Parylene-bonded micro-fluidic channels for cryogenic experiments at superfluid He-4 temperatures.

We present the manufacturing process of a (24.5 × 100) µm2-sized on-chip flow channel intended for flow experiments with normal and superfluid phases of 4He and showcase such a proof-of-concept experiment. This work proves the suitability of chip-to-chip bonding using a thin layer of Parylene-C for cryogenic temperatures as a simpler alternative to other techniques, such as anodic bonding. A monocrystalline silicon chip embeds the etched meander-shaped micro-fluidic channel and a deposited platinum heater and is bonded to a Pyrex glass top. We test the leak tightness of the proposed bonding method for superfluid 4He, reaching temperatures of ≈1.6 K and evaluate its possible effects on flow experiments. We demonstrate that powering an on-chip platinum heater affects the superfluid flow rate by local overheating of a section of the micro-fluidic channel.

Differential regulation of MAP2 by phosphorylation events in proline-rich versus C-terminal domains.

MAP2 is a critical cytoskeletal regulator in neurons. The phosphorylation of MAP2 (MAP2-P) is well known to regulate core functions of MAP2, including microtubule (MT)/actin binding and facilitation of tubulin polymerization. However, site-specific studies of MAP2-P function in regions outside of the MT-binding domain (MTBD) are lacking. We previously identified a set of MAP2 phosphopeptides which are differentially expressed and predominantly increased in the cortex of individuals with schizophrenia relative to nonpsychiatric comparison subjects. The phosphopeptides originated not from the MTBD, but from the flanking proline-rich and C-terminal domains of MAP2. We sought to understand the contribution of MAP2-P at these sites on MAP2 function. To this end, we isolated a series of phosphomimetic MAP2C constructs and subjected them to cell-free tubulin polymerization, MT-binding, actin-binding, and actin polymerization assays. A subset of MAP2-P events significantly impaired these functions, with the two domains displaying different patterns of MAP2 regulation: proline-rich domain mutants T293E and T300E impaired MT assembly and actin-binding affinity but did not affect MT-binding, while C-terminal domain mutants S426E and S439D impaired all three functions. S443D also impaired MT assembly with minimal effects on MT- or actin-binding. Using heterologous cells, we also found that S426E but not T293E had a lower capability for process formation than the wild-type protein. These findings demonstrate the functional utility of MAP2-P in the proline-rich and C-terminal domains and point to distinct, domain-dependent regulations of MAP2 function, which can go on to affect cellular morphology.

Multi-mode analysis of surface losses in a superconducting microwave resonator in high magnetic fields.

This paper reports on a surface impedance measurement of a bulk metal niobium-titanium superconducting radio frequency (SRF) cavity in a magnetic field (up to 10 T). A novel method is employed to decompose the surface resistance contributions of the cylindrical cavity end caps and walls using measurements from multiple TM cavity modes. The results confirm that quality factor degradation of a NbTi SRF cavity in a high magnetic field is primarily from surfaces perpendicular to the field (the cavity end caps), while parallel surface resistances (the walls) remain relatively constant. This result is encouraging for applications needing high Q cavities in strong magnetic fields, such as the Axion Dark Matter eXperiment because it opens the possibility of hybrid SRF cavity construction to replace conventional copper cavities.

Nonfuel Antineutrino Contributions in the High Flux Isotope Reactor.

Reactor neutrino experiments have seen major improvements in precision in recent years. With the experimental uncertainties becoming lower than those from theory, carefully considering all sources of ν ¯ e is important when making theoretical predictions. One source of ν ¯ e that is often neglected arises from the irradiation of the nonfuel materials in reactors. The ν ¯ e rates and energies from these sources vary widely based on the reactor type, configuration, and sampling stage during the reactor cycle and have to be carefully considered for each experiment independently. In this article, we present a formalism for selecting the possible ν ¯ e sources arising from the neutron captures on reactor and target materials. We apply this formalism to the High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory, the ν ¯ e source for the the Precision Reactor Oscillation and Spectrum Measurement (PROSPECT) experiment. Overall, we observe that the nonfuel ν ¯ e contributions from HFIR to PROSPECT amount to 1% above the inverse beta decay threshold with a maximum contribution of 9% in the 1.8-2.0 MeV range. Nonfuel contributions can be particularly high for research reactors like HFIR because of the choice of structural and reflector material in addition to the intentional irradiation of target material for isotope production. We show that typical commercial pressurized water reactors fueled with low-enriched uranium will have significantly smaller nonfuel ν ¯ e contribution.

