gebhart/patrepeval huggingface dataset:
Open reading frame 176 in the photosynthesis gene cluster of Rhodobacter capsulatus encodes idi, a gene for isopentenyl diphosphate isomerase (1996)

Isopentenyl diphosphate (IPP) isomerase catalyzes an essential activation step in the isoprenoid biosynthetic pathway. A database search based on probes from the highly conserved regions in three eukaryotic IPP isomerases revealed substantial similarity with ORF176 in the photosynthesis gene cluster in Rhodobacter capsulatus. The open reading frame was cloned into an Escherichia coli expression vector. The encoded 20-kDa protein, which was purified in two steps by ion exchange and hydrophobic interaction chromatography, catalyzed the interconversion of IPP and dimethylallyl diphosphate. Thus, the photosynthesis gene cluster encodes all of the enzymes required to incorporate IPP into the ultimate carotenoid and bacteriochlorophyll metabolites in R. capsulatus. More recent searches uncovered additional putative open reading frames for IPP isomerase in seed-bearing plants (Oryza sativa, Arabidopsis thaliana, and Clarkia breweri), a worm (Caenorhabditis elegans), and another eubacterium (Escherichia coli). The R. capsulatus enzyme is the smallest of the IPP isomerases to be identified thus far and may consist mostly of a fundamental catalytic core for the enzyme.
Mapping the extended substrate binding site of cathepsin G and human leukocyte elastase. Studies with peptide substrates related to the alpha 1-protease inhibitor reactive site. (1979)

The kinetic constants for the hydrolysis of a series of I-nitroanilide substrates by human leukocyte (HL) elastase and cathepsin G, porcine pancreatic elastase, and bovine chymotrypsin at pH 7.50 are reported.HL elastase and cathepsin G are currently thought to be the agents responsible for destruction of the lung in the disease emphysema.MeO-Sue-Ala-Ala-Pro-VaI-NA is an excellent substrate for HL elastase and is not hydrolyzed by cathepsin G.The MeO-Sue-group increases the solubility of a substrate relative to the acetyl group.With HL elastase, this structural change increases the reactivity of the enzyme toward both I-nitroanilide substrates and chloromethyl ketone inhibitors.This indicates that HL elastase is interacting with at least 5 residues of a substrate (or inhibitor).Cathepsin G prefers Pb groups which are negatively charged such as Sue-, Suc(4F)-, Glt-, or Mal-.This enzyme, in common with many other serine proteases cannot accept a Pro residue at its Ss subsite.One of the better substrates for cathepsin G, Sue-Ala-Ala-Pro-Phe-NA, was not hydrolyzed by HL elastase.These tools should be useful in the study of the biological function of HL elastase and cathepsin G. Two tetrapeptide 4-nitroanilide substrates related to the reactive site of the plasma (~1' protease inhibitor (ai-antitrypsin) were studied.Both have a P1 Met residue and one, MeO-Suc-Ala-Ile-Pro-Met-NA, has the exact sequence of the Pa to Pt residues at the proteolysis site of al-PI (Johnson, D. A., and Travis, J. (1978) J. BioL Clrem.253, 7142-7144).Both MeO-Sue-Ala-Ala-Pro-Met-NA and MeO-Suc-Ala-Ile-Pro-Met-NA react with cathepsin G, HL elastase, and bovine chymotrypsin.The former is in fact the best 4nitroanilide substrate of cathepsin G yet reported.Oxidation of MeO-Sue-Ala-Ala-Pro-Met-NA yielded two diastereomeric sulfoxides.Neither are bound to or was hydrolyzed by HL elastase or cathepsin G.Both reacted poorly
The Happiness Formula (2005)

