Targeting PI3K/Akt/mTOR signaling in rodent models of PMP22 gene-dosage diseases.

Haplo-insufficiency of the gene encoding the myelin protein PMP22 leads to focal myelin overgrowth in the peripheral nervous system and hereditary neuropathy with liability to pressure palsies (HNPP). Conversely, duplication of PMP22 causes Charcot-Marie-Tooth disease type 1A (CMT1A), characterized by hypomyelination of medium to large caliber axons. The molecular mechanisms of abnormal myelin growth regulation by PMP22 have remained obscure.

An apparatus to synthesize ceramic nanoparticles with a precisely adjusted temperature history and a significant mass output.

For gas phase nanoparticle production, hot wall reactors are widely used. In this article, we will describe the fundamental design considerations for a hot wall reactor system able to produce oxide nanoparticles. The system is outstanding in its ability to produce mostly spherical nanoparticles at particle sizes of up to 100 nm and even larger at mass outputs in the order of grams per hour by being able to rapidly quench the aerosol.

Apparatus for the measurement of the speed of sound of ammonia up to high temperatures and pressures.

An apparatus for the measurement of the speed of sound based on the pulse-echo technique is presented. It operates up to a temperature of 480 K and a pressure of 125 MPa. After referencing and validating the apparatus with water, it is applied to liquid ammonia between 230 and 410 K up to a pressure of 124 MPa.

Reactivation of multiple viruses in patients with sepsis.

A current controversy is whether patients with sepsis progress to an immunosuppressed state. We hypothesized that reactivation of latent viruses occurred with prolonged sepsis thereby providing evidence of clinically-relevant immunosuppression and potentially providing a means to serially-monitor patients' immune status. Secondly, if viral loads are markedly elevated, they may contribute to morbidity and mortality.

Targeting the programmed cell death 1: programmed cell death ligand 1 pathway reverses T cell exhaustion in patients with sepsis.

Introduction: A major pathophysiologic mechanism in sepsis is impaired host immunity which results in failure to eradicate invading pathogens and increased susceptibility to secondary infections. Although many immunosuppressive mechanisms exist, increased expression of the inhibitory receptor programmed cell death 1 (PD-1) and its ligand (PD-L1) are thought to play key roles. The newly recognized phenomenon of T cell exhaustion is mediated in part by PD-1 effects on T cells.

Blockade of the negative co-stimulatory molecules PD-1 and CTLA-4 improves survival in primary and secondary fungal sepsis.

Introduction: Fungal sepsis is an increasingly common problem in intensive care unit patients.Mortality from fungal sepsis remains high despite antimicrobial therapy that is highly active against most fungal pathogens, a finding consistent with defective host immunity that is present in many patients with disseminated fungemia.One recently recognized immunologic defect that occurs in patients with sepsis is T cell "exhaustion" due to increased expression of programmed cell death -1 (PD-1).