Search

Progressively, information systems (IS) researchers draw on digital trace data to capture the emergent dynamics of today’s digitalized world. Digital trace data enable researchers to generate highly context-specific insights into the features and dynamics of socio-technical phenomena. We suggest how IS researchers can use digital trace data to develop situated explanations, that is, explanations that capture the idiosyncratic features of real-world problems in order to generate impactful solutions to these problems. We outline five key principles to build situated explanations based on digital trace data. We make several suggestions on how the information system field can adjust its research and publication practices to embrace the development and dissemination of situated explanations.

The goals of this study were to determine whether children who took the bus to school on a regular basis felt safest during the commute to school, in school, or on the commute home from school, and to identify the factors that correlate with fear of being bullied on the bus. A sample of 610 students (296 boys, 313 girls; mean age = 11.25 years, SD = 0.51) was surveyed during the fall semester of their first year of middle school (sixth grade). Students indicated that they felt safer in school than they did on the commute to or from school, which nearly always occurred by bus. Sex differences were investigation and found to be small in number and magnitude. These differences were limited to slightly more girls than boys reporting feeling safer in school, slightly more boys than girls reporting feeling safer on the commute home from school, and a modestly stronger association between bullying victimization and fear of being bullied on the school bus in boys than in girls, although the effect was significant in both sexes. There were no significant differences between boys and girls in their overall level of fear of bullying on the bus. A full sample regression analysis revealed significant correlations between the risk factors of bullying victimization and depression, and a child’s fear of being bullied on the bus, suggesting that such fears are related to past victimization and current feelings of sadness, loneliness, and reduced energy.

Using nationally representative data, we determined the likelihood of adverse pathology at radical prostatectomy (RP) to better inform case selection for partial gland ablation (PGA).

In this paper, we respond to Grover and Lyytinen (2022). We agree with them that the advent of the digital age is calling for a reconsideration of the role of theory and theorizing. We also think their proposal does not go far enough. The time is ripe to question the role of theory in our field more fundamentally. We propose to instead focus on establishing IS research as a platform through which we can collect, organize, and provide access to digital trace data from various sources to analyze contemporary socio-technical phenomena. We believe that such a move allows us to more fully unleash the unique socio-technical competences of our field in the digital age.

Commonly referred to as data-driven product development, incorporating data science into product development to create value out of sensor data is a key challenge and involves unpredictability and invention risk. However, different studies in the current literature rely on different conceptualisations in this interdisciplinary research field, and the literature is scattered. To address this issue, this paper provides a review of recent academic literature on New Product Development (NPD) for the Internet of Things (IoT). The work reveals that distributed literature lacks a standardised process for guiding managers to handle the data product development process of smart products.

Effluent organic matter (EfOM), a major ozone consumer during wastewater ozonation, is a complex mixture of natural and anthropogenic organic molecules. Ozonation of EfOM adds to molecular complexity by introducing polar and potentially mobile ozonation byproducts (OBPs). Currently, nontargeted direct infusion (DI) ultrahigh resolution mass spectrometry (e.g. FT-ICR-MS) is used to study OBPs but requires sample extraction, limiting the accessible polarity range of OBPs. To better understand the impact of ozonation on EfOM and the formation of polar OBPs, nonextracted effluent was analyzed by direct injection onto a reversed-phase liquid chromatography system (RP-LC) online hyphenated with an FT-ICR-MS. Over four times more OBPs were detected in nonextracted EfOM compared to effluent extracted with solid phase extraction and measured with DI-FT-ICR-MS (13817 vs 3075). Over 1500 highly oxygenated OBPs were detected exclusively in early eluting fractions of nonextracted EfOM, indicating polar OBPs. Oxygenation of these newly discovered OBPs is higher than previously found, with an average molecular DBE-O value of −3.3 and O/C ratio of 0.84 in the earliest eluting OBP fractions. These polar OBPs are consistently lost during extraction but may play an important role in understanding the environmental impact of ozonated EfOM. Moreover, 316 molecular formulas classified as nonreactive to ozone in DI-FT-ICR-MS can be identified with LC-FT-ICR-MS as isomers with varying degrees of reactivity, providing for the first time experimental evidence of differential reactivity of complex organic matter isomers with ozone.

Dysglycaemia increases the risk of myocardial infarction and subsequent recurrent cardiovascular events. However, the role of dysglycaemia in ischemia/reperfusion injury with development of irreversible myocardial tissue alterations remains poorly understood.

Smoking habit at the time of surgery is associated with higher perioperative complications and mortality across different types of surgeries. In recent years, several studies have attempted to explore the influence of smoking on perioperative outcomes following radical cystectomy (RC) for urothelial bladder cancer (UBC) with contradictory results.

