The anti-coagulant activity of some carrageenans

Introduction The biological properties of the carrageenans and of certain other sulphated polysaccharides have been reviewed, and since the object of this work was to study the anticoagulant activity of intravenously-administered carrageenan, current theory of blood coagulation has been outlined. For comparison, the properties and mode of anticoagulant action of heparin have been reviewed. Experimental The practical work is reported in three sections. A preliminary section deals with the anticoagulant activity, in the rabbit, of a number of carrageenans, fractionated where appropriate, into k- and lambda-components. Doses fatal to rabbits vathin 24 hours are also recorded since many of these carrageenans were acutely toxic when administered intravenously. Frequently, lethal doses were close to anticoagulant doses and there seemed, from the preliminary work, reason to believe that the anticoagulant effect of these substances was associated with their toxic manifestations. In the main section, a more detailed study of the anticoagulant activity of the k- and lambda-carrageenana of Chondrus crisms from four habitats, of the carrageenan from Polyides rotundus and of degraded carrageenan from Kucheuma spinosum, is reported, and comparisons are made with heparin. Tests of clotting function were used to localise the anticoagulant activity in the clotting mechanism. The results of some preliminary experiments to determine the effects of carrageenan on platelets and fibrinogen are reported because it is believed that the toxicity of certain high molecular weight sulphated polysaccharides is caused by fibrinogen precipitation complicated by platelet and blood cell involvement in the precipitated complex, so blocking important vascular beds. These preliminary results give adequate confirmation that the toxic carrageenans behave similarly, while the non-toxic carrageenan does not. Conclusions The results of this study confirm the belief that the anticoagulant activity of lambda-carrageenan is greater than that of k-carrageenan and indicate that this holds for Chondrus carrageenans in general, in spite of marked variations in the properties of different carrageenans. They also show that the relationship between activity and ester sulphate, previously believed to be critical, is not a simple one, although the lambda-carrageenan from any seaweed is always higher in sulphate content than the corresponding k-carrageenan. Of all the carrageenans examined, that of Polyides showed greatest activity. Degraded Eucheuma carrageenan was the least toxic of those examined and of lowest molecular weight; hut although of high sulphate content, a much higher dose was required to show anticoagulant activity than of other carrageenans. The anticoagulant activity of the carrageenans can he detected at all stages of the clotting reaction examined, and this supports the view that a non-specific complexing reaction with many plasma proteins is involved, in contrast to the more localised action of heparin

Sustaining high-solar-activity research

Research efforts that require observations of high solar activity, such as multiwavelength studies of large solar flares and CMEs, must contend with the 11-year solar cycle to a degree unparalleled by other segments of heliophysics. While the "fallow" years around each solar minimum can be a great time frame to build the next major solar observatory, the corresponding funding opportunity and any preceding technology developments would need to be strategically timed. Even then, it can be challenging for scientists on soft money to continue ongoing research efforts instead of switching to other, more consistent topics. The maximum of solar cycle 25 is particularly concerning due to the lack of a US-led major mission targeting high solar activity, which could result in significant attrition of expertise in the field. We recommend the development of a strategic program of missions and analysis that ensures optimal science return for each solar maximum while sustaining the research community between maxima.Comment: White paper submitted to the Decadal Survey for Solar and Space Physics (Heliophysics) 2024-2033; 4 pages, 1 figur

Sampling Key Populations for HIV Surveillance: Results From Eight Cross-Sectional Studies Using Respondent-Driven Sampling and Venue-Based Snowball Sampling.

