gebhart/patrepeval huggingface dataset:
Roles of Bicarbonate, cAMP, and Protein Tyrosine Phosphorylation on Capacitation and the Spontaneous Acrosome Reaction of Hamster Sperm1 (1999)

Capacitation is a prerequisite for successful fertilization by mammalian spermatozoa. This process is generally observed in vitro in defined NaHCO3-buffered media and has been shown to be associated with changes in cAMP metabolism and protein tyrosine phosphorylation. In this study, we observed that when NaHCO3 was replaced by 4-(2-hydroxyethyl)1-piperazine ethanesulfonic acid (HEPES), hamster sperm capacitation, measured as the ability of the sperm to undergo a spontaneous acrosome reaction, did not take place. Addition of 25 mM NaHCO3 to NaHCO3-free medium in which spermatozoa had been preincubated for 3.5 h, increased the percentage of spontaneous acrosome reactions from 0% to 80% in the following 4 h. Addition of anion transport blockers such as 4,4'-diiso thiocyano-2, 2'-stilbenedisulfonate (DIDS) or 4-acetomido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS) to the NaHCO3-containing medium inhibited the acrosome reaction, with maximal inhibition at 600 microM, and with an EC50 of 100 microM. Increasing either extracellular or intracellular pH did not induce the acrosome reaction in NaHCO3-free medium. In contrast, addition of 500 microM dibutyryl cAMP (dbcAMP), alone or together with 100 microM 1-methyl-3-isobutylxanthine (IBMX), induced the acrosome reaction in spermatozoa incubated in NaHCO3-free medium. These compounds also partially reversed the inhibition of the acrosome reaction caused by the DIDS or SITS in complete medium. In contrast to these results, IBMX or dbcAMP did not induce acrosome reactions in cells incubated in Ca2+-free medium. When hamster sperm were incubated in the absence of NaHCO3 or in the presence of NaHCO3 and DIDS, cAMP concentrations were significantly lower than the values obtained from sperm incubated in complete medium. Protein tyrosine phosphorylation has also been shown to be highly correlated with the onset of capacitation in many species. During the first hour of capacitation, an increase in protein tyrosine phosphorylation was observed in complete medium. In the absence of NaHCO3, the increase in protein tyrosine phosphorylation was delayed for 45 min, and this delay was overcome by the addition of dbcAMP and IBMX. The induction of the acrosome reaction by calcium ionophore A23187 in NaHCO3-free medium was delayed 2 h, as compared with control medium. This delay was not observed in the presence of dbcAMP and IBMX. Taken together, these results suggest that a cAMP pathway may mediate the role of NaHCO3 in the capacitation of hamster spermatozoa and that protein tyrosine phosphorylation is necessary but not sufficient for complete capacitation.
In situ gene therapy for prostate cancer. (1999)

The natural history of prostate cancer presents a dilemma for those interested in developing effective treatment for the disease. When the disease is localized (and therefore potentially curable by localized therapies), it is often of uncertain biological potential and in many cases will not progress to clinical significance. However, both experimental and clinical studies indicate that prostate cancer can metastasize early and/or from relatively small foci of prostate cancer within the gland and is often systemic at the time of diagnosis. Unfortunately, there are no curative therapies for metastatic prostate cancer. In general, currently used therapies with the potential to be curative involve a single cytoablative modality (radical prostatectomy and irradiation therapy) and are directed exclusively at the malignant cells within the prostate gland. At present the widespread use of these treatments alone has not resulted in substantial reduction in mortality from the prostate cancer. Gene therapy used alone or as an adjuvant approach could, at least conceptually, provide a rational solution for the prostate cancer dilemma. With gene therapy, it may be possible to treat localized and systemic disease effectively and simultaneously. Indeed, in situ gene therapy protocols in which viral vectors are used to transduce specific genes that generate cytotoxic activity and/or systemic immunity to the cancer offer hope for significantly reducing the mortality from this disease. This commentary discusses early studies specifically aimed toward developing in situ-based gene therapies that can generate cytotoxic activities in localized prostate cancers and/or the generation of an immune response in the primary tumor that would affect systemic disease.
Scanning near-field photolithography—surface photochemistry with nanoscale spatial resolution (2006)

