Miracle-dz/UniFAR-FTUs huggingface dataset:
CHF6001 I: A Novel Highly Potent and Selective Phosphodiesterase 4 Inhibitor with Robust Anti-Inflammatory Activity and Suitable for Topical Pulmonary Administration

This study examined the pharmacologic characterization of CHF6001 [(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(cyclopropylmethoxy)-4-(methylsulfonamido)benzoyloxy)ethyl)pyridine 1-oxide], a novel phosphodiesterase (PDE)4 inhibitor designed for treating pulmonary inflammatory diseases via inhaled administration. CHF6001 was 7- and 923-fold more potent than roflumilast and cilomilast, respectively, in inhibiting PDE4 enzymatic activity (IC50 = 0.026 ± 0.006 nM). CHF6001 inhibited PDE4 isoforms A–D with equal potency, showed an elevated ratio of high-affinity rolipram binding site versus low-affinity rolipram binding site (i.e., >40) and displayed >20,000-fold selectivity versus PDE4 compared with a panel of PDEs. CHF6001 effectively inhibited (subnanomolar IC50 values) the release of tumor necrosis factor-α from human peripheral blood mononuclear cells, human acute monocytic leukemia cell line macrophages (THP-1), and rodent macrophages (RAW264.7 and NR8383). Moreover, CHF6001 potently inhibited the activation of oxidative burst in neutrophils and eosinophils, neutrophil chemotaxis, and the release of interferon-γ from CD4+ T cells. In all these functional assays, CHF6001 was more potent than previously described PDE4 inhibitors, including roflumilast, UK-500,001 [2-(3,4-difluorophenoxy)-5-fluoro-N-((1S,4S)-4-(2-hydroxy-5-methylbenzamido)cyclohexyl)nicotinamide], and cilomilast, and it was comparable to GSK256066 [6-((3-(dimethylcarbamoyl)phenyl)sulfonyl)-4-((3-methoxyphenyl)amino)-8-methylquinoline-3-carboxamide]. When administered intratracheally to rats as a micronized dry powder, CHF6001 inhibited liposaccharide-induced pulmonary neutrophilia (ED50 = 0.205 μmol/kg) and leukocyte infiltration (ED50 = 0.188 μmol/kg) with an efficacy comparable to a high dose of budesonide (1 μmol/kg i.p.). In sum, CHF6001 has the potential to be an effective topical treatment of conditions associated with pulmonary inflammation, including asthma and chronic obstructive pulmonary disease.
The Genome of Black Cottonwood, Populus trichocarpa (Torr. & Gray)

We report the draft genome of the black cottonwood tree, Populus trichocarpa. Integration of shotgun sequence assembly with genetic mapping enabled chromosome-scale reconstruction of the genome. More than 45,000 putative protein-coding genes were identified. Analysis of the assembled genome revealed a whole-genome duplication event; about 8000 pairs of duplicated genes from that event survived in the Populus genome. A second, older duplication event is indistinguishably coincident with the divergence of the Populus and Arabidopsis lineages. Nucleotide substitution, tandem gene duplication, and gross chromosomal rearrangement appear to proceed substantially more slowly in Populus than in Arabidopsis. Populus has more protein-coding genes than Arabidopsis, ranging on average from 1.4 to 1.6 putative Populus homologs for each Arabidopsis gene. However, the relative frequency of protein domains in the two genomes is similar. Overrepresented exceptions in Populus include genes associated with lignocellulosic wall biosynthesis, meristem development, disease resistance, and metabolite transport.
Standards Fragmentation in Electronic Markets : An Institutional Analysis of XML Innovation Deployment

Champions of XML have argued that the standard has the potential to influence interbusiness communications more than any other protocol in recent history. The improved structure and efficiency of XML, compared to comma separated value or electronic data interchange transmissions, are difficult to negate. However, diffusion of XML has been far less than anticipated. This study attempts to identify some of the barriers or constraints to XML adoption on a technological, administrative and institutional level. Our goal is to identify instances of sub-optimal XML deployment and trace their origins to institutional forces, thereby placing institutions at the forefront of technology innovation and diffusion research. We study an energy market that is undertaking the bilateral trades of electricity using XML. Through an analysis of industry trends and operational data, we identify several characteristics that have constrained the optimal adoption and use of XML, i.e., XML infusion. These include agency conflicts, misalignment of standardization incentives, path dependencies and technological legacies. These factors are mapped to institutional origins such as government regulation and deregulation, contract/vendor solicitation requirements, status and structure of competing and complementary markets, path dependent adoptions of best practice, political risk aversion, and technological codification of domain knowledge. These institutional forces map as key constraints of XML infusion. Implications for other industries and the diffusion of XML are explored.
The bacterial oxidation of aromatic compounds.

