gebhart/patrepeval huggingface dataset:
The Distance between N and C Termini of Tau and of FTDP-17 Mutants Is Modulated by Microtubule Interactions in Living Cells (2017)

The microtubule (MT)-associated protein Tau is a natively unfolded protein, involved in a number of neurodegenerative disorders, collectively called tauopathies, aggregating in neurofibrillary tangles (NFT). It is an open question how the conversion from a MT bound molecule to an aggregation-prone Tau species occurs and, also, if and how tauopathy-related mutations affect its behavior in the cell. To address these points, we exploited a genetically encoded FRET sensor based on the full length Tau protein, to monitor in real time Tau conformational changes in different conditions in live cells. By studying the FRET signal we found that soluble Tau molecules, detached from MTs, display an unfolded structure. On the contrary, we observed an increased FRET signal generated by Tau monomers bound to MT, indicating that the association with MTs induced a folding of Tau protein, decreasing the distance between its N and C termini. We exploited the FRET sensor to investigate the impact of FTDP-17 mutations and of phosphorylation-site mutations on Tau folding and mobility in live cells. We demonstrated that the FTDP-17 Tau mutations weaken the interaction of Tau with cellular MTs, shifting the equilibrium towards the soluble pool while, conversely, phosphorylation site mutations shift the equilibrium of Tau towards the MT-bound state and a more closed conformation.
New techniques for physical mapping of the human genome (1991)

We describe improvements in techniques and strategies used for making maps of the human genome. The methods currently used are changing and evolving rapidly. Today's techniques can produce ordered arrays of DNA fragments and overlapping sets of DNA clones covering extensive genomic regions, but they are relatively slow and tedious. Methods under development will speed the process considerably. New developments include a range of applications of the polymerase chain reaction, enhanced procedures for high resolution in situ hybridization, and improved methods for generating, manipulating, and cloning large DNA fragments. More detailed genetic and physical maps will be useful for finding genes, including those associated with human diseases, long before the complete DNA sequence of the human genome is available.
Low loss (1.7 dB/km) hollow core photonic bandgap fiber (2004)

We report a silica hollow core photonic bandgap fiber with a minimum attenuation of 1.72 dB/km at 1565 nm wavelength and discuss the scaling of attenuation with wavelength and the minimum loss wavelength in this type of fiber.
A system for insertional mutagenesis and chromosomal rearrangement using the Ds transposon and Cre—lox (1995)

A system for insertional mutagenesis and chromosomal rearrangement in Arabidopsis has been developed. The T-DNA vectors are based on the maize transposon Ds, lox sites from the Cre-lox site-specific recombination system, and transcriptional fusions expressing Ac transposase or Cre recombinase. The engineered transposon is termed Dslox. Transposed Dslox insertions were created by crossing plants bearing Dslox with plants expressing Ac transposase, then simultaneously selecting for excision and reinsertion in F2 seedlings using the herbicides chlorsulfuron and phosphonothricin, respectively. F2 plants bearing stable Dslox insertions were identified by scoring for the absence of the Ac transposase T-DNA, using a novel, visual marker in that T-DNA. Two independent Dslox insertions were characterized and placed 5.6 and 16.5 cM from their T-DNAlox, which mapped close to m506 on chromosome 4. Plants bearing either of the two different transposed Dsloxs and T-DNAlox were crossed to plants expressing Cre recombinase, which catalyzed recombination between the lox site in transposed Dslox and the lox site in T-DNAlox. Lox-lox recombinants were identified selectively amongst progeny of these crosses. Molecular and genetic analysis of the lox-lox rearrangements indicated that both were inversions. The smaller inversion was germinally transmitted from generation to generation as a simple trait, whereas the larger inversion was not transmitted to progeny of plants bearing the rearrangement.
Laser Pointers as Collaborative Pointing Devices (2002)

