Simple Structural Changes Research Articles

Górale and Farming – It Goes Hand in Hand. Agricultural Work as Part of Cultural Heritage in Podhale

Contrary to common associations linking Podhale with recreation and tourism, this region still retains its rural character. Rurality, thus, is a category inextricably connected with agriculture and largely shaped by work. That is why progressive changes in agriculture and general de-agrarianisation affect rural areas much more strongly than a simple change in occupational structure would suggest. The article concerns selected narratives and activities of Podhale farmers, showing agriculture as part of the cultural heritage of the countryside. Reffering to the specific agrarian structure, I argue that farmers in this regions use mountain conditions and the presence of the tourist business to undertake activities that go beyond economic aspects of work. The specific nature of agriculture makes it a space for realising individual ambitions that reach beyond earning a living and touch upon aspects of indentity. Even though the agricultural past is common to most inhabitants of Podhale, farmers, consciously referring to it, use techniques available only to them as specific continuators of highland farming methods.

Ultra-fast UPLC–MS/MS approach for estimating X-376 in human liver microsomes: Evaluation of metabolic stability via in silico software and in vitro analysis

X-376 is a novel anaplastic lymphoma kinase (ALK) inhibitor that is capable of penetrating the blood brain barrier. This makes it suitable for use in patients with ALK-positive non-small cell lung cancer (NSCLC) who have metastases in the central nervous system. This study developed a highly sensitive, fast, eco-friendly, and reliable UPLC-MS/MS approach to quantify X-376 in human liver microsomes (HLMs). This approach was used to evaluate X-376's metabolic stability in HLMs in vitro. The UPLC-MS/MS analytical technique validation followed US-FDA bio-analytical method validation guidelines. StarDrop software, containing P450 metabolic and DEREK modules, was utilized to scan X-376's chemical structure for metabolic lability and hazardous warnings. X-376 and Encorafenib (ENF as internal standard) were resoluted on the Eclipse Plus C18 column utilizing an isocratic mobile phase method. The X-376 calibration curve was linear from 1 to 3000 ng/mL. The precision and accuracy of this study's UPLC-MS/MS approach were tested for intra- and inter-day measurements. Inter-day accuracy was −1.32% to 9.36% while intra-day accuracy was −1.5% to 10.00%. The intrinsic clearance (Clint) and in vitro half-life (t1/2) of X-376 were 59.77 mL/min/kg and 13.56 min. The high extraction ratio of X-376 supports the 50 mg twice-daily dose for ALK-positive NSCLC and CNS metastases patients. In silico software suggests that simple structural changes to the piperazine ring or group substitution in drug design may improve metabolic stability and safety compared to X-376.

Adaptation of Agile Spotify Model at the Government Digital Service

Jabar Digital Service (JDS) took an innovative approach by smoothly integrating Spotify's agile model into the government's structure. This transformation went beyond simple structural changes. It completely reconfigured bureaucratic structures to match the agile culture required for effective digital service delivery. JDS proactively adapted its organizational structure by recruiting highly skilled professionals to meet the specific needs of the digital environment. In addition, the organization implemented the Agile at Scale and Heterogeneous Tailoring frameworks. These frameworks increased independence and promoted consistency in decision-making, enabling a fundamental change in the way JDS delivered projects and introducing collaborative groups such as squads, tribes and divisions. This integration required a complete restructuring of cultural standards, regulatory systems, risk mitigation procedures and thorough staff development. The process of communicating effectively with team stakeholders and achieving a balance between team autonomy and alignment in a changed organization was challenging. A variety of methods were used to support this research, including an in-depth exploration and observation of JDS, semi-structured interviews with relevant staff, a comprehensive case study approach using holistic single case design, and a detailed analysis of previous research, regulations and secondary data sources. The impact of this pioneering project was far-reaching. It facilitated the establishment of digital signatures to simplify bureaucratic procedures, the conversion of analogue forms into digital domains, and the digitalization of business activities. The development of JDS was an important milestone in the digital transformation process, as it facilitated collaboration between the community and the government on digital services. Significantly, this undertaking used Spotify's operational framework, adapting and customizing it to the specific needs and difficulties of JDS, which represents a notable advance in government digital integration

