Dynamics of a network mediated by IL-36 and involved in the pathogenesis of psoriasis.

The pathogenesis of the inflammatory, chronic, and common skin disease psoriasis involves immune cells, skin cells (keratinocytes), and the cytokines they secrete. Hyperproliferation and abnormal differentiation of keratinocytes are hallmarks of the disease. The roles of cytokines such as TNFα, IL-15, IL-17, and IL-23 in psoriasis have been studied through mathematical/computational models as well as experiments. However, the role of proinflammatory cytokine IL-36 in the onset and progression of psoriasis is still elusive. To explore the role of IL-36, we construct a network embodying indirect cell-cell interactions of a few immune and skin cells mediated by IL-36 based on existing knowledge. We also develop a mathematical model for the network and perform a global sensitivity analysis. Our results suggest that the model is most sensitive to a parameter that represents the level of cytokine IL-36. In addition, a steady-state analysis of the model suggests that an increase in the level of IL-36 could lead to the hyperproliferation of keratinocytes and, thus, psoriasis. Our analysis also highlights that the plaque formation and progression of psoriasis could occur through either a gradual or a switch-like increase in the keratinocyte population. We propose that the switch-like increase would be due to a bistable behavior of the network toward either a psoriatic or healthy state and could be used as a novel treatment strategy.

Preliminary study on cranial measurements and sexual dimorphism in skull bones of gaur (Bos gaurus gaurus, Smith 1827).

Cranial measurements have been widely used in various studies in wildlife sciences, ranging from understanding predator ecology to wildlife forensics. However, detailed description of morphometry and sexual dimorphism of the skull of gaur Bos gaurus gaurus is lacking. The present study was undertaken to determine the sexual dimorphism based on the cranial measurements of gaur. A total of 12 individual gaur skulls of male (n = 6) and female (n = 6) were studied in the field from the naturally deceased animals between January 2018 and December 2021 in different ranges of Bandhavgarh tiger reserve (BTR), Madhya Pradesh, India. The skull measurements were analysed using univariate and multivariate statistics to determine whether cranial dimensions could be used to differentiate male and female skulls reliably. A total of 43 morphometrical parameters grouped into nine indices were calculated. Select morphometrical parameters viz PL, GFL, AKI, LBB, LFB, GBEE, GBAN, BPOP and GTCH were significantly different (p < 0.05) between sexes, whereas GBAN were significantly higher in female skulls. The measurements demonstrated that the skull of the gaur was dolichocephalic as the profile length and the otion to otion breath in both male and female were <75% of the length. Overall, 28 linear measurements of both the sexes were statistically significant (p < 0.05; <0.01). The calculated indices revealed that the foramen magnum index in the female gaur were significantly higher. In calculated cranial indices the facial index (a) was higher in female and facial index (b) were higher in males. The two important parameters, facial breadth in facial index (a) and the greatest breadth in facial index (b) were positively correlated, though facial index (a) was statistically not significant between the sexes. The greater inner length of the foramen magnum in female skull resulted in foramen being oval whereas it was circular in males. These parameters were decisive for sexual dimorphism, skull comparison and craniological studies. This study ascertained that the frontal index and skull index had no significant influence and were not good indices for discriminating skulls between male and female. Based on the Principal Component Analysis, it was found that skull of male and female gaurs exhibits differences in cranial morphology viz. cranial profile length or total length (PL) and the least inner height of the temporal groove (LIHT). The findings of the present study provide baseline information on various craniometrical measurements of skull of gaur, indices and parameters for sex identification that can be effectively used in understanding sex biased predation ecology, provide base line information to describe variation across its geographic range, and in identifying skulls recovered in wildlife offence cases.

Phase-Specific Damage Tolerance of a Eutectic High Entropy Alloy.

Phase-specific damage tolerance was investigated for the AlCoCrFeNi2.1 high entropy alloy with a lamellar microstructure of L12 and B2 phases. A microcantilever bending technique was utilized with notches milled in each of the two phases as well as at the phase boundary. The L12 phase exhibited superior bending strength, strain hardening, and plastic deformation, while the B2 phase showed limited damage tolerance during bending due to micro-crack formation. The dimensionalized stiffness (DS) of the L12 phase cantilevers were relatively constant, indicating strain hardening followed by increase in stiffness at the later stages and, therefore, indicating plastic failure. In contrast, the B2 phase cantilevers showed a continuous drop in stiffness, indicating crack propagation. Distinct differences in micro-scale deformation mechanisms were reflected in post-compression fractography, with L12-phase cantilevers showing typical characteristics of ductile failure, including the activation of multiple slip planes, shear lips at the notch edge, and tearing inside the notch versus quasi-cleavage fracture with cleavage facets and a river pattern on the fracture surface for the B2-phase cantilevers.