^Phis complex of higher-order abstractions we call general semantics is .J. reflected in a set of high low-order abstractions we shall call attitudes. One such attitude vigorously endorsed by Alfred Korzybski is found in his formula for happiness: H = VE, or, as modified by Irving J. Lee, H = M/E. This is a compact way of saying that we ought to keep our expectations of achieving a goal low and our motivation for working to achieve it high. Korzybski argued that since our knowledge of anything is always limited, and that since the future is an uncertain inference, the proper attitude reflecting this state of affairs is one of keeping the expectations low. When we keep our expectations high we are not prepared for their not being fulfilled, which, in the light of our limited knowledge and the infinite complexity of the world, is much more likely than the fulfillment of our expectations. Consequently a person with chronically high expectations is a chronically disappointed man. He is likely to become a victim of Wendell Johnson's IFD disease he moves from Idealism to Frustration to Demoralization. On the other hand, if we keep our expectations low, we have a map that fits the territory. Whatever happens is likely to be better than we expected. Therefore life becomes a series of successes and no matter how minor many of them may be we are much more likely to be happy with this attitude than the other. There are those who claim that unless we have high expectations of succeeding in a task, we cannot work hard at it, cannot have high motivation. This is not necessarily so. Those who make this claim have never really tried or even
Induction of Squamous Differentiation by Interferon beta in a Human Non-Small-Cell Lung Cancer Cell Line (1994)

Interferon beta may have clinical usefulness in squamous differentiation strategies for the treatment of non-small-cell lung cancer. More must be learned about the mechanisms whereby interferons and other biologic agents induce differentiation, and clinical trials will be needed to determine whether in vitro results are pertinent in vivo.
Recombinant Anti-CD20 Antibody Fragments for Small-Animal PET Imaging of B-Cell Lymphomas (2009)

A radioiodinated minibody and a radioiodinated scFv-Fc fragment produced excellent, high-contrast images in vivo. These new immunoPET agents may prove useful for imaging CD20-positive lymphomas in preclinical models and in humans with NHL.
The capsular polysaccharide of Bacteroides fragilis comprises two ionically linked polysaccharides. (1992)

Recently, we have shown that the capsular polysaccharide of Bacteroides fragilis NCTC 9343 is composed of an aggregate of two discrete large molecular weight polysaccharides (designated polysaccharides A and B). Following disaggregation of this capsular complex by very mild acid treatment, high resolution NMR spectroscopy demonstrated that polysaccharides A and B consist of highly charged repeating unit structures with unusual substituent groups (Baumann, H., Tzianabos, A. O., Brisson, J.-R., Kasper, D.L., and Jennings, H.J. (1992) Biochemistry 31, 4081-4089). Presently, we report that the capsular polysaccharide of B. fragilis represents a complex structure that is formed as a result of ionic interactions between polysaccharides A and B. Electron microscopy of immunogold-labeled organisms (with monoclonal antibodies specific for polysaccharides A and B) demonstrated that the two polysaccharides are co-expressed on the cell surface of B. fragilis. We have shown that the purified capsule complex is made up exclusively of polysaccharide A and polysaccharide B (no other macromolecular structure was detected) in a 1:3.3 ratio and that disaggregation of this complex into the native forms of the constituent polysaccharides could be accomplished by preparative isoelectric focusing. Structural analyses of the native polysaccharides A and B showed that they possessed the same repeating unit structures as the respective acid-derived polysaccharides. The ionic nature of the linkage between polysaccharides A and B was demonstrated by reassociation of the native polysaccharides to form an aggregated polymer comparable to the original complex. The distinctive composition of this macromolecule may provide a rationale for the unusual biologic properties associated with the B. fragilis capsular polysaccharide.
Designing surfaces in 3-D (1976)

An experimental system for computer-aided design of free-form surfaces in three dimensions is described. The surfaces are represented in the system as parametric basis splines. The principal features of the system are: (1) the surfaces are rendered as isoparametric line drawings on a head-mounted display, and they are designed with the aid of a three-dimensional “wand,” which allows 3-D movements of the points controlling the shapes of the surfaces, (2) all of the interactions with the surfaces are in real-time, and (3) the mathematical formulations used assume no knowledge of them by the user of the system. Also examined are some of the features that should be part of a practical 3-D system for designing space-forms.
Direct rapid tooling: a review of current research (1998)

