Head-to-head comparison of treatment sequences in advanced pancreatic cancer-Real-world data from the prospective German TPK clinical cohort study.

There are no clear guidelines regarding the optimal treatment sequence for advanced pancreatic cancer, as head-to-head phase III randomised trials are missing. We assess real-world effectiveness of three common sequential treatment strategies by emulating a hypothetical randomised trial. This analysis included 1551 patients with advanced pancreatic cancer from the prospective, clinical cohort study Tumour Registry Pancreatic Cancer receiving FOLFIRINOX (n = 613) or gemcitabine/nab-paclitaxel (GEMNAB; n = 938) as palliative first-line treatment. We used marginal structural modelling to compare overall survival (OS) and time to deterioration (TTD) of health-related quality of life (HRQoL) between three common first- to second-line treatment sequences, adjusting for time-varying potential confounding. The sequences were: FOLFIRINOX→GEMNAB, GEMNAB→FOLFOX/OFF and GEMNAB→nanoliposomal irinotecan (NALIRI) + 5-fluorouracil. Outcome was also calculated stratified by patients' prognostic risk according to the Pancreatic Cancer Score. Median OS and TTD of HRQoL independent of risk were 10.7 [8.9, 11.9] and 6.4 [4.8, 7.7] months for FOLFIRINOX→GEMNAB, 8.4 [7.4, 9.7] and 5.8 [4.6, 7.1] months for GEMNAB→FOLFOX/OFF and 8.9 [7.8, 10.4] and 4.6 [4.1, 6.1] months for GEMNAB→NALIRI+5-fluorouracil. Compared to FOLFIRINOX→GEMNAB, OS and TTD were worse for poor-risk patients with GEMNAB→FOLFOX/OFF (OS: HR 2.09 [1.47, 2.98]; TTD: HR 1.97 [1.19, 3.27]) and those with GEMNAB→NALIRI+5-fluorouracil (OS: HR 1.35, [0.76, 2.39]; TTD: HR 2.62 [1.56, 4.42]). Brackets denote 95%-confidence intervals. The estimated real-world effectiveness of the three treatment sequences evaluated were largely comparable. Poor-risk patients might benefit from intensified treatment with FOLFIRINOX→GEMNAB in terms of clinical and patient-reported outcomes. Future randomised trials on sequential treatments in advanced pancreatic cancer are warranted.

An intronless tau class glutathione transferase detoxifies several herbicides in flufenacet resistant ryegrass.

Resistance to pre-emergence herbicides, e.g., inhibitors of the biosynthesis of very-long-chain fatty acids (VLCFAs), is evolving in response to increased use of these compounds. Grass weeds such as ryegrasses (Lolium spp.) have accumulated resistance to various herbicide modes of action. Here, an RNA-Seq analysis was conducted using three ryegrass populations resistant to the VLCFA biosynthesis inhibitor flufenacet to investigate this phenomenon. Besides various transcripts, including putative long non-coding RNAs (lncRNAs), a single putatively functional tau class glutathione transferase (GST) was constitutively differentially expressed. It was further induced by herbicide application. This GST was expressed as a recombinant protein in Escherichia coli along with other GSTs and detoxified flufenacet rapidly in vitro. Detoxification rates of other herbicides tested in vitro were in accordance with cross-resistance patterns previously determined in vivo. A genome-wide GST analysis revealed that the candidate GST was located in a cluster of three intronless GSTs. Their intronless nature possibly results from the retroposition of cellular mRNAs followed by tandem duplication and may affect gene expression. The large number of GSTs (≥ 195) in the genome of rigid ryegrass (L. rigidum) compared to other plant organisms is likely a key factor in the ability of this weed to evolve resistance to different herbicide chemistries. However, in the case of flufenacet resistance, a single upregulated GST with high affinity for the substrate flufenacet possibly contributes over-proportionally to rapid herbicide detoxification in planta. The regulation of this gene and the role of differentially expressed transcripts, including various putative lncRNAs, require further investigation.

