Epidemiological modeling has a long history and is often used to forecast the course of infectious diseases or pandemics. These models come in different complexities, ranging from systems of simple ordinary differential equations (ODEs) to complex agent-based models (ABMs). The former allow a fast and straightforward optimization, but are limited in accuracy, detail, and parameterization, while the latter can resolve spreading processes in detail, but are extremely expensive to optimize. Epidemiological modeling can also be used to propose and design non-pharmaceutical interventions such as lockdowns. In general, their optimal design often leads to nonlinear optimization problems. We consider policy optimization in a prototypical situation modeled as both ODE and ABM, review numerical optimization approaches, and propose a heterogeneous multilevel approach based on combining a fine-resolution ABM and a coarse ODE model. Numerical experiments, in particular with respect to convergence speed, are given for illustrative examples.
Weniger anzeigenThe genus Wetmoreana was studied using quantitative integrative taxonomy methods to resolve the genus delimitation and explore its taxonomy diversity at the species level. As a result, the genus Fulgogasparrea is synonymized with Wetmoreana, and the latter includes 15 formally described species, one subspecies, and three further, thus far undescribed species: W. appressa, W. awasthii comb. nov., W. bahiensis sp. nov., W. brachyloba comb. nov., W. brouardii, W. chapadensis comb. nov., W. circumlobata sp. nov., W. decipioides, W. intensa comb. nov., W. ochraceofulva comb. nov., W. rubra sp. nov., W. sliwae sp. nov., W. sliwae ssp. subparviloba subsp. nov., W. subnitida comb. nov., W. texana, and W. variegata sp. nov. Eleven of 19 examined taxa are newly placed within this genus or confirmed to belong to it. Two species, W. awasthii and W. intensa, are transferred to Wetmoreana without additional analysis but based on previous studies. The W. brouardii and W. ochraceofulva species complexes are discussed in detail. Additionally, Caloplaca muelleri and C. rubina var. evolutior are transferred to Squamulea, and the latter is elevated to the species rank.
Weniger anzeigenMotivation
The minimizer concept is a data structure for sequence sketching. The standard canonical minimizer selects a subset of k-mers from the given DNA sequence by comparing the forward and reverse k-mers in a window simultaneously according to a predefined selection scheme. It is widely employed by sequence analysis such as read mapping and assembly. k-mer density, k-mer repetitiveness (e.g. k-mer bias), and computational efficiency are three critical measurements for minimizer selection schemes. However, there exist trade-offs between kinds of minimizer variants. Generic, effective, and efficient are always the requirements for high-performance minimizer algorithms.
Results
We propose a simple minimizer operator as a refinement of the standard canonical minimizer. It takes only a few operations to compute. However, it can improve the k-mer repetitiveness, especially for the lexicographic order. It applies to other selection schemes of total orders (e.g. random orders). Moreover, it is computationally efficient and the density is close to that of the standard minimizer. The refined minimizer may benefit high-performance applications like binning and read mapping.
Availability and implementation
The source code of the benchmark in this work is available at the github repository https://github.com/xp3i4/mini_benchmark
Weniger anzeigenAlterations in thyroid hormones (TH) and thyroid-stimulating hormone levels are frequently found following exposure to chemicals of concern. Dysregulation of TH levels can severely perturb physiological growth, metabolism, differentiation, homeostasis in the adult and developmental processes in utero. A frequently identified mode of action for this interaction is the induction of hepatic detoxification mechanisms (e.g. SULTs and UGTs), which lead to TH conjugation and elimination and therefore interfere with hormonal homeostasis, fulfilling the endocrine disruptors (EDs) definition. A short-term study in rats with dietary exposure to cyproconazole, epoxiconazole and prochloraz was conducted and hepatocyte hypertrophy, hepatic UGT activity and Phase 1/2 gene expression inductions were observed together with changes in TH levels and thyroid follicular hypertrophy and hyperplasia. To test for specific interaction with the thyroid hormone system, in vitro assays were conducted covering thyroidal I-uptake (NIS), TH transmembranal transport via MCT8 and thyroid peroxidase (TPO) function. Assays for iodothyronine deiodinases (DIO1–DIO3) and iodotyrosine deiodinase (DEHAL1) were included, and from the animal experiment, Dio1 and Dehal1 activities were measured in kidney and liver as relevant local indicators and endpoints. The fungicides did not affect any TH-specific KEs, in vitro and in vivo, thereby suggesting hepatic conjugation as the dominant MoA.
