gebhart/patrepeval huggingface dataset:
Identification of Novel Protein Kinase A Phosphorylation Sites in the M-domain of Human and Murine Cardiac Myosin Binding Protein-C Using Mass Spectrometry Analysis (2010)

Cardiac myosin binding protein-C (cMyBP-C) is a large multidomain accessory protein bound to myosin thick filaments in striated muscle sarcomeres. It plays an important role in the regulation of muscle contraction, and mutations in the gene encoding cMyBP-C are a common cause of familial hypertrophic cardiomyopathy, the leading cause of sudden cardiac death in young people. (1) The N-terminal domains including the C0, C1, cMyBP-C motif, and C2 domains play a crucial role in maintaining and modulating actomyosin interactions (keeping normal cardiac function) in a phosphorylation-dependent manner. The cMyBP-C motif or "M-domain" is a highly conserved linker domain in the N-terminus of cMyBP-C that contains three to five protein kinase A (PKA) phosphorylation sites, depending on species. For the human isoform, three PKA sites were previously identified (Ser(275), Ser(284), and Ser(304)), while three homologous sites exist in the murine isoform (Ser(273), Ser(282), and Ser(302)). The murine cMyBP-C isoform contains an additional conserved consensus site, Ser(307) that is not present in the human isoform. In this study, we investigated sites of PKA phosphorylation of murine and human cMyBP-C by treating the recombinant protein C0C2 ( approximately 50 KDa, which contains the N-terminal C0, C1, M, and C2 domains) and C1C2 (approximately 35 KDa, contains C1, M, and C2 domains) with PKA and assessing the phosphorylation states using SDS-PAGE with ProQ Diamond staining, and powerful hybrid mass spectrometric analyses. Both high-accuracy bottom-up and measurements of intact proteins mass spectrometric approaches were used to determine the phosphorylation states of C0C2 and C1C2 proteins with or without PKA treatment. Herein, we report for the first time that there are four PKA phosphorylation sites in both murine and human M-domains; both murine Ser(307) and a novel human Ser(311) can be phosphorylated in vitro by PKA. Future studies are needed to investigate the phosphorylation state of murine and human cMyBP-C in vivo.
Taxol in advanced, hormone-refractory carcinoma of the prostate. A phase II trial of the eastern cooperative oncology group (1993)

In the subset of patients with hormone-refractory prostate cancer and bidimensionally measurable disease, Taxol at this dosage has only minor activity.
Undersulfated and Glycol-Split Heparins Endowed with Antiangiogenic Activity (2004)

Tumor neovascularization (angiogenesis) is regarded as a promising target for anticancer drugs. Heparin binds to fibroblast growth factor-2 (FGF2) and promotes the formation of ternary complexes with endothelial cell surface receptors, inducing an angiogenic response. As a novel strategy to generate antiangiogenic substances exploiting binding to FGF2 while preventing FGF receptor (FGFR) activation, sulfation gaps were generated along the heparin chains by controlled alkali-catalyzed removal of sulfate groups of iduronic acid 2-O-sulfate residues, giving rise to the corresponding epoxide derivatives. A new class of heparin derivatives was then obtained by opening the epoxide rings followed by oxidative glycol-splitting of the newly formed (and the preexisting) nonsulfated uronic acid residues. In vitro these heparin derivatives prevent the formation of FGFR/FGF2/heparan sulfate proteoglycan ternary complexes and inhibit FGF2-stimulated endothelial cell proliferation. They exert an antiangiogenic activity in the chick embryo chorioallantoic membrane assay, where the parent heparin is inactive. Low and very low molecular weight derivatives of a prototype compound, as well as its glycine and taurine derivatives obtained by reductive amination of glycol-split residues, retained the angiostatic activity. A significant relationship was found between the extent of glycol-splitting and the FGF2-antagonist/angiostatic activities of these heparin derivatives. Molecular dynamics calculations support the assumption that glycol-split residues act as flexible joints that, while favoring 1:1 binding to FGF2, disrupt the linearity of heparin chains necessary for formation of active complexes with FGFRs.
Doxorubicin induces calcium release from terminal cisternae of skeletal muscle. A study on isolated sarcoplasmic reticulum and chemically skinned fibers. (1985)

