gebhart/patrepeval huggingface dataset:
Genome-Wide Loss of Heterozygosity and Copy Number Analysis in Melanoma Using High-Density Single-Nucleotide Polymorphism Arrays (2007)

Although a number of genes related to melanoma development have been identified through candidate gene screening approaches, few studies have attempted to conduct such analyses on a genome-wide scale. Here we use Illumina 317K whole-genome single-nucleotide polymorphism arrays to define a comprehensive allelotype of melanoma based on loss of heterozygosity (LOH) and copy number changes in a panel of 76 melanoma cell lines. In keeping with previous reports, we found frequent LOH on chromosome arms 9p (72%), 10p (55%), 10q (55%), 9q (49%), 6q (43%), 11q (43%), and 17p (41%). Tumor suppressor genes (TSGs) can be identified through homozygous deletion (HD). We detected 174 HDs, the most common of which targeted CDKN2A (n = 33). The second highest frequency of HD occurred in PTEN (n = 8), another well known melanoma TSG. HDs were also common for PTPRD (n = 7) and HDAC4 (n = 3), TSGs recently found to be mutated or deleted in other cancer types. Analysis of other HDs and regions of LOH that we have identified might lead to the characterization of further melanoma TSGs. We noted 197 regional amplifications, including some centered on the melanoma oncogenes MITF (n = 9), NRAS (n = 3), BRAF (n = 3), and CCND1 (n = 3). Other amplifications potentially target novel oncogenes important in the development of a subset of melanomas. The numerous focal amplifications and HDs we have documented here are the first step toward identifying a comprehensive catalog of genes involved in melanoma development, some of which may be useful prognostic markers or targets for therapies to treat this disease.
Relationship Between Conformational Flexibility and Chelate Cooperativity (2011)

A family of four biscarbamates (AA) and four bisphenols (DD) were synthesized, and H-bonding interactions between all AA•DD combinations were characterized using (1)H NMR titrations in carbon tetrachloride. A chemical double mutant cycle analysis shows that there are no secondary electrostatic interactions or allosteric cooperativity in these systems, and the system therefore provides an ideal platform for investigating the relationship between chemical structure and chelate cooperativity. Effective molarities (EMs) were measured for 12 different systems, where the number of rotors in the chains connecting the two H-bond sites was varied from 5 to 20. The association constants vary by less than an order of magnitude for all 12 complexes, and the variation in EM is remarkably small (0.1-0.9 M). The results provide a relationship between EM and the number of rotors in the connecting chains (r): EM ≈ 10r(-3/2). The value of 10 M is the upper limit for the value of EM for a noncovalent intramolecular interaction. Introduction of rotors reduces the value of EM from this maximum in accord with a random walk analysis of the encounter probability of the chain ends (r(-3/2)). Noncovalent EMs never reach the very high values observed for covalent processes, which places limitations on the magnitudes of the effects that one is likely to achieve through the use of chelate cooperativity in supramolecular assembly and catalysis. On the other hand, the decrease in EM due to the introduction of conformational flexibility is less dramatic than one might expect based on the behavior of covalent systems, which limits the losses in binding affinity caused by poor preorganization of the interaction sites.
Structure-function studies on PEDF. A noninhibitory serpin with neurotrophic activity. (1997)

The neuronal differentiating and survival activities and presence of PEDF next to the neural retina support the idea that this serpin plays a neurotrophic role in vivo. The knowledge of the PEDF structure has provided information on the determinants for the noninhibitory and neurotrophic activities. PEDF has characteristics of a substrate rather than an inhibitor of serine proteases. Further studies are needed to identify the missing structural elements on PEDF that would confer serpin inhibitory activity. An N-terminus peptide region provides the neurotrophic function to the PEDF protein while other structural characteristics are dispensable (e.g. signal peptide, oligosaccharides on the polypeptide backbone, serpin exposed loop). During evolution PEDF might have lost its inhibitory activity and gained its neurotrophic function. Particular activities on other serpins have been reported (e.g. angiotensinogen, maspin, etc.). PEDF is an example of the separation of inhibitory and particular activities in a serpin.
Neutrophil extracellular traps: Is immunity the second function of chromatin? (2012)