COVID-19-associated case fatality rates up to 48% were reported among nursing facility residents. During the first wave of the COVID-19 pandemic, routine SARS-CoV-2 testing in long-term care facilities in the Province of Salzburg and centralized hospitalization in the COVID-19 unit of the Paracelsus Medical University Salzburg (Austria) irrespective of symptoms was implemented. Baseline characteristics and the course of COVID-19 disease were assessed among hospitalized long-term care facility residents within the COVID-19 Registry of the Austrian Group Medical Tumor Therapy (AGMT; NCT04351529). Between the 24thof March and the 20thof April 2020, 50 COVID-19-positive residents were hospitalized. The median age was 84.5 years (range: 79–88) and the median number of comorbidities and baseline medication classes was 6 (IQR: 4–7) and 5 (IQR: 3–6), respectively. At admission, 31 residents (62%) were symptomatic, nine residents (18%) pre-symptomatic whereas ten residents (20%) remained asymptomatic. The 30-day mortality rate from hospitalization was 32% and significantly higher in symptomatic residents at admission when compared to asymptomatic residents including pre-symptomatic residents (48% [95% CI: 27–63%] versus 5% [95% CI: 0–15%], p=0.006). The Early Warning Score (EWS) at admission was associated with 30-day mortality: high risk: 100%, intermediate risk: 50% (95% CI: 0–78%), and low risk: 21% (95% CI: 7-32%) (p<0.001). In light of comparably low mortality rates between asymptomatic and pre-symptomatic hospitalized COVID-19-positive residents, we suggest the supply of comparable intensity and quality of monitoring and care in long-term care facilities as an alternative to immediate hospitalization upon a positive COVID-19 test in asymptomatic residents.

Purpose: To evaluate the differential impact of postoperative radiotherapy (RT) on recurrence patterns in patients treated with radical prostatectomy (RP) using [68Ga]Ga-PSMAHBED-CCconjugate 11 positron emission tomography (PSMA 11-PET). Methods: We assessed 162 consecutive patients who experienced biochemical recurrence (BCR) after RP for nonmetastatic prostate cancer (PC). All had at least one positive lesion on imaging. No patient was on androgen deprivation therapy (ADT). Patients were categorized into those who had received adjuvant/salvage RT ± ADT and those who did not (RP only). Lesion- and patient-based analyses were performed. The impact of the radiation field was assessed. Results: Overall, 57 BCR patients underwent RP only, 105 received postoperative RT. Median PSA was 1.01 ng/ml (IQR 0.58–2). In the lesion-based analysis, compared to the RP only patients, those who had received postoperative RT, had less lymph node (LN) recurrences distal to the common iliac bifurcation (35.2 vs. 57.9%, p= 0.05), but were more likely to harbor positive LNs proximal to the iliac bifurcation and in the presacral (34.2 vs. 12.3%, p= 0.002) areas as well as bone metastases (25.7 vs. 8.8%, p= 0.01). In the patient-based analysis, the patients with postoperative RT after RP had less recurrence in the pelvis only (pelvic LNs and/or prostate bed) (52.4 vs. 79%, p= 0.002), but were more likely to harbor extrapelvic recurrence (41.9 vs. 15.8%, p= 0.001). Patients who received RT to the prostate bed only had more recurrence to the pelvic LN only (54.2% vs. 23.4%, p= 0.002), but less extrapelvic recurrence (31.3 vs. 53.2%, p= 0.03) and less bone recurrence (16.7 vs. 36.2%, p= 0.031) compared to those patients, who received RT to the prostate bed and pelvic nodes. Conclusions: Postoperative radiation treatment alters the recurrence pattern in BCR patients after RP. Further prospective studies are needed to establish a decision tree for optimal imaging/management according to previous treatments.

Purpose: To assess the prevalence of sarcopenia and whether body composition parameters are associated with disease progression and overall survival (OS) in castration-resistant prostate cancer (CRPC) patients. Materials and methods: This single-centre retrospective study evaluated data of 186 consecutive patients who underwent chemohormonal therapy between 2005 and 2016 as first-line systemic treatment for CRPC. Skeletal muscle and fat indices were determined using computerized tomography data before initiation of chemotherapy. Sarcopenia was defined as SMI of &lt;55 cm2/m2. Visceral-to-subcutaneous fat ratio and skeletal muscle volume were calculated with body composition specific areas. Harrell’s concordance index was used for predictive accuracy. Results: A total of 154 (82.8%) patients met the criteria for sarcopenia; 139 (74.7%) individuals completed at least six cycles of docetaxel. Within a median follow-up of 24.1 months, age (HR 1.03, 95% CI 1.01–1.06, p= 0.02), high PSA (1.55, 95% CI 1.07–2.25, p= 0.02) and low skeletal muscle volume (HR 1.61, 95% CI 1.10–2.35, p= 0.02) were the only independent prognostic factor for tumor progression. Overall, 93 (50%) patients died during the follow-up period. The established prognosticator, the prechemotherapy presence of liver metastases (HR 1.32, 95% CI 1.08–1.61, p&lt; 0.01) was associated with shorter OS. Moreover, we noted that patients with an elevated visceral-to-subcutaneous fat ratio tended to have a shorter OS (p= 0.06). Conclusion: The large majority of men with CRPC suffers from sarcopenia. In our cohort, low skeletal muscle volume was an independent adverse prognosticator for progression of disease. We could not detect a statistically significant body composition parameter for OS, although patients with a high proportion of visceral fat had a trend for shorter OS. However, we suggest that body composition parameters determined by CT data can provide useful objective prognostic factors that may support tailored treatment decision-making.

