gebhart/patrepeval huggingface dataset:
'VR-chitecture'-a new discipline (1993)

'VR-chitecture'-or virtual architecture, is the art/discipline of designing buildings that are never meant to be built. In traditional architectures such buildings are known as 'projects': designs that the architect would like to realise but for which there is no client, budget or sufficiently advanced technology. Virtual buildings are superficially similar in that they, too, never reach the point of going on site, remaining on the computer screen. The crucial difference is that the virtual building is not merely a representation of an object-to-be, but the object itself. It is not built in bricks and mortar because there is no need: it serves its purpose better in its non-material form. An example of such a 'building' is the virtual British Library-an online, interactive 3D environment available at any given time to thousands of users on the screens of their personal computers, via digital telephone lines, updated constantly and linked to similar databases at home and abroad. Structured like traditional and familiar libraries in a spatial setting of shelves and volumes set out according to subject and alphabetical order, books, journals and even videos and music are connected to respective to 3D icons. Televirtual shopping and the televirtual office are variants of the virtual library and are also discussed.
The Chinese Wall security policy (2003)

The authors explore a commercial security policy (the Chinese Wall) which represents the behavior required of those persons who perform corporate analysis for financial institutions. It can be distinguished from Bell-LaPadula-like policies by the way that a user's permitted accesses are constrained by the history of his previous accesses. It is shown that the formal representation of the policy correctly permits a market analyst to talk to any corporation which does not create a conflict of interest with previous assignments. The Chinese Wall policy combines commercial discretion with legally enforceable mandatory controls. It is required in the operation of many financial services organizations; the authors conclude that it is, therefore, perhaps as significant to the financial world as Bell-LaPadula's policies are to the military.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Aging Increased Amyloid Peptide and Caused Amyloid Plaques in Brain of Old APP/V717I Transgenic Mice by a Different Mechanism than Mutant Presenilin1 (2000)

Aging of transgenic mice that overexpress the London mutant of amyloid precursor protein (APP/V717I) (Moechars et al., 1999a) was now demonstrated not to affect the normalized levels of alpha- or beta-cleaved secreted APP nor of the beta-C-terminal stubs. This indicated that aging did not markedly disturb either alpha- or beta-secretase cleavage of APP and failed to explain the origin of the massive amounts of amyloid peptides Abeta40 and Abeta42, soluble and precipitated as amyloid plaques in the brain of old APP/V717I transgenic mice. We tested the hypothesis that aging acted on presenilin1 (PS1) to affect gamma-secretase-mediated production of amyloid peptides by comparing aged APP/V717I transgenic mice to double transgenic mice coexpressing human PS1 and APP/V717I. In double transgenic mice with mutant (A246E) but not wild-type human PS1, brain amyloid peptide levels increased and resulted in amyloid plaques when the mice were only 6-9 months old, much earlier than in APP/V717I transgenic mice (12-15 months old). Mutant PS1 increased mainly brain Abeta42 levels, whereas in aged APP/V717I transgenic mice, both Abeta42 and Abeta40 increased. This resulted in a dramatic difference in the Abeta42/Abeta40 ratio of precipitated or plaque-associated amyloid peptides, i.e., 3.11+/-0.22 in double APP/V717I x PS1/A246E transgenic mice compared with 0.43 +/- 0.07 in aged APP/V717I transgenic mice, and demonstrated a clear difference between the effect of aging and the effect of the insertion of a mutant PS1 transgene. In conclusion, we demonstrate that aging did not favor amyloidogenic over nonamyloidogenic processing of APP, nor did it exert a mutant PS1-like effect on gamma-secretase. Therefore, the data are interpreted to suggest that parenchymal and vascular accumulation of amyloid in aging brain resulted from failure to clear the amyloid peptides rather than from increased production.
Lattice thermal conductivity reduction and phonon localizationlike behavior in superlattice structures (2000)

