Tuning the molecular order of C60-based self-assembled monolayers in field-effect transistors

The control of order in organic semiconductor systems is crucial to achieve desired properties in electronic devices. We have studied the order in fullerene functionalized self-assembled monolayers by mixing the active molecules with supporting alkyl phosphonic acids of different chain length. By adjusting the length of the molecules, structural modifications of the alignment of the C60 head groups within the SAM can be tuned in a controlled way. These changes on the sub-nanometre scale were analysed by grazing incidence X-ray diffraction and X-ray reflectivity. To study the electron transport properties across these layers, self-assembled monolayer field-effect transistors (SAMFETs) were fabricated containing only the single fullerene monolayer as semiconductor. Electrical measurements revealed that a high 2D crystalline order is not the only important aspect. If the fullerene head groups are too confined by the supporting alkyl phosphonic acid molecules, defects in the crystalline C60 film, such as grain boundaries, start to strongly limit the charge transport properties. By close interpretation of the results of structural investigations and correlating them to the results of electrical characterization, an optimum chain length of the supporting alkyl phosphonic acids in the range of C10 was determined. With this study we show that minor changes in the order on the sub-nanometre scale, can strongly influence electronic properties of functional self-assembled monolayers

Stratifying patients with peripheral neuropathic pain based on sensory profiles : algorithm and sample size recommendations

In a recent cluster analysis, it has been shown that patients with peripheral neuropathic pain can be grouped into 3 sensory phenotypes based on quantitative sensory testing profiles, which are mainly characterized by either sensory loss, intact sensory function and mild thermal hyperalgesia and/or allodynia, or loss of thermal detection and mild mechanical hyperalgesia and/or allodynia. Here, we present an algorithm for allocation of individual patients to these subgroups. The algorithm is nondeterministic-ie, a patient can be sorted to more than one phenotype-and can separate patients with neuropathic pain from healthy subjects (sensitivity: 78%, specificity: 94%). We evaluated the frequency of each phenotype in a population of patients with painful diabetic polyneuropathy (n = 151), painful peripheral nerve injury (n = 335), and postherpetic neuralgia (n = 97) and propose sample sizes of study populations that need to be screened to reach a subpopulation large enough to conduct a phenotype-stratified study. The most common phenotype in diabetic polyneuropathy was sensory loss (83%), followed by mechanical hyperalgesia (75%) and thermal hyperalgesia (34%, note that percentages are overlapping and not additive). In peripheral nerve injury, frequencies were 37%, 59%, and 50%, and in postherpetic neuralgia, frequencies were 31%, 63%, and 46%. For parallel study design, either the estimated effect size of the treatment needs to be high (> 0.7) or only phenotypes that are frequent in the clinical entity under study can realistically be performed. For crossover design, populations under 200 patients screened are sufficient for all phenotypes and clinical entities with a minimum estimated treatment effect size of 0.5.Peer reviewe

Transient Receptor Potential Channel Polymorphisms Are Associated with the Somatosensory Function in Neuropathic Pain Patients

Transient receptor potential channels are important mediators of thermal and mechanical stimuli and play an important role in neuropathic pain. The contribution of hereditary variants in the genes of transient receptor potential channels to neuropathic pain is unknown. We investigated the frequency of transient receptor potential ankyrin 1, transient receptor potential melastin 8 and transient receptor potential vanilloid 1 single nucleotide polymorphisms and their impact on somatosensory abnormalities in neuropathic pain patients. Within the German Research Network on Neuropathic Pain (Deutscher Forscbungsverbund Neuropathischer Schmerz) 371 neuropathic pain patients were phenotypically characterized using standardized quantitative sensory testing. Pyrosequencing was employed to determine a total of eleven single nucleotide polymorphisms in transient receptor potential channel genes of the neuropathic pain patients and a cohort of 253 German healthy volunteers. Associations of quantitative sensory testing parameters and single nucleotide polymorphisms between and within groups and subgroups, based on sensory phenotypes, were analyzed. Single nucleotide polymorphisms frequencies did not differ between both the cohorts. However, in neuropathic pain patients transient receptor potential ankyrin 1 710G>A (rs920829, E179K) was associated with the presence of paradoxical heat sensation (p = 0.03), and transient receptor potential vanilloid 1 1911A>G (rs8065080, I585V) with cold hypoalgesia (p = 0.0035). Two main subgroups characterized by preserved (1) and impaired (2) sensory function were identified. In subgroup 1 transient receptor potential vanilloid 1 1911A>G led to significantly less heat hyperalgesia, pinprick hyperalgesia and mechanical hypaesthesia (p = 0.006, p = 0.005 and p<0.001) and transient receptor potential vanilloid 1 1103C>G (rs222747, M315I) to cold hypaesthesia (p = 0.002), but there was absence of associations in subgroup 2. In this study we found no evidence that genetic variants of transient receptor potential channels are involved in the expression of neuropathic pain, but transient receptor potential channel polymorphisms contributed significantly to the somatosensory abnormalities of neuropathic pain patients

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

A flexible high speed pulse chopper system for an inverted neutron time-of-flight option on backscattering spectrometers

