gebhart/patrepeval huggingface dataset:
Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi (2015)

Genetic engineering technologies can be used both to create transgenic mosquitoes carrying antipathogen effector genes targeting human malaria parasites and to generate gene-drive systems capable of introgressing the genes throughout wild vector populations. We developed a highly effective autonomous Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein 9 (Cas9)-mediated gene-drive system in the Asian malaria vector Anopheles stephensi, adapted from the mutagenic chain reaction (MCR). This specific system results in progeny of males and females derived from transgenic males exhibiting a high frequency of germ-line gene conversion consistent with homology-directed repair (HDR). This system copies an ∼ 17-kb construct from its site of insertion to its homologous chromosome in a faithful, site-specific manner. Dual anti-Plasmodium falciparum effector genes, a marker gene, and the autonomous gene-drive components are introgressed into ∼ 99.5% of the progeny following outcrosses of transgenic lines to wild-type mosquitoes. The effector genes remain transcriptionally inducible upon blood feeding. In contrast to the efficient conversion in individuals expressing Cas9 only in the germ line, males and females derived from transgenic females, which are expected to have drive component molecules in the egg, produce progeny with a high frequency of mutations in the targeted genome sequence, resulting in near-Mendelian inheritance ratios of the transgene. Such mutant alleles result presumably from nonhomologous end-joining (NHEJ) events before the segregation of somatic and germ-line lineages early in development. These data support the design of this system to be active strictly within the germ line. Strains based on this technology could sustain control and elimination as part of the malaria eradication agenda.
“Click Peptide“: pH‐Triggered in Situ Production and Aggregation of Monomer Aβ1–42 (2009)

The intense and uncontrollable self-assembling nature of amyloid beta peptide (Abeta) 1-42 is known to cause difficulties in preparing monomeric Abeta1-42; this results in irreproducible or discrepant study outcomes. Herein, we report novel features of a pH click peptide of Abeta1-42 that was designed to overcome these problems. The click peptide is a water-soluble precursor peptide of Abeta1-42 with an O-acyl isopeptide structure between the Gly25-Ser26 sequence. The click peptide adopts and retains a monomeric, random coil state under acidic conditions. Upon change to neutral pH (pH click), the click peptide converts to Abeta1-42 promptly (t(1/2) approximately 10 s) and quantitatively through an O-to-N intramolecular acyl migration. As a result of this quick and irreversible conversion, monomer Abeta1-42 with a random coil structure is produced in situ. Moreover, the oligomerization, amyloid fibril formation and conformational changes of the produced Abeta1-42 can be observed over time. This click peptide strategy should provide a reliable experimental system to investigate the pathological role of Abeta1-42 in Alzheimer's disease.
Oral administration of a new soluble branched β-1,3-D-glucan is well tolerated and can lead to increased salivary concentrations of immunoglobulin A in healthy volunteers (2005)

The soluble branched yeast beta-1,3-D-glucan (SBG) belongs to a group of carbohydrate polymers known to exert potent immunomodulatory effects when administered to animals and humans. A new oral solution of SBG has been developed for local application to the oropharyngeal and oesophageal mucosa in order to strengthen the defence mechanisms against microbial and toxic influences. In the present study oral administration of SBG has been investigated primarily for assessment of safety and tolerability in an early phase human pharmacological study (phase I). Eighteen healthy volunteers were included among non-smoking individuals. The study was an open 1:1:1 dose-escalation safety study consisting of a screening visit, an administration period of 4 days and a follow-up period. Groups of six individuals received SBG 100 mg/day, 200 mg/day or 400 mg/day, respectively, for 4 consecutive days. The dose increase was allowed after a careful review of the safety data of the lower dose group. No drug-related adverse event, including abnormalities in vital signs, was observed. By inspection of the oral cavity only minor mucosal lesions not related to the study medication were seen in seven subjects. Repeated measurements of beta-glucan in serum revealed no systemic absorption of the agent following the oral doses of SBG. In saliva, the immunoglobulin A concentration increased significantly for the highest SBG dose employed. SBG was thus safe and well tolerated by healthy volunteers, when given orally once daily for 4 consecutive days at doses up to 400 mg.
Amphiregulin expression in prostatic intraepithelial neoplasia and adenocarcinoma: A study of 93 cases (2003)