Caries status in 12-year-old children, geographical location and socioeconomic conditions across European countries: A systematic review and meta-analysis.

BACKGROUND: Understanding of socioeconomic context might enable more efficient evidence-based preventive strategies in oral health. AIM: The study assessed the caries-related socioeconomic macro-factors in 12-year-olds across European countries. DESIGN: This systematic review involved epidemiological surveys on the caries status of 12-year-olds from 2011 to 2022. DMFT was analyzed in relation to gross national income (GNI), United Nations Statistical Division geographical categorization of European countries (M49), unemployment rate, Human Development Index (HDI), and per capita expenditure on dental health care. A meta-analysis was performed for countries reporting data on DMFT, stratified by GNI, and geographical location of European countries, using a random-effects model. RESULTS: The study involved 493 360 children from 36 countries in the geographic region of Europe. The analysis confirmed a strong negative correlation between income and caries experience (p < .01). Children living in higher-income countries showed 90% lower odds of poor oral health than in middle-income countries. Children living in West Europe showed 90% lower odds of poor oral health than children living in East Europe. CONCLUSION: The strong effect of macro-level socioeconomic contexts on children's oral health suggests favoring upstream preventive oral health strategies in countries with economic growth difficulties, Eastern and Southern parts of Europe.

The Ring-Closing Reaction of Cyclopentadiene Probed with Ultrafast X-ray Scattering.

The dynamics of cyclopentadiene (CP) following optical excitation at 243 nm was investigated by time-resolved pump-probe X-ray scattering using 16.2 keV X-rays at the Linac Coherent Light Source (LCLS). We present the first ultrafast structural evidence that the reaction leads directly to the formation of bicyclo[2.1.0]pentene (BP), a strained molecule with three- and four-membered rings. The bicyclic compound decays via a thermal backreaction to the vibrationally hot CP with a time constant of 21 ± 3 ps. A minor channel leads to ring-opened structures on a subpicosecond time scale.

Micro-computed tomographic analysis of the morphology of maxillary lateral incisors.

OBJECTIVE: This study aimed to investigate the morphology of maxillary lateral incisors (MxLI) using micro-computed tomography (micro-CT). MATERIALS AND METHODS: The root canal configurations (RCC) of maxillary lateral incisors (MxLI) of a mixed Swiss-German population were examined using micro-CT, 3D imaging, and a 4-digit system code indicating the main root canal from coronal to apical thirds and the main foramina number. RESULTS: The most frequently observed RCC of MxLI were 1-1-1/1 (Vertucci I/Ve I, 80.0%), 1-1-2/2 (Ve V, 7.3%), 1-2-1/1 (Ve III, 6.4%), 2-1-1/1 (Ve II, 1.8%), and 1-1-1/2 (1.8%)(n = 110). Three additional RCC were observed less frequently (0.9%). The MxLI showed one physiological foramen in 89.1%, two in 9.1%, and seldom three (1.8%). Most accessory canals were identified in the apical third of a root (20.0%), and no accessory canals in 72.7% of the samples. CONCLUSIONS: Detailed information on the internal morphology of MxLI of a Swiss-German population is given. The most frequently observed RCC of MxLI is 1-1-1/1 (Ve I). However, accessory canals may occur in all apical thirds, and 20% of all teeth investigated showed a challenging RCC for clinical treatment. CLINICAL RELEVANCE: This study offers clinicians comprehensive data on MxLI morphology, emphasizing the significance of understanding varied RCC and accessory canal presence for improving root canal treatment outcomes. Over 25% of teeth exhibited complex RCC or accessory canals, influencing decisions during root canal treatment.

CIME4R: Exploring iterative, AI-guided chemical reaction optimization campaigns in their parameter space.