This tutorial review describes recent advances that have challenged the traditional view that the Rayleigh limit, of approximately lambda/2, represents the ultimate resolution accessible using optical methods. Near-field optical methods offer a powerful capability for optical measurement and manipulation of materials. Using a scanning near-field optical microscope coupled to a UV laser it is possible to create photopatterned molecular structures with dimensions nearly 15 times smaller than the Rayleigh limit. Near-field methods offer the possibility for selective initiation of surface chemical transformations with exquisite spatial resolution, bringing the prospect of unifying top-down and bottom-up nanofabrication into view.
Inactivation of S-Adenosyl-l-homocysteine Hydrolase by 6‘-Cyano-5‘,6‘-didehydro- 6‘-deoxyhomoadenosine and 6‘-Chloro-6‘- cyano-5‘,6‘-didehydro-6‘-deoxyhomoadenosine. Antiviral and Cytotoxic Effects (2006)

6'-Cyano-5',6'-didehydro-6'-deoxyhomoadenosine (E)-1, (Z)-1, and 6'-chloro-6'-cyano-5',6'-didehydro-6'-deoxyhomoadenosine (E)-2 were synthesized and tested as new mechanism-based inhibitors of AdoHcy hydrolase. Nucleoside (E)-1 was identified as a type I inhibitor of the enzyme, whereas inactivation of the enzyme by nucleosides (Z)-1 and (E)-2 was accompanied by the formation of a covalent labeling of AdoHcy hydrolase.
Expression, purification and crystallization of two peroxisomal acyl-CoA oxidases fromArabidopsis thaliana (2004)

Two members of the acyl-CoA oxidase family from Arabidopsis thaliana have been cloned, overexpressed, purified and crystallized. Long-chain-specific acyl-CoA oxidase 1 crystals are characterized by a large variation in diffraction quality and non-isomorphous unit-cell parameters. The best crystals diffract to 2.0 angstrom using synchrotron radiation, have unit-cell parameters a = 85.2, b = 117.0, c = 131.0 angstrom, alpha = beta = gamma = 90 degrees and show P2(1)2(1)2(1) symmetry. There are two polypeptide chains in the asymmetric unit. Short-chain-specific acyl-CoA oxidase 4 crystals are trigonal, space group P3(1)21/P3(2)21, with unit-cell parameters a = b = 198.7, c = 149.6 angstroms. The crystals are most likely to contain six polypeptide chains in the asymmetric unit. Freshly prepared acyl-CoA oxidase 4 crystals diffract to 3.9 angstroms at cryogenic temperature at beamline I711, Max-Lab, but the diffraction quality degenerates after storage for only a few days in the crystallization drop. A selenomethionine-substituted form of the protein was produced and two-wavelength MAD data were collected at beamline BW7A, EMBL Outstation, Hamburg.
Simplifying motion and structure analysis using planar parallax and image warping (2002)

Robust 3D motion and structure computation and segmentation has been the subject of an enormous body of work in reconstructive vision. For linear approximations to perspective projection (weak/para perspective), and for the case of image velocities, elegant linear methods have been devised for robust estimation. For reconstruction under arbitrary view transformations, linear projective methods using point correspondences have been suggested. In this paper, the authors present a formulation for 3D motion and structure analysis using motion parallax defined with respect to an arbitrary plane in the environment. It is shown that if an image coordinate system is warped using plane projective transformation with respect to a reference view, the residual image motion is dependent only on the epipoles and has a simple relation to the 3D structure. The author's computational scheme avoids point/line correspondence and is based on hierarchical estimation and image warping working directly with spatio-temporal image intensities. Results on real images demonstrate how this analysis simplifies ego and multiple motion analysis, and stable scene-centered 3D reconstruction.
Ribozyme inhibitors. Deoxyguanosine and dideoxyguanosine are competitive inhibitors of self-splicing of the Tetrahymena ribosomal ribonucleic acid precursor (1986)

