Emergent interface vibrational structure of oxide superlattices.

As the length scales of materials decrease, the heterogeneities associated with interfaces become almost as important as the surrounding materials. This has led to extensive studies of emergent electronic and magnetic interface properties in superlattices1-9. However, the interfacial vibrations that affect the phonon-mediated properties, such as thermal conductivity10,11, are measured using macroscopic techniques that lack spatial resolution. Although it is accepted that intrinsic phonons change near boundaries12,13, the physical mechanisms and length scales through which interfacial effects influence materials remain unclear. Here we demonstrate the localized vibrational response of interfaces in strontium titanate-calcium titanate superlattices by combining advanced scanning transmission electron microscopy imaging and spectroscopy, density functional theory calculations and ultrafast optical spectroscopy. Structurally diffuse interfaces that bridge the bounding materials are observed and this local structure creates phonon modes that determine the global response of the superlattice once the spacing of the interfaces approaches the phonon spatial extent. Our results provide direct visualization of the progression of the local atomic structure and interface vibrations as they come to determine the vibrational response of an entire superlattice. Direct observation of such local atomic and vibrational phenomena demonstrates that their spatial extent needs to be quantified to understand macroscopic behaviour. Tailoring interfaces, and knowing their local vibrational response, provides a means of pursuing designer solids with emergent infrared and thermal responses.

Subterahertz collective dynamics of polar vortices.

The collective dynamics of topological structures1-6 are of interest from both fundamental and applied perspectives. For example, studies of dynamical properties of magnetic vortices and skyrmions3,4 have not only deepened our understanding of many-body physics but also offered potential applications in data processing and storage7. Topological structures constructed from electrical polarization, rather than electron spin, have recently been realized in ferroelectric superlattices5,6, and these are promising for ultrafast electric-field control of topological orders. However, little is known about the dynamics underlying the functionality of such complex extended nanostructures. Here, using terahertz-field excitation and femtosecond X-ray diffraction measurements, we observe ultrafast collective polarization dynamics that are unique to polar vortices, with orders-of-magnitude higher frequencies and smaller lateral size than those of experimentally realized magnetic vortices3. A previously unseen tunable mode, hereafter referred to as a vortexon, emerges in the form of transient arrays of nanoscale circular patterns of atomic displacements, which reverse their vorticity on picosecond timescales. Its frequency is considerably reduced (softened) at a critical strain, indicating a condensation (freezing) of structural dynamics. We use first-principles-based atomistic calculations and phase-field modelling to reveal the microscopic atomic arrangements and corroborate the frequencies of the vortex modes. The discovery of subterahertz collective dynamics in polar vortices opens opportunities for electric-field-driven data processing in topological structures with ultrahigh speed and density.

Enhanced ferroelectricity in ultrathin films grown directly on silicon.

Ultrathin ferroelectric materials could potentially enable low-power perovskite ferroelectric tetragonality logic and nonvolatile memories1,2. As ferroelectric materials are made thinner, however, the ferroelectricity is usually suppressed. Size effects in ferroelectrics have been thoroughly investigated in perovskite oxides-the archetypal ferroelectric system3. Perovskites, however, have so far proved unsuitable for thickness scaling and integration with modern semiconductor processes4. Here we report ferroelectricity in ultrathin doped hafnium oxide (HfO2), a fluorite-structure oxide grown by atomic layer deposition on silicon. We demonstrate the persistence of inversion symmetry breaking and spontaneous, switchable polarization down to a thickness of one nanometre. Our results indicate not only the absence of a ferroelectric critical thickness but also enhanced polar distortions as film thickness is reduced, unlike in perovskite ferroelectrics. This approach to enhancing ferroelectricity in ultrathin layers could provide a route towards polarization-driven memories and ferroelectric-based advanced transistors. This work shifts the search for the fundamental limits of ferroelectricity to simpler transition-metal oxide systems-that is, from perovskite-derived complex oxides to fluorite-structure binary oxides-in which 'reverse' size effects counterintuitively stabilize polar symmetry in the ultrathin regime.

Publisher Correction: Enhanced ferroelectricity in ultrathin films grown directly on silicon.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

N-acetyl cysteine turns EPAC activators into potent killers of acute lymphoblastic leukemia cells.

