Scalable Manufacture of Built-to-Order Nanomedicine: Spray-Assisted Layer-by-Layer Functionalization of PRINT Nanoparticles

Scalable methods, PRINT particle fabrication, and spray-assisted Layer-by-Layer deposition are combined to generate uniform and functional nanotechnologies with precise control over composition, size, shape, and surface functionality. A modular and tunable approach towards design of built-to-order nanoparticle systems, spray coating on PRINT particles is demonstrated to achieve technologies capable of targeted interactions with cancer cells for applications in drug delivery.National Cancer Institute (U.S.) (Center for Cancer Nanotechnology Excellence Grant 5 U54 CA151884-02)National Science Foundation (U.S.). Graduate Research FellowshipNatural Sciences and Engineering Research Council of Canada (Postdoctoral Fellowship

Mattia Damiani (1705–1776), poet and scientist in eighteenth century Tuscany

Mattia Damiani da Volterra (1705–1776), “renowned Doctor,” was the author in 1754 of a collection of scientifi c poems, Le Muse Fisiche (The Physical Muses) on two subjects: Newtonian physics and the plurality of the worlds. Damiani’s interest in science was precocious, but even at that, it was superimposed on his studies in jurisprudence completed in Pisa in 1726. In 2003, Damiani’s lost text, De Hygrometris et eorum defectibus disputatio (Disputation about hygrometers and their defects), which was printed in 1726 in Pisa, was brought to light. It characterizes him as a young scientist who refl ected upon the properties and limits of laboratory instruments and on nascent aspects of climatology. In this Disputation, a delightful amalgamation of scientifi c and humanistic literature is pursued. A discussion of the properties and limits of contemporary hygrometers and a comparison of the Cartesian and Newtonian hypotheses about cloud formations are interspersed with quotations of verses on natural phenomena, mostly from poems of the classic age—a prelude to the author’s future involvement in writing scientifi c verses. The poetry of Damiani, which often shows a musicality comparable to that of the poet Giacomo Leopardi (1798–1837), deserves to be recognized and saved from oblivion. Especially remarkable is the implicit “multimedia” project of a union among science, poetry, theater, and music. The rediscovered Disputation about hygrometers opens a new window on the personages involved and on the evolution of meteorological concepts in Europe in the context of the then-new Galilean and Newtonian physics

Genome maps across 26 human populations reveal population-specific patterns of structural variation.

Large structural variants (SVs) in the human genome are difficult to detect and study by conventional sequencing technologies. With long-range genome analysis platforms, such as optical mapping, one can identify large SVs (>2 kb) across the genome in one experiment. Analyzing optical genome maps of 154 individuals from the 26 populations sequenced in the 1000 Genomes Project, we find that phylogenetic population patterns of large SVs are similar to those of single nucleotide variations in 86% of the human genome, while ~2% of the genome has high structural complexity. We are able to characterize SVs in many intractable regions of the genome, including segmental duplications and subtelomeric, pericentromeric, and acrocentric areas. In addition, we discover ~60 Mb of non-redundant genome content missing in the reference genome sequence assembly. Our results highlight the need for a comprehensive set of alternate haplotypes from different populations to represent SV patterns in the genome

A Latent Propriospinal Network Can Restore Diaphragm Function After High Cervical Spinal Cord Injury

Spinal cord injury (SCI) above cervical level 4 disrupts descending axons from the medulla that innervate phrenic motor neurons, causing permanent paralysis of the diaphragm. Using an ex vivo preparation in neonatal mice, we have identified an excitatory spinal network that can direct phrenic motor bursting in the absence of medullary input. After complete cervical SCI, blockade of fast inhibitory synaptic transmission caused spontaneous, bilaterally coordinated phrenic bursting. Here, spinal cord glutamatergic neurons were both sufficient and necessary for the induction of phrenic bursts. Direct stimulation of phrenic motor neurons was insufficient to evoke burst activity. Transection and pharmacological manipulations showed that this spinal network acts independently of medullary circuits that normally generate inspiration, suggesting a distinct non-respiratory function. We further show that this “latent” network can be harnessed to restore diaphragm function after high cervical SCI in adult mice and rats

Systemic inflammatory response syndrome, quick sequential organ function assessment, and organ dysfunction: insights from a prospective database of ED patients with infection

