Set Of Analogues Research Articles

MCCLESKEY ACCUSED Justice Powell and The Moral Price of Institutional Pride

<i>MCCLESKEY</i> ACCUSED Justice Powell and The Moral Price of Institutional Pride

Electronic Modeling for Resistive Textile Matrices

Textile pressure sensing has been proved to be useful for activity recognition in both wearable and ambient intelligence domains. The sensors are organized in a matrix format and their resistances are linked to the pressure asserted onto them. While there have been many works exploring its applications, the relationship between the resistance distribution and the numeric data output, has not been thoroughly studied. In this paper, we first demonstrate that there is not a simple, point-by-point mapping between the resistance distribution and the output voltage distribution, then build a generalized model to describe this relation, viz. to provide the answers to the forward and backward questions. The model’s correctness is verified using the data measured from a rheostats prototype board. We then demonstrate the model’s applications in helping 1) obtain the resistance distribution from the measured voltage matrix, 2) decide the proper analog settings to match the textile matrix, and 3) understand the effects of damages from the long-term usage. The methods and conclusions in this paper are also general for the other resistive textile matrices and could serve as a useful tool in both the design and application phases.

Synthesis and Assessment of the In Vitro and Ex Vivo Activity of Salicylate Synthase (Mbti) Inhibitors as New Candidates for the Treatment of Mycobacterial Infections.

Tuberculosis (TB) causes millions of deaths every year, ranking as one of the most dangerous infectious diseases worldwide. Because several pathogenic strains of M. tuberculosis (Mtb) have developed resistance against most of the established anti-TB drugs, new therapeutic options are urgently needed. An attractive target for the development of new anti-TB agents is the salicylate synthase MbtI, the first enzyme of the mycobacterial siderophore biochemical machinery, absent in human cells. In this work, a set of analogues of 5-(3-cyanophenyl)furan-2-carboxylic acid (I), the most potent MbtI inhibitor identified to date, was synthesized, characterized, and tested to further elucidate the structural requirements for achieving an efficient MbtI inhibition and potent antitubercular activity. The structure–activity relationships (SAR) discussed herein evidenced the importance of the side chain linked to the phenyl moiety to improve the in vitro antimycobacterial activity. In detail, 1f emerged as the most effective analogue against the pathogen, acting without cytotoxicity issues. To deepen the understanding of its mechanism of action, we established a fluorescence-based screening test to quantify the pathogen infectivity within host cells, using MPI-2 murine cells, a robust surrogate for alveolar macrophages. The set-up of the new assay demonstrates significant potential to accelerate the discovery of new anti-TB drugs.

Unravelling reservoir quality heterogeneity in mixed siliciclastic-carbonate deposits: An example from Miocene Red Sea rift, NW Saudi Arabia

The Miocene, syn-rift mixed siliciclastic-carbonate strata has been a long sought-after reservoir objective in the Red Sea rift basins. Despite being viable prospects, their depositional architecture, mechanisms of siliciclastics and carbonate mixing, and fundamental controls on their reservoir quality remained elusive and enigmatic. In this study, we used sedimentological, petrographical and outcrop permeametry measurements to investigate the stratigraphic record and reservoir quality of mixed siliciclastic-carbonate deposits. The latter are preserved at the transition between non-marine Al-Wajh Formation and marine carbonates of the Musayr Formation in one of the Red sea rift basins, NW Saudi Arabia. Three major facies associations were identified using detailed logging facies analysis, including siliciclastic-rich, mixed siliciclastic-carbonate and carbonate-rich facies association. These facies associations, represent a basinward transition from dominantly non-marine alluvial fans, braided streams and shallow-water delta into an open marine carbonate ramp. The permeability of siliciclastic facies is orders of magnitude higher (average permeability = 1884 md) than mixed siliciclastic-carbonate (average permeability = 109 md) and carbonate (average permeability = 46 md) facies. Likewise, siliciclastic facies have higher porosity (average porosity = 17%) compared to mixed (average porosity = 7%), and carbonate (average porosity = 15%) deposits. Petrographic analysis suggests that permeability and porosity variation within these facies is due to textural and diagenetic differences. Outcrop based permeability correlation separated the studied deposits into reservoir (excellent or good) and non-reservoir (baffles or barriers) elements. The relatively thick (5–10 m) and laterally continuous (hundreds of meters) siliciclastic deposits form excellent and good reservoir compared to usually thinner (1–2 m) mixed siliciclastic-carbonate and carbonate beds, which may act as baffles and barriers. This reservoir-seal configuration highlights the potential of stratigraphic trap formation in analogous settings in the subsurface, where non-marine siliciclastic deposits show lateral transition to marine carbonates.

