Precise measurements of radio-frequency magnetic susceptibility in (anti)ferromagnetic materials

Dynamic magnetic susceptibility, $\chi$, was studied in several intermetallic materials exhibiting ferromagnetic, antiferromagnetic and metamagnetic transitions. Precise measurements by using a 14 MHz tunnel diode oscillator (TDO) allow detailed insight into the field and temperature dependence of $\chi$. In particular, local moment ferromagnets show a sharp peak in $\chi(T)$ near the Curie temperature, $T_c$. The peak amplitude decreases and shifts to higher temperatures with very small applied dc fields. Anisotropic measurements of CeVSb$_3$ show that this peak is present provided the magnetic easy axis is aligned with the excitation field. In a striking contrast, small moment, itinerant ferromagnets (i.e., ZrZn$_2$) show a broad maximum in $\chi(T)$ that responds differently to applied field. We believe that TDO measurements provide a very sensitive way to distinguish between local and itinerant moment magnetic orders. Local moment antiferromagnets do not show a peak at the N\'eel temperature, $T_N$, but only a sharp decrease of $\chi$ below $T_N$ due to the loss of spin-disorder scattering changing the penetration depth of the ac excitation field. Furthermore, we show that the TDO is capable of detecting changes in spin order as well as metamagnetic transitions. Finally, critical scaling of $\chi(T,H)$ in the vicinity of $T_C$ is discussed in CeVSb$_3$ and CeAgSb$_2$

Multilevel human secondary lymphoid immune system compartmentalization revealed by complementary imaging approaches.

Secondary human lymphoid tissue immune reactions take place in a highly coordinated environment with compartmentalization representing a fundamental feature of this organization. In situ profiling methodologies are indispensable for the understanding of this compartmentalization. Here, we propose a complementary experimental approach aiming to reveal different aspects of this process. The analysis of human tonsils, using a combination of single cell phenotypic analysis based on flow cytometry and multiplex imaging and mass spectrometry-based methodologies, revealed a compartmentalized organization at the cellular and molecular levels. More specifically, the skewed distribution of highly specialized immune cell subsets and relevant soluble mediators was accompanied by a compartmentalized localization of several lipids across different anatomical areas of the tonsillar tissue. The performance of such combinatorial experimental approaches could lead to the identification of novel in situ interactions and molecular targets for the in vivo manipulation of lymphoid organ, particularly the germinal center, immune reactions

Polaron formation for a non-local electron-phonon coupling: A variational wave-function study

We introduce a variational wave-function to study the polaron formation when the electronic transfer integral depends on the relative displacement between nearest-neighbor sites giving rise to a non-local electron-phonon coupling with optical phonon modes. We analyze the ground state properties such as the energy, the electron-lattice correlation function, the phonon number and the spectral weight. Variational results are found in good agreement with analytic weak-coupling perturbative calculations and exact numerical diagonalization of small clusters. We determine the polaronic phase diagram and we find that the tendency towards strong localization is hindered from the pathological sign change of the effective next-nearest-neighbor hopping.Comment: 11 page

Vascular Endothelial Growth Factor-Related Pathways in Hemato-Lymphoid Malignancies

Angiogenesis is essential for malignant tumor growth. This has been documented for solid tumors, and there is an emerging evidence suggesting that tumor progression of hematolymphoid malignancies also depends on the induction of new blood vessel formation. The most important proangiogenic agent is vascular endothelial growth factor (VEGF), activating VEGF receptors 1 and 2. The available data on angiogenesis in hemato-lymphoid malignancies, such as acute leukemias, myelodysplastic syndromes, myeloproliferative neoplasms, multiple myeloma, and lymphomas, point towards the significance of autocrine and paracrine VEGF-mediated effects for proliferation and survival of leukemia/lymphoma cells in addition to tumor vascularization. Antiangiogenic strategies have become an important therapeutic modality for solid tumors. Several antiangiogenic agents targeting VEGF-related pathways are also being utilized in clinical trials for the treatment of hemato-lymphoid malignancies, and in some instances these pathways have emerged as promising therapeutic targets. This review summarizes recent advances in the basic understanding of the role of angiogenesis in hemato-lymphoid malignancies and the translation of such basic findings into clinical studies

Tasmanian devil CD28 and CTLA4 capture CD80 and CD86 from adjacent cells

Immune checkpoint immunotherapy is a pillar of human oncology treatment with potential for non-human species. The first checkpoint immunotherapy approved for human cancers targeted the CTLA4 protein. CTLA4 can inhibit T cell activation by capturing and internalizing CD80 and CD86 from antigen presenting cells, a process called trans-endocytosis. Similarly, CD28 can capture CD80 and CD86 via trogocytosis and retain the captured ligands on the surface of the CD28-expressing cells. The wild Tasmanian devil (Sarcophilus harrisii) population has declined by 77% due to transmissible cancers that evade immune defenses despite genetic mismatches between the host and tumors. We used a live cell-based assay to demonstrate that devil CTLA4 and CD28 can capture CD80 and CD86. Mutation of evolutionarily conserved motifs in CTLA4 altered functional interactions with CD80 and CD86 in accordance with patterns observed in other species. These results suggest that checkpoint immunotherapies can be translated to evolutionarily divergent species.</p

