Pivotal Features Research Articles

Ensembling of Efficient Deep Convolutional Networks and Machine Learning Algorithms for Resource Effective Detection of Tuberculosis Using Thoracic (Chest) Radiography

Tuberculosis (TB) is a communicable pulmonary disorder and countries with low and middle-income share a higher TB burden as compared to others. The year 2020–2021 universally saw a brutal pandemic in the form of COVID-19, that crushed various lives, health infrastructures, programs, and economies worldwide at an unprecedented speed. The gravity of this estimation gets intensified in systems with limited technological advancements. To assist in the identification of tuberculosis, we propose the ensembling of efficient deep convolutional networks and machine learning algorithms that do not entail heavy computational resources. In this paper, the three of the most efficient deep convolutional networks and machine learning algorithms are employed for resource-effective (low computational and basic Imaging requirements) detection of Tuberculosis. The pivotal features extracted from the deep networks are ensembled and subsequently, the machine learning algorithms are used to identify the images based on the extracted features. The said model underwent k-fold cross-validation and achieved an accuracy of 87.90% and 99.10% with an AUC of 0.94 and 1 respectively in identifying TB infected images from Normal and COVID infected images. Also, the model’s error rate, F-score, and youden’s index values of 0.0093, 0.9901, and 0.9812 for TB versus COVID identification along with the model’s accuracy claim that its use can be beneficial in identifying TB infections amid this COVID-19 pandemic, predominantly in countries with limited resources.

A novel solder joints inspection method using curvature and geometry features in high-density flexible IC substrates surface mount technology

The automatic optical inspection based defective diagnosis systems in the surface-mounted device is fairly important to the optimization of electronic manufacturing. The gist of this paper is that presents a novel inspection system for the distinction of defective solder joints on the high-density flexible IC substrates. Initially, an ultra-high precision 3D information acquirement system is elaborated. Then, several critical sub-regions are divided and pivotal features are extracted from them, in which the differential geometry based estimation scheme to obtain discrete curvatures directly and the crest line representation based shape characterization method are proposed. Finally, each type of the solder joints is described with different and ordered feature sequences, and the practical classification process is formulated as the pattern recognition and classification problem, which is also implemented by the set of predefined diagnosis rules of thumb and the introduced logical operations. By classifying seven categories of industrial solder joints and exhaustively comparing with other state-of-the-art methods, the performances of the proposed diagnosis system is validated. Experimental results verify the effectiveness and efficiency of the developed system from three aspects, i.e. inspection speed, total correct rate, and detectable types.

Melatonin hormone as a therapeutic weapon against neurodegenerative diseases.

Brain disorders such as Alzheimer's and Parkinson's disease (PD) are irreversible conditions with several cognitive problems, including learning disabilities, memory loss, movement abnormalities, and speech problems. These disorders are caused by a variety of factors, mainly due to the toxic pollutants-induced biochemical changes in protein production, uncontrolled neuronal electrical activity, and altered neurotransmitter levels. Oxidative stress and toxicity associated with the increased glutamate levels decreased acetylcholine levels, and brain inflammation is the main contributing factor. Melatonin hormone is considered one of the potent treatment approaches for neurodegenerative disorders. Melatonin is released from the pineal gland and has a critical role in brain function regulation. Membrane receptors, binding sites, and chemical interaction mediate hormonal actions having multiple phenotypic expressions. It acts as a neurodegenerative agent against some neurological disorders such as Alzheimer's disease (AD), PD, depression, and migraines. Melatonin inhibits neurotoxic pollutants-induced Tau protein hyperphosphorylation, especially in AD. Other pivotal features of melatonin are its anti-inflammatory properties, which decrease pro-inflammatory cytokines expression and factors such as IL-8, IL-6, and TNF. Melatonin also reduces NO (an inflammation factor). In this review, we have highlighted the protective effects of melatonin, mainly spotlighting its neuroprotective mechanisms that will be beneficial to assess their effects in environmental pollution-induced neurodegenerative pathology.

