gebhart/patrepeval huggingface dataset:
The part-time parliament (1998)

Recent archaeological discoveries on the island of Paxos reveal that the parliament functioned despite the peripatetic propensity of its part-time legislators. The legislators maintained consistent copies of the parliamentary record, despite their frequent forays from the chamber and the forgetfulness of their messengers. The Paxon parliament's protocol provides a new way of implementing the state machine approach to the design of distributed systems.
Functionalized Carbon Nanotubes in Drug Design and Discovery (2007)

Carbon nanotubes (CNTs) have been proposed and actively explored as multipurpose innovative carriers for drug delivery and diagnostic applications. Their versatile physicochemical features enable the covalent and noncovalent introduction of several pharmaceutically relevant entities and allow for rational design of novel candidate nanoscale constructs for drug development. CNTs can be functionalized with different functional groups to carry simultaneously several moieties for targeting, imaging, and therapy. Among the most interesting examples of such multimodal CNT constructs described in this Account is one carrying a fluorescein probe together with the antifungal drug amphotericin B or fluorescein and the antitumor agent methotrexate. The biological action of the drug in these cases is retained or, as in the case of amphotericin B constructs, enhanced, while CNTs are able to reduce the unwanted toxicity of the drug administered alone. Ammonium-functionalized CNTs can also be considered very promising vectors for gene-encoding nucleic acids. Indeed, we have formed stable complexes between cationic CNTs and plasmid DNA and demonstrated the enhancement of the gene therapeutic capacity in comparison to DNA alone. On the other hand, CNTs conjugated with antigenic peptides can be developed as a new and effective system for synthetic vaccine applications. What makes CNTs quite unique is their ability, first shown by our groups in 2004, to passively cross membranes of many different types of cells following a translocation mechanism that has been termed the nanoneedle mechanism. In that way, CNTs open innumerable possibilities for future drug discovery based on intracellular targets that have been hard to reach until today. Moreover, adequately functionalized CNTs as those shown in this Account can be rapidly eliminated from the body following systemic administration offering further encouragment for their development. CNT excretion rates and accumulation in organs and any reactivity with the immune system will determine the CNT safety profile and, consequently, any further pharmaceutical development. Caution is advised about the need for systematic data on the long-term fate of these very interesting and versatile nano-objects in correlation with the type of CNT material used. CNTs are gradually plyaing a bigger and more important role in the emerging field of nanomedicine; however, we need to guarantee that the great opportunities they offer will be translated into feasible and safe constructs to be included in drug discovery and development pipelines.
Requirements for the construction of antibody heterodimers for the direction of lysis of tumors by human T cells. (1988)

We constructed a series of MAb heterodimers consisting of the J5 (anti-common acute lymphoblastic leukemia antigen [CALLA]) antibody and antibodies to a variety of structures present on the surface of activated human T cells, including CD3 antigen (T cell receptor-associated glycoproteins), CD2 antigen (T11/E-rosette receptor), CD25 antigen (IL-2 receptor), and the transferrin receptor. We tested the ability of these heterodimers to direct a CD2 + CD3 + CD8 + CD4 - CD25 + transferrin receptor + MHC-restricted human cytolytic T lymphocyte (CTL) clone to lyse a CALLA + human tumor in vitro. Only heterodimers containing an anti-CD3 antibody or activating antibodies to CD2 could direct the clone to lyse these human tumor targets, even when the clone was additionally activated with anti-CD3 or anti-CD2 antibodies. Our findings may have implications in the design of strategies for the use of such reagents in the treatment of human neoplasia.
Single- and dual-wavelength monolithic spatial heterodyne spectrometers for Fraunhofer line discrimination spectroscopy (2009)

The background and beginning of this project have been described in a previous SPIE paper1. Since then, the Na monolithic Spatial Heterodyne Spectrometer (SHS) units were constructed, and the housing for the full SHIELDS unit designed and built. The dual-wavelength SHIELDS was designed, and its construction begun, while the LC reflectors used in the selection between wavelengths for the dual-wavelength monolith were tested for efficacy in an instrument-like configuration. Optical modeling and procurement of optical components was completed, making the Na unit nearly ready for lab tests with a low-pressure sodium source, and then appropriate Na-wavelength fluorophores. Atmospheric modeling showed the importance of both dealing with the Ring effect -- as it is at least equal to the fluorescence effect to be measured -- and selecting the best wavelength to observe to mitigate the effects of vegetative fluorescence and water vapor absorption. The full SHIELDS unit has been assembled and initially tested in May 2009, and the dual-wavelength monolith will be completed in July 2009.
Critical Role for Tumor Necrosis Factor–related Apoptosis-inducing Ligand in Immune Surveillance Against Tumor Development (2002)

