gebhart/patrepeval huggingface dataset:
Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation (2000)

Following a report of skeletal muscle regeneration from bone marrow cells, we investigated whether hepatocytes could also derive in vivo from bone marrow cells. A cohort of lethally irradiated B6D2F1 female mice received whole bone marrow transplants from age-matched male donors and were sacrificed at days 1, 3, 5, and 7 and months 2, 4, and 6 posttransplantation (n = 3 for each time point). Additionally, 2 archival female mice of the same strain who had previously been recipients of 200 male fluorescence-activated cell sorter (FACS)-sorted CD34(+)lin(-) cells were sacrificed 8 months posttransplantation under the same protocol. Fluorescence in situ hybridization (FISH) for the Y-chromosome was performed on liver tissue. Y-positive hepatocytes, up to 2.2% of total hepatocytes, were identified in 1 animal at 7 days posttransplantation and in all animals sacrificed 2 months or longer posttransplantation. Simultaneous FISH for the Y-chromosome and albumin messenger RNA (mRNA) confirmed male-derived cells were mature hepatocytes. These animals had received lethal doses of irradiation at the time of bone marrow transplantation, but this induced no overt, histologically demonstrable, acute hepatic injury, including inflammation, necrosis, oval cell proliferation, or scarring. We conclude that hepatocytes can derive from bone marrow cells after irradiation in the absence of severe acute injury. Also, the small subpopulation of CD34(+)lin(-) bone marrow cells is capable of such hepatic engraftment.
Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks (2003)

Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.
Toward a General Chemical Method for Rapidly Mapping Multi-Protein Complexes (2004)

Ru(II)(bpy2)32+Cl2, ammonium persulfate, and visible light irradiation has been shown to rapidly and efficiently cross-link several interacting proteins. However, this methodology has not yet been used to map the architecture of large multi-protein complexes. In this study, this chemistry is applied to the crystallographically characterized yeast proteasome. The data obtained demonstrate both the method's increased generality and fidelity in comparison to traditional bifunctional cross-linking reagents, while also highlighting the future need for developing better analytical techniques to separate cross-linked products.
Ticlopidine and Clopidogrel (1999)

The thienopyridines ticlopidine and clopidogrel are inhibitors of platelet function in vivo. Their mode of action has not been defined, but it appears that they require conversion to as yet unidentified metabolites that are noncompetitive antagonists of the platelet ADP receptor. Inhibition of platelet aggregation with these compounds is delayed until 24 to 48 hours after administration. Maximum inhibition occurs after 3 to 5 days, and recovery is slow after drug withdrawal. Ticlopidine is effective in preventing cardiovascular events in cerebrovascular, cardiovascular, and peripheral vascular disease, with an efficacy that is similar to aspirin. However, its use is associated with significant and sometimes fatal adverse reactions, specifically neutropenia and bone marrow aplasia. Gastrointestinal side effects and skin rashes are common and result in discontinuation of therapy in up to 10% of patients. Clopidogrel is at least as effective as aspirin in preventing cardiovascular events in patients with a history of vascular disease. It appears to be safer than ticlopidine, although its efficacy in acute coronary syndromes or post-coronary-stent insertion has not been reported. Important outstanding issues are whether clopidogrel adds to the benefit of aspirin and whether the combination of these agents is safe. If so, this combination may become the standard for antithrombotic therapy in cardiovascular disease.
Evidence for three tumor suppressor gene loci on chromosome 8p in human prostate cancer. (1995)

Allelic loss of human chromosome sequences is often equated with inactivation of putative tumor suppressor genes. Loss of sequences on the short arm of chromosome 8 (8p) has been observed in human cancers, especially of 8p22 in prostate tumors. By using PCR analysis of highly polymorphic microsatellite repeat markers at nine 8p loci in 135 tumors, we observed deletion of sequences at 8p22 and at two other proximal deletion domains. These novel deletion domains encompass the NEFL locus and D8S87-ANK1 loci, respectively. These data suggest that three 8p tumor suppressor gene loci may be independently deleted in human prostate cancers.
The molecular biology of plastid division in higher plants (2005)

Plastids are essential plant organelles vital for life on earth, responsible not only for photosynthesis but for many fundamental intermediary metabolic reactions. Plastids are not formed de novo but arise by binary fission from pre-existing plastids, and plastid division therefore represents an important process for the maintenance of appropriate plastid populations in plant cells. Plastid division comprises an elaborate pathway of co-ordinated events which include division machinery assembly at the division site, the constriction of envelope membranes, membrane fusion and, ultimately, the separation of the two new organelles. Because of their prokaryotic origin bacterial cell division has been successfully used as a paradigm for plastid division. This has resulted in the identification of the key plastid division components FtsZ, MinD, and MinE, as well as novel proteins with similarities to prokaryotic cell division proteins. Through a combination of approaches involving molecular genetics, cell biology, and biochemistry, it is now becoming clear that these proteins act in concert during plastid division, exhibiting both similarities and differences compared with their bacterial counterparts. Recent efforts in the cloning of the disrupted loci in several of the accumulation and replication of chloroplasts mutants has further revealed that the division of plastids is controlled by a combination of prokaryote-derived and host eukaryote-derived proteins residing not only in the plastid stroma but also in the cytoplasm. Based on the available data to date, a working model is presented showing the protein components involved in plastid division, their subcellular localization, and their protein interaction properties.
Saturable binding of halothane to rat brain synaptosomes. (1992)

