Opposite Chain Research Articles

Rapid and Highly Sensitive Detection of Target DNA Related to COVID-19 Virus With a Fluorescent Bio-conjugated Probe via a FRET Mechanism

A novel cyanine 3 (Cy3)-based bio-conjugated sensor has been developed to detect target DNA or extracted RNA from COVID -19 samples using the fluorescence resonance energy transfer (FRET) experiment. A special sequence of the COVID -19 genome was selected as a complementary DNA (target DNA) part. The opposite chain of this target sequence was designed in 2 parts; one part was attached to the Cy3 organic dye (capture DNA or Cy3- DNA), and the other part was attached to the BHQ2 molecule (quencher DNA or BHQ2- DNA). The Cy3 molecule acts as a donor pair, and BHQ2 acts as an acceptor pair in the FRET experiment. The capture DNA and quencher DNA can form a sandwiched complex in the presence of target DNA. The formation of the entitled sandwiched hybrid causes the decrement of emission intensity of the Cy3 donor in bio-conjugated Cy3-DNA via energy transfer from Cy3 (as a donor) to BHQ2 (as an acceptor). Indeed, in the presence of non-complementary DNA, the pairing of DNA strands does not occur, the FRET phenomenon does not exist, and therefore fluorescence intensity of Cy3 does not decrease. Moreover, this biosensor was successfully applied to analyze real samples containing extracted RNA of COVID -19 prepared for the reverse transcriptase-polymerase chain reaction (RT-PCR) test, and the results were promising.

Structural basis of HLX10 PD-1 receptor recognition, a promising anti-PD-1 antibody clinical candidate for cancer immunotherapy.

Cancer immunotherapies, such as checkpoint blockade of programmed cell death protein-1 (PD-1), represents a breakthrough in cancer treatment, resulting in unprecedented results in terms of overall and progression-free survival. Discovery and development of novel anti PD-1 inhibitors remains a field of intense investigation, where novel monoclonal antibodies (mAbs) and novel antibody formats (e.g., novel isotype, bispecific mAb and low-molecular-weight compounds) are major source of future therapeutic candidates. HLX10, a fully humanized IgG4 monoclonal antibody against PD-1 receptor, increased functional activities of human T-cells and showed in vitro, and anti-tumor activity in several tumor models. The combined inhibition of PD-1/PDL-1 and angiogenesis pathways using anti-VEGF antibody may enhance a sustained suppression of cancer-related angiogenesis and tumor elimination. To elucidate HLX10's mode of action, we solved the structure of HLX10 in complex with PD-1 receptor. Detailed epitope analysis showed that HLX10 has a unique mode of recognition compared to the clinically approved PD1 antibodies Pembrolizumab and Nivolumab. Notably, HLX10's epitope was closer to Pembrolizumab's epitope than Nivolumab's epitope. However, HLX10 and Pembrolizumab showed an opposite heavy chain (HC) and light chain (LC) usage, which recognizes several overlapping amino acid residues on PD-1. We compared HLX10 to Nivolumab and Pembrolizumab and it showed similar or better bioactivity in vitro and in vivo, providing a rationale for clinical evaluation in cancer immunotherapy.

Abstract P421: Analysis Of The Functional Relevance Of Human Beta-myosin Heavy Chain Post-translational Modifications