Natural killer (NK) cells and interferon (IFN)-gamma have been implicated in immune surveillance against tumor development. Here we show that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) plays a critical role in the NK cell-mediated and IFN-gamma-dependent tumor surveillance. Administration of neutralizing monoclonal antibody against TRAIL promoted tumor development in mice subcutaneously inoculated with a chemical carcinogen methylcholanthrene (MCA). This protective effect of TRAIL was at least partly mediated by NK cells and totally dependent on IFN-gamma. In the absence of TRAIL, NK cells, or IFN-gamma, TRAIL-sensitive sarcomas preferentially emerged in MCA-inoculated mice. Moreover, development of spontaneous tumors in p53(+/-) mice was also promoted by neutralization of TRAIL. These results indicated a substantial role of TRAIL as an effector molecule that eliminates developing tumors.
Effect of sildenafil on haemodynamic response to exercise and exercise capacity in Fontan patients (2008)

In Fontan patients, oral administration of a single dose of sildenafil improves exercise capacity and haemodynamic response to exercise.
The Effect of High Power Adjustable Ring Mode Fiber Laser for Material Cutting (2017)

In this Master of Science Thesis is researched Corelase Oy's performance of ARM fiber laser source’s in laser cutting with different metals. The cutting quality was measured with surface roughness values and cutting edges angularity. &#13;\nThe theoretical part covers the principles of the fiber laser, CO2 laser, disk laser and Nd: YAG laser and how they apply to in laser cutting. Also, there is introduction to laser cutting and how the cutting quality can be measured and validate along standard SFS-ISO EN 9013. The test materials were copper, aluminium, mild steel and stainless steel. The copper was tested in 6 mm, 10 mm and 20 mm in thicknesses. The aluminium was tested at 15 mm and 20 mm thick plates. The mild steel had 5 mm, 15 mm and 20 mm plates and the stainless steel had 10 mm and 15 mm thick plates. The experiments were made with one test setup where were used ARM fiber laser source with the output powers of 2+6 kW and cutting head from Precitec. The study focus to find parameters sets which give metals good surface roughness value and to lower the dross formations under the cut edge. Also, the kerf opening angle was measured for 15 mm and 20 mm thick plates which had the best surface roughness. &#13;\nThe most effecting parameters to the surface roughness were the feed rate, the focal plane’s position and the nozzle diameter with the assistant gas pressure for all materials. For the mild steel (5 mm and 15 mm), the copper and the stainless steel were achieved the quality class of two for the surface roughness with the ARM laser. For the aluminium and the mild steel (20 mm) achieved the quality class level three. The burr get most effect from the nozzle diameter and the gas pressure. &#13;\nThe tests show that the ARM fiber laser source provide good cutting quality with only one type of cutting head. The ARM laser source is versatile what comes to laser cutting.
Polyoxometalate clusters, nanostructures and materials: From self assembly to designer materials and devices (2006)

Polyoxometalates represent a diverse range of molecular clusters with an almost unmatched range of physical properties and the ability to form structures that can bridge several length scales. The new building block principles that have been discovered are beginning to allow the design of complex clusters with desired properties and structures and several structural types and novel physical properties are examined. In this critical review the synthetic and design approaches to the many polyoxometalate cluster types are presented encompassing all the sub-types of polyoxometalates including, isopolyoxometalates, heteropolyoxometalates, and reduced molybdenum blue systems. As well as the fundamental structure and bonding aspects, the final section is devoted to discussing these clusters in the context of contemporary and emerging interdisciplinary interests from areas as diverse as anti-viral agents, biological ion transport models, and materials science.
Si--Au Schottky barrier nuclear battery (1972)