A study of thermal conductivities perpendicular to the interfaces in ${\mathrm{Bi}}_{2}{\mathrm{Te}}_{3}{/\mathrm{S}\mathrm{b}}_{2}{\mathrm{Te}}_{3}$ superlattices is presented. The lattice thermal conductivities in these short-period superlattices are less than those in homogeneous solid-solution alloys and exhibit a minimum for a period of \ensuremath{\sim}50 \AA{}. For periods less than 50 \AA{}, the adjoining layers of the superlattice apparently become coupled and, in effect, make their thermal conductivities approach that of an alloy. Using the mean free path from kinetic theory, a diffusive transport analysis suggests a low-frequency cutoff $({\ensuremath{\omega}}_{\mathrm{cutoff}})$ in the spectrum of heat-conducting phonons. A physical model based on the coherent backscattering of phonon waves at the superlattice interfaces is outlined for the reduction of lattice thermal conductivity; this suggests conditions of localizationlike behavior for the low-frequency phonons. The ${\ensuremath{\omega}}_{\mathrm{cutoff}}$ from the diffusive transport model is comparable to that estimated from applying the Anderson criterion to the potential localization of phonon waves. The general behavior of localizationlike effects is not unique to ${\mathrm{Bi}}_{2}{\mathrm{Te}}_{3}{/\mathrm{S}\mathrm{b}}_{2}{\mathrm{Te}}_{3}$ superlattices; it is also apparent in the thermal conductivities of Si/Ge superlattices. These superlattice structures offer a scope for studying the phonon localization phenomena while the lattice thermal conductivity reduction could lead to high-performance thermoelectric materials.
RNA aptamers that specifically bind to a 16S ribosomal RNA decoding region construct (2000)

RNA-RNA recognition is a critical process in controlling many key biological events, such as translation and ribozyme functions. The recognition process governing RNA-RNA interactions can involve complementary Watson-Crick (WC) base pair binding, or can involve binding through tertiary structural interaction. Hence, it is of interest to determine which of the RNA-RNA binding events might emerge through an in vitro selection process. The A-site of the 16S rRNA decoding region was chosen as the target, both because it possesses several different RNA structural motifs, and because it is the rRNA site where codon/anticodon recognition occurs requiring recognition of both mRNA and tRNA. It is shown here that a single family of RNA molecules can be readily selected from two different sizes of RNA library. The tightest binding aptamer to the A-site 16S rRNA construct, 109.2-3, has its consensus sequences confined to a stem-loop region, which contains three nucleotides complementary to three of the four nucleotides in the stem-loop region of the A-site 16S rRNA. Point mutations on each of the three nucleotides on the stem-loop of the aptamer abolish its binding capacity. These studies suggest that the RNA aptamer 109.2-3 interacts with the simple 27 nt A-site decoding region of 16S rRNA through their respective stem-loops. The most probable mode of interaction is through complementary WC base pairing, commonly referred to as a loop-loop 'kissing' motif. High affinity binding to the other structural motifs in the decoding region were not observed.
Hot-electron effects in MOSFETs (1983)

The physics of several hot-electron currents and their impact on IC performance and reliability is reviewed, <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">V_{d} - V_{dsat}</tex> is emphasized as the driving force of all hot-electron effects. <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">V_{g}, V_{sub}</tex> , and <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">L</tex> affect the hot-electron effects only through their influence on V <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">dsat</inf> . A simple hot-electron sealing rule is to scale <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">V_{d}, V_{t}</tex> , and <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\sqrt{x_{ox}x_{j}}</tex> in proportion to <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">L</tex> . Several proposed structural changes should provide considerable relief to the hot-electron problem.
Toward an understanding of the molecular mechanisms of physiological cell death. (1993)

Cell death is a normal physiological process. Morphological studies have shown that cells that die by physiological mechanisms often undergo characteristic changes termed "apoptosis" or "programmed cell death." Recent work has begun to unravel the molecular mechanisms of these deaths and has shown that one of the primary cell-death pathways is conserved throughout much of evolution. In the nematode Caenorhabditis elegans programmed cell deaths are mediated by a mechanism controlled by the ced-9 gene; in mammals apoptosis can often be inhibited by expression of the bcl-2 gene. The ability of the human BCL2 gene to prevent cell deaths in C. elegans strongly suggests that bcl-2 and ced-9 are homologous genes. Although the process of cell death controlled by bcl-2 can occur in many cell types, there appears to be more than one physiological cell-death mechanism. Targets of cytotoxic T cells and cells deprived of growth factor both exhibit changes characteristic of apoptosis, such as DNA degradation. However, bcl-2 expression protects cells from factor withdrawal but fails to prevent cytotoxic T-cell killing. DNA degradation is, thus, not specific for any one cell-death mechanism. The ability of bcl-2 to protect cells from a wide variety of pathological, as well as physiological, stimuli indicates that many triggers can serve to activate the same suicide pathway, even some thought to cause necrosis, and not physiological cell death.
Heat shock fusion proteins as vehicles for antigen delivery into the major histocompatibility complex class I presentation pathway (1997)