AMP expression in prostate increases progressively from benign epithelium to PIN and cancer. Increased expression of AMP may contribute to the development of prostatic adenocarcinoma. Predominantly nuclear staining was observed in benign epithelium, whereas cytoplasmic or nuclear and cytoplasmic staining was observed in PIN and adenocarcinoma. The differences in nuclear and cytoplasmic localization of immunoreactivity may reflect the presence of two pathways of activation, and hence varying biological functions of AMP.
Effects of the application of Aloe vera (L.) and microcurrent on the healing of wounds surgically induced in Wistar rats (2009)

Simultaneous application of Aloe vera gel and microcurrent is an excellent choice for the treatment of open wounds thus indicating a synergistic action of these two applications.
Introduction of a foreign gene into medakafish using the particle gun method (2000)

We developed a procedure to introduce a foreign gene into fertilized eggs of medakafish (Oryzias latipes) using the particle gun method, which is one of the easiest and most reliable techniques for gene transfer. A plasmid construct with the green fluorescence protein (GFP) gene driven by the madakafish beta-actin gene promoter was successfully introduced into eggs, and the expression of GFP was observed in 20% of the primary transfectant (chimera) fish. In addition, germ line transmission of GFP was observed in 13% of the GFP-positive primary transfectant fish. The new application described here should enable us to investigate gene expression using the fish model on a routine basis without high technical sophistication. J. Exp. Zool. 287:285-293, 2000.
The idiotypic specificities of lymphocytes in human monoclonal gammopathies: analysis with the fluorescence activated cell sorter. (1983)

Four monoclonal IgG kappa gammopathies were studied with anti-idiotypic sera and the percentage of lymphocytes bearing such idiotypes was evaluated with a fluorescence activated cell sorter (FACS). A large percentage (10-15%) of peripheral lymphocytes bearing receptors with the same idiotypic specificities as the M component was observed in multiple myeloma (MM) and in monoclonal gammopathy of undetermined significance (MGUS), suggesting a malignant origin for both these diseases. Capping-endocytosis and resynthesis experiments showed that these idiotypic receptors were not simply adsorbed on the cell membrane, but actually synthesized by the cells bearing them. Experiments performed after effective conventional chemotherapy showed a strong reduction of the idiotypic compartment in only one MM patient.
Surface Studies of Solids by Total Reflection of X-Rays (1954)

Analysis of the shape of the curve of reflected x-ray intensity vs glancing angle in the region of total reflection provides a new method of studying certain structural properties of the mirror surface about 10 to several hundred angstroms deep. Dispersion theory, extended to treat any (small) number of stratified homogeneous media, is used as a basis of interpretation.Curves for evaporated copper on glass at room temperature are studied as an example. These curves may be explained by assuming that the copper (exposed to atmospheric air at room temperature) has completely oxidized about 150A deep. If oxidation is less deep, there probably exists some general reduction of density (e.g., porosity) and an electron density minimum just below an internal oxide seal. This seal, about 25A below the nominal surface plane, arrests further oxidation of more deeply-lying loose-packed copper crystallites.All measurements to date have been carried out under laboratory atmospheric conditions which do not allow satisfactory separation or control of the physical and chemical variables involved in the surface peculiarities. The method, under more controlled conditions of preparation and treatment of the surface, promises to be useful.
Combining Radiotherapy and Cancer Immunotherapy: A Paradigm Shift (2013)