Digital health for all: The turn to digitized healthcare in India.

In India, the use of digital technologies has become the key to the everyday operation of the welfare state in terms of accessing essential and life-sustaining entitlements. In this context, our article explores the genesis of India's digital turn in healthcare and maps the characteristics of a 'digital health for all' policy, based on empirical analysis of India's first digital-based universal health coverage programme - Rashtriya Swasthya Bima Yojana (RSBY) - with fieldwork material from the states of Jharkhand and Chhattisgarh. Being a smart-card-centred programme, RSBY marks the genesis of a digital approach to healthcare in India. The experiences of this scheme hold crucial implications for the digital healthcare landscape in India, as in the past its promoters pitched for its use to provide quality healthcare at lower cost. The technological design of the programme illustrates the construction and politics of a digitalized public-private welfare policy intended to meet the health needs of the poorest. By examining data on digital access to healthcare in the RSBY programme, as propounded and sustained by public health policies and a public-private model of governance, our article raises questions about the construction of new digital health policies and their contribution to private health markets. In doing so, it explores the key question of how digital technologies are transforming access to healthcare in India.

Multiscale hierarchical and heterogeneous mechanical response of additively manufactured novel Al alloy investigated by high-resolution nanoindentation mapping.

Smart alloying and microstructural engineering mitigate challenges associated with laser-powder bed fusion additive manufacturing (L-PBFAM). A novel Al-Ni-Ti-Zr alloy utilized grain refinement by heterogeneous nucleation and eutectic solidification to achieve superior performance-printability synergy. Conventional mechanical testing cannot delineate complex micromechanics of such alloys. This study combined multiscale nanomechanical and microstructural mapping to illustrate mechanical signatures associated with hierarchical heat distribution and rapid solidification of L-PBFAM. The disproportionate hardening effect imparted by Al3(Ti,Zr) precipitates in the pool boundaries and the semi-solid zone was successfully demonstrated. Nanomechanical response associated with heterogeneity in particle volume fraction and coherency across melt pool was interpreted from nanoindentation force-displacement curves. The hardness map effectively delineated the weakest and strongest sections in the pool with microscopic accuracy. The presented approach serves as a high throughput methodology to establish the chemistry-processing-microstructure-properties correlation of newly designed alloys for L-PBFAM.

Excellent ballistic impact resistance of Al0.3CoCrFeNi multi-principal element alloy with unique bimodal microstructure.

Multi-principal element alloys represent a new paradigm in structural alloy design with superior mechanical properties and promising ballistic performance. Here, the mechanical response of Al0.3CoCrFeNi alloy, with unique bimodal microstructure, was evaluated at quasistatic, dynamic, and ballistic strain rates. The microstructure after quasistatic deformation was dominated by highly deformed grains. High density of deformation bands was observed at dynamic strain rates but there was no indication of adiabatic shear bands, cracks, or twinning. The ballistic response was evaluated by impacting a 12 mm thick plate with 6.35 mm WC projectiles at velocities ranging from 1066 to 1465 m/s. The deformed microstructure after ballistic impact was dominated by adiabatic shear bands, shear band induced cracks, microbands, and dynamic recrystallization. The superior ballistic response of this alloy compared with similar AlxCoCrFeNi alloys was attributed to its bimodal microstructure, nano-scale L12 precipitation, and grain boundary B2 precipitates. Deformation mechanisms at quasistatic and dynamic strain rates were primarily characterized by extensive dislocation slip and low density of stacking faults. Deformation mechanisms at ballistic strain rates were characterized by grain rotation, disordering of the L12 phase, and high density of stacking faults.

High-throughput Analysis of Synaptic Activity in Electrically Stimulated Neuronal Cultures.

Synaptic dysfunction is a hallmark of various neurodegenerative and neurodevelopmental disorders. To interrogate synapse function in a systematic manner, we have established an automated high-throughput imaging pipeline based on fluorescence microscopy acquisition and image analysis of electrically stimulated synaptic transmission in neuronal cultures. Identification and measurement of synaptic signal fluctuations is achieved by means of an image analysis algorithm based on singular value decomposition. By exploiting the synchronicity of the evoked responses, the algorithm allows disentangling distinct temporally correlated patterns of firing synapse populations or cell types that are present in the same recording. We demonstrate the performance of the analysis with a pilot compound screen and show that the multiparametric readout allows classifying treatments by their spatiotemporal fingerprint. The image analysis and visualization software has been made publicly available on Github ( https://www.github.com/S3Toolbox ). The streamlined automation of multi-well image acquisition, electrical stimulation, analysis, and meta-data warehousing facilitates large-scale synapse-oriented screens and, in doing so, it will accelerate the drug discovery process.