Single Display Groupware (SDG) is a research area that focuses on providing collaborative computing environments. Traditionally, most hardware platforms for SDG support only one person interacting at any given time, which limits collaboration. In this paper, we present laser pointers as input devices that can provide concurrent input streams ideally required to the SDG environment. First, we discuss several issues related to utilization of laser pointers and present the new concept of computer controlled laser pointers. Then we briefly present a performance evaluation of laser pointers as input devices and a baseline comparison with the mouse according to the ISO 9241-9 standard. Finally, we describe a new system that uses multiple computer controlled laser pointers as interaction devices for one or more displays. Several alternatives for distinguishing between different laser pointers are presented, and an implementation of one of them is demonstrated with SDG applications.
Novel Cloning Method for Recombinant Adenovirus Construction in Escherichia coli (1999)

pAd(vantage) is a rapid cloning system for generating recombinant adenoviruses. The system is based on manipulating the full-length adenovirus genome as a stable plasmid in E. coli using intron-encoded endonucleases. These intron-encoded endonucleases cut their recognition sequences, which range from 15-39 bp, with high specificity. Their unusual long homing sequence makes them rare-cutting and ideal for use as cloning sites. We report how transgenes can easily be cloned directly into the E1 region of an adenoviral plasmid, followed by transfection into a mammalian packaging cell line, to produce homogeneous recombinant viruses without the need for plaque purification.
Plasmodium knowlesi: persistence of transmission blocking immunity in monkeys immunized with gamete antigens (1984)

Eight rhesus monkeys immunized with a partially purified preparation of Plasmodium knowlesi gametes were monitored for over 6 years to determine the extent of transmission blocking immunity. Monkeys were challenged regularly, and anti-gamete antibodies were assayed by in vivo and in vitro mosquito feedings. Transmission blocking immunity persisted at high levels in most of the monkeys. In those animals in which protection waned between challenges, a challenge infection provided a sufficient booster effect to prevent infection of mosquitoes. Immunity to other stages of malaria (i.e., sporozoites and asexual erythrocyte forms) failed to induce immunity against gametes.
Mitochondrial trifunctional protein deficiency. Catalytic heterogeneity of the mutant enzyme in two patients. (1994)

We examined the enzyme protein and biosynthesis of human trifunctional protein harboring enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase activity in cultured skin fibroblasts from two patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. The following results were obtained. (a) In cells from patient 1, immunoblot analysis and pulse-chase experiments indicated that the content of trifunctional protein was < 10% of that in control cells, due to a very rapid degradation of protein newly synthesized in the mitochondria. The diminution of trifunctional protein was associated with a decreased activity of enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase, when measured using medium-chain to long-chain substrates. (b) In cells from patient 2, the rate of degradation of newly synthesized trifunctional protein was faster than that in control cells, giving rise to a trifunctional protein amounting to 60% of the control levels. The 3-hydroxy-acyl-CoA dehydrogenase activity with medium-chain to long-chain substrates was decreased drastically, with minor changes in activities of the two other enzymes. These data suggest a subtle abnormality of trifunctional protein in cells from patient 2. Taken together, the results obtained show that in both patients, long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is caused by an abnormality in the trifunctional protein, even though there is a heterogeneity in both patients.
Application of Ultrasound to Selectively Localize Nanodroplets for Targeted Imaging and Therapy (2006)

Lipid-coated perfluorocarbon nanodroplets are submicrometer-diameter liquid-filled droplets with proposed applications in molecularly targeted therapeutics and ultrasound (US) imaging. Ultrasonic molecular imaging is unique in that the optimal application of these agents depends not only on the surface chemistry, but also on the applied US field, which can increase receptor-ligand binding and membrane fusion. Theory and experiments are combined to demonstrate the displacement of perfluorocarbon nanoparticles in the direction of US propagation, where a traveling US wave with a peak pressure on the order of megapascals and frequency in the megahertz range produces a particle translational velocity that is proportional to acoustic intensity and increases with increasing center frequency. Within a vessel with a diameter on the order of hundreds of micrometers or larger, particle velocity on the order of hundreds of micrometers per second is produced and the dominant mechanism for droplet displacement is shown to be bulk fluid streaming. A model for radiation force displacement of particles is developed and demonstrates that effective particle displacement should be feasible in the microvasculature. In a flowing system, acoustic manipulation of targeted droplets increases droplet retention. Additionally, we demonstrate the feasibility of US-enhanced particle internalization and therapeutic delivery.
Adenovirus-Mediated Gene Transfer of Dominant Negative Rasasn17 in 3T3L1 Adipocytes Does Not Alter Insulin-Stimulated PI3-Kinase Activity or Glucose Transport (1997)