A long-life, high-power-density, high-reliability, compact microwatt battery is needed in many applications. In the field of medicine, for example, such a battery could power an artificial pacemaker which would greatly extend the residence time of the device. Various alternatives are analyzed and discussed. Betavoltaic conversion systems with Si-Au Schottky barrier cells coupled with 147Pm metal foil were selected for investigation. Characterization experiments were performed to obtain optimized silicon resistivity and promethium metal foil thickness. Radiation dose rates were measured and the safety aspects of the battery were analyzed. A prototype battery was assembled and tested. The economics of the battery were demonstrated for special applications. It is concluded that a microwatt nuclear battery can be built with a conversion efficiency of 1 to 2%, a power density of 60 to 300 pW/cm3 depending on the power level, and a useful life of 5 to 10 years. Further research areas are recommended.
Characterization of Four Parainfluenza Virus Type 3 Proteins by Use of Monoclonal Antibodies (1986)

Monoclonal antibodies directed against four structural components of the ATCC strain C243 of parainfluenza virus type 3 were produced. The specific reaction of the antibodies with individual structural components was determined by radioimmune precipitation assay. In the collection of monoclonal antibodies, 21 reacted with the haemagglutinin-neuraminidase (HN) glycoprotein (mol. wt. 72,000), eight with the fusion (F) glycoprotein (mol. wt. 64,000), 27 with the nucleocapsid (NP) protein (mol. wt. 69,000) and 24 with the matrix (M) protein (mol. wt. 40,000). The F-specific monoclonal antibodies precipitated two proteins which were interpreted to represent intact F protein and the large cleavage product F1 (mol. wt. 52,000). The numbers of epitopes were determined in a competition ELISA with the monoclonal antibodies. The epitopes found were six for the HN, two for the F, six for the NP and six for the M protein. The six groups of antibodies reacting with different epitopes on the HN molecule showed varying capacities to inhibit biological activities. Two exhibited high neutralization (NT), haemagglutination inhibition (HI) and haemolysis inhibition (HLI) activity. Three groups had somewhat lower NT, lower HI and no detectable HLI activity. One group showed no activity in these tests. Of the eight monoclonal antibodies directed to the F protein two had demonstrable HLI activity.
Crystallization and preliminary crystallographic analysis of thermophilic cellulase fromFervidobacterium nodosumRt17-B1 (2009)

FnCel5A, a thermostable endoglucanase, is a member of glycohydrolase family 5 which catalyzes the hydrolysis of cellulose to glucose in the thermophilic bacterium Fervidobacterium nodosum Rt17-B1. FnCel5A is particularly interesting because of its high thermostability (T(opt) = 353 K, half-life 48 h) and its high specific activity towards carboxymethylcellulose. These properties make FnCel5A an attractive target for protein engineering to improve cellulase activity. In order to resolve the crystal structure of FnCel5A and to gain a better understanding of its biological function, recombinant FnCel5A was expressed, purified and crystallized at 291 K using NaH(2)PO(4)/KH(2)PO(4) as a precipitant. A 2.4 A resolution native data set was collected from a single flash-cooled crystal (100 K) using 20%(v/v) glycerol as a cryoprotectant. These crystals belonged to space group P2(1)2(1)2, with unit-cell parameters a = 53.5, b = 81.7, c = 85.2 A, alpha = beta = gamma = 90 degrees . One molecule is assumed to be present per asymmetric unit, which gives a Matthews coefficient of 2.5 A(3) Da(-1). A data set was also collected to 1.7 A resolution from a selenomethionyl derivative; it belonged to space group P2(1)2(1)2(1) with the same unit-cell parameters as the native crystals.
New Concepts in the Biology and Biochemistry of Ascorbic Acid (1986)

ASCORBIC acid, originally called vitamin C, is required for human health.1 In human beings deprived of ascorbic acid, the deficiency disease scurvy develops and can be life threatening. Although a disease remarkably similar to scurvy was described by the ancient Egyptians,2 , 3 it was not until 1753 that a Scottish physician, James Lind, systematically described scurvy and its prevention by dietary means.4 Even then, the dietary requirements were controversial. For four decades the British navy refused to accept Lind's findings, and countless sailors continued to die unnecessarily from scurvy until lemon juice was finally included in sailors' rations.Research since Lind's . . .
Role of Dynamic Interactions in Effective Signal Transfer for Gβ Stimulation of Phospholipase C-β2 (2002)

