gebhart/patrepeval huggingface dataset:
Human anti-CD30 recombinant antibodies by guided phage antibody selection using cell panning (2000)

In various clinical studies, Hodgkin's patients have been treated with anti-CD30 immunotherapeutic agents and have shown promising responses. One of the problems that appeared from these studies is the development of an immune response against the nonhuman therapeutics, which limits repeated administration and reduces efficacy. We have set out to make a recombinant, human anti-CD30 single-chain variable fragment (scFv) antibody, which may serve as a targeting moiety with reduced immunogenicity and more rapid tumour penetration in similar clinical applications. Rather than selecting a naive phage antibody library on recombinant CD30 antigen, we used guided selection of a murine antibody in combination with panning on the CD30-positive cell line L540. The murine monoclonal antibody Ki-4 was chosen as starting antibody, because it inhibits the shedding of the extracellular part of the CD30 antigen. This makes the antibody better suited for CD30-targeting than most other anti-CD30 antibodies. We have previously isolated the murine Ki-4 scFv by selecting a mini-library of hybridoma-derived phage scFv-antibodies via panning on L540 cells. Here, we report that phage display technology was successfully used to obtain a human Ki-4 scFv version by guided selection. The murine variable heavy (VH) and light (VL) chain genes of the Ki-4 scFv were sequentially replaced by human V gene repertoires, while retaining only the major determinant for epitope-specificity: the heavy-chain complementarity determining region 3 (CDR3) of murine Ki-4. After two rounds of chain shuffling and selection by panning on L540 cells, a fully human anti-CD30 scFv was selected. It competes with the parental monoclonal antibody Ki-4 for binding to CD30, inhibits the shedding of the extracellular part of the CD30 receptor from L540 cells and is thus a promising candidate for the generation of anti-CD30 immunotherapeutics.
Involvement of corepressor complex subunit GPS2 in transcriptional pathways governing human bile acid biosynthesis (2007)

Coordinated regulation of bile acid biosynthesis, the predominant pathway for hepatic cholesterol catabolism, is mediated by few key nuclear receptors including the orphan receptors liver receptor homolog 1 (LRH-1), hepatocyte nuclear factor 4alpha (HNF4alpha), small heterodimer partner (SHP), and the bile acid receptor FXR (farnesoid X receptor). Activation of FXR initiates a feedback regulatory loop via induction of SHP, which suppresses LRH-1- and HNF4alpha-dependent expression of cholesterol 7alpha hydroxylase (CYP7A1) and sterol 12alpha hydroxylase (CYP8B1), the two major pathway enzymes. Here we dissect the transcriptional network governing bile acid biosynthesis in human liver by identifying GPS2, a stoichiometric subunit of a conserved corepressor complex, as a differential coregulator of CYP7A1 and CYP8B1 expression. Direct interactions of GPS2 with SHP, LRH-1, HNF4alpha, and FXR indicate alternative coregulator recruitment strategies to cause differential transcriptional outcomes. In addition, species-specific differences in the regulation of bile acid biosynthesis were uncovered by identifying human CYP8B1 as a direct FXR target gene, which has implications for therapeutic approaches in bile acid-related human disorders.
Human growth hormone as a reporter gene in regulation studies employing transient gene expression. (1986)

The human growth hormone (hGH) transient assay system described here is based on the expression of hGH directed by cells transfected with hGH fusion genes. Levels of secreted hGH in the medium, measured by a simple radioimmunoassay, are proportional to both levels of cytoplasmic hGH mRNA and the amount of transfected DNA. The system is extremely sensitive, easy to perform, and is qualitatively different from other transient expression systems in that the medium is assayed and the cells themselves are not destroyed. The hGH transient assay system is appropriate for analyses of regulation of gene expression and was utilized here to investigate the effect of the simian virus 40 enhancer on the herpes simplex virus thymidine kinase promoter and the effect of zinc on the mouse metallothionein-I promoter. The expression of hGH can also be used as an internal control to monitor transfection efficiency along with any other transient expression system. All cell types tested thus far (including AtT-20, CV-1, GC, GH4, JEG, L, and primary pituitary cells) were able to secrete hGH into the medium.
Principle and applications of digital PCR (2004)

