gebhart/patrepeval huggingface dataset:
Harnessing stemness and PD-L1 expression by AT-rich interaction domain-containing protein 3B in colorectal cancer (2020)

<b>Background and Aims</b>: Cancer stem cells (CSCs) have been shown to be responsible for the tumor initiation, metastasis, and therapeutic resistance of colorectal cancer (CRC). Recent studies have also indicated the importance of CSCs in escaping immune surveillance. However, the coordinated epigenetic control of the stem cell signature and the key molecule(s) involved in immunosurveillance of colorectal CSCs (CRCSCs) are unclear. Here, we investigated the role of a histone modifier, AT-rich interaction domain-containing protein 3B (ARID3B), in CRC. <b>Methods</b>: CRC patient-derived xenografts (PDXs) with knockout of ARID3B induced by CRISPR/Cas9 <i>in vivo</i> were used<i>.</i> Molecular/cellular biology assays were performed. Clinical data obtained from The Cancer Genome Atlas, as well as from our cohort (Taipei Veterans General Hospital), were analyzed. <b>Results</b>: ARID3B was crucial for the growth of CRC, and ARID3B promoted the stem-like features of CRC. Mechanistically, ARID3B activated Notch target genes, intestinal stem cell (ISC) genes, and programmed death-ligand 1 (PD-L1) through the recruitment of lysine-specific demethylase 4C (KDM4C) to modulate the chromatin configuration for transcriptional activation. Clinical sample analyses showed that the coexpression of ARID3B and the Notch target HES1 correlated with a worse outcome and that ARID3B and PD-L1 were highly expressed in the consensus molecular subtype 4 of CRC. Pharmacological inhibition of KDM4 activity reversed the ARID3B-induced signature. <b>Conclusion</b>: We reveal a noncanonical Notch pathway for activating Notch target genes, ISC genes, and PD-L1 in CRC. This finding explains the immune escape of CRCSCs and indicates a potential group that may benefit from immune checkpoint inhibitors. Epigenetic drugs for reversing stem-like features of CRC should also be investigated.
Materials and design of spinal implants?A review (1997)

Man-made devices have been implanted into the body to relieve pain, to restore function, and to facilitate healing. The subjects of this review are the materials, and to a lesser extent, the design aspects of the numerous implants that are available to the surgeon in dealing with the ailing spine. Often it is the material aspects of such devices that are responsible for their success or failure. It may be that osteoconductive properties are desired for implants to assist fusion, whereas as inert a material as possible would be preferred for interpositional barriers. The materials composing the instrumentation used to facilitate healing of spinal fractures would ideally have properties that optimize strength and biocompatibility, while at the same time minimizing imaging artifacts and allowing a gradual transfer of load from the instrumentation to the vertebral body (i.e., viscoelastic effects). The application of biomaterials and biomechanics to the design of spinal devices is obvious; what may be more subtle though is what the in vivo interactions of these will be. The study of such aspects must continue in order to better evolve the designs and subsequent results of implanted spinal devices.
The Ras-RasGAP Complex: Structural Basis for GTPase Activation and Its Loss in Oncogenic Ras Mutants (1997)

The three-dimensional structure of the complex between human H-Ras bound to guanosine diphosphate and the guanosine triphosphatase (GTPase)-activating domain of the human GTPase-activating protein p120GAP (GAP-334) in the presence of aluminum fluoride was solved at a resolution of 2.5 angstroms. The structure shows the partly hydrophilic and partly hydrophobic nature of the communication between the two molecules, which explains the sensitivity of the interaction toward both salts and lipids. An arginine side chain (arginine-789) of GAP-334 is supplied into the active site of Ras to neutralize developing charges in the transition state. The switch II region of Ras is stabilized by GAP-334, thus allowing glutamine-61 of Ras, mutation of which activates the oncogenic potential, to participate in catalysis. The structural arrangement in the active site is consistent with a mostly associative mechanism of phosphoryl transfer and provides an explanation for the activation of Ras by glycine-12 and glutamine-61 mutations. Glycine-12 in the transition state mimic is within van der Waals distance of both arginine-789 of GAP-334 and glutamine-61 of Ras, and even its mutation to alanine would disturb the arrangements of residues in the transition state.
Labeled Nucleoside Triphosphates with Reversibly Terminating Aminoalkoxyl Groups (2010)