AbstractPurpose:To assess the prognostic significance of the nuclear receptor binding SET protein 2 (NSD2), a co-activator of the NFkB-pathway, on tumour progression in patients with advanced prostate cancer (PCa).Methods:We retrospectively assessed NSD2 expression in 53 patients with metastatic and castration-resistant PCa. Immunohistochemical staining for NSD2 was carried out on specimen obtained from palliative resection of the prostate. Univariable and multivariable analyses were performed to assess the association between NSD2 expression and PCa progression.Results:Of the 53 patients, 41 had castration-resistant PCa and 48 men had metastases at time of tissue acquisition. NSD2 expression was increased in tumour specimen from 42 patients (79.2%). In univariable Cox regression analyses, NSD2 expression was associated with PSA progression, progression on imaging and overall survival (p = 0.04, respectively). In multivariable analyses, NSD2 expression did not retain its association with these endpoints.Conclusions:NSD2 expression is abnormal in almost 80% of patients with advanced PCa. Expression levels of this epigenetic regulator are easily detected by immunohistochemistry while this biomarker exhibited prognostic value for PCa progression and death in univariable analysis. Further studies on NSD2 involvement in PCa proliferation, progression, metastasis and resistance mechanisms are needed.

The aim of this study was to evaluate the prognostic value of hyponatremia in patients with castration-resistant prostate cancer (CRPC) undergoing docetaxel chemotherapy.

Background: The diagnostic potential of multimodal MRI approaches to discriminate among progressive supranuclear palsy (PSP), Parkinson variant of multiple system atrophy (MSA-P) and Parkinson’s disease (PD) has not been well investigated.Objective: To identify disease-specific neurodegenerative patterns and evaluate the diagnostic accuracy of dedicated MRI, iron concentration (R2*), microstructural integrity (mean diffusivity; MD and fractional anisotropy; FA) as well as volumes were analyzed in patients with PSP, MSA-P and PD.Methods: 3T MRI of 18 PSP and 16 MSA-P patients were compared with 16 PD patients matched for age and disease duration as well as 21 healthy controls. Statistical parametric mapping (SPM) was applied to objectively identify focal MRI changes throughout the whole-brain. Following dimensionality reduction of significant and multiple comparison-corrected SPM clusters through principal component analysis (PCA), stepwise receiver-operating characteristic curve analysis (ROC) was applied to determine the diagnostic potential of multimodal MRI parameters.Results: PCA revealed two components involving multiple regions identified from SPM analysis. The first component was primarily composed of the mean MD value of the thalamus and the mean MD and FA values of the dentatorubrothalamic tract and the corpus callosum. The second component mainly consisted of mean MD and FA values of the middle cerebellar peduncle. ROC analysis showed 92% of PSP patients were differentiated correctly from MSA-P and PD and 80% of MSA-P patients could be distinguished from PD.Conclusion: Multimodal MRI improved the detection of disease-specific neurodegenerative patterns in PSP and MSA-P and highlights its potential to improve the diagnostic accuracy of atypical parkinsonian disorders.

The diagnostic potential of multimodal MRI approaches to discriminate among progressive supranuclear palsy (PSP), Parkinson variant of multiple system atrophy (MSA-P) and Parkinson’s disease (PD) has not been well investigated. To identify disease-specific neurodegenerative patterns and evaluate the diagnostic accuracy of dedicated MRI, iron concentration (R2*), microstructural integrity (mean diffusivity; MD and fractional anisotropy; FA) as well as volumes were analyzed in patients with PSP, MSA-P and PD. 3T MRI of 18 PSP and 16 MSA-P patients were compared with 16 PD patients matched for age and disease duration as well as 21 healthy controls. Statistical parametric mapping (SPM) was applied to objectively identify focal MRI changes throughout the whole-brain. Following dimensionality reduction of significant and multiple comparison-corrected SPM clusters through principal component analysis (PCA), stepwise receiver-operating characteristic curve analysis (ROC) was applied to determine the diagnostic potential of multimodal MRI parameters. PCA revealed two components involving multiple regions identified from SPM analysis. The first component was primarily composed of the mean MD value of the thalamus and the mean MD and FA values of the dentatorubrothalamic tract and the corpus callosum. The second component mainly consisted of mean MD and FA values of the middle cerebellar peduncle. ROC analysis showed 92% of PSP patients were differentiated correctly from MSA-P and PD and 80% of MSA-P patients could be distinguished from PD. Multimodal MRI improved the detection of disease-specific neurodegenerative patterns in PSP and MSA-P and highlights its potential to improve the diagnostic accuracy of atypical parkinsonian disorders.