Rapid prototyping technologies are now evolving toward rapid tooling. The reasons for this extension are found in the need to further reduce the time‐to‐market by shortening not only the development phase, but also the industrialization phase of the manufacturing process. The present state of rapid tooling is reviewed and the direct rapid tooling concept, aimed at developing direct and rapid tool manufacturing processes, is presented, along with three promising methods. Their intrinsic properties are outlined and compared. Necessary research and development are described in terms of direct rapid tooling requirements.
High Mobility Group Box Protein 1 (HMGB1)-Partner Molecule Complexes Enhance Cytokine Production by Signaling Through the Partner Molecule Receptor (2011)

The nuclear protein high mobility group box protein 1 (HMGB1) promotes inflammation upon extracellular release. HMGB1 induces proinflammatory cytokine production in macrophages via Toll-like receptor (TLR)-4 signaling in a redox-dependent fashion. Independent of its redox state and endogenous cytokine-inducing ability, HMGB1 can form highly immunostimulatory complexes by interaction with certain proinflammatory mediators. Such complexes have the ability to enhance the induced immune response up to 100-fold, compared with induction by the ligand alone. To clarify the mechanisms for these strong synergistic effects, we studied receptor requirements. Interleukin (IL)-6 production was assessed in supernatants from cultured peritoneal macrophages from mice each deficient in one of the HMGB1 receptors (receptor for advanced glycation end products [RAGE], TLR2 or TLR4) or from wild-type controls. The cultures were stimulated with the TLR4 ligand lipopolysaccaride (LPS), the TLR2 ligand Pam₃CysSerLys₄ (Pam₃CSK₄), noninflammatory HMGB1 or each TLR ligand in complex with noninflammatory HMGB1. The activity of the HMGB1-TLR ligand complexes relied on engagement of the same receptor as for the noncomplexed TLR ligand, since HMGB1-LPS complexes used TLR4 and HMGB1-Pam₃CSK₄ complexes used TLR2. Deletion of any of the intracellular adaptor molecules used by TLR2 (myeloid differentiation factor-88 [MyD88], TIR domain-containing adaptor protein [TIRAP]) or TLR4 (MyD88, TIRAP, TIR domain-containing adaptor-inducing interferon-β [TRIF], TRIF-related adaptor molecule [TRAM]) had similar effects on HMGB1 complex activation compared with noncomplexed LPS or Pam₃CSK₄. This result implies that the enhancing effects of HMGB1-partner molecule complexes are not regulated by the induction of additional signaling cascades. Elucidating HMGB1 receptor usage in processes where HMGB1 acts alone or in complex with other molecules is essential for the understanding of basic HMGB1 biology and for designing HMGB1-targeted therapies.
On the Impact of Phase Noise on Active Cancelation in Wireless Full-Duplex (2013)

Recent experimental results have shown that full-duplex communication is possible for short-range communications. However, extending full-duplex to long-range communication remains a challenge, primarily due to residual self-interference, even with a combination of passive suppression and active cancelation methods. In this paper, we investigate the root cause of performance bottlenecks in current full-duplex systems. We first classify all known full-duplex architectures based on how they compute their canceling signal and where the canceling signal is injected to cancel self-interference. Based on the classification, we analytically explain several published experimental results. The key bottleneck in current systems turns out to be the phase noise in the local oscillators in the transmit-and-receive chain of the full-duplex node. As a key by-product of our analysis, we propose signal models for wideband and multiple-input-multiple-output (MIMO) full-duplex systems, capturing all the salient design parameters, thus allowing future analytical development of advanced coding and signal design for full-duplex systems.
Oligonucleotide microarray analysis of distinct gene expression patterns in colorectal cancer tissues harboring BRAF and K- ras mutations (2005)

