of protein analytical assays. In contrast to previous non-site-directed conjugation methods, we also optimized the conjugation reaction for antibody specificity, confirmed by testing with knockout cell lines. The advantages of using single or double oligonucleotide-conjugated antibodies in regards to signal noise reduction are shown within immunofluorescence, proximity ligation assays, and single cell CITE-seq experiments.
Phenylation of pyrimidinones using diphenyliodonium salts (1999)

S. André Jacobsen, S. Rødbotten and T. Benneche, J. Chem. Soc., Perkin Trans. 1, 1999, 3265 DOI: 10.1039/A905519C
[Expression, export and one-step purification of proteins by fusion to the MalE protein of E. coli]. (1987)

Enzymes can be fused at the C-terminal end of the maltose binding protein (MalE), at the genetic level. Expression of the hybrid proteins, under control of promoter malEp and of the constitutive activator, MalTc1, can be repressed by glucose. The hybrid proteins are localised either in the bacterial cytoplasm or periplasmic space, depending on whether MalE harbors a signal peptide mutation or not; as MalE, they can be purified in one step by chromatography on cross-linked amylose. The Staphylococcus aureus Nuclease and the Klenow portion of E. coli DNA-polymerase I keep their specific activities when fused to MalE.
Annual report to the nation on the status of cancer, 1975‐2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates (2009)

Although the decrease in overall cancer incidence and death rates is encouraging, rising incidence and mortality for some cancers are of concern.
仪器的未来：软件设计的仪器正在掀起RF仪器、测试和设计的革命 (2015)

过去几十年来,软件在测试和测量系统中的作用发生了巨大变化。如今,软件已经成为现代高性能测量系统最关键的核心技术,因为软件是能够简化这些系统日益增长的复杂性的唯一方式。然而,仅仅在计算机处理器上运行软件是不够的。如果工程师无法使用软件来定义和设计仪器,是无法实现最具挑战性应用的。这种开发软件设计仪器的能力正是RF仪器行业,更广义来说是测试测量行业革命的核心所在。
A comparison of PET detector modules employing rectangular and round photomultiplier tubes (1995)

We have compared the high resolution BGO detector blocks from the EXACT HR PET system which use two dual-cathode rectangular photomultiplier (PM) tubes with a new block design, the EXACT HR PLUS, which uses four round PM tubes. Despite the lower coupling area between photocathode and scintillator, the HR PLUS block compares favorably with the HR block. The energy resolution averages 20% for the HR PLUS block and 23% for the HR block, with efficiency variations of 17% in both blocks. Additional measurements were carried out on the HR PLUS block to characterize depth of interaction effects and cross-talk between elements. Coincidence line spread function measurements had a FWHM of 3.0 mm in the axial direction and 2.9 mm in the transaxial direction. In light of these results, limitations of the BGO block design are discussed and some solutions proposed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The insulin receptor substrate 1 associates with the SH2-containing phosphotyrosine phosphatase Syp (1993)

The insulin receptor substrate 1 (IRS1) is a protein that is rapidly phosphorylated on tyrosine by the activated insulin receptor. Syp is a recently discovered, broadly expressed phosphotyrosine (Tyr(P)) phosphatase that contains two Src homology 2 (SH2) domains. We have found that insulin treatment of 3T3-L1 adipocytes leads to complex formation between IRS1 and Syp. Syp was detected in immunoadsorbates of IRS1 from extracts of insulin-treated but not basal cells by both immunoblotting and Tyr(P) phosphatase activity. The association of Syp with IRS1 apparently occurs between the SH2 domains of Syp and Tyr(P)-containing sequences of IRS1, since a fusion protein containing only the SH2 domains of Syp bound the Tyr(P) form of IRS1. Unlike the receptors for epidermal and platelet-derived growth factors, which in their activated state bind to the SH2 domains of Syp and elicit phosphorylation of Syp on tyrosine in intact cells, the Tyr(P) form of the insulin receptor did not bind to the SH2 domains of Syp, and no phosphorylation of Syp on tyrosine was detected in insulin-treated 3T3-L1 adipocytes. In combination with other findings these results indicate that IRS1 functions as a docking protein for SH2 domain-containing proteins participating in signaling from the insulin receptor.
Pharmacokinetics and pharmacodynamics of gliclazide in Caucasians and Australian Aborigines with type 2 diabetes (2000)

Gliclazide is equally effective in Caucasian and Aboriginal diabetic patients. The pharmacokinetics of oral gliclazide appear more complex than previously thought. Gliclazide pharmacodynamics are unrelated to rate and extent of absorption, consistent with a threshold concentration for hypoglycaemic effect.
On Principal Hessian Directions for Data Visualization and Dimension Reduction: Another Application of Stein's Lemma (1992)