THE NATURE OF COMPETITION IN US-EUROPEAN RELATIONS AND ITS DETERMINANTS

Competition is among the pivotal features and it considered as one of he international interaction movement. Generally, relationships between all countries, such as relations between individuals, no matter how close and cooperative they face, are not without manifestations of competition and conflict that may take a peaceful structure, and even take the method of violence that sometimes reaches the degree of physical confrontation. Since the end of the Cold War, international competition has become an inevitable phenomenon that characterizes international relations due to the absence of an ideological counterfactual, and as a result of many of these forces owe the same ideology as the strongest powers on the international scene. It can be noticed that they are competing forces rather than conflicting forces. Characterized by the rules of management of international relationships between these most powerful features is competition feature , not the conflict. Accordingly, the phenomenon of international competition is an aspect of international dealings. In addition it is a dominant characteristic of most international transactions between several states, especially when it comes to the economic aspect, as the conflict of interests between states necessitates the supremacy of competition in international relations. The US-European relations are stated as other manifestations of interaction between countries and do not differ too much from other international relationships, as they have cases of competition despite the manifestations of cooperation and understanding between them in many life aspects towards various international issues, but the competition between them has its nature and specifics. This topic aims to identify the nature of competition in relations between the United States of America and the European Union countries in several vital regions of the world, most notably the Middle East and the African continent. Keywords: International Competition, International Relations, International Conflict, The Middle East.

Sustainable Synthesis of 2-Hydroxymethylbenzimidazoles using D-Fructose as a C2 Synthon.

D-fructose, a biomass-derived carbohydrate has been identified as an environmentally benign C2 synthon in the preparation of synthetically useful 2-hydroxymethylbenzimidazole derivatives by coupling with 1,2-phenylenediamines. Proof of concept was established by synthesizing 23 examples using BF3 .OEt2 (20 mol%), TBHP (5.5 M, decane) (1.0 equiv.) in CH3 CN at 90 °C for 1 h. The pivotal features of this method include metal-free conditions, short time, good functional group tolerance, gram scale feasibility and the synthesis of benzimidazole fused 1,4-oxazine. Control studies with conventional C2 synthons did not produce the desired product, thus suggesting a new reaction pathway from D-fructose.

Premorbid personality and cognitive function impact on schizophrenia

Individuals with schizophrenia can experience family and social adjustment difficulties as well as significant barriers to independent living, with cognitive difficulties being one of the pivotal features of this mental health disorder. This article examines a decade of data for a sample of individuals living with schizophrenia and argues that comprehensive assessment of personality and cognitive function in the initial stage of disease should inform management and treatment to enable improved patient life outcomes.

Criteria for Good Qualitative Research: A Comprehensive Review

This review aims to synthesize a published set of evaluative criteria for good qualitative research. The aim is to shed light on existing standards for assessing the rigor of qualitative research encompassing a range of epistemological and ontological standpoints. Using a systematic search strategy, published journal articles that deliberate criteria for rigorous research were identified. Then, references of relevant articles were surveyed to find noteworthy, distinct, and well-defined pointers to good qualitative research. This review presents an investigative assessment of the pivotal features in qualitative research that can permit the readers to pass judgment on its quality and to condemn it as good research when objectively and adequately utilized. Overall, this review underlines the crux of qualitative research and accentuates the necessity to evaluate such research by the very tenets of its being. It also offers some prospects and recommendations to improve the quality of qualitative research. Based on the findings of this review, it is concluded that quality criteria are the aftereffect of socio-institutional procedures and existing paradigmatic conducts. Owing to the paradigmatic diversity of qualitative research, a single and specific set of quality criteria is neither feasible nor anticipated. Since qualitative research is not a cohesive discipline, researchers need to educate and familiarize themselves with applicable norms and decisive factors to evaluate qualitative research from within its theoretical and methodological framework of origin.