The purpose of this study was to investigate the prevalence and prognostic value of the polymorphic variant (1245A>C), a single nucleotide polymorphism (SNP) of the HSD3B1 gene, in the tumors of patients with castration-resistant prostate cancer (CRPC).

Many people consider Adam Smith the first economist to describe the functioning of capitalism. In fact, Smith must be considered less the discoverer of capitalism, but rather as its inventor. The economic laws Smith formulated are institutionally bound to the commercial society, to use the corresponding phrase of Smith, which at that time – at least in its liberal version – has not yet be materialized. In this sense, it represents a utopia of economic policy that still had to be realized. Smith’s comments on commercial society should therefore be understood less as a positive economic analysis than as a normative economic draft.

The partitioned stator flux reversal machine (PS-FRPM) is a novel stator PM machine topology, which exhibits a higher torque capability than its single stator counterpart and the conventional permanent magnet synchronous machine (PMSM). The PS-FRPM consists of two stators, one which carries the armature winding, and one which is equipped with surface mounted permanent magnets. The rotor is sandwiched between the two stators. The separation of the stator allows a better utilization of the machine volume which results in a higher torque density. Furthermore, because the magnets are placed on a stationary component, they can be cooled effectively. Consequently, critical rare-earth materials can be saved.The structure of the PS-FRPM is very similar to that of magnetic gears. In this paper the torque production of a PS-FRPM is described by means of the magnetic gearing effect. First the magnetic gearing effect is introduced and then the corresponding analytics is transferred to the PS-FRPM. Based on Maxwell's stress tensor, the torque contributions of the individual space harmonics are determined. In contrast to conventional machines, the torque in PS-FRPM is produced by several space harmonics in both air gaps.

Purpose: The growing concern about school violence and security has led to a dramatic increase in the number of police officers working in schools. This increase has been accompanied by a focus on the training of school-based law enforcement, the discretion that they exercise when interacting with youth, and the concern that these factors may lead to more youths facing arrest and formal processing by the juvenile and criminal justice system. What is not well understood is whether or not having formal school resource officer (SRO) training or higher education impacts the officer’s decision making when responding to an incident involving a student. The paper aims to discuss these issues. Design/methodology/approach: This paper uses survey data from school police officers within the USA (n=179) to examine the officer’s preferred post-incident method of disciplining the youth, from the most punitive and formal approach of suspension or referral to juvenile authorities, to the less punitive and informal approach such as diversion or warn and release. Findings: Overall, the study found that officers who have received formal SRO training were more likely to prefer a formal resolution to the incidents, and more highly educated officers tended to favor less punitive and informal responses. Originality/value: These findings question the current state of the effectiveness of SRO training at using diversionary tactics for conflict resolution in a school setting.

This paper presents a systematic analysis of the similarities and differences between the fields of open innovation and open strategy. In particular, we examine the concept of openness from a communication-centered perspective and compare processes of open innovation and open strategy with regard to the openness they exhibit. By distinguishing between openness in terms of sociality, factuality and temporality, we find that cases of open strategy tend to exhibit lower degrees of openness in the social dimension and higher degrees in the other two when compared to open innovation. Notwithstanding variation within and between the fields of open innovation and open strategy, opening up in one dimension of communication will generally result in pressures to decrease openness with regards to the other dimensions – unless particular tools are employed that help cope with the additional degrees of communicative complexity.

Background: Aortic stiffness is associated with increased left ventricular (LV) afterload, a process which is accompanied by a release of natriuretic peptides. Aortic pulse wave velocity (PWV) has been demonstrated to be the functional surrogate of aortic stiffness. We sought to investigate the impact of aortic PWV on N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations in patients with acute myocardial infarction (AMI).Methods: This prospective observational study included 86 consecutive patients undergoing percutaneous coronary intervention for AMI. Aortic PWV was determined 47 h (interquartile range (IQR) 27–64 h) after AMI using an established oscillometric device. NT-proBNP values were measured using a commercially available immunoassay.Results: The mean age of the study cohort was 60±11 years; 19% were female. Median aortic PWV was 7.8 m/s (IQR 6.8–9.4 m/s). Patients with a PWV above the median showed significantly higher NT-proBNP peak concentrations (median=1330 ng/l, IQR: 729–3180 ng/l vs median=498 ng/l, IQR: 124–1575 ng/l, p=0.001). Aortic PWV (beta=0.373, p=0.014) was independently associated with NT-proBNP peak concentrations even after correction for LV function, cardiac troponin T levels, heart rate, blood pressure, body mass index and the primary prevention European Society of Cardiology (ESC) SCORE (model: R=0.542, p=0.014).Conclusion: In patients with AMI, aortic PWV is independently associated with NT-proBNP concentrations. This finding suggests an impact of aortic PWV on myocardial wall stress after AMI.