RFID analysis of the complexity of cellular pathology workflow-An opportunity for digital pathology.

Digital pathology (DP) offers potential for time efficiency gains over an analog workflow however, to date, evidence supporting this claim is relatively lacking. Studies available concentrate on specific workflow points such as diagnostic reporting time, rather than overall efficiencies in slide logistics that might be expected. This is in part a result of the complexity and variation in analog working, and the challenge therefore in capturing this. We have utilized RFID technology to conduct a novel study capturing the movement of diagnostic cases within the analog pathway in a large teaching hospital setting, thus providing benchmark data for potential efficiency gains with DP. This technology overcomes the need to manually record data items and has facilitated the capture of both the physical journey of a case and the time associated with relevant components of the analog pathway predicted to be redundant in the digital setting. RFID tracking of 1,173 surgical pathology cases and over 30 staff in an analog cellular pathology workflow illustrates the complexity of the physical movement of slides within the department, which impacts on case traceability within the system. Detailed analysis of over 400 case journeys highlights redundant periods created by batching of slides at workflow points, including potentially 2–3 h for a case to become available for reporting after release from the lab, and variable lag-times prior to collection for reporting, and provides an illustration of patterns of lab and pathologist working within the analog setting. This study supports the challenge in evidencing efficiency gains to be anticipated with DP in the context of the variation and complexity of the analog pathway, but also evidences the efficiency gains that may be expected through a greater understanding of patterns of working and movement of cases. Such data may benefit other departments building a business case for DP.

God’s Goodness, Divine Purpose, and the Meaning of Life

The divine purpose theory (DPT)—according to which that human life is meaningful to the extent that it fulfills some purpose or plan to which God has directed us—encounters well-known Euthyphro problems. Some theists attempt to avoid these problems by appealing to God’s essential goodness, à la the modified divine command theory (DCT) of Adams and Alston. However, recent criticisms of the modified DCT show its conception of God’s goodness to be incoherent; and these criticisms can be shown to present an analogous set of problems for the DPT. Further, the argument can be extended to any account of meaningfulness according to which the value of what humans do can only be conferred by God. Thus, it would seem that there is no tenable version of the view that meaningfulness is conferred on human life by some act or attitude of God’s.

Hit-to-lead optimization of novel phenyl imidazole carboxamides that are active against Leishmania donovani

Visceral leishmaniasis is a potentially fatal disease caused by the parasitic protists, Leishmania donovani and L. infantum. Current treatments remain unsuitable due to cost, the need for hospitalization, variable efficacy against different species, toxicity and emerging resistance. Herein, we report the SAR exploration of the novel hit 4-Fluoro-N-(5-(4-methoxyphenyl)-1-methyl-1H-imidazole-2-yl)benzamide [1] previously identified from a high throughput screen against Trypanosoma brucei, Trypanosoma cruzi and Leishmania donovani. An extensive and informative set of analogues were synthesized incorporating key modifications around the scaffold resulting in improved potency, whilst the majority of compounds maintained low cytotoxicity against human THP-1 macrophages that are target cells for these pathogens. New lead compounds identified within this study also maintained desirable physicochemical properties, improved metabolic stability in vitro and displayed no significant mitotoxicity against HepG2 cell lines. This compound class warrants continued investigation towards development as a novel treatment for Visceral Leishmaniasis.

LARQS: An Analogical Reasoning Evaluation Dataset for Legal Word Embedding

Applying natural language processing-related algorithms is currently a popular project in legal applications, for instance, document classification of legal documents, contract review and machine translation. Using the above machine learning algorithms, all need to encode the words in the document in the form of vectors. The word embedding model is a modern distributed word representation approach and the most common unsupervised word encoding method. It facilitates subjecting other algorithms and subsequently performing the downstream tasks of natural language processing vis-à-vis. The most common and practical approach of accuracy evaluation with the word embedding model uses a benchmark set with linguistic rules or the relationship between words to perform analogy reasoning via algebraic calculation. This paper proposes establishing a 1,256 Legal Analogical Reasoning Questions Set (LARQS) from the 2,388 Chinese Codex corpus using five kinds of legal relations, which are then used to evaluate the accuracy of the Chinese word embedding model. Moreover, we discovered that legal relations might be ubiquitous in the word embedding model.

