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Sphingosine 1-phosphate (S1P), derived from membrane sphingolipids, is a pleiotropic bioactive lipid mediator capable of evoking complex immune phenomena. Studies have highlighted its importance regarding intracellular signaling cascades as well as membrane-bound S1P receptor (S1PR) engagement in various clinical conditions. In neurological disorders, the S1P–S1PR axis is acknowledged in neurodegenerative, neuroinflammatory, and cerebrovascular disorders. Modulators of S1P signaling have enabled an immense insight into fundamental pathological pathways, which were pivotal in identifying and improving the treatment of human diseases. However, its intricate molecular signaling pathways initiated upon receptor ligation are still poorly elucidated. In this review, the authors highlight the current evidence for S1P signaling in neurodegenerative and neuroinflammatory disorders as well as stroke and present an array of drugs targeting the S1P signaling pathway, which are being tested in clinical trials. Further insights on how the S1P–S1PR axis orchestrates disease initiation, progression, and recovery may hold a remarkable potential regarding therapeutic options in these neurological disorders.
Ziel des Lehr-Lern-Projektes war die Schaffung einer kollegialen Arbeitsgemeinschaft zwischen Lehramtsstudierenden der hochschulischen Ausbildungsphase und bereits im Beruf etablierten Lehrkräften im Fachbereich Geschichte. Traditionell hierarchische Strukturen wurden aufgebrochen, um die jeweiligen Kompetenzen der Teilnehmenden für beide Seiten gewinnbringend zu vereinen. Anders als in den hochschulischen Praktika treten Lehramtsstudierende den Lehrkräften mit Expertise gegenüber: Der Austausch ist daher weniger einseitig als vielmehr von doppelseitigem Nutzen. Dieses Konzept bietet im Sinne einer community of practice nicht nur den Lehramtsstudierenden die Chance, ihr theoretisch erworbenes Wissen praxisorientiert anzuwenden und zu reflektieren, sondern ermöglicht auch den Lehrkräften, an den aktuellen geschichtsdidaktischen Forschungen und Entwicklungen an den Hochschulen teilzuhaben und mithilfe der Studierenden in der eigenen Schulpraxis zu reflektieren und gegebenenfalls anzuwenden. Anliegen des Lehr-Lern-Projektes ist ein Plädoyer, das Potenzial der Hochschulen über die eigenen Studierenden im Fortbildungsbereich der Lehrkräfte gewinnbringend zu nutzen, die schulische Reichweite von fachdidaktischer For-schung auszuschöpfen und den Lehramtsstudierenden zugleich eine weitere Möglichkeit einer schulpraktischen Erfahrung zu bieten. Nicht zuletzt: Die Verzahnung von Ausbildungs- und Weiterbildungsphase ist eine weitere gewinnbringende Möglichkeit, Akteur*innen der Lehrer*innenbildung in einen gewinnbringenden und praxisnahen Dialog zu bringen.
Envy, the inclination to compare rewards, can be expected to unfold when inequalities in terms of pay-off differences are generated in competitive societies. It is shown that increasing levels of envy lead inevitably to a self-induced separation into a lower and an upper class. Class stratification is Nash stable and strict, with members of the same class receiving identical rewards. Upper-class agents play exclusively pure strategies, all lower-class agents the same mixed strategy. The fraction of upper-class agents decreases progressively with larger levels of envy, until a single upper-class agent is left. Numerical simulations and a complete analytic treatment of a basic reference model, the shopping trouble model, are presented. The properties of the class-stratified society are universal and only indirectly controllable through the underlying utility function, which implies that class-stratified societies are intrinsically resistant to political control. Implications for human societies are discussed. It is pointed out that the repercussions of envy are amplified when societies become increasingly competitive.
