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The rotational spectrum of 1,3,5-trisilapentane was observed on a chirped-pulse Fourier transform microwave spectrometer and is reported. During assignment, multiple conformations of the molecule were identified in the molecular beam. Prior quantum-chemical calculations performed on the molecule show that the identified spectra correspond to the lowest three calculated energetic structures. These structures are of C2(Conf.1), C2v(Conf.2), and C1(Conf.3) symmetry, with relative energy ordering of Conf.1 < Conf.3 < Conf.2, which is in stark contrast to n-pentane and all known silicon-substituted n-pentane derivatives. This is found to most likely arise from the elongation of the Si–C bond and the size of the silicon atoms providing for the C2and C1structures relieving steric hindrance in comparison to that of the C2v. In the C2vand C1conformers, splitting in the spectra due to internal rotation of the −SiH3end groups of 1,3,5-trisilapentane was observed and determined. The C2vequivalent V3values are 368.46(33) cm–1, and the C1V3values are 347.78(21) and 360.18(88) cm–1, respectively. These barriers are compared to similar species in order to help verify their veracity and are determined to be accurate based on similar molecular silyl rotors.

The definition and measurement of local and global aromaticity in fused ring polycyclic aromatic compounds is a complex issue. Historically, these types of molecules have been explored in this capacity by way of experimental (NMR, thermochemistry) and computational (NICS, HOMA) analyses. We previously showed how borepin rings with [b, f] arene fusions can be used as experimental magnetic aromaticity reporters via the remaining protons attached to the borepin rings. In this report, we describe a joint experimental and computational analysis of several borepin-containing polycyclic aromatic molecules in order to draw conclusions about the influence of ring fusion on aromaticity. We find that the borepin ring within these extended structures is a unique motif with limited σ-contribution to aromaticity while still displaying a wide range of structural and magnetic aromatic character.

Quinoidal compounds with proaromatic structures possess differing degrees of diradical character, where the open-shell diradical resonance form has restored aromaticity throughout the compound. Methods to tune the diradical character of these compounds have traditionally focused on altering the length and the molecular composition of the π-conjugated backbones. However, other molecular design strategies to tune the singlet–triplet gap of π-conjugated quinoidal molecules have not been extensively explored. We previously reported a strikingly small energy gap between the quinoidal and diradical states of a quinoidal small molecule containing methano[10]annulene (TMTQ) that was dictated in large part by the unusual aromaticity of the central annulene ring. Here, we report on two alkylated derivatives of TMTQ that present substantially different torsional biases to the planarity of the TMTQ π-system. Using a combination of electronic and vibrational spectroscopies, magnetic measurements, and quantum chemical calculations, we demonstrate here how a steric effect rather than π-electron compositional molecular engineering can dramatically narrow the singlet–triplet gap of a quinoidal compound to as small as −0.52 kcal/mol, determined experimentally. This study offers important insight for the continued development of open-shell diradical molecules that need not rely exclusively on the design of synthesis of new and complex π-conjugated systems.

Two large volcanic eruptions contributed to extreme cold temperatures during the early 1800s, one of the coldest phases of the Little Ice Age. While impacts from the massive 1815 Tambora eruption in Indonesia are relatively well‐documented, much less is known regarding an unidentified volcanic event around 1809. Here, we describe the spatial extent, duration, and magnitude of cold conditions following this eruption in northwestern North America using a high‐resolution network of tree‐ring records that capture past warm‐season temperature variability. Extreme and persistent cold temperatures were centered around the Gulf of Alaska, the adjacent Wrangell‐St Elias Mountains, and the southern Yukon, while cold anomalies diminished with distance from this core region. This distinct spatial pattern of temperature anomalies suggests that a weak Aleutian Low and conditions similar to a negative phase of the Pacific Decadal Oscillation could have contributed to regional cold extremes after the 1809 eruption. Extreme post‐1809 cooling in northwestern North America was centered around the Gulf of Alaska and the southern YukonSpatial temperature patterns in North America post‐1809 are consistent with the influence of North Pacific decadal variability Extreme post‐1809 cooling in northwestern North America was centered around the Gulf of Alaska and the southern Yukon Spatial temperature patterns in North America post‐1809 are consistent with the influence of North Pacific decadal variability