Various types of human cancers harbor BRAF somatic mutations, leading researchers to seek molecular targets for BRAF inhibitors. A mutually exclusive relationship has been observed between the BRAF-V600E mutation and K-ras mutations, suggesting that the BRAF-V600E mutation may differ from the other BRAF mutant types. Here, we used microarray analysis to examine differences between the BRAF and K-ras mutant colorectal samples and within the BRAF group (V600E versus non-V600E), in the hope that the identified gene sets could form the basis for new target development. Eleven colorectal cancers (CRCs) with BRAF mutations and nine with K-ras mutations were examined by high-density microarray analysis. We also tested whether other significant genetic or clinical status involved in CRC development, such as APC and TP53 mutations, MSI and TNM-Duke's staging, were related with the observed BRAF- or K-ras associated expression profiles. Unsupervised two-way hierarchical clustering and multidimensional scaling revealed that the differentially expressed genes clustered according to the mutation status of BRAF and K-ras, and that samples with the BRAF-V600E and non-V600E mutants could be distinguished from each other by gene profiling. Examination of TNM-Duke's staging, MSI and mutations in APC and TP53 revealed that these significant mutations could not account for the hierarchical clustering results observed in our study. We herein identified distinct gene expression patterns and gene sets that may form the basis for identification of BRAF-targeting molecules or provide researchers with a better understanding of the molecular pathogenesis underlying RAS-RAF signaling.
Flow cytometric determination of the sperm cell number in diluted bull semen samples by DNA staining method. (1987)

Flow cytometric determination of the number of bull sperm cells showed that the number of spermatozoa measured by light scattering may considerably differ from the actual number of sperm cells in the samples, depending on the proportion of contaminating particles, similar in size to sperm cells. No accurate information can be obtained from the sum of live and dead cells distinguished by means of double fluorescence staining, since a part of the sperm cell population is in a transitory state i.e. between the viable and dead states, so it cannot be stained by either dye. The number of spermatozoa in the sample can be determined very accurately if the sample is treated first with Nonidet-P-40 detergent then stained with propidium iodide. With this procedure the DNA content of each cell nucleus can be labeled and, through detecting the fluorescence signals, the actual sperm cell count of the sample can be determined with the accuracy of 95-98%.
The Structure of Dimeric ROCK I Reveals the Mechanism for Ligand Selectivity (2005)

ROCK or Rho-associated kinase, a serine/threonine kinase, is an effector of Rho-dependent signaling and is involved in actin-cytoskeleton assembly and cell motility and contraction. The ROCK protein consists of several domains: an N-terminal region, a kinase catalytic domain, a coiled-coil domain containing a RhoA binding site, and a pleckstrin homology domain. The C-terminal region of ROCK binds to and inhibits the kinase catalytic domains, and this inhibition is reversed by binding RhoA, a small GTPase. Here we present the structure of the N-terminal region and the kinase domain. In our structure, two N-terminal regions interact to form a dimerization domain linking two kinase domains together. This spatial arrangement presents the kinase active sites and regulatory sequences on a common face affording the possibility of both kinases simultaneously interacting with a dimeric inhibitory domain or with a dimeric substrate. The kinase domain adopts a catalytically competent conformation; however, no phosphorylation of active site residues is observed in the structure. We also determined the structures of ROCK bound to four different ATP-competitive small molecule inhibitors (Y-27632, fasudil, hydroxyfasudil, and H-1152P). Each of these compounds binds with reduced affinity to cAMP-dependent kinase (PKA), a highly homologous kinase. Subtle differences exist between the ROCK- and PKA-bound conformations of the inhibitors that suggest that interactions with a single amino acid of the active site (Ala215 in ROCK and Thr183 in PKA) determine the relative selectivity of these compounds. Hydroxyfasudil, a metabolite of fasudil, may be selective for ROCK over PKA through a reversed binding orientation.
SlipChip (2009)

The SlipChip is a microfluidic device designed to perform multiplexed microfluidic reactions without pumps or valves. The device has two plates in close contact. The bottom plate contains wells preloaded with many reagents; in this paper plates with 48 reagents were used. These wells are covered by the top plate that acts as a lid for the wells with reagents. The device also has a fluidic path, composed of ducts in the bottom plate and wells in the top plate, which is connected only when the top and bottom plate are aligned in a specific configuration. Sample can be added into the fluidic path, filling both wells and ducts. Then, the top plate is "slipped", or moved, relative to the bottom plate so the complementary patterns of wells in both plates overlap, exposing the sample-containing wells of the top plate to the reagent-containing wells of the bottom plate, and enabling diffusion and reactions. Between the two plates, a lubricating layer of fluorocarbon was used to facilitate relative motion of the plates. This paper implements this approach on a nanoliter scale using devices fabricated in glass. Stability of preloaded solutions, control of loading, and lack of cross-contamination were tested using fluorescent dyes. Functionality of the device was illustrated via crystallization of a model membrane protein. Fabrication of this device is simple and does not require a bonding step. This device requires no pumps or valves and is applicable to resource-poor settings. Overall, this device should be valuable for multiplexed applications that require exposing one sample to many reagents in small volumes. One may think of the SlipChip as an easy-to-use analogue of a preloaded multi-well plate, or a preloaded liquid-phase microarray.
Publisher’s Note: Local density fluctuations, hyperuniformity, and order metrics [Phys. Rev. E68, 041113 (2003)] (2003)

with inappropriate figure placement. Figure
A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis (2010)

