Normal Breathing Pattern and Arterial Blood Gases in Awake and Sleeping Goats after Near Total Destruction of the Presumed Pre-Bötzinger Complex and the Surrounding Region

Abrupt neurotoxic destruction of \u3e70% of the pre-Bötzinger complex (preBötzC) in awake goats results in respiratory and cardiac failure (Wenninger JM, Pan LG, Klum L, Leekley T, Bastastic J, Hodges MR, Feroah TR, Davis S, Forster HV. J Appl Physiol 97: 1629–1636, 2004). However, in reduced preparations, rhythmic respiratory activity has been found in other areas of the brain stem (Huang Q, St. John WM. J Appl Physiol 64: 1405–1411, 1988; Janczewski WA, Feldman JL. J Physiol 570: 407–420, 2006; Lieske SP, Thoby-Brisson M, Telgkamo P, Ramierz JM. Nature Neurosci 3: 600–607, 2000; St. John WM, Bledsoe TA. J Appl Physiol 59: 684–690, 1985); thus we hypothesized that, when the preBötzC is destroyed incrementally over weeks, time-dependent plasticity within the respiratory network will result in a respiratory rhythm capable of maintaining normal blood gases. Microtubules were bilaterally implanted into the presumed preBötzC of seven goats. After recovery from surgery, studies were completed to establish baseline values for respiratory parameters. At weekly intervals, increasing volumes (in order 0.5, 1, 5, and 10 μl) of ibotenic acid (IA; 50 mM) were then injected into the preBötzC. All IA injections resulted in an acute tachypnea and dysrhythmia featuring augmented breaths, apneas, and increased breath-to-breath variation in breathing. In studies at night, apneas were nearly all central and occurred in the awake state. Breath-to-breath variation in breathing was greater (P \u3c 0.05) during wakefulness than during non-rapid eye movement sleep. However, one week after the final IA injection, the breathing pattern, breath-to-breath variation, and arterial blood gases and pH were unchanged from baseline, but there was a 20% decrease in respiratory frequency (f) and CO2 sensitivity (P \u3c 0.05), as well as a 40% decrease in the ventilatory response to hypoxia (P \u3c 0.001). In subsequent histological analysis of the presumed preBötzC region of lesioned goats, it was determined that there was a 90 and 92% reduction from control goats in total and neurokinin-1 receptor neurons, respectively. Therefore, it was concluded that 1) the dysrhythmic effects on breathing are state dependent; and 2) after incremental, near total destruction of the presumed preBötzC region, time-dependent plasticity within the respiratory network provides a rhythm capable of sustaining normal arterial blood gases

The Effects of Lesions in the Dorsolateral Pons on the Coordination of Swallowing and Breathing in Awake Goats

The purpose of this retrospective study was to gain insight into the contribution of the dorsolateral pons to the coordination of swallowing and breathing in awake goats. In 4 goats, cannulas were chronically implanted bilaterally through the lateral (LPBN) and medial (MPBN) parabrachial nuclei just dorsal to the Kölliker–Fuse nucleus (KFN). After \u3e2 weeks recovery from this surgery, the goats were studied for 5½ h on a control day, and on separate days after receiving 1 and 10 μl injections of ibotenic acid (IA) separated by 1 week. The frequency of swallows did not change during the control and 1 μl IA studies, but after injection of 10 μl IA, there was a transient 65% increase in frequency of swallows (P \u3c 0.05). Under control conditions swallows occurred throughout the respiratory cycle, where late-E swallows accounted for 67.6% of swallows. The distribution of swallow occurrence throughout the respiratory cycle was unaffected by IA injections. Consistent with the concept that swallowing is dominant over breathing, we found that swallows increased inspiratory (TI) and expiratory (TE) time and decreased tidal volume (VT) of the breath of the swallow (n) and/or the subsequent (n + 1) breath. Injections of 10 μl IA attenuated the normal increases in TI and TE and further attenuated VT of the n breath. Additionally, E and I swallows reset respiratory rhythm, but injection of 1 or 10 μl IA progressively attenuated this resetting, suggesting a decreased dominance over respiratory motor output with increasing IA injections. Post mortem histological analysis revealed about 50% fewer (P \u3c 0.05) neurons remained in the KFN, LPBN, and MPBN in lesioned compared to control goats. We conclude that dorsolateral pontine nuclei have a modulatory role in a hypothesized holarchical neural network regulating swallowing and breathing particularly contributing to the normal dominance of swallowing over breathing in both rhythm and motor pattern generation

