Rotational constants and structure of para-difluorobenzene determined by femtosecond Raman coherence spectroscopy: A new transient type

Femtosecond Raman rotational coherence spectroscopy (RCS) detected by degenerate four-wave mixing is a background-free method that allows to determine accurate gas-phase rotational constants of non-polar molecules. Raman RCS has so far mostly been applied to the regular coherence patterns of symmetric-top molecules, while its application to nonpolar asymmetric tops has been hampered by the large number of RCS transient types, the resulting variability of the RCS patterns, and the 10³–10⁴ times larger computational effort to simulate and fit rotational Raman RCS transients. We present the rotational Raman RCS spectra of the nonpolar asymmetric top 1,4-difluorobenzene (para-difluorobenzene, p-DFB) measured in a pulsed Ar supersonic jet and in a gas cell over delay times up to ~2.5 ns. p-DFB exhibits rotational Raman transitions with ΔJ = 0, 1, 2 and ΔK = 0, 2, leading to the observation of J −, K −, A −, and C–type transients, as well as a novel transient (S–type) that has not been characterized so far. The jet and gas cell RCS measurements were fully analyzed and yield the ground-state (v = 0) rotational constants Aₒ = 5637.68(20) MHz, Bₒ = 1428.23(37) MHz, and Cₒ = 1138.90(48) MHz (1σ uncertainties). Combining the Aₒ, Bₒ, and Cₒ constants with coupled-cluster with single-, double- and perturbatively corrected triple-excitation calculations using large basis sets allows to determine the semi-experimental equilibrium bond lengths rₑ(C₁–C₂) = 1.3849(4) Å, rₑ(C₂–C³) = 1.3917(4) Å, rₑ(C–F) = 1.3422(3) Å, and rₑ(C₂–H₂) = 1.0791(5) Å.

Reference photographs for nasolabial appearance rating in unilateral cleft lip and palate

A popular method for nasolabial rating in unilateral cleft lip and palate (UCLP) is the Asher-McDade system consisting of a 5-point ordinal scale assessing nasal form, nasal symmetry, nasal profile, and vermilion border. The aim of the current study was to identify reference photographs illustrating this scale to facilitate its use.Four observers assessed nasolabial appearance on frontal and profile photographs of the nasolabial area of 42 children of Caucasian origin with a repaired UCLP at age 9 years. Cronbachs alpha, based on the individual scores of the 4 observers, ranged from 0.73 to 0.82 for the 4 nasolabial ratings, indicating a good reliability. The reliability of the overall score (mean of the 4 component scores) was also high (Cronbachs alpha, 0.83). Both for the nasolabial component ratings and for the overall score, duplicate measurement errors were small. The reliability for the mean of the 4 observers' scores was good, Spearman rank correlation coefficients ranging from 0.56 to 0.96.Subsequently, photographs were selected that showed the highest agreement among observers. For each of the 4 components (eg, nasal form, nasal deviation, nasal profile, and shape of the vermilion border), 5 photographs were selected to illustrate the whole range of the scale (score, 1-5), resulting in the selection of 20 pictures.It was concluded that nasolabial appearance rating can be performed reliably using a panel of judges and averaging the scores of all observers. Reference photographs, as developed from this study, may facilitate the rating task.

Estimating and quantifying uncertainties on level sets using the Vorob'ev expectation and deviation with Gaussian process models

Several methods based on Kriging have recently been proposed for calculating a probability of failure involving costly-to-evaluate functions. A closely related problem is to estimate the set of inputs leading to a response exceeding a given threshold. Now, estimating such a level set—and not solely its volume—and quantifying uncertainties on it are not straightforward. Here we use notions from random set theory to obtain an estimate of the level set, together with a quantification of estimation uncertainty. We give explicit formulae in the Gaussian process set-up and provide a consistency result. We then illustrate how space-filling versus adaptive design strategies may sequentially reduce level set estimation uncertainty.