Nucleoside triphosphates having a 3'-ONH₂ blocking group have been prepared with and without fluorescent tags on their nucleobases. DNA polymerases were identified that accepted these, adding a single nucleotide to the 3'-end of a primer in a template-directed extension reaction that then stops. Nitrite chemistry was developed to cleave the 3'-ONH₂ group under mild conditions to allow continued primer extension. Extension-cleavage-extension cycles in solution were demonstrated with untagged nucleotides and mixtures of tagged and untagged nucleotides. Multiple extension-cleavage-extension cycles were demonstrated on an Intelligent Bio-Systems Sequencer, showing the potential of the 3'-ONH₂ blocking group in "next generation sequencing."
Adenovirus tripartite leader sequence enhances translation of mRNAs late after infection. (1984)

A series of adenovirus type 5 variants was constructed to probe the function of the tripartite leader sequence, a 200-nucleotide, 5' noncoding sequence carried on the majority of late viral mRNAs. Recombinant plasmids were constructed that carried the major late transcriptional control region followed by portions of the tripartite leader sequence fused to the E1A coding region. These modified E1A genes were then rebuilt into intact viral chromosomes, replacing the corresponding wild-type region. The leader segments had no effect on the translation of E1A mRNAs early after infection, but the tripartite leader significantly enhanced (5-fold) the efficiency with which the mRNAs were translated late after infection.
Resource auction multiple access (RAMA) for statistical multiplexing of speech in wireless PCS (2002)

The excess capacity of resource auction multiple access (RAMA) is evaluated for statistical multiplexing of speech. Using selected GSM parameters in conjunction with M-ary frequency shift keying (FSK) for signaling, it is shown that, in cells with propagation delays of up to 45 /spl mu/s, 432 assignments/s are feasible. The aim is to exploit this large assignment capacity to increase channel utilization. It is shown that, for packet dropping probabilities of 1%, RAMA can provide a multiplexing gain as high as 2.63 with fast speech detection and 2.28 with slow speech detection. RAMA permits graceful degradation during peak traffic demand by operating at higher packet dropping probabilities. Simulation results also indicate that RAMA is suitable for fast handoffs and resource allocation with statistical speech multiplexing over areas with a wide variety of cell sizes.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Transluminal implantation of artificial heart valves. Description of a new expandable aortic valve and initial results with implantation by catheter technique in closed chest pigs (1992)

A new artificial aortic valve prosthesis was developed for implantation by the transluminal catheter technique without thoracotomy or extracorporal circulation. The new heart valve was prepared by mounting a porcine aortic valve into an expandable stent. Before implantation, the stent-valve was mounted on a balloon catheter and compressed around the deflated balloon. The stent-valve mounted balloon catheter was then advanced retrogradely to the ascending aorta or the aortic root in anaesthetized pigs. Implantation was performed by balloon inflation which expanded the stent-valve to a diameter exceeding the internal diameter of the vessel--thus ensuring a stable fixation against the vessel wall. A total of nine implantations were performed in seven 70 kg closed chest pigs. Sub- and supracoronary implantation was performed in two and three pigs, respectively, while implantation in both positions was done in two. Angiographic and haemodynamic evaluation after implantation revealed no significant stenosis (less than or equal to 16 mmHg) in any of the nine valves and trivial regurgitation in only two. Complications were associated with restriction of the coronary blood flow in three animals. This preliminary study indicates that artificial aortic valves can be implanted in closed chest animals by transluminal catheter technique.
Clustal W and Clustal X version 2.0 (2007)

The programs can be run on-line from the EBI web server: http://www.ebi.ac.uk/tools/clustalw2. The source code and executables for Windows, Linux and Macintosh computers are available from the EBI ftp site ftp://ftp.ebi.ac.uk/pub/software/clustalw2/
Enzymatic Catalysis and Transition-State Theory (1973)