We present the design and simulation of a high resolution inverted time-of-flight option for a neutron spectrometer with crystal analysers in backscattering, with specific reference to the IN16B spectrometer at the Institut Laue-Langevin, Grenoble. While the conventional configuration with Si 111 crystals provides sub-μeV resolution in an energy range limited to ±30 μeV, the novel BATS option (BATS: Backscattering and Time-of-flight Spectrometer) extends the energy window to 340 μeV with only a slightly increased resolution of 1.2 μeV. Moreover, the observation window can be shifted to inelastic energy transfers. To bring this about, a novel fast chopper system with disks of large diameter and complex slit pattern is used, offering high flexibility in resolution and repetition rate. The chopper system consists out of two counter rotating disk chopper pairs. It provides 7 different pulse lengths, three pulse repetition rates up to 237 Hz and can operate with Si 111 or Si 311 crystal analysers. The latter option is a unique feature which covers a Q-range up to 3.7 Å−1 with a resolution of 6.8 μeV. Extensive ray-tracing simulations have been used to validate the design of the pulse chopper system, set limits on the sample size, and assess the achievable energy resolutions of the different chopper configurations

Dose-Dependent Pain and Pain Radiation after Chemical Stimulation of the Thoracolumbar Fascia and Multifidus Muscle: A Single-Blinded, Cross-Over Study Revealing a Higher Impact of Fascia Stimulation

Acute low back pain can be experimentally induced by injections of hypertonic saline into deep tissues of the back, such as fascia and muscle. The current study investigated the dose-dependency of peak-pain and spatial extent of concomitant radiating pain following 50, 200 and 800 &mu;L bolus injections of hypertonic saline (5.8%) into the thoracolumbar fascia and multifidus muscle, since data on dose-dependency is lacking in humans. Sixteen healthy subjects rated (11 female, 5 male; 23.3 &plusmn; 3.1 years, mean &plusmn; SD) intensity and spatial extent of pain. Injections into the fascia resulted in significantly higher peak-pain (+86%, p &lt; 0.001), longer pain durations (p &lt; 0.05), and larger pain areas (+65%, p &lt; 0.02) and were less variable than intramuscular injections. Peak-pain ratings and pain areas were 2&ndash;3-fold higher/larger for 200 &mu;L vs. 50 &mu;L. In contrast, peak pain increased only marginally at 800 &mu;L by additional 20%, while pain areas did not increase further at all in both, fascia and muscle. Thus, higher injection volumes did also not compensate the lower sensitivity of muscle. Peak-pain ratings and pain areas correlated between fascia and muscle (r = 0.530, p &lt; 0.001 and r = 0.337, p &lt; 0.02, respectively). Peak-pain ratings and pain areas correlated overall (r = 0.490, p &lt; 0.0001), but a weak correlation remained when the impact of between-tissue differences and different injection volumes were singled out (partial r = 0.261, p &lt; 0.01). This study shows dose-dependent pain responses of deep tissues where an injection volume of 200 &mu;L of hypertonic saline is deemed an adequate stimulus for tissue differentiation. We suggest that pain radiation is not simply an effect of increased peripheral input but may afford an individual disposition for the pain radiation response. Substantially higher pain-sensitivity and wider pain areas support fascia as an important contributor to non-specific low back pain

Epidemiology of Bradykinin-mediated angioedema: a systematic investigation of epidemiological studies

Abstract Background Bradykinin-mediated angioedema (Bk-AE) can be life-threatening and requires specific targeted therapies. Knowledge of its epidemiology may help optimize its management. Methods We systematically searched the medical literature to identify abstracts of interest indexed between 1948 and March, 2016. We used published national survey data on the proportion of the population treated with angiotensin-converting enzyme inhibitors (ACEI) to derive estimates of the population prevalence of ACEI-AE in the USA, Germany and France. For hereditary angioedema (C1-INH-HAE) and C1-inhibitor related acquired angioedema (C1-INH-AAE), publications had to contain original epidemiologic data collection within a defined geographical area. Hereditary angioedema with normal C1-INH was not included in the analysis due to lack of clearly defined criteria. Results We identified 4 relevant publications on the prevalence of ACEI-AE, 6 on the prevalence of C1-INH-HAE, and 1 on the prevalence of C1-INH-AAE. The 1st year cumulative incidence of ACEI-AE was estimated to vary between 0.12 (population-based analyses) and 0.30 (meta-analyses of clinical trials) per 100 patient-years. The population prevalence of ACEI-AE was modeled to vary between 7 and 26 in 100,000. The prevalence of C1-INH-HAE was estimated to vary between 1.1 and 1.6 per 100,000. The prevalence of C1-INH-AAE was estimated to be 0.15 per 100,000 in one epidemiological investigation of AAE in Denmark. Conclusions Epidemiological evidence on Bk-AE is limited to North America and Europe. ACEI-AE is more common than C1-INH-HAE (~ 10:1), which is more common than C1-INH-AAE (~ 10:1). More studies are needed to comprehensively assess the epidemiological burden of Bk-AE

Tuning the molecular order of C60-based self-assembled monolayers in field-effect transistors

The control of order in organic semiconductor systems is crucial to achieve desired properties in electronic devices. We have studied the order in fullerene functionalized self-assembled monolayers by mixing the active molecules with supporting alkyl phosphonic acids of different chain length. By adjusting the length of the molecules, structural modifications of the alignment of the C60 head groups within the SAM can be tuned in a controlled way. These changes on the sub-nanometre scale were analysed by grazing incidence X-ray diffraction and X-ray reflectivity. To study the electron transport properties across these layers, self-assembled monolayer field-effect transistors (SAMFETs) were fabricated containing only the single fullerene monolayer as semiconductor. Electrical measurements revealed that a high 2D crystalline order is not the only important aspect. If the fullerene head groups are too confined by the supporting alkyl phosphonic acid molecules, defects in the crystalline C60 film, such as grain boundaries, start to strongly limit the charge transport properties. By close interpretation of the results of structural investigations and correlating them to the results of electrical characterization, an optimum chain length of the supporting alkyl phosphonic acids in the range of C10 was determined. With this study we show that minor changes in the order on the sub-nanometre scale, can strongly influence electronic properties of functional self-assembled monolayers