Measurement of the Antineutrino Spectrum from

This Letter reports the first measurement of the ^{235}U ν[over ¯]_{e} energy spectrum by PROSPECT, the Precision Reactor Oscillation and Spectrum experiment, operating 7.9 m from the 85 MW_{th} highly enriched uranium (HEU) High Flux Isotope Reactor. With a surface-based, segmented detector, PROSPECT has observed 31678±304(stat) ν[over ¯]_{e}-induced inverse beta decays, the largest sample from HEU fission to date, 99% of which are attributed to ^{235}U. Despite broad agreement, comparison of the Huber ^{235}U model to the measured spectrum produces a χ^{2}/ndf=51.4/31, driven primarily by deviations in two localized energy regions. The measured ^{235}U spectrum shape is consistent with a deviation relative to prediction equal in size to that observed at low-enriched uranium power reactors in the ν[over ¯]_{e} energy region of 5-7 MeV.

First Search for Short-Baseline Neutrino Oscillations at HFIR with PROSPECT.

This Letter reports the first scientific results from the observation of antineutrinos emitted by fission products of ^{235}U at the High Flux Isotope Reactor. PROSPECT, the Precision Reactor Oscillation and Spectrum Experiment, consists of a segmented 4 ton ^{6}Li-doped liquid scintillator detector covering a baseline range of 7-9 m from the reactor and operating under less than 1 m water equivalent overburden. Data collected during 33 live days of reactor operation at a nominal power of 85 MW yield a detection of 25 461±283 (stat) inverse beta decays. Observation of reactor antineutrinos can be achieved in PROSPECT at 5σ statistical significance within 2 h of on-surface reactor-on data taking. A reactor model independent analysis of the inverse beta decay prompt energy spectrum as a function of baseline constrains significant portions of the previously allowed sterile neutrino oscillation parameter space at 95% confidence level and disfavors the best fit of the reactor antineutrino anomaly at 2.2σ confidence level.

Abnormalities of gait caused by ankle arthritis are improved by ankle arthrodesis.

AIMS: The surgical management of ankle arthritis with tibiotalar arthrodesis is known to alter gait, as compared with normal ankles. The purpose of this study was to assess post-operative gait function with gait before arthrodesis. PATIENTS AND METHODS: We prospectively studied 20 patients who underwent three-dimensional gait analysis before and after tibiotalar arthrodesis. Cadence, step length, walking velocity and total support time were assessed. Kinetic parameters, including the moment and power of the ankle in the sagittal plane and hip power were also recorded. RESULTS: Significant improvement was recorded across numerous parameters compared with pre-operative measurements. Temporal-spatial data demonstrated a significant increase in step length (p = 0.003) and velocity (p = < 0.001). Total support time decreased for the unaffected limb (p = 0.01). Kinematic results demonstrated that in the affected limb, total sagittal range of movement did not change significantly (p = 0.1259). However, the arc of movement had a near congruent shift with mean maximal dorsiflexion increasing from 5° (-17° to 16°) to 12° (5° to 18°) (p < 0.001) and mean maximal plantarflexion decreasing from 6.8° (6° to 21°) to 0.9° (-9° to 8°) (p = 0.003). Mean hip joint range of movement increased by 6° (-7° to 24°; p = 0.003). Kinetic results demonstrated no statistically significant change in ankle power (p = 0.1292). However, there was an increase in ankle moment (p = 0.04) and hip power (p = 0.01) in the surgically treated extremity. Sagittal plane range of movement was not reduced after tibiotalar fusion. CONCLUSION: Although following tibiotalar arthrodesis the gait demonstrated never matched the gait shown in unaffected ankles, compared with the pre-operative analysis there was improvement in numerous temporal-spatial, kinematic, and kinetic measures. Cite this article: Bone Joint J 2016;98-B:1369-75.

Acquired nasopharyngeal stenosis in a patient with sarcoidosis.