Recent studies suggest that the ras-map kinase and PI3-kinase cascades converge. We sought to determine whether PI3-kinase is downstream of ras in insulin signaling in a classic insulin target cell. We generated a recombinant adenovirus encoding dominant negative ras by cloning the human H-ras cDNA with a ser to asn substitution at amino acid 17 (rasasn17) into the pACCMVpLpA vector and cotransfecting 293 cells with the pJM17 plasmid containing the adenoviral genome. Efficiency of gene transfer was assessed by infecting fully differentiated 3T3L1 adipocytes with a recombinant adenovirus expressing β-galactosidase (β-gal); greater than 70% of cells were infected. Infection of adipocytes with rasasn17 resulted in 10-fold greater expression than endogenous ras. This high efficiency gene transfer allowed biochemical assays. Insulin stimulation of ras-GTP formation was inhibited in rasasn17-expressing cells. Map kinase gel mobility shift revealed that insulin (1 um) or epidermal growth factor (100 ng/ml) resulted in the appearance of a hyperphosphorylated species of p42 map kinase in uninfected cells and those expressing β-gal but not in cells expressing rasasn17. In contrast, insulin increased IRS-1-associated PI3-kinase activity approximately 10-fold in control cells and high level overexpression of rasasn17 did not impair this effect. Similarly, insulin and epidermal growth factor activation of total (no immunoprecipitation) PI3-kinase activity in both cytosol and total cellular membranes and insulin stimulation of glucose transport were not affected by expression of dominant negative ras. Thus, adenovirus-mediated gene transfer is effective for studying insulin signaling in fully differentiated insulin target cells. Inhibition of ras activation abolishes insulin-stimulated phosphorylation of map kinase but does not affect insulin stimulation of PI3-kinase activity. In normal cell physiology, PI3-kinase does not appear to be downstream of ras in mediating the actions of insulin.
Tracking the Built Status of MEP Works: Assessing the Value of a Scan-vs-BIM System (2013)

Mechanical, electrical, and plumbing (MEP) works constitute a large portion of construction costs and thus need to be appropriately tracked. Assessment of the built status of MEP works in construction projects is however typically limited to subcontractor claims augmented and contrasted with periodic manual inspection. A more detailed manual inspection is costly and not considered worthwhile on most projects. Within a Scan-vs-BIM object recognition framework, three-dimensional laser scanning and project 3D/4D BIM models jointly offer the opportunity for a frequent, detailed, and semantically rich assessment of as-built status of construction projects at a cost that continues to decline. This potential has already been demonstrated for tracking structural works, but remains to be assessed in regard to other work sections, in particular MEP works. This paper explores that opportunity. A Scan-vs-BIM processing system is described with some enhancements over previous works. It is then tested with a representative and challenging case study of the construction of a utility corridor in a university engineering building. The results indicate that the proposed system is significantly challenged when tracking MEP systems constructed using traditional on-site fabrication, due to changes or adjustments made on-site that lead to actual component layouts varying in comparison to designed layouts. This performance could be revisited in cases where off-site prefabrication and preassembly is implemented. The results nonetheless lead the authors to propose a novel data processing system (conceptually described in this paper) integrating Scan-vs-BIM and Scan-to-BIM approaches. This system should provide superior performance over existing systems, enabling automated and robust quality control (including the estimation of the emerging performance metric percent built as designed) and delivery of true as-built BIM models to facility owners and managers.
MDARS Multiple Robot Host Architecture (1995)

