gebhart/patrepeval huggingface dataset:
Structural Basis for the Properties of Two Single‐Site Proline Mutants of CYP102A1 (P450<sub>BM3</sub>) (2010)

The crystal structures of the haem domains of Ala330Pro and Ile401Pro, two single-site proline variants of CYP102A1 (P450(BM3)) from Bacillus megaterium, have been solved. In the A330P structure, the active site is constricted by the relocation of the Pro329 side chain into the substrate access channel, providing a basis for the distinctive C-H bond oxidation profiles given by the variant and the enhanced activity with small molecules. I401P, which is exceptionally active towards non-natural substrates, displays a number of structural similarities to substrate-bound forms of the wild-type enzyme, notably an off-axial water ligand, a drop in the proximal loop, and the positioning of two I-helix residues, Gly265 and His266, the reorientation of which prevents the formation of several intrahelical hydrogen bonds. Second-generation I401P variants gave high in vitro oxidation rates with non-natural substrates as varied as fluorene and propane, towards which the wild-type enzyme is essentially inactive. The substrate-free I401P haem domain had a reduction potential slightly more oxidising than the palmitate-bound wild-type haem domain, and a first electron transfer rate that was about 10 % faster. The electronic properties of A330P were, by contrast, similar to those of the substrate-free wild-type enzyme.
Controlled Modification of Acidity in Cholecystokinin B Receptor Antagonists:  <i>N</i>-(1,4-Benzodiazepin-3-yl)-<i>N</i> ‘-[3-(tetrazol-5-ylamino)phenyl]ureas (1996)

The design, synthesis, and biological activity of a novel series of CCK-B receptor antagonists (1) which incorporate a tetrazol-5-ylamino functionality attached to the phenyl ring of the arylurea moiety of L-365,260 are described. In these compounds, the acidity of the tetrazole was gradually modified by utilization of simple conformational constraints, and X-ray crystallographic data were obtained to support the conformational depenence of the pK(a) of the aminotetrazoles. Compounds to emerge from the present work such as 1f and 2c,d are among the highest affinity and, in the case of 1f, most selective (CCK-A/CCK-B, 37 000) antagonists so far reported for this receptor. The C(5)-cyclohexyl compound 2c (L-736,380) dose-dependently inhibited gastric acid secretion in anesthetized rats (ID(50), 0.064 mg/kg) and ex vivo binding of [(125)I]CCK-8S in BKTO mice brain membranes (ED(50), 1.7 mg/kg) and is one of the most potent acidic CCK-B receptor antagonists yet described.
Evidence for the efficacy of interferon beta-1b in delaying the onset of clinically definite multiple sclerosis in individuals with clinically isolated syndrome (2014)

The BEtaferon®/BEtaseron® in Newly Emerging MS For Initial Treatment (BENEFIT) trial assessed the efficacy of early versus delayed treatment with interferon beta-1b for patients with clinically isolated syndrome (CIS). Patients were randomly assigned to receive either interferon beta-1b 250 μg every other day (early treatment, n = 292) or placebo (delayed treatment, n = 176) for 2 years or until progression to clinically definite multiple sclerosis. Clinical and magnetic resonance imaging (MRI) outcomes were assessed after 2 years (at the end of the placebo-controlled phase) and then again at 3, 5, and 8 years post randomization. MRI assessments were made after 2, 3, and 5 years. The results showed a consistent advantage of early treatment across most clinical and MRI variables, although median Expanded Disability Status Scale scores remained consistently low, with no differences between groups. These findings suggest that early treatment with interferon beta-1b improves long-term outcomes for patients presenting with CIS.
Low-Entropy States of Neutral Atoms in Polarization-Synthesized Optical Lattices (2017)

We create low-entropy states of neutral atoms by utilizing a conceptually new optical-lattice technique that relies on a high-precision, high-bandwidth synthesis of light polarization. Polarization-synthesized optical lattices provide two fully controllable optical lattice potentials, each of them confining only atoms in either one of the two long-lived hyperfine states. By employing one lattice as the storage register and the other one as the shift register, we provide a proof of concept using four atoms that selected regions of the periodic potential can be filled with one particle per site. We expect that our results can be scaled up to thousands of atoms by employing an atom-sorting algorithm with logarithmic complexity, which is enabled by polarization-synthesized optical lattices. Vibrational entropy is subsequently removed by sideband cooling methods. Our results pave the way for a bottom-up approach to creating ultralow-entropy states of a many-body system.
Using VHDL for board level simulation (1996)