INTRODUCTION: Acquired nasopharyngeal stenosis typically occurs as a result of surgery or irradiation of the nasopharynx. Sarcoidosis has numerous manifestations in the head and neck region, although an association with nasopharyngeal stenosis has not previously been reported. CASE REPORT: A 40-year-old man with sarcoidosis developed severe acquired nasopharyngeal stenosis. This was successfully managed with balloon dilatation, followed by pharyngoplasty with local pharyngeal flap reconstruction. CONCLUSION: This report is intended to prompt consideration of nasopharyngeal stenosis as a potential cause of nasal obstruction in patients with sarcoidosis, and to draw attention to the need to consider sarcoidosis in the differential diagnosis of patients with acquired nasopharyngeal stenosis. We also demonstrate the viability of pharyngoplasty in the management of nasopharyngeal stenosis in the setting of sarcoidosis.

Molecular chaperones and substrate ubiquitination control the efficiency of endoplasmic reticulum-associated degradation.

The endoplasmic reticulum (ER) must contend with a large protein flux, which is especially notable in cells dedicated to secreting hormone-regulated gene products. Because of the complexity of the protein folding pathway and the potential for genetic or stochastic errors, a significant percentage of these nascent secreted proteins fail to acquire their native conformations. If these species cannot be cleared from the ER, they may aggregate, which leads to cell death. To lessen the effects of potentially toxic polypeptides, aberrant ER proteins are destroyed via a process known as ER-associated degradation (ERAD). ERAD substrates are selected by molecular chaperones and chaperone-like proteins, and prior to degradation most substrates are ubiquitin-modified. Together with the unfolded protein response, the ERAD pathway is a critical component of the protein quality control machinery in the ER. Although emerging data continue to link ERAD with human diseases, most of our knowledge of this pathway arose from studies using a model eukaryote, the yeast Saccharomyces cerevisiae. In this review, we will summarize the discoveries that led to our current understanding of this pathway, focusing primarily on experiments in yeast. We will also indicate links between ERAD and disease and emphasize future research avenues.

Lung separation and the difficult airway.

Selective collapse of a lung and one-lung ventilation (OLV) is now performed for most thoracic surgical procedures. Modern double-lumen endobronchial tubes and bronchial blockers have made lung separation safe and relatively easy to achieve. However, OLV in the patient with a 'difficult airway' can present a challenge to the anaesthesiologist. This review considers the different techniques used to achieve lung separation and their application to the patient with a difficult airway.

Surgical aspects of the diabetic foot.

A comprehensive review of the literature relating to the pathology and management of the diabetic foot is presented. This should provide a guide for the treatment of ulcers, Charcot neuro-arthropathy and fractures involving the foot and ankle in diabetic patients.

Heat shock protein 101 effects in A. thaliana: genetic variation, fitness and pleiotropy in controlled temperature conditions.

The Hsp100/ClpB heat shock protein family is ancient and required for high temperature survival, but natural variation in expression and its phenotypic effects is unexplored in plants. In controlled environment experiments, we examined the effects of variation in the Arabidopsis cytosolic AtHsp101 (hereafter Hsp101). Ten wild-collected ecotypes differed in Hsp101 expression responses across a 22 to 40 degrees C gradient. Genotypes from low latitudes expressed the least Hsp101. We tested fitness and pleiotropic consequences of varying Hsp101 expression in 'control' vs. mild thermal stress treatments (15/25 degrees C D/N vs. 15/25 degrees D/N plus 3 h at 35 degrees C 3 days/week). Comparing wild type and null mutants, wt Columbia (Col) produced approximately 33% more fruits compared to its Hsp101 homozygous null mutant. There was no difference between Landsberg erecta null mutant NIL (Ler) and wt Ler; wt Ler showed very low Hsp101 expression. In an assay of six genotypes, fecundity was a saturating function of Hsp101 content, in both experimental treatments. Thus, in addition to its essential role in acquired thermal tolerance, Hsp101 provides a substantial fitness benefit under normal growth conditions. Knocking out Hsp101 decreased fruit production, days to germination and days to bolting, total dry mass, and number of inflorescences; it increased transpiration rate and allocation to root mass. Root : total mass ratio decayed exponentially with Hsp101 content. This study shows that Hsp101 expression is evolvable in natural populations. Our results further suggest that Hsp101 is primarily an emergency high-temperature tolerance mechanism, since expression levels are lower in low-latitude populations from warmer climates. Hsp101 expression appears to carry an important trade-off in reduced root growth. This trade-off may select for suppressed expression under chronically high temperatures.

The relevance of migraine in patients with Menière's disease.

