gebhart/patrepeval huggingface dataset:
Prostate Specific Antigen and Gleason Grade: An Immunohistochemical Study of Prostate Cancer (1994)

Prostate cancer is histologically heterogeneous as reflected in the 5 patterns of the Gleason grading system. Gleason grade correlates with volume, extent and prognosis. Serum prostate specific antigen (PSA) levels also correlate with tumor volume but the degree to which grade correlates with PSA has not been precisely defined. To quantify this relationship further, we prepared maps of each grade of cancer in 86 radical prostatectomy specimens from patients with clinical stage T2 cancer. The median per cent of the volume of cancer per prostate composed of grade 1 was 0%, while it was 1% for grade 2, 84% for grade 3, 5% for grade 4 and 0% for grade 5. We stained 95 cancer foci (grades 1 to 5) in 40 of these specimens for PSA. The presence and intensity (0 to 3+) of staining in more than 33,000 acini (or cells) correlated inversely with grade (p < 0.0001). Nearly all acini in grade 1 and most in grade 2 stained positive (2 to 3+) for PSA; 87% were positive but with less intensity in grade 3. While many grade 4 (79%) and grade 5 (49%) cells were positive, the intensity of staining was weak. Serum PSA levels correlated with total tumor volume (r = 0.67) but serum PSA levels per cm.3 of cancer decreased with increasing grade (r = -0.24 and p < 0.02). These studies confirm the strong inverse correlation between Gleason grade and the PSA content of prostate cancer. Since more than 85% of grade 3 acini stained for PSA and grade 3 made up the largest portion (84%) of cancer, the predominant contributor to serum PSA levels from prostate cancer was Gleason grade 3. The other grades contribute relatively little to the serum PSA levels either because of the small volume (grades 1 and 2) or the diminished PSA content (grades 4 and 5).
Animal Cell Cycle (1978)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
A new control strategy for high-speed atomic force microscopy (2003)

An advanced controller consisting of a feedback and feedforward part is presented to improve the performance of an atomic force microscope (AFM) enabling topography measurements at higher scan rates with a reduced measurement error. The tip–sample interaction force is held constant by an -controller while the scanner is simultaneously tracked to the topography of the last recorded scan line by a model-based feedforward controller. The designed controller is implemented on a commercial AFM system to compare the performance to a standard proportional integral controlled AFM. The new controller reduces the measurement error and enables imaging at higher speeds and at smaller tip–sample interaction forces.
Inhibition of NAD glycohydrolase and ADP-ribosyl transferases by carbocyclic analogs of oxidized nicotinamide adenine dinucleotide (1989)

Analogues of oxidized nicotinamide adenine dinucleotide (NAD+) in which a 2,3-dihydroxycyclopentane ring replaces the beta-D-ribonucleotide ring of the nicotinamide riboside moiety of NAD+ have recently been synthesized [Slama, J. T., & Simmons, A. M. (1988) Biochemistry 27, 183]. Carbocyclic NAD+ analogues have been shown to inhibit NAD glycohydrolases and ADP-ribosyl transferases such as cholera toxin A subunit. In this study, the diastereomeric mixture of dinucleotides was separated, and the inhibitory capacity of each of the purified diastereomers was defined. The NAD+ analogue in which the D-dihydroxycyclopentane is substituted for the D-ribose is designated carba-NAD and was demonstrated to be a poor inhibitor of the Bungarus fasciatus venom NAD glycohydrolase. The diastereomeric dinucleotide pseudo-carbocyclic-NAD (psi-carba-NAD), containing L-dihydroxycyclopentane in place of the D-ribose of NAD+, was shown, however, to be a potent competitive inhibitor of the venom NAD glycohydrolase with an inhibitor dissociation constant (Ki) of 35 microM. This was surprising since psi-carba-NAD contains the carbocyclic analogue of the unnatural L-ribotide and was therefore expected to be a biologically inactive diastereomer. psi-Carba-NAD also competitively inhibited the insoluble brain NAD glycohydrolase from cow (Ki = 6.7 microM) and sheep (Ki = 31 microM) enzyme against which carba-NAD is ineffective. Sensitivity to psi-carba-NAD was found to parallel sensitivity to inhibition by isonicotinic acid hydrazide, another NADase inhibitor. psi-Carba-NAD is neither a substrate for nor an inhibitor of alcohol dehydrogenase, whereas carba-NAD is an efficient dehydrogenase substrate.(ABSTRACT TRUNCATED AT 250 WORDS)
Endothelin has biological actions at pathophysiological concentrations. (1991)