Sarcomeric proteins have been shown to be a target of post-translational modifications (PTMs). Phosphorylation and acetylation of several sarcomeric proteins have been reported to be important for fine-tuning of myocardial contractility. Given the emerging importance of understanding the potential role of PTMs on cardiac muscle performance in healthy and diseased states, we sought to identify novel PTMs on human cardiac beta-myosin heavy chain (beta-MHC). We found several high confidence beta-MHC peptides modified by K-acetylation and S- and T-phosphorylation found in non-diseased, ischemic, and non-ischemic human heart samples. Using bottom-up proteomics and label-free quantification, we identified seven high-confidence peptides (K34, K58, S210, T215, K429, K951, K1195) with K951 displaying significant reduction in acetylation levels in both ischemic and non-ischemic failing hearts compared to donor hearts. Molecular dynamics simulations were performed to better understand the functional significance of the beta-MHC PTMs. Focus was placed on modifications in the regions with greatest potential functional significance as well as modified residues with significantly altered abundance in diseased states (K951-Ac at the myosin tail nearby a binding site for myosin heads in the super-relaxed state). K951 is located in the myosin tail (S2) at the C-terminal end of simulated structure. In both unmodified and modified simulations, the tail fragment showed significant flexibility and partial unfolding at the C-terminus. In the unmodified simulations, the inter- and intra-helical contacts were maintained. However, when beta-MHC is acetylated at residue 951, these helical contacts were altered as the uncharged acetylated residue no longer formed strong hydrogen bonds with a residue of the opposite chain. This facilitated changes increase in inter-helical contacts, an increase in inter-helical distance, and disruption of the coiled-coil tail domain structure. Our study suggests that there are distinct differences in beta-MHC acetylation levels that appear to be influenced more by location of the modified residues than the type of heart disease (ischemic- and non-ischemic heart failure). Additionally, we speculate that these PTMs have the potential to modulate the interactions between beta-MHC and other regulatory sarcomeric proteins, as well as ADP-release rate of myosin, flexibility of S2 fragment, and cardiac myofilament contractility under normal and heart failure condition.

Plasma Protein Profile of Carotid Artery Atherosclerosis and Atherosclerotic Outcomes: Meta-Analyses and Mendelian Randomization Analyses.

[Figure: see text].

Impact of tibetan plateau snow cover on tropical cyclogenesis via the Madden–Julian oscillation during the following boreal summer

This study investigates the role of the interannual variation of boreal winter (December–February) snow cover over the Tibetan Plateau (TPSC) in modulating the relationship between the Madden Julian Oscillation (MJO) and tropical cyclogenesis over the western North Pacific (WNP) during the following boreal summer (June–October). During the boreal summer following a high snow cover anomaly (SCA), MJO-associated convection tends to be confined to the west of 140 °E, coinciding with more frequent tropical cyclone (TC) activity in this region. By contrast, there tends to be stronger MJO-associated convection extending farther east during years following low SCA. The MJO-associated convection extends to ~ 160 °E over the WNP basin with a peak around 140 °E. Thus, more TCs form farther east in the WNP in these years. We use composite analyses of large-scale environmental factors to demonstrate that low-level relative vorticity is one of the most important factors in controlling TCs in response to the change of MJO-associated convection between years with high SCA and low SCA. Meanwhile, eddy kinetic energy variations associated with the MJO are consistent with changes in tropical cyclogenesis over the WNP basin between years with high and low SCA. The Asian summer monsoon plays an important role in linking prior winter TPSC to MJO activity in the following summer. During high-SCA years, increased snow cover results in positive soil moisture anomalies and cooling over the Tibetan Plateau, thus weakening the following summer Asian monsoon and weakening associated water vapor advection, while the opposite chain of events occurs in low-SCA years. These changes in high-SCA years are favorable for MJO propagation and are unfavorable for MJO propagation in low-SCA years. Meanwhile, the interannual variation of SCA exerts a significant impact on the upper-tropospheric circulation and thus changes in vertical wind shear. During high-SCA years, there are anomalous upper-level easterlies in the Indian Ocean and upper-level westerlies in the Pacific Ocean, which result in anomalous easterly wind shear in the Indian Ocean and anomalous westerly shear in the Pacific Ocean. The opposite shear pattern arises in low-SCA years. In addition to changes in wind shear, the background vertical motion associated with changes in TPSC may also be partly responsible for changes in MJO activity.

Dispersionless pulse transport in mass-spring chains: All possible perfect Newton's cradles.