Mice immunized with heat shock proteins (hsps) isolated from mouse tumor cells (donor cells) produce CD8 cytotoxic T lymphocytes (CTL) that recognize donor cell peptides in association with the major histocompatibility complex (MHC) class I proteins of the responding mouse. The CTL are induced apparently because peptides noncovalently associated with the isolated hsp molecules can enter the MHC class I antigen processing pathway of professional antigen-presenting cells. Using a recombinant heat shock fusion protein with a large fragment of ovalbumin covalently linked to mycobacterial hsp70, we show here that when the soluble fusion protein was injected without adjuvant into H-2b mice, CTL were produced that recognized an ovalbumin-derived peptide, SIINFEKL, in association with Kb. The peptide is known to arise from natural processing of ovalbumin in H-2b mouse cells, and CTL from the ovalbumin-hsp70-immunized mice and a highly effective CTL clone (4G3) raised against ovalbumin-expressing EL4 tumor cells (EG7-OVA) were equally effective in terms of the concentration of SIINFEKL required for half-maximal lysis in a CTL assay. The mice were also protected against lethal challenge with ovalbumin-expressing melanoma tumor cells. Because large protein fragments or whole proteins serving as fusion partners can be cleaved into short peptides in the MHC class I processing pathway, hsp fusion proteins of the type described here are promising candidates for vaccines aimed at eliciting CD8 CTL in populations of MHC-disparate individuals.
Phase I randomized study of KHK4083, an anti‐OX40 monoclonal antibody, in patients with mild to moderate plaque psoriasis (2017)

KHK4083 administration as a single dose up to 10 mg/kg IV or 1.0 mg/kg SC was generally safe and well tolerated in patients with mild to moderate plaque psoriasis with no dose-limiting AEs.
Factor VII binding to tissue factor in reconstituted phospholipid vesicles: induction of cooperativity by phosphatidylserine (1986)

The binding of factor VII and tissue factor produces a membrane-associated proteolytic complex which may be the primary biological initiator of coagulation. Homogeneous tissue factor, a glycoprotein purified from bovine brain, was reconstituted into phospholipid vesicles ranging from neutral (100% phosphatidylcholine) to highly charged (40% phosphatidylserine) with octyl glucoside. The vesicles were characterized with respect to size and tissue factor content and orientation. Employing data from protease digestion, we deduced that tissue factor is randomly oriented; thus, its effective concentration in these vesicles was half its total concentration. In all binding experiments, 1 mol of enzyme was bound per mole of available activator at saturation. This stoichiometry was not affected by the form of the enzyme employed or the phospholipid composition of the vesicles. With tissue factor incorporated into phosphatidylcholine vesicles, the Kd was 13.2 +/- 0.72 nM for factor VII and 4.54 +/- 1.37 nM for factor VIIa. Thus, the one-chain zymogen binds to the activator with only slightly less affinity than the more active two-chain enzyme. Active-site modification of factor VII and factor VIIa with diisopropyl fluorophosphate resulted in tighter binding of the derivatized molecules. Inclusion of phosphatidylserine in the vesicles altered the binding both quantitatively and qualitatively. With increasing acidic phospholipid, the concentration of enzyme required to occupy half the activator sites was decreased. In addition, positive cooperativity was observed, the degree of which depended on the vesicle charge and the form of the enzyme. An explicit two-site cooperative binding model is presented which fits these complex data. In this model, tissue factor is at least a dimer with two interacting enzyme binding sites.
UBM Formation on Single Die/Dice for Flip Chip Applications (1999)

