Alopecia Areata: Treatment of Today and Tomorrow

It is the aim of this article to review and appraise available data on treatments for alopecia areata (AA) according to the demands of evidence based medicine. Studies evaluating the efficacy of a treatment for AA should include appropriate controls, use cosmetically acceptable hair regrowth as a parameter for treatment success, include patients with AA totalis, universalis or extensive patchy AA, and exclude patients suffering from AA for less than 3 months. Moreover, the treatment must be safe over a prolonged period of time. Among the various therapeutic approaches presently available for AA, only treatment with contact sensitizers such as diphenylcyclopropenone or squaric acid dibutylester has been shown to be effective in studies that fulfill these criteria.Improved future treatments may be immunosup-pressive or immunomodulatory targeting of the autoimmune pathogenesis of AA, or they may otherwise protect hair follicles from the injurious effects of inflammation. Such possible future therapeutic approaches include the incorporation of immunomodulatory agents into liposomes as an improved vehicle; inhibition of apoptosis mediated by the Fas-FasL system; inhibition of the lymphocyte homing receptor CD44v10; induction of tolerance

Development and testing of the 3U+ CubeSat PCDU for SOURCE

SOURCE (Stuttgart Operated University CubeSat for Evaluation and Education) is a 3U+ re-search CubeSat that is being developed by students at the University of Stuttgart in coopera-tion with the Institute for Space Systems and the Small Satellite Student Society KSat e.V.. The objectives include technology demonstrations, atmospheric research and the investigation of satellite demise while also serving as an educational program. SOURCE was selected by ESA's "Fly your Satellite" program and is currently in Phase D. The electrical power supply system combines commercial off-the-shelf parts with self-devel-oped units to meet the requirements of the payloads. The solar array configuration and Power Conditioning and Distribution Unit (PCDU) are self-developed, while the battery is a commer-cial product. A total of 56 solar cells provides up to 32W under ideal conditions, which can be stored in a 75Wh space-qualified lithium-ion battery. To maximise the power output of the solar cells, maximum power point tracking is performed by the PCDU. This is controlled by a radiation hardened microcontroller. The PCDU provides regulated 3.3V, 5V and unregulated battery voltage to the subsystems with 32 switchable outputs, 27 of which are latch-up current protected. The microcontroller controls these individual output channels and the switching between the various CubeSat modes as commanded by the on-board computer. Additionally, every output channel power consumption is monitored for overcurrents. The PCDU functions as a watchdog by checking the health of the on-board computer, rebooting it in case of a failure. High priority commands can be sent directly to the PCDU from the ground via the communication system, bypassing the on-board computer. These can reset either the communication subsystem, the on-board computer or the entire satellite. Four hybrid inhibits, using a combination of mechanical switches and FETs are integrated in the PCDU, replacing the usual fully mechanical design. Three are used to deactivate the satellite in the deployer configuration and the fourth is a remove-before-flight inhibit. An engineering model was manufactured during phase C and is being tested functionally, en-vironmentally and for performance. This paper presents the detailed design of the PCDU, the acquired test results and outlines issues encountered during the test

Experimental evolution on a wild mammal species results in modifications of gut microbial communities

Comparative studies have shown that diet, life history, and phylogeny interact to determine microbial community structure across mammalian hosts. However, these studies are often confounded by numerous factors. Selection experiments offer unique opportunities to validate conclusions and test hypotheses generated by comparative studies. We used a replicated, 15-generation selection experiment on bank voles (Myodes glareolus) that have been selected for high swim-induced aerobic metabolism, predatory behavior toward crickets, and the ability to maintain body mass on a high-fiber, herbivorous diet. We predicted that selection on host performance, mimicking adaptive radiation, would result in distinct microbial signatures. We collected foregut and cecum samples from animals that were all fed the same nutrient-rich diet and had not been subjected to any performance tests. We conducted microbial inventories of gut contents by sequencing the V4 region of the 16S rRNA gene. We found no differences in cecal microbial community structure or diversity between control lines and the aerobic or predatory lines. However, the cecal chambers of voles selected for herbivorous capability harbored distinct microbial communities that exhibited higher diversity than control lines. The foregut communities of herbivorous-selected voles were also distinct from control lines. Overall, this experiment suggests that differences in microbial communities across herbivorous mammals may be evolved, and not solely driven by current diet or other transient factors