The application of transition-state theory to enzymatic catalysis provides an approach to understanding enzymatic catalysis in terms of the factors that determine the strength of binding of ligands to proteins. The prediction that the transition state should bind to the enzyme much more tightly than the substrate is supported by the experimental results with stable analogs of transition states. Transition-state analogs have great potential for use in understanding enzymatic catalysis and in inhibiting enzymes. Because of their potency and specificity as enzyme inhibitors, some of them may become very useful chemotherapeutic agents.
CD69 Expression Discriminates MHC-Dependent and -Independent Stages of Thymocyte Positive Selection (1999)

In the thymus, phenotypically and functionally mature single positive cells are generated from immature CD4+8+ precursors by a process known as positive selection. Although this event is known to involve alphabetaTCR ligation by peptide/MHC complexes expressed on thymic stromal cells, it is clear that positive selection is a multistage process involving transition through an intermediate CD4+8+69+ phase as well as subsequent postselection phases. By analyzing the development of preselection CD4+8+69- and intermediate CD4+8+69+ thymocytes in the presence of MHC class I-deficient, MHC class II-deficient, and MHC double-deficient thymic stromal cells, we investigated the role of MHC molecules at three distinct points during positive selection. Although the initiation of positive selection is critically dependent upon MHC interactions, we find the that later stages of maturation, involving the differentiation of CD4+8- and CD4-8+ cells from CD4+8+69+ thymocytes, occur in the absence of MHC molecules. Moreover, an analysis of the postselection proliferation of newly generated CD4+8- and CD4-8+ thymocytes shows that this also occurs independently of MHC molecules. Thus, our data provide direct evidence that, although positive selection is a multistage process initiated by TCR-MHC interactions, continuation of this process and subsequent postselection events are independent of ongoing engagement of the TCR.
CG island methylation changes near the GSTP1 gene in prostatic intraepithelial neoplasia. (1998)

Prostate intraepithelial neoplasia (PIN) is a purported prostate cancer precursor lesion and a candidate biomarker for efficacy assessment in prostate cancer chemoprevention trials. Loss of expression of the pi-class glutathione S-transferase enzyme GSTP1, which is associated with the hypermethylation of deoxycytidine residues in the 5'-regulatory CG island region of the GSTP1 gene, is a near-universal finding in human prostate cancer. GSTP1 expression was assessed by immunohistochemistry in 60 high-grade PIN samples adjacent to and distant from prostate adenocarcinoma. Whereas abundant enzyme polypeptide expression was evident in all normal prostatic tissues, all samples of high-grade PIN and adenocarcinoma were completely devoid of GSTP1. DNA from 10 high-grade PIN lesions was analyzed for GSTP1 CG island methylation changes using a PCR technique targeting a polymorphic (ATAAA)n repeat sequence in the promoter region of the GSTP1 gene. Somatic GSTP1 CG island methylation changes were detected in DNA from 7 of the 10 PIN lesions. Allele discrimination was possible for 5 of the 10 DNA samples: 2 of the 5 samples exhibited DNA methylation changes at both alleles; whereas 3 samples displayed no DNA methylation changes at either allele. GSTP1 CG island methylation changes were present in each of the five homozygous samples. Hypermethylation of the 5'-regulatory region of the GSTP1 gene may serve as an important molecular genetic biomarker for both prostate cancer and PIN. The finding of frequent GSTP1 methylation changes in PIN and prostate cancer supports a role for PIN lesions as a prostate cancer precursor and may provide insight to the molecular pathogenesis of prostate cancer.
NGM282 Improves Liver Fibrosis and Histology in 12 Weeks in Patients With Nonalcoholic Steatohepatitis (2019)