Semilinear problems for the fractional laplacian with a singular nonlinearity

The aim of this paper is to study the solvability of the problem (-Δ)s u = F(x,u) := λ f(x)/uγ + Mup in ω u > 0 in ω, u = 0 in RN \ ω, where Ω is a bounded smooth domain of RN, N > 2s, M ε {0, 1}, 0 0, λ > 0, p > 1 and f is a nonnegative function. We distinguish two cases: - For M = 0, we prove the existence of a solution for every γ > 0 and λ > 0. A1 - For M = 1, we consider f ≡ 1 and we find a threshold ∧ such that there exists a solution for every 0 ∧Work partially supported by project MTM2013-40846-P MINECO. The third author is also supported for the grant BES-2011-044216 associated to MTM2010-1812

Q2Q_2-free families in the Boolean lattice

For a family $\mathcal{F}$ of subsets of [n]=\{1, 2, ..., n} ordered by inclusion, and a partially ordered set P, we say that $\mathcal{F}$ is P-free if it does not contain a subposet isomorphic to P. Let $ex(n, P)$ be the largest size of a P-free family of subsets of [n]. Let $Q_2$ be the poset with distinct elements a, b, c, d, a<b, c<d; i.e., the 2-dimensional Boolean lattice. We show that $2N -o(N) \leq ex(n, Q_2)\leq 2.283261N +o(N),$ where $N = \binom{n}{\lfloor n/2 \rfloor}$. We also prove that the largest $Q_2$-free family of subsets of [n] having at most three different sizes has at most 2.20711N members.Comment: 18 pages, 2 figure

A Role for the Kolliker-Fuse Nucleus in Cholinergic Modulation of Breathing at Night During Wakefulness and NREM Sleep

For many years, acetylcholine has been known to contribute to the control of breathing and sleep. To probe further the contributions of cholinergic rostral pontine systems in control of breathing, we designed this study to test the hypothesis that microdialysis (MD) of the muscarinic receptor antagonist atropine into the pontine respiratory group (PRG) would decrease breathing more in animals while awake than while in NREM sleep. In 16 goats, cannulas were bilaterally implanted into rostral pontine tegmental nuclei (n = 3), the lateral (n = 3) or medial (n = 4) parabrachial nuclei, or the Kölliker-Fuse nucleus (KFN; n = 6). After \u3e2 wk of recovery from surgery, the goats were studied during a 45-min period of MD with mock cerebrospinal fluid (mCSF), followed by at least 30 min of recovery and a second 45-min period of MD with atropine. Unilateral and bilateral MD studies were completed during the day and at night. MD of atropine into the KFN at night decreased pulmonary ventilation and breathing frequency and increased inspiratory and expiratory time by 12–14% during both wakefulness and NREM sleep. However, during daytime studies, MD of atropine into the KFN had no effect on these variables. Unilateral and bilateral nighttime MD of atropine into the KFN increased levels of NREM sleep by 63 and 365%, respectively. MD during the day or at night into the other three pontine sites had minimal effects on any variable studied. Finally, compared with MD of mCSF, bilateral MD of atropine decreased levels of acetylcholine and choline in the effluent dialysis fluid. Our data support the concept that the KFN is a significant contributor to cholinergically modulated control of breathing and sleep

The Cerebellar Fastigial Nucleus Contributes to CO\u3csub\u3e2\u3c/sub\u3e-H\u3csup\u3e+\u3c/sup\u3e Ventilatory Sensitivity in Awake Goats

The purpose of this study was to test the hypothesis that an intact cerebellar fastigial nucleus (CFN) is an important determinant of CO2-H+ sensitivity during wakefulness. Bilateral, stainless steel microtubules were implanted into the CFN (N = 9) for injection (0.5–10 μl) of the neurotoxin ibotenic acid. Two or more weeks after implantation of the microtubules, eupneic breathing and CO2-H+ sensitivity did not differ significantly (P \u3e 0.10) from pre-implantation conditions. Injection of ibotenic acid (50 mM) did not significantly alter eupneic PaCO2 (P \u3e 0.10). The coefficient of variation of eupneic PaCO2 was 4.0 ± 0.6 and 3.7 ± 0.4% over the 2 weeks before and after the lesion, respectively. CO2-H+ sensitivity expressed as inspired ventilation/PaCO2 decreased from 2.15 ± 0.17 pre-lesion to 1.58 ± 0.26 l/(min mmHg) 3–6 days post-lesion (P \u3c 0.02, −27%). There was no significant (P \u3e 0.10) recovery of sensitivity between 7 and 10 days post-lesion. The lesion also increased (P \u3c 0.05) the day-to-day variability of this index by nearly 100%. When CO2 sensitivity was expressed as elevated inspired CO2/room air VI, values at 7%, but not 3 and 5% inspired CO2, were reduced and more variable (P \u3c 0.05) after the ibotenic acid injections. We conclude that during wakefulness, the CFN contributes relatively more to overall ventilatory drive at high relative to low levels of hypercapnia