Weniger anzeigenBackground
Swelling of the perineal region in male dogs is most commonly caused by a perineal hernia. Clinical signs associated with perineal hernia are constipation, tenesmus or stranguria. This case report documents a rare cause of perineal swelling created by the growth of a malignant tumour leading to urethral obstruction and subsequent stranguria.
Case presentation
An 11-year-old neutered male German Shepherd was presented for swelling in the perineal region and stranguria for three days. Complete blood count and serum biochemistry were unremarkable. Ultrasound revealed a heterogeneous mass in the perineal region. Retrograde urethrography showed a severe narrowing of the urethra caudal to the pelvis. A fine-needle aspirate of the mass was highly suspicious for liposarcoma. Staging was performed by computed tomography (CT) of the thorax and abdomen. Total penile amputation in combination with pubic-ischial pelvic osteotomy, transposition of the remaining urethra through the inguinal canal, V-Y-plasty cranial to the prepuce and preputial urethrostomy were performed to remove the tumour. Histopathology confirmed a well-differentiated liposarcoma with complete histological margins. Six months after the surgery the dog was doing well and there were no signs indicating local tumour recurrence.
Conclusions
Wide surgical excision is generally recommended for soft tissue sarcomas, however this is sometimes not feasible for large tumours. In the case reported here, tumour resection was achieved by a combination of several surgical techniques with a good clinical outcome.
Weniger anzeigenJayme Tiomno belonged to the ‘founder’s generation’ of physicists in Brazil. He began working in relativity theory early in his career, at a time when it was not at all ‘fashionable’, through the influence of his early mentor, Mario Schenberg in São Paulo. When he went to graduate school in Princeton, in February 1948, his advisor there, John Wheeler, gave him a project in General Relativity, even though this was more than 4 years before Wheeler’s ‘turn’ from nuclear and particle physics to field theory and gravitation.
Tiomno and Wheeler however soon discovered their mutual interest in meson decays, and Tiomno’s Masters and PhD theses were on topics from particle physics, which remained his major field of interest for the following 20 years, during which he collaborated with Abdus Salam, among others. Only when he returned to Princeton in 1971, a refugee from the oppressive dictatorship in Brazil, did he again begin working in gravitation and field theory, having missed the ‘golden age’ initiated in part by Wheeler’s group.
At the IAS, Tiomno experienced a renaissance of his interest in field theory, working with Remo Ruffini and others. He continued this work in the 1980’s after he was able to return to the CBPF in Rio de Janeiro (which he had helped to found). His participation in the Marcel Grossmann Meetings was limited but significant.
Weniger anzeigenMetal-organic frameworks (MOFs) are crystalline and porous, molecular solids consisting of metal nodes and organic ligands. An interesting example is the MOF-2 system, where Cu2+ ions form antiferromagnetically coupled dimers to yield so-called paddlewheels. In the case of surface-anchored MOF-2 (SURMOF-2) systems the Cu2+ ions are connected via carboxylate and OH groups in a zipperlike fashion. This unusual coupling of the spin-1/2 ions within the resulting one-dimensional chains stabilizes a low-temperature ferromagnetic (FM) phase. In this study, the magnetic properties of two SURMOF-2 systems (Cu(bdc) and Cu(bpdc) with bdc=1, 4-benzendicarboxylic acid, bpdc=4,4-biphenyldicarboxylic acid) were investigated using x-ray magnetic circular dichroism both in the absorption and in the scattering geometry. The presence of the FM phase in these SURMOF-2 systems is confirmed. Taking advantage of the element sensitivity of this technique. it was established that the magnetic signal originates from Cu2+ ions. After loading of SURMOF-2 with metallocene molecules, no remarkable changes of the magnetic properties of the host matrix were observed. However, the magnetic behavior of the guest molecules, as it turned out, is rather different. In the case of nickelocene loading, a polarization effect was found, resulting in ferromagnetic ordering of the guest molecules. However, in the case of manganocene derivatives, the polarization effect is not observed and these molecules remained in their paramagnetic state. The details of these effects are discussed.
