gebhart/patrepeval huggingface dataset:
Dysregulated Expression of FOXM1 Isoforms Drives Progression of Pancreatic Cancer (2013)

The transcription factor Forkhead box M1 (FOXM1) plays important roles in oncogenesis. However, the expression statuses of FOXM1 isoforms and their impact on and molecular basis in oncogenesis are unknown. We sought to determine the identities of FOXM1 isoforms in and the impact of their expression on pancreatic cancer development and progression using human tissues, cell lines, and animal models. Overexpression of FOXM1 mRNA and protein was pronounced in human pancreatic tumors and cancer cell lines. We identified five FOXM1 isoforms present in pancreatic cancer: FOXM1a, FOXM1b, and FOXM1c along with two isoforms tentatively designated as FOXM1b1 and FOXM1b2 because they were closely related to FOXM1b. Interestingly, FOXM1c was predominantly expressed in pancreatic tumors and cancer cell lines, whereas FOXM1a expression was generally undetectable in them. Functional analysis revealed that FOXM1b, FOXM1b1, FOXM1b2, and FOXM1c, but not FOXM1a, promoted pancreatic tumor growth and metastasis. Consistently, FOXM1b, FOXM1b1, FOXM1b2, and FOXM1c activated transcription of their typical downstream genes. Also, Sp1 mechanistically activated the FOXM1 promoter, whereas Krüppel-like factor 4 (KLF4) repressed its activity. Finally, we identified an Sp1- and KLF4-binding site in the FOXM1 promoter and showed that both Sp1 and KLF4 protein bound directly to it. Deletion mutation of this binding site significantly attenuated the transcriptional regulation of the FOXM1 promoter positively by Sp1 and negatively by KLF4. We showed that overexpression of specific FOXM1 isoforms critically regulates pancreatic cancer development and progression by enhancing tumor cell invasion and metastasis. Our findings strongly suggest that targeting specific FOXM1 isoforms effectively attenuates pancreatic cancer development and progression.
Heterocyclic Amides:  Inhibitors of Acyl-CoA:Cholesterol <i>O</i>-Acyl Transferase with Hypocholesterolemic Activity in Several Species and Antiatherosclerotic Activity in the Rabbit (1996)

A series of heterocyclic amides were synthesized and evaluated as inhibitors of acyl-CoA: cholesterol O-acyltransferase (ACAT) in vitro and for cholesterol lowering in cholesterol-fed rats. Compounds were evaluated for cell-based macrophage ACAT inhibition, bioactivity, and adrenal toxicity. Candidates were selected for evaluation in cholesterol-fed dogs and, ultimately, the injured cholesterol-fed rabbit model of atherosclerosis. The heterocyclic amides potently inhibited rabbit liver ACAT (IC50's = 0.014-0.11 microM), and the majority of compounds significantly lowered plasma cholesterol (42-68%) in an acute cholesterol-fed rat model at 3 mg/kg. The most efficacious compounds in the rat were evaluated for bioactivity in vivo and arterial ACAT inhibition in a cell-based macrophage ACAT assay. Two highly bioactive analogs, (+/-)-2-(3-dodecylisoxazol-5-yl)-2-phenyl-N-(2,4,6-trimethoxypheny l) acetamide (13a) and (+/-)-2-(5-dodecylisoxazol-3-yl)-2-phenyl-N-(2,4,6-trimethoxypheny l) acetamide (16a), were selected for further study and were found to be nontoxic in a guinea pig model of adrenal toxicity. Compounds 13a and 16a lowered total cholesterol in the cholesterol-fed rat, rabbit, and dog models of pre-established hypercholesterolemia. Compound 13a in the injured cholesterol-fed rabbit model of atherosclerosis was effective in slowing the development of cholesteryl ester-rich thoracic aortic lesions, reducing lesion coverage by 53% at a dose of 1 mg/kg.
Advanced Bioluminescence System for In Vivo Imaging with Brighter and Red-Shifted Light Emission (2020)