Tsetse flies are the transmitting vector of trypanosomes causing human sleeping sickness and animal trypanosomiasis in sub-saharan Africa. 3-alkylphenols are used as attractants in tsetse fly traps to reduce the spread of the disease. Here we present an inexpensive production method for 3-ethylphenol (3-EP) and 3-propylphenol (3-PP) by microbial fermentation of sugars. Heterologous expression in the yeast Saccharomyces cerevisiae of phosphopantetheinyltransferase-activated 6-methylsalicylic acid (6-MSA) synthase (MSAS) and 6-MSA decarboxylase converted acetyl-CoA as a priming unit via 6-MSA into 3-methylphenol (3-MP). We exploited the substrate promiscuity of MSAS to utilize propionyl-CoA and butyryl-CoA as alternative priming units and the substrate promiscuity of 6-MSA decarboxylase to produce 3-EP and 3-PP in yeast fermentations. Increasing the formation of propionyl-CoA by expression of a bacterial propionyl-CoA synthetase, feeding of propionate and blocking propionyl-CoA degradation led to the production of up to 12.5 mg/L 3-EP. Introduction of a heterologous ‘reverse ß-oxidation’ pathway provided enough butyryl-CoA for the production of 3-PP, reaching titers of up to 2.6 mg/L. As the concentrations of 3-alkylphenols are close to the range of the concentrations deployed in tsetse fly traps, the yeast broths might become promising and inexpensive sources for attractants, producible on site by rural communities in Africa.
The crystal structure of MgCO3-II has long been discussed in the literature where DFT-based model calculations predict a pressure-induced transition of the carbon atom from the sp2 to the sp3 type of bonding. We have now determined the crystal structure of iron-bearing MgCO3-II based on single-crystal X-ray diffraction measurements using synchrotron radiation. We laser-heated a synthetic (Mg0.85Fe0.15)CO3 single crystal at 2500 K and 98 GPa and observed the formation of a monoclinic phase with composition (Mg2.53Fe0.47)C3O9 in the space group C2/m that contains tetrahedrally coordinated carbon, where CO44− tetrahedra are linked by corner-sharing oxygen atoms to form three-membered C3O96− ring anions. The crystal structure of (Mg0.85Fe0.15)CO3 (magnesium iron carbonate) at 98 GPa and 300 K is reported here as well. In comparison with previous structure-prediction calculations and powder X-ray diffraction data, our structural data provide reliable information from experiments regarding atomic positions, bond lengths, and bond angles.
A new pseudopolymorph of perchlorinated neopentasilane: the benzene monosolvate Si(SiCl3)4·C6H6
(2020)
A new pseudopolymorph of dodecachloropentasilane, namely a benzene monosolvate, Si5Cl12·C6H6, is described. There are two half molecules of each kind in the asymmetric unit. Both Si5Cl12 molecules are completed by crystallographic twofold symmetry. One of the benzene molecules is located on a twofold rotation axis with two C—H groups located on this rotation axis. The second benzene molecule has all atoms on a general position: it is disordered over two equally occupied orientations. No directional interactions beyond normal van der Waals contacts occur in the crystal.
In this report, we present the contributions, outcomes, ideas, discussions and conclusions obtained at the PaleoMaps Workshop 2019, that took place at the Institute of Geography of the University of Cologne on 23 and 24 September 2019. The twofold aim of the workshop was: (1) to provide an overview of approaches and methods that are presently used to incorporate paleoenvironmental information in human–environment interaction modeling applications, and building thereon; (2) to devise new approaches and solutions that might be used to enhance the reconstruction of past human–environmental interconnections. This report first outlines the presented papers, and then provides a joint protocol of the often extensive discussions that came up following the presentations or else during the refreshment intervals. It concludes by adressing the open points to be resolved in future research avenues, e.g., implementation of open science practices, new procedures for reviewing of publications, and future concepts for quality assurance of the often complex paleoenvironmental data. This report may serve as an overview of the state of the art in paleoenvironment mapping and modeling. It includes an extensive compilation of the basic literature, as provided by the workshop attendants, which will itself facilitate the necessary future research.
Joschua Yesni Arnaut verwebt sein künstlerisches Schaffen eng mit seinen persönlichen Erfahrungen: In "Didn’t We Deserve A Look At You The Way You Really Are?" in der Schleuse der Rüsselheimer Opelvillen stellt er das Thema Gewalt in den Mittelpunkt. Ein Gespräch über Neurosen, Privilegien und den Charme des Zufalls.
This article provides a proposal to use IMF Article VIII, Section 2 (b) to establish a binding mechanism on private creditors for a sovereign debt standstill. The proposal builds on the original idea by Whitney Deveboise (1984). Using arguments brought forward by confidential IMF staff papers (1988, 1996) and the IMF General Counsel (1988), this paper shows how an authoritative interpretation of Article VIII, Section 2 (b) can provide protection from litigation to countries at risk of debt distress.
