Western blotting showed that both cytokines activate Jun N-terminal kinase (JNK), but with somewhat different kinetics, and that activation of JNK by both cytokines individually is inhibited by the combination. These results indicate that IL-4 inhibition of MMP-3 expression is associated with reduction of IL-1 selleck kinase inhibitor induced binding of active forms of the AP-1 dimer, while less active JunB-containing

dimers remain, and suggest that these changes are associated with decreased activation of JNK. (C) 2013 Elsevier Inc. All rights reserved.”
“To isolate acid- and bile-resistant Saccharomyces cerevisiae strains directly from food samples and to preliminarily select them on the basis of fundamental probiotic properties.\n\nA rapid screening method allowed the isolation and selection of 20 acid- and bile-resistant yeasts from foods, avoiding time-consuming isolation steps. The strains were characterized for their specific survival in simulated gastric juice and in intestinal fluid after pre-exposure at low pH. Ten isolates demonstrated a satisfactory survival percentage in intestinal fluid after pre-exposure to gastric juice and appreciable lipolytic and

proteolytic properties, as demonstrated by the API-ZYM test. By using molecular CP-456773 purchase methods five strains were identified as Saccharomyces cerevisiae, three as Candida spp., one as Candida pararugosa and one as Pichia selleckchem spp. The Saccharomyces cerevisiae strains showed considerable probiotic properties, achieving a 80 < % < 90 survival through the simulated gastrointestinal tract, as well as interesting

glucosidase activities.\n\nThe research represents an efficient strategy to select and identify Saccharomyces cerevisiae strains with desirable acid and bile resistances.\n\nThis paper reports the direct selection of potentially probiotic yeasts from foods and provides indications about the ability of Saccharomyces cerevisiae strains to survive conditions simulating the human gastrointestinal tract.”
“Background: Stem cells or immune cells targeting the central nervous system (CNS) bear significant promises for patients affected by CNS disorders. Brain or spinal cord delivery of therapeutic cells is limited by the blood-brain barrier (BBB) which remains one of the recognized rate-limiting steps. Osmotic BBB disruption (BBBD) has been shown to improve small molecule chemotherapy for brain tumors, but successful delivery of cells in conjunction with BBBD has never been reported. We have used a clinically relevant model (pig) of BBBD to attempt brain delivery of TALL-104, a human leukemic T cell line. TALL-104 cells are potent tumor killers and have demonstrated potential for systemic tumor therapy. The pig model used is analogous to the clinical BBBD procedure. Cells were injected in the carotid artery after labeling with the MRI T1 contrast agent GdHPDO3A.

The level of tumor hypoxia was assessed by converting the extent and intensity of the stainings by multiplication in an immunoreactive score (IRS) and statistically evaluated. The results were as follows. (1) While GLUT-1 expression was found to be mainly weak in WHO grade I meningiomas (IRS=1-4) and to be consistently strong in WHO grade

III meningiomas (IRS=6-12), in WHO grade II meningiomas GLUT-1 expression was variable (IRS=1-9). (2) Histologically typical, but brain invasive meningiomas (WHO grade II) showed no or similarly low levels of GLUT-1 expression as observed in WHO grade I meningiomas (IRS=0-4). (3) GLUT-1 expression was observed in the form of a patchy, multifocal staining reaction in 76% of stained WHO grade I-III meningiomas, GW786034 manufacturer while diffuse staining (in 11%) and combined multifocal and areas of diffuse staining (in 13%) were only detected in WHO grades II and III meningiomas, except for uniform staining in

angiomatous learn more WHO grade I meningioma. (4) Spontaneous necrosis and small cell change typically occurred away from the intratumoral capillary network embedded within the pattern of GLUT-1 staining. Taken together, GLUT-1 staining cannot be applied as a substitute for histologic grading in order to predict tumor behavior. However, assessment of tumor hypoxia in association with spontaneous necrosis and foci of small cell change may substantially contribute to the neuropathologic diagnosis of WHO grades II and III meningioma.”
“This retrospective study aimed to evaluate the clinical, laboratory, and quantitative cerebrospinal fluid (CSF) cryptococcal cell counts for associations with in-hospital outcomes this website of HIV-infected patients with cryptococcal meningitis. Ninety-eight HIV-infected adult patients with CSF culture-proven cryptococcal meningitis were admitted between January 2006 and June 2008 at a referral center in Sao Paulo, Brazil.

