Miracle-dz/UniFAR-FTUs huggingface dataset:
Synthesis, Biological Activity, and NMR‐Based Structural Studies of Deltorphin I Analogs Modified in Message Domain with a New α,α‐Disubstituted Glycines

This article describes new deltorphin I analogs in which phenylalanine residues were replaced by the corresponding (R) or (S)‐α‐benzyl‐β‐azidoalanine, α‐benzyl‐β‐(1‐pyrrolidinyl)alanine, α‐benzyl‐β‐(1‐piperidinyl)alanine, and α‐benzyl‐β‐(4‐morpholinyl)‐alanine residues. The potency and selectivity of the new analogs were evaluated by a competitive receptor binding assay in the rat brain using [3H]DAMGO (a μ ligand) and [3H]DELT (a δ ligand). The affinity of analogs containing (R) or (S)‐α‐benzyl‐β‐azidoalanine in position 3 to δ‐receptors strongly depended on the chirality of the α,α‐disubstituted residue. The conformational behavior of peptides modified with (R) or (S)‐α‐benzyl‐β‐(1‐piperidinyl)Ala, which displays the opposite selectivity, was analyzed by 1H and 13C NMR. The μ‐selective Tyr‐d‐Ala‐(R)‐α‐benzyl‐β‐(1‐piperidinyl)Ala‐Asp‐Val‐Val‐Gly‐NH2 lacks the helical conformation observed in the δ‐selective Tyr‐d‐Ala‐(S)‐α‐benzyl‐β‐(1‐piperidinyl)Ala‐Asp‐Val‐Val‐Gly‐NH2. Our results support the proposal that differences between δ‐ and μ‐selective opioid peptides are attributable to the presence or absence of a spatial overlap between the N‐terminal message domain and the C‐terminal address domain.
PCL-based nanofibers containing ibuprofen/cyclodextrins nanocontainers: A potential candidate for drug delivery application

Poor solubility and low dissolution rate of ibuprofen (IBU) in the aqueous gastro-intestinal fluids restrict its application, absorption, distribution, target organ delivery, and bioavailability. For improvement of aqueous solubility of IBU, supramolecular nanocontainers of IBU/cyclodextrin were prepared via formation of inclusion complex between ibuprofen and cyclodextrins (α-cyclodextrin and β-cyclodextrin) at various conditions (at room temperature at 25℃ and under sonic energy). The formation of inclusion complex between IBU and cyclodextrins can be confirmed by hydrogen nuclear magnetic resonance, differential scanning calorimetry, fourier transform Infrared spectroscopy (FTIR), X-ray diffraction, and scanning electron microscopy study. FTIR of pure IBU and cyclodextrins is similar to the obtained complex, which indicated intactness of drug in the complex. The encapsulation of IBU in cyclodextrins cavity improved its solubility, phase solubility, and in vitro dissolution and also controlled its release which ensures the long-term delivery. Electro-spun nanofibers of poly-ɛ-caprolactone containing IBU/cyclodextrins is a promising method for controlled drug delivery electro-spun which is bead-free without any aggregation on the surface.
On the Thermodynamics of NUT charged spaces

We discuss and compare at length the results of two methods used recently to describe the thermodynamics of Taub-NUT solutions in a deSitter background. In the ﬁrst approach ( C -approach), one deals with an analytically continued version of the metric while in the second approach ( R -approach), the discussion is carried out using the unmodiﬁed metric with Lorentzian signature. No analytic continuation is performed on the coordinates and/or the parameters that appear in the metric. We ﬁnd that the results of both these approaches are completely equivalent modulo analytic continuation and we provide the exact prescription that relates the results in both methods. The extension of these results to the AdS/ﬂat cases aims to give a physical interpretation of the thermodynamics of nut-charged spacetimes in the Lorentzian sector. We also brieﬂy discuss the higher dimensional spaces and note that, analogous with the absence of hyperbolic nuts in AdS backgrounds, there are no spherical Taub-Nut-dS solutions.
Interferon Consensus Sequence Binding Protein (ICSBP) Decreases β-Catenin Activity in Myeloid Cells by Repressing GAS2 Transcription