The present studies demonstrate that endothelin at pathophysiological plasma concentrations produced by exogenous endothelin has biological action. These studies support a functional role for endogenous endothelin as a potentially pathophysiological vasoconstrictor peptide hormone in the regulation of cardiovascular, renal, and endocrine function.
Yellow Fever: Victor, Victoria? Conqueror, Conquest? Epidemics and Research in the last Forty Years and Prospects for the Future (1991)

"Yellow Fever: Victor, Victoria? Conqueror, Conquest? Epidemics and Research in the last Forty Years and Prospects for the Future" published on Jul 1991 by The American Society of Tropical Medicine and Hygiene.
Development and Applications of Varieties of Bioactive Glass Compositions in Dental Surgery, Third Generation Tissue Engineering, Orthopaedic Surgery and as Drug Delivery System (2011)

Its high modulus and brittle nature makes its applications limited, but it has been used in combination with poly-methylmethacrylate to form bioactive bone cement and with metal implants as a coating to form a calcium-deficient carbonated calcium phosphate layer. Certain bioactive glass are strong enough to function in stress-bearing sites in the head and www.intechopen.com Biomaterials Applications for Nanomedicine 70 neck (e.g., mandible replacement); however, such implants cannot be easily contoured in the operating room, and screws cannot be easily placed into bioactive glass blocks because they defy drilling and have a tendency to fragment during creation of screw holes.
The TRANSPARENT TESTA GLABRA1 Locus, Which Regulates Trichome Differentiation and Anthocyanin Biosynthesis in Arabidopsis, Encodes a WD40 Repeat Protein (1999)

The TRANSPARENT TESTA GLABRA1 (TTG1) locus regulates several developmental and biochemical pathways in Arabidopsis, including the formation of hairs on leaves, stems, and roots, and the production of seed mucilage and anthocyanin pigments. The TTG1 locus has been isolated by positional cloning, and its identity was confirmed by complementation of a ttg1 mutant. The locus encodes a protein of 341 amino acid residues with four WD40 repeats. The protein is similar to AN11, a regulator of anthocyanin biosynthesis in petunia, and more distantly related to those of the beta subunits of heterotrimeric G proteins, which suggests a role for TTG1 in signal transduction to downstream transcription factors. The 1.5-kb TTG1 transcript is present in all major organs of Arabidopsis. Sequence analysis of six mutant alleles has identified base changes producing truncations or single amino acid changes in the TTG1 protein.
Palladium-Catalysed Functionalisation at 4- and 6-Position of the 7-Azaindole System (2001)

The synthesis of 4- and 6-substituted-7-azaindoles through palladium-catalysed coupling reactions of the corresponding halosubstituted-7-azaindoles is described.
Light chain editing in kappa-deficient animals: a potential mechanism of B cell tolerance. (1994)

The genetic organization of the kappa and lambda light chain loci permits multiple, successive rearrangement attempts at each allele. Multiple rearrangements allow autoreactive B cells to escape clonal deletion by editing their surface receptors. Editing may also facilitate efficient B cell production by salvaging cells with nonproductive light chain (L chain) rearrangements. To study receptor editing of kappa L chains, we have characterized B cells from mice hemizygous for the targeted inactivation of kappa (JCkD/wt) which have an anti-DNA heavy chain transgene, 3H9. Hybridomas from JCkD/wt mice exhibited an increased frequency of rearrangements to downstream Jk segments (such as Jk5) compared with most surveys from normal mice, consistent with receptor editing by sequential kappa locus rearrangements in JCkD/wt. We observed an even higher frequency of rearrangements to Jk5 in 3H9 JCkD/wt animals compared with nontransgenic JCkD/wt, consistent with editing of autoreactive kappa in 3H9 JCkD/wt. We also recovered a large number of 3H9 JCkD/wt lines with Vk12/13-Jk5 rearrangements and could demonstrate by PCR and Southern analysis that up to three quarters of these lines underwent multiple kappa rearrangements. To investigate editing at the lambda locus, we used homozygous kappa-deficient animals (JCkD/JCkD and 3H9 JCkD/JCkD). The frequencies of V lambda 1 and V lambda 2 rearrangements among splenic hybridomas in 3H9 JCkD/JCkD were reduced by 75% whereas V lambda X was increased 5-10-fold, compared with nontransgenic JCkD/JCkD animals. This indicates that V lambda 1 and V lambda 2 are negatively regulated in 3H9 JCkD/JCkD, consistent with earlier studies that showed that the 3H9 heavy chain, in combination with lambda 1 binds DNA. As successive lambda rearrangements to V lambda X do not inactivate V lambda 1, the consequence of lambda editing in 3H9 JCkD/JCkD would be failed allelic exclusion at lambda. However, analysis of 18 3H9 JCkD/JCkD hybridomas with V lambda 1 and V lambda X DNA rearrangements revealed that most of these lines do not have productive lambda 1 rearrangements. In sum, both kappa and lambda loci undergo editing to recover from nonproductive rearrangement, but only kappa locus editing appears to play a substantial role in rescuing autoreactive B cells from deletion.
Methods and instruments for continuous-flow PCR on a chip (2007)