The intervening sequence (IVS) of the Tetrahymena rRNA precursor catalyzes its own splicing. During splicing the 3'-hydroxyl of guanosine is ligated to the 5' terminus of the IVS. One catalytic strategy of the IVS RNA is to specifically bind its guanosine substrate. Deoxyguanosine (dG) and dideoxyguanosine (ddG) are found to be competitive inhibitors of self-splicing. Comparison of the kinetic parameters (Ki = 1.1 mM for dG; Ki = 5.4 mM for ddG; Km = 0.032 mM for guanosine) indicates that the ribose hydroxyls are necessary for optimal binding of guanosine to the RNA. dG is not a substrate for the reaction even at very high concentrations. Thus, in addition to aiding in binding, the 2'-hydroxyl is necessary for reaction of the 3'-hydroxyl. A second catalytic strategy of the IVS RNA is to enhance the reactivity of specific bonds. For example, the phosphodiester bond at the 3' splice site is extremely labile to hydrolysis. We find that dG and ddG, as well as 2'-O-methylguanosine and 3'-O-methylguanosine, reduce hydrolysis at the 3' splice site. These data are consistent with an RNA structure that brings the 5' and 3' splice sites proximal to the guanosine binding site.
Polygenic inheritance and minisatellites (1996)

S: 1996 World Congress on Psychiatric Genetics: V. GENETICS OF DRUG ABUSE (A) AND ALCOHOL (B) (A) DRUG ABUSE: PDF Only
A robust heterodimeric Fc platform engineered for efficient development of bispecific antibodies of multiple formats (2018)

Bispecific monoclonal antibodies can bind two protein targets simultaneously and enable therapeutic modalities inaccessible by traditional mAbs. Bispecific formats containing a heterodimeric Fc region are of particular interest, as a heterodimeric Fc empowers both bispecificity and altered valencies while retaining the developability and druggability of a monoclonal antibody. We present a robust heterodimeric Fc platform, called the XmAb® bispecific platform, engineered for efficient development of bispecific antibodies and Fc fusions of multiple formats. First, we engineer a purification solution for proteins containing a heterodimeric Fc using engineered isoelectric point differences in the Fc region that enable straightforward purification of the heterodimeric species. Then, we combine this purification solution with a novel set of Fc substitutions capable of achieving heterodimer yields over 95% with little change in thermostability. Next, we illustrate the flexibility of our heterodimeric Fc with a case study in which a wide range of tumor-associated antigen × CD3 bispecifics are generated, differing in choice of tumor antigen, affinities for both tumor antigen and CD3, and tumor antigen valency. Finally, we present manufacturing data reinforcing the robustness of the heterodimeric Fc platform at scale.
A multidimensional modeling approach for OLAP within the framework of the relational model based on quotient relations (1998)

Article Free Access Share on A multidimensional modeling approach for OLAP within the framework of the relational model based on quotient relations Authors: O. Mangisengi Institute of Software Technology, Technical University of Vienna, Austria Institute of Software Technology, Technical University of Vienna, AustriaView Profile , A. M. Tjoa Institute of Software Technology, Technical University of Vienna, Austria Institute of Software Technology, Technical University of Vienna, AustriaView Profile Authors Info & Claims DOLAP '98: Proceedings of the 1st ACM international workshop on Data warehousing and OLAPNovember 1998 Pages 40–46https://doi.org/10.1145/294260.294270Published:01 November 1998Publication History 1citation445DownloadsMetricsTotal Citations1Total Downloads445Last 12 Months11Last 6 weeks2 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
“I Hear You” (2018)

Graphical displays are a typical means for conveying awareness information in groupware systems to help users track joint activities, but are not ideal when vision is constrained. Understanding how people maintain awareness through non-visual means is crucial for designing effective alternatives for supporting awareness in such situations. We present a lab study simulating an extreme scenario where 32 pairs of participants use an audio-only tool to edit shared audio menus. Our aim is to characterise collaboration in this audio-only space in order to identify whether and how, by itself, audio can mediate collaboration. Our findings show that the means for audio delivery and choice of working styles in this space influence types and patterns of awareness information exchange. We thus highlight the need to accommodate different working styles when designing audio support for awareness, and extend previous research by identifying types of awareness information to convey in response to group work dynamics.
Oestrogen inhibition reverses pulmonary arterial hypertension and associated metabolic defects (2017)