Co-introduction of precipitate hardening and TRIP in a TWIP high-entropy alloy using friction stir alloying.

Tuning deformation mechanisms is imperative to overcome the well-known strength-ductility paradigm. Twinning-induced plasticity (TWIP), transformation-induced plasticity (TRIP) and precipitate hardening have been investigated separately and have been altered to achieve exceptional strength or ductility in several alloy systems. In this study, we use a novel solid-state alloying method-friction stir alloying (FSA)-to tune the microstructure, and a composition of a TWIP high-entropy alloy by adding Ti, and thus activating site-specific deformation mechanisms that occur concomitantly in a single alloy. During the FSA process, grains of the as-cast face-centered cubic matrix were refined by high-temperature severe plastic deformation and, subsequently, a new alloy composition was obtained by dissolving Ti into the matrix. After annealing the FSA specimen at 900 °C, hard Ni-Ti rich precipitates formed to strengthen the alloy. An additional result was a Ni-depleted region in the vicinity of newly-formed precipitates. The reduction in Ni locally reduced the stacking fault energy, thus inducing TRIP-based deformation while the remaining matrix still deformed as a result of TWIP. Our current approach presents a novel microstructural architecture to design alloys, an approach that combines and optimizes local compositions such that multiple deformation mechanisms can be activated to enhance engineering properties.

Role of subnetworks mediated by [Formula: see text], IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis.

Psoriasis is a chronic inflammatory skin disease clinically characterized by the appearance of red colored, well-demarcated plaques with thickened skin and with silvery scales. Recent studies have established the involvement of a complex signalling network of interactions between cytokines, immune cells and skin cells called keratinocytes. Keratinocytes form the cells of the outermost layer of the skin (epidermis). Visible plaques in psoriasis are developed due to the fast proliferation and unusual differentiation of keratinocyte cells. Despite that, the exact mechanism of the appearance of these plaques in the cytokine-immune cell network is not clear. A mathematical model embodying interactions between key immune cells believed to be involved in psoriasis, keratinocytes and relevant cytokines has been developed. The complex network formed of these interactions poses several challenges. Here, we choose to study subnetworks of this complex network and initially focus on interactions involving [Formula: see text], IL-23/IL-17, and IL-15. These are chosen based on known evidence of their therapeutic efficacy. In addition, we explore the role of IL-15 in the pathogenesis of psoriasis and its potential as a future drug target for a novel treatment option. We perform steady state analyses for these subnetworks and demonstrate that the interactions between cells, driven by cytokines could cause the emergence of a psoriasis state (hyper-proliferation of keratinocytes) when levels of [Formula: see text], IL-23/IL-17 or IL-15 are increased. The model results explain and support the clinical potentiality of anti-cytokine treatments. Interestingly, our results suggest different dynamic scenarios underpin the pathogenesis of psoriasis, depending upon the dominant cytokines of subnetworks. We observed that the increase in the level of IL-23/IL-17 and IL-15 could lead to psoriasis via a bistable route, whereas an increase in the level of [Formula: see text] would lead to a monotonic and gradual disease progression. Further, we demonstrate how this insight, bistability, could be exploited to improve the current therapies and develop novel treatment strategies for psoriasis.

Dynamic Shear Deformation of a Precipitation Hardened Al0.7CoCrFeNi Eutectic High-Entropy Alloy Using Hat-Shaped Specimen Geometry.

Lamellar eutectic structure in Al0.7CoCrFeNi high-entropy alloy (HEA) is emerging as a promising candidate for structural applications because of its high strength-ductility combination. The alloy consists of a fine-scale lamellar fcc + B2 microstructure with high flow stresses > 1300 MPa under quasi-static tensile deformation and >10% ductility. The response to shear loading was not investigated so far. This is the first report on the shear deformation of a eutectic structured HEA and effect of precipitation on shear deformation. A split-Hopkinson pressure bar (SHPB) was used to compress the hat-shaped specimens to study the local dynamic shear response of the alloy. The change in the width of shear bands with respect to precipitation and deformation rates was studied. The precipitation of L12 phase did not delay the formation of adiabatic shear bands (ASB) or affect the ASB width significantly, however, the deformed region around ASB, consisting of high density of twins in fcc phase, was reduced from 80 µm to 20 µm in the stronger precipitation strengthened condition. We observe dynamic recrystallization of grains within ASBs and local mechanical response of individual eutectic lamellae before and after shear deformation and within the shear bands was examined using nano-indentation.

