The nucleophilic iron complex Bu4NFe(CO)3(NO) (TBAFe) catalyzes the direct intramolecular C−H amination of α‐azidobiaryls and (azidoaryl)alkenes into the corresponding carbazoles and indoles, ...respectively, under mild conditions and with low catalyst loadings. These features and the broad functional‐group tolerance render this method a particularly attractive alternative to established noble‐metal‐based procedures.
The nucleophilic iron complex Bu4NFe(CO)3(NO) (TBAFe) catalyzes the selective intramolecular aryl/vinyl C(sp2)−H amination of aryl azides to give either substituted carbazole or indole derivatives in good to excellent yields. Kinetic isotope effects reveal a mechanistic similarity to the non‐catalyzed thermal and rhodium‐catalyzed variants.
The nucleophilic iron complex Bu4NFe(CO)3(NO) (TBAFe) catalyzes the direct intramolecular amination of unactivated C(sp3)−H bonds in alkylaryl azides, which results in the formation of substituted ...indoline and tetrahydroquinoline derivatives.
What a surprise: The anionic iron complex Bu4NFe(CO)3(NO) catalyzes the denitrogenative C(sp3)−H amination of a variety of alkylaryl azides to the corresponding indolines and, unexpectedly, tetrahydroquinolines in good yields.
Background:
Genetics of the adult autoimmune polyglandular syndrome (APS) is poorly understood.
Aim:
The aim of this study was to gain further insight into the genetics of the adult APS types.
Site:
...The study was conducted at a university referral center.
Methods:
The human leukocyte antigen (HLA) class II alleles, haplotypes, and genotypes were determined in a large cohort of patients with APS, autoimmune thyroid disease (AITD), and type 1 diabetes and in healthy controls by the consistent application of high-resolution typing at a four-digit level.
Results:
Comparison of the allele and haplotype frequencies significantly discriminated patients with APS vs AITD and controls. The HLA class II alleles DRB1*03:01 *04:01, DQA1*03:01, *05:01, DQB1*02:01, and *03:02 were observed more frequently (P < .001) in APS than in AITD and controls, whereas the alleles DRB1*15:01, DQB1*03:01, and *06:02 were underrepresented in APS vs AITD (Pc < .001) and controls (Pc < .01), respectively. The DRB1*03:01-DQA1*05:01-DQB1*02:01 (DR3-DQ2) and DRB1*04:01-DQA1*03:01:DQB1*03:02 (DRB1*04:01-DQ8) haplotypes were overrepresented in APS (Pc < .001). Combination of both haplotypes to a genotype was highly prevalent in APS vs AITD and controls (Pc < .001). Dividing the APS collective into those with Addison's disease (APS type II) and those without Addison's disease but including type 1 diabetes and AITD (APS type III) demonstrated DR3-DQ2/DRB1*04:01-DQ8 as a susceptibility genotype in APS III (Pc < .001), whereas the DR3-DQ2/DRB1*04:04-DQ8 genotype correlated with APS II (Pc < .001). The haplotypes DRB1*11:01-DQA1*05:05-DQB1*03:01 and DRB1*15:01-DQA1*01:02-DQB1*06:02 are protective in APS III but not in type II (Pc < .01).
Conclusions:
HLA class II haplotypes differentiate between the adult APS types II and III. Susceptible haplotypes favor the development of polyglandular autoimmunity in patients with AITD.
Integrated optoelectronic microprobes Rudmann, L; Alt, MT; Ashouri Vajari, D ...
Current opinion in neurobiology,
June 2018, 2018-06-00, 20180601, Volume:
50
Journal Article
Peer reviewed
•Miniaturization technologies enable multichannel optoelectronic neural probes.•No external laser is needed when light sources are directly integrated on the probes.•Connectors to recording equipment ...still limit further miniaturization.•Wireless systems with integrated multiplexers and amplifiers can replace connectors.•Longevity of probes is mandatory for chronic implantation.
Optogenetics opened not only new exciting opportunities to interrogate the nervous system but also requires adequate probes to facilitate these wishes. Therefore, a multidisciplinary effort is essential to match these technical opportunities with biological needs in order to establish a stable and functional material-tissue interface. This in turn can address an optical intervention of the genetically modified, light sensitive cells in the nervous system and recording of electrical signals from single cells and neuronal networks that result in behavioral changes. In this review, we present the state of the art of optoelectronic probes and assess advantages and challenges of the different design approaches. At first, we discuss mechanisms and processes at the material-tissue interface that influence the performance of optoelectronic probes in acute and chronic implantations. We classify optoelectronic probes by their property of delivering light to the tissue: by waveguides or by integrated light sources at the sites of intervention. Both approaches are discussed with respect to size, spatial resolution, opportunity to integrate electrodes for electrical recording and potential interactions with the target tissue. At last, we assess translational aspects of the state of the art. Long-term stability of probes and the opportunity to integrate them into fully implantable, wireless systems are a prerequisite for chronic applications and a transfer from fundamental neuroscientific studies into treatment options for diseases and clinical trials.