Digital PCR represents an example of the power of PCR and provides unprecedented opportunities for molecular genetic analysis in cancer. The technique is to amplify a single DNA template from minimally diluted samples, therefore generating amplicons that are exclusively derived from one template and can be detected with different fluorophores or sequencing to discriminate different alleles (e.g., wild type vs. mutant or paternal vs. maternal alleles). Thus, digital PCR transforms the exponential, analog signals obtained from conventional PCR to linear, digital signals, allowing statistical analysis of the PCR product. Digital PCR has been applied in quantification of mutant alleles and detection of allelic imbalance in clinical specimens, providing a promising molecular diagnostic tool for cancer detection. The scope of this article is to review the principles of digital PCR and its practical applications in cancer research and in the molecular diagnosis of cancer.
Design of nanoslotted photonic crystal waveguide cavities for single nanoparticle trapping and detection (2009)

We design and numerically simulate an on-chip photonic device that integrates both optical manipulation and detection functionalities for a single nanoparticle or macromolecule. A unique combination of a photonic crystal waveguide cavity and a nanoslot structure leads to a approximately 1300 times enhancement of the optical gradient trapping force compared with a conventional waveguide trapping device. Numerical simulations indicate that the designed device is capable of stably trapping a single nanoparticle inside the nanoslot cavity, and thus provides an ideal platform for single particle detection and analysis using cavity-enhanced spectroscopic technologies.
Synthesis of Non‐Natural Amino Acids from N‐(p‐Tolylsulfonyl)‐α,β‐didehydroamino Acid Derivatives (2003)

Abstract Carbon nucleophiles, amines, and oxygen nucleophiles were treated with the methyl ester of N ‐( tert ‐butoxycarbonyl)‐ N ‐( p ‐tolylsulfonyl)‐α,β‐didehydroalanine, and also with the methyl esters of N ‐( tert ‐butoxycarbonyl)‐ O ‐( p ‐tolylsulfinyl)‐α,β‐didehydroserine and N ‐( tert ‐butoxycarbonyl)‐β‐(1,2,4‐triazol‐1‐yl)‐α,β‐didehydroalanine, both of which were obtained from the former substrate. Carbon nucleophiles of the β‐dicarbonyl type gave furanic amino acids, which were converted into the corresponding pyrrole derivatives (dehydroprolines) in high yields, while use of amines allowed the synthesis of α,α‐diamino acids and β‐amino‐α,β‐didehydroamino acids. Different types of alkoxyamino acids were obtained by treatment of the above substrates with oxygen nucleophiles. The reactivities of the α,β‐didehydroaminobutyric and α,β‐didehydrophenylalanine analogues were also tested. Some of the methods developed were applied to the synthesis of cross‐linked amino acids, namely didehydrolanthionine and histidino‐α,β‐didehydroalanine derivatives. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)
Expression of CXCR4 and CXCL12 (SDF‐1) in human prostate cancers (PCa) in vivo (2003)

Human prostate cancers (PCa) express great variability in their ability to metastasize to bone. The identification of molecules associated with aggressive phenotypes will help to define PCa subsets and will ultimately lead to better treatment strategies. The chemokine stromal-derived factor-1 (SDF-1 or CXCL12) and its receptor CXCR4 are now known to modulate the migration and survival of an increasing array of normal and malignant cell types including breast, pancreatic cancers, glioblastomas, and others. The present investigation extends our previous investigations by determining the expression of CXCR4 and CXCL12 in humans using high-density tissue microarrays constructed from clinical samples obtained from a cohort of over 600 patients. These data demonstrate that CXCR4 protein expression is significantly elevated in localized and metastastic cancers. At the RNA level, human PCa tumors also express CXCR4 and message, but overall, they were not significantly different suggesting post-transcriptional regulation of the receptor plays a major role in regulating protein expression. Similar observations were made for CXCL12 message, but in this case more CXCL12 message was expressed by metastastic lesions as compared to normal tissues. PCa cell lines also express CXCL12 mRNA, and regulate mRNA expression in response to CXCL12 and secrete biologically active protein. Furthermore, neutralizing antibody to CXCL12 decreased the proliferation of bone homing LNCaP C4-2B and PC3 metastastic tumor cells. These investigations provide important new information pertaining to the molecular basis of how tumors may 'home' to bone, and the mechanisms that may account for their growth in selected end organs.
Dietary Antioxidants and Human Cancer (2004)