In this study, we investigated the effect of the anticancer drug doxorubicin on Ca2+ fluxes of isolated highly purified sarcoplasmic reticulum fractions (longitudinal tubules and terminal cisternae (Saito, A., Seiler, S., Chu, A., and Fleischer, S. (1984) J. Cell Biol. 99, 875-885] and of chemically skinned skeletal muscle fibers of the rabbit. In terminal cisternae, doxorubicin inhibits Ca2+ uptake (IC50 at 0.5 microM) and increases 2.6-fold Ca2+-dependent ATPase rate (half-maximal activation at 3 microM) and unidirectional Ca2+ efflux (8-fold stimulation at 25 microM). On the contrary, doxorubicin is without effect on longitudinal tubules. In skinned muscle fibers, doxorubicin induces rapid and transient Ca2+ release, as measured by tension development (half-maximal stimulation at 6 microM), which is completely and reversibly inhibited by ruthenium red, a known inhibitor of Ca2+ release from isolated terminal cisternae. Doxorubicin has no effect on the sarcoplasmic reticulum Ca2+ pump and on the contractile apparatus of skinned muscle fibers. It is concluded that doxorubicin activates Ca2+ release from sarcoplasmic reticulum and opens a Ca2+ efflux pathway (Ca2+ channel) selectively localized in terminal cisternae. Doxorubicin might interact with Ca2+ channels involved in physiological Ca2+ release.
Distribution of estrogen receptor in ductal carcinoma in situ of the breast. (1993)

The incidence of ER in DCIS is similar to the incidence of ER in invasive carcinoma, leading to the speculation that ER-positive invasive carcinoma originates from an ER-positive precursor lesion. Because only 60% of the cases have detectable ER and approximately 70% of positively stained ERs are expected to be functional (as in invasive carcinoma), it appears that approximately 42% of the patient population with DCIS will benefit from antiestrogen therapy.
Evidence for a third genetic locus causing familial hypercholesterolemia: a non-LDLR, non-APOB kindred (1999)

Monogenically inherited hypercholesterolemia is most commonly caused by mutations at the low density lipoprotein receptor (LDLR) locus causing familial hypercholesterolemia (FH) or at the apolipoprotein B (APOB) locus causing the disorder familial defective apoB (FDB). Probands from 47 kindreds with a strict clinical diagnosis of FH were selected from the Cardiovascular Genetics Research Lipid Clinic, Utah, for molecular genetic analysis. Using a combination of single-strand conformation polymorphism (SSCP) and direct sequencing, 12 different LDLR gene mutations were found in 16 of the probands. Three of the probands were carriers of the APOB R3500Q mutation. In five of the remaining 28 pedigrees where no mutation had been detected, samples from enough relatives were available to examine co-segregation with the LDLR region using the microsatellite marker D19S221, which is within 1 Mb centromeric of the LDLR locus, and D19S394, sited within 150 kb telomeric of the LDLR locus. In four of the families there was strong evidence for co-segregation between the LDLR locus and the phenotype of hypercholesterolemia, but in one large family with 18 living affected members and clear-cut bimodal hypercholesterolemia, there were numerous exclusions of co-segregation. Using length polymorphic markers within and outside the APOB gene, linkage of phenotype in this family to the APOB region was similarly excluded. In this large family, the degree of hypercholesterolemia, prevalence of tendon xanthomata, and occurrence of early coronary disease were indistinguishable from the other families studied. In summary, the data provide unequivocal evidence that a third locus can be etiological for monogenic familial hypercholesterolemia and should be reinvigorating to research in this field.
Ischemic Preconditioning and Brain Tolerance: Temporal Histological and Functional Outcomes, Protein Synthesis Requirement, and Interleukin-1 Receptor Antagonist and Early Gene Expression (1998)

PC is a powerful inducer of ischemic brain tolerance as reflected by preservation of brain tissue and motor function. PC induces IT that is dependent on de novo protein synthesis. New protein(s) that occurs at the PC brain site 1 to 7 days after PC contributes to the neuroprotection. Those proteins that are produced after the more severe PMCAO in PC animals apparently do not contribute to IT. The PC-induced IT is also associated with increased expression of the neuroprotective protein interleukin-1 receptor antagonist and a reduced postischemic expression of the early response genes c-fos and zif268. (Stroke. 1998;29:1937-1951.)
Neuregulin-1 immunoglobulin-like domain mutant mice: clozapine sensitivity and impaired latent inhibition (2005)

