On the shape of a pure O-sequence

An order ideal is a finite poset X of (monic) monomials such that, whenever M is in X and N divides M, then N is in X. If all, say t, maximal monomials of X have the same degree, then X is pure (of type t). A pure O-sequence is the vector, h=(1,h_1,...,h_e), counting the monomials of X in each degree. Equivalently, in the language of commutative algebra, pure O-sequences are the h-vectors of monomial Artinian level algebras. Pure O-sequences had their origin in one of Richard Stanley's early works in this area, and have since played a significant role in at least three disciplines: the study of simplicial complexes and their f-vectors, level algebras, and matroids. This monograph is intended to be the first systematic study of the theory of pure O-sequences. Our work, making an extensive use of algebraic and combinatorial techniques, includes: (i) A characterization of the first half of a pure O-sequence, which gives the exact converse to an algebraic g-theorem of Hausel; (ii) A study of (the failing of) the unimodality property; (iii) The problem of enumerating pure O-sequences, including a proof that almost all O-sequences are pure, and the asymptotic enumeration of socle degree 3 pure O-sequences of type t; (iv) The Interval Conjecture for Pure O-sequences (ICP), which represents perhaps the strongest possible structural result short of an (impossible?) characterization; (v) A pithy connection of the ICP with Stanley's matroid h-vector conjecture; (vi) A specific study of pure O-sequences of type 2, including a proof of the Weak Lefschetz Property in codimension 3 in characteristic zero. As a corollary, pure O-sequences of codimension 3 and type 2 are unimodal (over any field); (vii) An analysis of the extent to which the Weak and Strong Lefschetz Properties can fail for monomial algebras; (viii) Some observations about pure f-vectors, an important special case of pure O-sequences.Comment: iii + 77 pages monograph, to appear as an AMS Memoir. Several, mostly minor revisions with respect to last year's versio

Molecular Mechanisms of Circadian Regulation During Spaceflight

The physiology of both vertebrates and invertebrates follows internal rhythms coordinated in phase with the 24-hour daily light cycle. This circadian clock is governed by a central pacemaker, the suprachiasmatic nucleus (SCN) in the brain. However, peripheral circadian clocks or oscillators have been identified in most tissues. How the central and peripheral oscillators are synchronized is still being elucidated. Light is the main environmental cue that entrains the circadian clock. Under the absence of a light stimulus, the clock continues its oscillation in a free-running condition. In general, three functional compartments of the circadian clock are defined. The vertebrate retina contains endogenous clocks that control many aspects of retinal physiology, including retinal sensitivity to light, neurohormone synthesis (melatonin and dopamine), rod disk shedding, signalling pathways and gene expression. Neurons with putative local circadian rhythm generation are found among all the major neuron populations in the mammalian retina. In the mouse, clock genes and function are more localized to the inner retinal and ganglion cell layers. The photoreceptor, however, secrete melatonin which may still serve a an important circadian signal. The reception and transmission of the non-visual photic stimulus resides in a small subpopulation (1-3%) or retinal ganglion cells (RGC) that express the pigment melanopsin (Opn4) and are called intrisically photoreceptive RGC (ipRGC). Melanopsin peak absorption is at 420 nm and all the axons of the ipRGC reach the SCN. A common countermeasure for circadian re-entrainment utilizes blue-green light to entrain the circadian clock and mitigate the risk of fatigue and health and performance decrement due to circadian rhythm disruption. However, an effective countermeasure targeting the photoreceptor system requires that the basic circadian molecular machinery remains intact during spaceflight. We hypothesize that spaceflight may affect ipRGC and melanopsin expression, which may be a contributing cause of circadian disruption during spaceflight

The ATLAS Barrel Level-1 Muon Trigger Calibration

The ATLAS experiment uses a system of three concentric Resistive Plate Chambers detectors layers for the level-1 muon trigger in the air-core barrel toroid region. The trigger classifies muons within different programmable transverse momentum ranges, and tags the identified tracks with the corresponding bunch crossing number. The algorithm looks for hit coincidences within different detector layers inside the programmed geometrical road which defines the transverse momentum cut. The on-detector electronics providing the trigger and detector readout functionalities collects input signals coming from the RPC front-end. Because of the different time-of-flights and cables and optical fibres lengths, signals have to be adjusted in time in order to be correctly aligned before being processed. Programmable delay logics are provided in the trigger and readout system to allow for time adjustment, for hit signals as well as for LHC Timing, Trigger and Control signals. The trigger calibration provides the set of numbers used during electronics initialization for correctly aligning signals inside the trigger and readout system. The functionality scheme and the algorithm of the calibration are presented

70 Days of 6 Degrees-head Down Tilt Bed Rest and its Impact on Ocular Parameters

No abstract availabl

Comparison of Structural and Functional Ocular Outcomes Between 14- and 70-Day Bed Rest

To compare structural and functional ocular outcomes between14-and 70-day HDTBR in healthy human subjects

Ocular Outcomes Comparison Between 14- and 70-day Head-down Tilt Bed Rest

No abstract availabl

Mapping by VESGEN of Blood Vessels in the Retinas of ISS Crew Members and Bed Rest Subjects for Increased Understanding of VIIP