Prototyping is necessary for successful development of printed circuit boards built with complex components such as microprocessors, ASICs, and ASSPs. The European Space Agency uses VHDL models for board level simulation, optimizing such models for high functional accuracy and simulation performance.
Using a Gene-Splicing Based Search Technique for Complex Multi-level Resource Assignment Problems (2008)

The phrase "planning and scheduling" represents a class of problems where a resource in limited supply is to be optimally applied. Planning and scheduling problems are accommodated by a branch of mathematics known as operations research. The goal of operations research technology is to find a solution to a known set of conditions such that some minimum "cost" or maximum "profit" is achieved, within some defined constraints. Several algorithms, such as linear programming, dynamic programming, constraint logic programming, have arisen in the past three to four decades to solve particular classes of problems, but real-world problems continue to be extremely difficult to characterize and solve robustly. Therefore, good operations research is still dominated by the ability to transform the real problem into one or more simplified - and solvable - problems without sacrificing too much of the real problem's objectives and constraints.
Aneuploidy: Cells Losing Their Balance (2008)

A change in chromosome number that is not the exact multiple of the haploid karyotype is known as aneuploidy. This condition interferes with growth and development of an organism and is a common characteristic of solid tumors. Here, we review the history of studies on aneuploidy and summarize some of its major characteristics. We will then discuss the molecular basis for the defects caused by aneuploidy and end with speculations as to whether and how aneuploidy, despite its deleterious effects on organismal and cellular fitness, contributes to tumorigenesis.
Implantable Vascular Access Systems: Experience in 1500 Patients with Totally Implanted Central Venous Port Systems (1998)

Totally implantable venous access systems are widely used, but large-scale studies evaluating these systems are lacking. In this study 1500 patients (719 male, 781 female) with an average age of 49 years (15-86 years) were fitted with subcutaneously implanted venous access systems, in most cases for long-term chemotherapy. All patients were observed until removal of the system, death, or the end of treatment. A retrospective analysis showed an average catheter life of 284 patient-days. A total of 1308 (87%) of the patients had no implant-related complications. Catheter infections occurred in 3.2% of the patients and catheter thromboses in 2.5%. Rarer complications, such as catheter malfunction, migration of the catheter, skin necrosis, catheter fracture, catheter disconnection, and pneumothorax, occurred in another 4.3% of the patients. The complications led to explantation of 178 access systems (11.9%). There was a significant difference (p < 0.05) between the low rate of infections and other complications in the group of patients with solid tumors (2% and 4%, respectively) and the rate in patients with hematologic diseases (6% and 8%, respectively). This study confirms the safety and convenience of using totally implantable venous access systems in patients on long-term chemotherapy.
Contribution of Gene Amplification to Evolution of Increased Antibiotic Resistance in<i>Salmonella typhimurium</i> (2009)

The use of beta-lactam antibiotics has led to the evolution and global spread of a variety of resistance mechanisms, including beta-lactamases, a group of enzymes that degrade the beta-lactam ring. The evolution of increased beta-lactam resistance was studied by exposing independent lineages of Salmonella typhimurium to progressive increases in cephalosporin concentration. Each lineage carried a beta-lactamase gene (bla(TEM-1)) that provided very low resistance. In most lineages, the initial response to selection was an amplification of the bla(TEM-1) gene copy number. Amplification was followed in some lineages by mutations (envZ, cpxA, or nmpC) that reduced expression of the uptake functions, the OmpC, OmpD, and OmpF porins. The initial resistance provided by bla(TEM-1) amplification allowed the population to expand sufficiently to realize rare secondary point mutations. Mathematical modeling showed that amplification often is likely to be the initial response because events that duplicate or further amplify a gene are much more frequent than point mutations. These models show the importance of the population size to appearance of later point mutations. Transient gene amplification is likely to be a common initial mechanism and an intermediate in stable adaptive improvement. If later point mutations (allowed by amplification) provide sufficient adaptive improvement, the amplification may be lost.
Interaction of components in the poly(vinyl chloride) pilled in polymerization stage (1989)