Neutrophil extracellular traps (NETs) are made of processed chromatin bound to granular and selected cytoplasmic proteins. NETs are released by white blood cells called neutrophils, maybe as a last resort, to control microbial infections. This release of chromatin is the result of a unique form of cell death, dubbed "NETosis." Here we review our understanding of how NETs are made, their function in infections and as danger signals, and their emerging importance in autoimmunity and coagulation.
Cancer vaccines and immunotherapy (2002)

It is now clear that many human tumour antigens can be recognised by the immune system. These tumour antigens can be classified into several groups including cancer-testis, differentiation, tissue specific, over-expressed, and viral-associated antigens. In many cases, there is a known molecular basis of carcinogenesis which provides the explanation for the differentiated expression of these antigens in tumours compared with normal cells. Improved understanding of the biology of the immune response, particularly of immune recognition and activation of T-cells, allow better design of vaccines. Pre-clinical comparative studies allow evaluation of optimal vaccine strategies which can then be delivered to the clinic. Currently, a range of cancer vaccines are being tested including those using tumour cells, proteins, peptides, viral vectors, DNA or dendritic cells. Ultimately, this research should give rise to an entirely new modality of cancer treatments.
Crystal Structure of a Shark Single-Domain Antibody V Region in Complex with Lysozyme (2004)

Cartilaginous fish are the phylogenetically oldest living organisms known to possess components of the vertebrate adaptive immune system. Key to their immune response are heavy-chain, homodimeric immunoglobulins called new antigen receptors (IgNARs), in which the variable (V) domains recognize antigens with only a single immunoglobulin domain, akin to camelid heavy-chain V domains. The 1.45 angstrom resolution crystal structure of the type I IgNAR V domain in complex with hen egg-white lysozyme (HEL) reveals a minimal antigen-binding domain that contains only two of the three conventional complementarity-determining regions but still binds HEL with nanomolar affinity by means of a binding interface comparable in size to conventional antibodies.
GAP-43 transgenic mice: dispersed genomic sequences confer a GAP-43- like expression pattern during development and regeneration (1994)

Using transgenic mice, we have examined the expression pattern conferred by regions of genomic GAP-43 coupled to beta-galactosidase. We demonstrate that gene constructions that include the GAP-43 5′- flanking region along with sufficient sequences of the first intron drive beta-galactosidase (lacZ) expression to mimic in many regards the complex spatial and temporal pattern of endogenous GAP-43 expression. Transgene expression reaches peak levels during development, and persists at high levels in particular adult brain regions, such as the hippocampus and olfactory bulb. The inclusion of a stretch of the first intron in the construction is necessary to prevent expression outside of the nervous system, indicating that some of the cell specificity of GAP-43 expression is due to suppression of expression in inappropriate tissues. Injury caused by sciatic nerve crush causes reexpression of the transgene in adult sensory and motor neurons. This genomic region of GAP-43, therefore, includes elements responsive to neuronal growth signals that regulate both development and regeneration.
A Practical Method for the Removal of Ruthenium Byproducts by Supercritical Fluid Extraction (2006)

Supercritical CO2 was used to remove ruthenium catalyst and its derived by-products from a crude ring-closing metathesis reaction. The method was implemented in a semi-continuous fashion and allowed for efficient removal of the toxic metal impurities to meet the specifications for the final drug substance.
TEM-EDX study of mechanism of bonelike apatite formation on bioactive titanium metal in simulated body fluid (2001)