Potential and limitations of LiDAR altimetry in archaeological survey. Copper Age and Bronze Age settlements in southern Iberia

Potential and limitations of LiDAR altimetry in archaeological survey. Copper Age and Bronze Age settlements in southern Iberia

Forecasting Eruptions at Poorly Known Volcanoes Using Analogs and Multivariate Renewal Processes

AbstractForecasting future destructive eruptions from re‐awakening volcanoes remains a challenge, mainly due to a lack of previous event data. This sparks a search for similar volcanoes to provide additional information, especially those with better compiled and understood event records. However, we show that some of the most obviously geologically comparable volcanoes have differing statistical occurrence patterns. Using such matches produces large forecasting uncertainties. We created a statistical tool to identify and test the compatibility of potential analogue volcanoes based on repose‐time characteristics from world‐wide datasets. Selecting analogue volcanoes with compatible behavior for factors being forecast, such as repose time, significantly reduces forecasting uncertainties. Applying this tool to Tongariro volcano (NZ), there is a 5% probability for a Volcanic Explosivity Index (VEI) ≥ 3 explosive eruption in the next 50 years. Using pre‐historic geological records of a smaller available set of analogs, we forecast a 1% probability of a VEI ≥ 4 eruption in the next 50 years.

Anti-Proliferative and Cytoprotective Activity of Aryl Carbamate and Aryl Urea Derivatives with Alkyl Groups and Chlorine as Substituents.

Natural cytokinines are a promising group of cytoprotective and anti-tumor agents. In this research, we synthesized a set of aryl carbamate, pyridyl urea, and aryl urea cytokinine analogs with alkyl and chlorine substitutions and tested their antiproliferative activity in MDA-MB-231, A-375, and U-87 MG cell lines, and cytoprotective properties in H2O2 and CoCl2 models. Aryl carbamates with the oxamate moiety were selectively anti-proliferative for the cancer cell lines tested, while the aryl ureas were inactive. In the cytoprotection studies, the same aryl carbamates were able to counteract the CoCl2 cytotoxicity by 3–8%. The possible molecular targets of the aryl carbamates during the anti-proliferative action were the adenosine A2 receptor and CDK2. The obtained results are promising for the development of novel anti-cancer therapeutics.

“These People in This House”: Intermedial Approaches to Decentring the Domestic in Harold Pinter’s A Slight Ache and The Homecoming

This article explores the effects of moving two of Pinter’s earlier plays outside their original domestic settings by focusing on two productions staged in 2019: A Slight Ache (1958), directed by Jamie Lloyd for the “Pinter at the Pinter” season in London’s West End, and De Thuiskomst/ The Homecoming (1964), directed by Nanouk Leopold for Internationaal Theater Amsterdam (ITA). In relocating each play from its prescribed domestic interior, both productions explicitly drew on and incorporated the conventions of different media, specifically radio and film, in markedly different ways. Rather than transposing the country home of Pinter’s original radio play onto the stage in an analogous setting, Lloyd’s Slight Ache featured two performers appearing in a radio studio to voice their characters, thereby complicating the identities and motivations of the play’s characters by evoking a place of work, not a place of domestic retreat. In Leopold’s starkly minimalist Homecoming, video projections and visualizations of the human body as a kind of digital automaton replaced the trappings of domesticity, inviting audiences to focus instead on the live and mediatized bodies of the characters. Through their different means of representation, these productions demonstrate two different approaches to decentring domestic space in Pinter’s early plays via distinct intermedial strategies. In doing so, they offer a renewed focus on the embodied presence of the actors, thereby inviting new insights into how Pinter’s early characters can transcend the confines of their interior spaces on stage and underscoring the writer’s own inherently intermedial praxis.