Background A proposed revision of sepsis definitions has abandoned the systemic inflammatory response syndrome (SIRS), defined organ dysfunction as an increase in total Sequential Organ Function Assessment (SOFA) score of\ua0≥ 2, and conceived “qSOFA” (quick SOFA) as a bedside indicator of organ dysfunction. We aimed to (1) determine the prognostic impact of SIRS, (2) compare the diagnostic accuracy of SIRS and qSOFA for organ dysfunction, and (3) compare standard (Sepsis-2) and revised (Sepsis-3) definitions for organ dysfunction in ED patients with infection. Methods Consecutive ED patients admitted with presumed infection were prospectively enrolled over 3 years. Sufficient observational data were collected to calculate SIRS, qSOFA, SOFA, comorbidity, and mortality. Results We enrolled 8,871 patients, with SIRS present in 4,176 (47.1%). SIRS was associated with increased risk of organ dysfunction (relative risk [RR] 3.5) and mortality in patients without organ dysfunction (OR 3.2). SIRS and qSOFA showed similar discrimination for organ dysfunction (area under the receiver operating characteristic curve, 0.72 vs\ua00.73). qSOFA was specific but poorly sensitive for organ dysfunction (96.1%\ua0and 29.7%, respectively). Mortality for patients with organ dysfunction was similar for Sepsis-2 and Sepsis-3 (12.5%\ua0and 11.4%, respectively), although 29%\ua0of patients with Sepsis-3 organ dysfunction did not meet Sepsis-2 criteria. Increasing numbers of Sepsis-2 organ system dysfunctions were associated with greater mortality. Conclusions SIRS was associated with organ dysfunction and mortality, and abandoning the concept appears premature. A qSOFA score\ua0≥ 2 showed high specificity, but poor sensitivity may limit utility as a bedside screening method. Although mortality for organ dysfunction was comparable between Sepsis-2 and Sepsis-3, more prognostic and clinical information is conveyed using Sepsis-2 regarding number and type of organ dysfunctions. The SOFA score may require recalibration

Growth factor concentrations in platelet-rich plasma for androgenetic alopecia: an intra-subject, randomized, blinded, placebo-controlled, pilot study

YesBackground: Platelet rich plasma (PRP), processed from autologous peripheral blood, is used to treat androgenetic alopecia (AGA). Objective: To determine the efficacy of PRP for hair growth promotion in AGA patients in a randomized, blinded, placebo controlled, pilot clinical trial (NCT02074943). Methods: The efficacy of an 8 week, 5 session, PRP treatment course was determined by measuring hair density and hair caliber changes in 10 AGA affected patients. For each PRP sample, the concentrations of selected growth factors were determined using a multiplex assay system. The clinical results were then correlated to the growth factor concentrations in PRP. Results: At 16 weeks, 8 weeks after the last PRP injection, treated areas exhibited increased mean hair density (+12.76%) over baseline compared to placebo (+0.99%). Mean hair caliber decreased in both treated and placebo regions (-16.22% and -19.46% respectively). Serial analysis of PRP significant variability in concentrations between patients. Overall, there was a positive correlation between GDNF concentration and hair density (p= 0.004). Trends, though not statistically significant, were also observed for FGF2 and VEGF. Limitations: Small sample size and lack of comparative cohorts receiving protocol variations limit confidence in the study data. Conclusions: This small pilot clinical trial suggests PRP treatment may be beneficial for AGA. However, the variable hair growth responses between patients indicate there is a significant opportunity to improve PRP therapy protocols for hair growth promotion. The variability in growth factor concentration in PRP suggests standardization of growth factors post-processing might improve hair growth responses.RepliCel Life Sciences Inc. (Canada

Nonlinear electrochemical relaxation around conductors

We analyze the simplest problem of electrochemical relaxation in more than one dimension - the response of an uncharged, ideally polarizable metallic sphere (or cylinder) in a symmetric, binary electrolyte to a uniform electric field. In order to go beyond the circuit approximation for thin double layers, our analysis is based on the Poisson-Nernst-Planck (PNP) equations of dilute solution theory. Unlike most previous studies, however, we focus on the nonlinear regime, where the applied voltage across the conductor is larger than the thermal voltage. In such strong electric fields, the classical model predicts that the double layer adsorbs enough ions to produce bulk concentration gradients and surface conduction. Our analysis begins with a general derivation of surface conservation laws in the thin double-layer limit, which provide effective boundary conditions on the quasi-neutral bulk. We solve the resulting nonlinear partial differential equations numerically for strong fields and also perform a time-dependent asymptotic analysis for weaker fields, where bulk diffusion and surface conduction arise as first-order corrections. We also derive various dimensionless parameters comparing surface to bulk transport processes, which generalize the Bikerman-Dukhin number. Our results have basic relevance for double-layer charging dynamics and nonlinear electrokinetics in the ubiquitous PNP approximation.Comment: 25 pages, 17 figures, 4 table