Makromolekulare Hydrazon Hauptkettenphotoschalter

AbstractHydrazone – bestehend aus einer dynamischen Iminbindung und einem sauren NH‐Proton – haben sich in letzter Zeit aufgrund ihrer Fähigkeit zur Bildung thermisch bistabiler (Z) bzw. (E) Isomere als vielseitige Potoschalter erwiesen. In diesem Artikel stellen wir zwei lichtsensitive Homopolymere vor, die strukturell unterschiedliche Hydrazone als sich wiederholende Einheiten in der Hauptkette enthalten und durch „Kopf‐Schwanz“‐Polymerisation mittels azyklischer Dien‐METathese (ADMET) synthetisiert wurden. Der Hauptunterschied der beiden Polymere liegt dabei im Design des Hydrazon‐Photoschalters, insbesondere in der Lage des aliphatischen Arms, der den Rotor mit dem aliphatischen Polymerrückgrat verbindet. Es zeigt sich, dass sich das hydrodynamische Volumen der Polymere in verdünnter Lösung während der Photoisomerisierung (λ=410 nm) in entgegengesetzter Weise ändert. Darüber hinaus zeigt sich nach der Photoisomerisierung eine Veränderung der Glasübergangs‐temperatur (Tg) um fast 10 °C bei beiden Polymeren, unabhängig vom Design des jeweiligen Hydrazon‐Monomers. Die hier vorgestellte Designstrategie erlaubt es, makromolekulare Eigenschaften durch Strukturänderungen photochemisch zu kontrollieren.

Main-chain Macromolecular Hydrazone Photoswitches.

Hydrazones-consisting of a dynamic imine bond and an acidic NH proton-have recently emerged as versatile photoswitches underpinned by their ability to form thermally bistable isomers, (Z) and (E), respectively. Herein, we introduce two photoresponsive homopolymers containing structurally different hydrazones as main-chain repeating units, synthesized via head-to-tail Acyclic Diene METathesis (ADMET) polymerization. Their key difference lies in the hydrazone design, specifically the location of the aliphatic arm connecting the rotor of the hydrazone photoswitch to the aliphatic polymer backbone. Critically, we demonstrate that their main photoresponsive property, i.e., their hydrodynamic volume, changes in opposite directions upon photoisomerization (λ=410 nm) in dilute solution. Further, the polymers-independent of the design of the individual hydrazone monomer-feature a photoswitchable glass transition temperature (Tg ) by close to 10 °C. The herein established design strategy allows to photochemically manipulate macromolecular properties by simple structural changes.

Gender and competitive performance: Closing gaps with smaller competitions

AbstractWe examine whether gender gaps in competitive performance are moderated by the size of the competition. We hypothesize that women underperform in large, relative to small, competitions and that smaller competitions close gender performance gaps by enhancing women's performance. Study 1 demonstrates this effect using behavioral data from real marathon competitions. Study 2 experimentally replicates the effect with real behavior. Study 3 provides further experimental support that gender performance gaps are exacerbated under competition and that, in these situations, small groups help bring women's performance up to par with men's. We conclude with a discussion about how making simple structural changes can reduce gender equity gaps in organizations.

Phishing URL Detection using Machine Learning

Abstract: Phishing attacks continue to pose a major threat for computer system defenders, often forming the first step in a multistage attack. There have been great strides made in phishing detection; however,some phishing emails appear to pass through filters by making simple structural and semantic changes to the messages. We tackle this problem through the use of a machine learning classifier operating on a large corpus of phishing and legitimate emails. We design a system to extract features, elevating some to higherlevel feature, that are meant to defeat common phishing email detection strategies. This paper presents an approach to detect phishing URLs in an efficient way based on URL features only. For detecting the phishing URLs SVM classifier is used. The performances are evaluated for different size of datasets using different number of features. The results are compared with other machine learning classification techniques. The proposed system is able to detect phishing websites using URL features only.