‘Once I joined my motivations changed’: Exploring the initial and continuing motivations of police support volunteers in an English constabulary

Abstract Understanding and responding to motivations—both initial and continuing—are pivotal features of effectively involving volunteers within an organization, influencing satisfaction and ongoing commitment. This article explores the initial and continuing motivations of police support volunteers (PSVs)—citizens who give their time freely to perform tasks that complement the duties of police officers and staff. Drawing on survey and interview data with 160 PSVs in a large urban police service in England, the article considers motivations through three typologies—The Altruistic PSV, The Social PSV, and The Career PSV. It explores defining features of each typology and highlights the shifting nature of motivations as volunteer service progresses—most notably an increase in socially driven volunteers, and a fall in those seeking fulfilment of career goals. Implications for practice are considered, in particular investing in dedicated volunteer resources that recognize and respond to the heterogeneity of volunteer cohorts and fluidity of motivations.

Rapamycin Improves the Response of Effector and Memory CD8+ T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi.

Deficiency in memory formation and increased immunosenescence are pivotal features of Trypanosoma cruzi infection proposed to play a role in parasite persistence and disease development. The vaccination protocol that consists in a prime with plasmid DNA followed by the boost with a deficient recombinant human adenovirus type 5, both carrying the ASP2 gene of T. cruzi, is a powerful strategy to elicit effector memory CD8+ T-cells against this parasite. In virus infections, the inhibition of mTOR, a kinase involved in several biological processes, improves the response of memory CD8+ T-cells. Therefore, our aim was to assess the role of rapamycin, the pharmacological inhibitor of mTOR, in CD8+ T response against T. cruzi induced by heterologous prime-boost vaccine. For this purpose, C57BL/6 or A/Sn mice were immunized and daily treated with rapamycin for 34 days. CD8+ T-cells response was evaluated by immunophenotyping, intracellular staining, ELISpot assay and in vivo cytotoxicity. In comparison with vehicle-injection, rapamycin administration during immunization enhanced the frequency of ASP2-specific CD8+ T-cells and the percentage of the polyfunctional population, which degranulated (CD107a+) and secreted both interferon gamma (IFNγ) and tumor necrosis factor (TNF). The beneficial effects were long-lasting and could be detected 95 days after priming. Moreover, the effects were detected in mice immunized with ten-fold lower doses of plasmid/adenovirus. Additionally, the highly susceptible to T. cruzi infection A/Sn mice, when immunized with low vaccine doses, treated with rapamycin, and challenged with trypomastigote forms of the Y strain showed a survival rate of 100%, compared with 42% in vehicle-injected group. Trying to shed light on the biological mechanisms involved in these beneficial effects on CD8+ T-cells by mTOR inhibition after immunization, we showed that in vivo proliferation was higher after rapamycin treatment compared with vehicle-injected group. Taken together, our data provide a new approach to vaccine development against intracellular parasites, placing the mTOR inhibitor rapamycin as an adjuvant to improve effective CD8+ T-cell response.

Data-Driven and in Silico-Assisted Design of Broad Host-Range Minimal Intrinsic Terminators Adapted for Bacteria.