A pulse traveling on a uniform nondissipative chain of N masses connected by springs is soon destructured by dispersion. Here it is shown that a proper modulation of the masses and the elastic constants makes it possible to obtain a periodic dynamics and a perfect transmission of any kind of pulse between the chain ends, since the initial configuration evolves to its mirror image in the half period. This makes the chain behave as a Newton's cradle. By a known algorithm based on orthogonal polynomials one can numerically solve the general inverse problem leading from the spectrum to the dynamical matrix and then to the corresponding mass-spring sequence, so yielding all possible "perfect cradles." As quantum linear systems obey the same dynamics of their classical counterparts, these results also apply to the quantum case: For instance, a wave function localized at one end would evolve to its mirror image at the opposite chain end.

Haemodynamic Changes & Complications between Unilateral and Bilateral Spinal Anesthesia in Elderly Type-2 Diabetic Patient Undergoing Hemiarthoplasty – A Comparative Study

Background: During spinal anesthesia, extend of sympathetic blockade causes hemodynamic instability,such as hypotension and bradycardia.It can lead to develop cardiac arrest in some cases. Elderly patientdo not compensate these haemodynamic change easily because of aging process leads some physiologicalchanges in all system especially on cardio vascular system e.g; decreased elasticity of vessels, decreasedvascular and myocardial compliance and also decreased autonomic responsiveness. It is hypothesizedthat unilateral spinal anesthesia restrict the spread of hyperbaric bupivacaine to one side only (dependentside) thus sparing the opposite sympathetic chain and hence would cause less haemodynamic changes. Materials & Methods: This cross sectional study, took place in the department of Anaesthesiology andSICU, BIRDEM General Hospital, Shahbag, Dhaka. A total 60 elderly (age-60 to 80 years), ASA grade IIand III, type-2 Diabetic patients scheduled for hemiarthoplasty were enrolled in this study. Patients weredivided into two groups U & A, 30 patients in each. Subarachnoid (spinal) anaesthesia was performed inall patients with 0.5% hyperbaric bupivacaine intrathecally, at L3 - L4 interspinous spaces, with 25GQuinke’s spinal needle. Patients of group U were kept in lateral decubitus position which was maintainedfor 15 minutes after injecting bupivacaine and patients of group B were kept in supine position. Changesof BP, pulse and development of any complication was recorded in 5 minute interval after spinal anesthesia.All the informations were recorded in preformed data collection sheet. Result: Compared with group U, group B showed statistically significant increase inheart rate at 10 minafter spinal anesthesia (p<0.05).Systolic BP was significantly lower in group B compared to group U in allrecorded time interval except at 60 minute.Diastolic blood pressure was significantly lower in group Bcompared to group U at 15, 30 and 45 minute reading. Regarding maen arterial pressure we found it wasreduced significantly in group B compared to group U in all the recorded time except at 60 minute(p<0.05). Present study showed none of the patients in the unilateral group experienced vomiting; onlytwo patients noticed nausea. In the bilateral group, seven patients had nausea and three of them experiencedepisodes of vomiting (p = 0.02). In group U, no case found hypotensive, only single developed bradycardia.In Group B 7 patients experienced hypotensions and 4 patients had bradycardia. Conclusion: This study showed that the unilateral spinal anesthesia reduces the incidence and severityof hypotension, bradycardia and other complication in elderly type-2 diabetic patients. So unilateralspinal anaesthesia is more benifecial for elderly type-2 diabetic patient in hemiarthoplasty. JBSA 2020; 33(2): 62-68

Uptake and translocation of perfluoroalkyl acids (PFAAs) in hydroponically grown red chicory (Cichorium intybus L.): Growth and developmental toxicity, comparison with growth in soil and bioavailability implications