Abstract The enthalpies of the interaction between PVC or its copolymers and different fillers introduced into the polymerization mass were estimated by the microcalorimetric techniques. For highly filled compounds, the strength of the polymer ‐ filler interaction depends on the chemical nature of both components. The determination of the interaction enthalpy makes it possible to choose a polymeric cover providing for the best interaction and to calculate the lowest amount of the polymer covering entirely the filler surface.
Extraction of average doping density and junction depth in an ion-implanted deep-depletion transistor (1980)

A simple model for extracting the average doping density and the junction depth for an ion-implanted deep-depletion device is presented. Reasonable agreement between theory and experiment is shown.
Magic bullet: the history of oral rehydration therapy (1994)

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Bonded Thin Layer Detector for Integrating Solid State Dosemeters (1983)

Abstract Construction and features of new thin layer detectors for integrating solid state dosemeters, particularly thermoluminescence dosemeters based on LiF:Mg,Ti are described. Simultaneous application of high pressure and elevated temperature causes plastic flow of the LiF powder grains and physico-chemical bonding with aluminium substrates (Al/LiF-detectors), or with graphite substrates provided with a boron bonding layer and an Al2O3 reflection layer (C/B/Al2O3/LiF detectors).
Handbook of Metallurgical Process Design (2004)

Design principles: basic principles, Henry W. Stoll Risk-based metallurgical design, Mario Solari. Alloy design: designing with carbon-, low-, and medium-alloy steels, GuoXun Liu Designing with tool steel, Lin-Jiang Yang and David N. Collins Designing with high-strength low-alloy steels, Lin Li and Luoping Xu Designing with stainless steel, Joseph K. Leuk Lai Designing with microalloyed steels and interstitial-free steels, David V. Edmonds Cast iron design - processes, alloys and properties, Magnus Wessen and Ingvar L. Svensson Designing with aluminum alloys, Nack J. Kim Designing with magnesium - alloys, properties and casting processes, Trevor Abbott and Carlos Caceres Designing with titanium alloys, Michelle L. McCann and John Fannin Designing with ni-base alloys, Gerhard E. Fuchs and David U. Furrer Designing with copper alloys, Morris E. Fine and Junji Miyake Designing with powder metallurgy alloys, Joseph W. Newkirk and Ronald A. Kohser Designing with metal matrix alloys, Veikko K. Lindroos, J. Hellman, D. Lou, R. Nowak, E. Pagounis, X. Liu and I. Penttinen.
Electrochemically Generated Acid and Its Containment to 100 Micron Reaction Areas for the Production of DNA Microarrays (2006)

An addressable electrode array was used for the production of acid at sufficient concentration to allow deprotection of the dimethoxytrityl (DMT) protecting group from an overlaying substrate bound to a porous reaction layer. Containment of the generated acid to an active electrode of 100 micron diameter was achieved by the presence of an organic base. This procedure was then used for the production of a DNA array, in which synthesis was directed by the electrochemical removal of the DMT group during synthesis. The product array was found to have a detection sensitivity to as low as 0.5 pM DNA in a complex background sample.
Combinatorial strategies in biology and chemistry (2002)

Introduction Peptide Libraries - How it all Began Nonpeptide Libraries Chemical Libraries Based on the Use of Mixtures Parallel Syntheses and Automation Combinatorial Methods With Molecular Biological Techniques The Analysis of Libraries and Arrays
Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators (2016)

