gebhart/patrepeval huggingface dataset:
The SV40 large T-antigen helicase can unwind four stranded DNA structures linked by G-quartets (1997)

We describe a novel activity of the SV40 large T-ag helicase, the unwinding of four stranded DNA structures linked by stacked G-quartets, namely stacked groups of four guanine bases bound by Hoogsteen hydrogen bonds. The structures unwound by the helicase were of two types: (i) quadruplexes comprising four parallel strands that were generated by annealing oligonucleotides including clustered G residues in a buffer containing Na+ions. Each parallel quadruplex consisted of four oligonucleotide molecules. (ii) Complexes comprising two parallel and two antiparallel strands that were generated by annealing the above oligonucleotides in a buffer containing K+ions. Each antiparallel complex consisted of two folded oligonucleotide molecules. Unwinding of these unusual DNA structures by the T-ag was monitored by gel electrophoresis. The unwinding process required ATP and at least one single stranded 3'-tail extending beyond the four stranded region. These data indicated that the T-ag first binds the 3'-tail and moves in a 3'-->5'direction, using energy provided by ATP hydrolysis; then it unwinds the four stranded DNA into single strands. This helicase activity may affect processes such as recombination and telomere extension, in which four stranded DNA could play a role.
Glial Cells in the Rat Optic Nerve and Some Thoughts on Remyelination in the Mammalian Cns (1987)

Studies on the rat optic nerve in the past 5 years have produced two surprises. First, they demonstrated that there are two biochemically, developmentally and functionally distinct types of astrocytes in the optic nerve, and probably in white matter tracts throughout the CNS: one seems to be responsible for inducing endothelial cells to form the blood-brain barrier while the other seems to service nodes of Ranvier. Second, they showed that oligodendrocytes and type-2 astrocytes develop from a common bipotential (O-2A) progenitor cell that seems to migrate into the developing optic nerve, and may well migrate all over the CNS to wherever myelination is required; this implies that the neuroepithelial cells of the optic stalk are restricted to forming type-1 astrocytes. Some of the findings in the optic nerve may be relevant to the problem of CNS regeneration after injury. These include the following. (1) Reactive gliosis in white matter tracts seems to be mainly a function of type-1 astrocytes. (2) Proliferating O-2A progenitor cells are present in the adult CNS, raising the possibility that they may be able to produce new oligodendrocytes and type-2 astrocytes following injury and thereby aid regeneration. (3) Type-1 astrocytes seem to be able to respond to environmental signals and form localized barriers that block the migration of O-2A progenitor cells; it is conceivable that the same barriers block the migration of regenerating axonal growth cones.
A Facile Nonviral Method for Delivering Genes and siRNAs to Skeletal Muscle of Mammalian Limbs (2004)

Delivery is increasingly being recognized as the critical hurdle holding back the tremendous promise of nucleic acid-based therapies that include gene therapy and more recently siRNA-based therapeutics. While numerous candidate genes (and siRNA sequences) with therapeutic potential have been identified, their utility has not yet been realized because of inefficient and/or unsafe delivery technologies. We now describe an intravascular, nonviral methodology that enables efficient and repeatable delivery of nucleic acids to muscle cells (myofibers) throughout the limb muscles of mammals. The procedure involves the injection of naked plasmid DNA or siRNA into a distal vein of a limb that is transiently isolated by a tourniquet or blood pressure cuff. Nucleic acid delivery to myofibers is facilitated by its rapid injection in sufficient volume to enable extravasation of the nucleic acid solution into muscle tissue. High levels of transgene expression in skeletal muscle were achieved in both small and large animals with minimal toxicity. Evidence of siRNA delivery to limb muscle was also obtained. The simplicity, effectiveness, and safety of the procedure make this methodology well suited to limb muscle gene therapy applications.
Micrococcal Nuclease Analysis of Chromatin Structure (2005)

This unit describes methodology for using micrococcal nuclease to investigate the presence of nucleosomes at a particular location in chromatin and to map the positions of nucleosomes at various levels of resolution. The approaches are readily adaptable to other probes of chromatin structure that cause DNA cleavage. Results obtained from such chromatin studies provide a structural view of the molecular environment of gene in their native context in cells.
Transfer of carbetocin into human breast milk. (1993)