Efficient transcription termination relying on intrinsic terminators is critical to maintain cell fitness by avoiding unwanted read-through in bacteria. Natural intrinsic terminator (NIT) typically appears in mRNA as a hairpin followed by approximately eight conserved uridines (U-tract) at the 3' terminus. Owing to their simple structure, small size, and protein independence, assorted NITs have been redesigned as robust tools to construct gene circuits. However, most NITs exert functions to adapt to their physiological requirements rather than the demand for building synthetic gene circuits, rendering uncertain working performance when they are constructed intact in synthetic gene circuits. Here, rather than modifying NITs, we established a data-driven and in silico-assisted (DISA) design framework to forward engineer minimal intrinsic terminators (MITs). By comprehensively analyzing 75 natural intrinsic terminators from Bacillus subtilis, we revealed that two pivotal features, the length of the U-tract and the thermodynamics of the terminator hairpin, were involved in the sequence-activity relationship (SAR) of termination efficiency (TE). As per the SAR, we leveraged DISA to fabricate an array of MITs composed of in silico-assisted designed minimal hairpins and fixed U-tracts. Most of these MITs exhibited high TE in diverse Gram-positive and Gram-negative bacteria. In contrast, the TEs of the NITs were highly varied in different hosts. Moreover, TEs of MITs were flexibly tuned over a wide range by modulating the length of the U-tract. Overall, these results demonstrate an efficient framework to forward design functional and broad host-range terminators independent of tedious and iterative screening of mutagenesis libraries of natural terminators.

PCSK9 Induces Rat Smooth Muscle Cell Proliferation and Counteracts the Pleiotropic Effects of Simvastatin.

Human atherosclerotic plaque contains smooth muscle cells (SMCs) negative for the contractile phenotype (α-smooth muscle actin) but positive for proprotein convertase subtilisin/kexin type 9 (PCSK9). Thus, we generated rat SMCs which overexpressed human PCSK9 (SMCsPCSK9) with the aim of investigating the role of PCSK9 in the phenotype of SMCs. PCSK9 overexpression in SMCsPCSK9 led to a significant downregulation of the low-density lipoprotein receptor (Ldlr) as well as transgelin (Sm22α), a marker of the contractile phenotype. The cell proliferation rate of SMCsPCSK9 was significantly faster than that of the control SMCs (SMCspuro). Interestingly, overexpression of PCSK9 did not impact the migratory capacity of SMCs in response to 10% FCS, as determined by Boyden’s chamber assay. Expression and activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr) was significantly increased in the presence of PCSK9, both in SMCPCSK9 and after treatment with recombinant PCSK9. The transcriptional activity of sterol regulatory element-binding protein (SREBP) was also increased in the presence of PSCK9, suggesting a direct role of PCSK9 in the control of SRE-responsive genes, like HMGCR. We also observed that cholesterol biosynthesis is elevated in SMCPCSK9, potentially explaining the increased proliferation observed in these cells. Finally, concentration-dependent experiments with simvastatin demonstrated that SMCsPCSK9 were partially resistant to the antiproliferative and antimigratory effect of this drug. Taken together, these data further support a direct role of PCSK9 in proliferation, migration, and phenotypic changes in SMCs—pivotal features of atherosclerotic plaque development. We also provide new evidence on the role of PCSK9 in the pharmacological response to statins—gold standard lipid-lowering drugs with pleiotropic action.

A Data-Driven Approach for Online Inter-Area Oscillatory Stability Assessment of Power Systems Based on Random Bits Forest Considering Feature Redundancy

To utilize the rapidly refreshed operating data of power systems fully and effectively, an integrated scheme for inter-area oscillatory stability assessment (OSA) is proposed in this paper using a compositive feature selection unit and random bits forest (RBF) algorithm. This scheme consists of offline, update, and online stages, and it can provide fast and accurate estimation of the oscillatory stability margin (OSM) by using the real-time system operating data. In this scheme, a compositive feature selection unit is specially designed to realize efficient feature selection, which can significantly reduce the data dimensionality, effectively alleviate feature redundancy, and provide accurate correlation information to system operators. Then, the feature set consisting of the selected pivotal features is used for the RBF training to build the mapping relationships between the OSM and the system operating variables. Moreover, to enhance the robustness of the scheme in the face of variable operating conditions, an update stage is developed. The effectiveness of the integrated scheme is verified on the IEEE 39-bus system and a larger 1648-bus system. Tests of estimation accuracy, data processing speed, and the impact of missing data and noise data on this scheme are implemented. Comparisons with other methods reveal the superiority of the integrated scheme. In addition, the robustness of the scheme to variations in system topology, distribution among generators and loads, and peak and minimum load is studied.

