gebhart/patrepeval huggingface dataset:
The APC gene product in normal and tumor cells. (1993)

The APC gene has been found to be mutated during the development of sporadic colorectal tumors as well as in the germ line of familial adenomatous polyposis patients. To facilitate the characterization of both normal and mutant APC protein, a series of monoclonal and polyclonal antibodies specific for the APC protein was produced. When lymphoblastoid cell lines derived from seven familial adenomatous polyposis patients with known mutations were analyzed by Western blot, an approximately 300-kDa protein corresponding to the predicted size of full-length APC was detected in all 7 cell lines. In addition, truncated APC proteins corresponding to the product of the known mutated alleles could be detected in 4 of the 7 lines. Similar analysis of 23 colon carcinoma and 9 adenoma cell lines revealed truncated proteins in 24 (75%) of the cell lines. Moreover, 26 (81%) of the colon tumor lines were totally devoid of the normal, full-length protein. In contrast, Western blot analysis of 40 cell lines derived from sporadic tumors of other organs detected only full-length APC. Immunohistochemical analysis of APC in normal colonic mucosa revealed cytoplasmic staining with more intense staining in the basolateral margins of the epithelial cell. This staining was markedly increased in the upper portions of the crypts, suggesting an increased level of expression with maturation. These studies provide some initial clues to the function of the cytoplasmic protein APC and demonstrate the feasibility of identifying APC mutations by direct analysis of the APC protein.
HAE therapies: past present and future (2010)

Advances in understanding the pathophysiology and mechanism of swelling in hereditary angioedema (HAE) has resulted in the development of multiple new drugs for the acute and prophylactic treatment of patients with HAE. This review will recap the past treatment options, review the new current treatment options, and discuss potential future treatment options for patients with HAE.
Metabolic control of recombinant monoclonal antibody N‐glycosylation in GS‐NS0 cells (2001)

Variable N-glycosylation at Asn(297) in the Fc region of recombinant therapeutic immunoglobulin G (IgG) molecules, specifically terminal galactosylation and sialylation, may affect both pharmacokinetic behavior and effector functions of recombinant therapeutic antibodies. We investigated the hypothesis that IgG Fc glycosylation can be controlled by manipulation of cellular nucleotide-sugar metabolism. In control cultures, N-glycans associated with the Fc domain of a recombinant humanized IgG1 produced by GS-NS0 cells in culture were predominantly biantennary, variably beta-galactosylated (average 0.3 mol galactose complex N-glycan(-1)) structures with no bisecting N-acetylglucosamine residues, sialylation, or alpha1,3-linked galactosylation evident. However, a variable proportion (5% to 15%) of high-mannose (Man5 to Man9) oligosaccharides were present. To manipulate the cellular content of the nucleotide sugar precursor required for galactosylation, UDP-Gal, we included either 10 mM glucosamine or 10 mM galactose in the culture medium. In the case of the former, a 17-fold increase in cellular UDP-N-acetylhexosamine content was observed, with a concomitant reduction (33%) in total UDP-hexose, although the ratio of UDP-Glc:UDP-Gal (4:1) was unchanged. Associated with these alterations in cellular UDP-sugar content was a significant reduction (57%) in the galactosylation of Fc-derived oligosaccharides. The proportion of high-mannose-type N-glycans (specifically Man5, the substrate for N-acetylglucosaminyltransferase I) at Asn(297) was unaffected. In contrast, inclusion of 10 mM galactose in culture specifically stimulated UDP-Gal content almost five-fold. However, this resulted in only a minimal, insignificant increase (6%) in beta1,4-galactosylation of Fc N-glycans. Sialylation was not improved upon the addition of the CMP-sialic acid (CMP-SA) precursor N-acetylmannosamine (20 mM), even with an associated 44-fold increase in cellular CMP-SA content. Analysis of recombinant IgG1 Fc glycosylation during batch culture showed that beta1,4-linked galactosylation declined slightly during culture, although, in the latter stages of culture, the release of proteases and glycosidases by lysed cells were likely to have contributed to the more dramatic drop in galactosylation. These data demonstrate: (i) the effect of steric hindrance on Fc N-glycan processing; (ii) the extent to which alterations in cellular nucleotide-sugar content may affect Fc N-glycan processing; and (iii) the potential for direct metabolic control of Fc N-glycosylation.
Electric-Field-Enhanced Assembly of Single-Walled Carbon Nanotubes on a Solid Surface (2005)