The hypothesis that volatile anesthetics act directly on or bind specifically to membrane proteins remains controversial. In earlier in situ electron probe microanalysis studies in cardiac muscle we showed preferential partitioning of halothane into mitochondria. To determine whether partitioning represents saturable binding or simple solubility, a photoaffinity labeling method was developed for halothane to examine binding in rat brain synaptosomes. Radioligand binding assays were then used to determine binding parameters for this important inhalational anesthetic. UV-light exposure of synaptosomes incubated with clinical concentrations of [14C]halothane resulted in sufficient labeling to allow characterization of binding sites. Analysis of saturation and competition curves showed that greater than 60% of [14C]halothane photolysis product binding to synaptosomes was specific, with low affinity (Kd = 0.49 +/- 0.16 mM) and high binding site concentration (Bmax = 1.87 +/- 0.75 nmol/mg of protein). Halothane photoaffinity labeling was partially inhibited by isoflurane (20%), chloroform (44%), 2-bromotrifluoroethane (20%), and dichlorotrifluoroethane (20%) but not by ethanol. The Kd measured with this photoaffinity approach is similar to the concentration of halothane required to produce anesthesia in rats.
Liposome electroformation (1986)

Liposome formation and lipid swelling on platinum electrodes in distilled water and water solutions in d.c. electrical fields have been investigated for different amounts of a negatively charged lipid (mixture from 71% PC, 21.5% PE and 7.5% PS), and a neutral lipid (DMPC). Negatively charged lipids do not form liposomes without field when the thickness of the dried lipid layer is of the order or less than that corresponding to 90 bilayers. The rate and extent of swelling of layers thicker than 90 bilayers is largest on the cathode, smaller without fields and smallest on the anode. The theory, based on the assumption that osmotic and electrostatic forces drive lipid swelling and liposome formation, is in semi-quantitative agreement with the experimental data; in particular, it gives the observed linear dependence of the rate of swelling on the inverse lipid layer thickness. To induce liposome formation for layers thinner than 90 bilayers it was necessary to apply a negative potential which is proportional to the logarithm of the inversed layer thickness. The characteristic critical potential is proportional to RTk/F; R being the gas constant, Tk the absolute temperature and F the Faraday constant. This indicates that redistribution of counterions may be the cause which increases the repulsive electrostatic intermembrane forces to overcome van der Waals attraction. For thicknesses below 10 bilayers, formation of very thin-walled liposomes of narrow size distribution and mean diameter of the order of 30 µm was observed. These liposomes grow in size before detachment and a formula for the kinetics of growth has been derived, which is in very good agreement with the experimental data. The effects of d.c. fields on DMPC swelling are smaller and lead to formation of liposome-like structures of different appearence. Bilayer separation and bending are prerequisites for liposome formation from hydrating lipids. Therefore, a possible molecular mechanism is that membranes should be destabilized to bend and fuse to form liposomes. This requires the right proportion between structured regions, in the form of bilayers, and defects and/or non-bilayer structures, and in many cases external constraints, in particular, electrical fields.
Role of Dlx-1 and Dlx-2 genes in patterning of the murine dentition (1997)

The molecular events of odontogenic induction are beginning to be elucidated, but until now nothing was known about the molecular basis of the patterning of the dentition. A role for Dlx-1 and Dlx-2 genes in patterning of the dentition has been proposed with the genes envisaged as participating in an 'odontogenic homeobox gene code' by specifying molar development. This proposal was based on the restricted expression of the genes in molar ectomesenchyme derived from cranial neural crest cells prior to tooth initiation. Mice with targeted null mutations of both Dlx-1 and Dlx-2 homeobox genes do not develop maxillary molar teeth but incisors and mandibular molars are normal. We have carried out heterologous recombinations between mutant and wild-type maxillary epithelium and mesenchyme and show that the ectomesenchyme underlying the maxillary molar epithelium has lost its odontogenic potential. Using molecular markers of branchial arch neural crest (Barx1) and commitment to chondrogenic differentiation (Sox9), we show that this population alters its fate from odontogenic to become chondrogenic. These results provide evidence that a subpopulation of cranial neural crest is specified as odontogenic by Dlx-1 and Dlx-2 genes. Loss of function of these genes results in reprogramming of this population of ectomesenchyme cells into chondrocytes. This is the first indication that the development of different shaped teeth at different positions in the jaws is determined by independent genetic pathways.
Sulfonated aluminium phthalocyanines as sensitizers for photochemotherapy. Effects of small light doses on localization, dye fluorescence and photosensitivity in V79 cells (1994)