BACKGROUND: In using regularly collected or existing surveillance data to characterize engagement in human immunodeficiency virus (HIV) services among marginalized populations, differences in sampling methods may produce different pictures of the target population and may therefore result in different priorities for response. OBJECTIVE: The objective of this study was to use existing data to evaluate the sample distribution of eight studies of female sex workers (FSW) and men who have sex with men (MSM), who were recruited using different sampling approaches in two locations within Sub-Saharan Africa: Manzini, Swaziland and Yaoundé, Cameroon. METHODS: MSM and FSW participants were recruited using either respondent-driven sampling (RDS) or venue-based snowball sampling. Recruitment took place between 2011 and 2016. Participants at each study site were administered a face-to-face survey to assess sociodemographics, along with the prevalence of self-reported HIV status, frequency of HIV testing, stigma, and other HIV-related characteristics. Crude and RDS-adjusted prevalence estimates were calculated. Crude prevalence estimates from the venue-based snowball samples were compared with the overlap of the RDS-adjusted prevalence estimates, between both FSW and MSM in Cameroon and Swaziland. RESULTS: RDS samples tended to be younger (MSM aged 18-21 years in Swaziland: 47.6% [139/310] in RDS vs 24.3% [42/173] in Snowball, in Cameroon: 47.9% [99/306] in RDS vs 20.1% [52/259] in Snowball; FSW aged 18-21 years in Swaziland 42.5% [82/325] in RDS vs 8.0% [20/249] in Snowball; in Cameroon 15.6% [75/576] in RDS vs 8.1% [25/306] in Snowball). They were less educated (MSM: primary school completed or less in Swaziland 42.6% [109/310] in RDS vs 4.0% [7/173] in Snowball, in Cameroon 46.2% [138/306] in RDS vs 14.3% [37/259] in Snowball; FSW: primary school completed or less in Swaziland 86.6% [281/325] in RDS vs 23.9% [59/247] in Snowball, in Cameroon 87.4% [520/576] in RDS vs 77.5% [238/307] in Snowball) than the snowball samples. In addition, RDS samples indicated lower exposure to HIV prevention information, less knowledge about HIV prevention, limited access to HIV prevention tools such as condoms, and less-reported frequency of sexually transmitted infections (STI) and HIV testing as compared with the venue-based samples. Findings pertaining to the level of disclosure of sexual practices and sexual practice-related stigma were mixed. CONCLUSIONS: Samples generated by RDS and venue-based snowball sampling produced significantly different prevalence estimates of several important characteristics. These findings are tempered by limitations to the application of both approaches in practice. Ultimately, these findings provide further context for understanding existing surveillance data and how differences in methods of sampling can influence both the type of individuals captured and whether or not these individuals are representative of the larger target population. These data highlight the need to consider how program coverage estimates of marginalized populations are determined when characterizing the level of unmet need

Designing a Photonic Physically Unclonable Function Having Resilience to Machine Learning Attacks

Physically unclonable functions (PUFs) are designed to act as device 'fingerprints.' Given an input challenge, the PUF circuit should produce an unpredictable response for use in situations such as root-of-trust applications and other hardware-level cybersecurity applications. PUFs are typically subcircuits present within integrated circuits (ICs), and while conventional IC PUFs are well-understood, several implementations have proven vulnerable to malicious exploits, including those perpetrated by machine learning (ML)-based attacks. Such attacks can be difficult to prevent because they are often designed to work even when relatively few challenge-response pairs are known in advance. Hence the need for both more resilient PUF designs and analysis of ML-attack susceptibility. Previous work has developed a PUF for photonic integrated circuits (PICs). A PIC PUF not only produces unpredictable responses given manufacturing-introduced tolerances, but is also less prone to electromagnetic radiation eavesdropping attacks than a purely electronic IC PUF. In this work, we analyze the resilience of the proposed photonic PUF when subjected to ML-based attacks. Specifically, we describe a computational PUF model for producing the large datasets required for training ML attacks; we analyze the quality of the model; and we discuss the modeled PUF's susceptibility to ML-based attacks. We find that the modeled PUF generates distributions that resemble uniform white noise, explaining the exhibited resilience to neural-network-based attacks designed to exploit latent relationships between challenges and responses. Preliminary analysis suggests that the PUF exhibits similar resilience to generative adversarial networks, and continued development will show whether more-sophisticated ML approaches better compromise the PUF and -- if so -- how design modifications might improve resilience.Comment: 14 pages, 8 figure