Experimental Study of the Impact of Notches Made in the Front Edge of Adherends on the Properties of Static and Fatigue Strength of Adhesive Joints

This paper presents the effect of simple structural changes consisting in making notches on the edge of adherends on the static and fatigue properties of adhesive joints. The study is based on the set of experimental static strength tests of the single lap shear adhesive joints. It has been shown that a slight increase in load capacity is possible by using adhesive-filled notches. However, this structural modification leads to an increase in the standard deviation of test results. Based on the fatigue strength tests done at the limit number of cycles equal to 2×106, it was shown that the use of notches on the front edge of adherends, which are filled with adhesive, can significantly increase the fatigue lifetime of the joint. The effect is shown in the area of low-cycle fatigue, where for fatigue stress with a maximum value of 11.5 MPa, an increase in the average value of fatigue lifetime by 481.5% was shown for joints with notches. On the basis of fractography analyses using SEM microscopy, it was shown that the positive effect of the notches is caused by the absorption of some energy by the adhesive filling the notches, due to the increased susceptibility of the adhesive in this area to elastic deformations.

Aging Effects on Optic Nerve Neurodegeneration.

Common risk factors for many ocular pathologies involve non-pathologic, age-related damage to the optic nerve. Understanding the mechanisms of age-related changes can facilitate targeted treatments for ocular pathologies that arise at any point in life. In this review, we examine these age-related, neurodegenerative changes in the optic nerve, contextualize these changes from the anatomic to the molecular level, and appreciate their relationship with ocular pathophysiology. From simple structural and mechanical changes at the optic nerve head (ONH), to epigenetic and biochemical alterations of tissue and the environment, multiple age-dependent mechanisms drive extracellular matrix (ECM) remodeling, retinal ganglion cell (RGC) loss, and lowered regenerative ability of respective axons. In conjunction, aging decreases the ability of myelin to preserve maximal conductivity, even with "successfully" regenerated axons. Glial cells, however, regeneratively overcompensate and result in a microenvironment that promotes RGC axonal death. Better elucidating optic nerve neurodegeneration remains of interest, specifically investigating human ECM, RGCs, axons, oligodendrocytes, and astrocytes; clarifying the exact processes of aged ocular connective tissue alterations and their ultrastructural impacts; and developing novel technologies and pharmacotherapies that target known genetic, biochemical, matrisome, and neuroinflammatory markers. Management models should account for age-related changes when addressing glaucoma, diabetic retinopathy, and other blinding diseases.

Construction of Aluminum‐Porphyrin‐Based Hypercrosslinked Ionic Polymers (HIPs) by Direct Knitting Approach for CO2 Capture and In‐Situ Conversion to Cyclic Carbonates

AbstractHypercrosslinked polymers (HCPs) constructed by Friedel‐Crafts reaction have drawn increasing attention in recent decades, but their multifunctionalization remains a huge challenge. Herein, a series of aluminum‐porphyrin‐based hypercrosslinked ionic polymers have been successfully synthesized by direct knitting approach without additional electrophilic comonomers, which involves the copolymerization of neutral porphyrin monomers and ionic building. By increasing the connected nodes numbers of ionic monomers, the introduction of abundant tetraphenylmethane fragements into the porphyrin backbones endows them with high‐density ionic active sites. Accordingly, the well‐matched molar ratios of aluminum sites to nucleophilic chloride anions that work synergistically for CO2/epoxide coupling can be achieved. Al‐HIP‐2 with flexible ionic pendants and a high Al/Cl ratio allows CO2 cycloaddition to be performed at ambient conditions or with diluted CO2; while Al‐HIP‐3 with rigid ionic moieties and a relatively low Al/Cl ratio exhibits higher specific surface area and stronger CO2 capture ability. Therefore, this co‐condensation strategy provides a simple and feasible pathway for adjusting the reactivity ratios of comonomers via simple structural changes in the knitting process, thus achieving the rational construction of multifunctionalized HCPs for CO2 capture and in‐situ conversion to cyclic carbonates.

Restricted rotation and tunable fluorescence in atropisomeric naphthyl pyridine chromophores.