Extreme points of Lorenz and ROC curves with applications to inequality analysis

We find the extreme points of the set of convex functions ℓ:[0,1]→[0,1] with a fixed area and ℓ(0)=0, ℓ(1)=1. This collection is formed by Lorenz curves with a given value of their Gini index. The analogous set of concave functions can be viewed as Receiver Operating Characteristic (ROC) curves. These functions are extensively used in economics (inequality and risk analysis) and machine learning (evaluation of the performance of binary classifiers). We also compute the maximal L1-distance between two Lorenz (or ROC) curves with specified Gini coefficients. This result allows us to introduce a bidimensional index to compare two of such curves, in a more informative and insightful manner than with the usual unidimensional measures considered in the literature (Gini index or area under the ROC curve). The analysis of real income microdata illustrates the practical use of this proposed index in statistical inference.

Integrating Homogeneous Current-Saturation Graphene Transistors Into High-Linearity Amplifiers

In this work, a new type of graphene ICs only comprising multiple graphene field-effect transistor (GFET) components is first reported. Based on the GFET design that enables homogeneous electrical characteristics in batch-made devices, the practicality and functionality significances of multi-GFET integration are experimentally demonstrated via high-fidelity amplifiers for baseband analog signals. Different from the quadratic relationship of the gate-controlled current output (in saturation region) in the traditional silicon-based MOSFETs, the saturation current output of GFETs relating to the gate-controls possesses high linearity. This advantage overcomes the inherent nonlinear distortion issues in the existing silicon MOSFET amplifiers and potentially provides a promising scenario for the accurate preamplification of weak analog signals. Besides, the novel circuit configuration and signaling principle may expand the developmental paradigm of analog amplifiers and set groundwork for the development and practicalization of advanced carbon-based nanoelectronic ICs.

Valorisation of the diterpene podocarpic acid – Antibiotic and antibiotic enhancing activities of polyamine conjugates

As part of our search for new antimicrobials and antibiotic adjuvants, a series of podocarpic acid-polyamine conjugates have been synthesized. The library of compounds made use of the phenolic and carboxylic acid moieties of the diterpene allowing attachment of polyamines (PA) of different lengths to afford a structurally-diverse set of analogues. Evaluation of the conjugates for intrinsic antimicrobial properties identified two derivatives of interest: a PA3-4–3 (spermine) amide-bonded variant 7a that was a non-cytotoxic, non-hemolytic potent growth inhibitor of Gram-positive Staphylococcus aureus (MRSA) and 9d, a PA3-8-3 carbamate derivative that was a non-toxic selective antifungal towards Cryptococcus neoformans. Of the compound set, only one example exhibited activity towards Gram-negative bacteria. However, in the presence of sub-therapeutic amounts of either doxycycline (4.5 µM) or erythromycin (2.7 μM) several analogues were observed to exhibit weak to modest antibiotic adjuvant properties against Pseudomonas aeruginosa and/or Escherichia coli. The observation of strong cytotoxicity and/or hemolytic properties for subsets of the library, in particular those analogues bearing methyl ester or n-pentylamide functionality, highlighted the fine balance of structural requirements and lipophilicity for antimicrobial activity as opposed to mammalian cell toxicity.

An Assessment of Geophysical Survey Techniques for Characterising the Subsurface Around Glacier Margins, and Recommendations for Future Applications

Geophysical surveys provide an efficient and non-invasive means of studying subsurface conditions in numerous sedimentary settings. In this study, we explore the application of three geophysical methods to a proglacial environment, namely ground penetrating radar (GPR), seismic refraction and multi-channel analysis of surface waves (MASW). We apply these geophysical methods to three glacial landforms with contrasting morphologies and sedimentary characteristics, and we use the various responses to assess the applicability and limitations of each method for these proglacial targets. Our analysis shows that GPR and seismic (refraction and MASW) techniques can provide spatially extensive information on the internal architecture and composition of moraines, but careful survey designs are required to optimise data quality in these geologically complex environments. Based on our findings, we define a number of recommendations and a potential workflow to guide future geophysical investigations in analogous settings. We recommend the initial use of GPR in future studies of proglacial environments to inform (a) seismic survey design and (b) the selection of seismic interpretation techniques. We show the benefits of using multiple GPR antenna frequencies (e.g., 25 and 100 MHz) to provide decimetre scale imaging in the near surface (e.g., &amp;lt; 15 m) while also enabling signal penetration to targets at up to ∼40 m depth (e.g., bedrock). This strategy helps to circumvent changes in radar signal penetration resulting from variations in substrate conductivity or abundant scatterers. Our study also demonstrates the importance of combining multiple geophysical methods together with ground-truthing through sedimentological observations to reduce ambiguity in interpretations. Implementing our recommendations will improve geophysical survey practice in the field of glacial geology and allow geophysical methods to play an increasing role in the interpretation of glacial landforms and sediments.