Today, the majority of patients with pediatric B cell precursor acute lymphoblastic leukemia (BCP-ALL, hereafter ALL) survive their disease, but many of the survivors suffer from life-limiting late effects of the treatment. ALL develops in the bone marrow, where the cells are exposed to cAMP-generating prostaglandin E2. We have previously identified the cAMP signaling pathway as a putative target for improved efficacy of ALL treatment, based on the ability of cAMP signaling to reduce apoptosis induced by DNA damaging agents. In the present study, we have identified the antioxidant N-acetyl cysteine (NAC) as a powerful modifier of critical events downstream of the cell-permeable cAMP analog 8-(4-chlorophenylthio) adenosine-3', 5'- cyclic monophosphate (8-CPT). Accordingly, we found NAC to turn 8-CPT into a potent killer of ALL cells in vitro both in the presence and absence of DNA damaging treatment. Furthermore, we revealed that NAC in combination with 8-CPT is able to delay the progression of ALL in a xenograft model in NOD-scid IL2Rγnull mice. NAC was shown to rely on the ability of 8-CPT to activate the guanine-nucleotide exchange factor EPAC, and we demonstrated that the ALL cells are killed by apoptosis involving sustained elevated levels of calcium imposed by the combination of the two drugs. Taken together, we propose that 8-CPT in the presence of NAC might be utilized as a novel strategy for treating pediatric ALL patients, and that this powerful combination might be exploited to enhance the therapeutic index of current ALL targeting therapies.

Author Correction: Spatially resolved steady-state negative capacitance.

In this Letter, the first name of author Bhagwati Prasad was misspelled Bhagawati. This error has been corrected online.

Spatially resolved steady-state negative capacitance.

Negative capacitance is a newly discovered state of ferroelectric materials that holds promise for electronics applications by exploiting a region of thermodynamic space that is normally not accessible1-14. Although existing reports of negative capacitance substantiate the importance of this phenomenon, they have focused on its macroscale manifestation. These manifestations demonstrate possible uses of steady-state negative capacitance-for example, enhancing the capacitance of a ferroelectric-dielectric heterostructure4,7,14 or improving the subthreshold swing of a transistor8-12. Yet they constitute only indirect measurements of the local state of negative capacitance in which the ferroelectric resides. Spatial mapping of this phenomenon would help its understanding at a microscopic scale and also help to achieve optimal design of devices with potential technological applications. Here we demonstrate a direct measurement of steady-state negative capacitance in a ferroelectric-dielectric heterostructure. We use electron microscopy complemented by phase-field and first-principles-based (second-principles) simulations in SrTiO3/PbTiO3 superlattices to directly determine, with atomic resolution, the local regions in the ferroelectric material where a state of negative capacitance is stabilized. Simultaneous vector mapping of atomic displacements (related to a complex pattern in the polarization field), in conjunction with reconstruction of the local electric field, identify the negative capacitance regions as those with higher energy density and larger polarizability: the domain walls where the polarization is suppressed.

Revolutionizing Veterinary Health with Viral Vector-Based Vaccines.

Vaccines signify one of the economical and reasonable means to prevent and eradicate the important infectious diseases. Conventional vaccines like live attenuated and inactivated vaccines comprise of whole pathogen either in attenuated or killed form. While, new generation vaccines have been designed to elicit immune response by genetically modifying only the nucleic acid portion of that pathogen. These new generation therapeutics include mRNA vaccines, DNA plasmid vaccines, chimeric vaccines and recombinant viral vector-based vaccines. Nucleic acid based vaccines use genetic material itself thus, they are highly stable and potent in nature to induce long-lasting immune response. Amongst these novel vaccine platforms, viral vector-based vaccines is one such emerging field which has proven to be extremely effective and potent. Nowadays, veterinary medicine has also accepted this innovative vectored vaccine platform to develop an effective control strategy against certain important viral diseases of animals. Viral vector-based vaccine uses various DNA and RNA viruses of human or animal origin to carry an immunogenic transgene of target pathogen. These vaccines enhance both humoral and cell mediated immune response without use of any accessory immune-stimulants. Till today, several viruses have been modified to be characterized as vaccine vectors. Currently, large number of research programs are going on to develop vectored vaccines and novel viral vector for veterinary use. In the present review, different kinds of viral vectored vaccines having veterinary importance have been discussed.