The Nordic Hamstring Exercise (NHE) is effective for selective hamstring strengthening to improve muscle balance between knee flexors and extensors. The purpose of this study (within subject design ...of repeated measures) was to determine the effects of a standardized 4‐week NHE training on thigh strength and muscle balance with concomitant kinetic and kinematic monitoring. Sixteen male sprinters (22 years, 181 cm, 76 kg) performed a standardized 4‐week NHE training consisting of three sessions per week (each 3×3 repetitions). Six rope‐assisted and six unassisted sessions were performed targeting at a constant knee extension angular velocity of ~15°/s across a ~90‐100° knee joint range of motion. Kinetic (peak and mean moment, impulse) and kinematic parameters (eg, ROM to downward acceleration, ROMDWA) were recorded during selected sessions. Unilateral isokinetic tests of concentric and eccentric knee flexors and extensors quantified muscle group‐, contraction mode‐, and velocity‐specific training adaptations. Peak moments and contractional work demonstrated strong interactions of time with muscle group, contraction modes, and angular velocities (η²>.150). NHE training increased eccentric hamstring strength by 6%‐14% as well as thigh muscle balance with biggest adaptations at 150°/s 2 weeks after NHE training. Throughout the training period significant increases (P<.001) of peak (η²=.828) and mean moments (η²=.611) became apparent, whereas the impulse and the ROMDWA of unassisted NHE repetitions remained unchanged (P>.05). A 4‐week NHE training significantly strengthened the hamstrings and improved muscle balance between knee flexors and extensors. Despite the slow training velocity, biggest adaptations emerged at the highest velocity 2 weeks after training ended.
Background and Objectives
Bacterial contamination represents the major infectious hazard associated with transfusion of platelet concentrates (PCs). As bacterial screening of PCs is not mandatory in ...Germany, the BactiFlow flow cytometry test has been introduced as a rapid detection method to increase product safety.
Materials and Methods
During a period of 25 months, a total of 34 631 PCs (26 411 pooled and 8220 apheresis‐derived PCs) were tested at the end of day 3 of their shelf life using the BactiFlow system. PCs initially reactive in BactiFlow testing and expired PCs not reactive in BactiFlow on day 3 were also investigated by the BacT/ALERT system and by microbiological cultivation in order to identify the contaminating bacterial species and to confirm reactive BactiFlow results.
Results
Two hundred and twenty‐eight PCs (0·7%) had an initially reactive result, 24 of them remained reactive in a second test run. Out of these reproducible reactive BactiFlow results, 12 could not be verified by parallel BacT/ALERT culturing, resulting in a confirmed false‐positive rate of 0·03%. The bacterial species were identified as S. aureus, S. epidermidis, S. dysgalactiae ssp. equisimilis and B. cereus. In 10 out of 9017 expired PCs (0·11%), a confirmed‐positive result was obtained in the BacT/ALERT system which had a negative result in the BactiFlow system.
Conclusion
Testing of PCs by BactiFlow was successfully implemented in our blood donation service and proved sufficient as a rapid and reliable screening method. False reactive results are in an acceptable range since the transfusion of 12 bacterially contaminated PCs was prevented.
Background
A 100% apheresis platelet supply is considered to increase transfusion safety by lowering donor exposures for transfusion recipients. We performed a risk benefit analysis to contrast the ...reduction of donor exposures and the risk of contaminated blood products in the nation‐wide inventory with the donor risks associated with a switch to a 100% apheresis platelet supply in Germany.
Methods
Donor exposures and the number of contaminated blood products resulting from HIV‐like, HBV‐like, HCV‐like pathogens and two theoretical agents with infection rates of 10 and 1000 in 100 000, respectively, were calculated for a 100% apheresis platelet supply in Germany based on the 2006–2012 hemovigilance reports. These numbers were compared with the current mixed platelet supply of pooled and apheresis platelets. Moreover, additional donation time and apheresis donor complications resulting from a 100% apheresis platelet supply were estimated.
Results
Per million total blood products (red cells, platelets, fresh frozen plasma), a 100% apheresis platelet supply would reduce donor exposures by 87 100 and the number of contaminated blood products ranging from 0·8 to 871·1. On the other hand, this requires additional 29 478 apheresis donations, 3·4 years additional donor time, and would be associated with 58 additional donor complications, respectively.
Conclusions
A 100% apheresis platelet supply would reduce donor exposures and the number of contaminated blood products in the inventory, but would increase apheresis complications in donors. Potential risks for patients must be carefully weighed against the risks for donors, dependent on the specific pathogen scenario.