Consensus-Based Odor Source Localization by Multiagent Systems Under Resource Constraints.

With advancements in mobile robot olfaction, networked multiagent systems (MASs) are used in odor source localization (OSL). These MASs are often equipped with small microprocessors that have limited computing capabilities, and they usually operate in a bandwidth and energy-constrained environment. The exigent need for a faster localizing algorithm under communication and computational resource constraints invites many design challenges. In this paper, we have designed a two-level hierarchical cooperative control strategy for heterogeneous nonlinear MASs for OSL. The agents are forced toward consensus expeditiously once the information on the whereabouts of the source is attained. The synthesis of the controller occurs in a hierarchical manner-obtaining a group decision, followed by resource-efficient robust control. Odor concentration and wind information have been used in a group decision-making layer to predict a probable location of the source as a tracking reference. This reference is then fed to the control layer that is synthesized using event-triggered sliding-mode control (SMC). The advantage of using event-triggered control scheduling in conjunction with the SMC is rooted in retaining the robustness of the SMC while lowering the resource utilization burden. Numerical simulations confirm the efficiency of the scheme put forth.

On the evolving nature of c/a ratio in a hexagonal close-packed epsilon martensite phase in transformative high entropy alloys.

Activation of different slip systems in hexagonal close packed (h.c.p.) metals depends primarily on the c/a ratio, which is an intrinsic property that can be altered through alloying addition. In conventional h.c.p. alloys where there is no diffusion-less phase transformation and associated transformation volume change with deformation, the c/a ratio remains constant during deformation. In the present study, c/a ratio and transformation volume change of h.c.p. epsilon martensite phase in transformative high entropy alloys (HEAs) were quantified as functions of alloy chemistry, friction stir processing and tensile deformation. The study revealed that while intrinsic c/a is dependent on alloying elements, c/a of epsilon in transformative HEAs changes with processing and deformation. This is attributed to transformation volume change induced dependence of h.c.p. lattice parameters on microstructure and stress state. Lower than ideal c/a ratio promotes non-basal pyramidal 〈c + a〉 slip and deformation twinning in epsilon phase of transformative HEAs. Also, a unique twin-bridging mechanism was observed, which provided experimental evidence supporting existing theoretical predictions; i.e., geometrical factors combined with grain orientation, c/a ratio and plastic deformation can result in characteristic twin boundary inclination at 45-50°.

A novel nano-particle strengthened titanium alloy with exceptional specific strength.

Various ecological and economical concerns have spurred mankind's quest for materials that can provide enhanced weight savings and improved fuel efficiency. As part of this pursuit, we have microstructurally tailored an exceptionally high-strength titanium alloy, Ti-6Al-2Sn-4Zr-6Mo (Ti6246) through friction stir processing (FSP). FSP has altered the as-received bimodal microstructure into a unique modulated microstructure comprised of fine acicular α″-laths with nano precipitates within the laths. The sequence of phase transformations responsible for the modulated microstructure and consequently for the strength is discussed with the help of scanning electron microscopy, transmission electron microscopy, and synchrotron X-ray diffraction studies. The specific strength attained in one of the conditions is close to 450 MPa m3/mg, which is about 22% to 85% greater than any commercially available metallic material. Therefore, our novel nano particle strengthened Ti alloy is a potential replacement for many structural alloys, enabling significant weight reduction opportunities.

Influence of ordered L12 precipitation on strain-rate dependent mechanical behavior in a eutectic high entropy alloy.

