gebhart/patrepeval huggingface dataset:
Progress Toward the Genetic Treatment of the β‐Thalassemias (2005)

The beta-thalassemias are congenital anemias that are caused by mutations that reduce or abolish expression of the beta-globin gene. They can be cured by allogeneic hematopoietic stem cell (HSC) transplantation, but this therapeutic option is not available to most patients. The transfer of a regulated beta-globin gene in autologous HSCs is a highly attractive alternative treatment. This strategy, which is simple in principle, raises major challenges in terms of controlling expression of the globin transgene, which ideally should be erythroid specific, differentiation- and stage-restricted, elevated, position independent, and sustained over time. Using lentiviral vectors, May et al. demonstrated in 2000 that an optimized combination of proximal and distal transcriptional control elements permits lineage-specific and elevated beta-globin expression, resulting in therapeutic hemoglobin production and correction of anemia in beta-thalassemic mice. Several groups have by now replicated and extended these findings to various mouse models of severe hemoglobinopathies, thus fueling enthusiasm for a potential treatment of beta-thalassemia based on globin gene transfer. Current investigation focuses on safety issues and the need for improved vector production methodologies. The safe implementation of stem cell-based gene therapy requires the prevention of the formation of replication-competent viral genomes and minimization of the risk of insertional oncogenesis. Importantly, globin vectors, in which transcriptional activity is highly restricted, have a lesser risk of activating oncogenes in hematopoietic progenitors than non-tissue-specific vectors, by virtue of their late-stage erythroid specificity. As such, they provide a general paradigm for improving vector safety in stem cell-based gene therapy.
Will "DNA Chip" Speed Genome Initiative? (1991)

One of the biggest challenges facing researchers on the Human Genome Project is finding faster ways to sequence DNA. Current automated methods turn out about 2,000 bases of finished sequence per day - a rate that would require 1.5 million person-days to sequence the whole genome. So the search continues for a means of boosting sequencing rates by orders of magnitude. Stanford researchers may have found a fast method in the DNA chip, a clever but as yet unproven idea with the potential to generate sequence at rates 100 times or more faster than now possible. Despite its nickname, the chip is not a piece of electronic equipment, but an array of short pieces of DNA - each with a known sequence - arranged on a substrate. Splash a solution containing a longer DNA of unknown sequence onto the array, and it will react with some of the short DNAs there, yielding a pattern from which a computer can deduce its sequence. A pilot experiment at Argonne National Laboratory used a variation of the method to deduce a 100-base sequence - a far cry from a whole genome or even the average gene (which has more than 1,000 bases) -more » but enough of a start to tantalize biochemists and mathematicians alike.« less
Chromosomal assignment of amplified genes in hydroxyurea-resistant hamster cells (1987)

We have shown previously that cDNAs for the M1 and M2 subunits of ribonucleotide reductase, ornithine decarboxylase (ODC), and p5-8, a 55,000-Dalton protein, hybridize to amplified genomic sequences in a highly hydroxyurea-resistant hamster cell line. We have extended these observations to include two additional, independently isolated, hydroxyurea-resistant cell lines: SC8, a single-step hamster ovary cell line, and KH450, a multistep human myeloid leukemic cell line, have also undergone genomic amplification for sequences homologous to ODC and p5-8 cDNAs. However, neither SC8 nor KH450 contains amplified genomic sequences homologous to an M1 cDNA probe. A panel of mouse-hamster somatic cell hybrids was used to map sequences homologous to M1, M2, ODC, and 5-8 cDNAs in the hamster genome. The M2, ODC, and p5-8 cDNAs hybridized to DNA fragments that segregated with hamster chromosome 7. In contrast, M1 cDNA hybridized to DNA fragments that segregated with hamster chromosome 3. These data suggest that the genes RRM2, (M2), ODC, and p5-8, but not RRMI (M1), are linked and may have been co-amplified in the selection of the hydroxyurea-resistant hamster and human cell lines.
Hemoglobin of the Antarctic Fishes Trematomus bernacchii and Trematomus newnesi: Structural Basis for the Increased Stability of the Liganded Tetramer Relative to Human Hemoglobin (2001)

