A Direct Limit for Limit Hilbert-Kunz Multiplicity for Smooth Projective Curves

This paper concerns the question of whether a more direct limit can be used to obtain the limit Hilbert-Kunz multiplicity, a possible candidate for a characteristic zero Hilbert-Kunz multiplicity. The main goal is to establish an affirmative answer for one of the main cases for which the limit Hilbert-Kunz multiplicity is even known to exist, namely that of graded ideals in the homogeneous coordinate ring of smooth projective curves. The proof involves more careful estimates of bounds found independently by Brenner and Trivedi on the dimensions of the cohomologies of twists of the syzygy bundle as the characteristic p goes to infinity and uses asymptotic results of Trivedi on the slopes of Harder-Narasimham filtrations of Frobenius pullbacks of bundles. In view of unpublished results of Gessel and Monsky, the case of maximal ideals in diagonal hypersurfaces is also discussed in depth.Comment: Minor typos fixe

Relationship between corneal temperature and i0ntraocular pressure in healthy Individuals. a clinical thermographic analysis

To study the geographical distribution of corneal temperature (CT) and its influence on the intraocular pressure (IOP) of healthy human volunteers. Materials and Methods. Fifteen subjects (7 M, 8 F), 33.8 +/- 17.4 years old, were enrolled in this pilot, cross-sectional study. Measurements of CT were taken after one hour with closed eyelids (CET) or closed eyelids with a cooling mask (cm-CET) and compared to baseline. Results. If compared to baseline, after CET, average CT significantly increased by 0.56 degrees C in the RE and by 0.48 degrees C in the LE (p < 0.001) and IOP concomitantly significantly increased by 1.13 mm Hg and 1.46 mm Hg, respectively, in each eye (p < 0.001). After cm-CET, average CT significantly decreased by 0.11 degrees C and 0.20 degrees C, respectively, in the RE and LE (RE p = 0.04; LE p = 0.024), followed by a significant IOP decrease of 2.19 mm Hg and 1.54 mm Hg, respectively, in each eye (RE p < 0.001; LE = 0.0019). Conclusion. Significant variations of CT occurred after CET and cm-CET and were directly correlated with significant differences of IOP. It can be speculated that both oxidative stress and sympathetic nerve fiber stimulation by temperature oscillations may affect the regulation of AH vortex flow and turnover, thus influencing IOP values

Selection of third party software in Off-The-Shelf-based software development: an interview study with industrial practitioners

The success of software development using third party components highly depends on the ability to select a suitable component for the intended application. The evidence shows that there is limited knowledge about current industrial OTS selection practices. As a result, there is often a gap between theory and practice, and the proposed methods for supporting selection are rarely adopted in the industrial practice. This paper's goal is to investigate the actual industrial practice of component selection in order to provide an initial empirical basis that allows the reconciliation of research and industrial endeavors. The study consisted of semi-structured interviews with 23 employees from 20 different software-intensive companies that mostly develop web information system applications. It provides qualitative information that help to further understand these practices, and emphasize some aspects that have been overlooked by researchers. For instance, although the literature claims that component repositories are important for locating reusable components; these are hardly used in industrial practice. Instead, other resources that have not received considerable attention are used with this aim. Practices and potential market niches for software-intensive companies have been also identified. The results are valuable from both the research and the industrial perspectives as they provide a basis for formulating well-substantiated hypotheses and more effective improvement strategies.Peer ReviewedPostprint (author's final draft

Understanding neurodevelopmental disorders using human pluripotent stem cell-derived neurons

Research into psychiatric disorders has long been hindered by the lack of appropriate models. Induced pluripotent stem cells (iPSCs) offer an unlimited source of patient-specific cells, which in principle can be differentiated into all disease-relevant somatic cell types to create in vitro models of the disorder of interest. Here, neuronal differentiation protocols available for this purpose and the current progress on iPSCs-based models of schizophrenia, autism spectrum disorders and bipolar disorder were reviewed. We also discuss the impact of the recently developed CRISPR/Cas9 genome editing tool in the disease modeling field. Genetically engineered mutation of disease risk alleles in well characterized reference “control” hPSCs or correction of disease risk variants in patient iPSCs has been used as a powerful means to establish causality of the identified cellular pathology. Together, iPSC reprogramming and CRISPR/CAS9 genome editing technology have already significantly contributed to our understanding of the developmental origin of some major psychiatric disorders. The challenge ahead is the identification of shared mechanisms in their etiology, which will ultimately be relevant to the development of new treatments

