Multivalent Probes in Molecular Imaging:Reality or Future?

The rapidly developing field of molecular medical imaging focuses on specific visualization of (patho)physiological processes through the application of imaging agents (IAs) in multiple clinical modalities. Although our understanding of the principles underlying efficient IAs design has increased tremendously, many IAs still show poor in vivo imaging performance because of low binding affinity and/or specificity. These limitations can be addressed by taking advantage of multivalency, in which multiple copies of a ligand are employed to strengthen the interaction. We critically address specific challenges associated with the application of multivalent compounds in molecular imaging, and we give directions for a stepwise approach to the design of multivalent imaging probes to improve their target binding and pharmacokinetics (PK) for improved diagnostic potential. The rapidly developing field of molecular medical imaging focuses on specific visualization of (patho)physiological processes through the application of imaging agents (IAs) in multiple clinical modalities. Although our understanding of the principles underlying efficient IAs design has increased tremendously, many IAs still show poor in vivo imaging performance because of low binding affinity and/or specificity. These limitations can be addressed by taking advantage of multivalency, in which multiple copies of a ligand are employed to strengthen the interaction. We critically address specific challenges associated with the application of multivalent compounds in molecular imaging, and we give directions for a stepwise approach to the design of multivalent imaging probes to improve their target binding and pharmacokinetics (PK) for improved diagnostic potential. Challenges and Applications of Molecular Imaging in Medicine Medical imaging enables the visualization of anatomical structures and physiological processes for diagnostic purposes [1,2], and is commonly subcategorized into structural, functional, and molecular imaging [3]. Molecular imaging reveals diagnostically relevant biochemical information [4,5] at cellular and molecular levels in vivo [6,7]. Therefore, in addition to diagnostic applications

The US in Uterus: A Collaborative Autoethnography of Psychologists Advocating for Reproductive Justice

In light of the recent Supreme Court decision to overturn Roe v. Wade, millions of people with uteruses have been forced to navigate precarious access to reproductive care. Although health service psychologists have an ethical responsibility to engage in reproductive justice advocacy, training programs often do not adequately address sexual and reproductive health. Therefore, we sought to better understand how health service psychologists’ personal and professional experiences influence each other and explore the ways in which we as reproductive beings and advocates sustain ourselves amidst tremendous sociopolitical uncertainty. In order to do so, we employed a feminist collaborative autoethnography approach grounded in critical theory. Attending to intersectional identities that help shape diverse expectations and experiences, two early career psychologists and four trainees uncovered 12 domains: barriers in academia; reproductive (dis)empowerment; relational connection; power(lessness) associated with social locations; internalization of sex-negative messages; the influence of sociopolitical climate; burdens related to reproductive rights; evaluations of reproductive justice efforts; component of professional identity; expectations from family and community; overwhelming and exhausting advocacy; and fears of inadequacy. We conclude with limitations and implications for the continued promotion of advocacy through practice and training within and beyond the field of psychology

Atypical presentation of acute pancreatitis in a man with pancreatic insufficiency and cystic fibrosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Whether acute pancreatitis can occur in pancreatically insufficient individuals with cystic fibrosis remains a matter of debate.</p> <p>Case presentation</p> <p>We describe a case of acute pancreatitis occurring in a 52-year-old Caucasian Australian man with moderately severe cystic fibrosis lung disease and pancreatic insufficiency. An inflammatory mass within the head of his pancreas was confirmed using computed tomography, magnetic resonance imaging and pancreatic biopsy, but serum amylase and lipase remained normal throughout the acute phase of his illness. His symptoms and the pancreatic mass resolved following the insertion of a biliary stent and the introduction of ursodeoxycholic acid.</p> <p>Conclusion</p> <p>Our case report highlights the potential for acute pancreatitis to occur in patients with pancreatic insufficiency and cystic fibrosis. We further demonstrate that conventional biochemical markers that are normally assessed to confirm the diagnosis may not be of particular use. As patients with cystic fibrosis survive into their fourth and fifth decades of life, atypical presentations of acute pancreatitis may become more common.</p

Spectral Evidence for Emergent Order in Ba1−x_{1-x}Nax_xFe2_2As2_2

We report an angle-resolved photoemission spectroscopy study of the iron-based superconductor family, Ba$_{1-x}$Na$_x$Fe$_2$As$_2$. This system harbors the recently discovered double-Q magnetic order appearing in a reentrant C$_4$ phase deep within the underdoped regime of the phase diagram that is otherwise dominated by the coupled nematic phase and collinear antiferromagnetic order. From a detailed temperature-dependence study, we identify the electronic response to the nematic phase in an orbital-dependent band shift that strictly follows the rotational symmetry of the lattice and disappears when the system restores C$_4$ symmetry in the low temperature phase. In addition, we report the observation of a distinct electronic reconstruction that cannot be explained by the known electronic orders in the system

