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Systemic amyloidosis is a devastating group of disorders for which there is no current cure. The treatment goal is to reduce the burden of amyloidogenic protein precursors. The treatment is only effective if applied early in the disease process before significant and irreversible end organ damage has taken place. Congo red is still the standard stain used in most histopathology laboratories to identify amyloid material in tissues. The identification of Congophilic amyloid material is challenging because of multiple interfering factors. Here we describe improved sensitivity of identifying Congophilic materials in histologic sections using a metallurgical polarized microscope specifically constructed for polarized microscopy. The microscope is equipped with strain-free optics, matching polarizers, dis-integrated compensators, and a circular mobile stage. Compared to a standard clinical microscope, this setup significantly improves sensitivity of identifying amyloid material in Congo red-stained slides. We also describe the deleterious effect of plastic coverslip which can interfere with the ability to examine the slides under polarized light. We present a series of 10 different patients who had cardiac, brain, and salivary gland biopsies that were either equivocal or deemed negative using a standard clinical microscope but were positive using the equipment described above. These samples were confirmed to be positive by other methods including electron microscopy. We conclude that use of the correct equipment is needed before ruling out amyloidosis in tissue sections.

Etymologically, the word 'sarcasm' is derived from the Greek "sarkazein," meaning "to speak bitterly or sneer", or, more literally, "to tear flesh" ("sarcasm," 2014). Sarcasm, then, is far from a benign feature of language, and there appears to be an inherent acerbity, or even a note of provocation, located within. In spite of any innate or perceived aggression, sarcasm is, in fact, quite a common feature in spoken discourse. Studies have placed the use of sarcastic language at roughly 8% of conversational turns (Gibbs, 2000, p. 5; Tannen, 1984, p. 131), so it is certainly a notable and oft-tapped linguistic resource. As technology progresses, however, computer-mediated communication is becoming increasingly common and, with the advent of social media (Twitter, Facebook, Whatsapp, etc.), increasingly conversational. In this vein, perhaps sarcasm's role as a feature of primarily spoken discourse needs to be re-evaluated. This article offs a descriptive analysis of sarcasm as produced in an exclusively digital space, as well as bring attention to a novel use of sarcasm specific to this environment: sarcasm used as a "pseudo-argument."

CONTENTS I. INTRODUCTION II. HOW DID WE GET HERE? A. The Mezzanatto Case 1. The Holding 2. The Case Itself 3. The Mezzanatto Appeal; The Mezzanatto Proviso B. Plea Bargaining [...], Plea bargaining is the dominant means of disposing of criminal charges in the United States, in both state and federal courts. This administrative mechanism has become a system that is grossly abusive of individual rights, leading to many well-known maladies of the criminal justice system, which include overcharging, overincarceration, convictions on charges that would likely fail at trial, and even conviction of "factually innocent" persons. Instrumental in the abuses of plea bargaining is the so-called Mezzanatto waiver, which takes its name from a 1995 Supreme Court decision that approved the practice of getting defendants to agree that anything they say in negotiations with prosecutors can be admitted against them if a trial ensues, despite Evidence Rule 410, which provides that such statements are inadmissible. These waivers, which are largely overlooked in the vast literature that criticizes plea bargaining, are in fact lynchpins in a system that is horrifying to contemplate. These waivers mean that the very act of negotiation almost guarantees conviction of something, imposing one-sided risks on defendants that can only benefit prosecutors. They amount to a kind of palpable unfairness that the system tolerates. They not only contribute to the maladies described above, but they produce rulings (if a trial goes forward) that admit unreliable statements. There are many reasons why these waivers should be disapproved, including policy arguments (they are unfair, produce bad results and unreliable statements) and arguments based on contract law, on Rule 410 itself, on a widely-recognized but seldom enforced "unitary" principle, and--finally--on the "Mezzanatto proviso" (a widely ignored term in the decision itself). This Article explores the origins and operation of Mezzanatto waivers, examines and expounds the reasons for disapproving them and taking a new direction, and offers a reply to standard arguments that prosecutors need them (they really do not and have other means to hold defendants to their bargains).

Pseudomonas aeruginosa is a Gram‐negative bacterium causing morbidity and mortality in immuno‐compromised humans. It produces a lectin, LecB, that is considered a major virulence factor, however, its impact on the immune system remains incompletely understood. Here we show that LecB binds to endothelial cells in human skin and mice and disrupts the transendothelial passage of leukocytes in vitro. It impairs the migration of dendritic cells into the paracortex of lymph nodes leading to a reduced antigen‐specific T cell response. Under the effect of the lectin, endothelial cells undergo profound cellular changes resulting in endocytosis and degradation of the junctional protein VE‐cadherin, formation of an actin rim, and arrested cell motility. This likely negatively impacts the capacity of endothelial cells to respond to extracellular stimuli and to generate the intercellular gaps for allowing leukocyte diapedesis. A LecB inhibitor can restore dendritic cell migration and T cell activation, underlining the importance of LecB antagonism to reactivate the immune response against P. aeruginosa infection. Synopsis: Pseudomonas aeruginosa lectin B binds to endothelial cells and inflicts junctional and cytoskeletal changes. Lectin B restricts migration of dendritic cells from tissue to lymph nodes and thereby has negative repercussion on adaptive immune responses. Pseudomonas aeruginosa lectin B binds to the lymphatics.Endothelial cells undergo cell structural changes upon LecB binding.Leukocyte diapedesis is inhibited by LecB.LecB inhibits T cell priming by impeding dendritic cell migration to the lymph node paracortex. [ABSTRACT FROM AUTHOR]

A data-parallel, multiprocessor and clustered implementation of the dot plot algorithm is presented and challenges in developing high performance software to develop large data sets are demonstrated. The model-driven development style helped in rigorous approach towards implementation and studies the system parameters that affected it.

CD169+ macrophages reside in lymph node (LN) and spleen and play an important role in the immune defense against pathogens. As resident macrophages, they are responsive to environmental cues to shape their tissue-specific identity. We have previously shown that LN CD169+ macrophages require RANKL for formation of their niche and their differentiation. Here, we demonstrate that they are also dependent on direct lymphotoxin beta (LTβ) receptor (R) signaling. In the absence or the reduced expression of either RANK or LTβR, their differentiation is perturbed, generating myeloid cells expressing SIGN-R1 in LNs. Conditions of combined haploinsufficiencies of RANK and LTβR revealed that both receptors contribute equally to LN CD169+ macrophage differentiation. In the spleen, the Cd169-directed ablation of either receptor results in a selective loss of marginal metallophilic macrophages (MMMs). Using a RANKL reporter mouse, we identify splenic marginal zone stromal cells as a source of RANKL and demonstrate that it participates in MMM differentiation. The loss of MMMs had no effect on the splenic B cell compartments but compromised viral capture and the expansion of virus-specific CD8+ T cells. Taken together, the data provide evidence that CD169+ macrophage differentiation in LN and spleen requires dual signals from LTβR and RANK with implications for the immune response. [ABSTRACT FROM AUTHOR]