Chemical reaction optimization (RO) is an iterative process that results in large, high-dimensional datasets. Current tools allow for only limited analysis and understanding of parameter spaces, making it hard for scientists to review or follow changes throughout the process. With the recent emergence of using artificial intelligence (AI) models to aid RO, another level of complexity has been added. Helping to assess the quality of a model's prediction and understand its decision is critical to supporting human-AI collaboration and trust calibration. To address this, we propose CIME4R-an open-source interactive web application for analyzing RO data and AI predictions. CIME4R supports users in (i) comprehending a reaction parameter space, (ii) investigating how an RO process developed over iterations, (iii) identifying critical factors of a reaction, and (iv) understanding model predictions. This facilitates making informed decisions during the RO process and helps users to review a completed RO process, especially in AI-guided RO. CIME4R aids decision-making through the interaction between humans and AI by combining the strengths of expert experience and high computational precision. We developed and tested CIME4R with domain experts and verified its usefulness in three case studies. Using CIME4R the experts were able to produce valuable insights from past RO campaigns and to make informed decisions on which experiments to perform next. We believe that CIME4R is the beginning of an open-source community project with the potential to improve the workflow of scientists working in the reaction optimization domain. SCIENTIFIC CONTRIBUTION: To the best of our knowledge, CIME4R is the first open-source interactive web application tailored to the peculiar analysis requirements of reaction optimization (RO) campaigns. Due to the growing use of AI in RO, we developed CIME4R with a special focus on facilitating human-AI collaboration and understanding of AI models. We developed and evaluated CIME4R in collaboration with domain experts to verify its practical usefulness.

A double-blind randomized clinical trial on the suggestive effect of anxiety management questionnaires in dental emergencies.

Objective: Dental anxiety is widespread among both children and adults. To diagnose dental anxiety, standardized anxiety questionnaires are recommended. Based on the suggestive nature of the questionnaires, the study aimed to find out whether asking respondents about personal coping strategies before dental treatment influences their anxiety. Methods: This prospective, double-blind, randomized controlled clinical trial included a total of 158 patients of a university dental clinic on emergency service. The intervention group (n = 82) received the Coping with Anxiety Questionnaire (CAQ) and the control group (n = 76) the Hierarchical Anxiety Questionnaire (HAF). State anxiety scores were assessed by using the State-Trait Anxiety Inventory (STAI) before and after the completion of each questionnaire. Results: Anxiety decreased in the intervention group (CAQ) (p < 0.001) and increased in the control group (HAF) (p < 0.001). Conclusion: Within the limitations of the current study, a diagnostic tool of a standardized questionnaire for the assessment to assess personal coping strategies decreased state anxiety in comparison to a questionnaire assessing anxiety. Clinical trial registration: https://www.drks.de, German Trials Register (DRKS00032450).

Oral Microbiota of Infants in Maternal Gestational Diabetes: A Systematic Review.

Gestational diabetes mellitus (GDM) affects approximately 5-20% of pregnant women and is associated with adverse pregnancy outcomes. This review aimed to assess whether the oral microbiota of infants and their mothers with GDM had a different composition from that found in unaffected women and offspring. PubMed, Embase, Scopus, and Google Scholar were searched in December 2023 after protocol registration in the International Prospective Register of Systematic Reviews (CRD42023406505). Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal tools. Overall, 1113 articles were identified; after evaluating the full texts, 12 papers were included in the qualitative analysis. In six studies of the eight included, significant differences in microbiota between M-GDM and M-nGDM were found. In four studies, a depletion of Firmicutes and an enrichment of Proteobacteria was found in the microbiota of infants. Since all included studies were judged to have high risk of bias, a quantitative synthesis of the results was not carried out. In conclusion, although the oral microbiota of infants from mothers with GDM could be different from that of infants from mothers without GDM, there is insufficient evidence to clarify this aspect so far.

Morphology of the Physiological Foramen: II. Maxillary and Mandibular Premolars.

