gebhart/patrepeval huggingface dataset:
Dual display: phage selection driven by co-engagement of two targets by two different antibody fragments (2017)

Antibody phage display technology has supported the emergence of numerous therapeutic antibodies. The development of bispecific antibodies, a promising new frontier in antibody therapy, could be facilitated by new phage display approaches that enable pairs of antibodies to be co-selected based on co-engagement of their respective targets. We describe such an approach, making use of two complementary leucine zipper domains that heterodimerize with high affinity. Phagemids encoding a first antibody fragment (scFv) fused to phage coat protein via the first leucine zipper are rescued in bacteria expressing a second scFv fused to the second leucine zipper as a soluble periplasmic protein, so that it is acquired by phage during assembly. Using a soluble scFv specific for a human CD3-derived peptide, we show that its acquisition by phage displaying an irrelevant antibody is sufficiently robust to drive selection of rare phage (1 in 10(5)) over three rounds of panning. We then set up a model selection experiment using a cell line expressing the chemokine receptor CCR5 fused to the CD3 peptide together with a panel of phage clones capable displaying either an anti-CCR5 scFv or an irrelevant antibody, with or without the capacity to acquire the soluble anti-CD3 scFv. In this experiment we showed that rare phage (1 in 10(5)) capable of displaying the two different scFvs can be specifically enriched over four rounds of panning. This approach has the potential to be applied to the identification of pairs of ligands capable of co-engaging two different user-defined targets, which would facilitate the discovery of novel bispecific antibodies.
Inverse agonism of amino-terminally truncated parathyroid hormone (PTH) and PTH-related peptide (PTHrP) analogs revealed with constitutively active mutant PTH/PTHrP receptors (1996)

Inverse agonists, ligands that suppress spontaneous receptor signaling activity, have been described for a growing number of G protein-coupled receptors; however, none have been reported for the PTH/calcitonin/secretin receptor family. We took advantage of the constitutive signaling activity of two mutant forms of the PTH/PTH-related peptide (PTHrP) receptor, recently identified in patients with Jansen's metaphyseal chondrodysplasia, to screen for PTH and PTHrP analogs with inverse agonist activity. Two antagonist peptides, [Leu11, D-Trp12]hPTHrP(7-34)NH2 and [D-Trp12, Tyr34]bPTH-(7-34)NH2, displayed inverse agonist activity and reduced cAMP in COS-7 cells expressing either mutant receptor by 30-50% (EC50 approximately 50 nM). These data demonstrate that the concept of inverse agonism can be extended to this distinct family of G protein-coupled receptors and their cognate antagonist peptide ligands. Such ligands shall be useful probes of the multi-state conformational equilibria proposed for these receptors and could lead to new approaches for treating human diseases caused by receptor activating mutations.
Deleterious Variants of FIG4, a Phosphoinositide Phosphatase, in Patients with ALS (2009)

Mutations of the lipid phosphatase FIG4 that regulates PI(3,5)P(2) are responsible for the recessive peripheral-nerve disorder CMT4J. We now describe nonsynonymous variants of FIG4 in 2% (9/473) of patients with amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). Heterozygosity for a deleterious allele of FIG4 appears to be a risk factor for ALS and PLS, extending the list of known ALS genes and increasing the clinical spectrum of FIG4-related diseases.
Statistics collection in oracle spatial and graph (2013)

Oracle Spatial and Graph is a geographic information system (GIS) which provides users the ability to store spatial data alongside conventional data in Oracle. As a result of the coexistence of spatial and other data, we observe a trend towards users performing increasingly complex queries which involve spatial as well as non-spatial predicates. Accurate selectivity values, especially for queries with multiple predicates requiring joins among numerous tables, are essential for the database optimizer to determine a good execution plan. For queries involving spatial predicates, this requires that reasonably accurate statistics collection has been performed on the spatial data. For extensible data cartridges such as Oracle Spatial and Graph, the optimizer expects to receive accurate predicate selectivity and cost values from functions implemented within the data cartridge. Although statistics collection for spatial data has been researched in academia for a few years; to the best of our knowledge, this is the first work to present spatial statistics collection implementation details for a commercial GIS database. In this paper, we describe our experiences with implementation of statistics collection methods for complex geometry objects within Oracle Spatial and Graph. Firstly, we exemplify issues with previous partitioning-based algorithms in presence of complex geometry objects and suggest enhancements which resolve the issues. Secondly, we propose a main memory implementation which not only speeds up the disk-based partitioning algorithms but also utilizes existing R-tree indexes to provide surprisingly accurate selectivity estimates. Last but not the least, we provide extensive experimental results and an example study which displays the efficacy of our approach on Oracle query performance.
Gain of Glucose-Independent Growth upon Metastasis of Breast Cancer Cells to the Brain (2014)