Programme of the 21st European Conference on Eye Movements

About ECEM ECEM was initiated by Rudolf Groner (Bern), Dieter Heller (Bayreuth at the time) and Henk Breimer (Tilburg) in the 198 to provide a forum for an interdisciplinary group of scientists interested in eye movements. Since the inaugural meeting in Bern, the conference has been held every two years in different venues across Europe until 2021, when it was planned to take place in Leicester but was cancelled due to the COVID pandemic. It was decided to hold the meeting in Leicester in August 2022 instead, and as an in person meeting rather than an online or hybrid event. Incidentally, the present meeting is the third time the conference has come to the English East Midlands, now in Leicester following previous meetings in the neighbouring cities of Derby and Nottingham. The sites of previous ECEMs and webpages can be found here

Accelerating biphasic biocatalysis through new process windows

Process intensification through continuous flow reactions has increased the production rates of fine chemicals and pharmaceuticals. Catalytic reactions are accelerated through an unconventional and unprecedented use of a high‐performance liquid/liquid counter current chromatography system. Product generation is significantly faster than in traditional batch reactors or in segmented flow systems, which is exemplified through stereoselective phase‐transfer catalyzed reactions. This methodology also enables the intensification of biocatalysis as demonstrated in high yield esterifications and in the sesquiterpene cyclase‐catalyzed synthesis of sesquiterpenes from farnesyl diphosphate as high‐value natural products with applications in medicine, agriculture and the fragrance industry. Product release in sesquiterpene synthases is rate limiting due to the hydrophobic nature of sesquiterpenes, but a biphasic system exposed to centrifugal forces allows for highly efficient reactions

PENGARUH STOCK SPLIT TERHADAP HARGA SAHAM DI BURSA EFEK INDONESIA (BEI) (Studi Empiris Pada Perusahaan Yang Melakukan Stock Split Pada Tahun 2015-2018)

In Indonesia, the announcement of a stock split becomes meaningful for investors and potential investors in terms of decision making. Stock split is a form of information that is carried out by issuers to increase the number of shares outstanding. The reason for issuers to do a stock split is that the price of the shares is not too high and is easily reached by investors and can increase liquidity. The purpose of this research is to look at the effect of stock split on stock prices by looking at abnormal return movements and trading volume activity. The population in this study were 58 companies listed on the Indonesian Stock Exchange that did a stock split in 2015-2018, while the sample in this study was 27 companies. Sampling was done by puposive sampling and data analysis techniques using Uji-t paired simple t-test. based on analysis with a significant level of 5%, it can be seen that the abnormal return shows the results of p-value (0.062)> a (0.05), which means that Ho is accepted and Hi is rejected, or there is no influence between abnormal returns before and after the stock split. In stock trading volume (TVA), shows the results of p-value (0.017) <a (0.05) which means that Ho is rejected and Hi is accepted, or there is an influence between trading volume activity before and after the stock split

TMEM16A and TMEM16B modulate pheromone-evoked action potential firing in mouse vomeronasal sensory neurons

The mouse vomeronasal system controls several social behaviors. Pheromones and other social cues are detected by sensory neurons in the vomeronasal organ (VNO). Stimuli activate a transduction cascade that leads to membrane potential depolarization, increase in cytosolic Ca2+ level, and increased firing. The Ca2+-activated chloride channels TMEM16A and TMEM16B are co-expressed within microvilli of vomeronasal neurons, but their physiological role remains elusive. Here, we investigate the contribution of each of these channels to vomeronasal neuron firing activity by comparing wild-type (WT) and knock-out (KO) mice. Performing loosepatch recordings from neurons in acute VNO slices, we show that spontaneous activity is modified by Tmem16a KO, indicating that TMEM16A, but not TMEM16B, is active under basal conditions. Upon exposure to diluted urine, a rich source of mouse pheromones, we observe significant changes in activity. Vomeronasal sensory neurons (VSNs) from Tmem16a cKO and Tmem16b KO mice show shorter interspike intervals (ISIs) compared with WT mice, indicating that both TMEM16A and TMEM16B modulate the firing pattern of pheromone-evoked activity in VSNs