Bioactive titanium metal, which forms a bonelike apatite layer on its surface in the body and bonds to the bone through the apatite layer, can be prepared by NaOH and heat treatments to form an amorphous sodium titanate layer on the metal. In the present study, the mechanism of apatite formation on the bioactive titanium metal has been investigated in vitro. The metal surface was examined using transmission electron microscopy and energy dispersive X-ray spectrometry as a function of the soaking time in a simulated body fluid (SBF) and complemented with atomic emission spectroscopy analysis of the fluid. It was found that, immediately after immersion in the SBF, the metal exchanged Na(+) ions from the surface sodium titanate with H(3)O(+) ions in the fluid to form Ti-OH groups on its surface. The Ti-OH groups, immediately after they were formed, incorporated the calcium ions in the fluid to form an amorphous calcium titanate. After a long soaking time, the amorphous calcium titanate incorporated the phosphate ions in the fluid to form an amorphous calcium phosphate with a low Ca/P atomic ratio of 1.40. The amorphous calcium phosphate thereafter converted into bonelike crystalline apatite with a Ca/P ratio of 1.65, which is equal to the value of bone mineral. The initial formation of the amorphous calcium titanate is proposed to be a consequence of the electrostatic interaction of negatively charged units of titania, which are dissociated from the Ti-OH groups, with the positively charged calcium ions in the fluid. The amorphous calcium titanate is speculated to gain a positive charge and to interact with the negatively charged phosphate ions in the fluid to form the amorphous calcium phosphate, which eventually stabilizes into bonelike crystalline apatite.
Microfluidic System for Transmission Electron Microscopy (2010)

We present a microfluidic system that maintains liquid flow in a specimen chamber for scanning transmission electron microscope (STEM) imaging. The specimen chamber consists of two ultrathin silicon nitride windows supported by silicon microchips. They are placed in a specimen holder that seals the sample from the vacuum in the electron microscope and incorporates tubing to and from the sample connected to a syringe pump outside the microscope. Using results obtained from fluorescence microscopy of microspheres flowing through the system, an equation to characterize the liquid flow through the system was calibrated. Gold nanoparticles of diameters of 30 and 100 nm moving in liquid were imaged with a 200 kV STEM. It was concluded that despite strong influences from Brownian motion, and sensitivity to small changes in the depth of the bypass channel, the electron microscopy flow data matched the calculated flow speed within an order of magnitude. The system allows for rapid (within a minute) liquid exchange, which can potentially be used, for example, to investigate the response of specimens, e.g., eukaryotic or bacterial cells, to certain stimuli.
Flow cytometric analysis of tetanus toxin binding to neuroblastoma cells (1985)

A neuroblastoma cell line was assessed for its capacity to bind tetanus toxin (TT) by using immunofluorescence and flow cytometry to analyze cells on a single cell basis. A clone of Neuro 2a, N2AB-1, was shown to bind variable amounts of TT per cell and this binding could be saturated by increasing doses of the toxin. Toxin binding was specific for neuronal cells, as the non-neuronal cell line, C6 glioma, bound negligible amounts of toxin. Variability of immunofluorescence staining was due in part to the increase in size of N2AB-1 cells as they progress through the cell cycle as measured by cell surface densities of toxin binding and DNA levels by propidium iodide (PI) staining. When N2AB-1 cells were treated with exogenous gangliosides for 24 h, cells were induced to sprout neurites and cell growth was inhibited. Analysis of DNA histograms indicated that ganglioside treatment caused more cells to appear in G0G1 of the cell cycle than that seen for untreated controls. Upon cytometric analysis of TT binding to ganglioside treated cells, it was apparent that treatment stimulated all cells to bind TT in larger amounts per cell than that seen with untreated N2AB-1 cells. These data suggest that TT binding and, therefore, toxin receptors are constant in density throughout the cell cycle of these neuroblastoma cells and that exogenous gangliosides can cause differentiation followed by increased toxin binding.
Electromagnetic-bandgap layers for broad-band suppression of TEM modes in power planes (2005)

A practical set of engineering design equations are derived for predicting stopband performance of electromagnetic-bandgap (EBG) structures within parallel power planes. The EBG circuits suppress the TEM-mode noise within parallel plates used within digital power distribution networks. Stopbands are realized over designed frequency bands of interest in the microwave spectrum. The mathematical relationships between the physical hardware and the electrical models are clearly stated. Several examples are given and proof-of-concept experiments are described and compared to the predicted results with good agreement.
Topographic distribution of black‐pigmenting anaerobes before and after periodontal treatment by local delivery of tetracycline (1996)

