The insecticidal spider toxin SFI1 is a knottin peptide that blocks the pore of insect voltage-gated sodium channels via a large β-hairpin loop

Spider venoms contain a plethora of insecticidal peptides that act on neuronal ion channels and receptors. Because of their high specificity, potency and stability, these peptides have attracted much attention as potential environmentally friendly insecticides. Although many insecticidal spider venom peptides have been isolated, the molecular target, mode of action and structure of only a small minority have been explored. Sf1a, a 46-residue peptide isolated from the venom of the tube-web spider Segesteria florentina, is insecticidal to a wide range of insects, but nontoxic to vertebrates. In order to investigate its structure and mode of action, we developed an efficient bacterial expression system for the production of Sf1a. We determined a high-resolution solution structure of Sf1a using multidimensional 3D/4D NMR spectroscopy. This revealed that Sf1a is a knottin peptide with an unusually large β-hairpin loop that accounts for a third of the peptide length. This loop is delimited by a fourth disulfide bond that is not commonly found in knottin peptides. We showed, through mutagenesis, that this large loop is functionally critical for insecticidal activity. Sf1a was further shown to be a selective inhibitor of insect voltage-gated sodium channels, consistent with its 'depressant' paralytic phenotype in insects. However, in contrast to the majority of spider-derived sodium channel toxins that function as gating modifiers via interaction with one or more of the voltage-sensor domains, Sf1a appears to act as a pore blocker.

Louis Kraft papers undated, 1914-1975.

Correspondence, memoranda, minutes, reports, official documents and other similar materials pertaining to Kraft's long career in Jewish Social Service at the JWB, the JDC and related organizations.

Baron de Hirsch Fund records undated, 1870-1991.

Contains Deed of Trust, By-Laws, Annual Reports, Corporation Minutes (1909, 1913-1919, 1923-1924, 1926-1933), Minutes of the Board of Trustees (1893, 1899, 1907, 1910, 1915-1916, 1918, 1923, 1926-1927, 1930-1933), and the minutes, correspondence, and reports of the various national and local committees. Financial materials include income and expenditure records (1891-1933), audits (1919-1923, 1926-1928), the records of agricultural loans and mortgages, bond and real estate holdings, and bequests. Includes also correspondence and other materials regarding the establishment of the Fund, correspondence of and other papers concerning the Baron and Baroness de Hirsch, and several histories of the Fund. Included in the wide range of activities are material on the work of the Agriculture Bureau and the Jewish Agriculture Society, Housing, English Classes, Immigration (including monthly reports for several ports of entry 1885-1916) and Immigrant Aid, German Refugee Aid in the early years of the Holocaust, Kings Park, N.Y. Test Farm, the Laundry Project, Peekskill Farm, Public Baths, Student Loans, the Baron de Hirsch Trade School, and the Woodbine Colony and Baron De Hirsch Agricultural & Industrial School. Contains also materials on the Colonization attempts made in Colorado, Connecticut, Florida, Louisiana, Michigan, Minnesota, North Dakota, New Jersey, New York, Pennsylvania, South Dakota, Galveston, Texas, The Southwest, Washington, Canada, and Mexico.

On linear order and computation : The expressiveness of interactive computations on linear orders and computations indexed by ordinals

We solve the Dynamic Ehrenfeucht-Fra\"iss\'e Game on linear orders for both players, yielding a normal form for quantifier-rank equivalence classes of linear orders in first-order logic, infinitary logic, and generalized-infinitary logics with linearly ordered clocks. We show that Scott Sentences can be manipulated quickly, classified into local information, and consistency can be decided effectively in the length of the Scott Sentence. We describe a finite set of linked automata moving continuously on a linear order. Running them on ordinals, we compute the ordinal truth predicate and compute truth in the constructible universe of set-theory. Among the corollaries are a study of semi-models as efficient database of both model-theoretic and formulaic information, and a new proof of the atomicity of the Boolean algebra of sentences consistent with the theory of linear order -- i.e., that the finitely axiomatized theories of linear order are dense.

Letter to Dr. Simeon Leo

Letter to Doctor Leo from Charles Frank, patient at Montefiore Hospital

The Wieruszowski ancestry : from the mid 1700’s to the late 1900’s /

Family trees of the descendants of the Wieruszowski and of the Apt families from the mid 1700’s to the late 1900’s, from family sources and from other places.