The therapeutic application of ionizing radiation has been largely based on its cytocidal power combined with the ability to selectively target tumors. Radiotherapy effects on survival of cancer patients are generally interpreted as the consequence of improved local control of the tumor, directly decreasing systemic spread. Experimental data from multiple cancer models have provided sufficient evidence to propose a paradigm shift, whereby some of the effects of ionizing radiation are recognized as contributing to systemic antitumor immunity. Recent examples of objective responses achieved by adding radiotherapy to immunotherapy in metastatic cancer patients support this view. Therefore, the traditional palliative role of radiotherapy in metastatic disease is evolving into that of a powerful adjuvant for immunotherapy. This combination strategy adds to the current anticancer arsenal and offers opportunities to harness the immune system to extend survival, even among metastatic and heavily pretreated cancer patients. We briefly summarize key evidence supporting the role of radiotherapy as an immune adjuvant. A critical appraisal of the current status of knowledge must include potential immunosuppressive effects of radiation that can hamper its capacity to convert the irradiated tumor into an in situ, individualized vaccine. Moreover, we discuss some of the current challenges to translate this knowledge to the clinic as more trials testing radiation with different immunotherapies are proposed.
Selective Feedback Control of Spastic Musculature in a Canine Model (1992)

Muscular spasm, the etiology of which remains elusive, has been difficult to control. The authors, therefore, proposed selective restraint of forced contractions by a closed-loop circuit. In four dogs, the strap (n = 6) and thyroarytenoid (n = 4) muscles were submitted to tetanic contractions via bipolar supramaximal stimulation (30 Hz, 6 mA, 0.5 msec) of ansa hypoglossi and recurrent laryngeal nerves, respectively. Subsequent reduction of distance between two sonomicrometer crystals embedded into muscle was used in lieu of "spastic information" for a stimulator to deliver blocking signals through tripolar electrodes passed downstream. By modifying frequency (30-110 Hz) and current (60-95%) distribution between the central cathode and the peripheral anodes, significant relaxation (up to 100%) was recorded within "blocking windows," varying with each nerve (3-18 mA sweeps). The selective restraint of unwanted contractions, leaving "normal" subthreshold tone undisturbed, may offer a more mature approach to spastic disorders than destructive procedures, such as nerve section and its chemical counterpart, botulinum toxin injection.
Coagulation, Fibrinolysis and Angiogenesis: New Insights from Knockout Mice (2002)

Angiogenesis plays a key role in a broad array of physiologic and pathologic processes. Two major systems--coagulation and fibrinolysis--maintaining hemostasis, have recently been implicated in angiogenesis. Generation of mice deficient in components of coagulation and plasminogen systems has provided an extraordinary opportunity to define the role of each of these systems in vivo and to elucidate molecular mechanisms involved in angiogenesis. It appears that several factors of the coagulation system, such as the tissue factor, the factor V and the thrombin receptor, play an important role in embryonic vessel formation, most probably in the formation of the primitive vascular wall. In addition, the plasminogen system appears to play a significant role in angiogenesis in adulthood, regulating the migration of endothelial and smooth muscle cells, the degradation of the extracellular matrix and activity of the metalloproteinase system. These new revelations open a possibility for future therapeutic strategies to specifically control angiogenesis in different pathological processes where abnormalities of tissue vascularization are pathogenetically prominent.
Hormonal Control of the Cervix in Pregnant Gilts. III. Relaxin's Influence on Cervical Biochemical Properties in Ovariectomized Hormone-Treated Pregnant Gilts* (1991)

The effects of relaxin on the biochemical properties of both the uterine and vaginal portions of the cervix were examined between days 80-110 of pregnancy in ovariectomized gilts given progesterone to maintain pregnancy. In the cervix of control gilts and those ovariectomized and given progesterone plus relaxin, wet and dry weights, water content, and the glycosaminoglycan/collagen ratio increased between days 80-110 of gestation. Collagen concentrations based on wet or dry weight and glycosaminoglycan concentrations based on wet weight decreased during this period. After ovariectomy, there were no changes in these cervical connective tissue components when relaxin was not given. The glycosaminoglycans hyaluronic acid, heparan sulfate, and dermatan sulfate were found in the cervices of all treatment groups, with dermatan sulfate predominating. The ratio of the individual glycosaminoglycans did not change during pregnancy or with treatment. The major dermatan sulfate proteoglycan from the pig cervix was isolated and found to be similar in size, immunoreactivity, amino acid composition, and amino acid sequence to the major dermatan sulfate proteoglycans isolated from the cervices of other mammals. It is concluded that the relaxin-induced changes in the connective tissue composition of the cervix may contribute at least in part to increased extensibility and growth of the cervix during the last third of gestation in pigs.
.beta.-Adrenergic blocking agents. 22. 1-Phenoxy-3-[[(substituted-amido)alkyl]amino]-2-propanols (1982)