The envisaged mechanism presents several advantages over recent proposals for a binding standstill mechanism, such as the International Developing Country Debt Authority (IDCDA) by UNCTAD and a Central Credit Facility (CFF) by the Bolton Committee. First, this approach would not require the creation of new intergovernmental mechanisms or facilities. Second, the activation of the standstill mechanism can be set in motion by any IMF member country and does not require a modification of its Articles of Agreement. Third, debtor countries acting in good faith under an IMF program would be protected from aggressive litigation strategies from holdout creditors in numerous jurisdictions, including the US and the UK. Fourth, courts in key jurisdictions would avoid becoming overburdened by a cascade of sovereign debt litigation covering creditors and debtors across the globe. Fifth, private creditors would receive uniform treatment and ensure intercreditor equality. Sixth and last, the mechanism would provide additional safeguards to protect emergency multilateral financing provided to tackle Covid-19.
Using a novel experimental design, I test how the exposure to information about a group’s relative performance causally affects the members’ level of identification and thereby their propensity to harm affiliates of comparison groups. I find that both, being informed about a high and poor relative performance of the ingroup similarly fosters identification. Stronger ingroup identification creates increased hostility against the group of comparison. In cases where participants learn about poor relative performance, there appears to be a direct level effect additionally elevating hostile discrimination. My findings shed light on a specific channel through which social media may contribute to intergroup fragmentation and polarization.
Measurements of halogenated trace gases in ambient air frequently rely on canister sampling followed by offline laboratory analysis. This allows for a large number of compounds to be analysed under stable conditions, maximizing measurement precision. However, individual compounds might be affected during the sampling and storage of canister samples. In order to assess halocarbon stability in whole-air samples from the upper troposphere and lowermost stratosphere, we performed stability tests using the high-resolution sampler (HIRES) air sampling unit, which is part of the Civil Aircraft for the Regular Investigation of the atmosphere Based on an Instrument Container (CARIBIC) instrument package. The HIRES unit holds 88 lightweight stainless-steel cylinders that are pressurized in flight to 4.5 bar using metal bellows pumps. The HIRES unit was first deployed in 2010 but has up to now not been used for regular halocarbon analysis with the exception of chloromethane analysis. The sample collection unit was tested for the sampling and storage effects of 28 halogenated compounds. The focus was on compound stability in the stainless-steel canisters during storage of up to 5 weeks and on the influence of ozone, since flights take place in the upper troposphere and lowermost stratosphere with ozone mixing ratios of up to several hundred parts per billion by volume (ppbv). Most of the investigated (hydro)chlorofluorocarbons and long-lived hydrofluorocarbons were found to be stable over a storage time of up to 5 weeks and were unaltered by ozone being present during pressurization. Some compounds such as dichloromethane, trichloromethane, and tetrachloroethene started to decrease in the canisters after a storage time of more than 2 weeks or exhibited lowered mixing ratios in samples pressurized with ozone present. A few compounds such as tetrachloromethane and tribromomethane were found to be unstable in the HIRES stainless-steel canisters independent of ozone levels. Furthermore, growth was observed during storage for some species, namely for HFC-152a, HFC-23, and Halon 1301.