Gold nanoparticles provide a template for preparing supported lipid layers with well-defined curvature. Here, we utilize the localized surface plasmon resonance (LSPR) of gold nanoparticles as a sensor for monitoring the preparation of lipid layers on nanoparticles. The LSPR is very sensitive to the immediate surroundings of the nanoparticle surface, and it is used to monitor the coating of lipids and subsequent conversion of a supported bilayer to a hybrid membrane with an outer lipid leaflet and an inner leaflet containing hydrophobic alkanethiol. We demonstrate that both decanethiol and propanethiol are able to form hybrid membranes and that the membrane created over the shorter thiol can be stripped from the gold along with the lipid leaflet using β-mercaptoethanol. The sensitivity of the nanoparticle LSPR to the refractive index (RI) of its surroundings is greater when the shorter thiol is used (37.8 ± 1.5 nm per RI unit) than when the longer thiol is used (27.5 ± 0.5 nm per RI unit). Finally, C-reactive protein binding to the membrane is measured using this sensor allowing observation of both protein–membrane and nanoparticle–nanoparticle interactions without chemical labeling of protein or lipids.

Early detection of disease can speed treatment, slow spread of disease in a herd, and improve health status of animals. Immune stimulation increases rectal temperature (RT). Injectable radio-frequency implants (RFI) can provide temperature at the site of implantation. The fidelity of peripheral site temperature, determined by RFI, relative to RT is unknown in cattle. We hypothesized that during lipopolysaccharide (LPS) challenge, temperature at 3 peripheral sites would be similar to RT in steers (n = 4; BW 77 ± 2.1 kg). The 3 sites were 1) subcutaneous (SC) at the base of the ear (ET); 2) SC posterior to the poll (PT); and 3) SC beneath the umbilical fold (UT). Steers were housed in controlled temperature (CT) rooms (between 18 and 21°C; n = 2/room). Rectal temperature, ET, PT, and UT were recorded every 8 h daily. On d 7, 21, 22, 36, and 37, RT and RFI were taken every 5 min for 6 h, every 15 min for 3 h, and every 30 min for 15 h. To test RFI during a simulated immune challenge, LPS (E. coli055:B5) was injected intravenously (IV) at 1000 h on d 22 and 37. Basal temperatures (°C) were RT (38.7 ± 0.20), ET (37.1 ± 0.86), PT (36.7 ± 0.57), and UT (36.3 ± 0.97). Rectal temperature increased to 39.9 ± 0.30°C after LPS, but ET, PT, and UT decreased. Heat stress also increases RT, which makes it difficult to identify sick animals using RT. The second hypothesis tested was that ET positively correlates to RT and negatively correlates to RT during LPS under heat stress. Four steers (127 ± 7.3 kg) were housed in CT chambers (n = 2/chamber), implanted with a RFI, and allowed 2 wk to acclimate. One chamber remained at 20°C, the other was increased to 34°C starting at 0800 h for a period of 48 h. The LPS was administered IV to all steers at 1000 h on d 2. After a 2-wk recovery at 20°C, the temperature was increased in the other chamber, resulting in a crossover design with each steer serving as its own control. Pearson's correlation coefficients for ET and RT were 0.30 (P< 0.01) during heat stress, 0.20 (P< 0.05) during heat stress with LPS challenge, 0.34 (P< 0.01) during thermoneutrality, and −0.42 (P< 0.01) during thermoneutrality with LPS. These data refute the hypothesis that RT and peripheral temperature move in synchrony after LPS challenge. These data suggest that individual response be considered when identifying models for use of ET, but these RFI have potential for use in the early detection of diseases that alter basal temperature.

AMP-activated protein kinase (AMPK) activity may alter blood pressure by directly influencing vascular tone. The purpose of this study is to examine if these effects occur acutely in a model of hypertension.

Objective: The purpose of this research was to test the hypothesis that parental satisfaction with neonatal intensive care is greater in a single-family room facility as compared with a conventional open-bay neonatal intensive care unit (NICU).Methods: This investigation was a prospective cohort study comparing satisfaction survey results for parents who responded to a commercially available parent NICU satisfaction survey following the provision of NICU care in open-bay and single-family room facilities. A subset of 16 items indicative of family-centered care was also computed and compared for these two NICU facilities.Results: Parents whose babies received care in the single-family room facility expressed significantly improved survey responses in regard to the NICU environment, overall assessment of care, and total survey score than did parents of neonates in the open-bay facility. With the exception of the section on nursing in which scores in both facilities were high, nonsignificant improvement in median scores for the sections on delivery, physicians, discharge planning, and personal issues were noted. The total median item score for family-centered care was significantly greater in the single-family room than the open-bay facility.Conclusions: Parental satisfaction with care in the single-family room NICU was improved in comparison with the traditional open-bay NICU. The single-family room environment appears more conducive to the provision of family-centered care. Improved parental satisfaction with care and the potential for enhanced family-centered care need to be considered in decisions made regarding the configuration of NICU facilities in the future.