Hemoglobins extracted from fishes that live in temperate waters show little or no dissociation even in the liganded form, unlike human hemoglobin (HbA). To establish whether cold adaptation influences the tendency to dissociate, the dimer-tetramer association constants (L(2,4)) of the carbonmonoxy derivatives of representative hemoglobins from two Antarctic fishes, Trematomus newnesi (Hb1Tn) and Trematomus bernacchii (Hb1Tb), were determined by analytical ultracentrifugation as a function of pH in the range 6.0-8.6 and compared to HbA. HbA is more dissociated than fish hemoglobins at all pH values and in particular at pH 6.0. In contrast, both fish hemoglobins are mostly tetrameric over the whole pH range studied. The extent of hydrophobic surface area buried at the alpha(1)beta(2) interface upon association of dimers into tetramers and the number of hydrogen bonds formed are currently thought to play a major role in the stabilization of the hemoglobin tetramer. These contributions were derived from the X-ray structures of the three hemoglobins under study and found to be in good agreement with the experimentally determined L(2,4) values. pH affects oxygen binding of T. bernacchii and T. newnesi hemoglobins in a different fashion. The lack of a pH effect on the dissociation of the liganded proteins supports the proposal that the structural basis of such effects resides in the T (unliganded) structure rather than in the R (liganded) one.
Nucleotide Sequence of the Nicotiana tabacum cv Xanthi Gene Encoding 1-Aminocyclopropane-1-Carboxylate Synthase (1992)

Ethylene is a plant hormone that influences many aspects of plant growth and development (10). The biosynthetic pathway of ethylene production in higher plants is well defined. The rate-limiting step in this pathway is the reaction
Morphogenesis of Respiratory Syncytial Virus in a Green Monkey Kidney Cell Line (Vero) (1970)

The structure and morphogenesis of respiratory syncytial (RS) virus particles in a green monkey kidney cell line (Vero) were examined. Infected cells contained dense intracytoplasmic inclusions composed of filamentous structures. In places where inclusion material was associated with membranes, structural modifications were induced. There was a thickening of the membrane and an addition of projections 12 to 15 nm in length. The same changes were most frequently observed after association of isolated filamentous structures with the cytoplasmic membrane. The budding-off process was clearly visualized. The diameter of mature virus particles varied between 90 and 130 nm and that of the internal component varied between 11 and 15 nm. The similarities between ultrastructural features of cells infected with RS virus and pneumonia virus of mice are pointed out. It is proposed that these two viruses should be classified together in a third subgroup of myxoviruses.
Tyrosine-Dependent and -Independent Mechanisms of STAT3 Activation by the Human Granulocyte Colony-Stimulating Factor (G-CSF) Receptor Are Differentially Utilized Depending on G-CSF Concentration (1999)

The granulocyte colony-stimulating factor receptor (G-CSF-R) activates multiple STAT proteins. Although the membrane-proximal cytoplasmic region of the G-CSF-R is necessary and sufficient for activation of STAT1 and STAT5, activation of STAT3 requires the membrane distal region that contains four tyrosines. Although one of these (Y704) has previously been shown to be involved in STAT3 activation from a truncated G-CSF-R derived from a patient with severe chronic neutropenia (SCN), this tyrosine is not required for STAT3 activation by the full-length G-CSF-R. To investigate possible alternative mechanisms of STAT3 activation, we generated a series of Ba/F3 cell transfectants expressing the wild-type G-CSF-R or mutant receptors that either completely lack tyrosines or retain just one of the four cytoplasmic tyrosines of the G-CSF-R. We show that, at saturating G-CSF concentrations, STAT3 activation from the full-length G-CSF-R is efficiently mediated by the C-terminal domain in a manner independent of receptor tyrosines. In contrast, at low G-CSF concentrations, Y704 and Y744 of the G-CSF-R play a major role in STAT3 activation. Both tyrosine-dependent and -independent mechanisms of STAT3 activation are sensitive to the Jak2 inhibitor AG-490, follow similar kinetics, and lead to transactivation of a STAT3 reporter construct, indicating functional equivalence. STAT3 activation is also impaired, particularly at nonsaturating G-CSF concentrations, in bone marrow cells from mice expressing a truncated G-CSF-R (gcsfr-triangle up715). These findings suggest that G-CSF-induced STAT3 activation during basal granulopoiesis (low G-CSF) and "emergency" granulopoiesis (high G-CSF) are differentially controlled. In addition, the data establish the importance of the G-CSF-R C-terminus in STAT3 activation in primary cells, which has implications for understanding why truncated G-CSF-R derived from SCN patients are defective in maturation signaling.
Structure and Properties of Blend Films Prepared from Castor Oil-Based Polyurethane/Soy Protein Derivative (2008)