Short-chain perfluoroalkyl acids (PFAAs) have shown a high potential for plant (crop) uptake, making them possibly significant contributors to the total dietary exposure to PFAAs. The plant uptake of PFAAs is a complex process that needs better characterization, as it does not only depend on perfluoroalkyl chain length, but also on their polar terminal group, on the plant species and the exposure media. Here, a plant uptake study with nine perfluoroalkyl acids (PFAAs) was carried out under the hydroponic (soilless) exposure conditions. Red chicory was grown in a nutrient solution, spiked with PFAAs mixture at three different concentrations (i.e. 62.5, 125 and 250μg/L), in order to extend the range of levels tested and reported in the literature so far. Bioaccumulation metrics and transpiration stream concentration factors (TSCFs) were employed for the plant uptake characterization and consequent comparison with the results of soil uptake experiment we previously performed with the same crop. The results showed that calculated root concentration factors (RCFs) increase with PFAA chain length, while the opposite chain length dependence was present for shoots. Plants from two treatments with the highest PFAAs concentrations manifested physiological changes (discoloration, inhibited roots and leaves growth), despite of the used exposure concentrations being much lower than previously published phytotoxicity thresholds. A comparison among RCFs and TSCFs derived from hydroponic and from the soil experiment has emphasized their different magnitudes and PFAAs chain length dependence patterns. They could not be ascribed only to soil sorption as a process decreasing PFAAs bioavailability for plants, but also to developmental differences between the root systems formed in soil and in nutrient solution and to the potential competitive PFAAs sorption to roots in hydroponics. The interchangeable use of bioaccumulation and translocation parameters derived in hydroponic and soil systems would lead to erroneous conclusions and plant uptake predictions.

Exploring Subunit Communication of Malate Dehydrogenase through Interface Point‐ Mutations

Malate Dehydrogenase (MDH) catalyzes the oxidation/reduction of malate/oxaloacetate through coupling with NAD+/NADH conversion, a key area in cellular metabolism and has been shown to be regulated by citrate. MDH is a homo‐dimer and x‐ray structures show a flexible loop, which upon substrate or citrate binding induces a closed conformational in one subunit, while the other remains open. This implies an as of yet unknown means of communication between the two subunits to convey the open/closed loop response. Concurrent work in the Bell Lab has shown two mutations, S266A & L269A, located in the active site and interface regions display significant changes in kinetic parameters. To further probe these regions and assess individual residue contributions to subunit communication several additional point mutants (I88A, K261M/Q, S270A/C, T255E/V) located between the active site and the subunit interface have been constructed, expressed, purified and characterized. The I88A mutant protein has a 10,000 fold decrease in Vmax while that of the T255E mutant is decreased 1,000 fold. Km for NADH is significantly increased in the I88A mutant while that for T255E remains unchanged. This suggests that decreased affinity for NADH in the I88A mutant results from disruption of the subunit interface., I88 is thought to interact with L269 on the opposite chain, while T255 may be involved in oxaloacetate/malate/citrate binding at the active site. This data is consistent with predicted effects of interface and active site mutations and contributes to a detailed understanding of a predicted inter‐subunit relay system to induce asymmetric conformational changes and ligand binding in this homo‐dimeric enzyme.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A new approach for generating bispecific antibodies based on a common light chain format and the stable architecture of human immunoglobulin G1

Bispecific antibodies combine two different antigen-binding sites in a single molecule, enabling more specific targeting, novel mechanisms of action, and higher clinical efficacies. Although they have the potential to outperform conventional monoclonal antibodies, many bispecific antibodies have issues regarding production, stability, and pharmacokinetic properties. Here, we describe a new approach for generating bispecific antibodies using a common light chain format and exploiting the stable architecture of human immunoglobulin G1 We used iterative experimental validation and computational modeling to identify multiple Fc variant pairs that drive efficient heterodimerization of the antibody heavy chains. Accelerated stability studies enabled selection of one Fc variant pair dubbed "DEKK" consisting of substitutions L351D and L368E in one heavy chain combined with L351K and T366K in the other. Solving the crystal structure of the DEKK Fc region at a resolution of 2.3 Å enabled detailed analysis of the interactions inducing CH3 interface heterodimerization. Local shifts in the IgG backbone accommodate the introduction of lysine side chains that form stabilizing salt-bridge interactions with substituted and native residues in the opposite chain. Overall, the CH3 domain adapted to these shifts at the interface, yielding a stable Fc conformation very similar to that in wild-type IgG. Using the DEKK format, we generated the bispecific antibody MCLA-128, targeting human EGF receptors 2 and 3. MCLA-128 could be readily produced and purified at industrial scale with a standard mammalian cell culture platform and a routine purification protocol. Long-term accelerated stability assays confirmed that MCLA-128 is highly stable and has excellent biophysical characteristics.