Small-Conductance Ca2+-Activated K+ Channels 2 in the Hypothalamic Paraventricular Nucleus Precipitates Visceral Hypersensitivity Induced by Neonatal Colorectal Distension in Rats.

Visceral hypersensitivity is one of the pivotal pathophysiological features of visceral pain in irritable bowel syndrome (IBS). Small-conductance Ca2+-activated K+ channel (SK) is critical for a variety of functions in the central nervous system (CNS), nonetheless, whether it is involved in the pathogenesis of visceral hypersensitivity remain elusive. In this study, we examined mechanism of SK2 in hypothalamic paraventricular nucleus (PVN) in the pathogenesis of visceral hypersensitivity induced by neonatal colorectal distension (CRD). Rats undergoing neonatal CRD presented with visceral hypersensitivity as well as downregulated membrane SK2 channel and p-PKA. Intra-PVN administration of either the membrane protein transport inhibitor dynasore or the SK2 activator 1-EBIO upregulated the expression of membrane SK2 in PVN and mitigated visceral hypersensitivity. In addition, 1-EBIO administration reversed the increase in neuronal firing rates in PVN in rats undergoing neonatal CRD. On the contrary, intra-PVN administration of either the SK2 inhibitor apamin or PKA activator 8-Br-cAMP exacerbated the visceral hypersensitivity. Taken together, these findings demonstrated that visceral hypersensitivity is related to the downregulation of membrane SK2 in PVN, which may be attributed to the activation of PKA; pharmacologic activation of SK2 alleviated visceral hypersensitivity, which brings prospect of SK2 activators as a new intervention for visceral pain.

A theory of internationalisation practice in New Zealand and Indonesia: a rationality-relationality approach

ABSTRACT The article outlines the making of an explanatory theory for internationalisation of higher education (IoHE) in the emerging global knowledge economy. A grounded theory method with reference to a Theory of Practice is utilised to theorise IoHE in New Zealand. The pivotal features of IoHE are conceptualised as rationality and relationality, reflecting the global neoliberal agenda and national strategic priorities. The emergent theory is tested by investigating whether rationality and relationality are applicable for IoHE practices in the non-western context of Indonesia. The proposed theory results in a new definition for IoHE and revisits its role in the knowledge economy.

L’Italia fascista e la questione austriaca,1922-1938

Aim of this essay is to analyse the pivotal moments and features of Fascist Italy’s policy toward Austria from Mussolini’s conquest of power in 1922 to the destruction of the independent Austrian State in 1938. By using and comparing Italian and Austrian diplomatic documents and memories we tried to clarify some of the most controversial aspects of Italian-Austrian relations in the Twenties and in the Thirties: from the nature of the cooperation among the Heimwehren, the Christian-Social Party and the Fascist regime, to Mussolini’s attitude toward Habsburg political restoration and Austro-German union, as well as to the interdependence between the Fascist policy towards the German speaking people in Alto Adige-South Tyrol and the course of Italian-Austrian and Italian-German relations