We successfully prepared a series of transparent blend films from castor oil-based polyurethane (PU) and p-phenylene diamine soy protein (PDSP). The miscibility, morphology, and properties of the blend films were investigated with Fourier transform infrared spectroscopy, differential scanning calorimetry, dynamic mechanical thermal analysis, scanning electron microscopy, moisture adsorption, thermal degradation, and tensile testing. The results revealed that the PDSP exhibited certain miscibility with PU varied its content from 10 to 80 wt % and also showed the strong hydrogen-bond and chemical cross-linking interactions lied between PU and PDSP. With an increase in the PU content, the elongation at break, thermal stability, and water resistance were improved whereas the tensile strength and Young’s modulus decreased. It is worth noting that modified soy protein could be blended with hydrophobic polyurethane to obtain the blend films having good mechanical properties and optical transmittance.
Exercise and noninvasive ventilatory support. (2000)

Breathlessness is the most common symptom that limits exercise in patients with chronic obstructive pulmonary disease and who may receive benefit from exercise training programmes. Exercise intensity may influence the physiological benefits of the programme. Although the exact underlying physiopathological mechanism is still unclear, there is laboratory evidence that continuous positive airway pressure and other modalities of mechanical ventilation (delivered either by mouthpiece or facial or nasal masks) may reduce breathlessness and increase exercise tolerance in these patients, in order to allow them to reach a higher exercise intensity. Respiratory muscle unloading and a reduction in intrinsic positive end-expiratory pressure have been considered among the potential mechanisms underlying these effects. The role of mechanical ventilation in pulmonary rehabilitation programmes, if any, is still to be defined.
Mice Lacking Metabotropic Glutamate Receptor 5 Show Impaired Learning and Reduced CA1 Long-Term Potentiation (LTP) But Normal CA3 LTP (1997)

Class I metabotropic glutamate receptors (mGluRs) have been postulated to play a role in synaptic plasticity. To test the involvement of one member of this class, we have recently generated mutant mice that express no mGluR5 but normal levels of other glutamate receptors. The CNS revealed normal development of gross anatomical features. To examine synaptic functions we measured evoked field EPSPs in the hippocampal slice. Measures of presynaptic function, such as paired pulse facilitation in mutant CA1 neurons, were normal. The response of mutant CA1 neurons to low concentrations of (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid (ACPD) was missing, which suggests that mGluR5 may be the primary high affinity ACPD receptor in these neurons. Long-term potentiation (LTP) in mGluR5 mutants was significantly reduced in the NMDA receptor (NMDAR)-dependent pathways such as the CA1 region and dentate gyrus of the hippocampus, whereas LTP remained intact in the mossy fiber synapses on the CA3 region, an NMDAR-independent pathway. Some of the difference in CA1 LTP could lie at the level of expression, because the reduction of LTP in the mutants was no longer observed 20 min after tetanus in the presence of 2-amino-5-phosphonopentanoate. We propose that mGluR5 plays a key regulatory role in NMDAR-dependent LTP. These mutant mice were also impaired in the acquisition and use of spatial information in both the Morris water maze and contextual information in the fear-conditioning test. This is consistent with the hypothesis that LTP in the CA1 region may underlie spatial learning and memory.
Mechanism and Clinical Significance of Wear Debris-Induced Osteolysis (1992)

Loosening of joint replacement components is often multifactorial. The quality of initial fixation is very important to the outcome of the arthroplasty and is often a factor in short-term and long-term failure. This paper discusses another important factor of implant loosening, namely wear debris induced osteolysis. Macrophages activated by the phagocytosis of particulate wear debris are the key cells in this process, which can potentially occur in any implant system regardless of implant design or fixation mode. This is because each implant system creates wear debris from the articulating surfaces and the interfaces. The clinical consequences of wear debris cover a broad spectrum from radiolucencies to massive osteolysis and implant failure. For this reason, the reduction of wear debris should be a primary goal of orthopedic research in the future.
Precise manipulation of GUI on a touch screen with haptic cues (2009)