The synthesis of a series of 1-phenoxy-3-[[(substituted-amido)alkyl]amino]-2-propanols is described. Many of the compounds are more potent than propanolol as beta blockers, while having cardioselectivity comparable to that of practolol, when given intravenously to anesthetized cats. The structure-activity relationships shown by this series of compounds provide further evidence that the addition of substituents to the alkylamino moeity of a beta blocker can confer cardioselectivity and that amidic substituents are remarkably effective.
Cardiac gene therapy with adeno-associated virus-based vectors (2017)

Here, we describe the successes and challenges in cardiac AAV gene therapy, a treatment modality that has the potential to transform current treatment approaches for cardiac diseases.
Patterned polymer growth on silicon surfaces using microcontact printing and surface-initiated polymerization (1999)

Patterned polymer films were grown on SiO2/Si surfaces by a process starting with microcontact printing (μCP) of octadecyltrichlorosilane (OTS), formation of a monolayer derived from norbornenyl trichlorosilane (Nbn–SiCl3) in areas not protected by OTS, activation of the surfaces derived from Nbn–SiCl3 with a ruthenium catalyst, and surface-initiated ring-opening metathesis polymerization of derivatives of norbornene by the catalytically active ruthenium species. These patterned polymer films were successfully used as reactive ion etching resists. The combination of μCP and surface-initiated polymerization makes possible molecular-level control of polymer composition and thickness in both lateral and vertical directions: the smallest patterned lateral features were 2 μm lines; this width was determined by the features of the stamp used in μCP and is not the intrinsic limit of the method. The thickness of the polymer film was, typically, 5–100 nm and could be controlled by monomer concentration and reaction time.
Quartz crystal microbalance setup for frequency and Q-factor measurements in gaseous and liquid environments (1995)

An experimental setup has been constructed for simultaneous measurements of the frequency, the absolute Q factor, and the amplitude of oscillation of a quartz crystal microbalance (QCM). The technical solution allows operation in vacuum, air, or liquid. The crystal is driven at its resonant frequency by an oscillator that can be intermittently disconnected causing the crystal oscillation amplitude to decay exponentially. From the recorded decay curve the absolute Q factor (calculated from the decay time constant), the frequency of the freely oscillating crystal, and the amplitude of oscillation are obtained. All measurements are fully automated. One electrode of the QCM in our setup was connected to true ground which makes possible simultaneous electrochemistry. The performance is illustrated by experiments in fluids of varying viscosity (gas and liquid) and by protein adsorption in situ. We found, in addition to the above results, that the amplitude of oscillation is not always directly proportional to the Q factor, as the commonly used theory states. This puts limitations on the customary use of the amplitude of oscillation as a measure of the Q factor.
Interaction of α‐synuclein and synphilin‐1: effect of Parkinson's disease‐associated mutations (2001)

alpha-Synuclein is a major component of Lewy bodies, a neuropathological feature of Parkinson's disease. Two alpha-synuclein mutations, Ala53Thr and Ala30Pro, are associated with early onset, familial forms of the disease. Recently, synphilin-1, a protein found to interact with alpha-synuclein by yeast two hybrid techniques, was detected in Lewy bodies. In this study we report the interaction of alpha-synuclein and synphilin-1 in human neuroglioma cells using a sensitive fluorescence resonance energy transfer technique. We demonstrate that the C-terminus of alpha-synuclein is closely associated with the C-terminus of synphilin-1. A weak interaction occurs between the N-terminus of alpha-synuclein and synphilin-1. The familial Parkinson's disease associated mutations of alpha-synuclein (Ala53Thr and Ala30Pro) also demonstrate a strong interaction between their C-terminal regions and synphilin-1. However, compared with wild-type alpha-synuclein, significantly less energy transfer occurs between the C-terminus of Ala53Thr alpha-synuclein and synphilin-1, suggesting that the Ala53Thr mutation alters the conformation of alpha-synuclein in relation to synphilin-1.
Direct Visualization of Hyaluronic Acid Polymer Chain by Self-Assembled One-Dimensional Array of Gold Nanoparticles (2005)

