Holographic dual of the Standard Model on the throat

We apply recent techniques to construct geometries, based on local Calabi-Yau manifolds, leading to warped throats with 3-form fluxes in string theory, with interesting structure at their bottom. We provide their holographic dual description in terms of RG flows for gauge theories with almost conformal duality cascades and infrared confinement. We describe a model of a throat with D-branes at its bottom, realizing a 3-family Standard Model like chiral sector. We provide the explicit holographic dual gauge theory RG flow, and describe the appearance of the SM degrees of freedom after confinement. As a second application, we describe throats within throats, namely warped throats with discontinuous warp factor in different regions of the radial coordinate, and discuss possible model building applications.Comment: 46 pages, 21 figures, reference adde

Haptoglobin improves shock, lung injury, and survival in canine pneumonia

During the last half-century, numerous antiinflammatory agents were tested in dozens of clinical trials and have proven ineffective for treating septic shock. The observation in multiple studies that cell-free hemoglobin (CFH) levels are elevated during clinical sepsis and that the degree of increase correlates with higher mortality suggests an alternative approach. Human haptoglobin binds CFH with high affinity and, therefore, can potentially reduce iron availability and oxidative activity. CFH levels are elevated over approximately 24-48 hours in our antibiotic-treated canine model of S. aureus pneumonia that simulates the cardiovascular abnormalities of human septic shock. In this 96-hour model, resuscitative treatments, mechanical ventilation, sedation, and continuous care are translatable to management in human intensive care units. We found, in this S. aureus pneumonia model inducing septic shock, that commercial human haptoglobin concentrate infusions over 48-hours bind canine CFH, increase CFH clearance, and lower circulating iron. Over the 96-hour study, this treatment was associated with an improved metabolic profile (pH, lactate), less lung injury, reversal of shock, and increased survival. Haptoglobin binding compartmentalized CFH to the intravascular space. This observation, in combination with increasing CFHs clearance, reduced available iron as a potential source of bacterial nutrition while decreasing the ability for CFH and iron to cause extravascular oxidative tissue injury. In contrast, haptoglobin therapy had no measurable antiinflammatory effect on elevations in proinflammatory C-reactive protein and cytokine levels. Haptoglobin therapy enhances normal host defense mechanisms in contrast to previously studied antiinflammatory sepsis therapies, making it a biologically plausible novel approach to treat septic shock

Analytical methods in wineries: is it time to change?

A review of the methods for the most common parameters determined in wine—namely, ethanol, sulfur dioxide, reducing sugars, polyphenols, organic acids, total and volatile acidity, iron, soluble solids, pH, and color—reported in the last 10 years is presented here. The definition of the given parameter, official and usual methods in wineries appear at the beginning of each section, followed by the methods reported in the last decade divided into discontinuous and continuous methods, the latter also are grouped in nonchromatographic and chromatographic methods because of the typical characteristics of each subgroup. A critical comparison between continuous and discontinuous methods for the given parameter ends each section. Tables summarizing the features of the methods and a conclusions section may help users to select the most appropriate method and also to know the state-of-the-art of analytical methods in this area

Electronic identification of the actual parental phase of KxFe2-ySe2 superconductor and its intrinsic mesoscopic phase separation

While the parent compounds of the cuprate high temperature superconductors (high-Tc's) are Mott insulators, the iron-pnictide high-Tc's are in the vicinity of a metallic spin density wave (SDW) state, which highlights the difference between these two families. However, insulating parent compounds were identified for the newly discovered KxFe2-ySe2. This raises an intriguing question as to whether the iron-based high-Tc's could be viewed as doped Mott insulators like the cuprates. Here we report angle-resolved photoemission spectroscopy (ARPES) evidence of two insulating and one semiconducting phases of KxFe2-ySe2, and the mesoscopic phase separation between the superconducting/semiconducting phase and the insulating phases. The insulating phases are characterized by the depletion of electronic states over a 0.5 eV window below the chemical potential, giving a compelling evidence for the presence of Mott-like physics. The charging effects and the absence of band folding in the superconducting/semiconducting phase further prove that the static magnetic and vacancy orders are not related to the superconductivity. Instead, the electronic structure of the superconducting phase is much closer to the semiconducting phase, indicating the superconductivity is likely developed by doping the semiconducting phase rather than the insulating phases.Comment: 6 pages, 5 figure

Recurrent de novo SPTLC2 variant causes childhood-onset amyotrophic lateral sclerosis (ALS) by excess sphingolipid synthesis

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the upper and lower motor neurons with varying ages of onset, progression and pathomechanisms. Monogenic childhood-onset ALS, although rare, forms an important subgroup of ALS. We recently reported specific SPTLC1 variants resulting in sphingolipid overproduction as a cause for juvenile ALS. Here, we report six patients from six independent families with a recurrent, de novo, heterozygous variant in SPTLC2 c.778G>A [p.Glu260Lys] manifesting with juvenile ALS. METHODS: Clinical examination of the patients along with ancillary and genetic testing, followed by biochemical investigation of patients' blood and fibroblasts, was performed. RESULTS: All patients presented with early-childhood-onset progressive weakness, with signs and symptoms of upper and lower motor neuron degeneration in multiple myotomes, without sensory neuropathy. These findings were supported on ancillary testing including nerve conduction studies and electromyography, muscle biopsies and muscle ultrasound studies. Biochemical investigations in plasma and fibroblasts showed elevated levels of ceramides and unrestrained de novo sphingolipid synthesis. Our studies indicate that SPTLC2 variant [c.778G>A, p.Glu260Lys] acts distinctly from hereditary sensory and autonomic neuropathy (HSAN)-causing SPTLC2 variants by causing excess canonical sphingolipid biosynthesis, similar to the recently reported SPTLC1 ALS associated pathogenic variants. Our studies also indicate that serine supplementation, which is a therapeutic in SPTLC1 and SPTCL2-associated HSAN, is expected to exacerbate the excess sphingolipid synthesis in serine palmitoyltransferase (SPT)-associated ALS. CONCLUSIONS: SPTLC2 is the second SPT-associated gene that underlies monogenic, juvenile ALS and further establishes alterations of sphingolipid metabolism in motor neuron disease pathogenesis. Our findings also have important therapeutic implications: serine supplementation must be avoided in SPT-associated ALS, as it is expected to drive pathogenesis further