We report a novel electric-field-enhanced chemical assembly approach for fabricating highly aligned SWNT arrays on a solid surface with remarkably improved efficiency and packing density, which is very important for the real applications of carbon nanotube arrays. With the enhancement of the electric field, the assembling kinetics of SWNTs is remarkably speeded up to effectively decrease the assembling time, and the packing density can even exceed the saturated density of conventional assembly method by four times within only half an hour. The molecular dynamics simulation results illustrated the alignment of SWNTs with their long axes along the electric flux in solution, leading to the increase of packing density and efficiency through overcoming the steric hindrance of the "giant" carbon nanotubes.
Enumeration and targeted analysis of KRAS, BRAF and PIK3CA mutations in CTCs captured by a label-free platform: Comparison to ctDNA and tissue in metastatic colorectal cancer (2016)

Treatment of advanced colorectal cancer (CRC) requires multimodal therapeutic approaches and need for monitoring tumor plasticity. Liquid biopsy biomarkers, including CTCs and ctDNA, hold promise for evaluating treatment response in real-time and guiding therapeutic modifications. From 15 patients with advanced CRC undergoing liver metastasectomy with curative intent, we collected 41 blood samples at different time points before and after surgery for CTC isolation and quantification using label-free Vortex technology. For mutational profiling, KRAS, BRAF, and PIK3CA hotspot mutations were analyzed in CTCs and ctDNA from 23 samples, nine matched liver metastases and three primary tumor samples. Mutational patterns were compared. 80% of patient blood samples were positive for CTCs, using a healthy baseline value as threshold (0.4 CTCs/mL), and 81.4% of captured cells were EpCAM+ CTCs. At least one mutation was detected in 78% of our blood samples. Among 23 matched CTC and ctDNA samples, we found a concordance of 78.2% for KRAS, 73.9% for BRAF and 91.3% for PIK3CA mutations. In several cases, CTCs exhibited a mutation that was not detected in ctDNA, and vice versa. Complementary assessment of both CTCs and ctDNA appears advantageous to assess dynamic tumor profiles.
Area-Efficient Temporally Hardened by Design Flip-Flop Circuits (2010)

Two temporally hardened master-slave flip-flops are presented. Both designs utilize master latches containing Muller C-elements and dual redundant temporal hardening, as well as spatially interleaved circuits in both the master and slave latches to obtain large critical node spacing for immunity to multiple node charge collection. Heavy ion test results on the first flip-flop, which uses a DICE slave latch, demonstrates effectiveness of the temporal hardening approach. The second design uses a temporally hardened slave latch, which also hardens the flip-flop against clock transients. The use of automated CAD synthesis and layout techniques using these multibit flip-flops is also described, as is the hardening impact on design size and power.
Off-pump epicardial compartmentalization for ablation of atrial fibrillation (2002)

The Cox-Maze-III procedure still remains the gold standard in surgical treatment of atrial fibrillation. The major hazard of atrial fibrillation is thromboembolic event to the brain. Left atrial appendage (LAA) represents the source of thrombus and subsequent embolism although LAA obliteration is a key point to prevent thrombogenesis. We describe a simplified off-pump compartmentalization procedure using epicardial radiofrequency ablation of the left atrium and LAA stapling on the beating heart without cardiopulmonary bypass.
Space-frequency codes for broadband fading channels (2002)

The use of space-frequency coding in orthogonal frequency division multiplexing (OFDM)-based broadband multi-antenna systems has been proposed. The design criteria for space-frequency codes derived by Bolcskei and Paulraj (see Proc. IEEE WCNC-2000, Chicago, IL, vol.1, p.1-6, 2000) are vastly different from the well-known design criteria for space-time codes. In this paper, we provide an explicit construction of a class of space-frequency codes which achieve full spatial and frequency diversity.
Molecular Cloning of the Yeast Mitochondrial Aconitase Gene (ACO1) and Evidence of a Synergistic Regulation of Expression by Glucose plus Glutamate (1990)