The Naval Command Control and Ocean Surveillance Center (NCCOSC) RDT&amp;amp;E Division (NRaD) has developed a command and control architecture to provide coordinated control of multiple autonomous interior and exterior vehicles from a single host console. The Multiple Robot Host Architecture (MRHA) is a distributed multiprocessing system that can be expanded to accommodate as many as 32 remote platforms. The initial application will employ eight Cybermotion K2A Navmaster robots configured as remote security platforms in support of the Mobile Detection Assessment Response System (MDARS) Program. This paper discusses the evolution of the command, control, and communications aspects of the MRHA, including the current status of Interior developmental testing in an operational warehouse environment at Camp Elliott in San Diego, CA. 2. Background The MDARS program is a joint Army-Navy effort to develop a robotic security and automated inventory assessment capability for use in Department of Defen...
Integrated ARROW waveguides with hollow cores (2004)

We report the design, fabrication, and demonstration of antiresonant reflecting optical (ARROW) waveguides with hollow cores. We describe the design principles to achieve low waveguide loss in both transverse and lateral directions. A novel fabrication process using silicon dioxide and silicon nitride layers as well as sacrificial polyimide core layers was developed. Optical characterization of 3.5mum thick waveguides with air cores was carried out. We demonstrate single-mode propagation through these hollow ARROW waveguides with propagation loss as low as 6.5cm-1 and mode cross sections down to 6.7mum2. Applications of these waveguides to sensing and quantum communication are discussed.
Mammographic Density and the Risk and Detection of Breast Cancer (2007)

Extensive mammographic density is strongly associated with the risk of breast cancer detected by screening or between screening tests. A substantial fraction of breast cancers can be attributed to this risk factor.
Binding affinity of surface functionalized gold nanoparticles to hydroxyapatite (2011)

Gold nanoparticles (Au NPs) have been investigated for a number of biomedical applications, including drug and gene delivery vehicles, thermal ablation therapy, diagnostic sensors, and imaging contrast agents. Surface functionalization with molecular groups exhibiting calcium affinity can enable targeted delivery of Au NPs to calcified tissue, including damaged bone tissue. Therefore, the objective of this study was to investigate the binding affinity of functionalized Au NPs for targeted delivery to bone mineral, using hydroxyapatite (HA) crystals as a synthetic analog in vitro. Au NPs were synthesized to a mean particle size of 10-15 nm and surface functionalized with either L-glutamic acid, 2-aminoethylphosphonic acid, or alendronate, which exhibit a primary amine for binding gold opposite carboxylate, phosphonate, or bisphosphonate groups, respectively, for targeting calcium. Bisphosphonate functionalized Au NPs exhibited the most rapid binding kinetics and greatest binding affinity to HA, followed by glutamic acid and phosphonic acid. All functional groups reached complete binding after 24 h. Equilibrium binding constants in de-ionized water, determined by nonlinear regression of Langmuir isotherms, were 3.40, 0.69, and 0.25 mg/L for bisphosphonate, carboxylate, and phosphonate functionalized Au NPs, respectively. Functionalized Au NPs exhibited lower overall binding in fetal bovine serum compared to de-ionized water, but relative differences between functional groups were similar.
Visible action spectrum for melanin‐specific selective photothermolysis (1989)