V79 cells incubated with di- or tetrasulfonated aluminium phthalocyanines (AlPcS2 or AlPcS4) showed a granular fluorescence pattern. Co-staining with the lysosomotropic dye acridine orange (AO) indicated that the granules that were stained by these photoactive phthalocyanines were identical to lysosomes. Small light exposures made the lysosomes permeable to the dyes without inactivating the cells. Also, the lysosomal enzymes beta-AGA and cathepsin (L+B) were inactivated by small light exposures when AlPcS4 was present. Such small and almost nontoxic light exposures caused a redistribution of the dyes in the cells that was accompanied by a more than 10-fold increase in the fluorescence quantum yields of the dyes. Surprisingly, this redistribution and increase in fluorescence did not result in any significant increase in the photosensitivity of the cells.
Sustained miRNA-mediated Knockdown of Mutant AAT With Simultaneous Augmentation of Wild-type AAT Has Minimal Effect on Global Liver miRNA Profiles (2012)

α-1 antitrypsin (AAT) deficiency can exhibit two pathologic states: a lung disease that is primarily due to the loss of AAT's antiprotease function, and a liver disease resulting from a toxic gain-of-function of the PiZ-AAT (Z-AAT) mutant protein. We have developed several recombinant adeno-associated virus (rAAV) vectors that incorporate microRNA (miRNA) sequences targeting the AAT gene while also driving the expression of miRNA-resistant wild-type AAT-PiM (M-AAT) gene, thus achieving concomitant Z-AAT knockdown in the liver and increased expression of M-AAT. Transgenic mice expressing the human PiZ allele treated with dual-function rAAV9 vectors showed that serum PiZ was stably and persistently reduced by an average of 80%. Treated animals showed knockdown of Z-AAT in liver and serum with concomitant increased serum M-AAT as determined by allele-specific enzyme-linked immunosorbent assays (ELISAs). In addition, decreased globular accumulation of misfolded Z-AAT in hepatocytes and a reduction in inflammatory infiltrates in the liver was observed. Results from microarray studies demonstrate that endogenous miRNAs were minimally affected by this treatment. These data suggests that miRNA mediated knockdown does not saturate the miRNA pathway as has been seen with viral vector expression of short hairpin RNAs (shRNAs). This safe dual-therapy approach can be applied to other disorders such as amyotrophic lateral sclerosis, Huntington disease, cerebral ataxia, and optic atrophies.
First-order sideband transitions with flux-driven asymmetric transmon qubits (2013)

We demonstrate rapid, first-order sideband transitions between a superconducting resonator and a frequency-modulated transmon qubit. The qubit contains a substantial asymmetry between its Josephson junctions leading to a linear portion of the energy band near the resonator frequency. The sideband transitions are driven with a magnetic flux signal of a few hundred MHz coupled to the qubit. This modulates the qubit splitting at a frequency near the detuning between the dressed qubit and resonator frequencies, leading to rates up to 85 MHz for exchanging quanta between the qubit and resonator.
ChemInform Abstract: Oxidative Pyrolysis of CH2Cl2, CHCl3, and CCl4. Part 1. Incineration Implications. (1992)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Rapid assessment of bacterial viability and vitality by rhodamine 123 and flow cytometry (1992)

A.S. KAPRELYANTS AND D.B. KELL. 1992. The fluorescent dye rhodamine 123 (Rh 123) is concentrated by microbial cells in an uncoupler‐sensitive fashion. Steady‐state fluorescence measurements with Micrococcus luteus indicated that provided the added dye concentration is below approximately 1 mmol/1, uptake is fully uncoupler‐sensitive and is not accompanied by significant self‐quenching of the fluorescence of accumulated dye molecules. ‘Viable’ and ‘non‐viable’ cells are easily and quantitatively distinguished in a flow cytometer by the extent to which they accumulate the dye. The viability of a very slowly growing chemostat culture of Mic. luteus is apparently only about40–50%, as judged by plate counts, but most of the ‘non‐viable’ cells can be resuscitated by incubation of the culture in nutrient medium before plating. The extent to which individual cells accumulate rhodamine 123 can be rapidly assessed by flow cytometry, and reflects the three distinguishable physiological states exhibited by the culture (‘non‐viable’, ‘viable’ and ‘non‐viable‐but‐resuscitable’). Gram‐negative bacteria do not accumulate rhodamine 123 significantly because their outer membrane is not permeable to it; a simple treatment overcomes this. Flow cytometry using rhodamine 123 should prove of general utility for the rapid assessment of microbial viability and vitality.
Sixth-order cascaded Raman amplification (2005)