SUMMARY: Adaptive patterns for a vibrio indicate that the oxidation of phenylalanine to homogentisic acid by this organism may proceed by two different pathways, one through phenylpyruvic and phenylacetic acids and the other through tyrosine and p-hydroxyphenylpyruvic acid. That the former pathway is used is confirmed by the isolation from metabolism fluids of the phenylhydrazone of phenylpyruvic acid. The vibrio does not appear to oxidize the side chains of phenylpropionic and phenylacetic acids before ring fission. The influence of cell suspension density on rates of oxidation of various highly polar compounds which may penetrate slowly into the cells has been studied.
Assessment and Instruction of Object Permanence in Children with Blindness and Multiple Disabilities

Introduction This article discusses the impact of blindness and low vision on the development of object permanence and provides suggestions for assessment and instruction. Methods The reviewed literature was identified by searching both ERIC and Psych Info using combinations of search terms such as object permanence and visual impairment or low vision and blindness. Books, assessment tools, and nonpeer-reviewed literature were also reviewed. Results Although children with low vision use vision as the basis to master object permanence, children who are blind rely primarily on their tactile experiences of objects. Recommended instructional practices include the consistent and repeated naming of the concealed object, concealment of motivating and varied objects, and direct reinforcement. Discussion Direct instruction that is grounded in careful assessment may accelerate the mastery of object permanence, with unique strategies being applied to the instruction of children who are blind, including the coactive concealment of objects. Implications for practitioners Practitioners may use the structured informal assessment and the identified items within commercially produced assessment tools to identify a child's current knowledge of object permanence. Practitioners may integrate the research-based and promising practices to improve instruction.
HUMORAL AND CELLULAR ASPECTS OF THE IMMUNE RESPONSE TO THE SOMATIC ANTIGEN OF SALMONELLA ENTERITIDIS

A study was made of the cellular and humoral aspects of the immune response of the rabbit to the somatic polysaccharide of Salmonella enteritidis. The response to a single intravenous injection was characterized by the appearance of elevated titers of bactericidal antibody between 2 and 3 days later. The maximum titer was dose-dependent and occurred between 5 and 7 days, thereafter declining rapidly during the first month. The significant stabilized levels which then persisted for at least 1 year were also dose-dependent. Most of the antibody produced (>99 per cent) was associated with the macroglobulin fraction of serum. Plaque-forming cells (PFC) elaborating antibody specific for this somatic antigen were detected and enumerated by the technique of localized hemolysis in gel employing polysaccharide-coated sheep erythrocytes. Significant numbers of PFC were encountered in the spleen as early as 14 to 18 hours after a single intravenous injection of antigen; after 36 hours the number of PFC rose rapidly and culminated in a maximum population at 5 days, followed by a rapid decline and plateau similar to that for circulating antibody. The spleen was the principal organ involved in the systemic response, but other lymphoid tissues including bone marrow, peripheral blood leucocytes, and thymus contributed significantly. After an interval of 3 months the effect on humoral antibody titers of a second injection of antigen was dependent on the amount of polysaccharide administered; markedly greater titers were now obtained with 0.02 to 0.002 µg, whereas 0.2 to 20 µg resulted in a duplication of the initial humoral response. The cellular response to a second dose of 5 µg was accelerated; larger numbers of PFC appeared more rapidly, attained a maximum population by day 3, and exceeded the primary response by a factor of two. This acceleration in the attainment of maximum numbers of PFC and the increased bactericidal antibody titers following a second injection of limiting amounts of antigen suggest that these somatic polysaccharides may in fact evoke a "secondary" type of response in the rabbit.
ANALISIS PENGARUH KEPERCAYAAN, KEAMANAN, KUALITAS PELAYANAN DAN PERSEPSI AKAN RESIKO TERHADAP KEPUTUSAN PEMBELIAN MELALUI SITUS JEJARING SOSIAL (SOCIAL NETWORKING WEBSITES) (Studi Pada Mahasiswa di Kota Semarang)