Epidemiological studies show that a high intake of anti-oxidant-rich foods is inversely related to cancer risk. While animal and cell cultures confirm the anticancer effects of antioxidants, intervention trials to determine their ability to reduce cancer risk have been inconclusive, although selenium and vitamin E reduced the risk of some forms of cancer, including prostate and colon cancer, and carotenoids have been shown to help reduce breast cancer risk. Cancer treatment by radiation and anticancer drugs reduces inherent antioxidants and induces oxidative stress, which increases with disease progression. Vitamins E and C have been shown to ameliorate adverse side effects associated with free radical damage to normal cells in cancer therapy, such as mucositis and fibrosis, and to reduce the recurrence of breast cancer. While clinical studies on the effect of anti-oxidants in modulating cancer treatment are limited in number and size, experimental studies show that antioxidant vitamins and some phytochemicals selectively induce apoptosis in cancer cells but not in normal cells and prevent angiogenesis and metastatic spread, suggesting a potential role for antioxidants as adjuvants in cancer therapy.
Elasticity of the spinal cord, pia, and denticulate ligament in the dog (1978)

✓ The longitudinal elasticities of the dog spinal cord, pia, and denticulate ligaments were obtained by measuring the load-elongation curves. Both pia and denticulate ligaments were moderately elastic, but the spinal cord substance showed an upward curve, which indicated a predominantly viscous character. In situ, the spinal cord and pia were moderately strained. A 40-mm segment of the cord with dorsal and ventral roots severed and denticulate ligaments removed became 1 mm shorter when the cord and pia were transected at both ends. It was estimated that the cord and pia in situ were stressed by a force of 2 to 3 gm, the denticulate ligaments with 3 to 5 gm, and the dura with 50 to 70 gm. The elastic moduli of the spinal cord substance were 1.68 × 10 5 dynes/sq cm for loading between 5 and 10 gm and 1.19 × 10 5 dynes/sq cm between 30 and 35 gm.
Mechanism of the Chemical Deposition of Nickel on Silicon Wafers in Aqueous Solution (1999)

The deposition of metallic nickel on n‐Si(100) wafers was performed without external potential control in aqueous solutions of different compositions at pH 8.0. Without giving any catalyzation treatment, the deposition of nickel on hydrogen‐terminated Si(100) was confirmed in a conventional electroless plating bath containing as the reducing agent, sodium citrate as the complexing agent, and as the buffering agent. The deposition of nickel was found to take place also in a bath without the reducing agent, and even in a simple solution consisting of and . By using a transmission electron microscope equipped with an energy dispersive X‐ray spectrometer, the cross sections of the films deposited from these solutions were examined, which revealed formation of silicon oxide between the Ni deposit and Si substrate. Based on these results, the mechanism of the entire process of electroless Ni deposition on Si is discussed. © 1999 The Electrochemical Society. All rights reserved.
A systematic review and meta-analysis on the efficacy and acceptability of bilateral repetitive transcranial magnetic stimulation (rTMS) for treating major depression (2012)

Bilateral rTMS is a promising treatment for MD as it provides clinically meaningful benefits that are comparable with those of standard antidepressants and unilateral rTMS. Furthermore, bilateral rTMS seems to be an acceptable treatment for depressed subjects.
[The change of ACh metabolism in the dorsal horn of spinal cord and spinal ganglia during electroacupuncture analgesia (EAA)]. (1990)

