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Due to fundamental and technological concerns, investigating materials with topological magnetic structures has always been a focus of significant research. We explored Sb1.9Fe0.1Te2.85S0.15where a unique combination of disordered glassy phases, competitive FM–AFM interactions, and nontrivial surface state coexisted at the same time. We have discussed the impact of those complicated magnetic phases upon the observed AHE in Sb1.9Fe0.1Te2.85S0.15with magneto-transport studies. The AC susceptibility results demonstrate a shift in the freezing temperature with excitation frequency, the comprehensive analysis verifies the slower dynamics, and a nonzero Vogel–Fulcher temperature T0suggests cluster spin glass. This, together with an intermediate value of the Mydosh parameter, provides an evidence for the formation of a cluster spin glass state in the present system. Topological frustrated magnets, which can host both magnetic frustrations and Dirac quasi-particles, are highly sought after class of compounds. Furthermore, as seen by the de Haas–van Alphen (dHvA) oscillation study, the fermiology deviates with doping and produces multiple Fermi pockets, revealing a rich complexity in the underlying electronic structure.

ABSTRACTTo exploit highly conserved and difficult drug targets, including multipass membrane proteins, monoclonal antibody discovery efforts increasingly rely on the advantages offered by divergent species such as rabbits, camelids, and chickens. Here, we provide an overview of antibody discovery technologies, analyze gaps in therapeutic antibodies that stem from the historic use of mice, and examine opportunities to exploit previously inaccessible targets through discovery now possible in alternate species. We summarize the clinical development of antibodies raised from divergent species, discussing how these animals enable robust immune responses against highly conserved binding sites and yield antibodies capable of penetrating functional pockets via long HCDR3 regions. We also discuss the value of pan-reactive molecules often produced by these hosts, and how these antibodies can be tested in accessible animal models, offering a faster path to clinical development.

Photodetectors based on n‐Mg0.25Zn0.75O/p‐Si heterojunctions are not only suitable for integration with existing semiconductor technology, but also circumvent the difficulty of stable p‐type doping in MgxZn1–xO. However, the use of Si leads to photoresponse in the visible part of the light spectrum, which renders n‐MgxZn1–xO/p‐Si heterojunction devices unsuitable for visible blind UV photodetection. Herein, it is demonstrated that the visible photoresponse in the n‐Mg0.25Zn0.75O/p‐Si photodetectors can be significantly suppressed by inserting a thin interlayer of MgO at the heterojunction. The MgO layer serves as a blocking layer for the drift of photo‐excited electrons from p‐Si to n‐Mg0.25Zn0.75O, thereby limiting the visible photoresponse. It is found that on increasing the thickness of the MgO interlayer from 3 to 15 nm, the UV to visible rejection ratio increases from ≈25 to 200. This enhancement in the UV to visible rejection ratio demonstrates that n‐Mg0.25Zn0.75O/p‐Si heterojunction devices with MgO interlayer are promising for visible‐blind UV photodetection applications. The visible photoresponse in n‐Mg0.25Zn0.75O/p‐Si heterojunction could be significantly reduced by inserting a MgO barrier layer between the p‐Si substrate and the Mg0.25Zn0.75O film. The visible light suppression is caused by the presence of a high conduction band offset at the p‐Si/MgO interface that works as a barrier for the drift of the visible excited electrons from the p‐Si to n‐Mg0.25Zn0.75O.

ABSTRACTThe identification of novel antiretroviral agents is required to provide alternative treatment options for HIV-1-infected patients. The screening of a phenotypic cell-based viral replication assay led to the identification of a novel class of 4,5-dihydro-1H-pyrrolo[3,4-c]pyrazol-6-one (pyrrolopyrazolone) HIV-1 inhibitors, exemplified by two compounds: BI-1 and BI-2. These compounds inhibited early postentry stages of viral replication at a step(s) following reverse transcription but prior to 2 long terminal repeat (2-LTR) circle formation, suggesting that they may block nuclear targeting of the preintegration complex. Selection of viruses resistant to BI-2 revealed that substitutions at residues A105 and T107 within the capsid (CA) amino-terminal domain (CANTD) conferred high-level resistance to both compounds, implicating CA as the antiviral target. Direct binding of BI-1 and/or BI-2 to CANTDwas demonstrated using isothermal titration calorimetry and nuclear magnetic resonance (NMR) chemical shift titration analyses. A high-resolution crystal structure of the BI-1:CANTDcomplex revealed that the inhibitor bound within a recently identified inhibitor binding pocket (CANTDsite 2) between CA helices 4, 5, and 7, on the surface of the CANTD, that also corresponds to the binding site for the host factor CPSF-6. The functional consequences of BI-1 and BI-2 binding differ from previously characterized inhibitors that bind the same site since the BI compounds did not inhibit reverse transcription but stabilized preassembled CA complexes. Hence, this new class of antiviral compounds binds CA and may inhibit viral replication by stabilizing the viral capsid.