Heterotrimeric G protein subunits regulate their effectors by protein-protein interactions. The regions involved in these direct interactions have either signal transfer or general binding functions (Buck, E., Li, J., Chen, Y., Weng, G., Scarlata, S., and Iyengar, R. (1999) Science 283, 1332-1335). Although key determinants of signal transfer regions for G protein subunits have been identified, the mechanisms of signal transfer are not fully understood. We have used a combinatorial peptide approach to analyze one Gbeta region, Gbeta86-105, involved in signal transfer to the effector phospholipase C (PLC)-beta2 to gain a more mechanistic understanding of Gbeta/PLC-beta2 signaling. Binding and functional studies with the combinatorial peptides on interaction with and stimulation/inhibition of phospholipase Cbeta2 indicate that binding affinity can be resolved from EC(50) for functional effects, such that peptides that have wild type binding affinities have 15- to 20-fold lower EC(50) values. Although more potent, these peptides display a much lower extent of maximal stimulation. These peptides synergize with Gbetagamma or peptides encoding the second Gbeta42-54 signal transfer region in maximally stimulating phospholipase C-beta2. Other combinatorial peptides from the Gbeta86-105 region that bind to PLC-beta2 by themselves submaximally stimulate and extensively inhibit Gbetagamma stimulation of PLC-beta2. The intrinsic stimulation function can be attributed to Arg-96 and Ser-97, the synergy function to Trp-99, and the binding affinity to Thr-87, Val-90, Pro-94, Arg-96, Ser-97, and Val-100. These results indicate that, even within signal transfer regions, residues involved in binding can be resolved from those involved in signal transfer and that signal transfer is likely to be achieved through dynamic rather than steady-state interactions.
Phosphorylation of Parkin by the Cyclin-dependent Kinase 5 at the Linker Region Modulates Its Ubiquitin-Ligase Activity and Aggregation (2007)

Mutations in Parkin are responsible for a large percentage of autosomal recessive juvenile parkinsonism cases. Parkin displays ubiquitin-ligase activity and protects against cell death promoted by several insults. Therefore, regulation of Parkin activities is important for understanding the dopaminergic cell death observed in Parkinson disease. We now report that cyclin-dependent kinase 5 (Cdk5) phosphorylates Parkin both in vitro and in vivo. We found that highly specific Cdk5 inhibitors and a dominant negative Cdk5 construct inhibited Parkin phosphorylation, suggesting that a significant portion of Parkin is phosphorylated by Cdk5. Parkin interacts with Cdk5 as observed by co-immunoprecipitation experiments of transfected cells and rat brains. Phosphorylation by Cdk5 decreased the auto-ubiquitylation of Parkin both in vitro and in vivo. We identified Ser-131 located at the linker region of Parkin as the major Cdk5 phosphorylation site. The Cdk5 phosphorylation-deficient S131A Parkin mutant displayed a higher auto-ubiquitylation level and increased ubiquitylation activity toward its substrates synphilin-1 and p38. Additionally, the S131A Parkin mutant more significantly accumulated into inclusions in human dopaminergic cells when compared with the wild-type Parkin. Furthermore, S131A Parkin mutant increased the formation of synphilin-1/alpha-synuclein inclusions, suggesting that the levels of Parkin phosphorylation and ubiquitylation may modulate the formation of inclusion bodies relevant to the disease. The data indicate that Cdk5 is a new regulator of the Parkin ubiquitin-ligase activity and modulates its ability to accumulate into and modify inclusions. Phosphorylation by Cdk5 may contribute to the accumulation of toxic Parkin substrates and decrease the ability of dopaminergic cells to cope with toxic insults in Parkinson disease.
Intravesical gene therapy: in vivo gene transfer using recombinant vaccinia virus vectors. (1994)