DDX3-mediated miR-34 expression inhibits autophagy and HBV replication in hepatic cells.

HBV entry to the host cells and its successful infection depends on its ability to modulate the host restriction factors. DEAD box RNA helicase, DDX3, is shown to inhibit HBV replication. However, the exact mechanism of inhibition still remains unclear. DDX3 is involved in multitude or RNA metabolism processes including biogenesis of miRNAs. In this study, we sought to determine the mechanism involved in DDX3-mediated HBV inhibition. First, we observed that HBx protein of HBV downregulated DDX3 expression in HBV-infected cells. Overexpression of DDX3 inhibited HBx, HBsAg and total viral load, while its knockdown reversed the result in Hep G2.2.15 cells. Expression of miR-34 was downregulated in HBV-infected cells. Overexpression of pHBV1.3 further confirmed that HBV downregulates miR-34 expression. Consistent with the previous finding that DDX3 is involved in miRNA biogenesis, we observed that expression of miR-34 positively corelated with DDX3 expression. miRNA target prediction tools showed that miR-34 can target autophagy pathway which is hijacked by HBV for the benefit of its own replication. Indeed, transfection with miR-34 oligos downregulated the expression of autophagy marker proteins in HBV-expressing cells. Overexpression of DDX3 in HBV-expressing cells, downregulated expression of autophagy proteins while silencing of DDX3 reversed the results. These results led us to conclude that DDX3 upregulates miR-34 expression and thus inhibits autophagy in HBV-expressing cells while HBx helps HBV evade DDX3-mediated inhibition by downregulating DDX3 expression in HBV-infected cells.

Development of multiplex PCR assay for simultaneous detection of African swine fever, porcine circo and porcine parvo viral infection from clinical samples.

A diagnostic method for simultaneously detecting and distinguishing African Swine Fever (ASF), porcine circovirus type 2 (PCV2), and porcine parvovirus (PPV) in clinical specimens is critical for differential diagnosis, monitoring, and control in the field. Three primer pairs were designed and used to create a multiplex PCR assay. In addition, 356 porcine post mortem tissue samples from various parts of India's North Eastern region were tested by the developed multiplex PCR assay to demonstrate its accuracy. Using the designed primers, each of the ASF, PCV2 and PPV target genes was amplified, but no other porcine virus genes were detected. The assay's limit of detection was 102 copies/µl of PCV2, PPV, or ASFV. The detection of PCV2, PPV, and ASF in postmortem tissue samples revealed that they are co-circulating in India's North-Eastern region. The percentage positivity (PP) for PCV2, PPV and ASF single infection were 7.02% (25/356), 3.93% (14/356), and 3.37% (12/356), respectively, while the PP for PCV2& PPV co-infection was 2.80% (10/356), ASF & PCV2 co infection was 1.4% (5/356) and the ASF, PPV& PCV2 co-infection was1.40% (5/356). The results also indicate that the ASF can infect pigs alongside PCV and PPV.

Direct N-Me Aziridination of Enones.

The first direct general method for N-Me aziridination of electron-deficient olefins, enones, is described using N-methyl-O-tosylhydroxylamine as the aminating agent in the presence of a Cu(OTf)2 catalyst. The aziridination of vinyl ketones, hitherto unknown for N-Me as well as N-H, has been achieved efficiently. The open-flask reaction is stereospecific, operationally simple, and additive-free. It also efficiently affords N-H aziridinated products under a similar reaction condition.

Vortex Domain Walls in Ferroelectrics.

Controlling the domain formation in ferroelectric materials at the nanoscale is a fertile ground to explore emergent phenomena and their technological prospects. For example, charged ferroelectric domain walls in BiFeO3 and ErMnO3 exhibit significantly enhanced conductivity which could serve as the foundation for next-generation circuits (Estévez and Laurson, Phys. Rev. B 2015, 91, 054407). Here, we describe a concept in which polar vortices perform the same role as a ferroelectric domain wall in classical domain structures with the key difference being that the polar vortices can accommodate charged (i.e., head-to-head and tail-to-tail) domains, for example, in ferroelectric PbTiO3/dielectric SrTiO3 superlattices. Such a vortex domain wall structure can be manipulated in a reversible fashion under an external applied field.