A Concise Synthesis of Triazole Analogues of Lavendustin A via Click Chemistry Approach and Preliminary Evaluation of Their Antiparasitic Activity Against Trypanosoma cruzi

AbstractLavendustin A is a natural product isolated from the actinobacteria Streptomyces griseolavendus that presents a potent inhibitory activity on the Epidermal Growth Factor Receptor Protein Tyrosine Kinase (EGFR PTK). In addition, some of its analogues have also shown potent inhibitory activity against the polymerization of tubulin to microtubules, a pivotal process for the cell mitosis. From strategic structural modifications, two useful unprecedented alkynes bearing lavendustin A pharmacophoric subunit were rapidly accessed. Next, a set of novel triazole analogues of lavendustin A were synthesized in good yields employing CuI‐catalyzed azide‐alkyne cycloadditions (CuAAC) under mild conditions. Furthermore, preliminary evaluation of their biological activity against the epimastigote stage of Trypanosoma cruzi points towards promising trypanocidal properties.

Somatostatin venom analogs evolved by fish-hunting cone snails: From prey capture behavior to identifying drug leads.

Somatostatin (SS) is a peptide hormone with diverse physiological roles. By investigating a deep-water clade of fish-hunting cone snails, we show that predator-prey evolution has generated a diverse set of SS analogs, each optimized to elicit specific systemic physiological effects in prey. The increased metabolic stability, distinct SS receptor activation profiles, and chemical diversity of the venom analogs make them suitable leads for therapeutic application, including pain, cancer, and endocrine disorders. Our findings not only establish the existence of SS-like peptides in animal venoms but also serve as a model for the synergy gained from combining molecular phylogenetics and behavioral observations to optimize the discovery of natural products with biomedical potential.

Surprise information in Major League Baseball: how teams and betting markets respond

ABSTRACT Studies of financial markets have shown markets inefficiently underreacting to surprise information, discounting it too heavily in the short term. This paper explores this phenomenon in a new but analogous setting: Major League Baseball. I analyze how surprise information – the deviation between a team’s realized win total and the preseason expectations of betting markets – is incorporated into the teams’ personnel investments and into betting markets. Using fixed effect panel regressions, I find that higher win totals are associated with increased investment in the following season (as measured by team payroll and investment in free agents) and that, conditional on win totals, underperforming (overperforming) expectations in the prior season is associated with more (less) investment. This is consistent with teams discounting some of the surprise information. The effect is more pronounced for teams near the threshold of a playoff appearance. I find that some discounting is rational since roughly 27% of the gap between realized performance and expected performance does not persist into the following season. I find no evidence that betting markets are inefficient in their incorporation of surprise information. However, estimates suggest that teams significantly underreact to surprise information, an inefficiency analogous to those observed in financial markets.

Synthesis, In Silico, and Biological Evaluation of a Borinic Tryptophan-Derivative That Induces Melatonin-like Amelioration of Cognitive Deficit in Male Rat

Preclinical and clinical evidence supports melatonin and its analogues as potential treatment for diseases involving cognitive deficit such as Alzheimer’s disease. In this work, we evaluated by in silico studies a set of boron-containing melatonin analogues on MT1 and MT2 receptors. Then, we synthesized a compound (borolatonin) identified as potent agonist. After chemical characterization, its evaluation in a rat model with cognitive deficit showed that it induced ameliorative effects such as those induced by equimolar administration of melatonin in behavioral tests and in neuronal immunohistochemistry assays. Our results suggest the observed effects are by means of action on the melatonin system. Further studies are required to clarify the mechanism(s) of action, as the beneficial effects on disturbed memory by gonadectomy in male rats are attractive.