The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens for which no effective vaccines exist. The subunit vaccine technology exploits pathogen subunits as antigens, e.g., recombinant proteins or synthetic peptides, allowing for highly specific immune responses against the pathogens. However, such antigens are usually not sufficiently immunogenic to induce protective immunity, and they are often combined with adjuvants to ensure robust immune responses. Adjuvants are capable of enhancing and/or modulating immune responses by exposing antigens to antigen-presenting cells (APCs) concomitantly with conferring immune activation signals. Few adjuvant systems have been licensed for use in human vaccines, and they mainly stimulate humoral immunity. Thus, there is an unmet demand for the development of safe and efficient adjuvant systems that can also stimulate cell-mediated immunity (CMI). Adjuvants constitute a heterogeneous group of compounds, which can broadly be classified into delivery systems or immunostimulators. Liposomes are versatile delivery systems for antigens, and they can carefully be customized towards desired immune profiles by combining them with immunostimulators and optimizing their composition, physicochemical properties and antigen-loading mode. Immunostimulators represent highly diverse classes of molecules, e.g., lipids, nucleic acids, proteins and peptides, and they are ligands for pattern-recognition receptors (PRRs), which are differentially expressed on APC subsets. Different formulation strategies might thus be required for incorporation of immunostimulators and antigens, respectively, into liposomes, and the choice of immunostimulator should ideally be based on knowledge regarding the specific PRR expression profile of the target APCs. Here, we review state-of-the-art formulation approaches employed for the inclusion of immunostimulators and subunit antigens into liposome dispersion and their optimization towards robust vaccine formulations.
Synthesis of aldehyde and carboxylic acid derivatives from 2‐hydroxymethyl‐3‐hydroxy‐4<i>H</i>‐pyran‐4‐one (α‐hydroxymaltol) (1986)

Abstract α‐Hydroxymaltol (2‐hydroxymethyl‐3‐hydroxy‐4 H ‐pyran‐4‐one) ( 1 ) has been converted to the 3‐ O ‐methyl ether 2 and 3‐ O‐p ‐nitrobenzyl ether 4 by standard methods. The ethers 2 and 4 have been oxidized by barium manganate to the corresponding aldehydes, 3 and 5 , in 91 and 77% yields respectively. Long‐term reaction of 5 with hydrogen bromide in acetic acid gives 3‐hydroxy‐4 H ‐pyran‐4‐one‐2‐carboxaldehyde ( 6 ). The aldehyde 3 is readily oxidized by short‐term reaction with silver oxide to the corresponding acid 7 .
Sensitivity to human serum of gammaretroviruses produced from pig endothelial cells transduced with glycosyltransferase genes (2003)

Reduction of pig cell-surface alpha-galactosyl (Gal) epitope, Galalpha1, 3Galbeta1, 4GlcNAc-R, by the introduction of glycosyltransferase genes is effective in suppressing hyperacute rejection (HAR) in pig-to-human xenotransplantation. The transmission of porcine endogenous retroviruses (PERVs) has been recognized as a potential risk factor associated with xenotransplantation. In this study, effects of the introduction of glycosyltransferase genes to pig cells on the sensitivity of gammaretroviruses to human serum were investigated. Pig endothelial cells (PEC), PEC transduced with alpha1,2 fucosyltransferase (FT), alpha2,3 sialyltransferase (ST), or N-acetylglucosaminyltransferase III (GnT-III), and human embryonic kidney (HEK) 293 cells were transduced with the LacZ gene with the packaging signal of murine leukemia virus (MuLV) under the control of the long terminal repeat of MuLV by a pseudotype infection. Then, the cells were further infected with PERV subtype B (PERV-B) or feline leukemia virus subgroup B (FeLV-B). Culture supernatants of the infected cells were mixed with human serum (HS) and then inoculated to HEK293 cells. The inoculated cells were histochemically stained and lacZ-positive blue foci were counted. Glycosyltransferase activity, xenoantigenicity, and alpha-Gal epitope density in the cells were measured at the time of the infection experiments. PERV-B or FeLV-B particles from the parental PEC were efficiently neutralized by HS, while those from PEC transduced with alpha1,2FT, alpha2,3ST or GnT-III were less sensitive to HS. The transduced PEC exhibited high levels of activity of the introduced glycotransferases, and expressed fewer xenoantigens and cell-surface alpha-Gal epitopes. Our results suggest that gammaretroviruses including PERVs produced by transgenic pigs, that are generally modified to reduce the cell-surface alpha-Gal epitope to overcome the HAR in xenotransplantation, are less sensitive to HS.
Synthesis of the arene complex [{RuCl<sub>2</sub>(η<sup>6</sup>-o-MeC<sub>6</sub>H<sub>4</sub>CO<sub>2</sub>Me)}<sub>2</sub>] and separation of its diastereomeric (–)(S)-1-phenylethylamine adducts (1988)