In this paper a preliminary study was made about the relationship between ACh and the primary input of acupuncture sensation based on the changes of content of ACh, its synthetic enzyme (choline acetylase, or ChAC) and its degradation enzyme (acetylcholinesterase, or AChE) in the dorsal horn of the spinal cord and spinal ganglia. The results were found that: 1) EA at "huantiao" exerted a marked analgesia effect, the acupuncture analgesia was inhibited when the lateral dorsal root was cut off. 2) The content of ACh of the EA group were slightly lower than those of the control group. 3) AChE activity in the spinal ganglia and the dorsal horn increased markedly under electroacupuncture stimulation. 4) The activity of ChAC in the dorsal horn of rats under acupuncture stimulation was significantly higher than those of the control group. 5) ACh content in the spinal ganglia increased obviously when the degradation of peripheral ACh was inhibited by prostigmine. 6) With the lumber dorsal roots excised, AChE activity of the operative side were much lower than those of the intact side during EA stimulation. It suggest that the metabolism of ACh in the dorsal horn of the spinal cord and spinal ganglia change during the course of EAA, and only when signals produced at the acupoints are delivered to the spinal cord via ACh-containing primary somatosensory nerves, can they exert analgesic and therapeutic effect of acupuncture.
Regulation of the Synthesis of Nerve Growth Factor (1987)

Through nearly 40 years of research nerve growth factor (NGF) has become a paradigm for neurotrophic factors. NGF is synthesized and released from innervated target tissues in limiting amounts, thereby regulating the cell number and the differentiated properties of responsive neurones. Three distinct cell types are responsive to NGF: peripheral sensory and sympathetic neurones and certain types of central cholinergic ones. The effects of NGF are mediated through interaction with a specific receptor which activates a transmembrane second-messenger system. NGF synthesis is regulated during development and in the adult animal. In the developing whisker pad, NGF synthesis commences with its sensory innervation, but sensory neurones lack NGF receptors at the stage when their fibres are growing to their target. These findings indicate that NGF does not attract sensory nerve fibres chemotactically to their target fields during development, but is involved in target-controlled neuronal cell death and in regulation of the density of innervation of target tissues. In non-neuronal cells of the sciatic nerve, NGF synthesis is up-regulated during development and after nerve lesion. Thus the changes in NGF levels after lesion in the adult animal are consistent with the hypothesis that the non-neuronal cells relapse into an earlier developmental stage. Regenerating fibres penetrating into the distal nerve stump restore the low adult levels of NGF. Recent evidence indicates that macrophages invading the nerve after transection produce signals which increase NGF synthesis.
Formation and Schottky barrier height of metal contacts to β-SiC (1990)

Formation of Schottky barrier contacts to n-type β-SiC(100) was systematically investigated for several metals with various physical and chemical properties. The metals (Pd, Au, Co, Ti, Ag, Tb, and Al) were deposited onto oxygen terminated (∼1 monolayer) surfaces. Metal/β-SiC interface chemistry and Schottky barrier height φB during contact formation were obtained by x-ray photoemission spectroscopy; the corresponding electrical properties of thick contacts were characterized by capacitance-voltage and current-voltage methods. The metal/β-SiC interface is unreactive at room temperature. X-ray photoemission spectroscopy and electrical measurements demonstrate that these metal contacts exhibit a wide range of φB , 0.95–0.16 eV; within this range an individual contact φB value depends strongly on the metal work function in general accord with the Schottky–Mott limit.
Fine structure of the human hypoxanthine phosphoribosyltransferase gene. (1986)

The human hypoxanthine phosphoribosyltransferase (HPRT) gene has been characterized by molecular cloning, mapping, and DNA sequencing techniques. The entire gene, which is about 44 kilobases in length, is composed of nine exon elements. The positions of the introns within the coding sequence are identical to those of the previously-characterized mouse HPRT gene, although there are significant differences between intron sizes for the two genes. HPRT minigenes have been used in a transient expression assay involving microinjection into HPRT- cells to demonstrate functional promoter activity within a 234-base-pair region upstream from the ATG codon. The promoter of this gene resembles those of other recently characterized "housekeeping" genes in that it lacks CAAT- and TATA-like sequences, but contains several copies of the sequence GGGCGG. Both RNase protection and primer extension analysis indicate that human HPRT mRNA is heterogeneous at the 5' terminus, with transcription initiation occurring at sites located congruent to 104 to congruent to 169 base pairs upstream from the ATG codon. Comparison of the mouse and human HPRT 5'-flanking sequences indicates that there are only limited stretches of conserved sequence, although there are other shared features, such as an extremely high density of potential methylation sites, that may have functional significance.
Focused ion beam fabrication of silicon print masters (2003)