Penelitian ini bertujuan untuk mengetahui pengaruh kepercayaan, keamanan, kualitas pelayanan dan persepsi akan resiko terhadap keputusan pembelian melalui situs jejaring sosial (Social Networking Websites) pada mahasiswa di kota Semarang. Populasi dalam penelitian adalah seluruh konsumen yang melakukan pembelian produk melalui media jejaring sosial (facebook dan twitter) yang jumlahnya sangat banyak atau tidak diketahui. Jenis data yang dipakai adalah data primer dengan metode pengumpulan data menggunakan kuesioner. Teknik penggambilan sampling adalah non probability sampling dengan sampel sebanyak 113 responden. Teknik analisis yang digunakan adalah regresi berganda. Hasil analisis menunjukkan bahwa: 1) Kepercayaan berpengaruh positif dan tidak signifikan terhadap keputusan.pembelian 2). Keamanan berpengaruh negatif dan tidak signifikan keputusan pembelian. 3). Kualitas Pelayanan berpengaruh positif dan signifikan terhadap keputusan pembelian. 4). Persepsi akan Resiko berpengaruh positif dan signifikan terhadap keputusan pembelian. Adjusted R Square sebesar 64,9%.
Coping and Complaining: Attachment and the Language of Disease

Illness, Sickness and Disease. Genes, Brains and the Internal Milieu. Learning and Memory: A Basis for Understanding Development and Change in the Face of Threat and Danger. The Ideal Patient. The 'Balanced' Type B Attachment Strategies. The 'Dismissing' Type A Attachment Strategies. The 'Pre-occupied' Type C Attachment Strategies, and Other Classifications. Ambiguous Symptoms and the Attachment Strategies of Health Professionals. Goal Corrected Partnerships for Health.
Evaluation of the growth inhibitory activities of triphala against common bacterial isolates from HIV infected patients

The isolation of microbial agents less susceptible to regular antibiotics and the rising trend in the recovery rates of resistant bacteria highlights the need for newer alternative principles. Triphala has been used in traditional medicine practice against certain diseases such as jaundice, fever, cough, eye diseases etc. In the present study phytochemical (phenolic, flavonoid and carotenoid) and antibacterial activities of aqueous and ethanol extracts of Triphala and its individual components (Terminalia chebula, Terminalia belerica and Emblica officinalis) were tested against certain bacterial isolates (Pseudomonas aeruginosa, Klebsiella pneumoniae, Shigella sonnei, S. flexneri, Staphylococcus aureus, Vibrio cholerae, Salmonella paratyphi‐B, Escherichia coli, Enterococcus faecalis, Salmonella typhi) obtained from HIV infected patients using Kirby‐Bauer's disk diffusion and minimum inhibitory concentration (MIC) methods. T. chebula was found to possess high phytochemical content followed by T. belerica and E. officinalis in both aqueous and ethanol extracts. Further, most of the bacterial isolates were inhibited by the ethanol and aqueous extracts of T. chebula followed by T. belerica and E. officinalis by both disk diffusion and MIC methods. The present study revealed that both individual and combined aqueous and ethanol extracts of Triphala have antibacterial activity against the bacterial isolates tested. Copyright © 2007 John Wiley & Sons, Ltd.
Semi-Markov state estimation and policy optimization for energy efficient mobile sensing

User/environmental context detection on mobile devices benefits end-users by providing information support to various kinds of applications. A pervasive question, however, is how the sensors on the mobile device should be sampled energy efficiently without sacrificing too much detection accuracy. In this paper, we formulate the user state sensing problem as the intermittent sampling of a semi-Markov process, a model that provides general and flexible capturing of realistic data with any type of state sojourn distributions. We propose (a) a semi-Markov state estimation mechanism that selects the most likely user state while observations are missing, and (b) a semi-Markov optimal sensing policy us* which minimizes the expected state estimation error while maintaining a given energy budget. Their performance are shown to significantly outperform Markov algorithms on simulated two-state processes and real user state traces pertaining to different types of state distributions. Finally, in order to evaluate the performance of us*, we implement a client-server based basic human activity recognition system on N95 smartphones and desktops which automatically computes user-specific optimal sensing policy based on historically collected data. We show that us* improves the estimation accuracy by 27.8% and 48.6% respectively over Markov-optimal policy and uniform sampling through a set of experiments.
Evidence for a two membrane–spanning autonomous mitochondrial DNA replisome