Weniger anzeigenHydrogen chloride is produced as a by-product in industrial processes on a million-ton scale. Since HCl is inherently dangerous, its storage and transport are avoided by, e.g., on-site electrolysis providing H2 and Cl2 which usually requires complex cell designs and PFAS-based membranes. Here we report a complementary approach to safely store 0.61 kilogram HCl per kilogram storage material [NEt3Me]Cl forming the bichloride [NEt3Me][Cl(HCl)n]. Although HCl release is possible from this ionic liquid by heat or vacuum, the bichloride can be used directly to produce base chemicals like vinyl chloride. Alternatively, [NEt3Me][Cl(HCl)n] is electrolyzed under anhydrous conditions using a membrane-free cell to generate H2 and the corresponding chlorination agent [NEt3Me][Cl(Cl2)n], enabling the combination of these ionic liquids for the production of base chemicals.
Weniger anzeigenDer Berufsverband Deutscher Psychologinnen und Psychologen (BDP) und die Deutsche Gesellschaft für Psychologie (DGPs) bilden seit 1964 eine Föderation. Als Föderation haben die beiden Vereinigungen die deutsche Psychologie in internationalen Verbänden vertreten und die Reform des Psychologiestudiums sowie die Professionalisierung des Psychologieberufs in Deutschland mitgestaltet. Dabei sind BDP und DGPs selbständige Vereinigungen geblieben, welche auch voneinander abweichende fachpolitische Positionen einnehmen konnten.
Weniger anzeigenChris Hann's essay serves as a valuable intervention against the tendency to normalize primordial ethnonationalism following the full-scale Russian invasion. It is not immune to the common pitfalls and omissions in the writings of many authors whose point of criticism is aimed primarily at the role of Western elites in the conflict within and around Ukraine. But surely, Hann's core argument contains essential truths. Many social scientists have contributed to the construction of a theoretically shallow, methodologically nationalist, and culturally essentializing narrative. It is a telling fact that someone engaging the discussion has to begin with some basic facts of Ukrainian national identity formation, such as its diversity, or has to remind that the interests of the Western ruling classes in the war do not necessarily coincide with the interests of the Ukrainian subaltern classes, or that those are also likely to diverge from the interests and ideologies of their own comprador middle classes calling themselves “civil society.”
Weniger anzeigenAs the robust maximum likelihood 𝜒2 goodness-of-fit test had been found to yield inflated type-I error rates for certain two-level confirmatory factor analysis (CFA) models, a new correction for the test was implemented in Mplus version 8.7. In this simulation study, we inspected whether the corrected test statistics follow the expected 𝜒2 distributions when applying more complex two-level models for multitrait-multimethod data with varying sample sizes and correlations within trait factors. Investigating rejection rates and probability-probability plots, we found that the new correction markedly and sufficiently reduced previously inflated rejection rates in conditions with within-trait correlations equal to 1, 100 between-level units, and 10 or 20 within-level units. In other conditions, rejection rates were hardly affected or not sufficiently reduced by the new correction. While in most conditions, 2 within-level units did not suffice, 5 within-level units and 250 between-level units were enough to yield correct rejection rates given within-trait correlations did not exceed 0.80. Correlations above 0.80 required larger sample sizes. In planning studies with multilevel CFA models, researchers should be aware that sample size requirements for likelihood-based model fit evaluations can depend on several different factors and might consider conducting Monte Carlo simulations tailored to their specific modeling conditions.
