Wang-Landau molecular dynamics technique to search for low-energy conformational space of proteins

Multicanonical molecular dynamics (MD) is a powerful technique for sampling conformations on rugged potential surfaces such as protein. However, it is notoriously difficult to estimate the multicanonical temperature effectively. Wang and Landau developed a convenient method for estimating the density of states based on a multicanonical Monte Carlo method. In their method, the density of states is calculated autonomously during a simulation. In this paper we develop a set of techniques to effectively apply the Wang-Landau method to MD simulations. In the multicanonical MD, the estimation of the derivative of the density of states is critical. In order to estimate it accurately, we devise two original improvements. First, the correction for the density of states is made smooth by using the Gaussian distribution obtained by a short canonical simulation. Second, an approximation is applied to the derivative, which is based on the Gaussian distribution and the multiple weighted histogram technique. A test of this method was performed with small polypeptides, Met-enkephalin and Trp-cage, and it is demonstrated that Wang-Landau MD is consistent with replica exchange MD but can sample much larger conformational space.Comment: 8 pages, 7 figures, accepted for publication in Physical Review

Longitudinal evaluation of cognitive functioning in young children with type 1 diabetes over 18 months

OBJECTIVE: Decrements in cognitive function may already be evident in young children with type 1 diabetes (T1D). Here we report prospectively acquired cognitive results over 18 months in a large cohort of young children with and without T1D. METHODS: 144 children with T1D (mean HbA1c: 7.9%) and 70 age-matched healthy controls (mean age both groups 8.5 years; median diabetes duration 3.9 yrs; mean age of onset 4.1 yrs) underwent neuropsychological testing at baseline and after 18-months of follow-up. We hypothesized that group differences observed at baseline would be more pronounced after 18 months, particularly in those T1D patients with greatest exposure to glycemic extremes. RESULTS: Cognitive domain scores did not differ between groups at the 18 month testing session and did not change differently between groups over the follow-up period. However, within the T1D group, a history of diabetic ketoacidosis (DKA) was correlated with lower Verbal IQ and greater hyperglycemia exposure (HbA1c area under the curve) was inversely correlated to executive functions test performance. In addition, those with a history of both types of exposure performed most poorly on measures of executive function. CONCLUSIONS: The subtle cognitive differences between T1D children and nondiabetic controls observed at baseline were not observed 18 months later. Within the T1D group, as at baseline, relationships between cognition (VIQ and executive functions) and glycemic variables (chronic hyperglycemia and DKA history) were evident. Continued longitudinal study of this T1D cohort and their carefully matched healthy comparison group is planned

Theory of Systematic Computational Error in Free Energy Differences

Systematic inaccuracy is inherent in any computational estimate of a non-linear average, due to the availability of only a finite number of data values, N. Free energy differences (DF) between two states or systems are critically important examples of such averages in physical, chemical and biological settings. Previous work has demonstrated, empirically, that the ``finite-sampling error'' can be very large -- many times kT -- in DF estimates for simple molecular systems. Here, we present a theoretical description of the inaccuracy, including the exact solution of a sample problem, the precise asymptotic behavior in terms of 1/N for large N, the identification of universal law, and numerical illustrations. The theory relies on corrections to the central and other limit theorems, and thus a role is played by stable (Levy) probability distributions.Comment: 5 pages, 4 figure

Modelling societal transitions with agent transformation

Transition models explain long-term and large-scale processes fundamentally changing the structure of a societal system. Our concern is that most transition models are too static. Although they capture a move of focus from static equilibria to transitions between dynamic equilibria, they are still rooted in an "equilibriumist" approach. Improvement is possible with agent-based models that give attention to endogenous system processes called "transformation processes". These models can render far more dynamic pictures of societal systems in transition, and are no longer remote from descriptions in the emerging transition literature

Differential role for trehalose metabolism in salt-stressed maize

Little is known about how salt impacts primary metabolic pathways of C4 plants, particularly related to kernel development and seed set. Osmotic stress was applied to maize (Zea mays) B73 by irrigation with increasing concentrations of NaCl from the initiation of floral organs until 3 d after pollination. At silking, photosynthesis was reduced to only 2% of control plants. Salt treatment was found to reduce spikelet growth, silk growth, and kernel set. Osmotic stress resulted in higher concentrations of sucrose (Suc) and hexose sugars in leaf, cob, and kernels at silking, pollination, and 3 d after pollination. Citric acid cycle intermediates were lower in salt-treated tissues, indicating that these sugars were unavailable for use in respiration. The sugar-signaling metabolite trehalose-6-phosphate was elevated in leaf, cob, and kernels at silking as a consequence of salt treatment but decreased thereafter even as Suc levels continued to rise. Interestingly, the transcripts of trehalose pathway genes were most affected by salt treatment in leaf tissue. On the other hand, transcripts of the SUCROSE NONFERMENTING-RELATED KINASE1 (SnRK1) marker genes were most affected in reproductive tissue. Overall, both source and sink strength are reduced by salt, and the data indicate that trehalose-6-phosphate and SnRK1 may have different roles in source and sink tissues. Kernel abortion resulting from osmotic stress is not from a lack of carbohydrate reserves but from the inability to utilize these energy reserves