Evolution of domain structures across the martensitic transition (Tm) in the ferromagnetic shape memory alloy system Ni-Mn-Ga is studied using an optical microscope with a temperature variation. Compositions chosen have Tm < Tc, Tm = Tc and Tm > Tc, (Tc=Curie temperature) so that one can compare the nature of martensitic domains. There are no appreciable domain structures when Tm < Tc as compared to the one with Tm > Tc. However, giant morphological changes in the form of appearance of well-developed domains that are propagating with different directions are seen for the composition in which Tm=Tc. The results are discussed in the light of Magnetic Force Microscopy observations as well as giant entropy changes known to occur on samples with co-occurrence of Tm and Tc.

We report a detailed investigation of the magneto-transport and magnetic properties of Mn excess Ni-Mn-Ga using the resistivity and magnetization measurements. Magnetoresistance (MR) has been measured in the ferromagnetic state for different compositions in the austenitic, premartensitic and martensitic phases. With Mn doping in Ni2-yMn1+yGa, a decrease in magnetization and MR has been found, since the doped Mn atoms in Ni position are in the antiferromagnetic configuration with the Mn atoms in Mn position. MR for the parent stoichiometric composition Ni2MnGa varies almost linearly with field in the austenitic and pre-martensitic phases, and shows a cusp-like shape in the martensitic phase. This has been explained by the changes in twin and domain structures in the martensitic phase. Hysteresis in the heating and cooling cycles is a characteristic of the first order nature of the martensitic phase transition.

We present the first ever theoretical and experimental charge Compton profiles of Ni2MnGa Heusler alloy. The measurements have been made using magnetic Compton spectrometer at SPring8, Japan. The Compton profiles and energy bands have been computed using Hartree-Fock, density functional theory with local density and generalized gradient approximations. It is seen that the Hartree-Fock based Compton profile is relatively in better agreement with the experimental profiles. In addition, we also report the energy bands, density of states and valence charge densities using full potential linearized augmented plane-wave method.

The XANES studies at Mn, Ni and Ga K-edge of Ni2MnGa compound have been carried out at room and low temperatures. The Mn K-edge and Ni K-edge spectra shows modulation in the post edge features when the sample is cooled below martensitic transition temperature. It is strongly reflected in the XANES of Mn K-edge where the peak after the edge gets totally suppressed when the sample is in martensitic phase. This peak shows a hysteretic behaviour when thermal cycling was done across the martensitic transition temperature. This clearly shows that the peak height is a measure of austenitic phase present at a particular temperature. This demonstrates the strong correlations of electronic states and crystal structures in these compounds.

Influence of structural transition in the evolution of the magnetic domains in the ferromagnetic shape memory alloy system Ni2+xMn1-xGa is reported here using Magnetic Force Microscopy (MFM) studies. Studies reported are with two samples with their martensite transition temperature TM less than and greater than the Curie temperature Tc. Present results show an evolution of MFM across the Tc with a clear twin domains and sub domain structures inside the twins. The higher spatial resolution of MFM (~50nm) as compared to optical microscope (400nm) is useful in probing the domain walls. Force derivative of the MFM signal that may be used as an order parameter seems to scale the onset of magnetic order in the system. One can clearly see the vanishing of the MFM patterns for T>Tc. Results are discussed in the light of models available for tip-sample interactions that track the local magnetization.

We report the structural studies on Mn excess and Ga deficient Ni2Mn1+zGa1-z specimens with z= 0, 0.05, 0.1, 0.15, 0.2 and 0.25. The crystal structure at room temperature was determined by the x-ray diffraction (XRD). Rietveld analysis has been performed to obtain the lattice parameters. For z= 0, 0.05 and 0.1, a cubic austenitic phase is observed. For 0.15≤ z ≤0.25, a tetragonal martensitic phase is obtained, whose lattice constant c increases and a decreases linearly with increasing z following Vegard’s law. Phase coexistence is observed for z= 0.15, confirming the first-order nature of the martensitic transition.