Genetic and behavioral studies in humans and mouse mutants have implicated the gene encoding neuregulin-1 (Nrg-1) as a candidate susceptibility gene for schizophrenia. We examined the behavior of mice heterozygous for a mutation in neuregulin-1's immunoglobulin (Ig)-like domain (Ig-nrg-1 mice). We found that these animals displayed behaviors related to a schizophrenia-like phenotype, such as clozapine suppression of open-field and running wheel activity and impaired latent inhibition. Contrary to findings with other nrg-1 mutants, Ig-nrg-1 mice did not exhibit significantly elevated locomotion relative to littermate controls. These results suggest that Ig-Nrg-1's contribute to some - but not all - aspects of the schizophrenia-like phenotype of nrg-1 mutants, and further support nrg-1 as a candidate gene for schizophrenia.
Organic solvent tolerance and antibiotic resistance increased by overexpression of marA in Escherichia coli (1997)

We previously reported that overexpression of the soxS or robA gene causes in several Escherichia coli strains the acquisition of higher organic solvent tolerance and also increased resistance to a number of antibiotics (H. Nakajima, K. Kobayashi, M. Kobayashi, H. Asako, and R. Aono, Appl. Environ. Microbiol. 61:2302-2307, 1995). Most E. coli strains cannot grow in the presence of cyclohexane. We isolated the marRAB genes from a Kohara lambda phage clone and cyclohexane-tolerant mutant strain OST3408. We found a substitution of serine for arginine at position 73 in the coding region of marR of OST3408 and designated the gene marR08. Our genetic analysis revealed that marR08 is responsible for the cyclohexane-tolerant phenotype. We observed that the marA gene on high-copy-number plasmids increased the organic solvent tolerance of E. coli strains. Furthermore, exposure of E. coli cells to salicylate, which activates the mar regulon genes, also raised organic solvent tolerance. Overexpression of the marA, soxS, or robA gene increased resistance to numerous antibiotics but not to hydrophilic aminoglycosides.
Synthesis of a new zinc finger peptide; comparison of its `code' deduced and `CASTing' derived binding sites (1997)

Using two synthetic oligonucleotides, we have constructed a new gene containing three zinc finger motifs of the Cys2-His2 type. We named this artificial gene 'Mago'. The Mago nucleotide triplets encoding the amino acid positions, described to be crucial for DNA binding specificity, have been chosen on the basis of the proposed recognition 'code' that relates the zinc finger's primary structure to the DNA binding target. Here we demonstrate that Mago protein specifically binds the 'code' DNA target, with a dissociation constant (Kd) comparable to the Kd of the well known Zif268 protein with its binding site. Moreover, we show that the deduced Mago 'code' and the 'experimental' selected DNA binding sites are almost identical, differing only in two nucleotides at the side positions.
Quantitation of genomic methylation using ligation-mediated PCR. (1993)

We have developed a new technique for the quantitation of CpG methylation of genomic DNA. This method measures the conversion of a larger amplified DNA fragment to a shorter DNA product correlating with demethylation. The procedure uses pairs of non-isoschizomeric enzymes, one of which is methylation-sensitive, to cleave genomic DNA at closely spaced sites. The extent of cleavage by the methylation-sensitive restriction enzyme is quantitated by amplification of these digestion products with ligation-mediated PCR and radioactive labeling of the product. The ratio of the two amplified fragments correlates with the degree of methylation at the restriction site. The analysis is rapid, quantitative, internally controlled and requires small quantities of genomic DNA.
Small focal cortical dysplasia lesions are located at the bottom of a deep sulcus (2008)

Focal cortical dysplasia (FCD) is often characterized by minor structural changes that may go unrecognized by standard radiological analysis. Visual assessment of morphological characteristics of FCD and sulci harbouring them is difficult due to the complexity of brain convolutions. Our purpose was to elucidate and quantify the spatial relationship between FCD lesions and brain sulci using automated sulcal extraction and morphometry. We studied 43 consecutive FCD patients using high-resolution MRI. Lesions were classified into small and large using qualitative (detection on initial clinical assessment of conventional MRI) and quantitative (volume) criteria. Sulci were identified and labelled automatically using an algorithm based on a congregation of neural networks. Segmented FCD lesions and sulci were then simultaneously visualized in 3D. We measured mean and maximum depth of sulci related to each FCD and of the corresponding sulci in 21 healthy controls. In addition, we calculated sulcal depth within the FCD neighbourhood. Twenty-one (21/43 = 49%) patients had small FCD lesions (volume range: 128-3093 mm(3)). Among them, 17 (81%) had been overlooked during initial radiological evaluation and were subsequently identified using image processing. Eighteen (18/21 = 86%) small FCD lesions were located at the bottom of a sulcus. Two others were related to the walls of two sulci and one was located at the crown of a gyrus. Mean and maximum depth of sulci related to the FCD was higher than that of the corresponding sulci in controls (P < 0.008). Sulcal depth within lesional neighbourhood had larger mean depth than that of the entire sulcus (P < 0.0002). Evidence that small FCD lesions are preferentially located at the bottom of an abnormally deep sulcus may be used to direct the search for developmental abnormalities, particularly in patients in whom large-scale MRI features are only mildly abnormal or absent.
Morphological, Chemical, and Antigenic Organization of Mammalian C-Type Viruses (2015)