INTRODUCTION: Information concerning the anatomy of the physiological foramen is still limited. The aim of this study was to investigate the distance between the physiological and anatomic apex, the shape and diameter of the physiological foramen in maxillary (Mx) and mandibular premolars (Mn). METHODS: The anatomy of the apex of 229 maxillary (first: MxP1; second: MxP2) and 221 mandibular premolars (first: MnP1; second: MnP2) from a mixed Swiss-German population was investigated by means of microcomputed tomography and 3-dimensional software imaging. RESULTS: The following results were obtained in the presence of a main physiological foramen. 1. The distance between the physiological and anatomic foramen was 0.29-0.99 mm (MxP1), 0.21-1.03 mm (MxP2), 0.13-0.8 (MnP1), and 0.15-1.41 (MnP2). 2. The mean narrow and wide diameters of the physiological foramen were 0.19-0.33 mm (MxP1), 0.25-0.42 mm (MxP2), 0.28-0.37 (MnP1), and 0.28-0.40 (MnP2). 3. The most common physiological foramen shape was oval (66.7% MxP1, 89.7% MxP2, 91.8% MnP1, 64.4% MnP2). CONCLUSION: Considering the recommended preparation sizes based on a size corresponding to the friction, that is at the narrowest point in the area of the apical constriction (physiological foramen), and within the limitations of this ex vivo microcomputed tomography study, a final preparation size could be chosen when considering the pertaining morphologic considerations; yet, to a minimum ISO 30 size.

Effects of Hydroxyapatite-Containing Toothpastes on Some Caries-Related Variables: A Randomised Clinical Trial.

OBJECTIVES: This randomised clinical trial was designed and carried out with the aim to evaluate the capacity of fluoride-substituted hydroxyapatite (HAF) toothpaste to modulate oral microflora composition and biofilm acidogenicity in schoolchildren. METHODS: In all, 610 children (4 to 5 and 6 to 7 years) were enrolled. Four toothpastes were randomly administered during 24 months: 2 contained fluoride-substituted hydroxyapatite (HAF1000 and HAF1450; 1000 and 1450 ppmF) and magnesium-, strontium-, and carbonate-substituted hydroxyapatite in a chitosan matrix, and 2 were monofluorophosphate fluoridated toothpastes (F1000 and F1450; 1000 and 1450 ppmF). Caries lesions were assessed by International Caries Detection and Assessment System scores, supragingival plaque was sampled from the approximal sites between primary molars using sterile Gracey curettes for microbiological analysis, and plaque pH curves after sucrose challenge were assessed at baseline and reevaluated after 1 year and after 2 years. The minimum and maximum pH decrease was calculated for caries-free patients and participants with a caries lesion(s) at baseline and at the end of the experimental period (24 months). Differences amongst measurements were analysed with 1-way analysis of variance. RESULTS: During the trial, the minimum pH value increased statistically significantly in all groups; in HAF1000 and HAF1450, the increase was greatest. At the end of trial, in the 2 HAF groups all primary cariogenic bacteria were statistically significantly lower with respect to F groups (P = .03 for Streptococcus mutans and sobrinus, for Lactobacillus casei, and for Lactobacillus fermentum). CONCLUSIONS: The trial provides robust but still inconclusive evidence on the efficacy of HAF toothpastes compared to traditional fluoridated toothpastes to reduce caries risk factors and to prevent caries lesions.

Dental Students' and Dental School Graduates' Practical Skills: An International Survey of Perceptions of National Dental Associations in Europe.