CCK2 receptor splice variant with intron 4 retention in human gastrointestinal and lung tumours

The wild-type cholecystokinin type 2 (CCK(2)) receptor is expressed in many gastrointestinal and lung tumours. A splice variant of the CCK(2) receptor with retention of intron 4 (CCK(2)Ri4sv) showing constitutive activity associated with increased tumour growth was described in few colorectal, pancreatic and gastric cancers. Given the potential functional and clinical importance of this spliceoform, its occurrence was quantitatively characterized in a broad collection of 81 gastrointestinal and lung tumours, including insulinomas, ileal carcinoids, gastrointestinal stromal tumours (GIST), gastric, colorectal and pancreatic ductal adenocarcinomas, cholangiocellular and hepatocellular carcinomas, small cell lung cancers (SCLC), non-SCLC (nSCLC) and bronchopulmonary carcinoids, as well as 21 samples of corresponding normal tissues. These samples were assessed for transcript expression of total CCK(2) receptor, wild-type CCK(2) receptor and CCK(2)Ri4sv with end-point and real-time RT-PCR, and for total CCK(2) receptor protein expression on the basis of receptor binding with in vitro receptor autoradiography. Wild-type CCK(2) receptor transcripts were found in the vast majority of tumours and normal tissues. CCK(2)Ri4sv mRNA expression was present predominantly in insulinomas (incidence 100%), GIST (100%) and SCLC (67%), but rarely in pancreatic, colorectal and gastric carcinomas and nSCLC. It was not found in wild-type CCK(2) receptor negative tumours or any normal tissues tested. CCK(2)Ri4sv transcript levels in individual tumours were low, ranging from 0.02% to 0.14% of total CCK(2) receptor transcripts. In conclusion, the CCK(2)Ri4sv is a marker of specific gastrointestinal and lung tumours. With its high selectivity for and high incidence in SCLC and GIST, it may represent an attractive clinical target.

Meta-analyses qualify metzincins and related genes as acute rejection markers in renal transplant patients

Definition of acute renal allograft rejection (AR) markers remains clinically relevant. Features of T-cell-mediated AR are tubulointerstitial and vascular inflammation associated with excessive extracellular matrix (ECM) remodeling, regulated by metzincins, including matrix metalloproteases (MMP). Our study focused on expression of metzincins (METS), and metzincins and related genes (MARGS) in renal allograft biopsies using four independent microarray data sets. Our own cases included normal histology (N, n = 20), borderline changes (BL, n = 4), AR (n = 10) and AR + IF/TA (n = 7). MARGS enriched in all data sets were further examined on mRNA and/or protein level in additional patients. METS and MARGS differentiated AR from BL, AR + IF/TA and N in a principal component analysis. Their expression changes correlated to Banff t- and i-scores. Two AR classifiers, based on METS (including MMP7, TIMP1), or on MARGS were established in our own and validated in the three additional data sets. Thirteen MARGS were significantly enriched in AR patients of all data sets comprising MMP7, -9, TIMP1, -2, thrombospondin2 (THBS2) and fibrillin1. RT-PCR using microdissected glomeruli/tubuli confirmed MMP7, -9 and THBS2 microarray results; immunohistochemistry showed augmentation of MMP2, -9 and TIMP1 in AR. TIMP1 and THBS2 were enriched in AR patient serum. Therefore, differentially expressed METS and MARGS especially TIMP1, MMP7/-9 represent potential molecular AR markers.

Semantic memory involvement in the default mode network: a functional neuroimaging study using independent component analysis

The Default Mode Network (DMN) is a higher order functional neural network that displays activation during passive rest and deactivation during many types of cognitive tasks. Accordingly, the DMN is viewed to represent the neural correlate of internally-generated self-referential cognition. This hypothesis implies that the DMN requires the involvement of cognitive processes, like declarative memory. The present study thus examines the spatial and functional convergence of the DMN and the semantic memory system. Using an active block-design functional Magnetic Resonance Imaging (fMRI) paradigm and Independent Component Analysis (ICA), we trace the DMN and fMRI signal changes evoked by semantic, phonological and perceptual decision tasks upon visually-presented words. Our findings show less deactivation during semantic compared to the two non-semantic tasks for the entire DMN unit and within left-hemispheric DMN regions, i.e., the dorsal medial prefrontal cortex, the anterior cingulate cortex, the retrosplenial cortex, the angular gyrus, the middle temporal gyrus and the anterior temporal region, as well as the right cerebellum. These results demonstrate that well-known semantic regions are spatially and functionally involved in the DMN. The present study further supports the hypothesis of the DMN as an internal mentation system that involves declarative memory functions.