CONCLUSION: Coexistent migraine affects relevant clinical features of patients with Ménière's disease (MD). OBJECTIVE: Epidemiological studies have shown an association between migraine and MD. We sought to determine whether the coexistence of migraine affects any clinical features in patients with MD. PATIENTS AND METHODS: In this retrospective case-control study of University Neurotology Clinic patients, 50 patients meeting 1995 AAO-HNS criteria for definite MD were compared to 18 patients meeting the same criteria in addition to the 2004 IHS criteria for migraine (MMD). All had typical low frequency sensorineural hearing loss and episodes of rotational vertigo. Outcome measures included: sex, age of onset of episodic vertigo or fluctuating hearing loss, laterality of hearing loss, aural symptoms, caloric responses, severity of hearing loss, and family history of migraine, episodic vertigo or hearing loss. RESULTS: Age of onset of episodic vertigo or fluctuating hearing loss was significantly lower in patients with MMD (mean +/- 1.96*SE = 37.2 +/- 6.3 years) than in those with MD (mean +/- 1.96*SE = 49.3 +/- 4.4 years). Concurrent bilateral aural symptoms and hearing loss were seen in 56% of MMD and 4% of MD patients. A family history of episodic vertigo was seen in 39% of MMD and 2% of MD patients.

Biomarker-assisted diagnosis of ovarian, cervical and pulmonary small cell carcinomas: the role of TTF-1, WT-1 and HPV analysis.

AIMS: Small cell carcinoma of the ovary, hypercalcaemic-type (SCCOH) is morphologically similar to small cell carcinomas from other sites. The aims of this study were to (i) determine if a biomarker panel would distinguish small cell carcinomas of the ovary, cervix (SCCCx) and lung (SCCLu) and (ii) potentially determine the histogenesis of SCCOH. METHODS AND RESULTS: Nine ovarian small cell carcinomas (seven hypercalcaemic type; two pulmonary type), eight SCCCx and 22 SCCLu were immunostained for thyroid transcription factor (TTF)-1, WT-1, p16, cKIT and OCT3/4; a subset of cases were tested for human papillomavirus (HPV). WT-1 was diffusely positive in 6/7 SSCOH versus two of 33 other small cell carcinomas (P

The history of anesthesia for thoracic surgery.

Today, thoracic surgeons routinely perform complex operations on even the most complicated patient. However, just 75 years ago the ability to operate within the chest was strictly limited to only the simplest and quickest procedures. The dramatic advances in the specialty of thoracic surgery have closely paralleled the introduction of new anesthetic practices, equipment and drugs. This review will identify major events in the history of anesthesia for thoracic surgery.

Nitrous oxide and laparoscopic bariatric surgery.

BACKGROUND: Nitrous oxide (N2O) is frequently used to supplement more potent anesthetic agents. One side-effect of N2O is its ability to expand an air-containing space. We investigated if N2O adversely affected operating conditions by distending normal bowel during laparoscopic bariatric procedures. METHODS: 50 morbidly obese patients were divided into 2 study groups. Group 1 patients were ventilated with a halogenated anesthetic/oxygen/air mixture, while Group 2 received a halogenated anesthetic/oxygen/N2O mixture. At 30, 60, and 90 min intervals during the operation, the surgeon was asked if N2O was being used. RESULTS: The surgeons responded correctly only 42% (30 min), 50% (60 min), and 48% (90 min) of the time. In Group 2 (N2O) patients, they incorrectly answered that N2O was not being used 88% (30 min), 68% (60 min), and 68% (90 min); and in Group 1 (air) patients, they incorrectly answered that N2O was being used 28% (30 min), 32% (60 min), and 36% (90 min) of the time. CONCLUSION: We found that using N2O did not cause noticeable bowel distention during laparoscopic bariatric procedures of relatively short duration.

Recognition and delivery of ERAD substrates to the proteasome and alternative paths for cell survival.

Endoplasmic reticulum-associated protein degradation (ERAD) is a protein quality control mechanism that minimizes the detrimental effects of protein misfolding in the secretory pathway. Molecular chaperones and ER lumenal lectins are essential components of this process because they maintain the solubility of unfolded proteins and can target ERAD substrates to the cytoplasmic proteasome. Other factors are likely required to aid in the selection of ERAD substrates, and distinct proteinaceous machineries are required for substrate retrotranslocation/dislocation from the ER and proteasome targeting. When the capacity of the ERAD machinery is exceeded or compromised, multiple degradative routes can be enlisted to prevent the detrimental consequences of ERAD substrate accumulation, which include cell death and disease.