Cryptococcal meningitis was the first AIDS-defining illness in 69%, of whom 97% (95/98) had known prior HIV infection. The median CD4+ T-cell count was 39 cells/mu L (interquartile range 17-87 cells/mu L). Prior antiretroviral therapy was reported in 50%. Failure to sterilize the CSF by 7-14 days was associated with baseline fungal burden of >= 10 yeasts/mu L by quantitative CSF microscopy (odds ratio [OR] = 15.3, 95% confidence interval [CI] 4.1-56.7; P < 0.001) and positive blood cultures (OR = 11.5,95% CI 1.2-109; P = 0.034). At 7-14 days, 10 yeasts/mu L CSF was associated with positive CSF cultures in 98% versus 36% with <10 yeasts/mu L CSF (P < 0.001). In-hospital mortality was 30% and was associated with symptoms duration for >14 days, altered mental status (P< 0.

The calculation method uses a large fraction of the pixels available within the measured images and requires minimal human guidance in its operation. The method is demonstrated using measurements where residual stresses are made on a microscopic scale with hole drilling done using a Focused Ion Beam – Scanning Electron Microscope (FIB-SEM).

This is a very challenging application because SEM images are subject to fluctuations that can introduce large artifacts when using DIC. Several series of measurements are described to illustrate the operation and effectiveness of the proposed residual stress Nutlin3 computation technique.”
“The introduction of spherical forms of hydroxyapatite has enabled protein scientists to separate and purify proteins multiple times

with the same packed column. Biopharmaceutical companies have driven single column applications of complex samples to simpler samples obtained from upstream column purification steps on affinity, ion exchange or hydrophobic interaction columns. Multiple column purification permits higher protein loads to spherical forms of hydroxyapatite and improved reduction in host cell protein, aggregates, endotoxin, and DNA from recombinant proteins. Adsorption and desorption mechanisms covering the multimodal properties of hydroxyapatite are discussed. TH-302 price The chemical interactions high throughput screening of hydroxyapatite surface with common ions, metals, and phosphate species affect column lifetimes. Adsorbed hydroxonium ions from low ionic strength buffers are noted by a shift in effluent pH during column equilibration. Hydroxonium ion

desorption is observed by acidic shifts in the column effluent with the magnitude and duration surprisingly extreme. Buffering reagents with high buffering capacity reduce both the magnitude and duration of the acidic shift. Column packing methods for the robust spherical particles as well as the microcrystalline hydroxyapatite particles are reviewed. Applications covering extracted proteins and recombinant protein purification, especially monoclonal antibodies, with multiple chromatography media in concert with hydroxyapatite are reviewed.”
“We have demonstrated previously that n-3 PUFA endogenously produced by fat-1 transgenic mice regulate CD4(+) T-cell function by affecting the formation of lipid rafts, liquid-ordered mesodomains in the plasma membrane. In the present study, we tested the effects of dietary sources of n-3 PUFA, i.e. fish oil (FO) or purified DHA, when compared with an n-6 PUFA-enriched maize oil control diet in DO11.10 T-cell receptor transgenic mice. Dietary n-3 PUFA were enriched in CD4(+) T-cells, resulting in the increase of the n-3:n-6 ratio.

001; energy to failure (mJ/mm) in controls was 0.85 (SD, 0.378) versus NPT at 1.128 (SD, 0.638) with a P value of 0.035. Blinded grading of clinical wound appearance and cross-sectional hematoma size were also improved at 72 hours.\n\nConclusions: NPT dressings applied to surgically closed wounds enhance the healing characteristics of porcine wounds at 3 days.\n\nClinical Relevance: We have observed that primarily closed surgical wounds may benefit from treatment with NPT. The benefit of using NPTs may be most pronounced in situations in which

wounds are closed under tension, involve considerable soft tissue trauma, or may be at risk of subdermal hematoma formation.”
“Autologous fat grafting for breast augmentation VX-680 Cell Cycle inhibitor has faced some historical hurdles. However, in recent years it has been gaining acceptance from the medical community. This prospective, nonrandomized open-label study of 20 Japanese women supports the use of autologous fat grafting in breast augmentation and explores enhancement of fat graft tissue with autologous adipose-derived regenerative cells (ADRCs). After adipose harvesting using syringe liposuction, the tissue is processed