Recent studies indicate that eutectic high-entropy alloys can simultaneously possess high strength and high ductility, which have potential industrial applications. The present study focuses on Al0.7CoCrFeNi, a lamellar dual-phase (fcc + B2) precipitation-strengthenable eutectic high entropy alloy. This alloy exhibits an fcc + B2 (B2 with bcc nano-precipitates) microstructure resulting in a combination of the soft and ductile fcc phase together with hard B2 phase. Low temperature annealing leads to the precipitation of ordered L12 intermetallic precipitates within the fcc resulting in enhanced strength. The strengthening contribution due to fine scale L12 is modeled using Orowan dislocation bowing and by-pass mechanism. The alloy was tested under quasi-static (strain-rate = 10-3 s-1) tensile loading and dynamic (strain-rate = 103 s-1) compressive loading. Due to the fine lamellar microstructure with a large number of fcc-bcc interfaces, the alloy show relatively high flow-stresses, ~1400 MPa under quasi-static loading and in excess of 1800 MPa under dynamic loading. Interestingly, the coherent nano-scale L12 precipitate caused a significant rise in the yield strength, without affecting the strain rate sensitivity (SRS) significantly. These lamellar structures had higher work hardening due to their capability for easily storing higher dislocation densities. The back-stresses from the coherent L12 precipitate were insufficient to cause improvement in twin nucleation, owing to elevated twinning stress under quasi-static testing. However, under dynamic testing high density of twins were observed.

Small-Scale Plastic Deformation of Nanocrystalline High Entropy Alloy.

High entropy alloys (HEAs) have attracted widespread interest due to their unique properties at many different length-scales. Here, we report the fabrication of nanocrystalline (NC) Al0.1CoCrFeNi high entropy alloy and subsequent small-scale plastic deformation behavior via nano-pillar compression tests. Exceptional strength was realized for the NC HEA compared to pure Ni of similar grain sizes. Grain boundary mediated deformation mechanisms led to high strain rate sensitivity of flow stress in the nanocrystalline HEA.

Mechanical Properties of High Entropy Alloy Al0.1CoCrFeNi for Peripheral Vascular Stent Application.

High entropy alloys (HEAs) are new class of metallic materials with five or more principal alloying elements. Due to this distinct concept of alloying, the HEAs exhibit unique properties compared to conventional alloys. The outstanding properties of HEAs include increased strength, superior wear resistance, high temperature stability, increased fatigue properties, good corrosion, and oxidation resistance. Such characteristics of HEAs have generated significant interest among the scientific community. However, their applications are yet to be explored. This paper discusses the mechanical behavior and microstructure of Al0.1CoCrFeNi HEA subjected to thermo-mechanical processing, and its potential application in peripheral vascular stent implants that are prone to high failure rates. Results show that Al0.1CoCrFeNi alloy possesses characteristics that compare well against currently used stent materials and it can potentially find use in peripheral vascular stent implants and extend their life-cycle.

Symmetric spike timing-dependent plasticity at CA3-CA3 synapses optimizes storage and recall in autoassociative networks.

CA3-CA3 recurrent excitatory synapses are thought to play a key role in memory storage and pattern completion. Whether the plasticity properties of these synapses are consistent with their proposed network functions remains unclear. Here, we examine the properties of spike timing-dependent plasticity (STDP) at CA3-CA3 synapses. Low-frequency pairing of excitatory postsynaptic potentials (EPSPs) and action potentials (APs) induces long-term potentiation (LTP), independent of temporal order. The STDP curve is symmetric and broad (half-width ∼150 ms). Consistent with these STDP induction properties, AP-EPSP sequences lead to supralinear summation of spine [Ca(2+)] transients. Furthermore, afterdepolarizations (ADPs) following APs efficiently propagate into dendrites of CA3 pyramidal neurons, and EPSPs summate with dendritic ADPs. In autoassociative network models, storage and recall are more robust with symmetric than with asymmetric STDP rules. Thus, a specialized STDP induction rule allows reliable storage and recall of information in the hippocampal CA3 network.

Cytological diagnosis of microfilariae in filariasis endemic areas of eastern Uttar Pradesh.

BACKGROUND: Filariasis is a major health problem in tropical countries including India. Fine needle aspiration cytology plays an important role in prompt recognition of disease. AIM: To assess the role of fine needle aspiration cytology (FNAC) in diagnosis of filariasis at all possible sites. MATERIALS AND METHODS: Total 250 cases of superficial swellings at various sites were subjected to fine needle aspiration cytology. RESULTS: Out of 250 cases, 24 cases of filariasis were detected which include breast lumps (8 cases), lymph nodes (6 cases), scrotal swellings (4 cases), thyroid swellings (3 cases), soft tissue swellings (2 cases) and ascitic fluid (1 case). Eosinophilia was present in 8 out of 24 cases with a percentage ranging from 12-24%. Significant adherence of inflammatory cells and macrophages to microfilariae was present in 3 out of 24 cases. CONCLUSIONS: In endemic areas, it should be considered one of the differential diagnoses of a superficial swelling. Careful screening of FNAC smears help in detecting microfilaria even in asymptomatic patients and thus plays a significant role in recognition of the disease and institution of specific treatment.