Weniger anzeigenThe successful advancement of xenotransplantation has led to the development of highly sensitive detection systems for the screening of potentially zoonotic viruses in donor pigs and preventing their transmission to the recipient. To validate these methods, genetically modified pigs generated for xenotransplantation, numerous minipigs and other pig breeds have been tested, thereby increasing our knowledge concerning the pig virome and the distribution of pig viruses. Of particular importance are the porcine cytomegalovirus, a porcine roseolovirus (PCMV/PRV) and the hepatitis E virus genotype 3 (HEV3). PCMV/PRV has been shown to reduce the survival time of pig transplants in non-human primates and was also transmitted in the first pig heart transplantation to a human patient. The main aim of this study was to determine the sensitivities of our methods to detect PCMV/PRV, HEV3, porcine lymphotropic herpesvirus-1 (PLHV-1), PLHV-2, PLHV-3, porcine circovirus 2 (PCV2), PCV3, PCV4 and porcine parvovirus 1 (PPV1) and to apply the methods to screen indigenous Greek black pigs. The high number of viruses found in these animals allowed for the evaluation of numerous detection methods. Since porcine endogenous retroviruses (PERVs) type A and B are integrated in the genome of all pigs, but PERV-C is not, the animals were screened for PERV-C and PERV-A/C. Our detection methods were sensitive and detected PCMV/PRV, PLHV-1, PLHV-1, PLHV-3, PVC3 and PERV-C in most animals. PPV1, HEV3, PCV4 and PERV-A/C were not detected. These data are of great interest since the animals are healthy and resistant to diseases.
Weniger anzeigenThe repertoire of currently available antiviral drugs spans therapeutic applications against a number of important human pathogens distributed worldwide. These include cases of the pandemic severe acute respiratory coronavirus type 2 (SARS-CoV-2 or COVID-19), human immunodeficiency virus type 1 (HIV-1 or AIDS), and the pregnancy- and posttransplant-relevant human cytomegalovirus (HCMV). In almost all cases, approved therapies are based on direct-acting antivirals (DAAs), but their benefit, particularly in long-term applications, is often limited by the induction of viral drug resistance or side effects. These issues might be addressed by the additional use of host-directed antivirals (HDAs). As a strong input from long-term experiences with cancer therapies, host protein kinases may serve as HDA targets of mechanistically new antiviral drugs. The study demonstrates such a novel antiviral strategy by targeting the major virus-supportive host kinase CDK7. Importantly, this strategy focuses on highly selective, 3D structure-derived CDK7 inhibitors carrying a warhead moiety that mediates covalent target binding. In summary, the main experimental findings of this study are as follows: (1) the in vitro verification of CDK7 inhibition and selectivity that confirms the warhead covalent-binding principle (by CDK-specific kinase assays), (2) the highly pronounced antiviral efficacies of the hit compounds (in cultured cell-based infection models) with half-maximal effective concentrations that reach down to picomolar levels, (3) a particularly strong potency of compounds against strains and reporter-expressing recombinants of HCMV (using infection assays in primary human fibroblasts), (4) additional activity against further herpesviruses such as animal CMVs and VZV, (5) unique mechanistic properties that include an immediate block of HCMV replication directed early (determined by Western blot detection of viral marker proteins), (6) a substantial drug synergism in combination with MBV (measured by a Loewe additivity fixed-dose assay), and (7) a strong sensitivity of clinically relevant HCMV mutants carrying MBV or ganciclovir resistance markers. Combined, the data highlight the huge developmental potential of this host-directed antiviral targeting concept utilizing covalently binding CDK7 inhibitors.