in the Celution 800 System(A (R)), which washes the graft and isolates ADRCs. The average cells per gram of harvested adipose tissue was 3.42 x 10(5), and the mean cell viability measured using an automated cell counting system before graft delivery was 85.3%. All patients ubiquitin-Proteasome pathway demonstrated improvement in circumferential breast measurement (BRM) from their baseline state, and breast measurements were stable by 3 months after surgery. The mean BRM 9 months Go 6983 concentration after surgery had increased 3.3 cm from preoperative measurements. Through 9 months, overall physician satisfaction was 69% and patient satisfaction was 75%. No serious or unexpected adverse events were reported, and the procedure was safe and well tolerated in all patients. Postoperative

cyst formation was seen in two patients. These prospective results demonstrate that ADRC-enriched fat grafts processed with a closed automated system maintain high cell viability and that the procedure is safe and effective, with all patients showing improvement after a single treatment.”
“The Gompertz state-space (GSS) model is a stochastic model for analyzing time-series observations of population abundances. The GSS model combines density dependence, environmental process noise, and observation error toward estimating quantities of interest in biological monitoring and population viability analysis. However, existing methods for estimating the model parameters apply only to population data with equal time intervals between observations. In the present paper, we extend the GSS model to data with unequal time intervals, by embedding it within a state-space version of the Ornstein-Uhlenbeck process, a continuous-time model of an equilibrating stochastic system.

“
“Obese individuals are characterized by a chronic, low-grade inflammatory state. Increased levels Selleckchem JQ1 of C-reactive protein (CRP), a marker of inflammation, have been observed in subjects with the metabolic syndrome. We have previously reported that genes encoding proteins involved in

the anti-inflammatory and immune response are differentially expressed in visceral adipose tissue of obese men with or without the metabolic syndrome. Among these genes, the interferon-gamma-inducible protein 30 (IFI30), CD163 molecule (CD163), chemokine (C-X-C motif) ligand 9 (CXCL9) and thymic stromal lymphopoietin (TSLP), were selected for further genetic analyses. The aim of the study was to verify whether IFI30, CD163, CXCL9 and TSLP gene polymorphisms contribute to explain the inter-individual variability of the inflammatory profile of obesity assessed by plasma high-sensitivity CRP concentrations. A total of 1185 severely obese individuals were genotyped for single nucleotide polymorphisms (SNPs) covering most of the sequence-derived genetic variability at this website the IFI30, CD 163, CXCL9 and TSLP gene loci (total of 27 SNPs). Following measurement of plasma CRP levels, subjects were divided into two groups, low vs. high

using the median value of plasma CRP levels (8.31 mg/L) as a cutoff point. Genotype frequencies were compared between groups. Associations between genotypes and plasma CRP levels (continuous variable) were also tested after adjustments for age, sex, smoking and BMI. The rs11554159 and rs7125 IFI30 SNPs showed a significant difference in genotype frequencies (p < 0.05) between subgroups

of low vs. high plasma CRP levels (wild type homozygotes: rs11554159 = 47% vs. 55%, rs7125 = Bindarit mouse 31% vs. 24%, for low vs. high CRP groups, respectively). The association between rs11554159 and CRP levels as a continuous variable remained significant (p = 0.004). Both carriers of the GA and AA genotypes demonstrated, on average, a 13% lower CRP levels in comparison with GG homozygotes. No association was observed between SNPs in the CD163. CXCL9 and TSLP genes and CRP levels. The IFI30 rs11554159 polymorphism could partially explain the inter-individual variability observed in the inflammatory profile associated with obesity. (C) 2011 Elsevier Inc. All rights reserved.”
“To compare the outcome and complications of augmentation cystoplasty before or after renal transplantation in children with neurogenic bladders, with those after kidney transplantation in children with normal bladders.\n\nAugmentation cystoplasty preceded transplantation in 21 children (group 1) and after transplantation in 23 (group 2) operated from 1985 to 2006; these two groups were compared with a control group of 45 children with a normal bladder (group 3) who also received a transplant, for kidney function, episodes of urinary tract infection (UTI), surgical and medical complications.