The purpose of this study was to determine the distribution of black-pigmenting Gram-negative bacteria in the dentition of 10 adult periodontitis patients before and after treatment by local delivery of tetracycline. The subjects were selected based on a screening for high counts of Porphyromonas gingivalis and multiple deep pockets. Subgingival microbial samples were taken from the mesial and distal aspect of every tooth (44 to 56 sites per patient) before treatment, and after one and two months. Therapy included full mouth scaling and root planing, chlorhexidine mouth rinsing and placement of tetracycline HCl fibers (Actisite) on all teeth. 63.4% of 524 baseline samples yielded total anaerobic viable counts > or = 10(6) CFU/ml; P. gingivalis was found in 59.2% and Prevotella intermedia in 56.9%. One month after treatment, the % of samples with > or = 10(6) CFU/ml was reduced to 9.4%, 5.3% were P. gingivalis- and 5.1% P. intermedia- positive. After 2 months, 9.6% samples yielded > or = 10(6) CFU/ml, 5.2% were P. gingivalis- and 9.4% P. intermedia- positive. 20 of the 39 sites with a persistence of P. gingivalis were located on second molars. Logistic regression models were utilized to explain the persistence of P. gingivalis, using site location and other clinical parameters as independent variables. These analyses indicated a strong association of site location, pocket depth and bleeding on sampling with persistence of P. gingivalis. The study shows that local delivery of tetracycline is highly effective in reducing the prevalence and proportions of black-pigmenting anaerobes within a dentition. Bleeding deep pockets of second molars have an increased risk for persistence of these anaerobes.
Interleukin-6 interacts with interleukin-4 and other hematopoietic growth factors to selectively enhance the growth of megakaryocytic, erythroid, myeloid, and multipotential progenitor cells (1989)

The growth-promoting activities of interleukin-6 (IL-6) in combination with different factors were assessed in bone marrow (BM) cultures prepared from normal mice and from mice treated with 5-fluorouracil (5- FU). Effects on hematopoietic colony formation with respect to number, size, and cellular composition were evaluated. In agreement with previous reports, IL-6 acts synergistically with IL-3 to stimulate increased numbers of granulocyte/macrophage (GM) and multilineage colonies in day-2 and day-4 post-5-FU BM cultures. Furthermore, day 4 but not day 2 post-5-FU BM showed enhanced GM colony formation when stimulated with IL-6 plus interleukin-4 (IL-4) or granulocyte colony- stimulating factor (G-CSF). In contrast, IL-6 did not increase the number of colonies supported by M-CSF or GM-CSF. Nevertheless IL-6 interacted with all factors, including M-CSF and GM-CSF, to stimulate an increase in colony size. Many of these myeloid colonies attained a diameter of greater than or equal to 0.5 mm, suggesting they derive from high proliferative potential cells (HPP-CFC). The response of normal and day-8 post-5-FU BM containing high numbers of more mature progenitors was also assessed. We found IL-6 enhanced colony formation by lineage-restricted megakaryocytic and erythroid progenitors in the presence of IL-3 and IL-4 plus erythropoietin (Epo), respectively. The sum of these results shows that IL-6 interacts with a variety of factors to regulate the growth of progenitor cells at different stages of lineage commitment and maturation.
Enzyme-Catalyzed Acylation of Homoserine:  Mechanistic Characterization of the Escherichia coli metA-Encoded Homoserine Transsuccinylase (1999)

The first unique step in bacterial and plant methionine biosynthesis involves the activation of the gamma-hydroxyl of homoserine. In Escherichia coli, this activation is accomplished via a succinylation reaction catalyzed by homoserine transsuccinylase. The activity of this enzyme is closely regulated in vivo and therefore represents a critical control point for cell growth and viability. We have cloned homoserine transsuccinylase from E. coli and present the first detailed enzymatic study of this enzyme. Steady-state kinetic experiments demonstrate that the enzyme utilizes a ping-pong kinetic mechanism in which the succinyl group of succinyl-CoA is initially transferred to an enzyme nucleophile before subsequent transfer to homoserine to form the final product, O-succinylhomoserine. The maximal velocity, V/K(succinyl)(-)(CoA), and V/K(homoserine) all exhibited a bell-shaped pH dependence with apparent pK's of 6.6 and approximately 7.9. The enzyme was inhibited by iodoacetamide in a pH-dependent manner, with an apparent pK of the group being inactivated of 6.4. This suggests the presence of an active site cysteine which forms a succinyl-cysteine intermediate during enzymatic turnover. Solvent kinetic isotope effect studies yielded inverse effects of 0.7 on V and 0.61 on V/K in the reverse reaction only. On the basis of these observations, we propose a detailed chemical mechanism for this important member of the acyltransferase family.
Radiation-grafted hydrogels for biomaterial applications as studied by the ESCA technique (1978)