The development of efficient Friedel-Crafts alkylations of arenes and heteroarenes using only catalytic amounts of a Lewis acid has gained much attention over the last decade. The new catalytic approaches described in this review are favoured over classical Friedel-Crafts conditions as benzyl-, propargyl- and allyl alcohols, or styrenes, can be used instead of toxic benzyl halides. Additionally, only low catalyst loadings are needed to provide a wide range of products. Following a short introduction about the origin and classical definition of the Friedel-Crafts reaction, the review will describe the different environmentally benign substrates which can be applied today as an approach towards greener processes. Additionally, the first diastereoselective and enantioselective Friedel-Crafts-type alkylations will be highlighted.
Unusually high frequencies of HIV-specific cytotoxic T lymphocytes in humans. (1989)

CTL specific for the HIV belong to the CD8 subset of T lymphocytes, and their activity is restricted by class I HLA transplantation Ag. In this report, HIV-specific CTL and their precursor cells were quantified by limiting dilution analysis. CTL were recovered from the lungs, lymph nodes, and blood of asymptomatic seropositive carriers and of patients with AIDS. HIV was found to be very immunogenic. High frequencies of both HIV-specific CTL and CTL precursor cells were detected in infected individuals. These CTL killed autologous HIV-infected macrophages and T4 lymphoblasts. They also killed doubly transfected P815-A2-env-LAV mouse tumor cells, which express the human HLA-A2 gene and the HIV-1 env gene. In the longitudinal studies of two HIV-infected patients, CTL and CTL precursor cell frequencies decreased as the clinical and immunologic status of the patients deteriorated. Most surprisingly, PBL from seronegative donors also responded to HIV stimulation in vitro and generated large numbers of HLA-restricted, HIV-specific CTL.
Chromosome 17p deletions and p53 gene mutations associated with the formation of malignant neurofibrosarcomas in von Recklinghausen neurofibromatosis. (1990)

von Recklinghausen neurofibromatosis (NF1) is a common hereditary disorder characterized by neural crest-derived tumors, particularly benign neurofibromas whose malignant transformation to neurofibrosarcomas can be fatal. The NF1 gene has been mapped to a small region of chromosome 17q, but neither the nature of the primary defect nor the mechanisms involved in tumor progression are understood. We have tested whether NF1 might be caused by the inactivation of a tumor suppressor gene on 17q, analogous to that on chromosome 22 in NF2, by searching for deletions of chromosome 17 in NF1-derived tumor specimens. Both neurofibrosarcomas from patients with "atypical" NF and 5 of 6 neurofibrosarcomas from NF1 patients displayed loss of alleles for polymorphic DNA markers on chromosome 17. However, the common region of deletion was on 17p and did not include the NF1 region of 17q. Since no loss of markers on chromosome 17 was observed in any of 30 benign tumors from NF1 patients, the 17p deletions seen in neurofibrosarcomas are probably associated with tumor progression and/or malignancy. This region contains a candidate gene for tumor progression, p53, which has recently been implicated in the progression of a broad array of human cancers. In a preliminary search for p53 aberrations by direct sequencing of polymerase chain reaction-amplified DNA from 7 neurofibrosarcomas, 2 tumors that contained point mutations in exon 4 of the p53 gene were found, suggesting a role for this gene in at least some neurofibrosarcomas. Thus the formation of malignant neurofibrosarcomas may result from several independent genetic events including mutation of the NF1 gene, whose mechanism of tumorigenesis remains uncertain, and subsequent loss of a "tumor suppressor" gene on 17p, most likely p53.