Trichilemmal cyst nevus with a sebaceous nevus component

A 23-year-old man with a typical trichilemmal cyst nevus is reported. This recently described disorder is sufficiently characteristic to differentiate it from sebaceous nevus, nevus comedonicus, porokeratotic eccrine nevus, nevus corniculatus, follicular basaloid hamartoma, Munro's nevus and Gardner's syndrome.

Lipid and lipoprotein profile in HIV-infected patients treated with lopinavir/ritonavir as a component of the first combination antiretroviral therapy

We characterized lipid and lipoprotein changes associated with a lopinavir/ritonavir-containing regimen. We enrolled previously antiretroviral-naive patients participating in the Swiss HIV Cohort Study. Fasting blood samples (baseline) were retrieved retrospectively from stored frozen plasma and posttreatment (follow-up) samples were collected prospectively at two separate visits. Lipids and lipoproteins were analyzed at a single reference laboratory. Sixty-five patients had two posttreatment lipid profile measurements and nine had only one. Most of the measured lipids and lipoprotein plasma concentrations increased on lopinavir/ritonavir-based treatment. The percentage of patients with hypertriglyceridemia (TG >150?mg/dl) increased from 28/74 (38%) at baseline to 37/65 (57%) at the second follow-up. We did not find any correlation between lopinavir plasma levels and the concentration of triglycerides. There was weak evidence of an increase in small dense LDL-apoB during the first year of treatment but not beyond 1 year (odds ratio 4.5, 90% CI 0.7 to 29 and 0.9, 90% CI 0.5 to 1.5, respectively). However, 69% of our patients still had undetectable small dense LDL-apoB levels while on treatment. LDL-cholesterol increased by a mean of 17?mg/dl (90% CI -3 to 37) during the first year of treatment, but mean values remained below the cut-off for therapeutic intervention. Despite an increase in the majority of measured lipids and lipoproteins particularly in the first year after initiation, we could not detect an obvious increase of cardiovascular risk resulting from the observed lipid changes.

Mortality and morbidity in the city of Bern, Switzerland, 1805-1815 with special emphasis on infant, child and maternal deaths

This article contributes to the research on demographics and public health of urban populations of preindustrial Europe. The key source is a burial register that contains information on the deceased, such as age and sex, residence and cause of death. This register is one of the earliest compilations of data sets of individuals with this high degree of completeness and consistency. Critical assessment of the register's origin, formation and upkeep promises high validity and reliability. Between 1805 and 1815, 4,390 deceased inhabitants were registered. Information concerning these individuals provides the basis for this study. Life tables of Bern's population were created using different models. The causes of death were classified and their frequency calculated. Furthermore, the susceptibility of age groups to certain causes of death was established. Special attention was given to causes of death and mortality of newborns, infants and birth-giving women. In comparison to other cities and regions in Central Europe, Bern's mortality structure shows low rates for infants (q0=0.144) and children (q1-4=0.068). This could have simply indicated better living conditions. Life expectancy at birth was 43 years. Mortality was high in winter and spring, and decreased in summer to a low level with a short rise in August. The study of the causes of death was inhibited by difficulties in translating early 19th century nomenclature into the modern medical system. Nonetheless, death from metabolic disorders, illnesses of the respiratory system, and debilitation were the most prominent causes in Bern. Apparently, the worst killer of infants up to 12 months was the "gichteren", an obsolete German term for lethal spasmodic convulsions. The exact modern identification of this disease remains unclear. Possibilities such as infant tetanus or infant epilepsy are discussed. The maternal death rate of 0.72% is comparable with values calculated from contemporaneous sources. Relevance of childbed fever in the early 1800s was low. Bern's data indicate that the extent of deaths related to childbirth in this period is overrated. This research has an explicit interdisciplinary value for various fields including both the humanities and natural sciences, since information reported here represents the complete age and sex structure of a deceased population. Physical anthropologists can use these data as a true reference group for their palaeodemographic studies of preindustrial Central Europe of the late 18th and early 19th century. It is a call to both historians and anthropologists to use our resources to a better effect through combination of methods and exchange of knowledge.