Breast cancer brain metastasis is resistant to therapy and a particularly poor prognostic feature in patient survival. Altered metabolism is a common feature of cancer cells, but little is known as to what metabolic changes benefit breast cancer brain metastases. We found that brain metastatic breast cancer cells evolved the ability to survive and proliferate independent of glucose due to enhanced gluconeogenesis and oxidations of glutamine and branched chain amino acids, which together sustain the nonoxidative pentose pathway for purine synthesis. Silencing expression of fructose-1,6-bisphosphatases (FBP) in brain metastatic cells reduced their viability and improved the survival of metastasis-bearing immunocompetent hosts. Clinically, we showed that brain metastases from human breast cancer patients expressed higher levels of FBP and glycogen than the corresponding primary tumors. Together, our findings identify a critical metabolic condition required to sustain brain metastasis and suggest that targeting gluconeogenesis may help eradicate this deadly feature in advanced breast cancer patients.
Thermal-Mechanical and Physical-Chemical Properties of Phosphate Laser Glasses (2024)

A compositional study of the effects of various network formers on the physical properties of phosphate laser glasses used in fusion research lasers is reported. The network formers include P<sub>2</sub>O<sub>5</sub>, AI<sub>2</sub>O<sub>3</sub>, SiO<sub>2</sub> and B<sub>2</sub>O<sub>3</sub> and most glass compositions are metaphosphates or near ultraphosphates. We have chosen Schott's commercial LG-750 laser glass as a reference composition. The results show that laser glasses having improved physical properties compared to LG-750 can be prepared by decreasing the AI<sub>2</sub>O<sub>3</sub> and increasing the P<sub>2</sub>O<sub>5</sub> content. Figures-of-merit are used to characterize the relative improvements of the various glasses studied.
Abstract A135: Uncovering tumor suppressive and oncogenic microRNAs in lung cancer (2008)

Abstract A135 MicroRNAs (miRNAs) are noncoding small RNAs that regulate gene expression. Expression profiles of miRNAs are useful to improve classification, diagnosis, and prognostic information of specific human malignancies, including lung cancer. We sought to uncover miRNAs preferentially repressed or over-expressed in pre-malignant and malignant lung lesions in recently described transgenic cyclin E mice. These transgenic mice expressed in the lung under control of the human surfactant C promoter wild-type or proteasome degradation-resistant cyclin E species. These mice developed pulmonary dysplasia and adenocarcinoma, recapitulating pre-malignant and malignant lung lesions frequently found in lung cancer patients. Comprehensive miRNA microarray analyses were conducted using independently harvested normal and malignant lung tissues from these transgenic mice. A cluster of miRNAs was preferentially repressed in transgenic lung cancers versus normal lung tissues including: miR-34c, miR-145, miR142-5p, and other miRNAs previously associated with lung carcinogenesis. Expression profiles were independently validated by semi-quantitative and real-time polymerase chain reaction assays. In transgenic mice, single cell expression profiles were studied in pre-malignant and malignant lung lesions by in situ hybridization assays. Concordant results were obtained after analyses of paired normal-malignant human lung tissues representing each histopathologic subtype of non-small cell lung cancer. To address functional roles of repressed miRNAs, novel lung cancer cell lines were derived from murine transgenic wild-type (ED-1 cells) or proteasome-degradation resistant (ED-2 cells) cyclin E expressing lung cancers. ED-1 and ED-2 cells each caused lung adenocarcinomas to form after tail-vein injections into syngeneic FVB mice. Engineered over-expression of each basally repressed miRNA in ED-1 as well as in ED-2 cells markedly (P &lt; 0.001) repressed cell growth. Anti-miR co-transfections antagonized these effects. A mechanism for this growth suppression was found by showing cyclin E, a predicted miR-34c bioinformatic target, was significantly repressed in miR-34c transfectants. Other miRNAs were selected for knock-down in ED-1 and ED-2 cells by virtue of their high basal expression in these cells as well as in murine transgenic lung cancers and human lung cancers versus normal lung tissues. Knock-down of candidate oncogenic miRNAs repressed lung cancer cell growth, which was antagonized by over-expression of the same miRNA. Experiments are underway in miRNA transfected ED-1 cells to assess in vivo tumorigenicity in FVB mice. Taken together, these studies uncovered candidate tumor suppressive and oncogenic miRNAs. We propose these miRNAs are molecular pharmacologic targets for lung cancer therapy and chemoprevention. Citation Information: Cancer Prev Res 2008;1(7 Suppl):A135.
Learning Face Hallucination in the Wild (2015)