A detailed kinetics study of the first-order structural transition in virgin NiTi, Ni47Fe3Ti50, and Ni2+xMn1-xGa (x= 0 and 0.26) manifests the varying role of renucleation-driven austenitic growth with the doping-induced disorder and the magnetization state. The austenite transitions were investigated using differential scanning calorimeter (DSC) at heating rates spanning over a decade. They revealed the existence of two Arrhenius processes, with their relative presence, nucleationbarrier energies, and validity-timescales suggesting that both intra- and inter-domain texturalorderings undergo de-structuring. In the stoichiometric Ni2MnGa, a single low-energy barrier ( ) fast kinetics observed may be attributed wholly to the short-distance textural order-disorder (a near absence of bigger, inter-domain interactions). On the other hand, two distinct Arrhenicities are found in equal strength in NITINOL (NiTi) and Ni47Fe3Ti50, and in unequal proportion in Ni2.26Mn0.74Ga, over the full range of temperature scanning rates covered (q= 2.5 to 50°C/min). The relatively fast nucleation-driven growth dominates higher T-scanning rates, with lower barrier activation (qhi) (albeit > , due to a change in the twins’ character). Another kinetics with higher barrier energy (qlo) manifests at slow heatings. The crossover in Ni47Fe3Ti50 is interpreted as increase in the (disorder-induced) A-domain-size dispersion, which also causes a broadening of the transition. Parameters characterizing the kinetics of various specimens are examined; comparisons of the relative energy/time scales of inter- and intra-domain processes made, and their transition/crossover temperature discussed.

Most human cancer cells are thought to acquire the ability to divide beyond the capacity of normal somatic cells through illegitimately activating the gene hTERT, which encodes the catalytic subunit of telomerase. While telomerase reverse transcriptase (TERT) is conserved in most eukaryotes, mounting evidence suggests that the C terminus of the human protein may have functions unique to higher eukaryotes. To search for domains responsible for such functions, we assayed a panel of tandem substitution mutations encompassing this region of human TERT for in vitro and in vivo functionality. We found four clusters of mutations that inactivated the biochemical and biological functions of telomerase, separated by mutations that had little or no effect on enzyme activity. We also identified a region where mutations generate catalytically active but biologically inert proteins. This C-terminal region that dissociates activities of telomerase (C-DAT) does not appear to be involved in nuclear localization or protein multimerization. Instead, it appears that the C-DAT region is involved in a step of in vivo telomere synthesis after the assembly of a catalytically active enzyme. Intriguingly, all of the described regions reside in a portion of TERT that is dispensable for cellular viability in yeast, arguing for a divergent role of the C terminus in higher eukaryotes.

ABSTRACTMost human cancer cells are thought to acquire the ability to divide beyond the capacity of normal somatic cells through illegitimately activating the gene hTERT, which encodes the catalytic subunit of telomerase. While telomerase reverse transcriptase (TERT) is conserved in most eukaryotes, mounting evidence suggests that the C terminus of the human protein may have functions unique to higher eukaryotes. To search for domains responsible for such functions, we assayed a panel of tandem substitution mutations encompassing this region of human TERT for in vitro and in vivo functionality. We found four clusters of mutations that inactivated the biochemical and biological functions of telomerase, separated by mutations that had little or no effect on enzyme activity. We also identified a region where mutations generate catalytically active but biologically inert proteins. This C-terminal region that dissociates activities of telomerase (C-DAT) does not appear to be involved in nuclear localization or protein multimerization. Instead, it appears that the C-DAT region is involved in a step of in vivo telomere synthesis after the assembly of a catalytically active enzyme. Intriguingly, all of the described regions reside in a portion of TERT that is dispensable for cellular viability in yeast, arguing for a divergent role of the C terminus in higher eukaryotes.

Telomerase is the enzyme essential to complete the replication of the terminal DNA of most eukaryotic chromosomes. In humans, this enzyme is composed of the telomerase reverse transcriptase (hTERT) and telomerase RNA (hTR) subunits. hTR has been found in the nucleolus, a site of assembly of ribosomes as well as other ribonucleoproteins (RNPs). We therefore tested whether the hTERT component is also found in the nucleolus, where it could complex with the hTR RNA to form a functional enzyme. We report here that hTERT does indeed localize to the nucleolus, and we mapped the domain responsible for this localization to the hTR-binding region of the protein by deletion analysis. Substitution mutations in two of the three conserved hTR-binding domains in this nucleolarlocalization domain (NoLD) abolished nucleolar localization. However, another mutation that impeded hTR binding did not alter this subcellular localization. Additionally, wild type hTERT was detected in the nucleolus of cells that failed to express hTR. Taken together, we propose that the nucleolar localization of hTERT involves more than just the association with the hTR subunit. Furthermore, the coincidental targeting of both the hTR and hTERT subunits to the nucleolus supports the premise that the assembly of telomerase occurs in the nucleolus.

