The topic of two-dimensional topological insulators has blossomed after the first observation of the quantum spin Hall (QSH) effect in HgTe quantum wells. However, studies have been hindered by the ...relative fragility of the edge states. Their stability has been a subject of both theoretical and experimental investigation in the past decade. Here, we present a new generation of high quality (Cd,Hg)Te/HgTe-structures based on a new chemical etching method. From magnetotransport measurements on macro- and microscopic Hall bars, we extract electron mobilities μ up to about 400 × 103 cm2/(V s), and the mean free path λmfp becomes comparable to the sample dimensions. The Hall bars show quantized spin Hall conductance, which is remarkably stable up to 15 K. The clean and robust edge states allow us to fabricate high quality side-contacted Josephson junctions, which are significant in the context of topological superconductivity. Our results open up new avenues for fundamental research on QSH effect as well as potential applications in spintronics and topological quantum computation.
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IJS, KILJ, NUK, PNG, UL, UM
Hyperglycaemia is frequent in acute ischemic stroke and denotes a bad prognosis, even in the absence of pre-existing diabetes. However, in clinical trials treatment of elevated glucose levels with ...insulin did not improve stroke outcome, suggesting that collateral effects rather than hyperglycaemia itself aggravate ischemic brain damage. As reactive glucose metabolites, glyoxal and methylglyoxal are candidates for mediating the deleterious effects of hyperglycaemia in acute stroke.
In 135 patients with acute stroke, we used liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) to measure glyoxal, methylglyoxal and several of their glycated amino acid derivatives in serum. Results were verified in a second cohort of 61 stroke patients. The association of serum concentrations with standard stroke outcome scales (NIHSS, mRS) was tested.
Glucose, glyoxal, methylglyoxal, and the glyoxal-derived glycated amino acid N
-(5-hydro-4-imidazolon-2-yl)ornithine (G-H1) were positively correlated with a bad stroke outcome at 3 months as measured by mRS90, at least in one of the two cohorts. However, the glycated amino acids N
-carboxyethyllysine (CEL) and in one cohort pyrraline showed an inverse correlation with stroke outcome probably reflecting lower food intake in severe stroke. Patients with a poor outcome had higher serum concentrations of glyoxal and methylglyoxal.
The glucose-derived α-dicarbonyl glyoxal and glycated amino acids arising from a reaction with glyoxal are associated with a poor outcome in ischemic stroke. Thus, lowering α-dicarbonyls or counteracting their action could be a therapeutic strategy for hyperglycaemic stroke.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Expression of Bcr-Abl in hematopoietic stem cells is sufficient to cause chronic myeloid leukemia (CML) and tyrosine kinase inhibitors (TKI) induce molecular remission in the majority of CML ...patients. However, the disease driving stem cell population is not fully targeted by TKI therapy, and leukemic stem cells (LSC) capable of re-inducing the disease can persist. Single-cell RNA-sequencing technology recently identified an enriched inflammatory gene signature with TNFα and TGFβ being activated in TKI persisting quiescent LSC. Here, we studied the effects of human TNFα antibody infliximab (IFX), which has been shown to induce anti-inflammatory effects in mice, combined with TKI treatment on LSC function.
We first performed GSEA-pathway analysis using our microarray data of murine LSK cells (lin
; Sca-1
; c-kit
) from the SCLtTA/Bcr-Abl CML transgenic mouse model. Bcr-Abl positive cell lines were generated by retroviral transduction. Clonogenic potential was assessed by CFU (colony forming unit). CML mice were treated with nilotinib or nilotinib plus infliximab, and serial transplantation experiments were performed.
Likewise to human CML, TNFα signaling was specifically active in murine CML stem cells, and ectopic expression of Bcr-Abl in murine and human progenitor cell lines induced TNFα expression. In vitro exposure to human (IFX) or murine (MP6-XT22) TNFα antibody reduced clonogenic growth of CML cells. Interestingly, TNFα antibody treatment enhanced TKI-induced effects on immature cells in vitro. Additionally, in transplant and serial transplant experiments, using our transgenic CML mouse model, we could subsequently show that IFX therapy boosted TKI-induced effects and further reduced the proportion of malignant stem cells in vivo.
TNFα signaling is induced in CML stem cells, and anti-inflammatory therapy enhances TKI-induced decline of LSC, confirming that successful targeting of persisting CML stem cells can be enhanced by addressing their malignant microenvironment simultaneously.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
As the most commonly used illicit substance, cannabis is gaining global acceptance through increasing legalization efforts. This shift intensifies the need for research to guide ...policymakers and healthcare providers in harm reduction and treatment strategies. Nonetheless, the relationship between psychopathological symptoms and cannabis use remains inadequately understood.