Effect of fuel preheating on performance, emission and combustion characteristics of a diesel engine fuelled with Vateria indica methyl ester blends at various loads.

The present study examines the preheated (95 °C) and unheated (35 °C) Vateria indica methyl ester (VIME) blends by studying the engine performance, combustion, and emission characteristics at various loads. A single-cylinder, TV1 Kirloskar direct injection diesel engine is used to carry out the tests. Biodiesel produced from Dhupa fat through the transesterification process is used as a renewable fuel in a diesel engine. In this work, diesel (B0), VIME (B100), and two binary blends (B30 and B50) are used. VIME has a higher viscosity, higher density, and lower calorific value than diesel, resulting in lesser brake thermal efficiency (BTE) and higher brake specific energy consumption (BSEC). Due to high viscosity of the biodiesel, preheating of fuel is done before injecting into cylinder. Preheating reduces the viscosity, and enhances the atomization and vaporization of fuel, resulting in improved engine performance. For a given blend of VIME biodiesel and diesel, the preheated blend has better BTE, decreased BSEC and lesser CO and HC emissions, with a slight increment in NOX emission compared to the unheated blend. The preheated B30 blend has a BTE value of 30.3% which is close to the BTE value of 30.1% of unheated diesel at 100% load condition. CO, HC, and soot emissions are decreased by 16.2%, 34.4%, and 16.5%, respectively, for preheated B100 fuel compared to unheated B100, at full load.

A prospective, multicenter, clinical Study to evaluate the Safety, Pharmacokinetics, and Efficacy of Bleed Outcomes, with HemoRel-A® in severe Hemophilia A Patients.

PURPOSE: To evaluate efficacy for an on-demand treatment of acute bleeding events, pharmacokinetics, safety, and tolerability of HemoRel-A® in severe hemophilia A. METHODS: A total of 44 male subjects with severe hemophilia A with an annualized bleed rate of 12 while on-demand treatment with factor VIII (FVIII) were enrolled in the study and received HemoRel-A® for bleed treatment. The efficacy of HemoRel-A® was evaluated based on a four-point scale (excellent, good, moderate, or none). Six-point pharmacokinetic (PK) assessment was performed following a single dose of 50 IU/kg in 12 subjects after a 7-day wash-out period. Safety evaluations were performed at each visit and inhibitor testing was performed in all patients at screening and end of study. RESULTS: Forty-four male subjects received at least a single dose of the study medication and were included in the intent-to-treat (ITT) analysis and safety outcome. In 23 (7.52%) out of the 306 bleeding events, HemoRel-A® efficacy was rated as excellent, in 272 (88.89 %) bleeds it was rated as good, and in 11 (3.68%) bleeding events it was rated as moderate. No failure of efficacy was noted in any of the bleeding events. Thus overall out of 306 bleeding events, 295 (96.41%) showed excellent or good efficacy. Pharmacokinetic assessment based on plasma FVIII activity measured by the chromogenic assay in 12 patients showed comparative results similar to FVIII preparations. A total of 12 adverse events (AEs) were reported in this study. There was no inhibitor development in this previously treated patients (PTP) cohort. CONCLUSION: HemoRel-A® was established to be efficacious and safe in the treatment of acute bleeding events in subjects with severe hemophilia A. TRIAL REGISTRATION NUMBER: CTRI/2018/05/013790. Registration date: 9th May 2018.

Applications of Sentinel-2 satellite data for spatio-temporal mapping of deep pools for monitoring the riverine connectivity and assessment of ecological dynamics: a case from Godavari, a tropical river in India (2016-2021).