Background: Myocardial perfusion with cardiovascular magnetic resonance (CMR) imaging is an established diagnostic test for evaluation of myocardial ischaemia. For quantification purposes, the 16 segment American Heart Association (AHA) model poses limitations in terms of extracting relevant information on the extent/severity of ischaemia as perfusion deficits will not always fall within an individual segment, which reduces its diagnostic value, and makes an accurate assessment of outcome data or a result comparison across various studies difficult. We hypothesised that division of the myocardial segments into epi- and endocardial layers and a further circumferential subdivision, resulting in a total of 96 segments, would improve the accuracy of detecting myocardial hypoperfusion. Higher (sub-)subsegmental recording of perfusion abnormalities, which are defined relatively to the normal reference using the subsegment with the highest value, may improve the spatial encoding of myocardial blood flow, based on a single stress perfusion acquisition. Objective: A proof of concept comparison study of subsegmentation approaches based on transmural segments (16 AHA and 48 segments) vs. subdivision into epi- and endocardial (32) subsegments vs. further circumferential subdivision into 96 (sub-)subsegments for diagnostic accuracy against invasively defined obstructive coronary artery disease (CAD). Methods: Thirty patients with obstructive CAD and 20 healthy controls underwent perfusion stress CMR imaging at 3 T during maximal adenosine vasodilation and a dual bolus injection of 0.1mmol/kg gadobutrol. Using Fermi deconvolution for blood flow estimation, (sub-)subsegmental values were expressed relative to the (sub)subsegment with the highest flow. In addition, endo−/epicardial flow ratios were calculated based on 32 and 96 (sub-)subsegments. A receiver operating characteristics (ROC) curve analysis was performed to compare the diagnostic performance of discrimination between patients with CAD and healthy controls. Observer reproducibility was assessed using Bland-Altman approaches. Results: Subdivision into more and smaller segments revealed greater accuracy for #32, #48 and # 96 compared to the standard #16 approach (area under the curve (AUC): 0.937, 0.973 and 0.993 vs 0.820, p<0.05). The #96-based endo−/epicardial ratio was superior to the #32 endo−/epicardial ratio (AUC 0.979, vs. 0.932, p<0.05). Measurements for the #16 model showed marginally better reproducibility compared to #32, #48 and #96 (mean difference± standard deviation: 2.0±3.6 vs. 2.3±4.0 vs 2.5±4.4 vs. 4.1±5.6). Conclusions: Subsegmentation of the myocardium improves diagnostic accuracy and facilitates an objective cutoff-based description of hypoperfusion, and facilitates an objective description of hypoperfusion, including the extent and severity of myocardial ischaemia. Quantification based on a single (stress-only) pass reduces the overall amount of gadolinium contrast agent required and the length of the overall diagnostic study.
Körpersymmetrie gilt unter Evolutionswissenschaftlern als Hinweis auf eine stabile Entwicklungsgeschichte von der Eizelle bis hin zum erwachsenen Lebewesen mit daraus resultierender Gesundheit. Symmetrie steht für gute Abwehrmechanismen trotz einflussnehmender Störfaktoren, die allgegenwärtig sind. Symmetrische Körper und Gesichter werden vom anderen Geschlecht bevorzugt und als attraktiver bewertet. Das Gegenstück der Symmetrie bildet die fluktuierende Asymmetrie als Abweichung von perfekter, bilateraler Symmetrie an verschiedenen Stellen des Körpers. Symmetrie kann somit als Fitnessindikator angesehen werden, also als ein Merkmal des erfolgreichen Umwerbens in der Partnerwahl. Dies geschieht typischerweise durch die Entwicklung eines Merkmals oder durch aufwändigeres Verhalten, dessen Ausbildung für ein weniger „fittes“ Individuum zu kostspielig wäre. Die Kernfragen der vorliegenden Studie waren, ob sich diese Anforderung des Fitnessindikators Symmetrie auf die verborgene Struktur des Kehlkopfes übertragen lässt und ob die Asymmetrie des Kehlkopfes mit der Attraktivität der Stimme assoziiert ist. Die fluktuierende Asymmetrie des Larynx wurde bisher noch nicht untersucht. An der Untersuchung nahmen 80 Versuchspersonen im Alter von 20 bis 70 Jahren teil. Hauptzielgrößen waren Larynxasymmetrie und Stimmattraktivität. Die Larynxasymmetrie wurde mittels Videolaryngostroboskopie und anschließender Asymmetriebewertung auf einer 7-stufigen Skala durch Experten erfasst. Die Attraktivität der Stimme wurde auf Basis eines vorgelesenen phonetischen Standardtexts durch Dritte bewertetet. Weitere Variablen waren die Gesichtsasymmetrie, die durch Vermessung von Fotografien bestimmt wurde, und die durch Dritte bewertete Gesichtsattraktivität. Mit Hilfe eines Fragebogens, der abgesehen von