Change to costs and lengths of stay in the emergency department and the Brisbane protocol: An observational study

- Objective To compare health service cost and length of stay between a traditional and an accelerated diagnostic approach to assess acute coronary syndromes (ACS) among patients who presented to the emergency department (ED) of a large tertiary hospital in Australia. - Design, setting and participants This historically controlled study analysed data collected from two independent patient cohorts presenting to the ED with potential ACS. The first cohort of 938 patients was recruited in 2008–2010, and these patients were assessed using the traditional diagnostic approach detailed in the national guideline. The second cohort of 921 patients was recruited in 2011–2013 and was assessed with the accelerated diagnostic approach named the Brisbane protocol. The Brisbane protocol applied early serial troponin testing for patients at 0 and 2 h after presentation to ED, in comparison with 0 and 6 h testing in traditional assessment process. The Brisbane protocol also defined a low-risk group of patients in whom no objective testing was performed. A decision tree model was used to compare the expected cost and length of stay in hospital between two approaches. Probabilistic sensitivity analysis was used to account for model uncertainty. - Results Compared with the traditional diagnostic approach, the Brisbane protocol was associated with reduced expected cost of $1229 (95% CI −$1266 to $5122) and reduced expected length of stay of 26 h (95% CI −14 to 136 h). The Brisbane protocol allowed physicians to discharge a higher proportion of low-risk and intermediate-risk patients from ED within 4 h (72% vs 51%). Results from sensitivity analysis suggested the Brisbane protocol had a high chance of being cost-saving and time-saving. - Conclusions This study provides some evidence of cost savings from a decision to adopt the Brisbane protocol. Benefits would arise for the hospital and for patients and their families.

Sleep quantity and quality during heat-based training and the effects of cold-water immersion recovery

- Introduction Heat-based training (HT) is becoming increasingly popular as a means of inducing acclimation before athletic competition in hot conditions and/or to augment the training impulse beyond that achieved in thermo-neutral conditions. Importantly, current understanding of the effects of HT on regenerative processes such as sleep and the interactions with common recovery interventions remain unknown. This study aimed to examine sleep characteristics during five consecutive days of training in the heat with the inclusion of cold-water immersion (CWI) compared to baseline sleep patterns. - Methods Thirty recreationally-trained males completed HT in 32 ± 1 °C and 60% rh for five consecutive days. Conditions included: 1) 90 min cycling at 40 % power at VO2max (Pmax) (90CONT; n = 10); 90 min cycling at 40 % Pmax with a 20 min CWI (14 ± 1 °C; 90CWI; n = 10); and 30 min cycling alternating between 40 and 70 % Pmax every 3 min, with no recovery intervention (30HIT; n = 10). Sleep quality and quantity was assessed during HT and four nights of 'baseline' sleep (BASE). Actigraphy provided measures of time in and out of bed, sleep latency, efficiency, total time in bed and total time asleep, wake after sleep onset, number of awakenings, and wakening duration. Subjective ratings of sleep were also recorded using a 1-5 Likert scale. Repeated measures analysis of variance (ANOVA) was completed to determine effect of time and condition on sleep quality and quantity. Cohen's d effect sizes were also applied to determine magnitude and trends in the data. - Results Sleep latency, efficiency, total time in bed and number of awakenings were not significantly different between BASE and HT (P > 0.05). However, total time asleep was significantly reduced (P = 0.01; d = 1.46) and the duration periods of wakefulness after sleep onset was significantly greater during HT compared with BASE (P = 0.001; d = 1.14). Comparison between training groups showed latency was significantly higher for the 30HIT group compared to 90CONT (P = 0.02; d = 1.33). Nevertheless, there were no differences between training groups for sleep efficiency, total time in bed or asleep, wake after sleep onset, number of awakenings or awake duration (P > 0.05). Further, cold-water immersion recovery had no significant effect on sleep characteristics (P > 0.05). - Discussion Sleep plays an important role in athletic recovery and has previously been demonstrated to be influenced by both exercise training and thermal strain. Present data highlight the effect of HT on reduced sleep quality, specifically reducing total time asleep due to longer duration awake during awakenings after sleep onset. Importantly, although cold water recovery accelerates the removal of thermal load, this intervention did not blunt the negative effects of HT on sleep characteristics. - Conclusion Training in hot conditions may reduce both sleep quantity and quality and should be taken into consideration when administering this training intervention in the field.

Understanding video based parent training intervention for children with autism

This paper investigates the challenges of delivering parent training intervention for autism over video. We conducted a qualitative field study of an intervention, which is based on a well-established training program for parents of children with autism, called Hanen More Than Words. The study was conducted with a Hanen Certified speech pathologist who delivered video based training to two mothers, each with a son having autism. We conducted observations of 14 sessions of the intervention spanning 3 months along with 3 semi-structured interviews with each participant. We identified different activities that participants performed across different sessions and analysed them based upon their implications on technology. We found that all the participants welcomed video based training but they also faced several difficulties, particularly in establishing rapport with other participants, inviting equal participation, and in observing and providing feedback on parent-child interactions. Finally, we reflect on our findings and motivate further investigations by defining three design sensitivities of Adaptation, Group Participation, and Physical Setup.