Methods
A sample of regular cannabis consumers completed self-reported assessments for depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), Attention-Deficit/Hyperactivity Disorder (ADHD; Adult ADHD Self-Report Scale V1.1), and psychosis (Early Recognition Inventory based on IRAOS) as well as previous black-market cannabis use patterns. Cannabis Use Disorder Identification Test Revised (CUDIT-R) was used to identify cannabis use disorder (CUD). To understand psychopathological symptom load related to cannabis consumption as well as cannabis use motives, multiple regression models were performed to identify psychopathological variables predicting cannabis use frequency and quantity. Linear regression and correlation analyses were conducted, adjusting for relevant covariates (age, gender, education, alcohol, other substance use).
Results
Three-hundred-sixty regular cannabis users interested in a study on regulated cannabis access in Basel, Switzerland were examined. In bivariate analysis, cannabis use frequency correlated with depressive (
r
(358) = 0.16,
p
= 0.003) and anxiety symptom load (
r
(358) = 0.11,
p
= 0.034). Cannabis quantity correlated with depressive (
r
(358) = 0.15,
p
= 0.005), ADHD (
r
(358) = 0.14,
p
= 0.008), and psychosis symptom load (
r
(358) = 0.16,
p
= 0.002). However, in the adjusted regression models only depressive and ADHD symptom loads were significantly associated with cannabis use frequency (
p
= 0.006 and
p
= 0.034, respectively) and quantity (
p
= 0.037 and
p
= 0.019, respectively). No significant correlations between cannabis consumption and anxiety or psychosis remained after adjustment.
Conclusion
ADHD and depressive symptoms correlate with increased cannabis use in a cohort of regular users, suggesting potential self-medication in nonclinical populations. With the rising availability of cannabis worldwide, these results highlight the necessity for longitudinal studies to disentangle the complex dynamics between cannabis consumption and mental health symptoms.
Surprisingly few studies deal with the implications of large events for hotel prices. We address this issue by modeling hotel prices in Munich under the influence of the Oktoberfest. By utilizing ...internet data from a metasearch provider for check-in dates prior to and during the Oktoberfest 2012, it is analyzed how the event affected the daily price level as well as price differentials between hotels. In general, average hotel prices are very volatile over time. Apparently, Munich hotels tend to set prices according to expected demand and vary those depending on the day of the week during the event. Ceteris paribus, roomrates are highest on Oktoberfest Friday and Saturday nights, followed by Oktoberfest weekdays and Oktoberfest Sunday nights, but there is a general and strong price-raising impact. Prices differ across hotels mainly due to the star category attributed to a hotel and the proximity to the event. Both price premia are time-dependent.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Existing experimental evidence suggests that PPARgamma may play a beneficial role in neuroprotection from various brain pathologies. Here we found that focal cerebral ischemia induced by middle ...cerebral/common carotid arteries occlusion (MCA/CCAo) induced up-regulation of PPARgamma messenger RNA in the ischemic hemisphere as early as 6 h after the ischemic event. The increased PPARgamma mRNA expression was primarily associated with neurons in the ischemic penumbra, suggesting an important role for PPARgamma in neurons after ischemia. Intraventricular injection of 15d-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), a proposed endogenous PPARgamma agonist, into the ischemic rat brains significantly increased the PPARgamma-DNA-binding activity and reduced infarction volume at 24 h after reperfusion. We propose that PPARgamma up-regulation in response to ischemia may contribute to PPARgamma activation in the presence of PPARgamma agonists. Activation of PPARgamma in neurons at an early stage after ischemia may represent a pro-survival mechanism against ischemic injury.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Although the function of fever is still unclear, it is now beyond doubt that body temperature influences the outcome of brain damage. An elevated body temperature is often found in stroke patients ...and denotes a bad prognosis. However, the pathophysiologic basis and treatment options of elevated body temperature after stroke are still unknown. Cerebral ischemia rapidly induced neuronal interleukin-6 (IL-6) expression in mice. In IL-6–deficient mice, body temperature was markedly decreased after middle cerebral artery occlusion (MCAO), but infarct size was comparable to that in control mice. If body temperature was controlled by external warming after MCAO, IL-6–deficient mice had a reduced survival, worse neurologic status, and larger infarcts than control animals. In cell culture, IL-6 exerted an antiapoptotic and neuroprotective effect. These data suggest that IL-6 is a key regulator of body temperature and an endogenous neuroprotectant in cerebral ischemia. Neuroprotective properties apparently compensate for its pyretic action after MCAO and enhance the safety of this endogenous pyrogen.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Tumor Suppressor Analysis in CML Herrmann, Oliver; Schemionek, Mirle
Methods in molecular biology (Clifton, N.J.),
01/2016, Volume:
1465
Journal Article
Retroviral models have tremendously contributed to our understanding of CML development and have been indispensable for preclinical drug testing which facilitated the implementation of a targeted ...therapy. The retroviral insertion of Bcr-Abl into mice that are genetically depleted for a potential tumor suppressor is a tool to test for a specific gene function in Bcr-Abl disease. Here we describe how to generate a Bcr-Abl retrovirus that is subsequently used for infection of primary murine BM cells, which are genetically depleted for a potential tumor suppressor gene. We will suggest control experiments and outline further methods that are required to allow for assessment of disease development upon tumor suppressor knockout in CML.