The sodium-activated potassium channels Slick (Slo2.1, KCNT2) and Slack (Slo2.2, KCNT1) are paralogous channels of the Slo family of high-conductance potassium channels. Slick and Slack channels are widely distributed in the mammalian CNS and they play a role in slow afterhyperpolarization, generation of depolarizing afterpotentials and in setting and stabilizing the resting potential. In the present study we used a combined approach of (co)-immunoprecipitation studies, Western blot analysis, double immunofluorescence and mass spectrometric sequencing in order to investigate protein–protein interactions of the Slick and Slack channels. The data strongly suggest that Slick and Slack channels co-assemble into identical cellular complexes. Double immunofluorescence experiments revealed that Slick and Slack channels co-localize in distinct mouse brain regions. Moreover, we identified the small cytoplasmic protein beta-synuclein and the transmembrane protein 263 (TMEM 263) as novel interaction partners of both, native Slick and Slack channels. In addition, the inactive dipeptidyl-peptidase (DPP 10) and the synapse associated protein 102 (SAP 102) were identified as constituents of the native Slick and Slack channel complexes in the mouse brain. This study presents new insights into protein–protein interactions of native Slick and Slack channels in the mouse brain.

Transport of carbonyl sulfide (OCS) from the troposphere to the stratosphere contributes sulfur to the stratospheric aerosol layer, which reflects incoming short‐wave solar radiation, cooling the climate system. Previous analyses of OCS observations have shown no significant trend, suggesting that OCS is unlikely to be a major contributor to the reported increases in stratospheric aerosol loading and indicating a balanced OCS budget. Here we present analyses of ground‐based Fourier transform spectrometer measurements of OCS at three Southern Hemisphere sites spanning 34.45°S to 77.80°S. At all three sites statistically significant positive trends are seen from 2001 to 2014 with an observed overall trend in total column OCS at Wollongong of 0.73 ± 0.03%/yr, at Lauder of 0.43 ± 0.02%/yr, and at Arrival Heights of 0.45 ± 0.05%/yr. These observed trends in OCS imply that the OCS budget is not balanced and could contribute to constraints on current estimates of sources and sinks. First observed positive trend in OCS in the Southern HemisphereObserved trends indicate imbalanced OCS budgetTemporal structure of trend is similar across middle‐ and high‐latitude sites

The article lists a number of blog and newsletters talking about roses like "Twin Cities Rosarian" talking about a cross,Above and Beyond in 2000,"Connecticut Rose" talking about the amount of water a rose bush should get or "The Rambling Rose" discussing whether wood chips really tie up Nitrogen.

To delineate the role of peroxisomes in the pathophysiology of hypoxia-reoxygenation we examined the functions of peroxisomes and mitochondria in cultured skin fibroblasts from controls and from patients with cells lacking peroxisomes (Zellweger cells). The loss of peroxisomal functions (lignoceric acid oxidation and dihydroxyacetonephosphate acyltransferase [DHAP-AT] activities) in control cells following hypoxia and hypoxia followed by reoxygenation, suggests that peroxisomes are sensitive to oxidative injury. The sensitivity of peroxisomes to oxidative stress was compared to that of mitochondria by examining the oxidation of palmitic acid (a function of both mitochondria and peroxisomes) in control and Zellweger cell lines, following hypoxia-reoxygenation. The greater loss of activity of palmitic acid oxidation observed in control cells as compared to that seen in Zellweger cells suggests that the peroxisomal β-oxidation system is relatively more labile to hypoxia- reoxygenation induced oxidative stress. This data clearly demonstrates the difference in the response of mitochondria and peroxisomes to oxidative stress.

Proponents of liberal economic policies in the financial market often refer to the moral and economic authority of Adam Smith, the founder of economics as a science, to add weight to their recommendations. They think, they can do so, because Adam Smith is in these circles considered a prominent representative of an economically unbridled laissez-faire liberalism. The fact that Adam Smith also advocated several measures of economic policies for the regulation of banking, like a limit for interest rates of 5 %, the prohibition of paper money under a nominal value of £ 5 and the use of option clauses on banknotes, is little known to the recipients. For this reason, this paper wants to give an answer to the question, whether Adam Smith’s advocacy of banking regulation is a contradiction to his otherwise liberal economic policy or not.