Non-minimal Quintessence: Dynamics and coincidence problem

Brans--Dicke scalar--tensor theory provides a conformally coupling of the scalar field with gravity in Einstein's frame. This model is equivalent to an interacting quintessence in which dark matter is coupled to dark energy. This provides a natural mechanism to alleviate the coincidence problem. We investigate the dynamics of this model and show that it leads to comparable dark energy and dark matter densities today.Comment: To appear in Pramana Journal of Physics, 201

Lattice dynamics and correlated atomic motion from the atomic pair distribution function

The mean-square relative displacements (MSRD) of atomic pair motions in crystals are studied as a function of pair distance and temperature using the atomic pair distribution function (PDF). The effects of the lattice vibrations on the PDF peak widths are modelled using both a multi-parameter Born von-Karman (BvK) force model and a single-parameter Debye model. These results are compared to experimentally determined PDFs. We find that the near-neighbor atomic motions are strongly correlated, and that the extent of this correlation depends both on the interatomic interactions and crystal structure. These results suggest that proper account of the lattice vibrational effects on the PDF peak width is important in extracting information on static disorder in a disordered system such as an alloy. Good agreement is obtained between the BvK model calculations of PDF peak widths and the experimentally determined peak widths. The Debye model successfully explains the average, though not detailed, natures of the MSRD of atomic pair motion with just one parameter. Also the temperature dependence of the Debye model largely agrees with the BvK model predictions. Therefore, the Debye model provides a simple description of the effects of lattice vibrations on the PDF peak widths.Comment: 9 pages, 11 figure

Spinning Loop Black Holes

In this paper we construct four Kerr-like spacetimes starting from the loop black hole Schwarzschild solutions (LBH) and applying the Newman-Janis transformation. In previous papers the Schwarzschild LBH was obtained replacing the Ashtekar connection with holonomies on a particular graph in a minisuperspace approximation which describes the black hole interior. Starting from this solution, we use a Newman-Janis transformation and we specialize to two different and natural complexifications inspired from the complexifications of the Schwarzschild and Reissner-Nordstrom metrics. We show explicitly that the space-times obtained in this way are singularity free and thus there are no naked singularities. We show that the transformation move, if any, the causality violating regions of the Kerr metric far from r=0. We study the space-time structure with particular attention to the horizons shape. We conclude the paper with a discussion on a regular Reissner-Nordstrom black hole derived from the Schwarzschild LBH and then applying again the Newmann-Janis transformation.Comment: 18 pages, 18 figure

Microscopic Theory of Heterogeneity and Non-Exponential Relaxations in Supercooled Liquids

Recent experiments and computer simulations show that supercooled liquids around the glass transition temperature are "dynamically heterogeneous" [1]. Such heterogeneity is expected from the random first order transition theory of the glass transition. Using a microscopic approach based on this theory, we derive a relation between the departure from Debye relaxation as characterized by the $\beta$ value of a stretched exponential response function $\phi(t) =e^{-(t/ \tau_{KWW})^{\beta}}$, and the fragility of the liquid. The $\beta$ value is also predicted to depend on temperature and to vanish as the ideal glass transition is approached at the Kauzmann temperature.Comment: 4 pages including 3 eps figure

CLEC-2 and Syk in the megakaryocytic/platelet lineage are essential for development

The C-type lectin receptor CLEC-2 signals through a pathway that is critically dependent on the tyrosine kinase Syk. We show that homozygous loss of either protein results in defects in brain vascular and lymphatic development, lung inflation and perinatal lethality. Furthermore, we find that conditional deletion of Syk in the haematopoietic lineage, or conditional deletion of CLEC-2 or Syk in the megakaryocyte/platelet lineage, also causes defects in brain vascular and lymphatic development, although the mice are viable. In contrast, conditional deletion of Syk in other haematopoietic lineages had no effect on viability or brain vasculature and lymphatic development. We show that platelets, but not platelet releasate, modulate the migration and intercellular adhesion of lymphatic endothelial cells through a pathway that is dependent on CLEC-2 and Syk. These studies demonstrate that megakaryocyte/platelet expression of CLEC-2 and Syk is required for normal brain vasculature and lymphatic development and that platelet CLEC-2 and Syk directly modulate lymphatic endothelial cell behaviour in vitro