Sixth-order Raman amplification is demonstrated for the first time and shown to provide >10 dB budget improvement. Raman amplifiers of differing orders are compared in several commercial fibers and optimal Raman gains are presented.
Cu(II)-Catalyzed Olefin Migration and Prins Cyclization: Highly Diastereoselective Synthesis of Substituted Tetrahydropyrans (2011)

Metal-ligand complexes of Cu(OTf)(2) with an appropriate bisphosphine ligand have been shown to effectively catalyze the formation of substituted tetrahydropyrans via a sequential olefin migration and Prins-type cyclization. This methodology provides convenient access to a variety of functionalized tetrahydropyrans in excellent diastereoselectivities and good to excellent yields.
Bilateral Orchiectomy with or without Flutamide for Metastatic Prostate Cancer (1998)

The addition of flutamide to bilateral orchiectomy does not result in a clinically meaningful improvement in survival among patients with metastatic prostate cancer.
Discovery of Small Molecule Mer Kinase Inhibitors for the Treatment of Pediatric Acute Lymphoblastic Leukemia (2012)

Ectopic Mer expression promotes pro-survival signaling and contributes to leukemogenesis and chemoresistance in childhood acute lymphoblastic leukemia (ALL). Consequently, Mer kinase inhibitors may promote leukemic cell death and further act as chemosensitizers increasing efficacy and reducing toxicities of current ALL regimens. We have applied a structure-based design approach to discover novel small molecule Mer kinase inhibitors. Several pyrazolopyrimidine derivatives effectively inhibit Mer kinase activity at sub-nanomolar concentrations. Furthermore, the lead compound shows a promising selectivity profile against a panel of 72 kinases and has excellent pharmacokinetic properties. We also describe the crystal structure of the complex between the lead compound and Mer, opening new opportunities for further optimization and new template design.
A principal components analysis of human odontometrics (1988)

It has long been recognized that tooth crown diameters in hominoids are all positively intercorrelated one with another. This study reports on sex-specific correlation matrices derived from 2,650 individuals from the Solomon Islands, Melanesia. Mesiodistal and buccolingual diameters of all permanent teeth from one side are used, excluding third molars. Analysis discloses significant sex dimorphism in the strengths of the intercorrelations, with females being better integrated. Principal components analysis (PCA) provides an objective means of data reduction (shown here to be preferable to simple size summation methods) and decorrelation of the resulting linear combinations. Four components are extracted (with results being virtually identical in the two sexes) and arguments are put forth that varimax rotation to "a simpler solution" may be counterproductive. Before rotation, the four components are 1) overall size, 2) buccolingual widths contrasted with mesiodistal lengths, 3) anterior (I,C) contrasted with posterior (P,M) teeth, and 4) premolars contrasted with molars. Most of the explained (shared) variance (63%) extracted by PCA is in overall size of the dentition. There is a strong urge to view the results of these principal components analyses as reflective of biologically and genetically meaningful entities.
Using the Domain Name System for System Break-ins (1995)

The DARPA Internet uses the Domain Name System (DNS), a distributed database, to map host names to network addresses, and vice-versa. Using a vulnerability first noticed by P.V. Mockapetris, we demonstrate how the DNS can be abused to subvert system security. We also show what tools are useful to the attacker. Possible defenses against this attack, including one implemented by Berkeley in response to our reports of this problem, are discussed, and the limitations on their applicability are demonstrated.
Cyclische Nitrone, IV. Darstellung und Eigenschaften des Δ1‐Pyrrolin‐N‐oxyds (1959)

Abstract Δ 1 ‐Pyrrolin‐ N ‐oxyd wird durch Dehydrierung des aus N ‐Äthyl‐pyrrolidin‐ N ‐oxyd erhältlichen N ‐Hydroxy‐pyrrolidins monomer gewonnen. Umsetzungen dieses bisher einfachsten Nitrons mit Lithiumalanat, Phenylmagnesiumbromid und Phenylisocyanat werden beschrieben. Die Dehydrierung des 1‐Hydroxy‐2‐phenyl‐pyrrolidins mit Quecksilberoxyd führt zum 2‐Phenyl‐Δ 1 ‐pyrrolin‐ N ‐oxyd, im Gegensatz zum Verhalten des analogen Piperidinderivats, das zum 6‐Phenyl‐Δ 1 ‐piperidein‐ N ‐oxyd dehydriert wird. Das unterschiedliche Verhalten analoger Pyrrolidin‐ und Piperidinderivate wird aus der Stereochemie erklärt.