NGM282, an engineered fibroblast growth factor 19 analogue, rapidly and significantly reduced liver fat content in a multicenter, randomized, double-blind, placebo-controlled study in patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH). However, it is unclear whether these changes would be accompanied by histological improvement. In this open-label study, we assessed the histological efficacy of NGM282 in patients with biopsy-confirmed nonalcoholic steatohepatitis. Paired liver biopsies from 43 patients who received subcutaneous NGM282 (1 mg, n = 24; 3 mg, n = 19) once daily for 12 weeks were evaluated blinded to time point, subject, and clinical information. At week 12, NGM282 significantly reduced nonalcoholic fatty liver disease activity score (NAS; -1.9; 95% confidence interval, -2.6 to -1.2; P < 0.001 in the 1 mg group; -2.2, -3.1 to -1.3; P < 0.001 in the 3 mg group) and fibrosis (-0.5; -0.9 to 0; P = 0.035 in the 3 mg group) scores. Overall, 50% and 63% of the patients receiving NGM282 1 mg or 3 mg, respectively, improved NAS by 2 or more points without fibrosis worsening. Of the patients receiving NGM282 1 mg or 3 mg, 25% and 42%, respectively, improved liver fibrosis by one stage or more without worsening of steatohepatitis. Treatment with NGM282 led to relative reductions in liver fat content (-58% and -67% in the 1 mg and 3 mg groups, respectively), corrected T1 (cT1; -8% and -9%), alanine aminotransferase (ALT) (-67% and -60%), aspartate aminotransferase (-57% and -52%), and fibrogenesis biomarkers neoepitope-specific N-terminal propeptide of type III collagen (Pro-C3; -22% and -33%) and enhanced liver fibrosis score (ELF; -3% and -6%) at week 12. Greater reductions in Pro-C3, ELF, and cT1, but not in liver fat content, 7alpha-hydroxy-4-cholesten-3-one, or ALT, were observed in histological responders than in nonresponders. Conclusion: In this open-label study, NGM282 improved the histological features of NASH in 12 weeks with significant reductions in NAS and fibrosis scores, accompanied by improvements in noninvasive imaging and serum markers.
A combined genome-wide linkage and association approach to find susceptibility loci for platelet function phenotypes in European American and African American families with coronary artery disease (2010)

Our study supports the hypothesis that platelet phenotypes in response to ASA likely have genetic control and the combined approach of linkage and association offers an alternative approach to prioritizing regions of interest for subsequent follow-up.
Pronounced Intraspecific Haplotype Divergence at the RPP5 Complex Disease Resistance Locus of Arabidopsis (1999)

In Arabidopsis ecotype Landsberg erecta (Ler), RPP5 confers resistance to the pathogen Peronospora parasitica. RPP5 is part of a clustered multigene family encoding nucleotide binding-leucine-rich repeat (LRR) proteins. We compared 95 kb of DNA sequence carrying the Ler RPP5 haplotype with the corresponding 90 kb of Arabidopsis ecotype Columbia (Col-0). Relative to the remainder of the genome, the Ler and Col-0 RPP5 haplotypes exhibit remarkable intraspecific polymorphism. The RPP5 gene family probably evolved by extensive recombination between LRRs from an RPP5-like progenitor that carried only eight LRRs. Most members have variable LRR configurations and encode different numbers of LRRs. Although many members carry retroelement insertions or frameshift mutations, codon usage analysis suggests that regions of the genes have been subject to purifying or diversifying selection, indicating that these genes were, or are, functional. The RPP5 haplotypes thus carry dynamic gene clusters with the potential to adapt rapidly to novel pathogen variants by gene duplication and modification of recognition capacity. We propose that the extremely high level of polymorphism at this complex resistance locus is maintained by frequency-dependent selection.
Multispectral Imaging Using Multiplexed Illumination (2007)

Many vision tasks such as scene segmentation, or the recognition of materials within a scene, become considerably easier when it is possible to measure the spectral reflectance of scene surfaces. In this paper, we present an efficient and robust approach for recovering spectral reflectance in a scene that combines the advantages of using multiple spectral sources and a multispectral camera. We have implemented a system based on this approach using a cluster of light sources with different spectra to illuminate the scene and a conventional RGB camera to acquire images. Rather than sequentially activating the sources, we have developed a novel technique to determine the optimal multiplexing sequence of spectral sources so as to minimize the number of acquired images. We use our recovered spectral measurements to recover the continuous spectral reflectance for each scene point by using a linear model for spectral reflectance. Our imaging system can produce multispectral videos of scenes at 30fps. We demonstrate the effectiveness of our system through extensive evaluation. As a demonstration, we present the results of applying data recovered by our system to material segmentation and spectral relighting.
Remote office work (1983)

