Biomimetic Promotion and Inhibition of Crystal Growth in Calcium Carbonate

Living organisms have evolved effective mechanisms to control the growth of inorganic crystalline materials as structural elements. Previous research has shown that proteins rich in aspartic acid play a pivotal role in driving crystalline orientation, structure, and morphology of calcium carbonate biominerals in the formation of shells in marine bivalves (mussels, clams, abalone). In our research, we examine the effect of aspartic acid on the growth of calcium carbonate by a novel vapor diffusion-based growth technique. The vapor diffusion approach uses a gas-permeable membrane as a barrier to control the physical location of crystal growth. In this way, we are able to directly observe the crystal nucleation and growth using optical microscopy and record changes in growth rates and crystal orientation as we add peptide or polyelectrolyte-based modifiers to the growing crystals. Raman spectroscopy was employed to characterize the resulting crystals and provide insight into the actions of the growth modifiers. Our work is directed towards understanding how molecular modifiers interact with inorganic materials. Developing controls for the growth of calcium carbonate materials could have impacts in many industries which rely on the materials (including pharmaceutical development, household products, and paper, rubber, and paint manufacturing)

Cylindrical shells under uniform bending in the framework of Reference Resistance Design

The resistance of cylindrical shells and tubes under uniform bending has received significant research attention in recent times, with a number of major projects aiming to characterise their strength through both experimental and numerical studies. However, the investigated cross-section slenderness ranges have mostly addressed low radius to thickness ratios where buckling occurs after significant plasticity and the influence of geometric imperfections is relatively minor. The behaviour under uniform bending of thinner imperfection-sensitive cylinders that fail by elastic buckling was largely omitted, as was the influence of finite length effects. The value of such resistance models that are only useful for thicker cylinders is therefore somewhat limited.This paper offers the most comprehensive known characterisation of the buckling and collapse resistance of isotropic cylindrical shells and tubes under uniform bending. Expressed within the modern framework of Reference Resistance Design (RRD), it holistically incorporates the effects of material plasticity, geometric nonlinearity and sensitivity to realistic and damaging weld depression imperfections. The characterisation was made possible by the authors’ recently-developed novel methodology for mass automation of nonlinear shell buckling finite element analyses. A modification of the RRD formulation is proposed which facilitates its application to systems of low slenderness, and offers a compact algebraic characterisation of all potential imperfection amplitudes for this common shell structural condition. A reliability analysis is also performed.<br/

Hysteresis of Electronic Transport in Graphene Transistors

Graphene field effect transistors commonly comprise graphene flakes lying on SiO2 surfaces. The gate-voltage dependent conductance shows hysteresis depending on the gate sweeping rate/range. It is shown here that the transistors exhibit two different kinds of hysteresis in their electrical characteristics. Charge transfer causes a positive shift in the gate voltage of the minimum conductance, while capacitive gating can cause the negative shift of conductance with respect to gate voltage. The positive hysteretic phenomena decay with an increase of the number of layers in graphene flakes. Self-heating in helium atmosphere significantly removes adsorbates and reduces positive hysteresis. We also observed negative hysteresis in graphene devices at low temperature. It is also found that an ice layer on/under graphene has much stronger dipole moment than a water layer does. Mobile ions in the electrolyte gate and a polarity switch in the ferroelectric gate could also cause negative hysteresis in graphene transistors. These findings improved our understanding of the electrical response of graphene to its surroundings. The unique sensitivity to environment and related phenomena in graphene deserve further studies on nonvolatile memory, electrostatic detection and chemically driven applications.Comment: 13 pages, 6 Figure

Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Aβ amyloidosis

The apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for Alzheimer’s disease (AD). The influence of apoE on amyloid β (Aβ) accumulation may be the major mechanism by which apoE affects AD. ApoE interacts with Aβ and facilitates Aβ fibrillogenesis in vitro. In addition, apoE is one of the protein components in plaques. We hypothesized that certain anti-apoE antibodies, similar to certain anti-Aβ antibodies, may have antiamyloidogenic effects by binding to apoE in the plaques and activating microglia-mediated amyloid clearance. To test this hypothesis, we developed several monoclonal anti-apoE antibodies. Among them, we administered HJ6.3 antibody intraperitoneally to 4-mo-old male APPswe/PS1ΔE9 mice weekly for 14 wk. HJ6.3 dramatically decreased amyloid deposition by 60–80% and significantly reduced insoluble Aβ40 and Aβ42 levels. Short-term treatment with HJ6.3 resulted in strong changes in microglial responses around Aβ plaques. Collectively, these results suggest that anti-apoE immunization may represent a novel AD therapeutic strategy and that other proteins involved in Aβ binding and aggregation might also be a target for immunotherapy. Our data also have important broader implications for other amyloidosis. Immunotherapy to proteins tightly associated with misfolded proteins might open up a new treatment option for many protein misfolding diseases

FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells

Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours

Carcinoma and multiple lymphomas in one patient: establishing the diagnoses and analyzing risk factors

Multiple malignancies may occur in the same patient, and a few reports describe cases with multiple hematologic and non-hematologic neoplasms. We report the case of a patient who showed the sequential occurrence of four different lymphoid neoplasms together with a squamous cell carcinoma of the lung. A 62-year-old man with adenopathy was admitted to the hospital, and lymph node biopsy was positive for low-grade follicular lymphoma. He achieved a partial remission with chemotherapy. Two years later, a PET-CT scan showed a left hilar mass in the lung; biopsy showed a squamous cell carcinoma. Simultaneously, he was diagnosed with diffuse large B cell lymphoma in a neck lymph node; after chemo- and radiotherapy, he achieved a complete response. A restaging PET-CT scan 2 years later revealed a retroperitoneal nodule, and biopsy again showed a low-grade follicular lymphoma, while a biopsy of a cutaneous scalp lesion showed a CD30-positive peripheral T cell lymphoma. After some months, a liver biopsy and a right cervical lymph node biopsy showed a CD30-positive peripheral T cell lymphoma consistent with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma. Flow cytometry and cytogenetic and molecular genetic analysis performed at diagnosis and during the patient’s follow-up confirmed the presence of two clonally distinct B cell lymphomas, while the two T cell neoplasms were confirmed to be clonally related. We discuss the relationship between multiple neoplasms occurring in the same patient and the various possible risk factors involved in their development

Properties of Graphene: A Theoretical Perspective

In this review, we provide an in-depth description of the physics of monolayer and bilayer graphene from a theorist's perspective. We discuss the physical properties of graphene in an external magnetic field, reflecting the chiral nature of the quasiparticles near the Dirac point with a Landau level at zero energy. We address the unique integer quantum Hall effects, the role of electron correlations, and the recent observation of the fractional quantum Hall effect in the monolayer graphene. The quantum Hall effect in bilayer graphene is fundamentally different from that of a monolayer, reflecting the unique band structure of this system. The theory of transport in the absence of an external magnetic field is discussed in detail, along with the role of disorder studied in various theoretical models. We highlight the differences and similarities between monolayer and bilayer graphene, and focus on thermodynamic properties such as the compressibility, the plasmon spectra, the weak localization correction, quantum Hall effect, and optical properties. Confinement of electrons in graphene is nontrivial due to Klein tunneling. We review various theoretical and experimental studies of quantum confined structures made from graphene. The band structure of graphene nanoribbons and the role of the sublattice symmetry, edge geometry and the size of the nanoribbon on the electronic and magnetic properties are very active areas of research, and a detailed review of these topics is presented. Also, the effects of substrate interactions, adsorbed atoms, lattice defects and doping on the band structure of finite-sized graphene systems are discussed. We also include a brief description of graphane -- gapped material obtained from graphene by attaching hydrogen atoms to each carbon atom in the lattice.Comment: 189 pages. submitted in Advances in Physic

HIV Promoter Integration Site Primarily Modulates Transcriptional Burst Size Rather Than Frequency

Mammalian gene expression patterns, and their variability across populations of cells, are regulated by factors specific to each gene in concert with its surrounding cellular and genomic environment. Lentiviruses such as HIV integrate their genomes into semi-random genomic locations in the cells they infect, and the resulting viral gene expression provides a natural system to dissect the contributions of genomic environment to transcriptional regulation. Previously, we showed that expression heterogeneity and its modulation by specific host factors at HIV integration sites are key determinants of infected-cell fate and a possible source of latent infections. Here, we assess the integration context dependence of expression heterogeneity from diverse single integrations of a HIV-promoter/GFP-reporter cassette in Jurkat T-cells. Systematically fitting a stochastic model of gene expression to our data reveals an underlying transcriptional dynamic, by which multiple transcripts are produced during short, infrequent bursts, that quantitatively accounts for the wide, highly skewed protein expression distributions observed in each of our clonal cell populations. Interestingly, we find that the size of transcriptional bursts is the primary systematic covariate over integration sites, varying from a few to tens of transcripts across integration sites, and correlating well with mean expression. In contrast, burst frequencies are scattered about a typical value of several per cell-division time and demonstrate little correlation with the clonal means. This pattern of modulation generates consistently noisy distributions over the sampled integration positions, with large expression variability relative to the mean maintained even for the most productive integrations, and could contribute to specifying heterogeneous, integration-site-dependent viral production patterns in HIV-infected cells. Genomic environment thus emerges as a significant control parameter for gene expression variation that may contribute to structuring mammalian genomes, as well as be exploited for survival by integrating viruses