Chlortetracycline is an antibiotic that is used to increase weight gain, efficiency of gain, carcass grade, and conception rates. The objective of this experiment was to evaluate the effects of supplementation of 350 mg/d of chlortetracycline on ADG, G:F, BCS, thyroxine, and systemic glucose concentrations in yearling dairy heifers. Forty 12-mo-old Holstein heifers (initial BW = 363 ± 21 kg) were housed in a free-stall barn with ad libitum access to feed and water for 104 d. A transition period was begun 14 d before the age of 12 mo to acclimate the heifers to the diet. The chlortetracycline-fed group (n = 20) consumed 328 ± 8.2 mg of chlortetracycline/heifer daily. Measurements for BW, withers and hip heights, BCS, and health score were recorded weekly. Dry matter intake was measured daily. Blood was sampled every 4 d to determine plasma thyroxine and glucose concentrations and every 2 d to determine progesterone concentrations. Heifers were artificially inseminated on the first observed standing heat after 13 mo of age. There were no effects of chlortetracycline on ADG, G:F, withers and hip heights, BCS, blood glucose concentrations, peak progesterone concentrations, health, or conception rate. There was an interaction between treatment and time for chlortetracycline on serum thyroxine concentration. In the beginning of the experiment, serum thyroxine concentration was lower in heifers supplemented with chlortetracycline. There was no difference between treatments in thyroxine concentration at the end of the experiment. Chlortetracycline supplementation was not beneficial for yearling dairy heifers.

Isolated FSH deficiency due to a mutation in the FSHbeta subunit is characterized by an extremely low serum FSH concentration. We report a patient who presented with an FSH of 0.8 mIU/ml and infertility associated with anovulation. Endocrinological assessment and immunohistochemistry revealed that a granulosa cell tumour was secreting inhibin B and suppressing FSH; however, LH and estradiol were within their normal ranges. Upon removal of the tumour, inhibin B decreased and FSH levels rose to normal values. The patient subsequently conceived and delivered successfully. Based on this case and on those previously described in the literature, we suggest that inhibin B levels should be evaluated in anovulatory patients having a clinical presentation consistent with functional hypothalamic amenorrhoea and very low to normal values of FSH.

BackgroundHereditary spastic paraparesis is a genetically heterogeneous condition. Recently, mutations in the spastin gene were reported in families linked to the common SPG4 locus on chromosome 2p21-22.ObjectivesTo study a population of patients with hereditary spastic paraparesis for mutations in the spastin gene (SPG4) on chromosome 2p21-22.MethodsDNA from 32 patients (12 from families known to be linked to SPG4) was analysed for mutations in the spastin gene by single strand conformational polymorphism analysis and sequencing. All patients were also examined clinically.ResultsThirteen SPG4 mutations were identified, 11 of which are novel. These mutations include missense, nonsense, frameshift, and splice site mutations, the majority of which affect the AAA cassette. We also describe a nucleotide substitution outside this conserved region which appears to behave as a recessive mutation.ConclusionsRecurrent mutations in the spastin gene are uncommon. This reduces the ease of mutation detection as a part of the diagnostic work up of patients with hereditary spastic paraparesis. Our findings have important implications for the presumed function of spastin and schemes for mutation detection in HSP patients.

To map the gene responsible for autosomal dominant pure hereditary spastic paraplegia (ADPHSP) in a large affected family.