ABSTRACT The interferon consensus sequence binding protein (ICSBP) is an interferon regulatory transcription factor, also referred to as IRF8. ICSBP acts as a suppressor of myeloid leukemia, although few target genes explaining this effect have been identified. In the current studies, we identified the gene encoding growth arrest specific 2 (GAS2) as an ICSBP target gene relevant to leukemia suppression. We find that ICSBP, Tel, and histone deacetylase 3 (HDAC3) bind to a cis element in the GAS2 promoter and repress transcription in myeloid progenitor cells. Gas2 inhibits calpain protease activity, and β-catenin is a calpain substrate in these cells. Consistent with this, ICSBP decreases β-catenin protein and activity in a Gas2- and calpain-dependent manner. Conversely, decreased ICSBP expression increases β-catenin protein and activity by the same mechanism. This is of interest, because decreased ICSBP expression and increased β-catenin activity are associated with poor prognosis and blast crisis in chronic myeloid leukemia (CML). We find that the expression of Bcr/abl (the CML oncoprotein) increases Gas2 expression in an ICSBP-dependent manner. This results in decreased calpain activity and a consequent increase in β-catenin activity in Bcr/abl-positive (Bcr/abl+) cells. Therefore, these studies have identified a Gas2/calpain-dependent mechanism by which ICSBP influences β-catenin activity in myeloid leukemia.
The Schmidtea mediterranea database as a molecular resource for studying platyhelminthes, stem cells and regeneration

Platyhelminthes are excellent models for the study of stem cell biology, regeneration and the regulation of scale and proportion. In addition, parasitic forms infect millions of people worldwide. Therefore, it is puzzling that they remain relatively unexplored at the molecular level. We present the characterization of ∼3000 non-redundant cDNAs from a clonal line of the planarian Schmidtea mediterranea. The obtained cDNA sequences, homology comparisons and high-throughput whole-mount in situ hybridization data form part of the S. mediterranea database (SmedDb; http://planaria.neuro.utah.edu). Sixty-nine percent of the cDNAs analyzed share similarities with sequences deposited in GenBank and dbEST. The remaining gene transcripts failed to match sequences in other organisms, even though a large number of these (∼80%) contained putative open reading frames. Taken together, the molecular resources presented in this study, along with the ability of abrogating gene expression in planarians using RNA interference technology, pave the way for a systematic study of the remarkable biological properties displayed by Platyhelminthes.
AFAX : Rich client / server web applications in F #

“Ajax” programming is becoming a de-facto standard for certain types of web applications, but unfortunately developing this kind of application is a difficult task. Developers have to deal with problems like a language impedance mismatch, limited execution runtime for the code running in web browser on the client-side and no integration between client and serverside parts that are developed as a two independent applications, but typically form a single and homogenous application. In this paper we present the first project that deals with all three mentioned problems but which still integrates with existing web development technologies such as ASP.NET on the server and JavaScript on the client. We use the F# language for writing both client and server-side part of the web application, which lets us develop client-side code in a type-safe programming language using a subset of the F# library, and we provide a way to write both server-side and client-side code as a part of single homogeneous module defining the web page logic. This code is executed heterogeneously, part as JavaScript on the client, and part as native code on the server. Finally we use monadic syntax for the separation of client and server-side code, tracking this separation through the F# type system.
A Rap on the Knuckles and a Twist in the Tale From Tweeting Affective Metaphors to Generating Stories with a Moral

Rules offer a convenient means of limiting the operational scope of our AI programs so as to not transgress predictable moral boundaries. Yet the imposition of an operational morality based on mere rules will not turn our machines into moral agents, just the unthinking tools of moral designers. If we are to imbue our machines with a profound functional morality, we must first gift them with a moral imagination, for empathic morality — where one agent treats another as it would want to be treated itself — requires an ability to project oneself into the realms of the counterfactual. In this paper we thus explore the role of the moral imagination in generating new and inspiring stories. The creation of novel tales with a built-in moral requires that an artificial system possess the ability to guess at the morality of characters and their actions in novel settings and events. Our moralizing tale-spinner — which generates Aesop-style tales about human-like animals with identifiable human qualities — also faces another challenge: it must render these tales as micro-texts that can be distributed as tweets. As we shall also use metaphor to lend elasticity to our moral conceptions, these short stories, rich in animal metaphors, will comprise part of the daily output of the @MetaphorMagnet Twitterbot.
Flexible vertical-channel thin-film transistors using In-Ga-Zn-O active channel and polyimide spacer on poly(ethylene naphthalate) substrate

