gebhart/patrepeval huggingface dataset:
Self-Assembly of Model DNA-Binding Peptide Amphiphiles (2005)

Peptide amphiphiles combine the specific functionality of proteins with the engineering convenience of synthetic amphiphiles. These molecules covalently link a peptide headgroup, typically from an active fragment of a larger protein, to a hydrophobic alkyl tail. Our research is aimed at forming and characterizing covalently stabilized, self-assembled, peptide-amphiphile aggregates that can be used as a platform for the examination and modular design and construction of systems with engineering biological activity. We have studied the self-assembly properties of a model DNA-binding amphiphile, having a GCN4 peptide as the headgroup and containing a polymerizable methacrylic group in the tail region, using a combination of small-angle X-ray scattering, small-angle neutron scattering, and cryo- transmission electron microscopy. Our results reveal a variety of morphologies in this system. The peptide amphiphiles assembled in aqueous solution to helical ribbons and tubules. These structures transformed into lamella upon DNA binding. In contrast with common surfactants, the specific interaction between the headgroups seems to play an important role in determining the microstructure. The geometry of the self-assembled aggregate can be controlled by means of adding a cosurfactant. For example, the addition of SDS induced the formation of spherical micelles.
Planning for retirement and anticipatory attitudes towards withdrawal from work (1974)

Abstract Inferences from previous studies on the socio-psychological meaning of the transition from work to retirement are reviewed. Data are reported on the nature and scope of pre-retirement planning in a sample of 215 older male and female industrial workers. Particular reference is made to the extent to which planning of leisure activities is related to the worker's attitudes towards retirement, and several intervening variables affecting this relation-ship are examined. Finally, some theoretical and practical implications for pre-retirement counselling and training are discussed. It is suggested that pre-retirement counselling schemes may not be able to compensate for failure to develop life-long habits of using free time constructively, or for inadequate financial provision for retirement.
In Vivo Identification of the Transforming Gene Product of Simian Sarcoma Virus (1982)

Simian sarcoma virus (SSV) deletion mutants were constructed from a molecular clone containing the entire infectious provirus. Transfection analysis of these mutants localized the SSV transforming gene to a small region of the viral genome encompassing its cell-derived sequence (v-sis). Antiserum to a peptide synthesized on the basis of the predicted amino acid sequence of the SSV transforming gene detected a 28,000-dalton protein that was specifically expressed in SSV transformed cells and that corresponded in size to that predicted from the v-sis coding sequence. The v-sis gene product designated p28sis was not a phosphoprotein, nor did it possess detectable protein kinase activity. These findings distinguish p28sis from a number of other retroviral onc proteins.
Efficacy of lamotrigine in the management of chemotherapy‐induced peripheral neuropathy (2008)

The results suggest that lamotrigine is not effective for relieving neuropathic symptoms in patients because of CIPN.
Whole-exome sequencing to identify novel somatic mutations in squamous cell lung cancers (2013)

Squamous cell lung cancer is a major histotype of non-small cell lung cancer (NSCLC) that is distinct from lung adenocarcinoma. We used whole-exome sequencing to identify novel non-synonymous somatic mutations in squamous cell lung cancer. We identified 101 single-nucleotide variants (SNVs) including 77 non-synonymous SNVs (67 missense and 10 nonsense mutations) and 11 INDELs causing frameshifts. We also found four SNVs located within splicing sites. We verified 62 of the SNVs (51 missense, 10 nonsense and 1 splicing-site mutation) and 10 of the INDELs as somatic mutations in lung cancer tissue. Sixteen of the mutated genes were also mutated in at least one patient with a different type of lung cancer in the Catalogue of Somatic Mutation in Cancer (COSMIC) database. Four genes (LPHN2, TP53, MYH2 and TGM2) were mutated in approximately 10% of the samples in the COSMIC database. We identified two missense mutations in C10orf137 and MS4A3 that also occurred in other solid-tumor tissues in the COSMIC database. We found another somatic mutation in EP300 that was mutated in 4.2% of the 2,020 solid-tumor samples in the COSMIC database. Taken together, our results implicate TP53, EP300, LPHN2, C10orf137, MYH2, TGM2 and MS4A3 as potential driver genes of squamous cell lung cancer.
Telavancin, a Multifunctional Lipoglycopeptide, Disrupts both Cell Wall Synthesis and Cell Membrane Integrity in Methicillin-Resistant Staphylococcus aureus (2005)