Enhanced fluorescence quantum yields are enabled by simple reactions at the heterocyclic nitrogen in naphthyl-pyridine chromophores in which the electronic properties can be tuned through protonation, oxidation, and alkylation at the nitrogen center. Fluorescence quantum yield is increased by reacting the pyridine lone pair with either a proton or an alkyl group. Restricted intramolecular rotation (RIR) was observed upon alkylation, as evidenced by the presence of atropisomers. These simple structural changes allow application-driven tuning of electronic properties.

Detecting Phishing Website using Machine Learning

Phishing attacks continue to pose a major threat for computer system defenders, often forming the first step in a multi-stage attack. There have been great strides made in phishing detection; however, some phishing emails appear to pass through filters by making simple structural and semantic changes to the messages. We tackle this problem through the use of a machine learning classifier operating on a large corpus of phishing and legitimate emails. We design SAFEPC (Semi-Automated Feature generation for Phish Classification), a system to extract features, elevating some to higher level features, that are meant to defeat common phishing email detection strategies. To evaluate SAFE-PC, we collect a large corpus of phishing emails from the central IT organization at a tier-1 university. The execution of SAFE-PC on the dataset exposes hitherto unknown insights on phishing campaigns directed at university users. SAFEPC detects more than 70a state-of-the-art email filtering tool. It also outperforms Spam Assassin, a commonly used email filtering tool. We also developed an online version of SAFE-PC, that can be incrementally retrained with new samples. Its detection performance improves with time as new samples are collected, while the time to retrain the classifier stays constant.

Tuning the DNA binding properties of phenolic hemicyanine dyes for host-guest fluorescent aptasensor applications

Fluorescent dyes that bind specifically to DNA aptamers with turn-on emission serve as powerful tools for biosensor development. DNA three-way junctions (3WJs) consisting of a Y-shaped hydrophobic branch point connecting three double-stranded stems serve as recognition elements for DNA aptasensors for a wide variety of diagnostic applications. Herein, we highlight the tunability of phenolic hemicyanine dyes for host-guest fluorescent aptasensor applications using the cocaine-binding aptamer (MN4) as a representative 3WJ-aptamer substrate. The DNA aptamer MN4 exhibits ligand binding promiscuity and binds the alkaloid quinine with ∼26-fold greater affinity than its intended cocaine target. Combining the cationic N-methylbenzothiazolium (Btz) acceptor with a 2-fluoro-phenolic (FPhO) donor through a vinyl-linkage creates the FPhOBtz hemicyanine as a universal fluorescent turn-on probe for DNA 3WJs. The FPhOBtz dye binds MN4 with higher affinity than cocaine, but with weaker affinity than quinine. Consequently, FPhOBtz displacement from the 3WJ with turn-off fluorescence is effectively mediated by quinine, but not cocaine, resulting in poor detection of cocaine by the dye-displacement assay. Our current results demonstrate superior cocaine detection by replacing the planar cationic Btz group with the non-planar indolenium (Ind) acceptor to afford FPhOInd as the signaling fluorescent probe. This simple change in dye structure strongly diminishes MN4 binding affinity (19-fold) with cocaine now possessing stronger affinity for the 3WJ of MN4 compared to FPhOInd. Consequently, FPhOInd displacement from MN4 is effectively mediated by cocaine to provide a 13-fold improvement in cocaine detection in undiluted urine using the host-guest biosensing platform.

Electrocatalytic Energy Release of Norbornadiene-Based Molecular Solar Thermal Systems: Tuning the Electrochemical Stability by Molecular Design.