05).\n\nConclusions: Testicular volume, which is a parameter of spermatogenesis, is impaired in patients on hemodialysis and oxidative stress is considered to be involved in the process. Serum ferritin is a useful parameter for predicting

oxidative stress in the testis.”
“Cerebrospinal fluid (CSF) is being analyzed for the diagnosis of a variety of neurological diseases. Among the methods employed, metabolomics and proteomics are JQ1 increasingly gaining popularity. At present, sensitivity and, in particular, specificity are limited in CSF metabolomics by nuclear magnetic resonance (NMR) spectroscopy. Nonetheless, progress is being made by studying more and more well-defined and homogeneous patient cohorts. This review starts off with a brief overview of classical CSF analysis in multiple sclerosis (MS), followed by a description of NMR spectroscopy in general metabolic CSF analysis. The subsequent sections focus on metabolomic profiling of CSF by NMR spectroscopy in MS and other neurological disorders. Currently existing results Screening Library screening are reviewed and compared, and the potential and limits of this approach are discussed. In addition, several methodological questions are addressed, and the prospects for future developments are briefly outlined.”
“BACKGROUND\n\nAlthough tonometry-based

devices have been applied in several population studies and clinical trials, the agreement between them remains unclear.\n\nMETHODS\n\nCarotid systolic blood pressure (SBP) and augmentation index (AI) were randomly measured from 3 devices, SphygmoCor, PulsePen, and A-Pulse, in 66 consecutive patients from our ambulatory cardiovascular department. The study contains 2 phases: in Study 1, SphygmoCor and PulsePen were performed on each participant by 2 experienced physicians (n = 66); in Study 2, A-Pulse was added after the measurements of SphygmoCor and PulsePen and performed OSI 744 by another technician on the last 34 patients.\n\nRESULTS\n\nCarotid SBP and AI measured by the 3 devices were strongly correlated (R >= 0.78; P < 0.001), but

with significant discrepancies. Specifically, in 66 participants of Study 1, PulsePen estimated higher carotid SBP and AI by 5 mm Hg and 5.7%, respectively, than SphygmoCor. In 34 patients of Study 2, A-Pulse estimated higher central SBP by 3.7 mm Hg than SphygmoCor, and lower central SBP by 5.7 mm Hg than PulsePen. However, no significant difference in interclass comparison was detected between the 3 devices (P >= 0.26). Furthermore, slopes of correlation plots of parameters between SphygmoCor and PulsePen were not significantly different from 1 (P >= 0.09), but were different in the case of A-Pulse (P <= 0.004).\n\nCONCLUSIONS\n\nTonometry-based devices were not consistent in measurements of central BP and wave reflections in clinical practice, with considerable and significant differences among them.

05). The LR group had the shortest mean length of stay compared with the OR and LS groups (2.0 vs 3.5 and 2.7 days, respectively, P < 0.05). No patient had a complete ureteral orifice, but a cystoscopically appreciable remnant of the resected ureteral orifice was noted in 50% of the LS group vs none with the LR and OR groups (P < 0.05). The estimated 2-year RFS was 65% for the entire cohort with no significant differences among groups.\n\nConclusions: Complete laparoscopic resection of the DUBC is feasible, particularly in low-stage, low-grade upper tract TCC and provides benefits such as shorter operative

times and length of stay compared with an open bladder cuff excision.”
“Objective: To present a method to classify health provider responses to patient cues and concerns according to the VR-CoDES-CC (Del Piccolo et al. (2009) [2] and

LXH254 solubility dmso Zimmermann et al. (submitted for publication) [3]). The system permits sequence analysis and a detailed description of how providers handle patient’s expressions of emotion.\n\nMethods: The Verona-CoDES-P system has been developed based on consensus views within the “Verona Network of Sequence Analysis”. The different phases of the creation process are described in detail. A reliability study has been conducted on 20 interviews from buy Galardin a convenience sample of 104 psychiatric consultations.\n\nResults: The VR-CoDES-P has two main classes of provider responses, corresponding to the degree selleck chemicals of explicitness (yes/no) and space (yes/no) that is given by the health provider to each cue/concern expressed