Intratumoral gene transfer may be a significant tool in active immunotherapy. The ability to insert functional genes into a tumor in vitro and in vivo using recombinant vaccinia vectors was examined in the murine bladder tumor model. Vaccinia recombinants expressing the influenza hemagglutinin or nucleoprotein antigens infected/transfected murine (MB-49 and MBT-2) and human (T24) bladder tumor cell lines in vitro. Systemic vaccinia immunity was induced with as few as 10 plaque-forming units of recombinant vaccinia instilled intravesically, and the encoded protein was expressed in vivo in tumor and urothelium. However, preimmunity to vaccinia did not inhibit intravesical tumor transfection. Thus, recombinant vaccinia virus is effective in introducing foreign antigens locally into tumor in vivo, supporting its use in clinical immunotherapy.
Bub1 kinase activity drives error correction and mitotic checkpoint control but not tumor suppression (2012)

The mitotic checkpoint protein Bub1 is essential for embryogenesis and survival of proliferating cells, and bidirectional deviations from its normal level of expression cause chromosome missegregation, aneuploidy, and cancer predisposition in mice. To provide insight into the physiological significance of this critical mitotic regulator at a modular level, we generated Bub1 mutant mice that lack kinase activity using a knockin gene-targeting approach that preserves normal protein abundance. In this paper, we uncover that Bub1 kinase activity integrates attachment error correction and mitotic checkpoint signaling by controlling the localization and activity of Aurora B kinase through phosphorylation of histone H2A at threonine 121. Strikingly, despite substantial chromosome segregation errors and aneuploidization, mice deficient for Bub1 kinase activity do not exhibit increased susceptibility to spontaneous or carcinogen-induced tumorigenesis. These findings provide a unique example of a modular mitotic activity orchestrating two distinct networks that safeguard against whole chromosome instability and reveal the differential importance of distinct aneuploidy-causing Bub1 defects in tumor suppression.
Diversity of locations for Bacillus thuringiensis crystal protein genes (1983)

The location of crystal protein genes in 22 crystalliferous Bacillus thuringiensis strains representing 14 subspecies was investigated by hybridization of an intragenic restriction fragment from a cloned crystal protein gene to whole plasmid preparations. Hybridization was found to a single plasmid in eight strains, to more than one plasmid in seven strains, and to one or both of two large, unresolved plasmids in two strains. The sizes of the hybridized plasmids ranged from 33 to over 150 megadaltons. In one additional subspecies, hybridization was only to linear DNA fragments, suggesting a chromosomal crystal protein gene, and for four other subspecies, not reported to be toxic to lepidopteran insects, no hybridization was found to either plasmids or to total cell DNA. Hybridization to restriction digests of plasmids and total cell DNA of several strains of subspecies thuringiensis and kurstaki revealed that all homology to the cloned crystal protein gene was plasmid associated and that several of these strains contained multiple regions of homology, implying the presence of multiple crystal protein genes.
Electrical maturation of neurons derived from human embryonic stem cells (2014)

In-vitro neuronal differentiation of human pluripotent stem cells has become a widely used tool in disease modeling and prospective regenerative medicine. Most studies evaluate neurons molecularly and only a handful of them use electrophysiological tools to directly indicate that these are genuine neurons. Therefore, the specific timing of development of intrinsic electrophysiological properties and synaptic capabilities remains poorly understood. Here we describe a systematic analysis of developing neurons derived in-vitro from human embryonic stem cells (hESCs). We show that hESCs differentiated in-vitro into early embryonic neurons, displaying basically mature morphological and electrical features as early as day 37. This early onset of action potential discharges suggests that first stages of neurogenesis in humans are already associated with electrical maturation. Spike frequency, amplitude, duration, threshold and after hyperpolarization were found to be the most predictive parameters for electrical maturity. Furthermore, we were able to detect spontaneous synaptic activity already at these early time-points, demonstrating that neuronal connectivity can develop concomitantly with the gradual process of electrical maturation. These results highlight the functional properties of hESCs in the process of their development into neurons. Moreover, our results provide practical tools for the direct measurement of functional maturity, which can be reproduced and implemented for stem cell research of neurogenesis in general, and neurodevelopmental disorders in particular.
Orientation of polyoxymethylene by plane strain compression and rolling with side constraints (2009)

In this paper, the authors describe the application of the constrained rolling process to produce highly oriented polyacetal bars with enhanced mechanical properties. The focus is on two commercial grades of polyoxymethylene Delrin 100 and Tarnoform 300. Tarnoform, unlike Delrin, is a copolymer. The structure and properties of the samples rolled to different compression ratios are described.