Lesbian and bisexual women's human rights, sexual rights and sexual citizenship: negotiating sexual health in England.

Lesbian and bisexual women's sexual health is neglected in much Government policy and practice in England and Wales. This paper examines lesbian and bisexual women's negotiation of sexual health, drawing on findings from a small research project. Themes explored include invisibility and lack of information, influences on decision-making and sexual activities and experiences of services and barriers to sexual healthcare. Key issues of importance in this respect are homophobic and heterosexist social contexts. Drawing on understandings of lesbian, gay and bisexual human rights, sexual rights and sexual citizenship, it is argued that these are useful lenses through which to examine and address lesbian and bisexual women's sexual health and related inequalities

Pediatric diabetes consortium T1D New Onset ( NeOn ) study: clinical outcomes during the first year following diagnosis

Objective There have been few prospective, multicenter studies investigating the natural history of type 1 diabetes ( T1D ) from the time of diagnosis. The objective of this report from the Pediatric Diabetes Consortium ( PDC ) T1D New Onset ( NeOn ) study was to assess the natural history and clinical outcomes in children during the first year after diagnosis of T1D . Research design and methods: Clinical measures from the first year following diagnosis were analyzed for 857 participants (mean age 9.1 yr, 51% female, 66% non‐Hispanic White) not participating in an intervention study who had a HbA1c result at 12 months. Results Mean HbA1c ± SD was 102 ± 25 mmol/mol (11.4 ± 2.3%) at diagnosis, 55 ± 12 mmol/mol (7.2 ± 1.1%) at 3 months, 56 ± 15 mmol/mol (7.3 ± 1.3%) at 6 months and 62 ± 16 mmol/mol (7.8 ± 1.5%) at 12 months from diagnosis. A severe hypoglycemic ( SH ) event occurred in 31 (4%) participants (44 events, 5.2 events per 100 person‐years). Diabetic ketoacidosis ( DKA ) not including diagnosis occurred in 10 (1%) participants (13 events, 1.5 events per 100 person‐years). Conclusions After onset of T1D , mean HbA1c reaches its nadir at 3–6 months with a gradual increase through 12 months. SH and DKA are uncommon but still occur during the first year with T1D . Data from large cohorts, such as the PDC T1D NeOn study, provide important insights into the course of T1D during the first year following diagnosis, which will help to inform the development of models to target future interventions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107374/1/pedi12068.pd

Efficient Passive ICS Device Discovery and Identification by MAC Address Correlation

Owing to a growing number of attacks, the assessment of Industrial Control Systems (ICSs) has gained in importance. An integral part of an assessment is the creation of a detailed inventory of all connected devices, enabling vulnerability evaluations. For this purpose, scans of networks are crucial. Active scanning, which generates irregular traffic, is a method to get an overview of connected and active devices. Since such additional traffic may lead to an unexpected behavior of devices, active scanning methods should be avoided in critical infrastructure networks. In such cases, passive network monitoring offers an alternative, which is often used in conjunction with complex deep-packet inspection techniques. There are very few publications on lightweight passive scanning methodologies for industrial networks. In this paper, we propose a lightweight passive network monitoring technique using an efficient Media Access Control (MAC) address-based identification of industrial devices. Based on an incomplete set of known MAC address to device associations, the presented method can guess correct device and vendor information. Proving the feasibility of the method, an implementation is also introduced and evaluated regarding its efficiency. The feasibility of predicting a specific device/vendor combination is demonstrated by having similar devices in the database. In our ICS testbed, we reached a host discovery rate of 100% at an identification rate of more than 66%, outperforming the results of existing tools.Comment: http://dx.doi.org/10.14236/ewic/ICS2018.

Clinical outcomes in youth beyond the first year of type 1 diabetes: Results of the Pediatric Diabetes Consortium (PDC) type 1 diabetes new onset (NeOn) study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138914/1/pedi12459.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138914/2/pedi12459_am.pd