We investigated a focused ion beam nanofabrication technique as a high-resolution patterning method suitable for nanocontact imprinting. Different ion beam currents, milling times, and dwell times are exploited to optimize focused ion beam milling conditions. Single-pixel lines are milled on a silicon master and replicated on polydimethylsiloxane through replica moulding. The profile of the grooves (the depth-to-width aspect ratio) was found to be depth dependent regardless of the beam current and dwell time. The depth of the line cuts was strongly dependent upon beam current and dwell time at a given dose. This technique holds great promise for mass production of nanostructures due to its simplicity and high reproducibility.
Recombinant Toxins for Cancer Treatment (1991)

Recombinant toxins target cell surface receptors and antigens on tumor cells. They kill by mechanisms different from conventional chemotherapy, so that cross resistance to conventional chemotherapeutic agents should not be a problem. Furthermore, they are not mutagens and should not induce secondary malignancies or accelerate progression of benign malignancies. They can be mass-produced cheaply in bacteria as homogeneous proteins. Either growth factor-toxin fusions or antibody-toxin fusions can be chosen, depending on the cellular target.
A new approach to identifying genotoxic carcinogens: p53 induction as an indicator of genotoxic damage (1998)

The tumor suppressor gene p53 encodes a nuclear phosphoprotein which is critical for cell cycle control and prevention of uncontrolled cell proliferation that can lead to cancer. Previous studies have shown that cells respond to DNA damage by increasing their levels of p53, which then acts to prevent replication of damaged DNA. This study examined the effects on p53 protein levels of several different categories of chemical carcinogens. N-Methyl-N'-nitro-nitrosoguanidine and N-ethyl-N-nitrosourea, two direct-acting genotoxic (DNA-reactive) carcinogens, caused p53 induction as early as 2 h following treatment, with peak increases within 4-12 h. Aflatoxin B1 and 2-acetylaminofluorene, indirect-acting genotoxic carcinogens, caused a later induction of p53, with the peak increase appearing between 16 and 24 h following treatment. These observations demonstrate a correlation between p53 induction pattern and DNA damaging mechanism of genotoxins. Phenol, diethylstilbestrol and ethylacrylate also induced increases in cellular p53. The half-life of p53 protein was increased in cells treated with genotoxic agents. On the other hand, the epigenetic (non-DNA-reactive) carcinogens azathioprine and saccharin, as well as two substances generally considered to be non-carcinogens, dimethylsulfoxide and benzethonium chloride, had no effect on p53 protein levels of treated cells. Measurement of the cytotoxic effects of each of these chemicals led to the conclusion that p53 protein induction is not a general, non-specific consequence of the cytotoxic effect of these genotoxins. These results suggest that measurement of p53 protein induction may be an effective tool to identify environmental genotoxins.
Tying the knot: The cystine signature and molecular‐recognition processes of the vascular endothelial growth factor family of angiogenic cytokines (2011)

The cystine-knot motif, made up of three intertwined disulfide bridges, is a unique feature of several toxins, cyclotides and growth factors, and occurs in a variety of species, including fungi, insects, molluscs and mammals. Growth factor molecules containing the cystine-knot motif serve as ligands for a diverse range of receptors and play an important role in extracellular signalling. This superfamily of polypeptides comprises several homodimeric and heterodimeric molecules that are central characters in both health and disease. Amongst these molecules are a group of proteins that belong to the vascular endothelial growth factor (VEGF) subfamily. The members of this family are known angiogenic factors that regulate processes leading to blood vessel formation in physiological and pathological conditions. The focus of the present review is on the structural characteristics of proteins that belong to the VEGF family and on signal-transduction pathways that become initiated via the VEGF receptors.