A flexible vertical-channel thin-film transistor (VTFT) with a channel length of 400 nm was fabricated on a poly(ethylene naphthalate) substrate. The vertical gate-stack composed of gate electrode/gate insulator/active channel was prepared by a conformal atomic layer deposition and a dry etching process of an organic polyimide spacer. The transfer characteristics of the fabricated flexible VTFT were well confirmed after the postannealing process at 200 °C, in which the on/off ratio was obtained to be 1.8 × 102. The threshold voltage shifts were estimated to be +6.1 and −4.5 V under the positive and negative bias-stress conditions for 104 s, respectively. The device characteristics showed no remarkable degradation when delaminating from the carrier glass substrate. Furthermore, there were no marked changes in transfer curves even when the device was bent with a radius of curvature of 10 mm. A suitable choice of spacer material, optimization of the dry etching process, and employment of ultra-thin flexible film substrate were suggested to appropriate solutions for enhancing the device performance of the proposed flexible VTFTs.A flexible vertical-channel thin-film transistor (VTFT) with a channel length of 400 nm was fabricated on a poly(ethylene naphthalate) substrate. The vertical gate-stack composed of gate electrode/gate insulator/active channel was prepared by a conformal atomic layer deposition and a dry etching process of an organic polyimide spacer. The transfer characteristics of the fabricated flexible VTFT were well confirmed after the postannealing process at 200 °C, in which the on/off ratio was obtained to be 1.8 × 102. The threshold voltage shifts were estimated to be +6.1 and −4.5 V under the positive and negative bias-stress conditions for 104 s, respectively. The device characteristics showed no remarkable degradation when delaminating from the carrier glass substrate. Furthermore, there were no marked changes in transfer curves even when the device was bent with a radius of curvature of 10 mm. A suitable choice of spacer material, optimization of the dry etching process, and employment of ultra-thin flexible .
Asynchronous Stochastic Gradient Descent with Variance Reduction for Non-Convex Optimization

We provide the first theoretical analysis on the convergence rate of the asynchronous stochastic variance reduced gradient (SVRG) descent algorithm on non-convex optimization. Recent studies have shown that the asynchronous stochastic gradient descent (SGD) based algorithms with variance reduction converge with a linear convergent rate on convex problems. However, there is no work to analyze asynchronous SGD with variance reduction technique on non-convex problem. In this paper, we study two asynchronous parallel implementations of SVRG: one is on a distributed memory system and the other is on a shared memory system. We provide the theoretical analysis that both algorithms can obtain a convergence rate of $O(1/T)$, and linear speed up is achievable if the number of workers is upper bounded. V1,v2,v3 have been withdrawn due to reference issue, please refer the newest version v4.
Modeling US adult obesity trends: a system dynamics model for estimating energy imbalance gap.

OBJECTIVES We present a system dynamics model that quantifies the energy imbalance gap responsible for the US adult obesity epidemic among gender and racial subpopulations. METHODS We divided the adult population into gender-race/ethnicity subpopulations and body mass index (BMI) classes. We defined transition rates between classes as a function of metabolic dynamics of individuals within each class. We estimated energy intake in each BMI class within the past 4 decades as a multiplication of the equilibrium energy intake of individuals in that class. Through calibration, we estimated the energy gap multiplier for each gender-race-BMI group by matching simulated BMI distributions for each subpopulation against national data with maximum likelihood estimation. RESULTS No subpopulation showed a negative or zero energy gap, suggesting that the obesity epidemic continues to worsen, albeit at a slower rate. In the past decade the epidemic has slowed for non-Hispanic Whites, is starting to slow for non-Hispanic Blacks, but continues to accelerate among Mexican Americans. CONCLUSIONS The differential energy balance gap across subpopulations and over time suggests that interventions should be tailored to subpopulations' needs.
Fast Secure Two-Party ECDSA Signing ? Yehuda Lindell ? ?