Novel Locus FER Is Associated With Serum HMW Adiponectin Levels

OBJECTIVE High molecular weight (HMW) adiponectin is a predominant isoform of circulating adiponectin and has been related to type 2 diabetes. Previous linkage studies suggest that different genetic components might be involved in determining HMW and total adiponectin levels. RESEARCH DESIGN AND METHODS We performed a genome-wide association study (GWAS) of serum HMW adiponectin levels in individuals of European ancestry drawn from the Nurses’ Health Study (NHS) (N = 1,591). The single nucleotide polymorphisms (SNPs) identified in the GWAS analysis were replicated in an independent cohort of Europeans (N = 626). We examined the associations of the identified variations with diabetes risk and metabolic syndrome. RESULTS We identified a novel locus near the FER gene (5q21) at a genome-wide significance level, best represented by SNP rs10447248 (P = 4.69 × 10−8). We also confirmed that variations near the adiponectin-encoding ADIPOQ locus (3q27) were related to serum HMW adiponectin levels. In addition, we found that FER SNP rs10447248 was related to HDL cholesterol levels (P = 0.009); ADIPOQ variation was associated with fasting glucose (P = 0.04), HDL cholesterol (P = 0.04), and a metabolic syndrome score (P = 0.002). CONCLUSIONS Our results suggest that different loci may be involved in regulation of circulating HMW adiponectin levels and provide novel insight into the mechanisms that affect HMW adiponectin homeostasis

Noise-Resilient Group Testing: Limitations and Constructions

We study combinatorial group testing schemes for learning $d$-sparse Boolean vectors using highly unreliable disjunctive measurements. We consider an adversarial noise model that only limits the number of false observations, and show that any noise-resilient scheme in this model can only approximately reconstruct the sparse vector. On the positive side, we take this barrier to our advantage and show that approximate reconstruction (within a satisfactory degree of approximation) allows us to break the information theoretic lower bound of $\tilde{\Omega}(d^2 \log n)$ that is known for exact reconstruction of $d$-sparse vectors of length $n$ via non-adaptive measurements, by a multiplicative factor $\tilde{\Omega}(d)$. Specifically, we give simple randomized constructions of non-adaptive measurement schemes, with $m=O(d \log n)$ measurements, that allow efficient reconstruction of $d$-sparse vectors up to $O(d)$ false positives even in the presence of $\delta m$ false positives and $O(m/d)$ false negatives within the measurement outcomes, for any constant $\delta < 1$. We show that, information theoretically, none of these parameters can be substantially improved without dramatically affecting the others. Furthermore, we obtain several explicit constructions, in particular one matching the randomized trade-off but using $m = O(d^{1+o(1)} \log n)$ measurements. We also obtain explicit constructions that allow fast reconstruction in time \poly(m), which would be sublinear in $n$ for sufficiently sparse vectors. The main tool used in our construction is the list-decoding view of randomness condensers and extractors.Comment: Full version. A preliminary summary of this work appears (under the same title) in proceedings of the 17th International Symposium on Fundamentals of Computation Theory (FCT 2009

Papier-mach(in)e: Thinking with “sticky” paper in the cloud

There is nothing less about paper and its use when it comes to academic study as we experience increasingly converging media spaces and functionalities of online applications within the screens of our laptops, mobile phones and tablet devices. The paper persists, and the paperless office, classroom and pedagogy become nothing but pure rhetoric. Hence, it is most pertinent to focus on paper and its “stickiness” in maintaining educational structures and practices. Usually hidden from view or neglected in educational technology studies is a consideration on how we think and interact not only with our mind but also with our heads and limbs. This paper will argue that paper has a composite place or bearing, a kind of stickiness to our technologised bodies, digital mobilities and hybrid practices in what I have coined here as papier-mach(in)e. This claim will be supported by evidence that demonstrates how we simply think both practically and pathically and that our mobilities in media and physical spaces are in one form or another meshed with paper. In fact, a drive towards a paperless classroom or pedagogy is without much foundation when it comes to mobilising a sustainable agenda for technology-enhanced learning