In this work, we designed a haptic stylus interface interacting with a touch screen. The stylus has functions of providing vibration, impact, and sound and it is a stand-alone system including its own battery and wireless communication module. We present a new interaction scheme on the Windows graphical user interface based on haptic feedback events for clicking, drag & drop, moving, scrolling, highlighting, and other things. From conducting experiments, we evaluated its performance that the haptic stylus improved precise control of GUI elements. A simple interactive digital sketchbook has been also implemented, which is providing haptic and auditory feedback while drawing and touching objects.
Self-Assembly and Adhesion of DOPA-Modified Methacrylic Triblock Hydrogels (2007)

Marine mussels anchor to a variety of surfaces by secreting liquid proteins that harden and form water-resistant bonds to a variety of surfaces. Studies have revealed that these mussel adhesive proteins contain an unusual amino acid, 3,4-dihydroxy-L-phenylalanine (DOPA), which is believed to be responsible for the cohesive and adhesive properties of these proteins. To separate the cohesive and adhesive roles of DOPA, we incorporated DOPA into the midblock of poly(methyl methacrylate)-poly(methacrylic acid)-poly(methyl methacrylate) (PMMA-PMAA-PMMA) triblock copolymers. Self-assembled hydrogels were obtained by exposing triblock copolymer solutions in dimethyl sulfoxide to water vapor. As water diffused into the solution, the hydrophobic end blocks formed aggregates that were bridged by the water-soluble midblocks. Strong hydrogels were formed with polymer weight fractions between 0.01 and 0.4 and with shear moduli between 1 and 5 kPa. The adhesive properties of the hydrogels on TiO2 surfaces were investigated by indentation with a flat-ended cylindrical punch. At pH values of 6 and 7.4, the fully protonated DOPA groups were highly adhesive to the TiO2 surfaces, giving values of approximately equal to 2 J/m2 for the interfacial fracture energy, which we believe corresponds to the cohesive fracture energy of the hydrogel. At these pH values, the DOPA groups are hydrophobic and have a tendency to aggregate, so contact times of 10 or 20 min are required for these high values of the interfacial strength to be observed. At a pH of 10, the DOPA groups were hydrophilic and highly swellable, but less adhesive gels were formed. Oxidation of DOPA groups, a process that is greatly accelerated at a pH of 10, decreased the adhesive performance of the hydrogels even further.
Temperature dependence of the optical properties of silicon (1979)

The spectral dependence of the absorption coefficient of silicon for photon energies up to 2.7 eV was determined for several temperatures in the range 298–473 K. The effect of a temperature increase appears as a red shift of the absorption spectrum. The magnitude of the shift is larger than that of the fundamental energy gap, increases with increasing photon energy in the range 1.1–1.7 eV, and is constant for energies greater than 1.7 eV. A phenomenological expression deduced by analysis of the data may be used to calculate α (E) at elevated temperature, given α (E) at room temperature. The reflectance was also measured at 299, 413, and 516 K in the photon energy range 2.5–3.8 eV.
Kinetics of implantation enhanced interdiffusion of Ga and Al at GaAs-GaxAl1−xAs interfaces (1986)

The kinetics of implantation enhanced interdiffusion at GaAs-GaxAl1−xAs interfaces is investigated by cathodoluminescence and transmission electron microscopy. Localized Ga+ implantation leads to enhancement of the interdiffusion by about two orders of magnitude at 950 °C. A complete recovery of the optical quality of the material and local alteration of the band gap is observed after rapid thermal annealing. The role of intrinsic interdiffusion is identified. Control of the interdiffusion kinetics has allowed the fabrication of ultrasmall structures with good optical properties.
A New Method for Determining the Status of p53 in Tumor Cell Lines of Different Origin (2003)

The tumor suppressor p53 is the most frequently mutated gene in human tumors. In response to DNA damage, aberrant growth signals, or chemotherapeutic drugs, p53 is stabilized and induces apoptosis and/or cell cycle arrest. While the mechanisms of p53-dependent apoptosis are not well understood, p53-dependent cycle arrest is primary mediated by the CDK inhibitor p21. p53 is a transcriptional activator and it is not surprising that a majority of p53 mutations occur in the core DNA binding domain and affect DNA binding and transactivation of p53 targets in tumors. We used the capability of p53 to activate transcription for developing a new assay that permits rapid determination of the status of p53 in cancer cell lines of different origin. Our strategy involved using a retrovirus containing a p53-regulated lacZ reporter gene that was introduced into colon and breast tumor cell lines to determine p53 status. Simple staining for beta-galactosidase allowed us to confirm that the colon cancer cell lines LIM1215 and HCT116, as well as the breast cancer cell line MCF7. have wild-type p53, and the colon cancer cell line Caco-2 as well as breast cancer cell lines MDA-MB-435 and MDA-MB-231 have mutant p53. This method may be applied to novel cell lines of any origin with unknown status of p53.
NF-κB Regulates PD-1 Expression in Macrophages (2015)