This study aimed to describe the clinical phenotype of a large collection of families with autosomal dominant pure hereditary spastic paraplegia (ADPHSP), to examine the relative frequency of each of the three known ADPHSP genes within this population, to assess locus–phenotype correlation in ADPHSP and to ascertain whether there are clinical subgroups within genetically defined populations of ADPHSP families. We examined 306 family members, 144 affected, from 28 families with ADPHSP. Linkage analysis at the three known ADPHSP loci allowed us to categorize the families into three groups: (i) those families showing linkage to the chromosome 2 ADPHSP locus (seven families); (ii) those in which linkage to all known loci was excluded (five families); and (iii) those in which linkage results were inconclusive. There was a correlation between linkage group and clinical features, with chromosome 2-linked families having a later age at onset of symptoms (P = 0.001) and later age before commencing walking stick use (P = 0.007) than those families in which linkage to all known ADPHSP loci was excluded. There were no clinical differences between the families showing linkage to the chromosome 2 locus, but there were clinical differences between the families in which linkage to all of the known loci had been excluded (P < 0.0001). We conclude that the chromosome 2 ADPHSP gene is a frequent cause of ADPHSP in UK families, that the responsible gene has not yet been mapped in a significant proportion of families and that certain clinical features of ADPHSP, including age at onset, are at least in part determined by genetic locus.

An ion-pair HPLC approach with ordinary silica has been applied, with detection by ultraviolet absorption, to the assay of plasma for chlorpromazine and its sulfoxide on the one hand, and for 7-hydroxychlorpromazine (an active metabolite) on the other hand. The respective sample-preparation procedures entail extraction of the plasma with heptane at strongly alkaline pH, or else with diethyl ether at a less alkaline pH and with ensuing back-extraction and re-extraction. For each of the compounds, levels as low as 10 ng. ml-1 are measurable. The conditions adopted are such that specificity and reproducibility are satisfactory although chlorpromazine and its various metabolites, especially 7-hydroxychlorpromazine, are chemically unstable and, moreover, are readily lost onto glass. With the unorthodox separation system adopted, adsorption rather than partition appears to be the dominant mechanism.

An ion-pair HPLC approach with ordinary silica has been applied, with detection by ultraviolet absorption, to the assay of plasma for chlorpromazine and its sulfoxide on the one hand, and for 7-hydroxychlorpromazine (an active metabolite) on the other hand. The respective sample-preparation procedures entail extraction of the plasma with heptane at strongly alkaline pH, or else with diethyl ether at a less alkaline pH and with ensuing back-extraction and re-extraction. For each of the compounds, levels as low as 10 ng.ml-1 are measurable. The conditions adopted are such that specificity and reproducibility are satisfactory although chlorpromazine and its various metabolites, especially 7-hydroxychlorpromazine, are chemically unstable and, moreover, are readily lost onto glass. With the unorthodox separation system adopted, adsorption rather than partition appears to be the dominant mechanism.

The novel method now described, for S-carboxymethylcysteine in plasma at levels that may be lower than 20 g/ml in therapeutic investigations, entails conversion into the corresponding phenylthiohydantoin (PTH) derivative, so as to confer ultraviolet detectability in a final separation step entailing reverse-phase HPLC. The conditions adopted take account of possible losses of the compound, associated with capricious water-solubility, of stability problems unexpectedly encountered with its PTH derivative, and of the risk of interferences from plasma constituents.

Raman spectroscopy, for well-understood fundamental reasons, is a relatively insensitive method of analysis, i.e., it is problematic to study dilute solutions, gases at low pressures, adsorbed species, etc. We describe instrumentation incorporating exit slit plane “multiplex” detection and demonstrate that the instrument improves in sensitivity over its conventional counterpart by a significant margin (in this case >X1000). The value that this increased optical efficiency provides is demonstrated and new applications of Raman spectroscopy are discussed. We include a discussion of the factors controlling the efficiency of illuminating and viewing opaque or highly scattering samples sensitive to high brightness lasers and demonstrate that most commercial spectrometers are set up in such a way that they perform in these cases much less adequately than need be.

Rheumatoid arthritis (RA) is the commonest form of chronic inflammatory joint disease and a major target for symptom-modifying and disease-modifying drug therapy. New approaches to the treatment of RA using biological agents targeted to cellular receptors, cytokines and other mediators of inflammation, together with the availability of new methods of outcome assessment, make it timely to reconsider the classification of anti-rheumatoid drugs and the requirements for the registration of new drug entities. Under the auspices of GREES (Group for the Respect of Ethics and Excellence in Science), a European Working Group of clinicians with experience in rheumatology, scientists and representatives from industry and national drug licensing authorities have formulated recommendations for the requirements for registration of anti-rheumatic drugs designed for symptom modification, structural modification and the suppression of inflammation, with particular emphasis placed on quality of life assessment by generic and disease-specific validated methods. This paper outlines the group's advice for pre-clinical testing, and Phase I, Phase II and Phase III trials to allow licences to be granted for each indication, while recognizing that a single drug may have reason to be approved under several headings.