Electron spectroscopy for chemical analysis (ESCA) was used to study the surface composition of several radiation-grafted polymers in both the dry and hydrated (frozen at 160°K) states. Poly(2-hydroxyethyl methacrylate) (HEMA) and polyacrylamide, both hydrophilic polymers, were readily detected in the hydrated or dehydrated states when grafted to polyethylene substrates. For silicone rubber substrates, both grafts were observed on the hydrated surface but were significantly decreased in surface concentration upon dehydration. For grafts on a polyester-urethane, acrylamide was not a major constituent of either the dry or hydrated surface, while HEMA appeared to increase in abundance upon drying. The amount of the hydrophobic poly(ethyl methacrylate) found on the graft surface depended upon the substrate polymer used, but the surface abundance of poly(ethyl methacrylate) was not affected by drying. These results were considered in terms of polar group orientation, polymer chain mobility, substrate permeability, and the limitations of the ESCA technique. The implications of these results with respect to the use of radiation-grafted hydrophilic polymers for biomedical applications are also discussed.
Dissociative extraction and reconstitution of extracellular matrix components involved in local bone differentiation. (1981)

Subcutaneous implantation of demineralized diaphyseal bone matrix in allogeneic rats results in the local induction of endochondral bone differentiation. We have explored the potential of three dissociative extractants, 4 M guanidine hydrochloride (Gdn . HCl), 8 M urea/1 M NaCl, and 1% NaDodSO4 at pH 7.4, containing protease inhibitors to solubilize putative inductive molecules in the bone matrix. Extraction of bone matrix with any one of these extracts resulted in the loss of the bone inductive property. The solubilized extracts were then reconstituted with the residue by dialysis against water. The various reconstituted matrices were bioassayed for bone inductive potential by quantitation of alkaline phosphatase activity and 45Ca incorporation on day 12 after implantation. There was complete recovery of biological activity after reconstitution of the residues with each of the three extracts. Polyacrylamide gel electrophoresis of the extracts revealed similar protein profiles. Gel filtration of the 4 M Gdn. HCl extract on Sepharose CL-4B showed a heterogeneous broad peak. When fractions of that peak containing proteins less than 50,000 daltons were reconstituted with inactive 4 M Gdn . HCl-treated bone matrix and then implanted, new bone was induced. These observations demonstrate the dissociative extraction and successful biological reconstitution of bone inductive macromolecules in demineralized bone matrix.
Prospective validation of single plasma sample 99mTc-ethylenedicysteine clearance in adults. (1999)

This study suggests that 99mTc-EC clearance can be estimated from 54-min plasma samples with an acceptable error of estimation for most routine clinical studies.
WELL CORED TO 9,800 FT IN PARAGUAY (1991)

The mining industry's slim hole drilling rigs have proven applicable to primary oil exploration. These machines are smaller than conventional drilling rigs and can be transported with relative ease to remote locations. A typical rig drills an entire well by coring, with the cores retrieved by wire line without tripping the pipe. The core drilling system is specially suited to drilling hard rock formations. This paper reports on the project which evaluated the geological aspects of the Parana basin and determined the applicability of slim hole, core drilling techniques as an exploration tool. The Parana basin is found in the eastern third of Paraguay, part of northeastern Argentina, and part of southern Brazil. Much of the basin is overlaid by basalt flows up to 5,000-ft thick, and there are numerous igneous intrusions and dikes within the sedimentary section. This combination makes seismic quality poor and interpretation extremely difficult. The formations are relatively old, with Triassic red beds occurring only a few feet below the surface or immediately below the basalt. Beneath the Triassic are Permian marine deposits, Permo-Carboniferous tillites, and then Devonian, Silurian, and Ordovician deposits to the basement. The section outcrops 100 miles west of the Mallorquin Well No.more » 1 site. The Parana basin has been only randomly explored. To date, success has been limited to a minor gas find near Sao Paulo, Brazil.« less