Face hallucination method is proposed to generate high-resolution images from low-resolution ones for better visualization. However, conventional hallucination methods are often designed for controlled settings and cannot handle varying conditions of pose, resolution degree, and blur. In this paper, we present a new method of face hallucination, which can consistently improve the resolution of face images even with large appearance variations. Our method is based on a novel network architecture called Bi-channel Convolutional Neural Network (Bi-channel CNN). It extracts robust face representations from raw input by using deep convolutional network, then adaptively integrates two channels of information (the raw input image and face representations) to predict the high-resolution image. Experimental results show our system outperforms the prior state-of-the-art methods.
Detection of microsatellite instability (MSI) in colorectal cancer samples with a novel set of highly sensitive markers by means of the Idylla MSI Test prototype. (2018)

e15639 Background: Detection of microsatellite instability (MSI) is currently recommended for all patients with colorectal cancer (CRC). Current clinical reference methods are immunohistochemical staining of mismatch repair proteins and/or PCR analysis of frequently mutated short tandem repeat regions of DNA. The Idylla™ MSI Test prototype is being developed using a new set of short homopolymers capable of faster detection with greater specificity and selectivity compared to current methods. Methods: Prototype Idylla™ MSI Test cartridges were developed up to a finalized design. Repeat length of a novel set of 7 biomarkers was determined on 348 formalin-fixed and paraffin-embedded (FFPE) CRC samples using these prototype tests which allow a complete automated workflow including sample preparation, DNA amplification followed by melting curve analysis and automated interpretation. Patient samples of several clinical sites and different ethnic groups were included to assess robustness of marker selection. All samples were additionally screened with a reference methodology for MSI detection (Promega MSI analysis system). Results: One hundred twenty-seven (36.5%) and 116 (33.3%) samples were classified as MSI-high (MSI-H), and 209 (60.1%) and 220 (57.3%) samples were classified as microsatellite stable (MSS) by Idylla™ and Promega respectively, while 12 samples (3.4%) could not be classified by either methodology. Concordance analysis revealed an overall agreement of 96.1% (93.4%-97.7% 95% CI). Fourteen cases were MSI-H by Idylla™ but MSS (11) or invalid (3) by Promega; with a median of 3/7 positive markers on Idylla™. Conclusions: This study validated the novel MSI biomarkers to discriminate MSI-H from MSS status on a large and diverse set of CRC samples. It also demonstrated the possibility of a fully automated analysis for MSI testing. The prototype Idylla™ MSI Test is compatible with the fully integrated Idylla™ platform providing accurate and reliable results within 150 minutes from just one FFPE tumour section (no reference sample required).
Hierarchical Micro/Nano-Porous Acupuncture Needles Offering Enhanced Therapeutic Properties (2016)