Weniger anzeigenMutations in activin-like kinase 2 (ALK2), e.g., ALK2-R206H, induce aberrant signaling to SMAD1/5/8, leading to Fibrodysplasia Ossificans Progressiva (FOP). In spite of extensive studies, the underlying mechanism is still unclear. Here, we quantified the homomeric and heteromeric interactions of ACVR2A, ACVR2B, ALK2-WT, and ALK2-R206H by combining IgG-mediated immobilization of one receptor with fluorescence recovery after photobleaching (FRAP) measurements on the lateral diffusion of a co-expressed receptor. ACVR2B formed stable homomeric complexes that were enhanced by Activin A (ActA), while ACVR2A required ActA for homodimerization. ALK2-WT, but not ALK2-R206H, exhibited homomeric complexes unaffected by ActA. ACVR2B formed ActA-enhanced heterocomplexes with ALK2-R206H or ALK2-WT, while ACVR2A interacted mainly with ALK2-WT. The extent of the homomeric complex formation of ACVR2A or ACVR2B was reflected in their ability to induce the oligomerization of ALK2-R206H and ALK2-WT. Thus, ACVR2B, which forms dimers without ligand, induced ActA-independent ALK2-R206H clustering but required ActA for enhancing the oligomerization of the largely dimeric ALK2-WT. In contrast, ACVR2A, which undergoes homodimerization in response to ActA, required ActA to induce ALK2-R206H oligomerization. To investigate whether these interactions are translated into signaling, we studied signaling by the FOP-inducing hyperactive ALK2-R206H mutant, with ALK2-WT signaling as control. The activation of SMAD1/5/8 signaling in cells expressing ALK2-R206H alone or together with ACVR2A or ACVR2B was measured by blotting for pSMAD1/5/8 and by transcriptional activation assays using BRE-Luc reporter. In line with the biophysical studies, ACVR2B activated ALK2-R206H without ligand, while activation by ACVR2A was weaker and required ActA. We propose that the homodimerization of ACVR2B or ACVR2A dictates their ability to recruit ALK2-R206H into higher complexes, enabling the homomeric interactions of ALK2-R206H receptors and, subsequently, their activation.
Weniger anzeigenAntimicrobial resistance (AMR) is considered one of the greatest threats to both human and animal health. Efforts to address AMR include implementing antimicrobial stewardship programs and introducing alternative treatment options. Nevertheless, effective treatment of infectious diseases caused by bacteria will still require the identification and development of new antimicrobial agents. Eight different natural products were tested for antimicrobial activity against seven pathogenic bacterial species (Brachyspira sp., Chlamydia sp., Clostridioides sp., Mannheimia sp., Mycobacterium sp., Mycoplasma sp., Pasteurella sp.). In a first pre-screening, most compounds (five out of eight) inhibited bacterial growth only at high concentrations, but three natural products (celastramycin A [CA], closthioamide [CT], maduranic acid [MA]) displayed activity at concentrations <2 µg/mL against Pasteurella sp. and two of them (CA and CT) also against Mannheimia sp. Those results were confirmed by testing a larger collection of isolates encompassing 64 Pasteurella and 56 Mannheimia field isolates originating from pigs or cattle, which yielded MIC90 values of 0.5, 0.5, and 2 µg/mL against Pasteurella and 0.5, 4, and >16 µg/mL against Mannheimia for CA, CT, and MA, respectively. CA, CT, and MA exhibited higher MIC50 and MIC90 values against Pasteurella isolates with a known AMR phenotype against commonly used therapeutic antimicrobial agents than against isolates with unknown AMR profiles. This study demonstrates the importance of whole-cell antibacterial screening of natural products to identify promising scaffolds with broad- or narrow-spectrum antimicrobial activity against important Gram-negative veterinary pathogens with zoonotic potential
Weniger anzeigenDue to the increasing risk of extreme events caused by climate change (i.e., floods, fires and hurricanes) or wars, European veterinary public health may need some improvement. Utilizing a mix of qualitative (participatory observation) and quantitative methods (Internet mining), we analyzed the Greek media’s responses to the millennial flood in Thessaly (September 2023), focusing on animal health (including wild, companion animals and livestock) and public sentiment towards epizootic/epidemic threats. The study revealed a gap in crisis management plans regarding veterinary-related issues, emphasizing the need for comprehensive emergency response strategies. Our findings show how (i) the lay referral system is projecting the perception of epidemic threats into the population; (ii) the emotional load of images of animal carcasses is misused by media creators aiming for a big audience; and (iii) pets’ owners are creating online communities for the searching and treatment of their pets. Our results stress the importance of integrating crisis communication in consecutive phases of the discourse, such as the following: (i) weather change; (ii) acute flood; (iii) recovery; and (iv) outbreaks, into veterinary practices to better prepare for such disasters.