ECDSA is a standard digital signature schemes that is widely used in TLS, Bitcoin and elsewhere. Unlike other schemes like RSA, Schnorr signatures and more, it is particularly hard to construct efficient threshold signature protocols for ECDSA (and DSA). As a result, the best-known protocols today for secure distributed ECDSA require running heavy zero-knowledge proofs and computing many large-modulus exponentiations for every signing operation. In this paper, we consider the specific case of two parties (and thus no honest majority) and construct a protocol that is approximately two orders of magnitude faster than the previous best. Concretely, our protocol achieves good performance, with a single signing operation for curve P-256 taking approximately 37ms between two standard machine types in Azure (utilizing a single core only). Our protocol is proven secure under standard assumptions using a game-based definition. In addition, we prove security by simulation under a plausible yet non-standard assumption regarding
Bacteroides reticulotermitis sp. nov., isolated from the gut of a subterranean termite (Reticulitermes speratus).

An obligately anaerobic, non-pigmented, non-spore-forming, Gram-staining-negative, rod-shaped bacterium, designated strain Rs-03(T), was isolated from the gut of the subterranean termite Reticulitermes speratus. The taxonomic position of the novel strain was determined by following a polyphasic approach. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain Rs-03(T) was a member of the genus Bacteroides and was most closely related to Bacteroides thetaiotaomicron JCM 5827(T) (95.0 % sequence similarity), Bacteroides faecis JCM 16478(T) (94.8 %) and Bacteroides xylanisolvens JCM 15633(T) (94.3 %). The results of hsp60 gene sequence analysis indicated that the novel strain was different from established members of the genus Bacteroides. Strain Rs-03(T) was saccharolytic and produced succinic and acetic acids, with small amounts of propionic acid, as metabolic end products. The major cellular fatty acids of strain Rs-03(T) were anteiso-C(15 : 0), C(18 : 1)ω9c and iso-C(17 : 0) 3-OH. The major menaquinones were MK-10 and MK-9 and the genomic DNA G+C content was 44.9 mol%. Based on these data, strain Rs-03(T) represents a novel species in the genus Bacteroides, for which the name Bacteroides reticulotermitis sp. nov. is proposed. The type strain is Rs-03(T) ( = JCM 10512(T) = CCUG 62153(T)).
Observer Design and Implementation for Packed Bed Thermal Energy Storage Systems

—This paper investigates the problem of designing a state observer for a Packed Bed Thermal Energy Storage System. In previous studies (see e.g. [21]), a mathematical model of the system, taking the form of two coupled partial differential equations, was derived and validated through comparison with experimental measurements. In this paper, the previously derived model is approximated by a lumped linear time-invariant model and then employed to design a Luenberger state observer capable of reconstructing the solid and fluid temperature profiles on the basis of few collocated fluid temperature measurements. Theoretical design and experimental results are presented throughout the paper.
World Wide Web Presentations for Volatile Hypermedia Database Output

The use of databases in current information systems is changing rapidly. The information contained in the database shows less structure, and contains multi-media objects and free-text, as well as hypertext links. To represent the information from a database a hypermedia platform such as World Wide Web often appears to be a right choice. Typical examples of such hypermedia applications are employee databases that include both administrative and personal information, museum databases that offer guided tours as well as query facilities for their collection, geographic information systems as used in tourist applications, and mail-order catalogs and services. The Relationship Management Methodology (RMM) [Isakowitz et al. 1995] is a hypermedia design method for generating hypermedia navigation and presentations of database information. However, most of the output of databases is the result of queries. Such output does not have a predefined structure for which a representation could be designed using RMM. In this paper we present an approach for extending the principles of RMM in order to generate hypermedia (HTML) presentations and navigational structures for query answers. First, we propose heuristics that are based on Relationship Management Design Model (RMDM) structures generated through RMM to provide presentational and navigational cues in a database query. Moreover, we give ways to override these defaults through extensions to the SQL query language.
Wear performance of multiwalled carbon nanotube‐reinforced ultra‐high molecular weight polyethylene composite