ОСОБЛИВОСТІ ІНТЕРНЕТ-ПРОДАЖІВ В B2B-СЕКТОРІ

All successful people in B2B business have one thing in common they understand their competitive advantages and effectively use digital tools to support them. Still, also you will truly easily lose guests, if your website can’t separate you from the competition. The B2B business world is huge and easily different, but ultimate of the features of a B2Be-commerce or business operation platform are truly similar. To offer the perfect customer experience and make it easier for others to do business with you, you need commerce platform with features erected specifically for the B2B sedulity. To successfully meet the conditions of their online shoppers and succeed in their competitive requests, B2B merchandisers must equip their online stores with a number of pivotal B2B ecommerce features. Features are the base for a great B2B experience. With the rapid-fire growth of B2Be-commerce demand, businesses are getting more habituated to online shopping and are getting more demanding when it comes to B2B networks. Whether you run a B2B business, upgrade a website, scrap it, or have preliminarily used the B2Be-commerce platform, make sure you can support all the B2B capabilities that this composition provides. The future off-commerce in the B2B sector is clear B2Be-commerce is the main deals channel for digital commerce. Changes in paperback gets caused by the epidemic will drive further relinquishment beyond 2021. Forrester predicts that B2Be-commerce deals will exceed$1.8 trillion by 2023, counting for 17 of all B2B deals in the United States. Of course, dispatch and phone calls continue to be in the B2B business. Still, there’s no mistrustfulness about it-e-commerce is pushing the boundaries of what B2B deals can be. This is great news for B2B merchandisers because buyers change. Nearly 73 of millennials generations raised on technology-are now engaged in the B2B buying process. These new shoppers anticipate convenience and applicability further than their Baby Boomer and Gen X counterparts. Individualized deals doors, mobile bookings, stoked reality tenures, tone- service features-B2B platforms continue to pave the way for cost-effective and affordable deals openings. The rise of B2B ecommerce isn’t only an epidemic trend. Buyers and merchandisers are moving to digital commerce because it streamlines operations and increases effectiveness. And this trend will continue until 2021 and further. While numerous people suppose that a B2B ecommerce platform is just a tool for listing products and accepting payments, true is more. It acts as a command center where you control everything from deals to marketable operations, whether for B2B and noncommercial guests or the D2C website. The composition examines the introductory tools of Internet marketing in the field of B2B, which are effective in promoting products by artificial enterprises. It’s determined that B2B Internet deals have their own features and for direct connections with implicit mates you need to use an optimized point and web analytics. The paper presents an algorithm for establishing commerce between buyer and dealer, considers the main deals channels of the B2B terrain and describes the problems faced by entrepreneurs in the B2B request. Also in the work the factual deals channels of B2B products are substantiated, the algorithm of decision- making on the company’s access to the Internet terrain is given and the failings of B2B Internet deals are considered. The results of the exploration can be useful in, which operate in conditions of high variability of business terrain factors.

Recombinant Acid Ceramidase Reduces Inflammation and Infection in Cystic Fibrosis.

Rationale: In cystic fibrosis the major cause of morbidity and mortality is lung disease characterized by inflammation and infection. The influence of sphingolipid metabolism is poorly understood with a lack of studies using human airway model systems.Objectives: To investigate sphingolipid metabolism in cystic fibrosis and the effects of treatment with recombinant human acid ceramidase on inflammation and infection.Methods: Sphingolipids were measured using mass spectrometry in fully differentiated cultures of primary human airway epithelial cells and cocultures with Pseudomonas aeruginosa. In situ activity assays, Western blotting, and quantitative PCR were used to investigate function and expression of ceramidase and sphingomyelinase. Effects of treatment with recombinant human acid ceramidase on sphingolipid profile and inflammatory mediator production were assessed in cell cultures and murine models.Measurements and Main Results: Ceramide is increased in cystic fibrosis airway epithelium owing to differential function of enzymes regulating sphingolipid metabolism. Sphingosine, a metabolite of ceramide with antimicrobial properties, is not upregulated in response to P. aeruginosa by cystic fibrosis airway epithelia. Tumor necrosis factor receptor 1 is increased in cystic fibrosis epithelia and activates NF-κB signaling, generating inflammation. Treatment with recombinant human acid ceramidase, to decrease ceramide, reduced both inflammatory mediator production and susceptibility to infection.Conclusions: Sphingolipid metabolism is altered in airway epithelial cells cultured from people with cystic fibrosis. Treatment with recombinant acid ceramidase ameliorates the two pivotal features of cystic fibrosis lung disease, inflammation and infection, and thus represents a therapeutic approach worthy of further exploration.

Understanding when real world data can be used to replicate a clinical trial: A cross-sectional study of medications approved in 2011.