ADVERTISEMENT RETURN TO ISSUEPREVCommunication to the...Communication to the EditorNEXTDirect Visualization of Hyaluronic Acid Polymer Chain by Self-Assembled One-Dimensional Array of Gold NanoparticlesHaeshin Lee, Seung Ho Choi, and Tae Gwan ParkView Author Information Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea 305-701 Cite this: Macromolecules 2006, 39, 1, 23–25Publication Date (Web):November 24, 2005Publication History Received5 September 2005Revised10 November 2005Published online24 November 2005Published inissue 1 January 2006https://pubs.acs.org/doi/10.1021/ma051929chttps://doi.org/10.1021/ma051929crapid-communicationACS PublicationsCopyright © 2006 American Chemical SocietyRequest reuse permissionsArticle Views2682Altmetric-Citations62LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Carbohydrates,Gold,Metal nanoparticles,Nanoparticles,Thiols Get e-Alerts
Variable expression of the translocated c-abl oncogene in Philadelphia-chromosome-positive B-lymphoid cell lines from chronic myelogenous leukemia patients. (1986)

The consistent cytogenetic translocation of chronic myelogenous leukemia (the Philadelphia chromosome, Ph1) has been observed in cells of multiple hematopoietic lineages. This translocation creates a chimeric gene composed of breakpoint-cluster-region (bcr) sequences from chromosome 22 fused to a portion of the abl oncogene on chromosome 9. The resulting gene product (P210c-abl) resembles the transforming protein of the Abelson murine leukemia virus in its structure and tyrosine kinase activity. P210c-abl is expressed in Ph1-positive cell lines of myeloid lineage and in clinical specimens with myeloid predominance. We show here that Epstein-Barr virus-transformed B-lymphocyte lines that retain Ph1 can express P210c-abl. The level of expression in these B-cell lines is generally lower and more variable than that observed for myeloid lines. Protein expression is not related to amplification of the abl gene but to variation in the level of bcr-abl mRNA produced from a single Ph1 template.
Hyperbranched polymers as scaffolds for multifunctional reversible addition–fragmentation chain‐transfer agents: A route to polystyrene‐core‐polyesters and polystyrene‐block‐poly(butyl acrylate)‐core‐polyesters (2003)

Abstract Polydisperse hyperbranched polyesters were modified for use as novel multifunctional reversible addition–fragmentation chain‐transfer (RAFT) agents. The polyester‐core‐based RAFT agents were subsequently employed to synthesize star polymers of n ‐butyl acrylate and styrene with low polydispersity (polydispersity index &lt; 1.3) in a living free‐radical process. Although the polyester‐core‐based RAFT agent mediated polymerization of n ‐butyl acrylate displayed a linear evolution of the number‐average molecular weight ( M n ) up to high monomer conversions (&gt;70%) and molecular weights [ M n &gt; 140,000 g mol −1 , linear poly(methyl methacrylate) equivalents)], the corresponding styrene‐based system reached a maximum molecular weight at low conversions (≈30%, M n = 45,500 g mol −1 , linear polystyrene equivalents). The resulting star polymers were subsequently used as platforms for the preparation of star block copolymers of styrene and n ‐butyl acrylate with a polyester core with low polydispersities (polydispersity index &lt; 1.25). The generated polystyrene‐based star polymers were successfully cast into highly regular honeycomb‐structured microarrays. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3847–3861, 2003