Application of single molecule technology to rapidly map long DNA and study the conformation of stretched DNA

Herein we describe the first application of direct linear analysis (DLA) to the mapping of a bacterial artificial chromosome (BAC), specifically the 185.1 kb-long BAC 12M9. DLA is a single molecule mapping technology, based on microfluidic elongation and interrogation of individual DNA molecules, sequence-specifically tagged with bisPNAs. A DNA map with S/N ratio sufficiently high to detect all major binding sites was obtained using only 200 molecule traces. A new method was developed to extract an oriented map from an averaged map that included a mixture of head-first and tail-first DNA traces. In addition, we applied DLA to study the conformation and tagging of highly stretched DNA. Optimal conditions for promoting sequence-specific binding of bisPNA to an 8 bp target site were elucidated using DLA, which proved superior to electromobility shift assays. DLA was highly reproducible with a hybridized tag position localized with an accuracy of ±0.7 µm or ±2.1 kb demonstrating its utility for rapid mapping of large DNA at the single molecule level. Within this accuracy, DNA molecules, stretched to at least 85% of their contour length, were stretched uniformly, so that the map expressed in relative coordinates, was the same regardless of the molecule extension

Proenkephalin and the risk of new-onset heart failure:data from prevention of renal and vascular end-stage disease

BACKGROUND: Enkephalins of the opioid system exert several cardiorenal effects. Proenkephalin (PENK), a stable surrogate, is associated with heart failure (HF) development after myocardial infarction and worse cardiorenal function and prognosis in patients with HF. The association between plasma PENK concentrations and new‐onset HF in the general population remains to be established. HYPOTHESIS: We hypothesized that plasma PENK concentrations are associated with new‐onset HF in the general population. METHODS: We included 6677 participants from the prevention of renal and vascular end‐stage disease study and investigated determinants of PENK concentrations and their association with new‐onset HF (both reduced [HFrEF] and preserved ejection fraction [HFpEF]). RESULTS: Median PENK concentrations were 52.7 (45.1–61.9) pmol/L. Higher PENK concentrations were associated with poorer renal function and higher NT‐proBNP concentrations. The main determinants of higher PENK concentrations were lower estimated glomerular filtration rate (eGFR), lower urinary creatinine excretion, and lower body mass index (all p < .001). After a median 8.3 (7.8–8.8) years follow‐up, 221 participants developed HF; 127 HFrEF and 94 HFpEF. PENK concentrations were higher in subjects who developed HF compared with those who did not, 56.2 (45.2–67.6) versus 52.7 (45.1–61.6) pmol/L, respectively (p = .003). In competing‐risk analyses, higher PENK concentrations were associated with higher risk of new‐onset HF (hazard ratio [HR] = 2.09[1.47–2.97], p < .001), including both HFrEF (HR = 2.31[1.48–3.61], p < .001) and HFpEF (HR = 1.74[1.02–2.96], p = .042). These associations were, however, lost after adjustment for eGFR. CONCLUSIONS: In the general population, higher PENK concentrations were associated with lower eGFR and higher NT‐proBNP concentrations. Higher PENK concentrations were not independently associated with new‐onset HFrEF and HFpEF and mainly confounded by eGFR

Quantification of collagen organization in histopathology samples using liquid crystal based polarization microscopy

Author Posting. © The Optical Society, 2017. This article is posted here by permission of The Optical Society for personal use, not for redistribution. The definitive version was published in Biomedical Optics Express 8 (2017): 4243-4256, doi:10.1364/BOE.8.004243.A number of histopathology studies have utilized the label free microscopy method of Second Harmonic Generation (SHG) to investigate collagen organization in disease onset and progression. Here we explored an alternative label free imaging approach, LC-PolScope that is based on liquid crystal based polarized light imaging. We demonstrated that this more accessible technology has the ability to visualize all fibers of interest and has a good to excellent correlation between SHG and LC-PolScope measurements in fibrillar collagen orientation and alignment. This study supports that LC-PolScope is a viable alternative to SHG for label free collagen organization measurements in thin histology sections.Morgridge Institute for Research and National Institutes of Health (NIH) (U54DK104310 and R01GM114274); The University of Wisconsin Carbone Cancer Center Cancer Center Biocore and Histology core (UWCCC) (P30 CA014520)