PURPOSE: Dental students learn knowledge and practical skills to provide oral health care to the population. Practical skills must be maintained or continuously developed throughout a professional career. This cross-sectional survey aimed to evaluate the perception of practical skills of dental students and dental-school graduates by national dental associations (NDAs) in international comparison in the European Regional Organization of the FDI World Dental Federation (ERO-FDI) zone. MATERIALS AND METHODS: A questionnaire of 14 items collected information on pre-/postgraduate areas. RESULTS: A total of 25 countries participated (response rate: 69.4%), with 80.0% having minimum requirements for practical skills acquisition and 64.0% starting practical training in the 3rd year of study. In countries where clinical practical work on patients begins in the 2nd year of study, practical skills of graduates are perceived as average, starting in the 3rd year of study as mainly good, starting in the 4th as varying widely from poor to very good. In total, 76.0% of respondents feel that improvements are needed before entering dental practice. Improvements could be reached by treating more patients in dental school (32.0%), increasing the quantity of clinical training (20.0%), or having more clinical instructors (12.0%). In 56.0% of the countries, it is possible to open one's own dental practice immediately after graduation, and in 16.0%, prior vocational training is mandatory. CONCLUSIONS: All participating countries in the ERO-FDI zone reported practical training in dental school, most starting in the 3rd year of study. The perception of practical skills of dental students and dental-school graduates among NDAs is very heterogeneous. Reasons for the perceived deficiencies should be further explored.

Monitoring the Evolution of Relative Product Populations at Early Times during a Photochemical Reaction.

Identifying multiple rival reaction products and transient species formed during ultrafast photochemical reactions and determining their time-evolving relative populations are key steps toward understanding and predicting photochemical outcomes. Yet, most contemporary ultrafast studies struggle with clearly identifying and quantifying competing molecular structures/species among the emerging reaction products. Here, we show that mega-electronvolt ultrafast electron diffraction in combination with ab initio molecular dynamics calculations offer a powerful route to determining time-resolved populations of the various isomeric products formed after UV (266 nm) excitation of the five-membered heterocyclic molecule 2(5H)-thiophenone. This strategy provides experimental validation of the predicted high (∼50%) yield of an episulfide isomer containing a strained three-membered ring within ∼1 ps of photoexcitation and highlights the rapidity of interconversion between the rival highly vibrationally excited photoproducts in their ground electronic state.

Bosonic excitation spectra of superconductingBi2Sr2CaCu2O8+δandYBa2Cu3O6+xextracted from scanning tunneling spectra.

A detailed interpretation of scanning tunneling spectra obtained on unconventional superconductors enables one to gain information on the pairing boson. Decisive for this approach are inelastic tunneling events. Due to the lack of momentum conservation in tunneling from or to the sharp tip, those are enhanced in the geometry of a scanning tunneling microscope compared to planar tunnel junctions. This work extends the method of obtaining the bosonic excitation spectrum by deconvolution from tunneling spectra to nodald-wave superconductors. In particular, scanning tunneling spectra of slightly underdopedBi2Sr2CaCu2O8+δwith aTcof 82 K and optimally dopedYBa2Cu3O6+xwith aTcof 92 K reveal a resonance mode in their bosonic excitation spectrum atΩres≈63 meVandΩres≈61 meVrespectively. In both cases, the overall shape of the bosonic excitation spectrum is indicative of predominant spin scattering with a resonant mode atΩres<2Δand overdamped spin fluctuations for energies larger than 2Δ. To perform the deconvolution of the experimental data, we implemented an efficient iterative algorithm that significantly enhances the reliability of our analysis.

The Presence of Women in the Dental Profession: A Global Survey.