Rivers are dynamic ecosystems with diverse habitats that require ample connectivity to ensure the flow of ecosystem services, thus empowering the sustainable development of an entire basin. Geo-spatial tools offer powerful prospects for monitoring of aquatic ecosystems. The usefulness of Sentinel-2 datasets to assess river connectivity has been explored for an un-gauged seasonal river system. The present study was undertaken in five ecologically unique river reaches viz. Wainganga, Wardha, Pranhita, Godavari-mid and Manair in Godavari Basin in the Indian Deccan Plateau to map water spread dynamics at various time scales, i.e., fortnightly, monthly, seasonal, annual and demi-decadal during 2016-2021. The maximum value of perennial water spread per square kilometre of total floodplain area (2016-2021), determined using Sentinel-2 imageries, was observed in river Wardha (0.18) followed by Pranhita (0.12) and Wainganga (0.11). The water spread showed a decreasing trend, while the number of patches in the river corridor increased over time from post-monsoon to pre-monsoon season. The copious perennial habitat with relatively larger patches, incessant flow in river Pranhita and obstructed flow, large-sized patches reported in river Wardha during summer months, hold importance in terms of providing refuge to aquatic biota. This study provides evidence for the impact of water projects on spatio-temporal water spread dynamics in Godavari Basin. The demonstrated utility of Sentinel-2 imagery coupled with gauge station measurements for river continuity assessment and deep pool mapping would aid in enhancing our understanding on environmental flow at a spatial scale, which in turn would aid in effective river management to achieve the Sustainable Development Goals. The implications of this study for sustainable environmental management and limitations are also discussed.

Replication competence of canine distemper virus in cell lines expressing signaling lymphocyte activation molecule (SLAM) of goat, sheep and dog origin.

Cellular receptors play an important role in entry and cell to cell spread of morbillivirus infections. The cells expressing SLAM and Nectin-4 have been used for successful and efficient isolation of canine distemper virus (CDV) in high titre. There are several methods for generation of cells expressing receptor molecules. Here, we have used a comparatively cheaper and easily available method, pcDNA 3.1 (+) for engineering Vero cells to express SLAM gene of goat, sheep and dog origin (Vero/Goat/SLAM (VGS), Vero/Sheep/SLAM (VSS) and Vero/Dog/SLAM (VDS), respectively). The generated cell lines were then compared to test their efficacy to support CDV replication. CDV could be grown in high titre in the cells expressing SLAM and a difference of log two could be recorded in virus titre between VDS and native Vero cells. Also, CDV could be grown in a higher titre in VDS as compared to VGS and VSS. The finding of this study supports the preferential use of SLAM expressing cells over the native Vero cells by CDV. Further, the higher titre of CDV in cells expressing dog-SLAM as compared to the cells expressing SLAM of non-CDV hosts (i.e. goat and sheep) points towards the preferential use of dog SLAM by the CDV and may be a plausible reason for differential susceptibility of small ruminants and Canines to CDV.

An Open-Label Randomized Controlled Trial Comparing the Efficacy and Safety of Pemetrexed-Carboplatin versus (Weekly) Paclitaxel-Carboplatin as First-Line Chemotherapy in Advanced Non-Squamous Non-Small Cell Lung Cancer.

BACKGROUND: Before the approval of first-line immune checkpoint inhibitors, platinum doublets were the standard of care in patients with treatment-naïve advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. Pemetrexed-platinum combinations are preferred in non-squamous NSCLC. However, there has been no direct comparison to paclitaxel-carboplatin. METHODS: This open-label randomized trial was designed to compare pemetrexed-carboplatin with (weekly) paclitaxel-carboplatin in treatment-naïve advanced/metastatic non-squamous NSCLC without driver mutations. Patients received either pemetrexed 500 mg/m2 and carboplatin AUC 5 every 3 weeks, or paclitaxel 80 mg/m2 on day 1, day 8, and day 15 with carboplatin AUC 5 every 4 weeks for 4 cycles. Patients in both arms were allowed to receive pemetrexed maintenance. RESULTS: A total of 180 patients were enrolled. The study was terminated early; however, at the time of analysis 75.8% of the required events had occurred. Finally, 164 patients were evaluable, 83 in the pemetrexed arm and 81 in the paclitaxel arm. After a median follow-up of 17 months, progression-free survival (PFS) rates at 6 months were not different in the two treatment arms (47.45 vs. 48.64%, p = 0.88). The median PFS values were 5.67 months (95% CI 3.73-7.3) and 5.03 months (95% CI 2.63-7.43) in each arm, respectively (HR 1.13, 95% CI 0.81-1.59, p = 0.44). The median overall survival was also not different: 14.83 months (95% CI 9.5-18.73) and 11.3 (95% CI 8.3-19.7; HR 1.19, 95% CI 0.8-1.78, p = 0.37). All grade toxicities were similar except for alopecia and peripheral neuropathy, which were higher in the paclitaxel arm. CONCLUSION: Pemetrexed-carboplatin is not superior to (weekly) paclitaxel-carboplatin as the first-line regimen in advanced non-squamous NSCLC in terms of PFS.