Molecular solar thermal (MOST) systems, such as the norbornadiene/quadricyclane (NBD/QC) couple, combine solar energy conversion, storage, and release in a simple one-photon one-molecule process. Triggering the energy release electrochemically enables high control of the process, high selectivity, and reversibility. In this work, the influence of the molecular design of the MOST couple on the electrochemically triggered back-conversion reaction was addressed for the first time. The MOST systems phenyl-ethyl ester-NBD/QC (NBD1/QC1) and p-methoxyphenyl-ethyl ester-NBD/QC (NBD2/QC2) were investigated by in-situ photoelectrochemical infrared spectroscopy, voltammetry, and density functional theory modelling. For QC1, partial decomposition (40 %) was observed upon back-conversion and along with a voltammetric peak at 0.6 Vfc , which was assigned primarily to decomposition. The back-conversion of QC2, however, occurred without detectable side products, and the corresponding peak at 0.45 Vfc was weaker by a factor of 10. It was concluded that the electrochemical stability of a NBD/QC couple is easy tunable by simple structural changes. Furthermore, the charge input and, therefore, the current for the electrochemically triggered energy release is very low, which ensures a high overall efficiency of the MOST system.

Controlling the fluorescence quantum yields of benzothiazole-difluoroborates by optimal substitution.

Precise tuning of the fluorescence quantum yield, vital for countless applications of fluorophores, remains exceptionally challenging due to numerous factors affecting energy dissipation phenomena often leading to its counterintuitive behavior. In contrast to the absorption and emission wavelength which can be precisely shifted to the desired range by simple structural changes, no general strategy exists for controllable modification of the fluorescence quantum yield. The rigidification of the molecular skeleton is known to usually enhance the emission and can be practically realized via the limiting molecular vibrations by aggregation. However, the subtle balance between the abundant possible radiative and non-radiative decay pathways makes the final picture exceptionally sophisticated. In the present study, a series of nine fluorophores obtained by peripheral substitution with two relatively mild electron donating and electron withdrawing groups are reported. The obtained fluorescence quantum yields range from dark to ultra-bright and the extreme values are obtained for the isomeric molecules. These severe changes in emission efficiency have been shown to arise from the complex relationship between the Franck-Condon excited state and conical intersection position. The experimental findings are rationalized by the advanced quantum chemical calculations delivering good correlation between the measured emission parameters and theoretical radiative and internal conversion rate constants. Therefore, the described substituent exchange provides a method to rigorously adjust the properties of molecular probes structurally similar to thioflavin T.

Targeted Delivery of mRNA with One-Component Ionizable Amphiphilic Janus Dendrimers.

Targeted and efficient delivery of nucleic acids with viral and synthetic vectors is the key step of genetic nanomedicine. The four-component lipid nanoparticle synthetic delivery systems consisting of ionizable lipids, phospholipids, cholesterol, and a PEG-conjugated lipid, assembled by microfluidic or T-tube technology, have been extraordinarily successful for delivery of mRNA to provide Covid-19 vaccines. Recently, we reported a one-component multifunctional sequence-defined ionizable amphiphilic Janus dendrimer (IAJD) synthetic delivery system for mRNA relying on amphiphilic Janus dendrimers and glycodendrimers developed in our laboratory. Amphiphilic Janus dendrimers consist of functional hydrophilic dendrons conjugated to hydrophobic dendrons. Co-assembly of IAJDs with mRNA into dendrimersome nanoparticles (DNPs) occurs by simple injection in acetate buffer, rather than by microfluidic devices, and provides a very efficient system for delivery of mRNA to lung. Here we report the replacement of most of the hydrophilic fragment of the dendron from IAJDs, maintaining only its ionizable amine, while changing its interconnecting group to the hydrophobic dendron from amide to ester. The resulting IAJDs demonstrated that protonated ionizable amines play dual roles of hydrophilic fragment and binding ligand for mRNA, changing delivery from lung to spleen and/or liver. Replacing the interconnecting ester with the amide switched the delivery back to lung. Delivery predominantly to liver is favored by pairs of odd and even alkyl groups in the hydrophobic dendron. This simple structural change transformed the targeted delivery of mRNA mediated with IAJDs, from lung to liver and spleen, and expands the utility of DNPs from therapeutics to vaccines.

Visible Light Mediated Photocatalytic N-Radical Cascade Reactivity of γ,δ-Unsaturated N-Arylsulfonylhydrazones: A General Approach to Structurally Diverse Tetrahydropyridazines.