Abstract 3693: Single cell RNA-Seq of primary lymphomas reveals the diverse transcriptional states of the cancer immunologic milieu

Abstract Follicular lymphoma (FL) is an incurable B-cell malignancy that has the potential to transform into highly aggressive, lethal lymphomas. To resolve the cellular characteristics of the underlying cancer immunologic milieu at single cell resolution, we leveraged droplet-based barcoding technology for highly parallel single cell RNA-Seq. We analyzed the transcriptomes across tens of thousands of indviidual cells derived from five primary FL tumors (average > 5,000 cells per sample). These tumors were obtained via direct surgical biopsies. In parallel, we conducted multi-dimensional flow cytometry that orthogonally confirmed our characterization of the various cell types including the various subsets of T cells that existed within each tumor. We identified multiple cellular subpopulations, matching known hematopoietic lineages that were present within each tumor. Despite some common features, such as MYC and BCL overexpression, transcriptional patterns and regulatory programs destinguished the different tumors from each other. We compared the transcriptional profiles of malignant cellular subpopulations to the matched normal B-cells within each sample. Malignant B-cells were characterized by expression of restricted immunoglobulin light chain type (either kappa or lambda), BCL2 expression, and CD20 expression. In each case a minor population of normal B-cells was characterized by expression of the opposite light chain type and a pattern of gene expression common to B cells in all tumor samples and normal peripheral blood. Tumor B cells consistently demonstrated downregulation of β-2-microglobulin and for those cases that harbored a founder CREBBP mutation, a downregulation of MHC II, that would cause an alteration in antigen presentation and evasion of the T cell immune system. Moreover, we characterized the transcriptional profiles of the infiltrating T-cell populations within each tumor, providing a high-resolution perspective of immunologic cellular interactions. Overall, we identified the diverse transcriptional states at single cell resolution among different tumors and discovered specific genes that were aberrantly expressed compared to normal B cells within the same microenvironment. Our findings provide an unprecedented resolution of distinct immune lineages as seen by transcriptionally characterized cell diversity. Studies using single cell genomics may have implications for considering immunotherapeutic efficacy. Citation Format: Noemi Andor, Erin Simonds, Jiamin Chen, Christina Wood, Susan Grimes, Debra Czerwinski, Grace Zheng, Ronald Levy, Hanlee P. Ji. Single cell RNA-Seq of primary lymphomas reveals the diverse transcriptional states of the cancer immunologic milieu [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3693. doi:10.1158/1538-7445.AM2017-3693

Wavepacket delocalization, self-trapping and fragmentation in discrete chains with relaxing nonlinearity

Abstract The discrete nonlinear Schrodinger equation (DNSE) describes wave phenomena in several physical contexts, ranging from electronic transport in crystalline chains to light propagation in nonlinear media and Bose-Einstein condensates. Here, we study the influence of the nonlinear response time on the temporal evolution of a wavepacket initially localized in a single site of a finite closed chain. Distinct long-time wavepacket distributions are identified as a function of the nonlinear strength χ and the characteristic relaxation time τ. Besides the more standard delocalized and self-trapped regimes, we report the occurrence of intermediate phases. In one of them the wavepacket self-focus in the opposite chain site. A phase with asymptotically fragmented wavepackets also develops. A crossover regime on which the ultimate wavepacket distribution is strongly dependent on the precise set of model parameters is also identified. We provide the full phase diagram related to the long-time wavepacket distribution in the (χ, τ) space.