Pairing technology and meals: A contextual enquiry in the family household

Recent research about technology during mealtime has been mostly concerned with developing technology rather than creating a deeper understanding of the context of family mealtimes and associated practices. In this paper, we present a two-phase study discussing how the temporal, social, and food related features are intertwined with technology use during mealtimes. Our findings show how people differentiate technology usage during weekday meals, weekend meals, and among different meals of the day. We identify and analyse prototypical situations ranging from the use of arbitrary technologies while eating solitary, to idiosyncratic family norms and practices associated with shared technologies. We discuss the use of mealtime technology to create appropriate ambience for meals with guests and demonstrate how technology can be used to complement food in everyday meals and special occasions. Our findings make recommendation about the need for HCI research to recognize the contextual nature of technology usage during family mealtimes and to adopt appropriate design strategies.

Social NUI: Social perspectives in natural user interfaces

Natural User Interfaces (NUI) offer rich ways for interacting with the digital world that make innovative use of existing human capabilities. They include and often combine different input modalities such as voice, gesture, eye gaze, body interactions, touch and touchless interactions. However much of the focus of NUI research and development has been on enhancing the experience of individuals interacting with technology. Effective NUIs must also acknowledge our innately social characteristics, and support how we communicate with each other, play together, learn together and collaboratively work together. This workshop concerns the social aspects of NUI. The workshop seeks to better understand the social uses and applications of these new NUI technologies -- how we design these technologies for new social practices and how we understand the use of these technologies in key social contexts.

Implicit and explicit interactions in video mediated collaboration

In this paper we report the results of a study comparing implicit-only and explicit-only interactions in a collaborative, video-mediated task with shared content. Expanding on earlier work which has typically only evaluated how implicit interaction can augment primarily explicit systems, we report issues surrounding control, anxiousness and negotiation in the context of video mediated collaboration. We conclude that implicit interaction has the potential to improve collaborative work, but that there are a multitude of issues that must first be negotiated.

Ambient air pollution exposure estimation for the global burden of disease 2013

Exposure to ambient air pollution is a major risk factor for global disease. Assessment of the impacts of air pollution on population health and the evaluation of trends relative to other major risk factors requires regularly updated, accurate, spatially resolved exposure estimates. We combined satellite-based estimates, chemical transport model (CTM) simulations and ground measurements from 79 different countries to produce new global estimates of annual average fine particle (PM2.5) and ozone concentrations at 0.1° × 0.1° spatial resolution for five-year intervals from 1990-2010 and the year 2013. These estimates were then applied to assess population-weighted mean concentrations for 1990 – 2013 for each of 188 countries. In 2013, 87% of the world’s population lived in areas exceeding the World Health Organization (WHO) Air Quality Guideline of 10 μg/m3 PM2.5 (annual average). Between 1990 and 2013, decreases in population-weighted mean concentrations of PM2.5 were evident in most high income countries, in contrast to increases estimated in South Asia, throughout much of Southeast Asia, and in China. Population-weighted mean concentrations of ozone increased in most countries from 1990 - 2013, with modest decreases in North America, parts of Europe, and several countries in Southeast Asia.

Ratios of T-cell immune-effectors with tumour associated macrophages and PD-1/PD-L1 axis immune-checkpoint molecules, as prognosticators in diffuse large B cell lymphoma: A population-based study

Background Risk-stratification of diffuse large B-cell lymphoma (DLBCL) requires identification of patients with disease that is not cured despite initial R-CHOP. Although the prognostic importance of the tumour microenvironment (TME) is established, the optimal strategy to quantify it is unknown. Methods The relationship between immune-effector and inhibitory (checkpoint) genes was assessed by NanoString™ in 252 paraffin-embedded DLBCL tissues. A model to quantify net anti-tumoural immunity as an outcome predictor was tested in 158 R-CHOP treated patients, and validated in tissue/blood from two independent R-CHOP treated cohorts of 233 and 140 patients respectively. Findings T and NK-cell immune-effector molecule expression correlated with tumour associated macrophage and PD-1/PD-L1 axis markers consistent with malignant B-cells triggering a dynamic checkpoint response to adapt to and evade immune-surveillance. A tree-based survival model was performed to test if immune-effector to checkpoint ratios were prognostic. The CD4*CD8:(CD163/CD68)*PD-L1 ratio was better able to stratify overall survival than any single or combination of immune markers, distinguishing groups with disparate 4-year survivals (92% versus 47%). The immune ratio was independent of and added to the revised international prognostic index (R-IPI) and cell-of-origin (COO). Tissue findings were validated in 233 DLBCL R-CHOP treated patients. Furthermore, within the blood of 140 R-CHOP treated patients immune-effector:checkpoint ratios were associated with differential interim-PET/CT+ve/-ve expression.