In vivo bioluminescence imaging (BLI), which is based on luminescence emitted by the luciferase-luciferin reaction, has enabled continuous monitoring of various biochemical processes in living animals. Bright luminescence with a high signal-to-background ratio, ideally red or near-infrared light as the emission maximum, is necessary for in vivo animal experiments. Various attempts have been undertaken to achieve this goal, including genetic engineering of luciferase, chemical modulation of luciferin, and utilization of bioluminescence resonance energy transfer (BRET). In this review, we overview a recent advance in the development of a bioluminescence system for in vivo BLI. We also specifically examine the improvement in bioluminescence intensity by mutagenic or chemical modulation on several beetle and marine luciferase bioluminescence systems. We further describe that intramolecular BRET enhances luminescence emission, with recent attempts for the development of red-shifted bioluminescence system, showing great potency in in vivo BLI. Perspectives for future improvement of bioluminescence systems are discussed.
Learning to Navigate in Cities Without a Map (2018)

Navigating through unstructured environments is a basic capability of intelligent creatures, and thus is of fundamental interest in the study and development of artificial intelligence. Long-range navigation is a complex cognitive task that relies on developing an internal representation of space, grounded by recognisable landmarks and robust visual processing, that can simultaneously support continuous self-localisation ("I am here") and a representation of the goal ("I am going there"). Building upon recent research that applies deep reinforcement learning to maze navigation problems, we present an end-to-end deep reinforcement learning approach that can be applied on a city scale. Recognising that successful navigation relies on integration of general policies with locale-specific knowledge, we propose a dual pathway architecture that allows locale-specific features to be encapsulated, while still enabling transfer to multiple cities. We present an interactive navigation environment that uses Google StreetView for its photographic content and worldwide coverage, and demonstrate that our learning method allows agents to learn to navigate multiple cities and to traverse to target destinations that may be kilometres away. The project webpage http://streetlearn.cc contains a video summarising our research and showing the trained agent in diverse city environments and on the transfer task, the form to request the StreetLearn dataset and links to further resources. The StreetLearn environment code is available at https://github.com/deepmind/streetlearn
Calibration and object correspondence in camera networks with widely separated overlapping views (2014)

This study contributes in two ways to the research of multi‐camera object tracking in the context of visual surveillance. Firstly, a semi‐automatic scene calibration method is proposed to deal with mapping a network of cameras with overlapped fields of view onto a single ground plane view, even when the overlap is not substantial. The proposed method uses a semi‐supervised approach that combines tracked blobs with user‐selected line scene features to recover the homographies between camera views that are both simple and accurate. Then, based on the scene calibration information, the intersection points of the projected vertical axis of single camera blobs are used to make object correspondences across multiple views. The method works in mixed environments of both pedestrians and vehicles, and is shown to be accurate and robust against segmentation noise and occlusions. Finally, the advantage of the proposed method is demonstrated by quantitative tracking performance evaluation and comparison against previous methods.
AP-1, ETS, and transcriptional silencers regulate retinoic acid-dependent induction of keratin 18 in embryonic cells. (1994)

The differentiation of both embryonal carcinoma (EC) and embryonic stem (ES) cells can be triggered in culture by exposure to retinoic acid and results in the transcriptional induction of both the endogenous mouse keratin 18 (mK18) intermediate filament gene and an experimentally introduced human keratin 18 (K18) gene as well as a variety of other markers characteristic of extraembryonic endoderm. The induction of K18 in EC cells is limited, in part, by low levels of ETS and AP-1 transcription factor activities which bind to sites within a complex enhancer element located within the first intron of K18. RNA levels of ETS-2, c-Jun, and JunB increase upon the differentiation of ES cells and correlate with increased expression of K18. Occupancy of the ETS site, detected by in vivo footprinting methods, correlates with K18 induction in ES cells. In somatic cells, the ETS and AP-1 elements mediate induction by a variety of oncogenes associated with the ras signal transduction pathway. In EC cells, in addition to the induction by these limiting transcription factors, relief from negative regulation is mediated by three silencer elements located within the first intron of the K18 gene. These silencer elements function in F9 EC cells but not their differentiated derivatives, and their activity is correlated with proteins in F9 EC nuclei which bind to the silencers and are reduced in the nuclei of differentiated F9 cells. The induction of K18, associated with the differentiation of EC cells to extraembryonic endoderm, is due to a combination of relief from negative regulation and activation by members of the ETS and AP-1 transcription factor families.
Attention Engagement and Cognitive State Analysis for Augmented Reality Text Display Functions (2015)