The unit of inheritance for mitochondrial DNA (mtDNA) is a complex nucleoprotein structure termed the nucleoid. The organization of the nucleoid as well as its role in mtDNA replication remain largely unknown. Here, we show in Saccharomyces cerevisiae that at least two populations of nucleoids exist within the same mitochondrion and can be distinguished by their association with a discrete proteinaceous structure that spans the outer and inner mitochondrial membranes. Surprisingly, this two membrane–spanning structure (TMS) persists and self-replicates in the absence of mtDNA. We tested whether TMS functions to direct the replication of mtDNA. By monitoring BrdU incorporation, we observed that actively replicating nucleoids are associated exclusively with TMS. Consistent with TMS's role in mtDNA replication, we found that Mip1, the mtDNA polymerase, is also a stable component of TMS. Taken together, our observations reveal the existence of an autonomous two membrane–spanning mitochondrial replisome as well as provide a mechanism for how mtDNA replication and inheritance may be physically linked.
An adaptive system architecture for mitigating asymmetric cryptography weaknesses on TPMs

A Trusted Platform Module (TPM) is a microcontroller-based chip, which provides a hardware-based security to the user's data, cryptographic keys, and other secrets. For this purpose, the TPM is equipped with hardwired cryptographic engines such as RSA, SHA-1, and HMAC that rely on correspondingly uncompromised cryptographic algorithms. For example, the RSA (asymmetric) engine on the TPM utilizes the RSA algorithm for encrypting and decrypting the user data as well as for signature generation and verification. Therefore, in case of a compromised RSA algorithm, not only the data protected by the TPM is lost but also the generated signatures become invalid. One possible solution to this problem is to replace (i.e., update) the RSA engine on the TPM with a new uncompromised asymmetric engine (e.g., ECC). However, the current TPMs are in general implemented as Application Specific Integrated Circuits (ASICs), thus they can not be modified after manufacture. Further, the update of an engine on the TPM leads to a loss of trust kept in the system before an update. Thus, in this contribution, we propose dedicated procedures for regaining the trust in the system after the RSA engine update utilizing the novel Sustainable Trusted Platform Module (STPM) architecture.
p53 enables metabolic fitness and self-renewal of nephron progenitor cells

Contrary to its classic role in restraining cell proliferation, we demonstrate here a divergent function of p53 in the maintenance of self-renewal of the nephron progenitor pool in the embryonic mouse kidney. Nephron endowment is regulated by progenitor availability and differentiation potential. Conditional deletion of p53 in nephron progenitor cells (Six2Cre+;p53fl/fl) induces progressive depletion of Cited1+/Six2+ self-renewing progenitors and loss of cap mesenchyme (CM) integrity. The Six2(p53-null) CM is disorganized, with interspersed stromal cells and an absence of a distinct CM-epithelia and CM-stroma interface. Impaired cell adhesion and epithelialization are indicated by decreased E-cadherin and NCAM expression and by ineffective differentiation in response to Wnt induction. The Six2Cre+;p53fl/fl cap has 30% fewer Six2(GFP+) cells. Apoptotic index is unchanged, whereas proliferation index is significantly reduced in accordance with cell cycle analysis showing disproportionately fewer Six2Cre+;p53fl/fl cells in the S and G2/M phases compared with Six2Cre+;p53+/+ cells. Mutant kidneys are hypoplastic with fewer generations of nascent nephrons. A significant increase in mean arterial pressure is observed in early adulthood in both germline and conditional Six2(p53-null) mice, linking p53-mediated defects in kidney development to hypertension. RNA-Seq analyses of FACS-isolated wild-type and Six2(GFP+) CM cells revealed that the top downregulated genes in Six2Cre+;p53fl/fl CM belong to glucose metabolism and adhesion and/or migration pathways. Mutant cells exhibit a ∼50% decrease in ATP levels and a 30% decrease in levels of reactive oxygen species, indicating energy metabolism dysfunction. In summary, our data indicate a novel role for p53 in enabling the metabolic fitness and self-renewal of nephron progenitors. Highlighted article: Although classically thought to restrain proliferation, p53 promotes self-renewal in nephron progenitors of the mouse kidney and also regulates their metabolic profile.
Expression of a lipocalin in prokaryote and eukaryote cells: quantification and structural characterization of recombinant bovine beta-lactoglobulin.