Effects of housing, perches, genetics, and 25-hydroxycholecalciferol on keel bone deformities in laying hens

Several studies have shown a high prevalence of keel bone deformities in commercial laying hens. The aim of this project was to assess the effects of perch material, a vitamin D feed additive (25-hydroxyvitamin D(3); HyD, DSM Nutritional Products, Basel, Switzerland), and genetics on keel bone pathology. The study consisted of 2 experiments. In the first experiment, 4,000 Lohmann Selected Leghorn hens were raised in aviary systems until 18 wk of age. Two factors were investigated: perch material (plastic or rubber-coated metal) and feed (with and without HyD). Afterward, the hens were moved to a layer house with 8 pens with 2 aviary systems. Daily feed consumption, egg production, mortality, and feather condition were evaluated. Every 6 wk, the keel bones of 10 randomly selected birds per pen were palpated and scored. In the second experiment, 2,000 Lohmann Brown (LB) hens and 2,000 Lohmann Brown parent stock (LBPS) hens were raised in a manner identical to the first experiment. During the laying period, the hens were kept in 24 identical floor pens but equipped with different perch material (plastic or rubber-coated metal). The same variables were investigated as in the first experiment. No keel bone deformities were found during the rearing period in either experiment. During the laying period, deformities gradually appeared and reached a prevalence of 35% in the first experiment and 43.8% in the second experiment at the age of 65 and 62 wk, respectively. In the first experiment, neither HyD nor the aviary system had any significant effect on the prevalence of keel bone deformities. In the second experiment, LBPS had significantly fewer moderate and severe deformities than LB, and rubber-coated metal perches were associated with a higher prevalence of keel bone deformities compared with plastic perches. The LBPS laid more but smaller eggs than the LB. Again, HyD did not affect the prevalence of keel bone deformities. However, the significant effect of breed affiliation strongly indicates a sizeable genetic component that may provide a basis for targeted selection.

Selective cloning, characterization, and production of the Culicoides nubeculosus salivary gland allergen repertoire associated with equine insect bite hypersensitivity

Salivary gland proteins of Culicoides spp. have been suggested to be among the main allergens inducing IgE-mediated insect bite hypersensitivity (IBH), an allergic dermatitis of the horse. The aim of our study was to identify, produce and characterize IgE-binding salivary gland proteins of Culicoides nubeculosus relevant for IBH by phage surface display technology. A cDNA library constructed with mRNA derived from C. nubeculosus salivary glands was displayed on the surface of filamentous phage M13 and enriched for clones binding serum IgE of IBH-affected horses. Ten cDNA inserts encoding putative salivary gland allergens were isolated and termed Cul n 2 to Cul n 11. However, nine cDNA sequences coded for truncated proteins as determined by database searches. The cDNA sequences were amplified by PCR, subcloned into high level expression vectors and expressed as hexahistidine-tagged fusion proteins in Escherichia coli. Preliminary ELISA results obtained with these fusions confirmed the specific binding to serum IgE of affected horses. Therefore, the putative complete open reading frames derived from BLAST analyses were isolated by RACE-PCR and subcloned into expression vectors. The full length proteins expressed in Escherichia coli showed molecular masses in the range of 15.5-68.7 kDa in SDS-PAGE in good agreement with the masses calculated from the predicted protein sequences. Western blot analyses of all recombinant allergens with a serum pool of IBH-affected horses showed their ability to specifically bind serum IgE of sensitized horses, and ELISA determinations yielded individual horse recognition patterns with a frequency of sensitization ranging from 13 to 57%, depending on the allergen tested. The in vivo relevance of eight of the recombinant allergens was demonstrated in intradermal skin testing. For the two characterized allergens Cul n 6 and Cul n 11, sensitized horses were not available for intradermal tests. Control horses without clinical signs of IBH did not develop any relevant immediate hypersensitivity reactions to the recombinant allergens. The major contribution of this study was to provide a repertoire of recombinant salivary gland allergens repertoire from C. nubeculosus potentially involved in the pathogenesis of IBH as a starting basis for the development of a component-resolved serologic diagnosis of IBH and, perhaps, for the development of single horse tailored specific immunotherapy depending on their component-resolved sensitization patterns.