PCR is the most commonly used method to identify DNA segments. Several methods have been used to miniaturize PCR and perform it in a microfluidic chip. A unique approach is the continuous-flow PCR, where the conventional thermocycling is replaced by pumping the sample through a channel which meanders over stationary temperature zones, allowing fast temperature changes in the sample due to the low thermal mass as well as a continuous production of PCR products. In this paper we present a system comprising a polymer microfluidic chip, a thermocycler unit and the protocols necessary to perform fast continuous-flow PCR including experimental results in comparison with a conventional PCR system.
Lipoxygenase inhibitors shift the yeast/mycelium dimorphism in Ceratocystis ulmi (1992)

The yeast-mycelium dimorphism in Ceratocystis ulmi, the causative agent of Dutch elm disease, was switched by gossypol, nordihydroguaiaretic acid, and propylgallate. In each case the mycelial form was converted to the yeast form. These compounds are recognized lipoxygenase inhibitors. Inhibitors of cyclooxygenase and thromboxane synthetase did not cause mycelia to shift to the yeast form. We suggest the following two-part hypothesis: (i) that lipoxygenase is a target for antifungal antibiotics and (ii) that many phytoalexins (antimicrobial compounds of plant origin) are targeted toward fungal lipoxygenases. In addition, in a study to determine potential lipoxygenase substrates, a fatty acid analysis indicated that C. ulmi conidiospores contained high levels of oleic, linoleic, and linolenic acids but no arachidonic acid.
The Molecular Basis for A‐Site Mutations Conferring Aminoglycoside Resistance: Relationship between Ribosomal Susceptibility and X‐ray Crystal Structures (2003)

Aminoglycoside antibiotics target the 16S ribosomal RNA (rRNA) bacterial A site and induce misreading of the genetic code. Point mutations of the ribosomal A site may confer resistance to aminoglycoside antibiotics. The influence of bacterial mutations (introduced by site-directed mutagenesis) on ribosomal drug susceptibility was investigated in vivo by determination of minimal inhibitory concentrations. To determine the origin of the various resistance phenotypes at a molecular level, the in vivo results were compared with the previously published crystal structures of paromomycin, tobramycin, and geneticin bound to oligonucleotides containing the minimal A site. Two regions appear crucial for binding in the A site: the single adenine residue at position 1408 and the non-Watson-Crick U1406.U1495 pair. The effects of mutations at those positions are modulated by the nature of the substituent at position 6' (either hydroxy or ammonium group) on ring I, by the number of positive charges on the antibiotic, and by the linkage between rings I and III (either 4,5 or 4,6). In particular, the analysis demonstrates: 1) that the C1409-G1491 to A1409-U1491 polymorphism (observed in 15 % of bacteria) is not associated with resistance, which indicates that it does not affect the stacking of ring I on residue 1491, 2) that the high-level resistance to 6'-NH3+ aminoglycosides exhibited by the A1408G mutation most probably results from the inability of ring I forming a pseudo base pair with G1408, which prevents its insertion inside the A site helix, and 3) that mutations of the uracil residues forming the U1406.U1495 pair either to cytosine or to adenine residues mostly confer low to moderate levels of drug resistance, whereas the U1406C/U1495A double mutation confers high-level resistance (except for neomycin), which suggests that aminoglycoside binding to the wild-type A site and its functional consequences strongly depend on a particular geometry of the U1406.U1495 pair. The relationships between the resistance phenotypes observed in vivo and the interactions described at the molecular level define the biological importance of the different structural interactions observed by X-ray crystallography studies.
Thermal stability of recorded information at high densities (1997)