Regional climate trends are of interest both for understanding natural climate processes and as tests of anthropogenic climate change signatures. Relative to global trends, however, their detection is hampered by smaller datasets and the influence of regional climate processes such as the Southern Oscillation. Regional trends are often presented by authors without demonstration of statistical significance. In this paper, regional-average annual series of air temperature and sea surface temperature for the New Zealand region are analyzed using a systematic statistical approach that selects the optimum statistical model (with respect to serial correlation, linearity, etc.), explicitly models the interannual variability associated with observable regional climate processes, and tests significance. It is found that the residuals are stationary and are a red noise process ARMA(1,0) for all the series examined. The SOI and a meridional circulation anomaly index (both high-pass filtered) are “explanatory variables” for interannual variability. For national-average air temperature (AT), linear and exponential trend models are equally valid but for simplicity the linear model is preferred. Failure to model the serial correlation in AT would result in an estimated confidence interval for trend that is too small by 36. The use of the explanatory variables tightens the confidence interval by 15.

Personal construct psychology researchers frequently have linked a low degree of construct relatedness to schizophrenia. However, researchers also have found a low degree of construct relatedness to be predictive of accuracy in person perception tasks. Attempting to clarify this, Landfield (1977,1980) proposed that the schizophrenic's construing is characterized by both a low degree of construct integration and a low degree of construct relatedness. The role of both these variables was explored by administering repertory grids to 20 schizophrenic and 20 nonschizophrenic adult psychiatric inpatients. The linkage of schizophrenia to both a low degree of construct relatedness and a low degree of construct integration was supported. The theoretical implications of these findings are discussed.

The New Zealand Meteorological Service has used a Robertson–Berger meter (RB meter) to monitor solar UV-B radiation for the past decade. The radiometric properties of the instrument have been analyzed and agree with the standard values published by Berger. A detailed theoretical treatment of the RB meter response that fully accounts for its cosine response is presented. Field measurements made with the RB meter and with a double monochromator spectral radiometer were used to validate the theoretical model and to derive a calibration for the RB meter. Only cloud-free data were considered so that the downward radiation field at the surface could be modeled as the sum of direct solar and isotropic diffuse components. The imperfect cosine responses of both instruments were modeled. A RB meter count was found to equate to 0.25 ± 0.02 Jm^−2 referenced to 300-nm radiation at vertical incidence.

A radioaerosol procedure using 99mTc-DTPA (diethylene triamine penta acetate) was used to evaluate the permeability of the pulmonary epithelium in smokers and nonsmokers. The average clearance of this indicator from the lungs of smokers without significant airway obstruction exceeded that found in normal subjects by an average factor of more than five. This abnormality was observed throughout all lung regions. 99mTc-DTPA clearance decreased rapidly during the week after smoking was discontinued. It is concluded that smoking results in a rapidly reversible increase in pulmonary epithelial permeability.

A case of post-biopsy renal arteriovenous fistula causing high output cardiac failure was diagnosed one year after the start of maintenance hemodialysis, confirmed by radionuclide studies, and successfully treated with nephrectomy. Management was complicated by superimposed digitalis intoxication. It is suggested that the presence of the renal arteriovenous fistula might account for the accelerated deterioration in renal function observed in this patient.

The New Zealand Meteorological Service has used a Robertson-Berger meter (RB meter) to monitor solar UV-B radiation for the past decade. The radiometric properties of the instrument have been analyzed and agree with the standard values published by Berger. A detailed theoretical treatment of the RB meter response that fully accounts for its cosine response is presented. Field measurements made with the RB meter and with a double monochromator spectral radiometer were used to validate the theoretical model and to derive a calibration for the RB meter. Only cloud-free data were considered so that the downward radiation field at the surface could be modeled as the sum of direct solar and isotropic diffuse components. The imperfect cosine responses of both instruments were modeled. A RB meter count was found to equate to 0.25 ± 0.02 Jm^-2 referenced to 300-nm radiation at vertical incidence.