cssi/SciSciGPT-SciSciNet huggingface dataset:
Hemophilia: New Protein Therapeutics

Therapeutic advances for patients with hemophilia have resulted in reduced mortality, improved joint outcomes, safety from blood-transmitted pathogens, improved quality of life, and a normalized life span in the developed world. The production of recombinant coagulation factors has increased the worldwide capacity for replacement therapy and facilitated aggressive prophylactic therapy. However, this has come at significant cost, and barriers remain to broad application of prophylaxis. Recombinant DNA technology remains a promising platform to develop novel hemophilia therapeutics with improved functional properties to try to overcome some of these remaining barriers. Bioengineering strategies have produced novel therapeutics with increased production efficiency, increased potency and resistance to inactivation, prolonged plasma half-lives, and reduced immunogenicity. Alternative nonbiologic therapies may lead to new treatment paradigms. The current pipeline of new technologies and products is promising and growing with several agents already advancing from preclinical to clinical trials. The recurrent hemarthroses and resultant crippling arthropathy of hemophilia have almost been completely eradicated through aggressive prophylactic therapy with clotting concentrates in the developed world when initiated at a young age. Quality-of-life measures in children now track similar to their unaffected peers, and patients engage regularly in sporting activities unimagined in previous generations. 1 Prophylaxis for severe hemophilia is now recognized as the standard of care with optimal initiation very early in life before the onset of repeated hemarthroses, typically between ages 1 to 3 years.2 Nevertheless, barriers remain to realizing the benefits of prophylaxis universally. The development of alloantibodies that inhibit the activity of infused replacement products remains a significant complication (up to 30% of patients with hemophilia A). The costs for prophylactic replacement therapy are much greater than $100,000 per patient per year. Repeated venous access (typically three times per week to every other day) is still a barrier for many. Suboptimal adherence to a prophylactic regimen also compromises outcomes. 3 There is also the frequent requirement for central venous access devices in the youngest boys to facilitate prophylactic infusion with associated risk for infection and thrombosis. 4 Despite the increased capacity of factor concentrate production, worldwide demand for factor VIII is now over 5 billion units per year, most of which is infused in North America and Europe, with 80% of the world still without proper access to replacement therapy. Recombinant DNA technology is now serving as a platform for continued innovation to try to overcome some of the remaining hurdles for hemophilia care. This article summarizes the current and future trends in hemophilia therapeutics, with a particular focus on targeted bioengineering strategies.
Exploring the role of alanine in the structure of the Lac repressor tetramerization domain, a ferritin-like Alacoil.

We are interested in the determinants that specify the structure of antiparallel coiled coils. Antiparallel coiled coils often contain alanine as an important interfacial packing residue; structures containing alanine at certain well-defined positions in the heptad-repeating unit are referred to as Alacoils. Two types have been identified, containing alanine at either the g position of the heptad repeating unit (defined as the d position in the Richardson nomenclature), referred to as a rop-like Alacoil, or the e position (a position in the Richardson nomenclature), referred to as a ferritin-like Alacoil. The Lac repressor tetramerization domain forms an antiparallel four-chain coiled coil, which falls into the second class of Alacoils based on recent crystal structures. The role of alanine in such structures has not yet been explored experimentally. We test the importance of alanine at the e positions on the oligomeric state and stability of the isolated coiled-coil domain of Lac repressor by testing the effect of mutations at this position. We find that mutation to leucine is tolerated and its moderately stabilizing effect is most likely a consequence of plasticity of this motif. The effects on stability of the mutations to either serine or glutamine can be largely accounted for by helix propensity differences between these residues and alanine. The ability of the helices to adjust to such mutations, while maintaining the basic fold of this coiled coil, was further tested by making the same changes at the more highly exposed g position. Leucine at the g positions also causes an increase in stability, presumably by subtle rearrangement of the helices to allow partial desolvation of this side-chain.
In-beam gamma-ray spectroscopy of even Mo and Ru isotopes