We have isolated genomic clones complementing the aconitase-deficient strain (glu1-1) of Saccharomyces cerevisiae. Identification of the aconitase gene was established by enzymatic assays and molecular analyses. The corresponding mRNA has been characterized, and its direction of transcription has been determined. The complete nucleotide sequence revealed strong amino acid homologies with the sequences of some peptides isolated from the mammalian protein. Disruption of the gene by deletion-insertion led to glutamate auxotrophy. Expression of the aconitase gene was sensitive to glucose repression and was synergistically down regulated by glucose and glutamate.
Introduction to Machine Learning and Bioinformatics (2008)

Lucidly Integrates Current Activities Focusing on both fundamentals and recent advances, Introduction to Machine Learning and Bioinformatics presents an informative and accessible account of the ways in which these two increasingly intertwined areas relate to each other. Examines Connections between Machine Learning & Bio
Quantitative determination of nuclear pore complexes in cycling cells with differing DNA content (1977)

The number of pore complexes per nucleus was determined for a wide variety of cultured cells selected for their variable DNA content over a range of 1-5,6000. The pore number was compared to DNA content, nuclear surface area, and nuclear volume. Values for pore frequency (pores/square micrometer) were relatively constant in the species studied. When the pore to DNA ratio was plotted against the DNA content, there was a remarkable correlation which decreased exponentially for the cells of vertebrae origin. Exceptions were the heteroploid mammalian cells which had the same ratio as the diploid mammalian cells despite higher DNA content. The results are interpreted to mean that neither the nuclear surface, the nuclear volume, nor the DNA content alone determines the pore number of the nucleus, but rather an as yet undetermined combination of different factors. The surface and volume of vertebrate nuclei do not decrease with decreasing DNA content below a given value. The following speculation is suggested to account for the anomalous size changes of the nucleus relative to DNA content in vertebrates. Species with small DNA complements have a relatively large proportion of active chromatin which determines the limits of the physical parameters of the nucleus. The amount of active chromatin maybe the same for at least the vertebrates with low DNA content, At high DNA content, the nuclear parameters may be determined by the relatively high proportion of inactive condensed chromatin which increases the nuclear surface and volume.
Purification and properties of a thermostable fumarate hydratase from the archaeobacterium Sulfolobus solfataricus (1990)

Fumarate hydratase (EC 4.2.1.2) from the extremely thermophilic archaeobacterium Solfolobus solfataricus has been purified to homogeneity by a rapid purification procedure using affinity chromatography and high-performance size-exclusion chromatography, and the enzyme's physical and biochemical properties have been determined. The native enzyme has a molecular mass of 170 kDa and is composed of identical subunits with a molecular mass of 45 kDa, thus indicating a tetrameric structure similar to fumarases isolated from other organisms. The enzyme was active at temperatures ranging from 40 degrees C to 90 degrees C, with a maximum activity at 85 degrees C. The pH optimum for generation of fumarate was found to be pH 8.0. The enzyme showed high stability to denaturation by heat and organic solvents.
Location Estimation in Ad Hoc Networks with Directional Antennas (2005)

With the development of location aware sensor applications, location determination has become an increasingly important middleware technology. Numerous current technologies for location determination of sensor nodes use the received signal strength from sensor nodes using omnidirectional antennas. However, an increasing number of sensor systems are now deploying directional antennas due to their advantages like energy conservation and better bandwidth utilization. In this paper, we present techniques for location determination in a sensor network with directional antennas under different kinds of deployment of the nodes. We show how the location estimation problem can be solved by measuring the received signal strength from just one or two anchors in a 2D plane with directional antennas. We implement our technique using Berkeley MICA2 sensor motes and show that it is up to three times more accurate than triangulation using omnidirectional antennas. We also perform Matlab simulations that show the accuracy of location determination with increasing node density
Mapping the Differential Distribution of Proteoglycan Core Proteins in the Adult Human Retina, Choroid, and Sclera (2012)