This thesis presents the low cost process for UBM formation on aluminum pads of single die/dice for Flip Chip applications. The UBM (Under Bump Metallization) is required in solder bump structure to provide adhesion/diffusion barrier layer, solder wettable layer, and oxidation barrier layer between the bonding pads of the die and the bumps. Typically, UBM is deposited on the whole wafers by sputtering, evaporation, or electroless plating. These deposition techniques are not practical for UBM formation on single die/dice, thus preventing Flip Chip technology to be applied in applications where the whole wafers are not available. The process presented in this thesis has been developed to overcome this problem. The developed UBM formation process allows the UBM layer to be deposited on a single die, thus eliminating the requirement to have the whole wafer in the deposition process. With the combination of the UBM formation process developed in this work and a suitable bump formation technique, solder bumping on a single die can be achieved, thus making Flip Chip technology available for use in low volume applications and prototyping stages. The developed UBM formation process consists of two major steps; temporary die attach process and UBM deposition process. The first process is developed using thermoplastic adhesive film. The second process is developed using lectroless nickel plating, followed by gold immersion. It has been demonstrated in this thesis that the developed process can be used to form the UBM layer on the die successfully regardless of the die size and the complexity of the die pattern, and that this process does not damage nor affect electrically the sensitive die. iii
Multiple Roles and Interactions of Tbx4 and Tbx5 in Development of the Respiratory System (2012)

Normal development of the respiratory system is essential for survival and is regulated by multiple genes and signaling pathways. Both Tbx4 and Tbx5 are expressed throughout the mesenchyme of the developing lung and trachea; and, although multiple genes are known to be required in the epithelium, only Fgfs have been well studied in the mesenchyme. In this study, we investigated the roles of Tbx4 and Tbx5 in lung and trachea development using conditional mutant alleles and two different Cre recombinase transgenic lines. Loss of Tbx5 leads to a unilateral loss of lung bud specification and absence of tracheal specification in organ culture. Mutants deficient in Tbx4 and Tbx5 show severely reduced lung branching at mid-gestation. Concordant with this defect, the expression of mesenchymal markers Wnt2 and Fgf10, as well as Fgf10 target genes Bmp4 and Spry2, in the epithelium is downregulated. Lung branching undergoes arrest ex vivo when Tbx4 and Tbx5 are both completely lacking. Lung-specific Tbx4 heterozygous;Tbx5 conditional null mice die soon after birth due to respiratory distress. These pups have small lungs and show severe disruptions in tracheal/bronchial cartilage rings. Sox9, a master regulator of cartilage formation, is expressed in the trachea; but mesenchymal cells fail to condense and consequently do not develop cartilage normally at birth. Tbx4;Tbx5 double heterozygous mutants show decreased lung branching and fewer tracheal cartilage rings, suggesting a genetic interaction. Finally, we show that Tbx4 and Tbx5 interact with Fgf10 during the process of lung growth and branching but not during tracheal/bronchial cartilage development.
Immunogenicity of biological therapeutics (2012)

Biological medications are able to induce an antidrug immune response. Immunogenicity impairs clinical response and is associated with adverse events. Several confounding factors influence the measurement of immunogenicity, including drug interference and background problems. Concomitant administration of methotrexate lowers the frequency and amount of antibodies formed, whereby the efficacy of biologicals is improved. Algorithms for therapeutic drug monitoring could aid in adapting treatment strategies in a controlled setting.
Efficient bacterial transcription of DNA nanocircle vectors with optimized single-stranded promoters (2001)

We describe experiments aimed at establishing whether circular single-stranded DNAs can form promoters for bacterial transcription from small folded motifs. In vitro selection experiments were carried out on circular 103-nt DNA libraries encoding 40-nt randomized sequences as well as self-processing hammerhead ribozymes. Rounds of rolling circle transcription, reverse transcription-PCR, and recyclization were carried out to optimize transcription efficiency. Sequences were identified that are 80-fold more actively transcribed than the initial library by E. coli RNA polymerase (RNAP). The selected motifs were found to be more active than canonical E. coli promoters in the same context. Experiments also demonstrated that a single-stranded pseudopromoter identified by this selection can be transplanted to other circular DNA contexts and retain transcriptional activity. Results suggest that the promoter is localized in a short ( approximately 40 nt) hairpin, which is smaller than canonical E. coli promoters. To test whether this pseudopromoter was active in bacterial cells, a synthetic DNA nanocircle vector encoding a ribozyme targeted to a site in the marA drug resistance gene was constructed to contain an optimized single-stranded promoter. It is shown that this DNA circle can act as a "Trojan horse" in E. coli, being actively transcribed by the cellular RNAP and producing ribozymes that cleave a sequence in the marA drug resistance gene. The use of optimized single-stranded promoters in combination with synthetic nanocircle DNA vectors represents a potentially useful way to engender the synthesis of biologically active RNAs in living cells.
Structure of oligosaccharides on Saccharomyces SUC2 invertase secreted by the methylotrophic yeast Pichia pastoris. (1991)