Abstract 3513: Promoting TRAIL apoptosis signaling using 17-beta-hydroxywithanolides

Abstract We have previously reported that withanolide E (WE), a steroidal lactone from Physalis peruviana, was highly active in sensitizing various human carcinoma cell lines to TRAIL-mediated apoptosis. Treatment of cancer cells with WE induced a reduction in the levels of the antiapoptotic proteins cFLIPL and cFLIPS, resulting in an increased activation of caspase-8 on subsequent TRAIL binding to its death receptors DR4 or DR5. The reduction in cFLIPL and cFLIPS was due to their destabilization and increased degradation by the proteasome. Interestingly, WE (a 17-beta-hydoxywithanolide, 17-BHW) was a far superior TRAIL sensitizer than more widely studied withaferin A (WFA) and its analogues, which lack the 17-beta-hydroxy group and bear an opposite side chain orientation, exhibit more promiscuous reactivity and are much more directly toxic to cells. Therefore, over 30 natural and semi-synthetic 17-BHWs were evaluated for their ability to promote death ligand-mediated cancer cell death. The 17-BHWs used in this work were obtained by the application of an efficient method of plant biomass production involving our innovative and patented soil-less aeroponic cultivation of P. crassifolia and P. peruviana and by chemical modification of natural withanolides produced by these plants. Our studies identified several 17-BHWs that were 4-8 fold more potent than WE in sensitizing the renal carcinoma cells ACHN to TRAIL-mediated apoptosis. These more active 17-BHWs were also more efficient at reducing cellular levels of cFLIPL and cFLIPS and enhancing caspase-8 activation. Preliminary structure activity relationship (SAR) studies suggested that the enone moiety in ring A was essential for activity. In addition acetoxylation at C-18, an alpha orientation of the lactone group and the double bond at C-24(25) of the lactone ring played important roles in determining the activity of 17-BHWs as TRAIL sensitizers. This suggests that the 17-BHW scaffold is amenable to optimization by a medicinal chemistry approach, which could lead to the identification of highly active natural product-based sensitizers of cancer cells to TRAIL-mediated apoptosis. The cellular molecular target(s) of active 17-BHWs are currently under further investigation. Funded by FNLCR Contract HHSN261200800001E Citation Format: Alan D. Brooks, Ya-ming Xu, E. M. Kithsiri Wijeratne, Poonam Tewary, Curtis J. Henrich, Cheryl L. Thomas, A. A. Leslie Gunatilaka, Thomas J. Sayers. Promoting TRAIL apoptosis signaling using 17-beta-hydroxywithanolides. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3513.

Stereocomplex- and homo-crystallization of blends from 2-armed poly(l-lactide) and poly(d-lactide) with identical and opposite chain directional architectures and of 2-armed stereo diblock poly(lactide)

Ethylene glycol (EG) and succinic anhydride (SA)-based 2-armed PLLA and PDLA correspondingly with tail-to-tail (T–T) and head-to-head (H–H) architectures, together with SA-based linear 2-armed stereo diblock copolymer, were synthesized and the SC crystallization and homo-crystallization behavior of blends of 2-armed PLLA and PDLA with various combinations of molecular architectures, together with that of neat polymers, were investigated. The crystallizability was higher for SC crystalline samples than for homo-crystalline samples during solvent evaporation and slow cooling from the melt. The hydrogen bonds of hydroxyl terminals and/or low molecular weight of EG-based polymer rather than specific chain directional architecture or its combination disturbed and delayed the crystallization, lowering the crystallization temperature (Tc), crystalline], the reciprocal of experimental crystallization half time [1/tc(1/2) (exp)], spherulite growth rate (G), enthalpy of crystallization (ΔHc) for 1st cooling, and total enthalpy of cold crystallization and melting [ΔH(tot)] for 2nd heating of both SC crystalline and homo-crystalline samples, the melting temperature (Tm) for 1st and 2nd heating, nucleus density and the degree of lamella orientation of spherulites of SC crystalline samples. The opposite chain directional architectures of polymers in blends should have increased ΔH(tot) for 1st heating, ΔHc for 1st cooling, ΔH(tot) for 2nd heating, and G of SC crystalline samples. The effects of hydrogen bonds of hydroxyl terminal groups, Mn (or Mn per one arm or block), and chain directional combination were determined by the crystallization temperature range and the presence or absence of a solvent. The Tm values of SC crystalline samples were determined by Mn (or Mn per one arm or block), whereas those of homo-crystalline samples did not show clear dependence on Mn (or Mn per one arm or block) values per one arm, hydroxyl terminal groups (hydrogen bonding), or chain direction. The intermolecular SC crystallization in the enantiomeric polymer blends was favored compared with intramolecular SC crystallization in the stereo diblock copolymer.