Very little carbetocin is transferred into human breast milk, presenting little risk to breast-fed infants.
Human Hepatic and Lipoprotein Lipase: The Loop Covering the Catalytic Site Mediates Lipase Substrate Specificity (1995)

Hepatic lipase (HL) and lipoprotein lipase (LPL) are key enzymes that mediate the hydrolysis of triglycerides (TG) and phospholipids (PL) present in circulating plasma lipoproteins. Relative to triacylglycerol hydrolysis, HL displays higher phospholipase activity than LPL. The structural basis for this difference in substrate specificity has not been definitively established. We recently demonstrated that the 22-amino acid loops ("lids") covering the catalytic sites of LPL and HL are critical for the interaction with lipid substrate (Dugi, K.A., Dichek, H.L., Talley, G.D., Brewer, H.B., Jr., and Santamarina-Fojo, S. (1992) J. Biol. Chem. 267, 25086-25091). To determine whether the lipase lid plays a role in conferring the different substrate specificities of HL and LPL, we have generated four chimeric lipases. Characterization of these chimeric enzymes using TG (triolein and tributyrin) or PL (dioleoylphosphatidylcholine (DOPC) vesicles, DOPC proteoliposomes, and DOPC-mixed liposomes) substrates demonstrated marked differences between their relative PL/TG hydrolyzing activities. Chimeric LPL containing the lid of HL had reduced triolein hydrolyzing activity (49% of the wild type), but increased phospholipase activity in DOPC vesicle, DOPC proteoliposome, and DOPC-mixed liposome assay systems (443, 628, and 327% of wild-type LPL, respectively). In contrast, chimeric HL containing the LPL lid was more active against triolein (123% of the wild type) and less active against DOPC (23, 0, and 30%, respectively) than normal HL. Similar results were obtained when the lipase lids were exchanged in chimeric enzymes containing the NH2-terminal end of LPL and the COOH-terminal domain of HL. Exchange of the LPL and HL lids resulted in a reversal of the phospholipase/neutral lipase ratio, establishing the important role of this region in mediating substrate specificity. In summary, the lid covering the catalytic domains in LPL and HL plays a crucial role in determining lipase substrate specificity. The lid of LPL confers preferential triglyceride hydrolysis, whereas the lid of HL augments phospholipase activity. This study provides new insight into the structural basis for the observed in vivo differences in LPL and HL function.
Synthesis of hybrid inorganic–organic mesoporous silica by co-condensation of siloxane and organosiloxane precursors (1996)

Organically functionalized mesoporous silicas are prepared at room temperature by the co-condensation of tetraethoxysilane and organosiloxanes in the presence of surfactant templates; the resulting materials are the first examples of covalently linked, ordered, hybrid inorganic–organic networks.
When peer-to-peer comes face-to-face: collaborative peer-to-peer computing in mobile ad-hoc networks (2002)

This paper motivates and describes the notion of mobile ad-hoc information systems. Such a system consists of a decentralized and self-organizing network of autonomous, mobile devices that interact as peers. Connectivity is determined by distance between devices; as hosts change their physical location they establish pair-wise communication links based on mutual proximity. We describe application scenarios for mobile ad-hoc information systems and identify technical challenges of a generic software infrastructure. Moreover, we present the goals and architecture of Proem, a peer-to-peer system and development platform for mobile ad-hoc applications. Proem has successfully been used as instructional tool in an advanced software engineering course on peer-to-peer computing.
New CNS-active drugs which are second-generation valproic acid: can they lead to the development of a magic bullet? (2003)

At present there are three compounds in clinical trials in patients with epilepsy that can be regarded as second-generation VPA: valproyl glycinamide, 3-methylbutanamide or isovaleramide and SPD421 (DP-VPA). For any one of these second-generation valproic acids to become a successful follow-up compound to VPA, it has to fulfil the above criteria and also possess favorable pharmacokinetics.
Ponatinib Inhibits Polyclonal Drug-Resistant KIT Oncoproteins and Shows Therapeutic Potential in Heavily Pretreated Gastrointestinal Stromal Tumor (GIST) Patients (2014)