New features in the architecture of mammalian type C viruses, in particular knoblike surface projections and hexagonally arranged subunits on the core shell could be demonstrated by electron microscopy, taking advantage of newly developed preparation techniques. As examples, murine leukemia viruses (MuLVs) and newly isolated porcine and bovine C viruses are presented. The major proteins of a MuLV were isolated and partially characterized in chemical terms and with respect to their serological and other biological activities, such as interfering and hemagglutinating (HA) capacity. Most of the characterized proteins could be localized in particular substructures of the virion either by selective removal or isolation of electron microscopically identifiable constituents. The information obtained allowed the design of a more detailed model of mammalian C viruses. Special attention was devoted to the further characterization of interspecies antigens of mammalian C viruses. Different antigenic determinants were revealed. Their distribution allows further subgrouping of mammalian C viruses.
Autologous Chondrocyte Implantation in Knee Joint: MR Imaging and Histologic Features at 1-year Follow-up (2005)

With the methods presented here, MR imaging findings cannot predict ACI graft histologic features, and graft histologic appearance determined at biopsy was not related to graft signal intensity, graft thickness, overgrowth, surface smoothness, integration with adjacent cartilage or underlying bone, signal intensity change in underlying bone marrow, or underlying bone contour. Overgrowth and bone marrow changes underneath the graft were common.
Lyophilization of Nonviral Gene Delivery Systems (2003)

This chapter presents a qualitative description of the freeze-drying process as it pertains to the development of stable, dry polycation-DNA complex formulations. It is not intended to be a comprehensive treatise on freeze-drying. Readers are referred to a series of excellent papers by Pikal (1-5) for more detailed, quantitative explanations of the freeze-drying process.
Learning visual groups from co-occurrences in space and time (2015)

We propose a self-supervised framework that learns to group visual entities based on their rate of co-occurrence in space and time. To model statistical dependencies between the entities, we set up a simple binary classification problem in which the goal is to predict if two visual primitives occur in the same spatial or temporal context. We apply this framework to three domains: learning patch affinities from spatial adjacency in images, learning frame affinities from temporal adjacency in videos, and learning photo affinities from geospatial proximity in image collections. We demonstrate that in each case the learned affinities uncover meaningful semantic groupings. From patch affinities we generate object proposals that are competitive with state-of-the-art supervised methods. From frame affinities we generate movie scene segmentations that correlate well with DVD chapter structure. Finally, from geospatial affinities we learn groups that relate well to semantic place categories.
A Stereoselective Anti-Aldol Route to (3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-ol: A Key Ligand for a New Generation of HIV Protease Inhibitors (2006)

A stereoselective synthesis of (3<i>R</i>,3a<i>S</i>,6a<i>R</i>)-hexahydrofuro[2,3-<i>b</i>]furan-3-ol, an important high affinity P<sub>2</sub>-ligand, in high enantiomeric excess (>99%) is reported. The synthesis features an ester-derived titanium enolate based highly stereoselective <i>anti</i>-aldol reaction as the key step.
Transmission of Hepatitis A to Patients with Hemophilia by Factor VIII Concentrates Treated with Organic Solvent and Detergent To Inactivate Viruses (1994)

Hepatitis A was transmitted by a factor VIII concentrate treated by a virucidal method (solvent-detergent) that ineffectively inactivates nonenveloped viruses.
Processing of Thionin Precursors in Barley Leaves by a Vacuolar Proteinase (1997)