The emergence and spread of multidrug-resistant gram-positive bacteria represent a serious clinical problem. Telavancin is a novel lipoglycopeptide antibiotic that possesses rapid in vitro bactericidal activity against a broad spectrum of clinically relevant gram-positive pathogens. Here we demonstrate that telavancin's antibacterial activity derives from at least two mechanisms. As observed with vancomycin, telavancin inhibited late-stage peptidoglycan biosynthesis in a substrate-dependent fashion and bound the cell wall, as it did the lipid II surrogate tripeptide N,N'-diacetyl-L-lysinyl-D-alanyl-D-alanine, with high affinity. Telavancin also perturbed bacterial cell membrane potential and permeability. In methicillin-resistant Staphylococcus aureus, telavancin caused rapid, concentration-dependent depolarization of the plasma membrane, increases in permeability, and leakage of cellular ATP and K(+). The timing of these changes correlated with rapid , concentration-dependent loss of bacterial viability, suggesting that the early bactericidal activity of telavancin results from dissipation of cell membrane potential and an increase in membrane permeability. Binding and cell fractionation studies provided direct evidence for an interaction of telavancin with the bacterial cell membrane; stronger binding interactions were observed with the bacterial cell wall and cell membrane relative to vancomycin. We suggest that this multifunctional mechanism of action confers advantageous antibacterial properties.
The fabrication of silicon nanostructures by focused-ion-beam implantation and TMAH wet etching (2010)

Local gallium implantation of silicon by a focused ion beam (FIB) has been used to create a mask for anisotropic tetramethylammonium hydroxide (TMAH) wet etching. The dependence of the etch stop properties of gallium-doped silicon on the implanted dose has been investigated and a dose of 4 x 10(13) ions cm(- 2) has been determined to be the threshold value for achieving observable etching resistance. Only a thin, approx. 50 nm, surface layer is found to be durable enough to serve as a mask with a high selectivity of at least 2000:1 between implanted and non-implanted areas. The combined FIB-TMAH process has been used to generate various types of 3D nanostructures including nanochannels separated by thin vertical sidewalls with aspect ratios up to 1:30, ultra-narrow (approx. 25 nm) freestanding bridges and cantilevers, and gratings with a resolution of 20 lines microm(- 1).
Synthesis and Characterization of 9 nm Pt–Ni Octahedra with a Record High Activity of 3.3 A/mgPt for the Oxygen Reduction Reaction (2013)

Nanoscale Pt-Ni bimetallic octahedra with controlled sizes have been actively explored in recent years owning to their outstanding activity for the oxygen reduction reaction (ORR). Here we report the synthesis of uniform 9 nm Pt-Ni octahedra with the use of oleylamine and oleic acid as surfactants and W(CO)6 as a source of CO that can promote the formation of {111} facets in the presence of Ni. Through the introduction of benzyl ether as a solvent, the coverage of both surfactants on the surface of resultant Pt-Ni octahedra was significantly reduced while the octahedral shape was still attained. By further removing the surfactants through acetic acid treatment, we observed a specific activity 51-fold higher than that of the state-of-the-art Pt/C catalyst for the ORR at 0.93 V, together with a record high mass activity of 3.3 A mgPt(-1) at 0.9 V (the highest mass activity reported in the literature was 1.45 A mgPt(-1)). Our analysis suggests that this great enhancement of ORR activity could be attributed to the presence of a clean, well-preserved (111) surface for the Pt-Ni octahedra.
Poly (dodecacarborane-siloxanes) (1979)

Abstract The need for elastomeric polymers which will maintain their elastic properties at high temperatures has led to a wide interest in inorganic-based polymers [l]. The development of carborane-siloxane polymers in the early 1960s was a breakthrough in the search for a high-temperature elastomer. Incorporation of a carborane moiety into the siloxane backbone significantly enhanced the overall thermal stability [2].
Two fatty acid Δ9-desaturase genes, ole1 and ole2, from Mortierella alpina complement the yeast ole1 mutation (1999)