Simulations have been carried out with the purpose of identifying the thermal stability limits on data storage density in longitudinal recording on thin film media. The simulations use a combination of molecular dynamics based upon the Landau-Lifshitz-Gilbert equation of motion and a Monte Carlo method for dealing with magnetic viscosity. Based upon the limits on media coercivity imposed by available heads and SNR considerations, but assuming that sufficient head resolution can be achieved, an upper bound of about 36 Gbit/in./sup 2/ is projected.
Molecular-Level Control of Feature Separation in One-Dimensional Nanostructure Assemblies Formed by Biomolecular Nanolithography (2004)

In this paper, we present a convenient and reliable method to organize small gold nanoparticles (d(CORE) = 1.5 nm) into linear chains with precisely controlled interparticle spacing over a range of 1.5-2.8 nm through biomolecular nanolithography. Controlling the feature separations of 1 to a few nanometers with angstrom-level precision is a key requirement in electronic and optical applications of nanostructures to tune the properties of the nanostructures and manipulate the interactions between neighboring structures. Here, chains are formed in solution by utilizing functional-group-directed self-assembly to organize ligand-stabilized gold nanoparticles onto DNA templates. The spacing between neighboring nanoparticles can be controlled chemically and tuned at the molecular level by utilizing nanoparticles possessing ligand shells of varying thickness to achieve angstrom-level resolution at spacings of 1.5, 2.1, and 2.8 nm. The small standard deviation (< or = 20%) in the values for the interparticle spacing illustrates the reproducibility of the approach. Because the interparticle spacing is enforced by the ligand shell rather than the scaffold, the spacing is uniform even in nonlinear sections of the chain. We further show that the assembly process is robust and produces extended linear nanoparticle chains of up to 1 microm in length and a total coverage of > 90%. All structures and interparticle spacings were analyzed using transmission electron microscopy. Our results demonstrate the potential of scaffold-assisted assembly approaches for patterning features with tunable dimensions on a length scale that is important for future applications of these materials in nanoscale electronics and optics.
Design and optimization of effector-activated ribozyme ligases (2000)

A selected ribozyme ligase, L1, has been engineered to respond to small organic effectors. Residues important for ribozyme catalysis were mapped to a compact core structure. Aptamers that bound adenosine and theophylline were appended to the core structure, and the resultant aptazymes proved to be responsive to their cognate effectors. Rational sequence substitutions in the joining region between the aptamer and the ribozyme yielded aptazymes whose activities were enhanced from 800-1600-fold in the presence of 1 mM ATP or theophylline, respectively. However, when an anti-flavin aptamer was appended to the core ribozyme structure flavin-responsivity was minimal. The joining region between the aptamer and the ribozyme core was randomized and a series of negative and positive selection steps yielded aptazymes that were activated by up to 260-fold in the presence of 100 microM FMN. The selected joining regions proved to be 'communication modules' that could be used to join other aptamers to the ribozyme core to form aptazymes. These results show that ribozyme ligases can be readily engineered to function as allosteric enzymes, and reveal that many of the techniques and principles previously demonstrated during the development of hammerhead aptazymes may be generalizable.
Helicobacter pylori: its discovery and relevance for medicine (2006)

In 1979, Warren was first to observe these bacteria in an inflamed gastric epithelium, and subsequently in peptic ulcer-associated gastritis. In 1981, Marshall starts his research and cultivates the bacteria, performs prospective studies, and administers therapy regimens using antibiotics and bismuth salts. The organism was designated Campylobacter-like after its similarity with said genus. In 1984, Marshall manages to meet Koch s postulates using self-inoculation by ingesting a bacterial culture, which resulted in gastritis that was then treated and cured with bismuth salts and metronidazole. The Gastroenterological Society of Australia rejected the abstract with preliminary data. In 1983, "The Lancet" published such data in two brief letters with the same heading, with each being signed by one of these two researchers. Cooperating with microbiologists they classify the new bacteria within the Helicobacter genus as the pylori species. Gastritis and peptic ulcer are currently considered infectious diseases. Their diagnosis and therapy include bacterial detection methods and antibiotics, respectively. In addition, a causal relationship between Helicobacter pylori and both gastric adenocarcinoma and gastric lymphoma has been established, and its association with some extra-digestive conditions has been suggested.
Injectable and Photopolymerizable Tissue-Engineered Auricular Cartilage Using Poly(Ethylene Glycol) Dimethacrylate Copolymer Hydrogels (2010)