OBJECTIVES: The aim of this research was to acquire knowledge about the female dental workforce, identifying factors to pursue specialty training and career choices and working in dental institutions/associations. METHODS: An original online questionnaire was developed, validated (n = 22), and sent to 189 member associations in 133 countries of the Women Dentists Worldwide section of the FDI World Dental Federation. RESULTS: In all, 3232 female dentists from 81 countries participated. Results were divided into 5 geographic areas by continent. Difference in proportion amongst questionnaire items was evaluated with χ2 test or Fisher exact test. Ordinal multinomial linear regression analysis was performed to evaluate the association of questionnaire items with total work experience in dentistry (in years), motivation to study dentistry, type of specialisation, working hours per week, perception of female dentists about working hours, sex-based inequalities, job security after maternity leaves, as well as involvement in political organisations within their country of residence and their role in dental associations. A majority of participating female dentists are self-employed (57.7%), and 60.0% have 10 to 30 years of experience. The most popular form of practice is the single private practice (29.7%), followed by the group private practice (28.8%). Further, 44.8% work 31 to 40 h/wk, 29.1% part-time up to 30 h/wk, and 26.0% more than 40 h/wk. CONCLUSIONS: Women are still poorly represented in professional organisations, and few are officers in representative assemblies, members of the board, or president. Family life with children influences perceptions and has an impact on professional life, especially in academia and political/professional associations, so that taking on leadership positions poses additional challenges.

The Study and Relevance of Pulp Chamber Anatomy in Endodontics - A Comprehensive Review.

With the ever-increasing understanding of tooth anatomy, there is a renewed focus on the pulp chamber as an important component of the root canal system. For example, the pulp chamber is of critical relevance during diagnostic procedures such as pulp sensibility tests, deep caries removal, vital pulp treatments, access cavity preparation, tooth whitening, tooth restoration as well as methods for examining the floor of the pulp chamber to aid the detection of root canal orifices or the presence of perforations and cracks. The more recent concept of minimal invasive endodontics has also created a need to understand better the anatomy of the pulp chamber. The purpose of this article is to discuss the research methods used to study pulp chamber anatomy and the significance of the pulp chamber in endodontic research and clinical practice. In addition, directions for future research are emphasised.

Internal Morphology of Mandibular Second Premolars Using Micro-Computed Tomography.

To examine root canal morphology of mandibular second premolars (Mn2P) of a mixed Swiss-German population by means of micro-computed tomography (micro-CT). Root canal configuration (RCC) of 102 Mn2P were investigated using micro-CT unit (µCT 40; SCANCO Medical AG, Brüttisellen, Switzerland) with 3D software imaging (VGStudio Max 2.2; Volume Graphics GmbH, Heidelberg, Germany), described with a four-digit system code indicating the main root canal from coronal to apical thirds and the number of main foramina. A total of 12 different RCCs were detected. 1-1-1/1 (54.9%) was most frequently observed RCC, followed by 1-1-1/2 (14.7%), 1-1-2/2 (10.8%), 1-2-2/2 (4.9%), 1-1-3/3 (3.9%), 1-1-1/3 (2.9%), 2-1-1/1 (2.9%) and less frequently 1-1-2/3, 1-2-1/2, 2-1-2/2, 1-1-2/5, 1-1-1/4 with each 1.0%. No accessory foramina were present in 35.3%, one in 35.3%, two in 21.6%, three and four in 2.9%, and five in 2.0%. In 55.9% Mn2Ps, accessory root canals were present in apical third and 8.8% in middle third of a root. Connecting canals were observed less frequently (6.9%) in apical and 2.9% in the middle third, no accessory/connecting canals in coronal third. Every tenth tooth showed at least or more than three main foramina. Almost two thirds of the sample showed accessory root canals, predominantly in apical third. The mainly single-rooted sample of Mn2Ps showed less frequent morphological diversifications than Mn1Ps.

The COVID-19 Pandemic and Dental Professionals' Infection Risk Perception: An International Survey.