Genes encoding two distinct fatty acid delta9-desaturases were isolated from strains of the oleaginous fungus Mortierella alpina. Two genomic sequences, delta9-1 and delta9-2, each containing a single intron, were cloned from strain CBS 528.72 while one cDNA clone, LM9, was isolated from strain CBS 210.32. The delta9-1 gene encoded a protein of 445 aa which shared 99% identity with the LM9 gene product. These proteins also showed 40-60% identity to the delta9-desaturases (Ole1p) of other fungi and contained the three conserved histidine boxes, C-terminal cytochrome b5 fusion and transmembrane domains characteristic of endoplasmic reticulum membrane-bound delta9-desaturases. LM9 and delta9-1 are therefore considered to represent the same gene (ole1). The ole1 gene was transcriptionally active in all M. alpina strains tested and its function was confirmed by complementation of the Saccharomyces cerevisiae ole1 mutation. Fatty acid analysis of yeast transformants expressing the CBS 210.32 ole1 gene showed an elevated level of oleic acid (18:1) compared to palmitoleic acid (16:1), the major fatty acid component of wild-type S. cerevisiae. This indicated that the M. alpina delta9-desaturase had a substrate preference for stearic acid (18:0) rather than palmitic acid (16:0). Genomic clone delta9-2 (ole2) also encoded a protein of 445 aa which had 86% identity to the delta9-1 and LM9 proteins and whose ORF also complemented the yeast ole1 mutation. The transcript from this gene could only be detected in one of the six M. alpina strains tested, suggesting that its expression may be strain-specific or induced under certain physiological conditions.
Fast adaptive eigenvalue decomposition: a maximum likelihood approach (2002)

A new adaptive subspace estimation algorithm is presented, based on the maximisation of the likelihood functional. It requires little computational cost and the particular structure of the algorithm ensures the orthonormality of the estimated basis of eigenvectors. Application to moving sources localization shows the very good behavior of the algorithm when applied to problems of practical interest.
HRTF magnitude modeling using a non-regularized least-squares fit of spherical harmonics coefficients on incomplete data (2012)

Head-related transfer functions (HRTFs) represent the acoustic transfer function from a sound source at a given location to the ear drums of a human. They are typically measured from discrete source positions at a constant distance. Spherical harmonics decom-positions have been shown to provide a flexible representation of HRTFs. Practical constraints often prevent the retrieval of measure-ment data from certain directions, a circumstance that complicates the decomposition of the measured data into spherical harmonics. A least-squares fit of coefficients is a potential approach to determin-ing the coefficients of incomplete data. However, a straightforward non-regularized fit tends to give unrealistic estimates for the region were no measurement data is available. Recently, a regularized least-squares fit was proposed, which yields well-behaved results for the unknown region at the expense of reducing the accuracy of the data representation in the known region. In this paper, we propose using a lower-order non-regularized least-squares fit to achieve a well-behaved estimation of the unknown data. This data then allows for a high-order non-regularized least-squares fit over the entire sphere. We compare the properties of all three approaches applied to modeling the magnitudes of the HRTFs measured from a manikin. The proposed approach reduces the normalized mean-square er-ror by approximately 7 dB in the known region and 11 dB in the unknown region compared to the regularized fit. Index Terms — head-related transfer functions, spherical har-monics, interpolation, extrapolation, regularization 1.
Expression of mRNA for DNA methyltransferases and methyl-CpG–binding proteins and DNA methylation status on CpG islands and pericentromeric satellite regions during human hepatocarcinogenesis (2001)