Saccharomyces SUC2 invertase, secreted by the methylotrophic yeast Pichia pastoris and purified to homogeneity from the growth medium by DE-52 chromatography, appeared on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a diffuse ladder of species at 85-90 kDa, while the secreted Saccharomyces form migrated as a broad band from 100 to 150 kDa. Endo-beta-N-acetylglucosaminidase H released the Pichia invertase carbohydrate generating a 60-kDa protein with residual Asn-linked GlcNAcs and oligosaccharides separated on Bio-Gel P-4 into Man8-11GlcNAc. Nearly 75% of the oligosaccharides were equally distributed between Man8,9GlcNAc, while 17% were Man10GlcNAc and 8% were Man11GlcNAc. Oligosaccharide pools were analyzed for homogeneity by high-pH anion-exchange chromatography, and structures were assigned using 500 MHz one- and two-dimensional 1H NMR spectroscopy. Pichia Man8GlcNAc was the same isomer as found in Saccharomyces, which arises by removing the alpha 1,2-linked terminal mannose from the middle arm of the lipid-oligosaccharide Man9GlcNAc (Byrd, J. C., Tarentino, A. L., Maley, F., Atkinson, P. H., and Trimble, R. B. (1982) J. Biol. Chem. 257, 14657-14666). The Man9GlcNAc pool was 5% lipid-oligosaccharide precursor and 95% Man8GlcNAc isomer with a terminal alpha 1,6-linked mannose on the lower-arm alpha 1,3-core-linked residue (Hernández, L. M., Ballou, L., Alvarado, E., Gillece-Castro, B. L., Burlingame, A. L., and Ballou, C. E. (1989) J. Biol. Chem. 264, 11849-11856). An alpha 1,2-linked mannose on the new alpha 1,6-linked branch in Man9GlcNAc provided 80% of the Man10GlcNAc, which is the structure on Saccharomyces invertase (Trimble, R. B., and Atkinson, P. H. (1986) J. Biol. Chem. 261, 9815-9824). A minor Man10GlcNAc (12%) and the principal Man11GlcNAc (82%) were the major Man9,10GlcNAc with novel alpha 1,2-linked mannoses on the preexisting alpha 1,2-linked termini. Although Pichia glycans did not have terminal alpha 1,3-linked mannoses as found on Saccharomyces core oligosaccharides, over 60% of the structures were isometric configurations unique to lower eukaryotes.
Characterization of the Porous CaO Particles Formed by Decomposition of CaCO 3 and Ca(OH) 2 in Vacuum (1980)

The solid products of decomposing CaCO 3 powder in vacuum at 510°C (sr‐CaO) and of decomposing Ca(OH) 2 powder at 320°C in vacuum (h‐CaO) are particles which have approximately the same exterior dimensions as the parent CaCO 3 or Ca(OH) 2 particles. N 2 adsorption and desorption isotherms show that sr‐and h‐CaO have high internal surface areas which for sr‐CaO have cylindrical symmetry, with the most common diameters being ∼ 10 nm, and for h‐CaO are slit‐shaped, with the most common slit width being ∼ 2.7 nm. The conclusions reached in earlier investigations, i.e that these decomposition reactions in vacuum initially yield a form of CaO which has the same unit cell dimensions as the parent solid, were in error, probably because water vapor converts much of the CaO to poorly crystalline Ca(OH) 2 before XRD measurements can be completed in air. From the volume of N 2 adsorbed by the porous powders, the porosity of h‐CaO is calculated to be 36±5% and of sr‐CaO 41.5±5%. These porosities imply that the linear dimensions of the 1 to 20 μm particles of h‐CaO and sr‐CaO are ∼5% smaller than those of the parent particles. XRD measurements made as a function of time show that particle shrinkage must occur by cooperative, diffusionless movement of crystallites of sr‐CaO or h‐CaO as they form.