Increased oestrogen is a strong epidemiological risk factor for development of pulmonary arterial hypertension (PAH) in patients, associated with metabolic defects. In addition, oestrogens drive penetrance in mice carrying mutations in bone morphogenetic protein receptor type II (BMPR2), the cause of most heritable PAH. The goal of the present study was to determine whether inhibition of oestrogens was effective in the treatment of PAH in these mice.The oestrogen inhibitors fulvestrant and anastrozole were used in a prevention and treatment paradigm in BMPR2 mutant mice, and tamoxifen was used for treatment. In addition, BMPR2 mutant mice were crossed onto oestrogen receptor (ESR)1 and ESR2 knockout backgrounds to assess receptor specificity. Haemodynamic and metabolic outcomes were measured.Oestrogen inhibition both prevented and treated PAH in BMPR2 mutant mice. This was associated with reduction in metabolic defects including oxidised lipid formation, insulin resistance and rescue of peroxisome proliferator-activated receptor-γ and CD36. The effect was mediated primarily through ESR2, but partially through ESR1.Our data suggest that trials of oestrogen inhibition in human PAH are warranted, and may improve pulmonary vascular disease through amelioration of metabolic defects. Although fulvestrant and anastrozole were more effective than tamoxifen, tamoxifen may be useful in premenopausal females, because of a reduced risk of induction of menopause.
Direct haplotype determination by double ARMS: specificity, sensitivity and genetic applications (1991)

We have developed a novel double Amplification Refractory Mutation System (double ARMS) using a highly polymorphic region 5' to the human delta-globin gene as a model system. The double ARMS approach involves using two allele-specific ARMS primers simultaneously during DNA amplification by the polymerase chain reaction (PCR). The resulting system is highly sensitive and more specific than single ARMS. In addition, this approach enables the elucidation of the relationship of polymorphic sites on the same chromosome and thus allows the direct determination of haplotypes. We have also demonstrated that this system can be used in conjunction with inverse PCR, the resulting double ARMS inverse PCR (DARMSI-PCR) may allow haplotype determination on polymorphic sites which are separated further apart than the length limit imposed by PCR. The double ARMS approach has numerous other applications in molecular biology including HLA typing, virology, forensic pathology and the investigation of the phenomenon of chimerism following bone marrow transplantation.
Finite Geometry by Coordinate Methods (1953)

This paper was originally planned as an exposition of finite geometry in a form in which it could be used to illustrate all the work covered in the normal school geometry course. The beginning of it, however, was anticipated by an article for the Gazette by Mr. H. Martyn Cundy (1), which he has kindly allowed me to read before publication. This present paper shows how a coordinate system can be constructed for the geometry described in his article by using the field of residue classes (mod. 5); that is, the Galois field GF(5). A definition of distance is introduced which extends that adopted by Cundy to a form suited to the discussion of a wider range of theorems.
Parathyroid hormone treatment after myocardial infarction promotes cardiac repair by enhanced neovascularization and cell survival (2007)

Aims An ongoing concept is that stem cells have the potential to regenerate the injured myocardium. In addition to direct vasorelaxing effects on the vasculature, which are mediated by an increased cAMP production leading to a decreased calcium influx in smooth muscle cells, parathyroid hormone (PTH) was recently shown to facilitate stem cell mobilization. Therefore, we analysed in a murine model of experimental myocardial infarction (MI) the influence of PTH treatment on survival, functional parameters, stem cell migration, and expression of vascular endothelial growth factor A (VEGF-A). Methods and results Mice (C57BL/6) were treated with PTH (80 mg/kg/d) for up to 14 days after coronary artery ligation. Functional and immunohistochemical analyses were performed at days 6 and 30 after MI. Stem cells and VEGF expression in the myocardium were analysed by FACS and qRT-PCR at day 2 after MI. PTH-treated animals revealed a significant improvement of post-MI survival and myocardial function that was related to a subsequent reduction of left ventricular wall thinning and scar extension. Infarcted hearts of PTH-treated mice revealed increased numbers of CD45 /CD34 progenitor cells as well as an upregulation of VEGF-A mRNA associated with increased neovascularization and cell survival. Conclusions PTH application after MI increases migration of angiogenic CD45 /CD34 progenitor cells to the ischaemic heart, which may attenuate ischaemic cardiomyopathy. As PTH is already used in patients with osteoporosis, our findings may have a direct impact on the initiation of clinical studies in patients with ischaemic heart disease.
General method for cloning Neurospora crassa nuclear genes by complementation of mutants. (1985)