Functional exploration of co-expression networks identifies a nexus for modulating protein and citric acid titres in Aspergillus niger submerged culture

Background: Filamentous fungal cell factories are used to produce numerous proteins, enzymes, and organic acids. Protein secretion and filamentous growth are tightly coupled at the hyphal tip. Additionally, both these processes require ATP and amino acid precursors derived from the citric acid cycle. Despite this interconnection of organic acid production and protein secretion/filamentous growth, few studies in fungi have identified genes which may concomitantly impact all three processes. Results: We applied a novel screen of a global co-expression network in the cell factory Aspergillus niger to identify candidate genes which may concomitantly impact macromorphology, and protein/organic acid fermentation. This identified genes predicted to encode the Golgi localized ArfA GTPase activating protein (GAP, AgeB), and ArfA guanine nucleotide exchange factors (GEFs SecG and GeaB) to be co-expressed with citric acid cycle genes. Consequently, we used CRISPR-based genome editing to place the titratable Tet-on expression system upstream of ageB, secG, and geaB in A. niger. Functional analysis revealed that ageB and geaB are essential whereas secG was dispensable for early filamentous growth. Next, gene expression was titrated during submerged cultivations under conditions for either protein or organic acid production. ArfA regulators played varied and culture-dependent roles on pellet formation. Notably, ageB or geaB expression levels had major impacts on protein secretion, whereas secG was dispensable. In contrast, reduced expression of each predicted ArfA regulator resulted in an absence of citric acid in growth media. Finally, titrated expression of either GEFs resulted in an increase in oxaloacetic acid concentrations in supernatants. Conclusion: Our data suggest that the Golgi may play an underappreciated role in modulating organic acid titres during industrial applications, and that this is SecG, GeaB and AgeB dependent in A. niger. These data may lead to novel avenues for strain optimization in filamentous fungi for improved protein and organic acid titres.TU Berlin, Open-Access-Mittel - 201

Modern fathers' dilemma of work-family reconciliation: Findings from the German Youth Institute Survey AID:A II

Objective: This study investigated how work and family demands and resources relate to fathers’ perceived work-family conflicts. Background: Increasing expectations for family involvement and the lingering centrality of employment in the male life course pose challenges for fathers to combine different life domains. However, most studies on work-family interface continue to focus on mothers and examine work-to-family conflict and family-to-work conflicts separately. Method: First, we used cluster analysis to identify a typology of four groups, each with different manifestations of work-to-family and family-to-work conflict. We then analyzed the relationship between fathers’ group membership in this typology and a number of relevant work and family demands and resources using multinomial logistic regression on a sample of 5,226 German nuclear families with at least one child under 18. Results: Our findings revealed that the greatest proportion of fathers (38.2%) reported being primarily pressured from work (=work-to-family conflict predominates), 19.8% primarily from the family (=family-to-work conflict predominates), but another 13.4% reported feeling conflicted in both directions; only 28.6% of fathers reported being more or less free of conflicts. Results of multinominal logistic regression suggested that long work hours, intrusive work demands, and long commute associated with fathers’ work-to-family conflict or dual conflicts. The higher the fathers’ weekday time investment in childcare and the better the perceived couple and family relationship, the lower the likelihood of fathers’ experience of work-to-family and dual conflict, although the likelihood of family-to-work conflict is unaffected. In addition, a higher family income and having a non-working partner negatively associated with fathers’ perceived work-family conflicts. Conclusion: These findings have strong implications for family-supportive practices and policies that are yet to focus on fathers in their difficult position between work and family obligations

Differentiation enhances Zika virus infection of neuronal brain cells.