Emergent chirality in the electric polarization texture of titanate superlattices.

Chirality is a geometrical property by which an object is not superimposable onto its mirror image, thereby imparting a handedness. Chirality determines many important properties in nature-from the strength of the weak interactions according to the electroweak theory in particle physics to the binding of enzymes with naturally occurring amino acids or sugars, reactions that are fundamental for life. In condensed matter physics, the prediction of topologically protected magnetic skyrmions and related spin textures in chiral magnets has stimulated significant research. If the magnetic dipoles were replaced by their electrical counterparts, then electrically controllable chiral devices could be designed. Complex oxide BaTiO3/SrTiO3 nanocomposites and PbTiO3/SrTiO3 superlattices are perfect candidates, since "polar vortices," in which a continuous rotation of ferroelectric polarization spontaneously forms, have been recently discovered. Using resonant soft X-ray diffraction, we report the observation of a strong circular dichroism from the interaction between circularly polarized light and the chiral electric polarization texture that emerges in PbTiO3/SrTiO3 superlattices. This hallmark of chirality is explained by a helical rotation of electric polarization that second-principles simulations predict to reside within complex 3D polarization textures comprising ordered topological line defects. The handedness of the texture can be topologically characterized by the sign of the helicity number of the chiral line defects. This coupling between the optical and novel polar properties could be exploited to encode chiral signatures into photon or electron beams for information processing.

Evaluation of ELISA and PCR in parallel to single intradermal cervical tuberculin test (SICT) for diagnosis of tuberculosis in buffaloes.

Bovine tuberculosis is an economically important disease with very high zoonotic potential. Single intradermal cervical tuberculin test (SICT) is considered a gold standard assay for the diagnosis of bovine tuberculosis. However, bovines especially buffaloes may produce a false negative result when the animal becomes cell-mediated immune (CMI) anergic in the advanced stage of the disease. In the present study, ELISA and PCR assays were successfully demonstrated to be useful in diagnosing tuberculosis especially in the CMI anergic buffaloes infected with Mycobacterium bovis. ELISA and PCR assays are able to detect 8.94% and 8.13%, respectively, more animals as positive in comparison to standard SICT assay in a selected population of 123 buffaloes. The moderate agreement between SICT and ELISA (k: 0.528; 0.249-0.807), a substantial agreement between SICT and PCR (k: 0.648; 0.364-0.931), and high agreement between ELISA and PCR (k: 0.856; 0.697-1.0) highlight that ELISA and PCR, if used in parallel with SICT, will provide better sensitivity over single assay. Reduction of false negative reactors may help in minimizing the zoonotic threat from bovine tuberculosis especially in disease endemic region where human and livestock interface is quite high.

Epidemiology of carbapenem-resistant Escherichia coli and first report of blaVIM carbapenemases gene in calves from India.

A cross-sectional study on six dairy farms was conducted to ascertain the occurrence of carbapenem-resistant Escherichia coli in calves. Two-hundred and seventy-nine isolates of E. coli were recovered from 90 faecal samples from apparently healthy (45) and diarrhoeal (45) calves. The isolates were screened for phenotypic susceptibility to carbapenems and production of metallo ß-lactamase, as well as five carbapenemase resistance genes by PCR, and overexpression of efflux pumps. Eighty-one isolates (29.03%) were resistant to at least one of three carbapenem antibiotics [meropenem (23.30%), imipenem (2.15%) and ertapenem (1.43%)], and one isolate was positive for the blaVIM gene which was located on an Incl1 plasmid of a novel sequence type (ST 297) by multilocus sequence typing. The majority (83.95%) of isolates had an active efflux pump. Calves housed on concrete floors were approximately seven times more likely to acquire meropenem-resistant isolates than those housed on earthen floors (95% CI 1.27-41.54). In India, carbapenem drugs are not used in food animal treatment, hence carbapenem-resistant strains in calves possibly originate from the natural environment or human contact and is of public health importance. To our knowledge, this is the first report of blaVIM carbapenemases gene in calves from India.