To evaluate the significance of alterations in DNA methylation during human hepatocarcinogenesis, we examined levels of mRNA for DNA methyltransferases and methyl-CpG-binding proteins and the DNA methylation status in 67 hepatocellular carcinomas (HCCs). The average level of mRNA for DNMT1 and DNMT3a was significantly higher in noncancerous liver tissues showing chronic hepatitis or cirrhosis than in histologically normal liver tissues, and was even higher in HCCs. Significant overexpression of DNMT3b and reduced expression of DNMT2 were observed in HCCs compared with the corresponding noncancerous liver tissues. DNA hypermethylation on CpG islands of the p16 (8% and 66%) and hMLH1 (0% and 0%) genes and methylated in tumor (MINT) 1 (6% and 34%), 2 (24% and 58%), 12 (21% and 33%), 25 (0% and 5%), and 31 (0% and 23%) clones, and DNA hypomethylation on satellites 2 and 3 (18% and 67%), were detected in noncancerous liver tissues and HCCs, respectively. There was no significant correlation between the expression level of any DNA methyltransferase and DNA methylation status. Reduced expression of DNA repair protein, MBD4, was significantly correlated with poorer tumor differentiation and involvement of portal vein. Slightly reduced expression of MBD2 was detected in HCCs, and the expression of MeCP2 was particularly reduced in HCCs with portal vein involvement. These data suggest that overexpression of DNMT1 and DNMT3a, DNA hypermethylation on CpG islands, and DNA hypomethylation on pericentromeric satellite regions are early events during hepatocarcinogenesis, and that reduced expression of MBD4 may play a role in malignant progression of HCC.
Senescent cells re‐engineered to express soluble programmed death receptor‐1 for inhibiting programmed death receptor‐1/programmed death ligand‐1 as a vaccination approach against breast cancer (2018)

Various types of vaccines have been proposed as approaches for prevention or delay of the onset of cancer by boosting the endogenous immune system. We previously developed a senescent-cell-based vaccine, induced by radiation and veliparib, as a preventive and therapeutic tool against triple-negative breast cancer. However, the programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) pathway was found to play an important role in vaccine failure. Hence, we further developed soluble programmed death receptor-1 (sPD1)-expressing senescent cells to overcome PD-L1/PD-1-mediated immune suppression while vaccinating to promote dendritic cell (DC) maturity, thereby amplifying T-cell activation. In the present study, sPD1-expressing senescent cells showed a particularly active status characterized by growth arrest and modified immunostimulatory cytokine secretion in vitro. As expected, sPD1-expressing senescent tumor cell vaccine (STCV/sPD-1) treatment attracted more mature DC and fewer exhausted-PD1<sup>+</sup> T cells in vivo. During the course of the vaccine studies, we observed greater safety and efficacy for STCV/sPD-1 than for control treatments. STCV/sPD-1 pre-injections provided complete protection from 4T1 tumor challenge in mice. Additionally, the in vivo therapeutic study of mice with s.c. 4T1 tumor showed that STCV/sPD-1 vaccination delayed tumorigenesis and suppressed tumor progression at early stages. These results showed that STCV/sPD-1 effectively induced a strong antitumor immune response against cancer and suggested that it might be a potential strategy for TNBC prevention.
Biological Dosimetry of Ionizing Radiation (2012)

A worsening of the accidental hazards linked to the use of ionizing radiation is currently being observed for four reasons. First, the increasing need for radiation sources in numerous industrial applications (food sterilization, construction, engineering) leads to an increasing probability of loss of the sources or abnormal/unsuitable use and storage. Second, advances in medicine generate new protocols and tools that are more efficient but also much more complex to carry out, increasing the risk of accidental overexposure. Third, the possibility of a terrorist attack using radiological or nuclear devices has to be taken into account. Finally, recent events in Fukushima (Japan) highlight the risks of exposure in the case of nuclear power plant accidents. All these issues could lead to the accidental exposure of one to several thousand individuals not wearing dosimeters. Thus, it is essential to be able to estimate the exposure level of victims. Nowadays, this evaluation is based on clinical diagnosis (mainly irradiation symptoms and hematological variations) supplemented with biological dosimetry and physical dose reconstruction. Biological dosimetry is especially important when the personal dosimeter is lacking or when the accidental context is unclear. All this information should help the medical staff to deliver appropriate medical care and to manage the long-term medical follow-up, if required. It has been known since the last century that ionizing radiation causes DNA damage and that DNA misrepair can induce chromosome aberrations: stable (translocations, deletions, insertions) or unstable (dicentrics, centric rings, acentric fragments). These aberrations are observed in metaphase cells. A misrepair can be also observed after anaphase in the form of micronuclei. The applicability of the available assays of biodosimetry is based on the analysis of the chromosome damage present in peripheral blood lymphocytes, which is a convenient because its collection is non-invasive and it is easy to obtain. Dicentric assay is currently the gold standard method for classic biodosimetry in cases of recent accidental exposure. The scoring of dicentrics allows assessment of the whole-body dose received by the individual. Moreover, in numerous accident contexts the exposure of victims is heterogeneous. In these cases, the fraction of the body irradiated and the dose received by this fraction can be estimated by dicentric scoring. In the case of large-scale accidents the dicentric aberration is always used as well as the micronuclei because its analysis is faster and easier. However, dicentrics and micronuclei are unstable aberrations and their rate decreases with time. Consequently, for past accidental exposure, the analysis of stable chromosome aberrations like translocations is required (Figure
Stable expression of selectable genes introduced into human hematopoietic stem cells by electric field-mediated DNA transfer. (1986)