The skin of black and albino guinea pigs was irradiated with single, 750 nsec-long laser pulses at 435, 488, 530, and 560 nm in order to determine an action spectrum for the gross threshold response of immediate epidermal whitening. In addition, the immediate and delayed gross and histologic changes induced at, above, and below the threshold radiant exposures at all four wavelengths were studied. The action spectrum in the black guinea pigs was consistent with the reported absorption spectrum of DOPA-melanin. Histologically, there was epidermal damage immediately after radiant exposures at and above threshold at all four wavelengths. In addition, radiant exposures greater than threshold caused an immediate decrease in stainable epidermal pigment that was most marked at 435 and 488 nm. The healing response was also wavelength- and dose-dependent. Seven days after above-threshold exposures, there was little epidermal pigment in the 435 nm specimens. As wavelength increased, there was progressively more pigment, and in the 560 nm specimens, the epidermal pigment was equivalent to that seen in nonirradiated black guinea pig control specimens. Seven days after subthreshold radiant exposures, there was increased epidermal pigmentation and melanocytes at all four wavelengths. This was the most pronounced in the 435 nm specimens. There was no observable epidermal damage in albino guinea pig skin.
Cross protection between an encapsulated strain of Staphylococcus hyicus and encapsulated strains of Staphylococcus aureus (1988)

Strain ST67P of Staphylococcus hyicus grew diffusely in regular serum-soft agar. With the addition of rabbit antisera prepared with Staph. aureus strains, Smith, NS58D or NS41D, capsular type A, B or C, respectively, the organisms converted to compact type growth. Mice immunized with heat-killed vaccine of strain ST67P showed significant resistance against either homologous or heterologous strains, Smith, NS58D and NS41D. Passive protective activities in rabbit antisera prepared with strains Smith, NS58D and NS41D were absorbed out with either homologous cell surface polysaccharide fraction or cell surface polysaccharide fraction extracted from strain ST67P. Well-defined large capsules were observed in ultra-thin sections treated with rabbit antiserum prepared with homologous strain conjugated with ferritin. Also, the capsule surrounded by ferritin granules was shown in ultra-thin sections treated with ferritin conjugated with antisera prepared with those heterologous strains although the capsular size was significantly smaller than those observed by homologous antiserum.
Chemotherapy enhances tumor cell susceptibility to CTL-mediated killing during cancer immunotherapy in mice (2010)

Cancer immunotherapy faces a serious challenge because of low clinical efficacy. Recently, a number of clinical studies have reported the serendipitous finding of high rates of objective clinical response when cancer vaccines are combined with chemotherapy in patients with different types of cancers. However, the mechanism of this phenomenon remains unclear. Here, we tested in mice several cancer vaccines and an adoptive T cell transfer approach to cancer immunotherapy in combination with several widely used chemotherapeutic drugs. We found that chemotherapy made tumor cells more susceptible to the cytotoxic effect of CTLs through a dramatic perforin-independent increase in permeability to GrzB released by the CTLs. This effect was mediated via upregulation of mannose-6-phosphate receptors on the surface of tumor cells and was observed in mouse and human cells. When combined with chemotherapy, CTLs raised against specific antigens were able to induce apoptosis in neighboring tumor cells that did not express those antigens. These data suggest that small numbers of CTLs could mediate a potent antitumor effect when combined with chemotherapy. In addition, these results provide a strong rationale for combining these modalities for the treatment of patients with advanced cancers.
A novel real-time quantitative PCR method using attached universal template probe (2003)

A novel real-time quantitative polymerase chain reaction (PCR) method using an attached universal template (UT) probe is described. The UT is an approximately 20 base attachment to the 5' end of a PCR primer, and it can hybridize with a complementary TaqMan probe. One of the advantages of this method is that different target DNA sequences can be detected employing the same UT probe, which substantially reduces the cost of real-time PCR set-up. In addition, this method could be used for simultaneous detection using a 6-carboxy-fluorescein-labeled UT probe for the target gene and a 5-hexachloro-fluorescein-labeled UT probe for the reference gene in a multiplex reaction. Moreover, the requirement of target DNA length for UT-PCR analysis is relatively flexible, and it could be as short as 56 bp in this report, suggesting the possibility of detecting target DNA from partially degraded samples. The UT-PCR system with degenerate primers could also be designed to screen homologous genes. Taken together, our results suggest that the UT-PCR technique is efficient, reliable, inexpensive and less labor-intensive for quantitative PCR analysis.