Mammalian kidneys are rich in sulfatides. Papillary sulfatides, especially, contribute to renal adaptation to chronic metabolic acidosis. Due to differences in their cer­amide (Cer) anchors, the structural diversity of renal sulfatides is large. However, the underling biological function of this complexity is not understood. As a compound's function and its tissue location are intimately connected, we analyzed individual renal sulfatide distributions of control and Cer synthase 2 (CerS)2-deficient mice by imaging MS (IMS) and by LC-MS2(in controls for the cortex, medulla, and papillae separately). To explain locally different structures, we compared our lipid data with regional mRNA levels of corresponding anabolic enzymes. The combination of IMS and in source decay-LC-MS2analyses revealed exclusive expression of C20-sphingosine-containing sulfatides within the renal papillae, whereas conventional C18-sphingosine-containing compounds were predominant in the medulla, and sulfatides with a C18-phytosphingosine were restricted to special cortical structures. CerS2 deletion resulted in bulk loss of sulfatides with C23/C24-acyl chains, but did not lead to decreased urinary pH, as previously observed in sulfatide-depleted kidneys. The reasons may be the almost unchanged C22-sulfatide levels and constant total renal sulfatide levels due to compensation with C16- to C20-acyl chain-containing compounds. Intriguingly, CerS2-deficient kidneys were completely depleted of phytosphingosine-containing cortical sulfatides without any compensation.

We present the first comprehensive capillary electrophoresis electrospray ionization mass spectrometry (CESI-MS) analysis of post-translational modifications derived from H1 and core histones. Using a capillary electrophoresis system equipped with a sheathless high-sensitivity porous sprayer and nano–liquid chromatography electrospray ionization mass spectrometry (nano-LC-ESI-MS) as two complementary techniques, we characterized H1 histones isolated from rat testis. Without any pre-separation of the perchloric acid extraction, a total of 70 different modified peptides, including 50 phosphopeptides, were identified in the rat linker histones H1.0, H1a-H1e, and H1t. Out of the 70 modified H1 histone peptides, 27 peptides could be identified with CESI-MS only, and 11 solely with LC-ESI-MS. Immobilized metal-affinity chromatography enrichment prior to MS analysis yielded a total of 55 phosphopeptides; 22 of these peptides could be identified only by CESI-MS, and 19 only by LC-ESI-MS, showing the complementarity of the two techniques. We mapped 42 H1 modification sites, including 31 phosphorylation sites, of which 8 were novel sites. For the analysis of core histones, we chose a different strategy. In a first step, the sulfuric-acid-extracted core histones were pre-separated using reverse-phase high-performance liquid chromatography. Individual rat testis core histone fractions obtained in this way were digested and analyzed via bottom-up CESI-MS. This approach yielded the identification of 42 different modification sites including acetylation (lysine and Nα-terminal); mono-, di-, and trimethylation; and phosphorylation. When we applied CESI-MS for the analysis of intact core histone subtypes from butyrate-treated mouse tumor cells, we were able to rapidly detect their degree of modification, and we found this method very useful for the separation of isobaric trimethyl and acetyl modifications. Taken together, our results highlight the need for additional techniques for the comprehensive analysis of post-translational modifications. CESI-MS is a promising new proteomics tool as demonstrated by this, the first comprehensive analysis of histone modifications, using rat testis as an example.

The aim of the present voxel-based morphometry study was to examine the link between brain structure and number skills in a group of 6–7-year-old children born prematurely, which are considered to be an at-risk population for mathematical learning disabilities. Therefore, gray and white matter density values were extracted from brain areas previously reported to be relevant for number processing in developing brain systems and, thereafter, correlated with response time results tapping semantic number knowledge i.e. numerical distance effect (NDE) derived from a number comparison task as well as with general math proficiency (as indexed by a standardized calculation test). Behavioral results disclosed a significant NDE, thus indicating well-established number magnitude representations for one-digit numerals in our study group. Significant positive correlations between gray matter and NDE emerged in parietal regions (including the right anterior inferior and the left superior parietal lobe) and in the right superior temporal gyrus. Moreover, white matter and NDE were negatively correlated in the right anterior inferior parietal lobe and the right inferior frontal gyrus. Overall, our results are novel insofar as they show that in 6–7-year-old children born prematurely, individual differences in gray and white matter structures are associated with numerical skills. Importantly, in our study group the observed link between brain structure and behavioral performance emerges only regarding an experimental task tapping semantic number knowledge, whereas general math proficiency does not seem to be related to individual differences in brain structure in our study group.

Introduction:A number of different laser systems have been used for volume reduction of hyperplastic nasal turbinates. In case of endonasal application, fiber-controlled diode lasers are preferred due to reasons of cost and practicability. The aim of this clinical feasibility study was to show the coagulative and tissue reducing effects using a novel Tm: fiber laser system emitting at λ=1940 nm.