Intraseasonal and Interdecadal Jet Shifts in the Northern Hemisphere: The Role of Warm Pool Tropical Convection and Sea Ice

Abstract This study uses cluster analysis to investigate the interdecadal poleward shift of the subtropical and eddy-driven jets and its relationship to intraseasonal teleconnections. For this purpose, self-organizing map (SOM) analysis is applied to the ECMWF Interim Re-Analysis (ERA-Interim) zonal-mean zonal wind. The resulting SOM patterns have time scales of 4.8–5.7 days and undergo notable interdecadal trends in their frequency of occurrence. The sum of these trends closely resembles the observed interdecadal trend of the subtropical and eddy-driven jets, indicating that much of the interdecadal climate forcing is manifested through changes in the frequency of intraseasonal teleconnection patterns. Two classes of jet cluster patterns are identified. The first class of SOM pattern is preceded by anomalies in convection over the warm pool followed by changes in the poleward wave activity flux. The second class of patterns is preceded by sea ice and stratospheric polar vortex anomalies; when the Arctic sea ice area is reduced, the subsequent planetary wave anomalies destructively interfere with the climatological stationary waves. This is followed by a decrease in the vertical wave activity flux and a strengthening of the stratospheric polar vortex. An increase in sea ice area leads to the opposite chain of events. Analysis suggests that the positive trend in the Arctic Oscillation (AO) up until the early 1990s might be attributed to increased warm pool tropical convection, while the subsequent reversal in its trend may be due to the influence of tropical convection being overshadowed by the accelerated loss of Arctic sea ice.

Opposite verging chains sharing the same foreland: Kinematics and interactions through analogue models (Central Po Plain, Italy)

Abstract In this study, we investigate the potential role played by different geological factors on the development of a thrust system. In particular our goal is to analyze how pre-existing compressional structures located in the foreland of a thrust-and-fold belt may affect the kinematics of a thrust system. We studied such circumstances both in a natural case and through analogue models. As a natural case, we selected the Central Po Plain (Italy), where the buried external fronts of the Northern Apennines and Southern Alps are very close to each other. Starting from a regional cross-section representative of this tectonic setting, we reconstructed the post-Messinian development of the Apennines thrust fronts, which includes out-of-sequence thrusting. Then, we modeled this evolution through a set of analogue experiments to evaluate the possible relationships of the out-of-sequence thrusting with the burial of the syntectonic sediments and/or the existence of the outer fronts of an opposite verging chain in its foreland. The comparison between natural case and models highlights that the presence of opposite verging thrust fronts in the foreland of a belt limits the propagation of new thrusts favoring the out-of-sequence reactivation of inner thrusts. An analysis of the study area with respect to adjacent tectonic settings, coupled with analogue models, revealed that syntectonic sedimentation as well has a role in the reactivation of the inner fronts, although secondary. In the Po Plain specific case, this implies that the presence of the buried Southern Alps fronts affects the Northern Apennines kinematics, even if the two fronts did not collide yet.