In this study we investigated the histological, biochemical, and integrative features of the neocartilage using swine auricular chondrocytes photoencapsulated into two poly(ethylene glycol) dimethacrylate (PEGDM) copolymer hydrogels of a different degradation profile: degradable (PEG-4,5LA-DM) and nondegradable (PEGDM) macromers in molar ratios of 60:40 and 70:30. Integration of the engineered tissue with existing native cartilage was examined using an articular cartilaginous ring model. Experimental group samples (total n=96) were implanted subcutaneously into nude mice and harvested at 6, 12, and 18 weeks. Nonimplanted constructs (total n=16) were used as controls for quantification of DNA, glycosaminoglycan, and hydroxyproline. Histologically, neocartilage resembled both the cellular population and composition of the extracellular matrix of the native swine auricular cartilage. DNA content demonstrated that the photoencapsulated chondrocytes were capable of survival and proliferation over time. Both glycosaminoglycan and hydroxyproline contents appeared higher in the neotissue, which was supported by less degradable PEGDM hydrogel. Integration of neocartilage with surrounding native cartilage improved with time, resulting in the development of tight integration interface. PEGDM copolymer hydrogels can support in vivo chondrogenesis by photoencapsulating auricular chondrocytes.
Differential-Private Data Publishing Through Component Analysis. (2013)

A reasonable compromise of privacy and utility exists at an "appropriate" resolution of the data. We proposed novel mechanisms to achieve privacy preserving data publishing (PPDP) satisfying ε-<i>differential privacy</i> with improved utility through <i>component analysis</i>. The mechanisms studied in this article are Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA). The differential PCA-based PPDP serves as a general-purpose data dissemination tool that guarantees better utility (i.e., smaller error) compared to Laplacian and Exponential mechanisms using the same "privacy budget". Our second mechanism, the differential LDA-based PPDP, favors data dissemination for classification purposes. Both mechanisms were compared with state-of-the-art methods to show performance differences.
Synthesis and modification of new biodegradable copolymers: Serine/glycolic acid based copolymers (1997)

Serine/glycolic acid-based biodegradable polymers have been prepared by ring-opening homopolymerization of 3-(O-benzyl)-L -serinylmorpholine-2,5-dione, and ring-opening copolymerization of the morpholine-2,5-dione derivative and L -lactide/ϵ-caprolactone. The homopolymerization was carried out in the melt at 165°C for 3 min using stannous octanoate as the initiator and continued at lower reaction temperatures (130–150°C) for 48 h, using a molar ratio of monomer and initiator of 1000 yielded a polymer of Mn = 4000. The polymer prepared by homopolymerization of the morpholine-2,5-dione derivative was composed of alternating protected serine and glycolic acid residues. Random copolymers of serine and glycolic acid and L -lactic acid/ϵ-caprolactone were synthesized by copolymerization reaction of 3-(O-benzyl)-L -serinylmorpholine-2,5-dione and lactide or ϵ-caprolactone in the melt at 165°C for 3 min and further reaction at 130°C using stannous octanoate as an initiator. The polymers were deprotected and functionalized through the side chain hydroxyl group of serine residues with an acrylate moiety for applications in injectable drug delivery, cell encapsulation. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35: 1901–1907, 1997
Spirocyclic β-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitors: From Hit to Lowering of Cerebrospinal Fluid (CSF) Amyloid β in a Higher Species (2013)

A hallmark of Alzheimer's disease is the brain deposition of amyloid beta (Aβ), a peptide of 36-43 amino acids that is likely a primary driver of neurodegeneration. Aβ is produced by the sequential cleavage of APP by BACE1 and γ-secretase; therefore, inhibition of BACE1 represents an attractive therapeutic target to slow or prevent Alzheimer's disease. Herein we describe BACE1 inhibitors with limited molecular flexibility and molecular weight that decrease CSF Aβ in vivo, despite efflux. Starting with spirocycle 1a, we explore structure-activity relationships of core changes, P3 moieties, and Asp binding functional groups in order to optimize BACE1 affinity, cathepsin D selectivity, and blood-brain barrier (BBB) penetration. Using wild type guinea pig and rat, we demonstrate a PK/PD relationship between free drug concentrations in the brain and CSF Aβ lowering. Optimization of brain exposure led to the discovery of (R)-50 which reduced CSF Aβ in rodents and in monkey.