Bei der Auslegung von Fahrzeuginnenräumen und Fahrerplätzen spielen digitale Menschmodelle eine erhebliche Rolle. Neben der Auslegung der Verstellbereiche von Sitz, Lenkrad und gegebenenfalls Pedalerie für optimale Körperhaltungen unterschiedlich großer Insassen können digitale Menschmodelle auch verstärkt in der frühen Phase, bei der Gestaltung von Anzeige- und Bedienkonzepten für sekundäre und tertiäre Fahrzeugfunktionen eingesetzt werden. Im Rahmen dieses Artikels wird beispielhaft der Auslegungsprozess des Elekt-rofahrzeugs MUTE mit dem digitalen Menschmodell RAM-SIS dargestellt. Neben einer Diskussion unterschiedlicher Auslegungsprinzipien für die Gestaltung des Fahrerplatzes von Straßenfahrzeugen werden exemplarisch die Simulationsmöglichkeiten von RAMSIS kognitiv bei der Auslegung eines zentralen Touchdisplays erläutert. Lors de la présentation d’intérieur de véhicule et des places conducteur, des modèles humains numériques jouent un rôle considérable. Parallèlement à la présentation des zones de réglage du siège, du volant et éventuellement des pédales, de grands modèles humains numériques peuvent également être insérés afin d’obtenir une posture optimale des occupants et ce de manière renforcée en début de phase, par l’installation de concept d’annonce et de commande pour les fonctions secondaires et tertiaires du véhicule. Dans le cadre de cet article, le processus d’intégration du véhicule électrique MUTE avec le modèle humain numérique RAMSIS est représenté de manière exemplaire. Parallèlement à une discussion sur les différents principes de présentation de la place du conducteur du véhicule, des possibilités de stimulation du système cog-nitif RAMSIS par l’intégration de l’affichage d’une touche centrale sont décrites de manière exemplaire One objective of the ergonomic car interior design process is to assure safe postures and postures with a minimum discomfort for vehicle occupants independent of their anthropometric measures like stature, proportion or corpulence. Another aspect is the positioning of control elements at locations that are good to reach and the positioning of displays at locations of optimal visibility. Furthermore, a high quality of sight regarding the traffic situation has to be assured for all anthropometries. This paper describes exemplary the ergonomic layout process of the driver workplace of the electric vehicle MUTE with the digital human model (DHM) RAMSIS.

A lot of experimental data has been produced which suggests that there is a crucial role for glycans during the different stages of melanoma progression. Malignant transformation is associated with various alterations in the glycosylation pattern of the protein glycans. The most common changes are associated with the presence of more branched and hypersialylated N-linked oligosaccharides, re-expression of fetal-type antigens and premature terminated glycans. Some of these changes may provide the tumor cells with an advantage in influencing their social behavior and facilitating metastasis formation so, glycan-target therapy in combination with existing protocols may have an important impact in the treatment of melanoma.

This functional magnetic resonance imaging (fMRI) study systematically investigates whether there is a neurofunctional overlap of nonsymbolic numerical and spatial cognition in (intra)parietal regions in children and adults. The study also explores the association between finger use and (nonsymbolic) number processing across development.

CZE and CIEF were so far applied to the analysis of tobacco mosaic virus, Semliki forest virus, human rhinovirus, adenovirus, norovirus and the bacteriophages T5 and MS2. The concentration of viral or subviral particles, of capsid proteins and viral genomes were determined, their electrophoretic mobilities and pI values were measured and bioaffinity reactions between viruses and antibodies, antibody fragments and receptor fragments were assessed. The role of detergents added to the BGE to obtain reproducible electrophoretic conditions was elucidated. The analytes were detectedviatheir UV‐absorbance or via fluorescence after derivatization of the viral capsid, the nucleic acid, or both. A new dimension to the detection is added by the possibility of making use of the viral infectivity. At least in theory, this allows for the unequivocal identification of a single infectious virus particle after collection at the capillary outlet. This review summarizes the 25 papers so far published on this topic.

Endometrial stromal tumors are rare uterine neoplasms including benign stromal nodules, low-grade endometrial stromal sarcomas (ESS), and undifferentiated endometrial sarcomas (UES), the latter representing the most aggressive form. Morphological characteristics and cytogenetic abnormalities are heterogeneous, making diagnosis difficult. Recently, a gene fusion on chromosome 7 that includes two zinc-finger genes (JAZF1and JJAZ1) has been discovered in these tumors. Hitherto only 31 cases, described by three different research groups, have shown JAZF1/JJAZ1fusion in ∼50% of all analyzed low-grade ESSs whereas it is less frequent in UESs. In this study we analyzed 20 ESS and 2 UES cases using two-step reverse transcriptase-polymerase chain reaction optimized for formalin-fixed, paraffin-embedded tissue. In our subset of samples, the JAZF1/JJAZ1fusion transcript occurred in 80% of analyzed ESS cases and in none of two UES cases. In comparison to published data, our results identified the JAZF1/JJAZ1gene fusion more frequently in endometrial stromal tumors than hitherto presumed. This cytogenetic abnormality was not present in normal endometria, leiomyomas, or leiomyosarcomas or in lung, gastric, or hepatic carcinomas, indicating its specificity for endometrial stromal tumors. In combination with other established methods, accurate reverse transcriptase-polymerase chain reaction analysis of JAZF1/JJAZ1gene fusion may be useful in diagnosing difficult or unusual ESS/UES cases.