Acupuncture as a therapeutic intervention has been widely used for treatment of many pathophysiological disorders. For achieving improved therapeutic effects, relatively thick acupuncture needles have been frequently used in clinical practice with, in turn, enhanced stimulation intensity. However due to the discomforting nature of the larger-diameter acupuncture needles there is considerable interest in developing advanced acupuncture therapeutical techniques that provide more comfort with improved efficacy. So motivated, we have developed a new class of acupuncture needles, porous acupuncture needles (PANs) with hierarchical micro/nano-scale conical pores upon the surface, fabricated via a simple and well known electrochemical process, with surface area approximately 20 times greater than conventional acupuncture needles. The performance of these high-surface-area PANs is evaluated by monitoring the electrophysiological and behavioral responses from the in vivo stimulation of Shenmen (HT7) points in Wistar rats, showing PANs to be more effective in controlling electrophysiological and behavioral responses than conventional acupuncture needles. Comparative analysis of cocaine induced locomotor activity using PANs and thick acupuncture needles shows enhanced performance of PANs with significantly less pain sensation. Our work offers a unique pathway for achieving a comfortable and improved acupuncture therapeutic effect.
Nanomeshed Si nanomembranes (2019)

Abstract One of the main challenges in stretchable electronics is to achieve high-performance stretchable semiconductors. Here, we introduce an innovative concept of nanomeshed semiconductor nanomembrane which can be regarded almost as intrinsically stretchable to conventional microelectronic layouts. By making a silicon film into homogeneous nanomeshes with spring-like nano traces, we demonstrated a high electron mobility of 50 cm 2 /V·s, and moderate stretchability with a one-time strain of 25% and cyclic strain of 14% after stretching for 1000 cycles, further improvable with optimized nanomesh designs. A simple analytic model covering both fractional material and trace sidewall surfaces well predicted the transport properties of the normally on silicon nanomesh transistors, enabling future design and optimizations. Besides potential applications in stretchable electronics, this semiconductor nanomesh concept provides a new platform for materials engineering and is expected to yield a new family of stretchable inorganic materials having tunable electronic and optoelectronic properties with customized nanostructures.
From perpendicular magnetic recording to Heat Assisted Magnetic Recording (2012)

Heat Assisted Magnetic Recording (HAMR) is considered as one of the leading technology candidates for enabling continuous areal density growth to beyond perpendicular magnetic recording (PMR) and increase the storage capacity of the hard disk drives. In this paper, we give a brief review of the technology development over the past decade, from PMR to the current progress in HAMR from various perspectives and show how HAMR can extend areal density growth beyond PMR. We will also look into the fundamental aspects of HDD technology and show the challenges for beyond current state of HAMR technology.
Application of the “cooled needle” technique to split and splitless sampling onto capillary columns (1985)

Abstract Cooled needle sampling using syringes was applied to splitless injection and to simulated distillation analyses. Slight changes of the construction of the previous device are also described. The changes concern the temperature profile within the injector and especially the vaporization insert. Even with the low carrier gas flow through the injector during splitless injection, discrimination by component volatility can be avoided. Precision and accuracy of simulated distillation data obtained with split sampling also can be improved by the cooled needle technique.
Neural network analysis of DNA flow cytometry histograms (1993)

A pattern recognition system based on Neural Network Analysis, a form of artificial intelligence, was used to search DNA flow cytometry histograms for features that correlated with breast cancer patients' risk of relapse. DNA flow cytometry histograms and clinical follow-up information from 796 breast cancer patients were used to train a Neural Network to predict the clinical outcome of patients in a separate independent set of 794 patients. Median follow-up in this patient data base was short, 23 months. Neural Network Analysis resulted in a model that evaluated DNA flow cytometry histograms differently than conventional analysis, which categorizes the histograms by ploidy and S-phase fraction. Neural Network Analysis appeared to identify low risk and high risk subsets of patients as accurately as conventional analysis. Neural Network Analysis placed heavy emphasis on the region to the right of the diploid G2/M peak, where a subpopulation of nuclei with high DNA content is seen even in many histograms scored as diploid by conventional techniques. The number of nuclei in this region was found to be a powerful predictor of patient outcome, and multivariate analysis showed that the number of nuclei in this region and the S-phase fraction both were independently predictive of relapse. This pilot study suggests that conventional analysis (based on a mechanistic interpretation of regions in flow cytometry histograms) might be used in conjunction with and improved by pattern recognition systems or insights derived from them.
BBAND Index: A No-Reference Banding Artifact Predictor (2020)