Ponatinib possesses potent activity against most major clinically relevant KIT mutants and has demonstrated preliminary evidence of activity in patients with refractory GIST. These data strongly support further evaluation of ponatinib in patients with GIST.
PAMINA: A Certificate Based Privilege Management System. (2002)

In this paper we present PAMINA (Privilege Administration and Management INfrAstructure), a privilege management system using authorization certificates. Our system supports distributed environments where autonomous authorities can manage and delegate privileges in accordance with their own policies. We introduce Improved Certification Verification Trees (I-CVTs) that guarantee very efficient and trustworthy certificate management. I-CVTs can provide undeniable proofs for the non-existence of a given certificate in contrast to CVTs as proposed in [1]. As a result, each authority can store its own I-CVT in a central, non-trusted, and replicable database. This database provides authenticated verifiers with basically only those certificates that are required to determine whether a user should be granted access to a resource or not. Since the system implements the pull model, clients need not to be involved in the access control decision process. PAMINA handles delegation trees instead of simple delegation chains because authorities can delegate privileges in one certificate that were assigned to them by several certificates. In the prototype that we describe here, PAMINA manages certificates based on X.509.
Calcium antagonists for acute ischemic stroke (2000)

No evidence is available to justify the use of calcium antagonists in patients with acute ischaemic stroke.
Improving Image Matting Using Comprehensive Sampling Sets (2013)

In this paper, we present a new image matting algorithm that achieves state-of-the-art performance on a benchmark dataset of images. This is achieved by solving two major problems encountered by current sampling based algorithms. The first is that the range in which the foreground and background are sampled is often limited to such an extent that the true foreground and background colors are not present. Here, we describe a method by which a more comprehensive and representative set of samples is collected so as not to miss out on the true samples. This is accomplished by expanding the sampling range for pixels farther from the foreground or background boundary and ensuring that samples from each color distribution are included. The second problem is the overlap in color distributions of foreground and background regions. This causes sampling based methods to fail to pick the correct samples for foreground and background. Our design of an objective function forces those foreground and background samples to be picked that are generated from well-separated distributions. Comparison on the dataset at and evaluation by www.alphamatting.com shows that the proposed method ranks first in terms of error measures used in the website.
An autoregulatory region in protein kinase C: the pseudoanchoring site. (1995)

We have previously identified receptors for activated C kinase (RACKs) as components of protein kinase C (PKC) signaling. RACK1, a recently cloned 36-kDa RACK, has short sequences of homology to PKC. A possible explanation for the homologous sequences between the ligand (PKC) and its intracellular receptor (RACK1) may be that, similar to the pseudosubstrate autoregulatory sequence on PKC, there is also a pseudo-RACK1 binding site on the enzyme. If this is the case, peptides with these sequences (derived from either RACK1 or PKC) are expected to affect PKC binding to RACK1 in vitro and PKC-mediated functions in vivo. Here, we show that the PKC-derived peptide (pseudo-RACK1 peptide), but not its RACK1 homologue, modulated PKC function both in vitro and in vivo. Our data suggest that the pseudo-RACK1 peptide binds and activates PKC in the absence of PKC activators and thereby acts as an agonist of PKC function in vivo. Therefore, the pseudo-RACK1 sequence in PKC appears to be another autoregulatory site; when PKC is in an inactive conformation, the pseudo-RACK1 site interacts with the RACK-binding site. Activation of PKC exposes the RACK-binding site, enabling the association of the enzyme with its anchoring RACK. Similar pseudoanchoring sites may regulate the function of other protein kinases.
Air Stable Doping and Intrinsic Mobility Enhancement in Monolayer Molybdenum Disulfide by Amorphous Titanium Suboxide Encapsulation (2015)