A combination of proteomics and immunohistochemistry approaches has provided for the first time a comprehensive analysis of the presence and distribution of PG core proteins throughout the human retina, choroid, and sclera. This complements our knowledge of glycosaminoglycan chain distribution in the human eye, and has important implications for understanding the structure and functional regulation of the eye in health and disease.
c‐myc over‐expression in human primary ovarian tumours: Its relevance to tumour progression (1992)

Expression of the c-myc gene was analyzed in 56 human primary ovarian cancer tissues, including 51 common epithelial and 5 non-epithelial tumours to determine molecular events in the carcinogenic process in ovaries. Over-expression of the c-myc gene was found in 37.3% of all ovarian tumour tissues, and in 63.5% of serous adenocarcinoma tissues. Significant over-expression of the c-myc gene at Stage III compared with other stages, and one remarkable case of over-expression in a serous tumour of low malignant potential suggest that c-myc expression is temporarily activated at some stage(s) during tumorigenesis of ovarian cancer, especially of serous tumours.
Gain of function Na V 1.7 mutations in idiopathic small fiber neuropathy (2011)

Abstract Objective: Small nerve fiber neuropathy (SFN) often occurs without apparent cause, but no systematic genetic studies have been performed in patients with idiopathic SFN (I‐SFN). We sought to identify a genetic basis for I‐SFN by screening patients with biopsy‐confirmed idiopathic SFN for mutations in the SCN9A gene, encoding voltage‐gated sodium channel Na V 1.7, which is preferentially expressed in small diameter peripheral axons. Methods: Patients referred with possible I‐SFN, who met the criteria of ≥2 SFN‐related symptoms, normal strength, tendon reflexes, vibration sense, and nerve conduction studies, and reduced intraepidermal nerve fiber density (IENFD) plus abnormal quantitative sensory testing (QST) and no underlying etiology for SFN, were assessed clinically and by screening of SCN9A for mutations and functional analyses. Results: Twenty‐eight patients who met stringent criteria for I‐SFN including abnormal IENFD and QST underwent SCN9A gene analyses. Of these 28 patients with biopsy‐confirmed I‐SFN, 8 were found to carry novel mutations in SCN9A . Functional analysis revealed multiple gain of function changes in the mutant channels; each of the mutations rendered dorsal root ganglion neurons hyperexcitable. Interpretation: We show for the first time that gain of function mutations in sodium channel Na V 1.7, which render dorsal root ganglion neurons hyperexcitable, are present in a substantial proportion (28.6%; 8 of 28) of patients meeting strict criteria for I‐SFN. These results point to a broader role of Na V 1.7 mutations in neurological disease than previously considered from studies on rare genetic syndromes, and suggest an etiological basis for I‐SFN, whereby expression of gain of function mutant sodium channels in small diameter peripheral axons may cause these fibers to degenerate. ANN NEUROL 2012;71:26–39
Robust data hiding for images (2002)

Data hiding is the process of encoding extra information in an image by making small modifications to its pixels. To be practical, the hidden data must be perceptually invisible yet robust to common signal processing operations. This paper introduces two schemes for hiding data in images. The techniques exploit perceptual masking properties to embed the data in an invisible manner. The first method employs spatial masking and data spreading to hide information by modifying the image coefficients. The second method uses frequency masking to modify the image spectral components. By using perceptual masking, we also increase the robustness of the hidden information. Experimental results of data recovery after applying noise and JPEG coding to the hidden data are included.
Mechanism of Retinoid X Receptor Partial Agonistic Action of 1-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-1H-benzotriazole-5-carboxylic Acid and Structural Development To Increase Potency (2013)