Research by NASA has established that significant risks for visual impairment in association with increased intracranial pressure (VIIP) are incurred by microgravity spaceflight, especially long-duration missions. Impairments include decreased near visual acuity, posterior globe flattening, choroidal folds, optic disc edema, and cotton wool spots. Much remains to be learned about the etiology of VIIP before effective countermeasures can be developed. Contributions of retinal vascular remodeling to the etiology of VIIP have not yet been investigated, primarily due to the current lack of ophthalmic tools for precisely measuring progressive pathophysiological remodeling of the retinal microvasculature. Although ophthalmic science and clinical practice are now highly sophisticated at detecting indirect, secondary signs of vascular remodeling such as cotton wool spots that arise during the progression of retinal vascular diseases, methods for quantifying direct, primary vascular changes are not yet established. To help develop insightful analysis of retinal vascular remodeling for aerospace medicine, we will map and quantify by our innovative VESsel GENeration Analysis (VESGEN) software the remodeling status of retinal blood vessels in crew members before and after ISS missions, and in healthy human subjects before and after head-down tilt bed rest. For this proof-of-concept study, we hypothesize that pathophysiological remodeling of retinal blood vessels occurs in coordination with microgravity-induced fluid shifts prior to development of visual impairments. VESGEN analysis in previous research supported by the US National Institutes of Health identified surprising new opportunities to regenerate retinal vessels during early-stage progression of the visually impairing, potentially blinding disease, diabetic retinopathy

Radioadaptive Cytoprotective Pathways in the Mouse Retina

Exposure to cosmic radiation implies a risk of tissue degeneration. Radiation retinopathy is a complication of radiotherapy and exhibits common features with other retinopathies and neuropathies. Exposure to a low radiation dose elicits protective cellular events (radioadaptive response), reducing the stress of a subsequent higher dose. To assess the risk of radiation-induced retinal changes and the extent to which a small priming dose reduces this risk, we used a mouse model exposed to a source of Cs-137-gamma radiation. Gene expression profiling of retinas from non-irradiated control C57BL/6J mice (C) were compared to retinas from mice treated with a low 50 mGy dose (LD), a high 6 Gy dose (HD), and a combined treatment of 50 mGy (priming) and 6 Gy (challenge) doses (LHD). Whole retina RNA was isolated and expression analysis for selected genes performed by RTqPCR. Relevant target genes associated with cell death/survival, oxidative stress, cellular stress response and inflammation pathways, were analyzed. Cellular stress response genes were upregulated at 4 hr after the challenge dose in LHD retinas (Sirt1: 1.5 fold, Hsf1: 1.7 fold, Hspa1a: 2.5 fold; Hif1a: 1.8 fold, Bag1: 1.7). A similar trend was observed in LD animals. Most antioxidant enzymes (Hmox1, Sod2, Prdx1, Cygb, Cat1) and inflammatory mediators (NF B, Ptgs2 and Tgfb1) were upregulated in LHD and LD retinas. Expression of the pro-survival gene Bcl2 was upregulated in LD (6-fold) and LHD (4-fold) retinas. In conclusion, cytoprotective gene networks activation in the retina suggests a radioadaptive response to a priming irradiation dose, with mitigation of the deleterious effects of a subsequent high dose exposure. The enhancement of these cytoprotective mechanisms has potential value as a countermeasure to ocular alterations caused by radiation alone or in combination with other factors in spaceflight environments

Association Between Cardiovascular and Intraocular Pressure Changes in a 14-day 6 deg Head Down Tilt (HDT) Bed Rest Study: Possible Implications in Retinal Anatomy

Mean IOP significantly increased while at 6deg HDT and returned towards pre-bed rest values upon leaving bed rest. While mean IOP increased during bed rest, it remained within the normal limits for subject safety. A diuretic shift and cardiovascular deconditioning occurs during in-bed rest, as expected. There was no demonstrable correlation between the largest change in IOP (pre/post) and cardiovascular measure changes (pre/post). Additional mixed effects linear regression modeling may reveal some subclinical physiological changes that might assist in describing the VIIP syndrome pathophysiology

Brain Gene Expression Signatures From Cerebrospinal Fluid Exosome RNA Profiling

While the Visual Impairment and Intracranial Pressure (VIIP) syndrome observations have focused on ocular symptoms, spaceflight has been also associated with a number of other performance and neurologic signs, such as headaches, cognitive changes, vertigo, nausea, sleep/circadian disruption and mood alterations, which, albeit likely multifactorial, can also result from elevation of intracranial pressure (ICP). We therefore hypothesize that these various symptoms are caused by disturbances in the neurophysiology of the brain structures and are correlated with molecular markers in the cerebrospinal fluid (CSF) as indicators of neurophysiological changes. Exosomes are 30-200 nm microvesicles shed into all biofluids, including blood, urine, and CSF, carrying a highly rich source of intact protein and RNA cargo. Exosomes have been identified in human CSF, and their proteome and RNA pool is a potential new reservoir for biomarker discovery in neurological disorders. The purpose of this study is to investigate changes in brain gene expression via exosome analysis in patients suffering from ICP elevation of varied severity (idiopathic intracranial hypertension -IIH), a condition which shares some of the neuroophthalmological features of VIIP, as a first step toward obtaining evidence suggesting that cognitive function and ICP levels can be correlated with biomarkers in the CSF. Our preliminary work, reported last year, validated the exosomal technology applicable to CSF analysis and demonstrated that it was possible to obtain gene expression evidence of inflammation processes in traumatic brain injury patients. We are now recruiting patients with suspected IIH requiring lumbar puncture at Baylor College of Medicine. Both CSF (5 ml) and human plasma (10 ml) are being collected in order to compare the pattern of differentially expressed genes observed in CSF and in blood. Since blood is much more accessible than CSF, we would like to determine whether plasma biomarkers for elevated ICP can be identified. This may eventually lead to a blood test to diagnose intracranial hypertension