Banding artifact, or false contouring, is a common video compression impairment that tends to appear on large flat regions in encoded videos. These staircase-shaped color bands can be very noticeable in high-definition videos. Here we study this artifact, and propose a new distortion-specific no-reference video quality model for predicting banding artifacts, called the Blind BANding Detector (BBAND index). BBAND is inspired by human visual models. The proposed detector can generate a pixel-wise banding visibility map and output a banding severity score at both the frame and video levels. Experimental results show that our proposed method outperforms state-of-the-art banding detection algorithms and delivers better consistency with subjective evaluations.
Balanced AT1/AT2 Receptor Antagonists. 4. XR510 and Related 5-(3-Amidopropanoyl)imidazoles Possessing Equal Affinity for the AT1 and AT2 Receptors (1995)

The identification of the AT1 and AT2 receptor subtypes has stimulated interest in developing balanced angiotensin II receptor antagonists. A series of 5-(3-amidopropanoyl)imidazoles has been prepared which possess balanced affinity for the AT1 and AT2 receptors. XR510 (1), 1-[[2'-[[(isopentoxycarbonyl)amino]sulfonyl]-3- fluoro(1,1'-biphenyl)-4-yl]methyl]-5-[3-(N-pyridin-3- ylbutanamido)propanoyl]-4-ethyl-2-propyl-1H-imidazole, potassium salt, exhibits subnanomolar affinity for both receptor sites. XR510 is very active in lowering blood pressure in renal hypertensive rats and furosemide-treated dogs following oral administration.
Detection of All Known Parechoviruses by Real-Time PCR (2008)

The Parechovirus genus of the Picornaviridae family contains two species, Human parechovirus (HPeV) and Ljungan virus (LV). The HPeVs (including the former echoviruses 22 and 23, now HPeV type 1 (HPeV1) and HPeV2, respectively) cause a wide spectrum of disease, including aseptic meningitis, gastroenteritis, encephalitis, acute respiratory illness, and neonatal sepsis-like disease. The LVs were isolated from bank voles in Sweden during a search for an infectious agent linked to fatal myocarditis cases in humans. Because of the decline in use of cell culture and neutralization to investigate enterovirus-like disease, very few laboratories currently have the capability to test for parechoviruses. We have developed a real-time reverse transcription-PCR (RT-PCR) assay for detection of all known members of the genus Parechovirus. The assay targets the conserved regions in the 5' nontranslated region (5'NTR) of the parechovirus genome and can detect both HPeVs and LVs, unlike other published parechovirus 5' NTR assays, which only detect known HPeVs or only LVs. HPeV and LV can be differentiated by sequencing the 5'NTR real-time RT-PCR amplicon, when needed. The assay is approximately 100 times more sensitive than cell culture and may be used to test original clinical specimens. The availability of a broad-specificity PCR method should facilitate the detection of new human parechoviruses, as well as new parechoviruses in other mammalian species, and provide an opportunity to investigate the role of these viruses in human and animal disease.
[123I]Iodooctyl fenbufen amide as a SPECT tracer for imaging tumors that over-express COX enzymes (2013)

This study is concerned with the development of an agent for single photon emission computer tomography (SPECT) for imaging inflammation and tumor progression. [(123)I]Iodooctyl fenbufen amide ([(123)I]IOFA) was prepared from the precursor N-octyl-4-oxo-4-(4'-(trimethylstannyl)biphenyl-4-yl)butanamide with a radiochemical yield of 15%, specific activity of 37 GBq/μmol, and radiochemical purity of 95%. Analysis of the binding of [(123)I]IOFA to COX-1 and COX-2 enzymes by using HPLC and a gel filtration column showed a selectivity ratio of 1:1.3. An assay for the competitive inhibition of substrate transfer showed that IOFA exhibited a comparable IC(50) value compared to fenbufen. In the normal rat liver, a lower level and homogeneous pattern of [(123)I]IOFA radioactivity was observed by SPECT. In contrast, in the rat liver with thioacetamide-induced cholangiocarcinoma, a higher uptake and heterogeneous pattern of [(123)I]IOFA radioactivity was seen as hot spots in tumor lesions by SPECT imaging. Importantly, elevated COX-1 and COX-2 expressions from immunostaining were found in the bile ducts of tumor rats but not of normal rats. Therefore, [(123)I]IOFA was found to exhibit the potential for imaging tumors that over-express COX.