Emergence of Anti-Cancer Drug Resistance: Exploring the Importance of the Microenvironmental Niche via a Spatial Model

Practically, all chemotherapeutic agents lead to drug resistance. Clinically, it is a challenge to determine whether resistance arises prior to, or as a result of, cancer therapy. Further, a number of different intracellular and microenvironmental factors have been correlated with the emergence of drug resistance. With the goal of better understanding drug resistance and its connection with the tumor microenvironment, we have developed a hybrid discrete-continuous mathematical model. In this model, cancer cells described through a particle-spring approach respond to dynamically changing oxygen and DNA damaging drug concentrations described through partial differential equations. We thoroughly explored the behavior of our self-calibrated model under the following common conditions: a fixed layout of the vasculature, an identical initial configuration of cancer cells, the same mechanism of drug action, and one mechanism of cellular response to the drug. We considered one set of simulations in which drug resistance existed prior to the start of treatment, and another set in which drug resistance is acquired in response to treatment. This allows us to compare how both kinds of resistance influence the spatial and temporal dynamics of the developing tumor, and its clonal diversity. We show that both pre-existing and acquired resistance can give rise to three biologically distinct parameter regimes: successful tumor eradication, reduced effectiveness of drug during the course of treatment (resistance), and complete treatment failure

Glutamate Concentration in the Serum of Patients with Schizophrenia

Glutamate is the major neurotransmitter with multiple functions in the central nervous system. Glutamate-mediated excitotoxicity is involved in the pathophysiological processes in schizophrenia. The purpose of this study was to determine the concentration of glutamate in the serum of patients with paranoid schizophrenia compared with healthy individuals, and depending on the duration of the schizophrenic process and leading clinical symptoms. We investigated the level of glutamate in the serum of 158 patients with paranoid schizophrenia and 94 healthy persons. Higher concentrations of glutamate in schizophrenic patients compared with healthy persons have been found. The maximum concentrations of glutamate were detected in patients with disease duration of more than ten years. Glutamate level in the serum does not depend on the prevailing negative or positive clinical symptoms. The increased concentration of glutamate can hypothetically contribute to dopaminergic and glutamatergic imbalance, leading to the development of psychotic symptoms and cognitive dysfunction

A novel system to map protein interactions reveals evolutionarily conserved immune evasion pathways on transmissible cancers

Around 40% of humans and Tasmanian devils (Sarcophilus harrisii) develop cancer in their lifetime, compared to less than 10% for most species. In addition, devils are affected by two of the three known transmissible cancers in mammals. Immune checkpoint immunotherapy has transformed human medicine, but a lack of species-specific reagents has limited checkpoint immunology in most species. We developed a cut-and-paste reagent development system and used the fluorescent fusion protein system to show that immune checkpoint interactions are conserved across 160,000,000 years of evolution, CD200 is highly expressed on transmissible tumor cells, and coexpression of CD200R1 can block CD200 surface expression. The system’s versatility across species was demonstrated by fusing a fluorescent reporter to a camelid-derived nanobody that binds human programmed death ligand 1. The evolutionarily conserved pathways suggest that naturally occurring cancers in devils and other species can be used to advance our understanding of cancer and immunological tolerance.</p

Electron Dynamics in Nd1.85_{1.85}Ce.15_{.15}CuO4+δ_{4+\delta}: Evidence for the Pseudogap State and Unconventional c-axis Response

Infrared reflectance measurements were made with light polarized along the a- and c-axis of both superconducting and antiferromagnetic phases of electron doped Nd$_{1.85}$Ce$_{.15}$CuO$_{4+\delta}$. The results are compared to characteristic features of the electromagnetic response in hole doped cuprates. Within the CuO$_2$ planes the frequency dependent scattering rate, 1/$\tau(\omega)$, is depressed below $\sim$ 650 cm$^{-1}$; this behavior is a hallmark of the pseudogap state. While in several hole doped compounds the energy scales associated with the pseudogap and superconducting states are quite close, we are able to show that in Nd$_{1.85}$Ce$_{.15}$CuO$_{4+\delta}$ the two scales differ by more than one order of magnitude. Another feature of the in-plane charge response is a peak in the real part of the conductivity, $\sigma_1(\omega)$, at 50-110 cm$^{-1}$ which is in sharp contrast with the Drude-like response where $\sigma_1(\omega)$ is centered at $\omega=0$. This latter effect is similar to what is found in disordered hole doped cuprates and is discussed in the context of carrier localization. Examination of the c-axis conductivity gives evidence for an anomalously broad frequency range from which the interlayer superfluid is accumulated. Compelling evidence for the pseudogap state as well as other characteristics of the charge dynamics in Nd$_{1.85}$Ce$_{.15}$CuO$_{4+\delta}$ signal global similarities of the cuprate phase diagram with respect to electron and hole doping.Comment: Submitted to PR