The successful introduction of DNA into human bone marrow cells by electric field-mediated transfer was initially demonstrated by the detection of transient chloramphenicol acetyltransferase (acetyl-CoA:chloramphenicol O3-acetyltransferase, EC 2,3.1.28) activity in marrow cell extracts. To determine whether DNA was transferred into hematopoietic stem cells, human nucleated marrow cells were subjected to electroporation in the presence of a plasmid construct containing the bacterial genes conferring resistance to the neomycin analogue G418 (neo) and to mycophenolic acid (gpt). The growth of granulocyte/macrophage colonies in selective media, followed by hybridization analyses of resistant cells, established that DNA was transferred into human granulopoietic progenitor cells and was stably maintained and expressed in their differentiated progeny. Electroporation, therefore, offers the opportunity to transfer genes effectively into human hematopoietic stem cells and avoids some of the disadvantages associated with other methods of gene transfer.
Sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO) in a sibling pair with a homozygous p.A467T POLG mutation (2009)

Two siblings who developed fifth-decade-onset, concurrent progressive sensory ataxia, dysarthria, and ophthalmoparesis were found to be homozygous for the p.A467T mutation of the polymerase gamma (POLG) gene. The clinical course in both subjects was progression to severe disability. The enlarging spectrum of sensory ataxic neuropathies associated with mitochondrial DNA (mtDNA) instability and POLG mutations should be recognized and considered in the differential diagnosis of this unusual presentation.
Expression of chemokine receptors by subsets of neurons in the central nervous system (1997)

IL-8 is expressed by activated and neoplastic astrocytes and enhances the survival of hippocampal neurons in vitro. Since mRNA encoding chemokine receptors have been demonstrated in brain, the expression of chemokine receptors by specific cell types in anatomic regions of the central nervous system (CNS) was investigated. Archival tissues from various regions of the CNS were stained with specific mAbs to the Duffy Ag/receptor for chemokines, a promiscuous receptor that binds selected chemokines; the specific receptor for IL-8 (CXCR1); and the receptor (CXCR2) shared by IL-8 and melanoma growth stimulatory activity. The Duffy Ag/receptor for chemokines was expressed exclusively by Purkinje cells in the cerebellum. Chemokine binding and radioligand cross-linking confirmed the presence of a high affinity, promiscuous chemokine receptor in the cerebellum. Although CXCR1 was not expressed in the CNS, CXCR2 was expressed at high levels by subsets of projection neurons in diverse regions of the brain and spinal cord, including the hippocampus, dentate nucleus, pontine nuclei, locus coeruleus, and paraventricular nucleus, and in the anterior horn, interomediolateral cell column, and Clarke's column of the spinal cord. Fibers that express CXCR2 included those in the superior cerebellar peduncle and the substantia gelatinosa. Immunohistochemical analysis of the involved brain tissues from patients with Alzheimer's disease revealed expression of CXCR2 in the neuritic portion of plaques surrounding deposits of amyloid. These data suggest that chemokines may play a role in reactive processes in normal neuronal function and neurodegenerative disorders.