Programmed cell death-1 (PD-1) is responsible for T cell exhaustion during chronic viral infections and is expressed on a variety of immune cells following activation. Despite its importance, the mechanisms that regulate PD-1 in cell types other than CD8 T cells are poorly defined. In this study, the molecular mechanisms for inducing PD-1 expression in CD4 T cells, macrophages, and B cells were explored. In CD4 T cells, PD-1 induction following TCR stimulation required NFAT, as the calcineurin/NFAT pathway inhibitor cyclosporin A was able to block PD-1 induction in a manner similar to that seen in CD8 T cells. In contrast, LPS but not PMA and ionomycin stimulation was able to induce PD-1 expression in macrophages in a manner insensitive to cyclosporin A-mediated inhibition. B cells could use both pathways, although the levels of PD-1 expression were highest with PMA and ionomycin. An NF-κB binding site located upstream of the gene in conserved region C was required for NF-κB-dependent PD-1 gene activation in macrophages. Chromatin immunoprecipitation showed NF-κB p65 binding to this region following stimulation of macrophages with LPS. PD-1 induction was associated with histone modifications characteristic of accessible chromatin; however, in contrast to CD8 T cells, conserved region B in macrophages did not lose CpG methylation upon stimulation and PD-1 expression. The linkage of TLR/NF-κB signaling to the induction of PD-1 suggests the possibility of an opportunistic advantage to microbial infections in manipulating immune inhibitory responses.
A CMOS-Compatible, Monolithically Integrated Snapshot-Mosaic Multispectral Imager (2015)

Imec is a research centre located in Belgium. Specialising in nanoelectronics, it is mostly known for advanced lithography and CMOS scaling research. However, building on that equipment and material knowledge, Imec works in a number of different application-oriented domains. Hyperspectral imaging, to which this article is devoted, is one of them.
Triple-helix formation by oligonucleotides containing the three bases thymine, cytosine, and guanine. (1992)

A homopurine-homopyrimidine sequence of human immunodeficiency virus (HIV) proviral DNA was chosen as a target for triple-helix-forming oligonucleotides. An oligonucleotide containing three bases (thymine, cytosine, and guanine) was shown to bind to its target sequence under physiological conditions. This oligonucleotide is bound in a parallel orientation with respect to the homopurine sequence. Thymines recognize A.T base pairs to form T.A.T base triplets and guanines recognize a run of G.C base pairs to form G.G.C base triplets. A single 5-methylcytosine was shown to stabilize the triple helix when incorporated in a stretch of thymines; it recognizes a single G.C base pair in a run of A.T base pairs. These results provide some of the rules required for choosing the more appropriate oligonucleotide sequence to form a triple helix at a homopurine-homopyrimidine sequence of duplex DNA. A psoralen derivative attached to the oligonucleotide containing thymine, 5-methylcytosine, and guanine was shown to photoinduce cross-linking of the two DNA strands at the target sequence in a plasmid containing part of the HIV proviral DNA sequence. Triplex formation and cross-linking were monitored by inhibition of Dra I restriction enzyme cleavage. The present results provide a rational basis for the development of triplex-forming oligonucleotides targeted to specific sequences of the HIV provirus integrated in its host genome.
Coupled amplification and sequencing of genomic DNA. (1991)

Addition of dideoxyribonucleotides during the exponential phase of the PCR should result in the synthesis of two complementary sequence ladders. We have explored this hypothesis to develop coupled amplification and sequencing of genomic DNA. Coupled amplification and sequencing is a biphasic method for sequencing both strands of template as they are amplified. Stage I selects and amplifies a single target from the genomic DNA sample. Stage II accomplishes the sequencing as well as additional amplification of the target using aliquots from the stage I reaction mixed with end-labeled primer and dideoxynucleotides. We have successfully applied coupled amplification and sequencing to a 300-base-pair fragment 4 kilobases upstream from HOX2B directly from human whole genomic DNA.