by the patient. The system can be further subdivided into 17 individual categories. Statistical analyses showed that the VR-CoDES-P is reliable (agreement 92.86%, Cohen’s kappa 0.90 (+/- 0.04) p < 0.0001).\n\nConclusion: Once validity and reliability are tested in different settings, the system should be applied to investigate the relationship between provider responses to patients’ expression of emotions and outcome variables.\n\nPractice implications: Research employing the VR-CoDES-P should be applied to develop research-based approaches to maximize appropriate responses to patients’ indirect and overt expressions of emotional needs. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“To assess the effect of vegetation types and of fire regime on the flammability of dead fuels, samples of litter were collected undisturbed (i.e. keeping the structure of litter layers) in 29 study sites spread over the limestone-derived soils of Provence. The sampling plan comprised the most representative ecosystems of the study area: pure Pinus halepensis stands, mixed pine-oak stands and shrublands. Three classes of litter depth were studied (low, medium and high) to account for the variability existing in the field.

This effect is thought to reflect category-specific

adaptation processes. Similarly, presenting two faces concurrently also reduces the N170, suggesting that stimuli compete for neural representations in the occipito-temporal cortex as early as 170 ms. Here we compared the ERPs obtained for two faces or for a face and a phase-scrambled face in three different conditions: (1) a first stimulus (Si) followed by a second one (S2), similarly to previous adaptation paradigms; (2) S1 remaining on screen when S2 appeared, as previously used in studies of competition; (3) or S1 and S2 having simultaneous onset and offset as well. We found a significant and stimulus specific reduction of the N170 in both conditions where the onset of S1 preceded the onset AZD6094 manufacturer of S2. In contrast, simultaneous presentation of the two stimuli had no specific effect on the ERPs at least until 200 ms post-stimulus onset. This suggests either that competition does not lead to early repetition suppression or that the absence of a larger N170 response to two simultaneously presented face stimuli compared to a single stimulus reflects competition between overlapping representations. Overall, our results

show that the asynchronous presentation of S1 and S2 is critical to observe stimulus specific reduction of the N170, presumably reflecting adaptation-related processes. (C) 2013 Elsevier Ltd. All rights reserved.”
“Recent data have shown that TLR4 performs a key role in cerebral ischemia-reperfusion injury which serves as BLZ945 supplier the origin of the immunological inflammatory reactions. However, the therapeutic effects of pharmacological inhibitions of TLR4 and its immediate down-stream pathway remain to be uncovered. In the present study, on mice, intracerebroventricular injection of resatorvid (TLR4 signal inhibitor; 0.01 mu g) significantly reduced JNK-IN-8 research buy infarct volume and improved neurological score after middle cerebral artery occlusion and reperfusion. The levels of phospho-p38,

nuclear factor-kappa B, and matrix metalloproteinase 9 expressions were significantly suppressed in the resatorvid-treated group. In addition, NOX4 associates with TLR4 after cerebral ischemia-reperfusion seen in mice and human. Genetic and pharmacological inhibitions of TLR4 each reduced NOX4 expression, leading to suppression of oxidative/nitrative stress and of neuronal apoptosis. These data suggest that resatorvid has potential as a therapeutic agent for stroke since it inhibits TLR4-NOX4 signaling which may be the predominant causal pathway.”
“We report the oxidation of the InP(100) surface promoted by adsorbed Cs by synchrotron radiation photoemission. Oxygen exposure causes reduction in the charge transferred to the InP substrate from Cs and the growth of indium oxide and phosphorous oxide. The oxide growth displays a clear dependence on the Cs coverage.

We report a patient with bilateral superior altitudinal hemianopia.\n\nCase Report: A 40-year-old man developed bilateral superior altitudinal hemianopia secondary to bilateral parahippocampal and fusiform gyrus lesions. Vision loss was acute, and onset bilateral and simultaneous. Complete neuro-ophthalmologic examinations were performed. His best corrected visual acuity was 20/20 in each eye. Macula and https://www.selleckchem.com/products/epz-5676.html retina examinations were normal. Visual fields were characterized by bilateral upper hemianopia. Cerebral magnetic resonance imaging (MRI) confirmed the presence of symmetrical lesions confined within both bilateral parahippocampal and fusiform gyri. Blood tests, transesophageal echocardiographic examination,