The synthesis of [{RuCl2(η6-o-MeC6H4CO2Me)}2], (o-MeC6H4CO2Me = methyl o-toluate), from RuCl3·3H2O and methyl 1,4-dihydro-o-toluate is reported. This is the first example of an arene–ruthenium complex having planar chirality with respect to the face of the co-ordinated arene. Its reactions with tertiary phosphines and primary amines have been examined. Using optically active amines, the complexes [RuCl2(η6-o-MeC6H4CO2Me) L′][L′=(–)(S)-1-phenylethylamine or (+)-dehydroabietylamine], and [RuCl(η6-o-MeC6H4CO2Me)(N–N)]PF6[N–N =(–)(R,R)-1,2-diphenyl-1,2-diaminoethane], have been obtained as diastereomeric mixtures. The diastereomers of [RuCl2(η6-o-MeC6H4CO2Me){(–)(S)-MeCH(Ph)NH2}] have been partially separated by fractional crystallisation, the less soluble one being obtained with > 90% enrichment. Their circular dichroism spectra have been compared with those of complexes containing achiral arene–ruthenium moieties.
Suppression of oxygen vacancy formation in Hf-based high-k dielectrics by lanthanum incorporation (2007)

The effects of lanthanum incorporation into HfO2 dielectrics were studied using first-principles total energy calculations. The author’s computational result clearly showed that the formation energy of a neutral oxygen vacancy (VO0) in the vicinity of substitutional La atoms at Hf sites is 0.7eV larger than that in pure HfO2, indicating that the concentration of VO0’s is drastically reduced by La incorporation. This effect is understood to be caused by the decrease in the local dielectric constant κL around La atoms due to the strong ionic character of the La–O bond compared to the Hf–O bond.
Electronics design of a multi-rate DPSK modem for free-space optical communications (2014)

We have designed and experimentally demonstrated a radiation-hardened modem suitable for NASA’s Laser Communications Relay Demonstration. The modem supports free-space DPSK communication over a wide range of channel rates, from 72 Mb/s up to 2.88 Gb/s. The modem transmitter electronics generate a bursty DPSK waveform, such that only one optical modulator is required. The receiver clock recovery is capable of operating over all channel rates at average optical signal levels below -70 dBm. The modem incorporates a radiation-hardened Xilinx Virtex 5 FPGA and a radiation-hardened Aeroflex UT699 CPU. The design leverages unique capabilities of each device, such as the FPGA’s multi-gigabit transceivers. The modem scrubs itself against radiation events, but does not require pervasive triple-mode redundant logic. The modem electronics include automatic stabilization functions for its optical components, and software to control its initialization and operation. The design allows the modem to be put into a low-power standby mode.
Directed evolution of an anti-carcinoembryonic antigen scFv with a 4-day monovalent dissociation half-time at 37 C (2004)

An scFv has been engineered to bind carcinoembryonic antigen (CEA) with a dissociation half-time >4 days at 37 degrees C. Two mutations responsible for this affinity increase were isolated by screening yeast surface-displayed mutant libraries by flow cytometry. Soluble expression of the mutant scFv in a yeast secretion system was increased 100-fold by screening mutant libraries for improved yeast surface display level. This scFv will be useful as a limiting case for evaluating the significance of affinity in tumor targeting to non-internalizing antigens.
Histone Acetyltransferase hALP and Nuclear Membrane Protein hsSUN1 Function in De-condensation of Mitotic Chromosomes (2007)

Replicated mammalian chromosomes condense to segregate during anaphase, and they de-condense at the conclusion of mitosis. Currently, it is not understood what the factors and events are that specify de-condensation. Here, we demonstrate that chromosome de-condensation needs the function of an inner nuclear membrane (INM) protein hsSUN1 and a membrane-associated histone acetyltransferase (HAT), hALP. We propose that nascently reforming nuclear envelope employs hsSUN1 and hALP to acetylate histones for de-compacting DNA at the end of mitosis.