To determine how commonly pre-approval clinical trials could potentially be replicated using real-world data from insurance claims databases. We conducted a cross-sectional study of medications approved by the FDA in 2011. For each medication, we reviewed the drug's label and the details of the pivotal clinical trials supporting its approval. We assessed whether each clinical trial could be replicated using an insurance claims databases by determining whether the following pivotal trial features could be reliably captured in claims data: study outcome, inclusion criteria, exclusion criteria, and the presence of an appropriate active comparator. In 2011, 28 new medications were approved. The most common disease areas were oncology (N = 8, 29%), infectious disease (N = 5, 18%), and neurology (N = 4, 14%). The primary outcome of pre-approval clinical trials was identifiable in claims databases for six (21%) of the medications. Two (ticagrelor and linagliptin) had at least 80% of inclusion and exclusion criteria that could be identified in claims databases and had an available active comparator. The non-identifiable primary outcomes were related to patient-reported symptoms (N = 9, 32%), imaging findings (N = 5, 18%), laboratory values (N = 5, 18%), or other measurements (eg, blood pressure) not typically available in insurance claims databases (N = 4, 14%). Among drugs FDA-approved in 2011, two (7%) had a pre-approval trial that could be replicated using insurance claims databases. In such qualifying trials, replication using claims databases could be useful in assessing whether they provide concordant results.

Research on a Cognitive Distraction Recognition Model for Intelligent Driving Systems Based on Real Vehicle Experiments.

The accurate and prompt recognition of a driver’s cognitive distraction state is of great significance to intelligent driving systems (IDSs) and human-autonomous collaboration systems (HACSs). Once the driver’s distraction status has been accurately identified, the IDS or HACS can actively intervene or take control of the vehicle, thereby avoiding the safety hazards caused by distracted driving. However, few studies have considered the time–frequency characteristics of the driving behavior and vehicle status during distracted driving for the establishment of a recognition model. This study seeks to exploit a recognition model of cognitive distraction driving according to the time–frequency analysis of the characteristic parameters. Therefore, an on-road experiment was implemented to measure the relative parameters under both normal and distracted driving via a test vehicle equipped with multiple sensors. Wavelet packet analysis was used to extract the time–frequency characteristics, and 21 pivotal features were determined as the input of the training model. Finally, a bidirectional long short-term memory network (Bi-LSTM) combined with an attention mechanism (Atten-BiLSTM) was proposed and trained. The results indicate that, compared with the support vector machine (SVM) model and the long short-term memory network (LSTM) model, the proposed model achieved the highest recognition accuracy (90.64%) for cognitive distraction under the time window setting of 5 s. The determination of time–frequency characteristic parameters and the more accurate recognition of cognitive distraction driving achieved in this work provide a foundation for human-centered intelligent vehicles.

Discovery of sulfonyl hydrazone derivative as a new selective PDE4A and PDE4D inhibitor by lead-optimization approach on the prototype LASSBio-448: In vitro and in vivo preclinical studies

Phosphodiesterase 4 (PDE4) inhibitors have emerged as a new strategy to treat asthma and other lung inflammatory diseases. Searching for new PDE4 inhibitors, we previously reported the discover of LASSBio-448, a sulfonamide with potential to prevent and reverse pivotal pathological features of asthma. In this paper, two novel series of sulfonamide (6a-6m) and sulfonyl hydrazone (7a-7j) analogues of LASSBio-448 have been synthetized and evaluated for selective inhibitory activity toward cAMP-specific PDE4 isoforms. From these studies, we have identified 7j (LASSBio-1632) as a new anti-asthmatic lead-candidate associated with selective inhibition of PDE4A and PDE4D isoenzymes and blockade of airway hyper-reactivity (AHR) and TNF-α production in the lung tissue. In addition, it was able to relax guinea pig trachea on non-sensitized and sensitized animals and showed great TGI permeability.