We have reported that retinoid X receptor (RXR) partial agonist 1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-1H-benzotriazole-5-carboxylic acid (CBt-PMN, 4a) shows a significant antidiabetes effect in the KK-A(y) type 2 diabetes model mice, with reduced side effects compared to RXR full agonists. To elucidate the mechanism of the RXR partial agonist activity of 4a, we synthesized derivatives of 4a, evaluated their RXR agonist activity, and performed structure-activity relationship analysis. Reporter gene assay revealed that though 6b, which possesses an amino group at the 2-position of 5-carboxybenzimidazole, showed RXR full-agonist activity, compounds 6d and 6e, which possess an oxygen atom and a sulfur atom at the corresponding position, respectively, showed weak RXR agonist activity. On the other hand, 6c, which has a trifluoromethyl group at the corresponding position, acts as an RXR partial agonist, having similar Emax (67 ± 2%) and lower EC50 (15 ± 0 nM) compared to those of 4a (Emax = 75 ± 4%, EC50 = 143 ± 2 nM). A fluorescence polarization assay of cofactor recruitment confirmed that fluorescein-labeled D22 coactivator peptide was less efficiently recruited to RXR by 4a and 6c than by LGD1069 (1), a known RXR full agonist. Electrostatic potential field calculations and computational docking studies suggested that full agonists show an electrostatic attraction, which stabilizes the holo structure and favors coactivator recruitment, between the side chain at the benzimidazole 2-position and the α-carbonyl oxygen of asparagine-306 in helix 4 (H4) of the RXR receptor. However, RXR partial agonists 4a and 6c lack this interaction. Like 4a, 6c showed a significant antidiabetes effect in KK-A(y) type 2 diabetes model mice with reduced levels of the side effects associated with RXR full agonists. These findings should aid the design of new RXR partial agonists as antitype 2 diabetes drug candidates.
Effects of interface layer sequencing on the transport properties of InAs/AlSb quantum wells: Evidence for antisite donors at the InAs/AlSb interface (1990)

Data are presented on the role of the InAs/AlSb interface in determining the electron transport in AlSb/InAs/AlSb quantum wells grown by molecular-beam epitaxy. Because both anion and cation change across an InAs/AlSb interface, it is possible to grow such wells with two different types of interfaces, one with an InSb-like bond configuration, the other AlAs-like. Electron mobility and concentration were found to depend very strongly on the manner in which the quantum well’s interfaces were grown, indicating that high mobilities are seen only if the bottom interface is InSb-like. An As-on-Al sites antisite defect model is postulated for bottom AlAs-like interfaces. Such antisites were used in subsequent samples as donors in modulation-doped high-mobility InAs/AlSb quantum wells.
Dietary Fat Content and Fiber Type Modulate Hind Gut Microbial Community and Metabolic Markers in the Pig (2013)

Obesity leads to changes in the gut microbial community which contribute to the metabolic dysregulation in obesity. Dietary fat and fiber affect the caloric density of foods. The impact of dietary fat content and fiber type on the microbial community in the hind gut is unknown. Effect of dietary fat level and fiber type on hindgut microbiota and volatile fatty acid (VFA) profiles was investigated. Expression of metabolic marker genes in the gut, adipose tissue and liver was determined. A 2 × 2 experiment was conducted in pigs fed at two dietary fat levels (5% or 17.5% swine grease) and two fiber types (4% inulin, fermentable fructo-oligosaccharide or 4% solka floc, non-fermentable cellulose). High fat diets (HFD) resulted in a higher (P<0.05) total body weight gain, feed efficiency and back fat accumulation than the low fat diet. Feeding of inulin, but not solka floc, attenuated (P<0.05) the HFD-induced higher body weight gain and fat mass accumulation. Inulin feeding tended to lead to higher total VFA production in the cecum and resulted in a higher (P<0.05) expression of acyl coA oxidase (ACO), a marker of peroxisomal β-oxidation. Inulin feeding also resulted in lower expression of sterol regulatory element binding protein 1c (SREBP-1c), a marker of lipid anabolism. Bacteria community structure characterized by DGGE analysis of PCR amplified 16S rRNA gene fragments showed that inulin feeding resulted in greater bacterial population richness than solka floc feeding. Cluster analysis of pairwise Dice similarity comparisons of the DGGE profiles showed grouping by fiber type but not the level of dietary fat. Canonical correspondence analysis (CCA) of PCR- DGGE profiles showed that inulin feeding negatively correlated with back fat thickness. This study suggests a strong interplay between dietary fat level and fiber type in determining susceptibility to obesity.