Alter, Geschlecht, Anzahl bisheriger Sexualpartner, Erkältungskrankheiten im vorherigen Jahr sowie eingenommener Medikamente und das Rauchverhalten die Beschwerdenliste nach Zerssen (1976) und die Kurzfassung des Voice Handicap Index (VHI-12) enthielt, wurde versucht, die Gesundheit zu registrieren. Darüber hinaus erbat der Fragebogen bei weiblichen Probanden Angaben zum Menstruationszyklus, um die Fertilität zum Messzeitpunkt zu erfassen. Der Erfassung der Körperkonstitution dienten die Messungen von Größe und Gewicht, des Körperfettanteils und der Muskelmasse sowie die Umfangsbestimmung von Hals, Schulter, Brust, Taille, Hüfte und Bizeps. Das 2D:4D-Längenverhältnis wurde mit Hilfe einer Fotokopie der palmaren Handseite als Indikator für pränatales Testosteron ermittelt. Der zentrale Zusammenhang zwischen Stimmattraktivität und Larynxasymmetrie bestätigte sich nur für Männer. Für diese bestand außerdem eine positive Relation der Stimmattraktivität mit dem Schulter-Hüft-Verhältnis und dem Verhältnis von Brust zu Taille, d. h. Stimmen von Männern mit verhältnismäßig breiter Schulter und breiter Brust wurden attraktiver bewertet. Umgekehrt galt: Je niedriger der BMI, Körperfettanteil, Halsumfang, das Alter und die Anzahl eingenommener rezeptpflichtiger Medikamente, umso höher war die Attraktivitätsbewertung ihrer Stimme. Weibliche Stimmen wurden umso attraktiver bewertet, je jünger die Frauen waren, je größer das Brust-Taille- Verhältnis, je niedriger das Taille Hüft-Verhältnis, je geringen der Halsumfang, je niedriger der Stimmstörungsindex (VHI-12) und je weniger Zigaretten sie geraucht haben. Erwartungsgemäß korrelierte die Larynxasymmetrie bei Männern signifikant negativ mit der Gesichtsattraktivität sowie beinahe signifikant mit dem Schulter-Hüft-Verhältnis. Männliche Larynges wurden außerdem asymmetrischer bewertet, je älter die Person, je höher der BMI, der Körperfettanteil, der Halsumfang und die Anzahl eingenommener Medikamente war. Für Frauen einzig (positiv) signifikant wurde der Zusammenhang zwischen Larynxasymmetrie und Nikotinabusus. Die zusätzlich erfolgten Regressionsanalysen erzielten ein signifikantes Ergebnis für den Zusammenhang zwischen der Stimmattraktivität mit der Muskelmasse für beide Geschlechter, außerdem gelang es, einen signifikanten Zusammenhang zwischen der Larynxasymmetrie und der SHR bei Männern darzustellen. Die (negativen) Korrelationen zwischen der Larynxasymmetrie für Männer mit Stimm- und Gesichtsattraktivität deuten darauf hin, dass Larynxasymmetrie als Fitnessindikator dienen kann. Darüber hinaus lieferte die vorliegende Studie keine einfach interpretierbaren Ergebisse; häufig waren sie geschlechtsspezifisch. Die Dissertation unterstrich damit die Komplexität der Zusammenhänge und wies auf den Stellenwert von Geschlechterunterschieden hin. Weiterführende Untersuchungen sind nötig, um die Ergebnisse zu bestätigen und um den Stellenwert der Larynxasymmetrie für Frauen zu klären.
Direct nanoscopic observation of plasma waves in the channel of a graphene field-effect transistor
(2020)
Plasma waves play an important role in many solid-state phenomena and devices. They also become significant in electronic device structures as the operation frequencies of these devices increase. A prominent example is field-effect transistors (FETs), that witness increased attention for application as rectifying detectors and mixers of electromagnetic waves at gigahertz and terahertz frequencies, where they exhibit very good sensitivity even high above the cut-off frequency defined by the carrier transit time. Transport theory predicts that the coupling of radiation at THz frequencies into the channel of an antenna-coupled FET leads to the development of a gated plasma wave, collectively involving the charge carriers of both the two-dimensional electron gas and the gate electrode. In this paper, we present the first direct visualization of these waves. Employing graphene FETs containing a buried gate electrode, we utilize near-field THz nanoscopy at room temperature to directly probe the envelope function of the electric field amplitude on the exposed graphene sheet and the neighboring antenna regions. Mapping of the field distribution documents that wave injection is unidirectional from the source side since the oscillating electrical potentials on the gate and drain are equalized by capacitive shunting. The plasma waves, excited at 2 THz, are overdamped, and their decay time lies in the range of 25-70 fs. Despite this short decay time, the decay length is rather long, i.e., 0.3-0.5 μm, because of the rather large propagation speed of the plasma waves, which is found to lie in the range of 3.5-7 × 106 m/s, in good agreement with theory. The propagation speed depends only weakly on the gate voltage swing and is consistent with the theoretically predicted 1/4 power law.