Abstract Modern graphical tools have enhanced our ability to learn many things from data directly. With much user-friendly graphical software available, we are encouraged to plot a lot more often than before. The benefits from direct interaction with graphics have been enormous. But trailing behind these high-tech advances is the issue of appropriate guidance on what to plot. There are too many directions to project a high-dimensional data set and unguided plotting can be time-consuming and fruitless. In a recent article, Li set up a statistical framework for study on this issue, based on a notion of effective dimension reduction (edr) directions. They are the directions to project a high dimensional input variable for the purpose of effectively viewing and studying its relationship with an output variable. A methodology, sliced inverse regression, was introduced and shown to be useful in finding edr directions. This article introduces another method for finding edr directions. It begins with the observation that the eigenvectors for the Hessian matrices of the regression function are helpful in the study of the shape of the regression surface. A notation of principal Hessian directions (pHd's) is defined that locates the main axes along which the regression surface shows the largest curvatures in an aggregate sense. We show that pHd's can be used to find edr directions. We further use the celebrated Stein lemma for suggesting estimates. The sampling properties of the estimated pHd's are obtained. A significance test is derived for suggesting the genuineness of a view found by our method. Some versions for implementing this method are discussed, and simulation results and an application to real data are reported. The relationship of this method with exploratory projection pursuit is also discussed.
A microRNA network regulates expression and biosynthesis of wild-type and ΔF508 mutant cystic fibrosis transmembrane conductance regulator (2012)

Production of functional proteins requires multiple steps, including gene transcription and posttranslational processing. MicroRNAs (miRNAs) can regulate individual stages of these processes. Despite the importance of the cystic fibrosis transmembrane conductance regulator (CFTR) channel for epithelial anion transport, how its expression is regulated remains uncertain. We discovered that miRNA-138 regulates CFTR expression through its interactions with the transcriptional regulatory protein SIN3A. Treating airway epithelia with an miR-138 mimic increased CFTR mRNA and also enhanced CFTR abundance and transepithelial Cl(-) permeability independent of elevated mRNA levels. An miR-138 anti-miR had the opposite effects. Importantly, miR-138 altered the expression of many genes encoding proteins that associate with CFTR and may influence its biosynthesis. The most common CFTR mutation, ΔF508, causes protein misfolding, protein degradation, and cystic fibrosis. Remarkably, manipulating the miR-138 regulatory network also improved biosynthesis of CFTR-ΔF508 and restored Cl(-) transport to cystic fibrosis airway epithelia. This miRNA-regulated network directs gene expression from the chromosome to the cell membrane, indicating that an individual miRNA can control a cellular process more broadly than recognized previously. This discovery also provides therapeutic avenues for restoring CFTR function to cells affected by the most common cystic fibrosis mutation.
Colonic Neuroendocrine Peptide Levels in Patients with Chronic Idiopathic Slow Transit Constipation (1998)

The motility disorders in patients with slow-transit constipation have been attributed to a disturbance in the peptidergic innervation of the colonic enteric nervous system. The nature of this disturbance is, however, controversial. In the present study 7 patients with long-standing severe slow- transit constipation were included, and normal tissues from the colon of 6 patients, which had undergone colonectomy because of polyp, chronic diverticulitis, prolapsis and volvulus were used as controls. The concentrations of several neuroendocrine peptides were measured in tissue extracts by radioimmuno-assays. The level of pancreatic polypeptide was high in 2 patients and low in one patient. Peptide YY level was high in 3 patients and low in one patient, and that of neuropeptide Y was high in 4 patients. Somatostatin and vasoactive intestinal polypeptide levels were high in 3 patients and substance P concentration was low in 3 patients. Neurotensin level was high in one patient and low in another patient. Galanin concentration was low in 2 patients and high in one patient. Gastrin-releasing peptide level was high in one patient and that of enkephalin was high in 2 patients. All patients had altered concentrations of several neuroendocrine peptides except one, who had only a low level of galanin. It is concluded that patients with slow-transit constipation have disturbed neuroendocrine peptides in common, though the nature of this disturbance varies between patients and in most patients several neuroendocrine peptides were affected. This may explain the controversial results obtained in previous studies.
Differentiation-specific element: a cis-acting developmental switch required for the sustained transcriptional expression of the angiotensinogen gene during hormonal-induced differentiation of 3T3-L1 fibroblasts to adipocytes. (1993)

The gene encoding angiotensinogen, the glycoprotein precursor for the vasopressor angiotensin II, is under coordinate tissue-specific, developmental, and hormonal regulation. We show here that the irreversible, developmentally regulated increase in angiotensinogen gene expression during the hormonal (dexamethasone, insulin, and isobutylmethylxanthine) differentiation of fibroblast-like 3T3-L1 cells into adipocytes is mediated by a 14-base pair cis-acting element located at -1000 in the 5'-flanking region of the gene. The sequence of this differentiation-specific element (DSE) is similar to sites that bind the homeotic and pou class of transcription factors found in the promoters of other genes known to be regulated during differentiation. Furthermore, we show that there are several high affinity DSE-specific binding proteins present in preadipocyte nuclear extracts that are competed with known homeotic and pou transcription factor DNA binding sequences. Thus the DSE appears to serve as a developmental switch for the expression of the angiotensinogen gene during the differentiation of fibroblasts to adipocytes and may be a binding site for one or more of the pou-homeodomain class of transcription factors.