Photoinduced charge separation in aqueous solution of porphyrin-quinone end-capped poly(methacrylic acid)

Photoinduced charge separation from porphyrin (P) to benzoquinone (Q) moieties covalently attached to the opposite chain ends of poly(methacrylic acid) (PMMA) was studied. The effect of polymer chain length, pH and ionic strength of the aqueous solution on the rate constant of charge separation and efficiency of P+• -Q - radical ion

Two Distinct 2D Cd(II)/Zn(II) Networks Based on Flexible 1,2-Phenylenediacetate and N-donor Co-Ligand: Synthesis, Structure, and Fluorescent Properties

Two novel Cd(II)/Zn(II) compounds based on flexible benzene dicarboxylate and N-donor auxiliary ligands, formulated as [Cd(phda)(dpe)]n (1) and [Zn(phda)(acpy)(H2O)]n (2), have been synthesized by the hydrothermal reaction and characterized by single-crystal X-ray diffraction, elemental analysis, IR, and fluorescent spectra (phda = 1,2-phenylenediacetate, dpe = 1,2-di(4-pyridyl)-ethylene, and acpy = 4-acetylpyridine). Complex 1 displays 2D bilayer network featuring phda-bridged binuclear cadmium (II) ribbon-like chain further pillared by dpe ligand, whereas complex 2 exhibits 2D thick-layer with {4.82}-fes topology featuring phda-bridging carboxylate layer constructed by the alternate opposite helix chain. In addition, luminescent properties of the both complexes are also investigated.

Tectono-sedimentary setting of the Po Plain and Adriatic foreland

Based on the substantial drilling and 2D/3D seismic control achieved during a 60-year-long hydrocarbon exploration history, a detailed reconstruction of the Adria plate foreland shared by the converging Southalpine, Dinaric/Albanian and Apennines chains is presented. Eight depth converted seismic transects joining the opposing belt margins and three time-scaled maps of the evolving tectono-sedimentary framework illustrate the shallow crustal geometry and evolution of the study area. Its Cenozoic compressional architecture results overprinted to and somewhere strongly controlled by the late Permian to early Cretaceous extensional features generated during the Mesozoic rift. The effects of the Cenozoic shortening affected the foreland at different times and with variable directions of tectonic deformation. The Dinaric and Albanian chain compression operated since Paleocene to, respectively, early Miocene and Pleistocene. The western and eastern Southalpine comparts acted on the area since early Oligocene to Messinian and middle Miocene to Pleistocene, respectively, whereas the Apennines system involved it since middle-late Miocene to Pleistocene. The result is a fragmented post-Eocene tectonic evolution of the Adriatic foreland controlled by both the diachronous chain segment activity and their coeval competition. The effect of the opposite chain segment interference was a multiple system of differently evolving foredeeps not exclusively ruled by the chain load at their back. Time and amount of the foreland flexuring were moreover accompanied by formation of transversal positive belts that played the role of transfer zones.

Converting Tumor-specific Markers Into Reporters of Oncolytic Virus Infection

Preferential killing of transformed cells, while keeping normal cells and organs unharmed, is the main goal of cancer gene therapy. Genetically engineered trackable markers and imaging reporters enable noninvasive monitoring of transduction efficiency and pharmacokinetics of anticancer virotherapeutics. However, none of these reporters can differentiate between infection in the targeted tumors and that in the normal tissue. Thus, we constructed oncolytic measles virus (MV) armed with a human light immunoglobulin chain reporter gene for the treatment of multiple myeloma (MM). Excessive production of monoclonal immunoglobulin is a key characteristic and marker for diagnostics of MM. Once expressed in infected target cells, vector-encoded lambda protein recombines with myeloma IgG-kappa immunoglobulin creating a unique IgG-kappa/lambda. A modified immunoassay technique allows precise quantification of converted marker molecules. Only antibody producing cells were able to assemble this chimeric immunoglobulin molecule, whereas other cells secreted only free lambda light chain. Human myeloma xenografts inoculated with lambda chain expressing MV secreted converted IgG-kappa/lambda in the plasma of tumor bearing animals and elevated reporter levels correlated with response to the therapy. This is the first report of a gene therapy vector engineered to discriminate between infection in malignant and normal cells by molecular modification of a tumor-specific protein.