Human eye gaze has recently been used as an effective input interface for wearable displays. In this paper, we propose a gaze-based interaction framework for optical see-through displays. The proposed system can automatically judge whether a user is engaged with virtual content in the display or focused on the real environment and can determine his or her cognitive state. With these analytic capacities, we implement several proactive system functions including adaptive brightness, scrolling, messaging, notification, and highlighting, which would otherwise require manual interaction. The goal is to manage the relationship between virtual and real, creating a more cohesive and seamless experience for the user. We conduct user experiments including attention engagement and cognitive state analysis, such as reading detection and gaze position estimation in a wearable display towards the design of augmented reality text display applications. The results from the experiments show robustness of the attention engagement and cognitive state analysis methods. A majority of the experiment participants (8/12) stated the proactive system functions are beneficial.
ChemInform Abstract: Cyclic β‐Peptoids. (2008)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Correction: Identification of a naturally processed cyclin D1 T‐helper epitope by a novel combination of HLA class II targeting and differential mass spectrometry (Vol. 34(12) 2004, p. 3644–3651) (2005)

Abstract Due to a technical error, the name of the second author, Patrice Decker, was unfortunately omitted from the Table of contents of the December 2004 issue. We apologize for any inconvenience caused. DOI 10.1002/eji.200425510
Tunable Dipolar Acenaphthopyrazine Derivatives Containing Diphenylamine (2004)

A series of acenaphthopyrazine derivatives containing diphenylamine were synthesized. These compounds are amorphous with glass transition temperatures ranging from 95 to 155 °C. They are highly fluorescent with emission in green-yellow to red region. The dipolar character of the compounds results in prominent solvatochromic effect on the emission spectra. Two-layer electroluminescent devices were fabricated using these compounds as hole-transporting and emitting materials, and 1,3,5-tris(N-phenylbenzimidazol-2-yl)benzene (TPBI) or tris(8-hydroxyquinoline)aluminum (Alq3) as the electron-transporting layer. Multilayer devices were also fabricated using the compounds as the emitting materials. Green-yellow-emitting devices exhibiting good performance (e.g., λem = 560−570 nm; ηext = 2.0−2.6%; ηp = 2.3−3.2 lm/W; ηc = 6.5−8.3 cd/A at a current density of 100 mA/cm2) can be achieved in multilayered devices.
Three-dimensional printed calcaneal prosthesis following total calcanectomy (2015)

Three-dimensional-printed prosthesis of the calcaneus is a viable alternative to amputation.
Towards analyzing the complexity landscape of solidity based ethereum smart contracts (2018)

The blockchain based decentralized cryptocurrency platforms are one of the hottest topics in tech at the moment. Though most of the interest is generated by cryptocurrency related activities, it is becoming apparent that a much wider spectrum of applications can leverage the blockchain technology.
Autonomous Agents for Participating in Mulitple On-line Auctions (2001)

The increasing number of online auctions poses a big challenge to e-consumers, especially to those who are actively looking for good deals. In this paper, we present the deisgn of an autonomous agent that can alleviate some of these problems by participating across multiple online auctions (in particular, English, Dutch, and Vickrey auctions). The agent makes decisions on behalf of the consumer and endeavours to guarantee the delivery of the item according to the user’s preferences. Our agent monitors and collects information from the ongoing auctions and determines which auction it wishes to participate in. The decision on how much to bid in the selected auction is made based on a series of tactics and strategies. The proposed bidding algorithm has been implemented in a simulated marketplace environment and its performance has been evaluated empirically.
High-protein diet selectively reduces fat mass and improves glucose tolerance in Western-type diet-induced obese rats (2013)