Brief Report: Elastin Microfibril Interface 1 and Integrin-Linked Protein Kinase Are Novel Markers of Islet Regenerative Function in Human Multipotent Mesenchymal Stromal Cells

Multipotent mesenchymal stromal cell (MSC) transplantation is proposed as a novel therapy for treating diabetes by promoting the regeneration of damaged islets. The clinical promise of such treatments may be hampered by a high degree of donor-related variability in MSC function and a lack of standards for comparing potency. Here, we set out to identify markers of cultured human MSCs directly associated with islet regenerative function. Stromal cultures from nine separate bone marrow donors were demonstrated to have differing capacities to reduce hyperglycemia in the NOD/SCID streptozotocin-induced diabetic model. Regenerative (R) and non-regenerative (NR) MSC cultures were directly compared using isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics. A total of 1,410 proteins were quantified resulting in the identification of 612 upregulated proteins and 275 downregulated proteins by ± 1.2-fold in R-MSC cultures. Elastin microfibril interface 1 (EMILIN-1), integrin-linked protein kinase (ILK), and hepatoma-derived growth factor (HDGF) were differentially expressed in R-MSCs, and Ingenuity Pathway Analyses revealed each candidate as known regulators of integrin signaling. Western blot validation of EMILIN-1, ILK, and HDGF not only showed significantly higher abundance levels in R-MSCs, as compared with NR-MSCs, but also correlated with passage-induced loss of islet-regenerative potential. Generalized estimating equation modeling was applied to examine the association between each marker and blood glucose reduction. Both EMILIN-1 and ILK were significantly associated with blood glucose lowering function in vivo. Our study is the first to identify EMILIN-1 and ILK as prospective markers of islet regenerative function in human MSCs. Stem Cells 2016;34:2249–2255

Accelerated electrons observed down to <7 keV in a NuSTAR solar microflare

We report the detection of emission from a nonthermal electron distribution in a small solar microflare (GOES class A5.7) observed by the Nuclear Spectroscopic Telescope Array, with supporting observation by the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI). The flaring plasma is well accounted for by a thick-target model of accelerated electrons collisionally thermalizing within the loop, akin to the "coronal thick-target" behavior occasionally observed in larger flares. This is the first positive detection of nonthermal hard X-rays from the Sun using a direct imager (as opposed to indirectly imaging instruments). The accelerated electron distribution has a spectral index of 6.3 ± 0.7, extends down to at least 6.5 keV, and deposits energy at a rate of ~2 × 1027 erg s−1, heating the flare loop to at least 10 MK. The existence of dominant nonthermal emission in X-rays down to &lt;5 keV means that RHESSI emission is almost entirely nonthermal, contrary to what is usually assumed in RHESSI spectroscopy. The ratio of nonthermal to thermal energies is similar to that of large flares, in contrast to what has been found in previous studies of small RHESSI flares. We suggest that a coronal thick target may be a common property of many small microflares based on the average electron energy and collisional mean free path. Future observations of this kind will enable understanding of how flare particle acceleration changes across energy scales, and will aid the push toward the observational regime of nanoflares, which are a possible source of significant coronal heating

Concert recording 2017-04-26

[Track 1]. Fantazia / Orlando Gibbons arranged by Fred Hemke -- [Track 2-3]. Quartette (Allegro de concert) / Caryl Florio -- [Track 4]. O magnum mysterium / Morten Lauridsen arranged by Chase Shumsky -- [Track 5]. Petite symphonie. Scherzo / Charles Gounod arranged by Aaron M. Durst -- [Track 6]. Grainger set. Mock Morris / Percy Aldridge Grainger arranged by Gary Bricault -- [Track 7]. Grainger set. Two British folk settings. I. Mo nighean dubh [Track 8]. II. The hunter in his career / Percy Aldridge Grainger arranged by Chalon Ragsdale -- [Track 9]. Molly on the shore / Percy Aldridge Grainger arranged by Jacques Larocque -- [Track 10]. The great gate of Kiev / Modest Mussorgsky and Maurice Ravel arranged by B.L. Bruske