A strong decline and thinning of the Arctic sea-ice cover over the past five decades has been documented. The former multiyear sea-ice system has largely changed to an annual system and with it the dynamics of sea-ice transport across the Arctic Ocean. Less sea ice is reaching the Fram Strait and more ice and ice-transported material is released in the northern Laptev Sea and the central Arctic Ocean. This trend is expected to have a decisive impact on ice associated (“sympagic”) communities. As sympagic fauna plays an important role in transmitting carbon from the ice-water interface to the pelagic and benthic food webs, it is important to monitor its community composition under the changing environmental conditions. We investigated the taxonomic composition, abundance and distribution of sea-ice meiofauna (here heterotrophs >10 μm; eight stations) and under-ice fauna (here metazoans >300 μm; fourteen stations) in Arctic 1.5 year-old pack ice north of Svalbard. Sampling was conducted during spring 2015 by sea-ice coring and trawling with a Surface and Under-Ice Trawl. We identified 42 taxa associated with the sea ice. The total abundance of sea-ice meiofauna ranged between 580 and 17,156 ind.m–2 and was dominated by Ciliophora (46%), Copepoda nauplii (29%), and Harpacticoida (20%). In contrast to earlier studies in this region, we found no Nematoda and few flatworms in our sea-ice samples. Under-ice fauna abundance ranged between 15 and 6,785 ind.m–2 and was dominated by Appendicularia (58%), caused by exceptionally high abundance at one station. Copepoda nauplii (23%), Calanus finmarchicus (9%), and Calanus glacialis (6%) were also very abundant while sympagic Amphipoda were comparatively rare (0.35%). Both sympagic communities showed regional differences in community composition and abundance between shelf and offshore stations, but only for the under-ice fauna those differences were statistically significant. Selected environmental variables moderately explained variations in abundances of both faunas. The results of this study are consistent with predictions of diversity shifts in the new Arctic.
Limb stump pain after amputation, due to sensitized neuromas, is a common condition that can cause a great deal of suffering in affected patients. Treatment is difficult, requiring a multidisciplinary approach that is often unsatisfactory. One treatment used to mitigate pain is electrical stimulation (EStim), administered using several different therapeutic approaches. The research described in this dissertation sought to characterize changes in peripheral nerve morphology, and neuroma formation, following limb amputation, with an eye toward developing better treatment strategies, that intervene before neuromas are fully formed. Another focus of this study was to evaluate the effect EStim has on changes in peripheral nerve morphology, and neuroma formation, following limb amputation.
Right forelimbs of 42 male Sprague Dawley rats were amputated. At 3, 7, 28, 60 and 90 days post amputation (DPA) 6 limb stumps, in each group, were harvested and changes in peripheral nerve morphology, and neuroma formation were measured. In addition, limb stumps of 6 EStim treated, 6 sham-treated (deactivated EStim devices), and 6 non-treated rats were harvested at 28 DPA.
Analysis revealed six distinct morphological characteristics of peripheral nerves during nerve regrowth and neuroma development; 1) normal nerve, 2) degenerating axons, 3) axonal sprouts, 4) unorganized bundles of axons in connective tissue, 5) unorganized axon growth into muscles, and 6) unorganized axon growth into fibrotic tissue (neuroma). At the early stages (3 & 7 DPA), normal nerves could be identified throughout the limb stump tissues and small areas of axonal sprouts were present near the distal tip of the stumps. Signs of degenerating axons were evident from 7 to 90 DPA. From day 28 on, variability of nerve characteristics, with signs of unorganized axon growth into muscle and fibrotic tissue, and neuroma formation, became visible in multiple areas of stump tissue. These pathological features became more evident at 60 and 90 DPA. EStim treated stumps revealed neuroma formation in 1 out of 6 animals, whereas in sham and controls, neuroma formation was seen in 4 out of 6 stumps respectively.
We were able to identify 6 separate histological stages of peripheral nerve regrowth and neuroma formation over 90 days following amputation. Axonal regrowth was observed as early as 3 DPA, and signs of unorganized axonal growth and neuroma formation were evident by 28 DPA. Our observations suggest that EStim-based treatment and/or other prevention strategies might be more effective if administered in the initial dynamic stages of neuroma development.