Tetrahydropyridazines are of particular interest for their versatility as intermediates in organic synthesis and display pharmacological activity in several domains. Here, we describe the photocatalytic synthesis of different tetrahydropyridazines starting from γ,δ-unsaturated N-arylsulfonylhydrazones. Simple structural changes of substrates result into three different pathways beginning from a common N-hydrazonyl radical, which evolves through a domino carboamination/dearomatization, a HAT process, or a photoinduced radical Smiles rearrangement to afford diverse tetrahydropyridazines. All reactions are carried out in very mild conditions, and the quite inexpensive [Ru(bpy)3]Cl2 is used as the catalyst. Preliminary mechanism studies are presented, among them luminescence and electrochemical characterization of the involved species. Computational studies allow to rationalize the mechanism in accord with the experimental findings.

Single Metal Photodetectors Using Plasmonically-Active Asymmetric Gold Nanostructures

Plasmonic-based photodetectors are receiving increased attention because simple structural changes can make the photodetectors spectrally sensitive. In this study, asymmetric gold nanostructures are used as simple structures for photodetection via the photothermoelectric response. These single metal photodetectors use localized optical absorption from plasmon resonances of gold nanowires at desired wavelengths to generate temperature gradients. Combined with a geometry-dependent Seebeck coefficient, the result is a net electrical signal when the whole geometry is illuminated, with spectral sensitivity and polarization dependence from the plasmon resonances. We show experimental results and simulations of single-wavelength photodetectors at two wavelengths in the near IR range: 785 and 1060 nm. Based on simulation results and a model for the geometry-dependent Seebeck response, we demonstrate a photodetector structure that generates polarization-sensitive responses of opposite signs for the two wavelengths. The experimental photothermoelectric results are combined with simulations to infer the geometry dependence of the Seebeck response. These results can be used to increase the responsivity of these photodetectors further.

Egalitarian mixed-species bird groups enhance winter survival of subordinate group members but only in high-quality forests

Only dominant individuals have unrestricted access to contested resources in group-living animals. In birds, subordinates with restricted access to resources may respond to intragroup contests by acquiring extra body reserves to avoid periods of food shortage. In turn, higher body mass reduces agility and increases predation and mortality risk to subordinates. Birds often live in hierarchically organized mixed-species groups, in which heterospecific individuals are considered to substitute for conspecifics as protection against predators at a significantly reduced competition cost. Crested tits (Lophophanes cristatus) and willow tits (Poecile montanus) form mixed-species groups during the non-reproductive season that typically exhibit a nearly linear dominance hierarchy (‘despotic’ social structure) in which the highest ranking male willow tit is fourth in the overall hierarchy after the dominant male, female and subordinate juvenile crested tit, respectively. Much less frequently, ‘egalitarian’ dominance structures occur in which the adult willow tits rank second and the hierarchy is less steep, or linear. We present a rare long-term data set in which egalitarian flocks are common enough to assess the consequences of this simple change in hierarchy structure as well as a potential driver of the pattern. A comparison of individuals in the despotic mixed-species groups revealed a strong negative correlation between subcutaneous fat stores and dominance rank in the interspecific dominance hierarchy, whereas in egalitarian groups, subordinate willow tits had significantly lower fat reserves and they foraged in safer parts of the canopy than willow tits in despotic groups. Moreover, egalitarian groups exhibited markedly less within-group aggression, higher group cohesion and improved winter survival in both tit species. However, winter survival of birds in egalitarian groups was impaired relative to despotic groups in forests recently affected by industrial forestry. This suggests that the more egalitarian bird societies may best be adapted to less-disturbed environments.

Method for Calculating the Injection Effect to Create Air Circulation Inside Containers

The paper investigates the process of air circulation inside the container due to the effect of injection by an external stream. It is shown in the paper that injection can be created using the open hatch of the container, which is fixed at a certain angle. To calculate the emerging turbulent flow, a new effective mathematical model is used. The obtained numerical results of the hydrodynamic equations show that by a simple structural change in a simple container, air circulation inside the container can be significantly improved. This phenomenon gives a good perspective for the use of containers in the transportation of food.