ABSTRACTMost tumor cells depend upon activation of the ribonucleoprotein enzyme telomerase for telomere maintenance and continual proliferation. The catalytic activity of this enzyme can be reconstituted in vitro with the RNA (hTR) and catalytic (hTERT) subunits. However, catalytic activity alone is insufficient for the full in vivo function of the enzyme. In addition, the enzyme must localize to the nucleus, recognize chromosome ends, and orchestrate telomere elongation in a highly regulated fashion. To identify domains of hTERT involved in these biological functions, we introduced a panel of 90 N-terminal hTERT substitution mutants into telomerase-negative cells and assayed the resulting cells for catalytic activity and, as a marker of in vivo function, for cellular proliferation. We found four domains to be essential for in vitro and in vivo enzyme activity, two of which were required for hTR binding. These domains map to regions defined by sequence alignments and mutational analysis in yeast, indicating that the N terminus has also been functionally conserved throughout evolution. Additionally, we discovered a novel domain, DAT, that “dissociates activities of telomerase,” where mutations left the enzyme catalytically active, but was unable to function in vivo. Since mutations in this domain had no measurable effect on hTERT homomultimerization, hTR binding, or nuclear targeting, we propose that this domain is involved in other aspects of in vivo telomere elongation. The discovery of these domains provides the first step in dissecting the biological functions of human telomerase, with the ultimate goal of targeting this enzyme for the treatment of human cancers.

Most tumor cells depend upon activation of the ribonucleoprotein enzyme telomerase for telomere maintenance and continual proliferation. The catalytic activity of this enzyme can be reconstituted in vitro with the RNA (hTR) and catalytic (hTERT) subunits. However, catalytic activity alone is insufficient for the full in vivo function of the enzyme. In addition, the enzyme must localize to the nucleus, recognize chromosome ends, and orchestrate telomere elongation in a highly regulated fashion. To identify domains of hTERT involved in these biological functions, we introduced a panel of 90 N-terminal hTERT substitution mutants into telomerase-negative cells and assayed the resulting cells for catalytic activity and, as a marker of in vivo function, for cellular proliferation. We found four domains to be essential for in vitro and in vivo enzyme activity, two of which were required for hTR binding. These domains map to regions defined by sequence alignments and mutational analysis in yeast, indicating that the N terminus has also been functionally conserved throughout evolution. Additionally, we discovered a novel domain, DAT, that “dissociates activities of telomerase,” where mutations left the enzyme catalytically active, but was unable to function in vivo. Since mutations in this domain had no measurable effect on hTERT homomultimerization, hTR binding, or nuclear targeting, we propose that this domain is involved in other aspects of in vivo telomere elongation. The discovery of these domains provides the first step in dissecting the biological functions of human telomerase, with the ultimate goal of targeting this enzyme for the treatment of human cancers.

In the present work, brownmillerite KBiFe2O5 (KBFO), a relatively new multifunctional compound, has been explored as an electrode material for applications in supercapacitors. Polycrystalline KBFO is synthesized via citrate combustion method. The phase formation, crystallinity, composition and morphology of KBFO samples are investigated using XRD, HRTEM, XPS and FESEM. As synthesized KBFO sample possesses rectangular rod-like morphology with monoclinic crystal system. The electrochemical properties of KBFO were analyzed using Galvanostatic charge/discharge (GCD), Cyclic voltammetry (CV) and Electrochemical Impedance Spectroscopy (EIS) in acidic, alkaline and neutral electrolyte media. GCD results show a promising energy storage property with remarkable 100% capacitive retention after 1000 cycles. CV results also establish the pseudocapacitive nature of KBFO in all electrolyte media. These features support the feasibility of exploitation of KBFO for advanced energy storage applications.

In the present work, KBiFe2O5(KBFO) films were implanted with 1 MeV N+-ions at different fluencies i.e., 1015, 1016and 1017ions cm?2and their structural, optical and electronic properties were analyzed. From the X-ray diffraction studies, it is evident that the crystal structure of these films belong to that of brownmillerite. Effective bandgaps of these implanted films, as observed from the UV-visible absorption spectroscopy, are tuned from 1.72 eV to 1.60 eV with increasing the ion fluences. X-ray photoelectron spectroscopy reveals that the valence states of Bi and Fe ions in both pristine and implanted films are in trivalent states and also confirm the presence of nitrogen in the implanted films. A clear shift in valence band (VB) edge position towards lower binding energy in N+-ion implanted films is observed due to the occupation of N 2p states above O 2p states in the VB.

The topological insulatorsBi2-xFexSe3–xSxhave been investigated by the dc magnetization, magneto-transport and angle resolved photoemission spectroscopy (ARPES)techniques.With dopingof Fe and S,a negative giant magneto-resistance (MR) is observed for parallel electric and magnetic fields (H||E). The MR behavior at lower magnetic field can be explained with the semi-classical theory whereas the MR behavior at higher field has been attributed to the axial anomaly. Interestingly, the system reached to the quantum limit at low magnetic field (∼4.5T). The magnetic ordering can be explained with the presence of both the RKKY (surface) and van-Vleck (bulk) interaction. The ARPES study reveals that a surface gap is suppressedwhen the magnetic ordering changes from ferromagnetic to anti-ferromagnetic ordering.The ARPES study and the appearance of quantum oscillations (SdH) in the resistivity pattern reveal that the topological surface property is preserved with the co-doping of Fe and S.