Thionins are synthesized as precursors with a signal peptide and a long C-terminal acidic peptide that is post-translationally processed. A fusion protein including the maltose-binding protein from Escherichia coli (MalE), thionin DG3 from barley leaves, and its acidic C-terminal peptide has been used to obtain antibodies that recognize both domains of the precursor. In barley leaf sections, mature thionins accumulated in the vacuolar content, while the acidic peptide was not detected in any cell fraction. Brefeldin A and monensin inhibited processing of the precursor but its export from the microsomal fraction was not inhibited. Both purified vacuoles and an acid (pH 5.5) extract from leaves processed the fusion protein into a MalE-thionin and an acidic peptide fragment. A 70-kDa proteinase that effected this cleavage was purified from the acid extract. Processing of the fusion protein by both lysed vacuoles and the purified proteinase was inhibited by Zn2+ and by Cu2+, but not by inhibitors of the previously described vacuolar processing thiol or aspartic proteinases. In vivo processing of the thionin precursor in leaf sections was also inhibited by Zn2+ and Cu2+. Variants of the fusion protein with altered processing sites that represented those of thionin precursors from different taxa were readily processed by the proteinase, whereas changing the polarity of either the C-terminal or N-terminal residues of the processing site prevented cleavage by the proteinase.
RACCOON: A Real-time Autonomous Car Chaser Operating Optimally At Night (2005)

Abstract : RACCOON is a vision system that tracks car taillights at night. It builds a global map in real time of the lead vehicle's position based on the location and separation of the taillights in a sequence of video images. RACCOON has been integrated into a car following experiment on the CMU Navlab II, a computer-controlled HMMWV testbed. The Navlab II safely followed a lead vehicle on a winding road in light traffic at 32 km/h.
Protective Efficacy against Respiratory Syncytial Virus following Murine Neonatal Immunization with BBG2Na Vaccine: Influence of Adjuvants and Maternal Antibodies (1999)

Alum-adsorbed BBG2Na, a recombinant vaccine derived in part from the respiratory syncytial virus (RSV) subgroup A G protein, induced moderate antibody titers after 1 immunization in 1-week-old mice but conferred complete lung protection upon RSV challenge. The anti-BBG2Na IgG1-IgG2a neonatal isotype profile was suggestive of dominant Th2 responses compared with those in adults. Formulation of BBG2Na with a Th1-driving adjuvant efficiently shifted neonatal responses toward a more balanced and adultlike IgG1-IgG2a profile without compromising its protective efficacy. BBG2Na-induced protective immunity was maintained even after early life immunization in the presence of high titers of maternal antibodies. Under these conditions, the protective efficacy (86%-100%) reflected the high capacity of the nonglycosylated G2Na immunogen to escape inhibition by RSV-A-induced maternal antibodies. Thus, immunization with BBG2Na protected against viral challenge despite neonatal immunologic immaturity and the presence of maternal antibodies, two major obstacles to neonatal RSV vaccine development.
Third-order intermodulation distortion in capacitively-driven VHF micromechanical resonators (2006)

Substantial increases by more than 22 dB in the third-order input intercept points (IIP3) of capacitively trans- duced MEMS-based vibrating micromechanical resonators have been attained by using contour-mode disk geometries to replace previous clamped-clamped beam versions. Specifically, a 156-MHz contour-mode disk resonator with Q = 20,500 exhibits a measured IIP3 = 19.49 dBm, which is substantially better than the -3 dBm previously measured for a 10-MHz clamped-clamped beam resonator, and which now erases any lingering skepticism regarding the linearity of micro-scale mechanical resonators. Indeed, with IIP3's about 20 dBm, high Q communication filters using the micromechanical resonators of this work should now be able to replace present-day receive path filters with little degra- dation (only 0.11 dB) in cumulative receiver IIP3.
A 500&#x00B5;W neural tag with 2&#x00B5;V<inf>rms</inf> AFE and frequency-multiplying MICS/ISM FSK transmitter (2009)

Advances in electronic-neural interfaces have shown great potential for both neuroscience research and medical devices. Much of the work to date has focused on short-range inductive links for power and communication transfer. There is an emerging need for active miniaturized systems that stream neural data in the far field, which would enable the observation of brain activity in unconstrained animals such as mice or moths. Such systems cannot rely on near-field power transfer, and must be powered by small batteries or energy harvesters. We present a 500 muW fully integrated neural interface that wirelessly streams a digitized neural waveform over 15 m.