To reduce Schottky-barrier-induced contact and access resistance, and the impact of charged impurity and phonon scattering on mobility in devices based on 2D transition metal dichalcogenides (TMDs), considerable effort has been put into exploring various doping techniques and dielectric engineering using high-κ oxides, respectively. The goal of this work is to demonstrate a high-κ dielectric that serves as an effective n-type charge transfer dopant on monolayer (ML) molybdenum disulfide (MoS2). Utilizing amorphous titanium suboxide (ATO) as the "high-κ dopant", we achieved a contact resistance of ∼180 Ω·μm that is the lowest reported value for ML MoS2. An ON current as high as 240 μA/μm and field effect mobility as high as 83 cm(2)/V-s were realized using this doping technique. Moreover, intrinsic mobility as high as 102 cm(2)/V-s at 300 K and 501 cm(2)/V-s at 77 K were achieved after ATO encapsulation that are among the highest mobility values reported on ML MoS2. We also analyzed the doping effect of ATO films on ML MoS2, a phenomenon that is absent when stoichiometric TiO2 is used, using ab initio density functional theory (DFT) calculations that shows excellent agreement with our experimental findings. On the basis of the interfacial-oxygen-vacancy mediated doping as seen in the case of high-κ ATO-ML MoS2, we propose a mechanism for the mobility enhancement effect observed in TMD-based devices after encapsulation in a high-κ dielectric environment.
Incomplete processing of mutant lamin A in Hutchinson–Gilford progeria leads to nuclear abnormalities, which are reversed by farnesyltransferase inhibition (2005)

Hutchinson-Gilford progeria syndrome (HGPS) is typically caused by mutations in codon 608 (G608G) of the LMNA gene, which activates a cryptic splice site resulting in the in-frame loss of 150 nucleotides from the lamin A message. The deleted region includes a protein cleavage site that normally removes 15 amino acids, including a CAAX box farnesylation site, from the lamin A protein. We investigated the processing of the C-terminus of the mutant protein, 'progerin', and found that it does not undergo cleavage and, indeed, remains farnesylated. The retention of the farnesyl group may have numerous consequences, as farnesyl groups increase lipophilicity and are involved in membrane association and in protein interactions, and is likely to be an important factor in the HGPS phenotype. To further investigate this, we studied the effects of farnesylation inhibition on nuclear phenotypes in cells expressing normal and mutant lamin A. Expression of a GFP-progerin fusion protein in normal fibroblasts caused a high incidence of nuclear abnormalities, as was also seen in HGPS fibroblasts, and resulted in abnormal nuclear localization of GFP-progerin in comparison with the localization pattern of GFP-lamin A. Expression of a GFP-lamin A fusion containing a mutation preventing the final cleavage step, causing the protein to remain farnesylated, displayed identical localization patterns and nuclear abnormalities as in HGPS cells and in cells expressing GFP-progerin. Exposure to a farnesyltransferase inhibitor (FTI), PD169541, caused a significant improvement in the nuclear morphology of cells expressing GFP-progerin and in HGPS cells. These results implicate the abnormal farnesylation of progerin in the cellular phenotype in HGPS cells and suggest that FTIs may represent a therapeutic option for patients with HGPS.
LIF/STAT3 Signaling Fails to Maintain Self‐Renewal of Human Embryonic Stem Cells (2004)

Murine embryonic stem (mES) cells remain undifferentiated in the presence of leukemia inhibitory factor (LIF), and activation of signal transducer and activator of transcription 3 (STAT3) via LIF receptor (LIFR) signaling appears sufficient for maintenance of mES cell pluripotency. Anecdotal and contradictory accounts exist for the action of LIF in the culture of human embryonic stem cells, and the nature of LIF signaling and whether the LIF-STAT3 pathway is conserved in human embryonic stem cells (hESCs) has not been systematically explored. In this study, we show that the LIFRbeta and the signaling subunit gp130 are expressed in hESCs and that human LIF can induce STAT3 phosphorylation and nuclear translocation in hESCs. Nevertheless, despite the functional activation of the LIF-STAT3 signaling pathway, human LIF is unable to maintain the pluripotent state of hESCs. Feeder-free culture conditions that maintain hESCs in an undifferentiated state do not show activation of STAT3, suggesting that distinct signaling mechanisms govern the self-renewal of hESCs.
Abnormalities of neural circuitry in Alzheimer's disease (1998)