In this paper we quantify and characterize the expression of recombinant beta-lactoglobulin (rBLG) in prokaryote and eukaryote cells. In Escherichia coli we used the pET26 vector, which permits the secretion of rBLG in periplasm. We studied the expression of rBLG in COS-7 cells and in vivo in mouse tibialis muscle. The expression of rBLG was measured by two immunoassays specific, respectively, for BLG in its native and denatured conformation. We observed that rBLG was essentially expressed in a denatured form in E. coli even in the periplasm, whereas rBLG in eukaryote cells was found in its native conformation.
Online scheduling and pricing for electric vehicle charging

ABSTRACT We design strategy-proof online scheduling and pricing mechanisms for Electric Vehicle (EV) charging in a competitive environment. EV drivers submit their requests for charging services dynamically over time, and they can name their own price on the charging services. The mechanisms schedule EV charging and determine charging prices considering the incentives of both EV drivers and power providers. In addition, our proposed online mechanisms do not assume availability of information about future demand. Our charging mechanisms are preemption aware, allowing flexibility on when charging takes place. This is in alignment with power providers’ load-balancing goals. We perform extensive experiments to investigate the performance of our proposed mechanisms compared to that of the optimal offline mechanism. We analyze the various properties of our proposed mechanisms, in particular, we prove that they are strategy proof; that is, truthful reporting of price and amount of charging is a dominant strategy for self-interested EV drivers.
Lack of tissue glucocorticoid reactivation in 11β-hydroxysteroid dehydrogenase type 1 knockout mice ameliorates age-related learning impairments

11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) intracellularly regenerates active corticosterone from circulating inert 11-dehydrocorticosterone (11-DHC) in specific tissues. The hippocampus is a brain structure particularly vulnerable to glucocorticoid neurotoxicity with aging. In intact hippocampal cells in culture, 11β-HSD-1 acts as a functional 11β-reductase reactivating inert 11-DHC to corticosterone, thereby potentiating kainate neurotoxicity. We examined the functional significance of 11β-HSD-1 in the central nervous system by using knockout mice. Aged wild-type mice developed elevated plasma corticosterone levels that correlated with learning deficits in the watermaze. In contrast, despite elevated plasma corticosterone levels throughout life, this glucocorticoid-associated learning deficit was ameliorated in aged 11β-HSD-1 knockout mice, implicating lower intraneuronal corticosterone levels through lack of 11-DHC reactivation. Indeed, aged knockout mice showed significantly lower hippocampal tissue corticosterone levels than wild-type controls. These findings demonstrate that tissue corticosterone levels do not merely reflect plasma levels and appear to play a more important role in hippocampal functions than circulating blood levels. The data emphasize the crucial importance of local enzymes in determining intracellular glucocorticoid activity. Selective 11β-HSD-1 inhibitors may protect against hippocampal function decline with age.
Modelling of the State of Systems with Defensive Deception

Cyber deception is usually synonymous with nefarious activities led by attackers. Motivated attackers will stop at nothing to accomplish their mission and deception is amongst the tools they use. Cyber defenders have also begun using deception as an instrument to further enhance overall defensive strength. Deception has been leveraged to research attacker behaviors and their associated tactic techniques and procedures using custom built monitoring systems commonly referred to as honeypots. More recently several cyber defense deception models have been proposed to better understand the mechanisms involved with applying deception as a defensive instrument. This paper surveys three models of deception and formulates an abstract view of the deception process. Using this abstract view a state machine model has been developed to characterize the flow of events and high level changes that occur with the elements under scrutiny during a deception. This model provides an insight into how the state of the system hosting the deception changes based on implementing the deception and the actions of attackers.