Weniger anzeigenFact-checking has been granted a pivotal role in mitigating the effects of online disinformation, but its effectiveness has nonetheless been questioned (Lee and Shin Citation2019). Like any persuasive communication, fact checkers depend on their recipients perceiving both their messages and them as credible (Lombardi, Seyranian, and Sinatra Citation2014; Lombardi, Nussbaum, and Sinatra Citation2016). This study investigates the role of the perceived credibility of the fact checker as possible detriment to the effectiveness of fact-checking efforts by means of an online survey-embedded experiment. Results show that the perceived credibility of the fact checker and fact-checking messages is best explained by normative expectations of the roles of fact checkers and trust in traditional media. Some users perceive fact checkers as elite power structures in journalism or, in other words, as collaborative-facilitators for state propaganda (Hanitzsch and Vos Citation2018; see also Fawzi Citation2020). Further, low trust in media and politics predicts perceived credibility of disinformation better than political partisanship. The findings suggest that fact checkers should be more transparent and proactive in communicating their motives and identities. Further implications are discussed.
Weniger anzeigenDas vietnamesische Berlin war lange Zeit hauptsächlich durch zwei Zuwanderungsgruppen gekennzeichnet: die vornehmlich aus Südvietnam geflüchteten sogenannten „Boatpeople“, die Ende der 1970er von der BRD im Rahmen von Kontingentvereinbarungen aufgenommen wurden und die einstigen Vertragsarbeiter*innen, die in den 1980er Jahren in die DDR kamen und nach der Wiedervereinigung zu einem großen Teil in Deutschland blieben. Seitdem wird die Zuwanderung aus Vietnam heterogener, seit Beginn der 2010er Jahre hat sie sich deutlich verstärkt. Diese ‚neue Migration‘, über die bisher kaum etwas bekannt ist, steht im Mittelpunkt der vorliegenden sozialanthropologischen Studie. Mittels eines qualitativen und anwendungsbezogenen ethnografischen ‚multi-sited‘ Ansatzes wurden die dieser Zuwanderung zugrundliegenden Push und Pull-Faktoren und die zentralen Migrationsstrategien untersucht. Daneben wurden die empirisch evidenten Probleme und Belastungen aus der Sicht von Migrant*innen sowie von Fachkräften aus u.a. der Sozialen Arbeit und der Verwaltung analysiert, um ein umfassendes Bild über die Lebenssituation nach Ankunft in Berlin zu erhalten. Ein besonderer Fokus liegt auf den spezifischen Herausforderungen, denen sich (werdende) Mütter und ihre Kinder sowie Auszubildende gegenübersehen.
Weniger anzeigenMolecular isomerization kinetics in liquid solvent depends on a complex interplay between the solvent friction acting on the molecule, internal dissipation effects (also known as internal friction), the viscosity of the solvent, and the dihedral free energy profile. Due to the absence of accurate techniques to directly evaluate isomerization friction, it has not been possible to explore these relationships in full. By combining extensive molecular dynamics simulations with friction memory-kernel extraction techniques we consider a variety of small, isomerising molecules under a range of different viscogenic conditions and directly evaluate the viscosity dependence of the friction acting on a rotating dihedral. We reveal that the influence of different viscogenic media on isomerization kinetics can be dramatically different, even when measured at the same viscosity. This is due to the dynamic solute-solvent coupling, mediated by time-dependent friction memory kernels. We also show that deviations from the linear dependence of isomerization rates on solvent viscosity, which are often simply attributed to internal friction effects, are due to the simultaneous violation of two fundamental relationships: the Stokes-Einstein relation and the overdamped Kramers prediction for the barrier-crossing rate, both of which require explicit knowledge of friction.
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