We have developed a sib selection procedure for cloning Neurospora crassa nuclear genes by complementation of mutants. This procedure takes advantage of a modified N. crassa transformation procedure that gives as many as 10,000 to 50,000 stable transformants per microgram of DNA with recombinant plasmids containing the N. crassa qa-2+ gene. Here, we describe the use of the sib selection procedure to clone genes corresponding to auxotrophic mutants, nic-1 and inl. The identities of the putative clones were confirmed by mapping their chromosomal locations in standard genetic crosses and using restriction site polymorphisms as genetic markers. Because we can obtain very high N. crassa transformation frequencies, cloning can be accomplished with as few as five subdivisions of an N. crassa genomic library. The sib selection procedure should, for the first time, permit the cloning of any gene corresponding to an N. crassa mutant for which an appropriate selection can be devised. Analogous procedures may be applicable to other filamentous fungi before the development of operational shuttle vectors.
A novel microfluidic concept for bioanalysis using freely moving beads trapped in recirculating flows (2003)

There are only a few examples in which beads are employed for heterogeneous assays on microfluidic devices, because of the difficulties associated with packing and handling these in etched microstructures. This contribution describes a microfluidic device that allows the capture, preconcentration, and controlled manipulation of small beads (<6 microm) in etched microchannels using fluid flows only. The chips feature planar diverging and converging channel elements connected by a narrow microchannel. Creation of bi-directional liquid movement by opposing electro-osmotic and pressure-driven flows can lead to the generation of controlled recirculating flow at these elements. Small polymer beads can actually be captured in the controlled rotating flow patterns. The clusters of freely moving beads that result can be perfused sequentially with different solutions. A preliminary binding curve was determined for the reaction of streptavidin-coated beads and fluorescein-labelled biotin, demonstrating the potential of this bead-handling approach for bioanalysis.
The Metalloporphyrin Antioxidant, MnTE-2-PyP, Inhibits Th2 Cell Immune Responses in an Asthma Model (2012)

MnTE-2-PyP, a superoxide dismutase mimetic, inhibited OVA-induced airway inflammation in mice suggesting an effect on Th2 responsiveness. Thus, we hypothesized that MnTE-2-PyP may alter dendritic cell-Th2 interactions. Bone marrow derived dendritic cells (DC) and OVA(323-339)-specific Th2 cells were cultured separately in the presence or absence of MnTE-2-PyP for 3 days prior to the co-culturing of the two cell types in the presence of an OVA(323-339) peptide and in some cases stimulated with CD3/CD28. MnTE-2-PyP-pretreated DC inhibited IL-4, IL-5 and IFNγ production and inhibited Th2 cell proliferation in the DC-Th2 co-culturing system in the presence of the OVA(323-339) peptide. Similar results were obtained using the CD3/CD28 cell-activation system; the addition of MnTE-2-PyP inhibited Th2 cell proliferation. MnTE-2-PyP suppressed CD25 expression on OVA-specific Th2 cells, which implied that MnTE-2-PyP can inhibit the activation of Th2 cells. MnTE-2-PyP also down-regulated co-stimulatory molecules: CD40, CD80 and CD86 on immature DC. Our studies suggest that the major mechanism by which MnTE-2-PyP inhibits airway inflammation is by acting on the DC and suppressing Th2 cell proliferation and activation.
Gene disruption and replacement in the rapamycin-producing Streptomyces hygroscopicus strain ATCC 29253 (1997)

A system for gene disruption and replacement based on a streptomycete temperate phage vector was developed to introduce DNA in the rapamycin-producing Streptomyces hygroscopicus strain ATCC 29253. This will be useful in attempts to produce, through genetic manipulation, novel forms of the therapeutically important immunosuppressive drug rapamycin. Recombinant phages were constructed from the phi C31 phage derivative KC515 (C+ attp) carrying a thiostrepton or viomycin resistance gene along with segments of the S. hygroscopicus chromosome. Each of the cloned segments also contained the aphll neomycin/kanamycin resistance gene to enable gene replacement by loss of the phage-derived DNA. Specific deletion of the entire polyketide synthase (PKS) believed to govern rapamycin biosynthesis resulted in the loss of rapamycin production. In contrast, disruption or deletion of a region predicted to encode four PKS open reading frames, or another region predicted to encode another PKS plus a cytochrome P450 hydroxylase and ferredoxin, had no effect on the production of rapamycin or nigericin, a polyether antibiotic also produced by S. hygroscopicus. Therefore, S. hygroscopicus may have the capacity to produce polyketides additional to rapamycin and nigericin.