A prospect-theory model of voter turnout Herrmann, Oliver; Jong-A-Pin, Richard; Schoonbeek, Lambert
Journal of economic behavior & organization,
12/2019, Volume:
168
Journal Article
Peer reviewed
Open access
We incorporate prospect-theory preferences in a game-theoretic model to study voter turnout. We show that voter turnout is heavily affected by agents having subjective reference points with respect ...to the vote or abstain decision and their subjective probability weighting in the decision-making process. Using empirically based parameter values, we show that our model has lower prediction error than other game-theoretic models with standard expected-utility preferences. We also find that our model maintains desirable comparative statics effects and leads to higher turnout predictions in larger electorates.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Partial or total avoidance of weight-bearing by a lower limb is regularly needed after trauma and surgery. There are approximately 200 such cases per 100 000 persons per year. Forearm crutches have ...mainly been used in Germany until now to keep these patients mobile. For those who lack the strength or coordination needed to use crutches, a wheelchair may become necessary, or they might find themselves forced to continue weight-bearing on the affected limb, with possible impending adverse consequences and complications.BACKGROUNDPartial or total avoidance of weight-bearing by a lower limb is regularly needed after trauma and surgery. There are approximately 200 such cases per 100 000 persons per year. Forearm crutches have mainly been used in Germany until now to keep these patients mobile. For those who lack the strength or coordination needed to use crutches, a wheelchair may become necessary, or they might find themselves forced to continue weight-bearing on the affected limb, with possible impending adverse consequences and complications.The supplementary use of a new type of orthopedic scooter by patients who must avoid weight-bearing by a lower limb, wholly or in part, was studied in a multicenter randomized controlled trial involving 88 subjects. The endpoints were improvement in quality of life (EQ5D, SF36) and improved abilities in everyday life (retrospective registration: DRKS00032980).METHODSThe supplementary use of a new type of orthopedic scooter by patients who must avoid weight-bearing by a lower limb, wholly or in part, was studied in a multicenter randomized controlled trial involving 88 subjects. The endpoints were improvement in quality of life (EQ5D, SF36) and improved abilities in everyday life (retrospective registration: DRKS00032980).Patients who used orthopedic knee scooters (KS) reported a better overall state of health more frequently than those who used forearm crutches (UC) (SF-36 score: 67 KS group, 95% CI 61; 73; 59 UC group, 53; 64). They also reported less anxiety and depressed mood, greater mobility, and more independence than the patients who used crutches. In addition, they more frequently reported being able to transport themselves 4 x 500 meters in less than 20 minutes (n = 30 KS, 63.8% 48.5; 77.3; n = 6 UC, 14.6% 5.6, 29.2).RESULTSPatients who used orthopedic knee scooters (KS) reported a better overall state of health more frequently than those who used forearm crutches (UC) (SF-36 score: 67 KS group, 95% CI 61; 73; 59 UC group, 53; 64). They also reported less anxiety and depressed mood, greater mobility, and more independence than the patients who used crutches. In addition, they more frequently reported being able to transport themselves 4 x 500 meters in less than 20 minutes (n = 30 KS, 63.8% 48.5; 77.3; n = 6 UC, 14.6% 5.6, 29.2).The supplementary use of an orthopedic knee scooter can improve these patients' mobility and independence and prolong the distance over which they can transport themselves. For many patients, this form of treatment may well shorten the time of their total or partial inability to work and thus lower the socioeconomic costs of lower limb injuries and surgery.CONCLUSIONThe supplementary use of an orthopedic knee scooter can improve these patients' mobility and independence and prolong the distance over which they can transport themselves. For many patients, this form of treatment may well shorten the time of their total or partial inability to work and thus lower the socioeconomic costs of lower limb injuries and surgery.
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