ENU-induced phenovariance in mice: inferences from 587 mutations

Background We present a compendium of N-ethyl-N-nitrosourea (ENU)-induced mouse mutations, identified in our laboratory over a period of 10 years either on the basis of phenotype or whole genome and/or whole exome sequencing, and archived in the Mutagenetix database. Our purpose is threefold: 1) to formally describe many point mutations, including those that were not previously disclosed in peer-reviewed publications; 2) to assess the characteristics of these mutations; and 3) to estimate the likelihood that a missense mutation induced by ENU will create a detectable phenotype. Findings In the context of an ENU mutagenesis program for C57BL/6J mice, a total of 185 phenotypes were tracked to mutations in 129 genes. In addition, 402 incidental mutations were identified and predicted to affect 390 genes. As previously reported, ENU shows strand asymmetry in its induction of mutations, particularly favoring T to A rather than A to T in the sense strand of coding regions and splice junctions. Some amino acid substitutions are far more likely to be damaging than others, and some are far more likely to be observed. Indeed, from among a total of 494 non-synonymous coding mutations, ENU was observed to create only 114 of the 182 possible amino acid substitutions that single base changes can achieve. Based on differences in overt null allele frequencies observed in phenotypic vs. non-phenotypic mutation sets, we infer that ENU-induced missense mutations create detectable phenotype only about 1 in 4.7 times. While the remaining mutations may not be functionally neutral, they are, on average, beneath the limits of detection of the phenotypic assays we applied. Conclusions Collectively, these mutations add to our understanding of the chemical specificity of ENU, the types of amino acid substitutions it creates, and its efficiency in causing phenovariance. Our data support the validity of computational algorithms for the prediction of damage caused by amino acid substitutions, and may lead to refined predictions as to whether specific amino acid changes are responsible for observed phenotypes. These data form the basis for closer in silico estimations of the number of genes mutated to a state of phenovariance by ENU within a population of G3 mice.

Effective wound closure with a new two-component wound closure device (Prineo™) in excisional body-contouring surgery: experience in over 200 procedures

In excisional body-contouring surgery the surgeon is often confronted with time-consuming closure of long wounds. Recently, a new combination of a self-adhering mesh together with a liquid 2-octyl cyanoacrylate adhesive (Prineo™; Ethicon, Inc., Somerville, NJ, USA) has been introduced to replace intracutaneous running suture.

Effects of glenoid component version on humeral head displacement and joint reaction forces: an experimental study

The purpose of this study was to determine whether changes in glenoid version are associated with humeral head displacement and changes in the joint reaction forces, as these might contribute to instability or loosening in total shoulder replacement. A total shoulder prosthesis was implanted in neutral version in 6 cadaveric shoulders. Glenoid version was then changed in steps of 4 degrees toward more anteversion and retroversion. An increase in anteversion resulted in anterior translation of the humeral head and in eccentric loading of the anterior part of the glenoid. Retroversion was associated with posterior displacement and posterior loading of the glenoid. A change in rotation of the humeral component did not compensate for altered version of the glenoid component. These results suggest that both instability and glenoid component loosening may be related to the version of the glenoid component. Therefore, assessment of loosening and instability justifies precise assessment of glenoid component version.