Ultra-high molecular weight polyethylene (UHMWPE) has proven to be a good counterpart articulating surface against Cr–Co–Mo femoral components in artificial joints. Nevertheless, UHMWPE wear damage and subsequent aseptic loosening continues to be the main reason for revision of knee replacements. There is an ongoing research effort to improve the metal-on-UHMWPE couple. This study compares the wear resistance of multiwalled carbon nanotube-reinforced UHMWPE composite with conventional orthopedic grade UHMWPE currently used in total knee replacements. Defined by previous studies, 1.25 wt. % multiwall carbon nanotubes (MWCNT) were incorporated into UHMWPE to fabricate UHMWPE-MWCNT composites by solution blending, achieving an even distribution in the polymeric matrix. UHMWPE-MWCNT samples were manufactured by compression molding and sterilized with γ-rays. Scanning electron microscopy confirmed a uniform distribution of the MWCNTs. The volumetric wear was reduced by 86.9%, and the indentation depth in creep testing decreased 68%. The composite displayed superior wear behavior producing less wear debris than conventional materials.
Integrins induce activation of EGF receptor: role in MAP kinase induction and adhesion‐dependent cell survival

Adhesion of human primary skin fibroblasts and ECV304 endothelial cells to immobilized matrix proteins, β1 or αv integrin antibodies stimulates tyrosine phosphorylation of the epidermal growth factor (EGF) receptor. This tyrosine phosphorylation is transiently induced, reaching maximal levels 30 min after adhesion, and it occurs in the absence of receptor ligands. Similar results were observed with EGF receptor‐transfected NIH‐3T3 cells. Use of a kinase‐negative EGF receptor mutant demonstrates that the integrin‐stimulated tyrosine phosphorylation is due to activation of the receptor's intrinsic kinase activity. Integrin‐mediated EGF receptor activation leads to Erk‐1/MAP kinase induction, as shown by treatment with the specific inhibitor tyrphostin AG1478 and by expression of a dominant‐negative EGF receptor mutant. EGF receptor and Erk‐1/MAP kinase activation by integrins does not lead per se to cell proliferation, but is important for entry into S phase in response to EGF or serum. EGF receptor activation is also required for extracellular matrix‐mediated cell survival. Adhesion‐dependent MAP kinase activation and survival are regulated through EGF receptor activation in cells expressing this molecule above a threshold level (5×103 receptors per cell). These results demonstrate that integrin‐dependent EGF receptor activation is a novel signaling mechanism involved in cell survival and proliferation in response to extracellular matrix.
Expressing Preferences with Price-Vector Agents in Combinatorial Auctions

A combinatorial auction is one in which preferences are expressed for combinations or bundles of items, rather than just for individual items. The importance of combinatorial auctions has grown tremendously in the past 15 years, which have seen an explosion in the use of auction mechanisms in both government allocation problems and businessto-business commerce. Chapter 2 of the dissertation outlines the many applications of combinatorial auction research (as do Anandalingam et al., 2005), including shipping-lane and procurement auctions in the private sector, as well as auctions for spectrum licenses by the FCC and airport landing slots by the FAA in the public sector. In each of these environments, the expression of aggregate information allows the bidders to realize synergies (e.g., economies-of-scale or owning complementary items) while the auction mechanism stimulates competition, aiding the seller of items with more competitive prices. There are, however, two major computational difficulties limiting the implementation of the combinatorial auction paradigm: (1) the underlying problem of finding an efficient allocation (called the winner-determination problem) is NP-hard, and (2) the amount of information necessary to describe a bidder’s preferences for all bundles grows exponentially in the number of items. For each of the real-world environments for which combinatorial auctions have been used (or are being heavily considered for use, as in the airport landing-slot case) the number of items being auctioned is large enough for problem (2) to have a limiting effect. The exponential growth of bundles makes it difficult for bidders to express preferences for every bundle that may be of interest. Clearly, a “bidding language” is necessary to ease the burden of preference expression, helping bidders by placing bids on many bundles simultaneously. The development of an easier to use language of preference expression can increase the efficiency of the auction, both by achieving better outcomes, and by reducing the time spent by the bidders communicating their preferences. The development of a bidding language to aid the bidder with problem (2) should be coupled with the development of a practically implementable solution technique, simultaneously addressing the auctioneer’s difficulty, (1) above. Viable solutions to this problem involve both restricted versions of the NP-hard winner-determination problem that remain NP-hard but are smaller in scale, and restricted versions that are polynomially solvable, but then are more