Zika virus (ZIKV) is an emerging, mosquito-borne pathogen associated with a widespread 2015-2016 epidemic in the Western Hemisphere and a proven cause of microcephaly and other fetal brain defects in infants born to infected mothers. ZIKV infections have been also linked to other neurological illnesses in infected adults and children, including Guillain-Barré syndrome (GBS), acute flaccid paralysis (AFP) and meningoencephalitis, but the viral pathophysiology behind those conditions remains poorly understood. Here we investigated ZIKV infectivity in neuroblastoma SH-SY5Y cells, both undifferentiated and following differentiation with retinoic acid. We found that multiple ZIKV strains, representing both the prototype African and contemporary Asian epidemic lineages, were able to replicate in SH-SY5Y cells. Differentiation with resultant expression of mature neuron markers increased infectivity in these cells, and the extent of infectivity correlated with degree of differentiation. New viral particles in infected cells were visualized by electron microscopy and found to be primarily situated inside vesicles; overt damage to the Golgi apparatus was also observed. Enhanced ZIKV infectivity in a neural cell line following differentiation may contribute to viral neuropathogenesis in the developing or mature central nervous system

Updated Phylogeny and Protein Structure Predictions Revise the Hypothesis on the Origin of MADS-box Transcription Factors in Land Plants

MADS-box transcription factors (TFs), among the first TFs extensively studied, exhibit a wide distribution across eukaryotes and play diverse functional roles. Varying by domain architecture, MADS-box TFs in land plants are categorized into Type I (M-type) and Type II (MIKC-type). Type I and II genes have been considered orthologous to the SRF and MEF2 genes in animals, respectively, presumably originating from a duplication before the divergence of eukaryotes. Here, we exploited the increasing availability of eukaryotic MADS-box sequences and reassessed their evolution. While supporting the ancient duplication giving rise to SRF- and MEF2-types, we found that Type I and II genes originated from the MEF2-type genes through another duplication in the most recent common ancestor (MRCA) of land plants. Protein structures predicted by AlphaFold2 and OmegaFold support our phylogenetic analyses, with plant Type I and II TFs resembling the MEF2-type structure, rather than SRFs. We hypothesize that the ancestral SRF-type TFs were lost in the MRCA of Archaeplastida (the kingdom Plantae sensu lato). The retained MEF2-type TFs acquired a Keratin-like domain and became MIKC-type before the divergence of Streptophyta. Subsequently in the MRCA of land plants, M-type TFs evolved from a duplicated MIKC-type precursor through loss of the Keratin-like domain, leading to the Type I clade. Both Type I and II TFs expanded and functionally differentiated in concert with the increasing complexity of land plant body architecture. The recruitment of these originally stress-responsive TFs into developmental programs, including those underlying reproduction, may have facilitated the adaptation to the terrestrial environment

Subspecies typing of Streptococcus agalactiae based on ribosomal subunit protein mass variation by MALDI-TOF MS

Background: A ribosomal subunit protein (rsp)-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method was developed for fast subspecies-level typing of Streptococcus agalactiae (Group B Streptococcus, GBS), a major cause of neonatal sepsis and meningitis. Methods: A total of 796 GBS whole genome sequences, covering the genetic diversity of the global GBS population, were used to in silico predict molecular mass variability of 28 rsp and to identify unique rsp mass combinations, termed “rsp-profiles”. The in silico established GBS typing scheme was validated by MALDI-TOF MS analysis of GBS isolates at two independent research sites in Europe and South East Asia. Results: We identified in silico 62 rsp-profiles, with the majority (>80%) of the 796 GBS isolates displaying one of the six rsp-profiles 1-6. These dominant rsp-profiles classify GBS strains in high concordance with the core-genome based phylogenetic clustering. Validation of our approach by in-house MALDI-TOF MS analysis of 248 GBS isolates and external analysis of 8 GBS isolates showed that across different laboratories and MALDI-TOF MS platforms, the 28 rsp were detected reliably in the mass spectra, allowing assignment of clinical isolates to rsp-profiles at high sensitivity (99%) and specificity (97%). Our approach distinguishes the major phylogenetic GBS genotypes, identifies hyper-virulent strains, predicts the probable capsular serotype and surface protein variants and distinguishes between GBS genotypes of human and animal origin. Conclusion: We combine the information depth of whole genome sequences with the highly cost efficient, rapid and robust MALDI-TOF MS approach facilitating high-throughput, inter-laboratory, large-scale GBS epidemiological and clinical studies based on pre-defined rsp-profiles