Remote work refers to organizational work that is performed outside of the normal organizational confines of space and time. The term telecommuting refers to the substitution of communications capabilities for travel to a central work location. Office automation technology permits many office workers to be potential telecommuters in that their work can be performed remotely with computer and communications support. This paper examines some behavioral, organizational, and social issues surrounding remote work, particularly work at home. An exploratory study was conducted of 32 organizational employees who were working at home. Important characteristics of jobs that can be performed at home were: minimum physical requirements, individual control over work pace, defined deliverables, a need for concentration, and a relatively low need for communication. The individuals who worked at home successfully were found to be highly self-motivated and self-disciplined and to have skills which provided them with bargaining power. They also made the arrangement either because of family requirements or because they preferred few social contacts beyond family.
Scanning Electrochemical Microscopy of Individual Single-Walled Carbon Nanotubes (2010)

Here we report on the novel application of scanning electrochemical microscopy (SECM) to enable spatially resolved electrochemical characterization of individual single-walled carbon nanotubes (SWNTs). The feedback imaging mode of SECM was employed to detect a pristine SWNT (approximately 1.6 nm in diameter and approximately 2 mm in length) grown horizontally on a SiO(2) surface by chemical vapor deposition. The resulting image demonstrates that the individual nanotube under an unbiased condition is highly active for the redox reaction of ferrocenylmethyltrimethylammonium used as a mediator. Micrometer-scale resolution of the image is determined by the diameter of a disk-shaped SECM probe rather than by the nanotube diameter as assessed using 1.5 and 10 microm diameter probes. Interestingly, the long SWNT is readily detectable using the larger probe although the active SWNT covers only approximately 0.05% of the insulating surface just under the tip. This high sensitivity of the SECM feedback method is ascribed to efficient mass transport and facile electron transfer at the individual SWNT.
Angiogenesis, vascular endothelial growth factor and the endometrium (1998)

Angiogenesis is an essential component of endometrial renewal. The formation of new vessels depends on interactions between various hormones and growth factors, and this review focuses on the expression of angiogenic growth factors in the human endometrium. Peptide and non-peptide angiogenic factors interact during endometrial renewal, including epidermal growth factor (EGF), transforming growth factors (e.g. TGF-beta), platelet-derived endothelial growth factor/thymidine phosphorylase (PD-ECGF/TP), tumour necrosis growth factors and vascular endothelial growth factor (VEGF). Their role in the proliferation and migration of endothelial cells from pre-existing vessels is described, concentrating on VGEF and its receptors (VEG-R1 and -R2), and the fibroblast growth factor (FGF) family. The actions of the products of the VEGF gene are outlined, and the hormonal and non-hormonal control of their localization in the human endometrium and biological actions on vasculature and coagulation are described. Finally, the role of VEGF in menorrhagia is assessed.
Characterization of diabetic nephropathy in a transgenic model of hypoinsulinemic diabetes (2006)

Genetic mouse models provide a unique opportunity to investigate gene function in the natural course of the disease. Although diabetic nephropathy (DN) in models of type II diabetes has been well characterized, diabetic renal disease in hypoinsulinemic diabetic mice is still incompletely understood. Here, we characterized renal changes in the pdx1(PB)-HNF6 transgenic mouse that exhibits beta-cell dysfunction and nonobese hypoinsulinemic diabetes. Male transgenic mice developed hyperglycemia by the age of 7 wk and survived for over 1 yr without insulin treatment. Diabetes ensued earlier and progressed more severely in the HNF6 males than the females. The HNF6 males exhibited albuminuria as early as 10 wk of age, and the urinary albumin excretion increased with age, exceeding 150 microg/24 h at 11 mo of age. Diabetic males developed renal hypertrophy after 7 wk of age, whereas glomerular hyperfiltration was not observed in the mice. Hypertension and hyperlipidemia were not observed in the diabetic mice. Histological analysis of the HNF6 kidneys displayed diabetic glomerular changes, including glomerular enlargement, diffuse mesangial proliferation and matrix expansion, thickened glomerular basement membrane, and arteriolar hyalinosis. Mesangial matrix accumulation increased with age, resulting in nodular lesions by 44 wk of age. Immunohistochemistry showed accumulation of type IV collagen and TGF-beta1 in the mesangial area. No significant immune complex deposition was observed in the HNF6 glomeruli. Thus the HNF6 mouse exhibits diabetic renal changes that parallel the early phase of human DN. The model should facilitate studies of genetic and environmental factors that may affect DN in hypoinsulinemic diabetes.