Obesity is an increasing health problem. Because drug treatments are limited, diets remain popular. High-protein diets (HPD) reduce body weight (BW), although the mechanisms are unclear. We investigated physiological mechanisms altered by switching diet induced obesity (DIO) rats from Western-type diet (WTD) to HPD. Male rats were fed standard (SD) or WTD (45% calories from fat). After developing DIO (50% of rats), they were switched to SD (15% calories from protein) or HPD (52% calories from protein) for up to 4 weeks. Food intake (FI), BW, body composition, glucose tolerance, insulin sensitivity, and intestinal hormone plasma levels were monitored. Rats fed WTD showed an increased FI and had a 25% greater BW gain after 9 wk compared with SD (P < 0.05). Diet-induced obese rats switched from WTD to HPD reduced daily FI by 30% on day 1, which lasted to day 9 (-9%) and decreased BW during the 2-wk period compared with SD/SD (P < 0.05). During these 2 wk, WTD/HPD rats lost 72% more fat mass than WTD/SD (P < 0.05), whereas lean mass was unaltered. WTD/HPD rats had lower blood glucose than WTD/SD at 30 min postglucose gavage (P < 0.05). The increase of pancreatic polypeptide and peptide YY during the 2-h dark-phase feeding was higher in WTD/HPD compared with WTD/SD (P < 0.05). These data indicate that HPD reduces BW in WTD rats, which may be related to decreased FI and the selective reduction of fat mass accompanied by improved glucose tolerance, suggesting relevant benefits of HPD in the treatment of obesity.
Construction of an Escherichia coli K-12 ada deletion by gene replacement in a recD strain reveals a second methyltransferase that repairs alkylated DNA (1988)

We constructed an ada deletion by gene replacement in a recD1014 strain of Escherichia coli. Characterization of a delta ada-25 recD+ strain revealed the presence of a second DNA methyltransferase activity in E. coli K-12 which transfers a methyl group from methylated DNA to a protein with a molecular weight of 18,000 to 20,000.
Whole exome sequencing and characterization of coding variation in 49,960 individuals in the UK Biobank (2019)

SUMMARY The UK Biobank is a prospective study of 502,543 individuals, combining extensive phenotypic and genotypic data with streamlined access for researchers around the world. Here we describe the first tranche of large-scale exome sequence data for 49,960 study participants, revealing approximately 4 million coding variants (of which ~98.4% have frequency < 1%). The data includes 231,631 predicted loss of function variants, a >10-fold increase compared to imputed sequence for the same participants. Nearly all genes (>97%) had ≥1 predicted loss of function carrier, and most genes (>69%) had ≥10 loss of function carriers. We illustrate the power of characterizing loss of function variation in this large population through association analyses across 1,741 phenotypes. In addition to replicating a range of established associations, we discover novel loss of function variants with large effects on disease traits, including PIEZO1 on varicose veins, COL6A1 on corneal resistance, MEPE on bone density, and IQGAP2 and GMPR on blood cell traits. We further demonstrate the value of exome sequencing by surveying the prevalence of pathogenic variants of clinical significance in this population, finding that 2% of the population has a medically actionable variant. Additionally, we leverage the phenotypic data to characterize the relationship between rare BRCA1 and BRCA2 pathogenic variants and cancer risk. Exomes from the first 49,960 participants are now made accessible to the scientific community and highlight the promise offered by genomic sequencing in large-scale population-based studies.
Implications of Lived and Packaged Religions for Intercultural Dialogue to Reduce Conflict and Terror (2018)

Abstract The use of intercultural dialogue (ICD) to promote intergroup understanding and respect is considered as a key to reduce tensions and the likelihood of conflict. This paper argues that understanding the differences among religions – those between packaged and lived religion – enhances the chances of success and makes the effort more challenging. Religions contained and packaged are found in formally organised expressions of religion – churches, denominations, synagogues, mosques, temples and so on. For packaged religions, religious identity is singular and adherents are expected to identify with only one religion and are assumed to accept the whole package of that religion. ICD in this context involves communicating with religious groups such as organisations and encouraging different leaders to speak with each other resulting in platforms filled with ‘heads of faith’ – bishops muftis, ayatollahs, chief rabbis, swamis and so on. In contrast, lived religions involve ritual practices engaged in by individuals and small groups, creation of shrines and sacred spaces, discussing the nature of life, sharing ethical concerns, going on pilgrimages and taking actions to celebrate and sustain hope.There is some evidence that, although packaged religions are declining, lived religions continue at persistent levels. Violent extremism is more likely to be associated with lived rather than packaged forms of religion, making a more balanced intercultural competences approach to ICD critical to countering conflict.
Synthesis and Structural Properties of New Oligodeoxynucleotide Analogues Containing a 2′,5′‐Internucleotidic Squaryldiamide Linkage Capable of Formation of a Watson−Crick Base Pair with Adenine and a Wobble Base Pair with Guanine at the 3′‐Downstream Junction Site (2004)