A global survey among dentists was used to identify the various impacts of the COVID-19 pandemic on this professional group. Special attention was given to perception and assessment of infection risk. From May to August 2020, the questionnaire was delivered in 36 countries by respective research groups and was completed by 52,491 dental professionals. The survey was designed as a cross-sectional survey based on a previously standardized questionnaire. This study focuses on the part of the questionnaire that deals with the perception of the infection risk of COVID-19 by dentists and their patients. A logistic regression model was used, which consisted of four Likert items as response options and the additional self-reported routine or emergency treatment as the dependent variable. Analysis by continent found that European and Asian dentists were particularly likely to be infected at work (OR = 1.45 95%CI = 1.02/1.84 and OR = 2.68, 95%CI = 1.45/3.22, respectively), while it was likely that Australian dentists did not feel particularly at risk due to low infection rates. Three quarters of Americans treated only emergencies during this survey period, while Europeans (64.71%) and Asians (66.67%) provided mostly routine care. This could affect the Europeans' confidence that they would not be able to protect themselves from infections in the long-term. The COVID-19 pandemic and its impact on dental professionals' infection risk perception is determined by the geographical origin of dentists. This study shows that, especially in high-incidence countries, infection risk perception was higher when dentists tried to provide routine dental procedures to their patients. Dental professionals can offer themselves and their patients good protection by maintaining high standards of hygiene. However, their concerns should be taken seriously and the dental professionals' group that is of great importance for oral health care and prevention, should not be neglected in the future, even in the event of emerging pandemics.

Distinct transcriptional responses to fludioxonil in Aspergillus fumigatus and its ΔtcsC and Δskn7 mutants reveal a crucial role for Skn7 in the cell wall reorganizations triggered by this antifungal.

BACKGROUND: Aspergillus fumigatus is a major fungal pathogen that causes severe problems due to its increasing resistance to many therapeutic agents. Fludioxonil is a compound that triggers a lethal activation of the fungal-specific High Osmolarity Glycerol pathway. Its pronounced antifungal activity against A. fumigatus and other pathogenic molds renders this agent an attractive lead substance for the development of new therapeutics. The group III hydride histidine kinase TcsC and its downstream target Skn7 are key elements of the multistep phosphorelay that represents the initial section of the High Osmolarity Glycerol pathway. Loss of tcsC results in resistance to fludioxonil, whereas a Δskn7 mutant is partially, but not completely resistant. RESULTS: In this study, we compared the fludioxonil-induced transcriptional responses in the ΔtcsC and Δskn7 mutant and their parental A. fumigatus strain. The number of differentially expressed genes correlates well with the susceptibility level of the individual strains. The wild type and, to a lesser extend also the Δskn7 mutant, showed a multi-faceted stress response involving genes linked to ribosomal and peroxisomal function, iron homeostasis and oxidative stress. A marked difference between the sensitive wild type and the largely resistant Δskn7 mutant was evident for many cell wall-related genes and in particular those involved in the biosynthesis of chitin. Biochemical data corroborate this differential gene expression that does not occur in response to hyperosmotic stress. CONCLUSIONS: Our data reveal that fludioxonil induces a strong and TcsC-dependent stress that affects many aspects of the cellular machinery. The data also demonstrate a link between Skn7 and the cell wall reorganizations that foster the characteristic ballooning and the subsequent lysis of fludioxonil-treated cells.

Compact single-shot soft X-ray photon spectrometer for free-electron laser diagnostics.

The photon spectrum from free-electron laser (FEL) light sources offers valuable information in time-resolved experiments and machine optimization in the spectral and temporal domains. We have developed a compact single-shot photon spectrometer to diagnose soft X-ray spectra. The spectrometer consists of an array of off-axis Fresnel zone plates (FZP) that act as transmission-imaging gratings, a Ce:YAG scintillator, and a microscope objective to image the scintillation target onto a two-dimensional imaging detector. This spectrometer operates in segmented energy ranges which covers tens of electronvolts for each absorption edge associated with several atomic constituents: carbon, nitrogen, oxygen, and neon. The spectrometer's performance is demonstrated at a repetition rate of 120 Hz, but our detection scheme can be easily extended to 200 kHz spectral collection by employing a fast complementary metal oxide semiconductor (CMOS) line-scan camera to detect the light from the scintillator. This compact photon spectrometer provides an opportunity for monitoring the spectrum downstream of an endstation in a limited space environment with sub-electronvolt energy resolution.