Purpose: To study changes of the apparent diffusion coefficient (ADC) measured by magnetic resonance imaging (MRI) in patients with primary rectal carcinoma during a course of combined chemoradiation. Patients and Methods: Diffusion-weighted echo-planar imaging at 1.5 T was performed in patients (n = 8) with primary rectal carcinoma (cT3) undergoing preoperative chemoradiation. Mean tumor ADC values and ADC histograms were determined and compared weekly during the course of therapy. Surgical resection of the tumors enabled a correlation of ADC values with the pathologic classification. Results: In four patients tumor T-downstaging (ypT0–2) was observed, and in four patients no downstaging (ypT3) was seen. In all patients, ADC values were higher before onset of chemoradiation therapy compared to the end of chemoradiation. Separating the patients into two groups, a significant increase in ADC value during week 1 of therapy, followed by a steady decrease, was found for the therapy-responder group. In the nonresponder group, no initial increase of ADC values was observed. After the 1st week of therapy, ADC values were significantly lower in the nonresponder group during the remaining duration of therapy. Conclusion: With these preliminary results it could be shown that MR diffusion imaging is able to detect individual changes of tumor ADC values during the course of combined chemoradiation reflecting biological changes within the tumor tissue. Further studies will be necessary to prove the possible value of totally noninvasive ADC imaging on predicting therapy outcome.

BackgroundSecretoneurin, a 33-amino-acid neuropeptide, is generated by proteolytic processing of secretogranin II, which belongs to the chromogranin family. This study aimed to investigate whether secretoneurin is present in the uninflamed rabbit aqueous humor and whether it is released in response to treatment with topical formaldehyde, an agent known to release sensory peptides originating from the trigeminal ganglion.MethodsBlood samples and aqueous humor of eyes pretreated with neutral formaldehyde and untreated controls were analyzed for secretoneurin immunoreactivity by a highly sensitive radioimmunoassay. Furthermore, the molecular form of the secretoneurin immunoreactivity was characterized by gel filtration high-performance liquid chromatography (HPLC).ResultsIn the blood, secretoneurin levels were found to be below the detection limit of 2 fmol/100 µl. In the aqueous humor, secretoneurin-immunoreactivity was detected in moderate but significant amounts. The mean concentration of secretoneurin was 8.1 (±0.34) fmol/100 µl in controls and 7.8 (±0.1) fmol/100 µl 15 min after formaldehyde application. Thirty minutes after treatment, the secretoneurin levels were significantly elevated by 63%. Gel filtration HPLC revealed that the main molecular form corresponded to the free peptide secretoneurin.ConclusionsThe neuropeptide secretoneurin has been detected in the anterior segment of the eye for the first time. The elevation of secretoneurin in formaldehyde-treated eyes may be induced by an enhanced release from the iris/ciliary body complex, as formaldehyde is known to provoke neurogenic inflammation in the anterior segment via release of sensory peptides originating from the trigeminal ganglion. This is why our results indicate a sensory origin of secretoneurin in the eye.

Abstract To investigate the prognostic value of Her2/neu expression in differentiated thyroid carcinomas 103 patients were retrospectively investigated. All of them received surgical and an identical follow-up treatment. The patients with papillary and follicular thyroid cancer were further separated into two groups concerning their clinical development, including one group without distant metastasis (follow-up of minimum 8 years). The second group presented with distant metastases as a sign of an aggressive behaviour. Her2/neu was immunohistochemically detected on sections from formalin-fixed, paraffin-embedded tissues using c-erbB-2/Her-2/neu oncoprotein Ab-17 monoclonal antibody (mAb). In statistical analysis using the Mann-Whitney U-test and χ² test, Her2/neu protein overexpression was significantly correlated with prognosis. Both tumour entities without distant metastases showed significantly less cytoplasmic immunostaining than patients with development of metastases. Concerning the clinical outcome, Her2/neu overexpression may be regarded as a prognostic factor in differentiated thyroid carcinomas. Moreover, in addition to standard radio-iodine elimination therapy, application of Herceptin could lead to new successful therapeutic concepts for a number of patients with progressive thyroid cancer.

The parkinson variant of multiple system atrophy (MSA-P) and progressive supranuclear palsy (PSP) present with atypical parkinsonism, which may be misdiagnosed as PD, particularly in early disease stages. It was previously shown that diffusion-weighted MRI (DWI) is a sensitive tool to discriminate MSA-P from PD based on increased apparent diffusion coefficients (ADCs) in the putamen. In this study DWI was evaluated in 10 patients with PSP compared with 13 patients with PD and 12 with MSA-P.

Routine MRI as well as MR volumetry and MRS have been shown to contribute to the differential diagnosis of the Parkinson variant of multiple system atrophy (MSA-P) and PD. However, it is currently unknown whether diffusion-weighted imaging (DWI) discriminates these disorders.