Abstract A TpT dimer analogue (U 2′ sq 5′ T), in which the 3′‐5′ phosphodiester linkage was replaced by a 2′‐5′ squaryldiamide linkage and the 5′‐upstream T was replaced by a 3′‐deoxyuridine, was synthesized in almost quantitative yield from diethyl squarate. This new dimer structural motif was designed to eliminate the squaryldiamide skeleton‐induced overall strain in T 3′ sq 5′ T, previously incorporated into DNA fragments as a new TpT mimic, through the change in the connection mode from the 3′‐5′ linkage to a 2′‐5′ linkage. Spectral analyses of U 2′ sq 5′ T suggest that the overall structure of this dimer mimic is basically similar to that of TpT. A DNA 10mer 5′‐d(CGCA U 2′ sq 5′ T AGCC)‐3′ incorporating this dimer was synthesized. From the CD analysis, it turned out that the overall structure of a DNA duplex of 5′‐d(CGCA U 2′ sq 5′ T AGCC)‐3′/3′‐d(GCGT AA TCGG)‐5′ is closer to that of the unmodified duplex than the DNA duplex of 5′‐d(CGCA T 3′ sq 5′ T AGCC)‐3′/3′‐d(GCGT AA TCGG)‐5′. Interestingly, extensive Tm experiments suggest that d(CGCA U 2′ sq 5′ T AGCC)‐3′ exhibits intriguing inherent hybridization affinity not only for the completely complementary oligodeoxynucleotide 3′‐d(GCG AA TCGG)‐5′, but also for 3′‐d(GCGT A G TCGG)‐5′, with a mismatched dG. The unique property of the 3′‐downstream dT moiety of U 2′ sq 5′ T − the ability to recognize both dA and dG − was also supported by more detailed computational analysis of U 2′ sq 5′ T and TpT. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Setting break-points in distributed time-triggered architecture (2003)

Setting a brake-point in a local node of a distributed real-time system freezes the execution of the application in the local node, while other nodes in the network continue execution of their part of a distributed application. This will lead to an inconsistent state of nodes in the system, because the physical time cannot be stopped and the system is no more consistent in the temporal domain. We present a new method for setting brake-points in distributed time-triggered systems. After a brake-point is set all nodes in the network freeze the execution of the local application at the same instant and enters a debug operation mode. This method can be applied on target systems, which use the concept of sparse time base, like the time-triggered architecture (TTA). During the debug mode a monitoring (debugger) node is used to exchange debugging commands and data with particular nodes in the network. The debugging process is transparent to distributed time-triggered applications. The proposed debugging technique can be applied also for software fault injection. It circumvents the problem of temporal intrusiveness during the debugging or software fault injection in time-triggered systems.
Thermal Performance of Pulsating Heat Stripes Built With Plastic Materials (2018)

A low-cost, flexible pulsating heat pipe (PHP) was built in a composite polypropylene sheet consisting of three layers joint together by selective laser welding, to address the demand of heat transfer devices characterized by low weight, small unit thickness, low cost, and high mechanical flexibility. A thin, flexible, and lightweight heat pipe is advantageous for various aerospace, aircraft, and portable electronic applications where the device weight, and its mechanical flexibility are essential. The concept is to sandwich a serpentine channel, cut out in a polypropylene sheet and containing a self-propelled mixture of a working fluid with its vapor, between two transparent sheets of the same material; this results into a thin, flat enclosure with parallel channels hence the name “pulsating heat stripes” (PHS). The transient and steady-state thermal response of the device was characterized for different heat input levels and different configurations, either straight or bent at different angles. The equivalent thermal resistance was estimated by measuring the wall temperatures at both the evaporator and the condenser, showing a multifold increase of the equivalent thermal conductance with respect to solid polypropylene.
Effect of hematite addition to CaSO<sub>4</sub> oxygen carrier in chemical looping combustion of coal char (2015)

Catalytic mechanism of synergy effect of iron oxide in gasification of char and in the reduction of CaSO<sub>4</sub> oxygen carrier.