Severe pathology in Alzheimer's disease (AD) results in marked disruption of cortical circuitry. Formation of neurofibrillary tangles, neuronal loss, decrease in dendritic extent, and synaptic depletion combine to halt communication among various cortical areas, resulting in anatomic isolation and fragmentation of many cortical zones. The clinical manifestation of this disruption is severe and debilitating cognitive dysfunction, often accompanied by psychiatric and behavioral disturbances and a diminished ability to perform activities of daily living. However, different cortical circuits are not equally vulnerable to AD pathology. In particular, two cortical systems that appear to be involved in the neural processing of memory are selectively vulnerable to degeneration in AD. One consists of connections between the hippocampus and its neighboring cortical structures within the temporal lobe. The second is the cortical cholinergic system that originates in neurons within the basal forebrain and innervates the entire cortical mantle. The circuitry in these systems shows early and severe degenerative changes in the course of AD. The selective vulnerability of these circuits is the probable reason for the early and marked loss of memory observed in these patients. This review presents current knowledge of the general pattern of cortical circuitry, followed by a summary of abnormalities of this circuitry in AD. The cortical circuits that exhibit selective pathology in AD are described in greater detail. Therapeutic implications of the abnormal circuitry in AD are also discussed. For therapies to be effective, early diagnosis of AD is necessary. Future efforts at AD therapy must be combined with an equally intense effort to develop tools capable of early diagnosis of AD, preferably at a preclinical stage before the onset of cognitive symptoms.
Superresolution Microscopy on the Basis of Engineered Dark States (2008)

New concepts for superresolution fluorescence microscopy by subsequent localization of single molecules using photoswitchable or photoactivatable fluorophores are rapidly emerging and provide new ways to resolve structures beyond the diffraction limit. Here, we demonstrate that superresolution imaging can be carried out with practically every single-molecule compatible, synthetic fluorophore by controlling their emission properties. We prepare dark states by removing oxygen that extends the triplet state lifetime to several milliseconds. We further increase the duration of the off-states using electron transfer reactions to create radical ion states of severalfold longer lifetimes. Imaging single molecules, actin filaments, and microtubules in fixed cells as well as simulations demonstrate that the thus created dark states are sufficiently long for resolution of approximately 50 nm.
Concise Review: Immune Recognition of Induced Pluripotent Stem Cells (2012)

Autologous-induced pluripotent stem cells (iPSCs) may eventually be used in cell replacement therapies to treat a wide range of diseases and have been touted as a solution to the vexing problem of immune rejection in this context. Emerging evidence suggests, however, that ostensibly histocompatible iPSCs may be rejected following transplantation. Here, we review the mechanisms that contribute to immunogenicity in iPSCs and forward approaches to permit their acceptance in potential cell replacement therapies.
An adhesive protein capsule of Escherichia coli (1985)

The nature of the adhesive capacity of three hemagglutinating Escherichia coli strains that had earlier been described as nonfimbriated was studied. The strains that were isolated from human disease adhered to human buccal and urinary tract epithelial cells, an adhesion that was not inhibited by D-mannose. By crossed immunoelectrophoresis it was shown that the three strains produced a common antigen, Z1, developed after growth at 37 degrees C but not 18 degrees C. One of the strains produced an additional antigen, Z2, of almost the same electrophoretic mobility in crossed immunoelectrophoresis. A mutant of this strain deficient of its polysaccharide K antigen had maintained the adhesive capacity, indicating that the K antigen was not responsible for adhesion. A further mutant of the acapsular mutant produced a strongly reduced amount of the Z antigens and had lost the ability to adhere. The Z1 (and Z2?) antigens were therefore deemed to be responsible for adhesion. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis of extracts of cells of the three strains, a heavy Coomassie-blue stained line was seen, indicating the presence of a protein subunit of molecular weight slightly above 14,400. By immunoblotting with absorbed antiserum, it was shown that this protein was the same as that detected by crossed immunoelectrophoresis. Protease from Streptomyces griseus, but not trypsin, digested the protein. Heating to 100 degrees C did not affect it. By immunoelectron microscopy of embedded and sectioned bacteria that had first been treated with specific antisera and ferritin-labeled antirabbit immunoglobulin, the protein adhesin-antibody complex was found to surround the bacteria as a heavy capsule. After negative staining with uranylacetate (pH approximately 4), the capsule appeared as a mesh of very fine filaments. The possible role of this capsule in the pathogenesis of disease is discussed.