and Doppler ultrasonography of the vertebrobasilar arterial system and carotids were normal.\n\nConclusion: We conclude that embolic events may induce a bilateral superior altitudinal hemianopia.”
“Background: Major surgery and severe trauma typically lead to massive blood loss requiring rapid transfusion of large amounts of blood products. It has been suggested that fresh, unrefrigerated whole blood provides a haemostatic advantage in this setting. The aim of the current study NCT-501 datasheet was to compare the clot formation parameters of fresh, unrefrigerated whole blood and whole blood reconstituted from components stored for varying

periods of time, using rotational thromboelastography (ROTEM (R)). Methods: Fresh whole blood and reconstituted whole blood using combinations of Selleck Semaxanib non-leucoreduced red cell units (stored for 7, 14, 21, 28, or 35 days), platelet concentrates (stored for 1, 3 or 5 days), and fresh frozen plasma (stored for 6 months) were analysed using ROTEM. Measurements of the clotting time (CT), clot formation time (CFT), and maximal clot firmness (MCF) were compared between units of fresh whole blood and reconstituted whole blood samples. Results: There was no difference in the haemostatic parameters measured of fresh whole blood

and reconstituted whole blood using red cell units stored for less than 21 days. ROTEM demonstrated that the CT and CFT were significantly shorter for reconstituted whole blood samples using red cells stored for longer than 21 days when compared to fresh whole blood and to reconstituted whole blood samples using red cell units stored for less than 21 days. The CT was inversely correlated to the duration of platelet storage. The MCF was unchanged regardless of duration of blood product storage. Conclusion: Fresh unrefrigerated whole blood and blood products stored for short duration (less than 21 days) were not superior to those stored for longer durations.”
“Immune responses and DNA damage repair are two fundamental processes that have been characterized extensively, but the links between them remain largely unknown. We report that multiple bacterial, fungal and oomycete plant pathogen species induce double-strand breaks (DSBs) in host plant DNA.

Interestingly, overexpression of SEPT10 increased cells sensitivity to paclitaxel; we also found that SEPT10 is an important regulator for microtubule stability. Furthermore, we found that paclitaxel-resistant tumors had decreased expression of SEPT10. Thus, SEPT10 may be a novel candidate molecule that acts as a good indicator of paclitaxel-resistant carcinomas (Cancer Sci 2012; 103: 821827)”
“Somitogenesis is controlled by the segmentation clock, where the oscillatory expression of cyclic genes such as

Hes7 leads to the periodic expression of Mesp2, a master gene for somite formation. KU-57788 datasheet Fgf signaling induces the oscillatory expression of Hes7 while Hes7 drives coupled oscillations in Fgf and Notch signaling, which inhibits and activates Mesp2 expression, respectively. Because of different oscillatory dynamics,

oscillation in Fgf signaling dissociates from oscillation in Notch signaling in S-1, a prospective somite region, where Notch signaling induces Mesp2 expression when Fgf signaling becomes off. Thus, oscillation in Fgf signaling regulates the timing of Mesp2 expression and the pace of somitogenesis. In addition, Fgf signaling was found to be a primary target for hypoxia, which causes phenotypic variations of heterozygous mutations in Hes7 or Mesp2, suggesting gene-environment interaction through this signaling.”
“In order to optimize plant regeneration techniques for bulbing fennel [Foeniculum vulgare Mill. subsp. vulgare var. azoricum Etomoxir Metabolism inhibitor (Mill.) Thell] via somatic embryogenesis, three different media were tested on four Sicilian fennel ecotypes derived from seed collections. Plant regeneration was obtained through the use of immature inflorescences as explants. Through comparison of different auxins,

naphthoxyacetic acid resulted in high-level induction of embryogenic callus at the lowest concentration (4 mu M), in combination with 6-benzylaminopurine or thidiazuron. After germination of somatic embryos, regenerated plantlets were recovered on medium containing half-strength Murashige and Skoog salts and vitamins FRAX597 order in the absence of plant growth regulators. Regenerated plants were successfully acclimatized (70 %) in a growth chamber prior to transplantation into an open field. The plants appeared phenotypically normal, and both genetic stability and uniformity were confirmed by random amplified polymorphism DNA analysis. The results represent a significant advance on previous reports, due to the high embryogenic ability of immature inflorescence from different ecotypes and the high percentage of regenerated plantlets acclimatized in ex vitro conditions.”
“The discovery of the rhythmogenic pre-Botzinger complex (preBotC) inspiratory network, which remains active in a transverse brainstem slice, greatly increased the understanding of neural respiratory control.