Over the past decades, optical technologies have entered neural implant technologies. Applications such as optogenetics, near-infrared spectroscopy (NIRS), and direct-near-infrared stimulation (NIS) ...request technical devices that combine electrical and optical recording as well as stimulation capabilities using light sources and/or optical sensors. Optoprobes are the technical devices that meet these requirements. This paper provides basic insights into optogenetic mechanisms, the background of NIRS and NIS, and focuses on fundamental requirements of technical systems from a biological background. The state of the art of optoprobes is reviewed and attention is drawn on the potential long-term stability of these technical devices for chronic neural implants. Further, material selection for stiff and flexible devices, applicable light sources, waveguide and coupling concepts, packaging paradigms as well as system assembly and integration aspects are discussed in view of biocompatible and biostable devices. This paper also considers the physical background of light scattering and heat generation when light sources are implanted into biological tissue.
Surfaces may be rendered superhydrophobic by engineering the surface morphology to control the extent of the liquid–air interface and by the use of low-surface-energy coatings. The droplet state on a ...superhydrophobic surface under static and dynamic conditions may be explained in terms of the relative magnitudes of the wetting and antiwetting pressures acting at the liquid–air interface on the substrate. In this paper, we discuss the design and fabrication of hollow hybrid superhydrophobic surfaces which incorporate both communicating and noncommunicating air gaps. The surface design is analytically shown to exhibit higher capillary (or nonwetting) pressure compared to solid pillars with only communicating air gaps. Six hybrid surfaces are fabricated with different surface parameters selected such that the Cassie state of a droplet is energetically favorable. The robustness of the surfaces is tested under dynamic impingement conditions, and droplet dynamics are explained using pressure-based transitions between Cassie and Wenzel states. During droplet impingement, the effective water hammer pressure acting due to the sudden change in the velocity of the droplet is determined experimentally and is found to be at least 2 orders of magnitude less than values reported in the literature. The experiments show that the water hammer pressure depends on the surface morphology and capillary pressure of the surface. We propose that the observed reduction in shock pressure may be attributed to the presence of air gaps in the substrate. This feature allows liquid deformation and hence avoids the sudden stoppage of the droplet motion as opposed to droplet behavior on smooth surfaces.
Background In view of demographic changes, it is becoming increasingly necessary to make allowance for the fact that older individuals in good health are generally more willing to donate blood and ...hence they should be allowed to do so irrespective of an upper age limit. In this respect, evidence has to be produced that there is neither an age‐related increase in risks to the donor nor any influence on the safety and efficacy of the blood components. It was therefore of interest to examine the quality of therapeutic plasma in relation to a donor’s age and also a donor’s gender in view of the preferred use of male donor plasma for reducing the risk of transfusion related acute lung injury.
Study Design and Methods Citrate‐phosphate‐dextrose (CPD) units of whole blood taken in each case from 50 blood donors (30 men and 20 women) of three age groups (cohort 1 = 69–71 years, cohort 2 = 66–68 years and cohort 3 = 50–52 years) were filtered, centrifuged and then separated into the relevant blood components. The plasma samples were assessed for international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, factor V (FV), factor VIII (FVIII), antithrombin (AT), protein S and plasminogen.
Results While aPTT showed only slight age‐related differences of no significance, the INR levels of cohort 1 were significantly higher than those of cohorts 2 and 3. However, in terms of gender, this applied to male donors only. The differences in INR are demonstrated by lower FV levels of male cohort 1 donors, although this is not statistically significant in comparison with the other two age groups and with female donors. Female donors of all cohorts, however, exhibited noticeably lower aPTT levels than male donors. Lower INR and aPTT values in women could be a sign of a lower dilution affected by CPD anticoagulant as compared to male plasma. An increase in FVIII levels was also apparent with increasing age (P < 0·05), particularly in male donor plasma. The fibrinogen levels suggest a slight, though insignificant, age‐related increase and no significant gender‐dependent effect. The plasma levels of AT and plasminogen were unremarkable. The plasma of female cohort 3 donors exhibited a protein S concentration that was slightly lower by comparison. Compared with the other two cohorts, cohort 1 plasma levels were similarly above or below the normal range derived from cohort 3 (central 95% range) for all parameters tested.
Conclusion International Normalized Ratio, aPTT, FVIII, FV, fibrinogen and protein S, as quality indicators for the efficacy of therapeutic plasma, revealed a moderate correlation with age and gender. Compared with the usual reference ranges, the differences were not significant enough to identify any relevant imbalance between procoagulating, anticoagulating and fibrinolytic factors that might influence product quality where the increasing age of the donors or the preference of male donor plasma was concerned.
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