Abstract Excited states of 92, 94, 96, 98Mo and 94, 96, 98, 100,102Ru were studied by in-beam γ-ray spectroscopy. The decays of levels populated by the (α, 2n) reaction on even isotopes of Zr and Mo were studied by measurement of the γ-singles spectrum, beam-γ-delay, γγ- coincidences (prompt and delayed), and γ-ray angular distributions. The most notable new feature of these experiments is the use, in-beam, of a sensitive coincidence technique, employing two Ge(Li) spectrometers in conjunction with a two-parameter incremental data-acquisition system, to establish the placement of weak transitions. The level schemes are compared with previous studies of these nuclei. A considerable number of new levels, predominantly of high spin (I > 6), were observed. The observed levels are analyzed in terms of systematics and, where available, detailed shell-model calculations. A general description in terms of excitations in the low-lying orbitals outside a 38-proton+50-neutron core appears adequate to explain much of the data, particularly in those nuclei near the 50-neutron shell. The data are also compared to recent macroscopic calculations of quasi-rotational bands, the VMI model. The observed spin distribution in the residual nuclei indicates a net loss of angular momentum in the emission of neutrons and/or unresolved γ-rays. Calculations based on a microscopic model for neutron evaporation suggest that, with a moment-of-inertia parameter ∮ = 0.5 ∮rigid, the angular-momentum loss can be accounted for entirely by the neutrons, whereas for ∮ > 0.5 /t0rigid, some of it must reside in the unplaced γ-ray transitions.
Conjunctive-management models for sustained yield of stream-aquifer systems

Conjunctive-management models that couple numerical simulation with linear optimization were developed to evaluate trade-offs between groundwater withdrawals and streamflow depletions for alluvial-valley stream-aquifer systems representative of those of the northeastern United States. A conjunctive-management model developed for a hypothetical stream-aquifer system was used to assess the effect of interannual hydrologic variability on minimum monthly streamflow requirements. The conjunctive-management model was applied to the Hunt-Annaquatucket-Pettaquamscutt stream-aquifer system of central Rhode Island. Results show that it is possible to increase the amount of current withdrawal from the aquifer by as much as 50% by modifying current withdrawal schedules, modifying the number and configuration of wells in the supply-well network, or allowing increased streamflow depletion in the Annaquatucket and Pettaquamscutt rivers. Alternatively, it is possible to reduce current rates of streamflow depletion in the Hunt River by as much as 35% during the summer, but such reductions would result in smaller increases in groundwater withdrawals.
Cutting your teeth: The beginning of the learning curve

We explore learning-by-doing in an important setting not previously explored — the context of one or more complex experiences encountered in novel circumstances. We explore characteristics that lead to learning at the beginning of the learning curve. We use data from survey responses of 2,111 entrepreneurs to examine performance of startup firms as a measure of outcomes produced by learning-by-doing from prior founding experience. Results indicate substantial productivity benefits accruing from prior entrepreneurial experience. We are the first to exploit panel data on the entire individual history of firm founding to control for individual fixed effects. Areas where entrepreneurs show possible learning effects include the inclination and/or ability to more quickly go through the process of recognizing an opportunity, developing it, and executing the exit strategy.
How do hydrologic modeling decisions affect the portrayal of climate change impacts

End users face a range of subjective decisions when evaluating climate change impacts on hydrology, but the importance of these decisions is rarely assessed. In this paper, we evaluate the implications of hydrologic modelling choices on projected changes in the annual water balance, monthly simulated processes, and signature measures (i.e. metrics that quantify characteristics of the hydrologic catchment response) under a future climate scenario. To this end, we compare hydrologic changes computed with four different model structures – whose parameters have been obtained using a common calibration strategy – with hydrologic changes computed with a single model structure and parameter sets from multiple options for different calibration decisions (objective function, local optima, and calibration forcing dataset). Results show that both model structure selection and the parameter estimation strategy affect the direction and magnitude of projected changes in the annual water balance, and that the relative effects of these decisions are basin dependent. The analysis of monthly changes illustrates that parameter estimation strategies can provide similar or larger uncertainties in simulations of some hydrologic processes when compared with uncertainties coming from model choice. We found that the relative effects of modelling decisions on projected changes in catchment behaviour depend on the signature measure analysed. Furthermore, parameter sets with similar performance, but located in different regions of the parameter space, provide very different projections for future catchment behaviour. More generally, the results obtained in this study prompt the need to incorporate parametric uncertainty in multi-model frameworks to avoid an over-confident portrayal of climate change impacts. Copyright © 2015 John Wiley & Sons, Ltd.
Is Microfinance Too Micro? Examining Loan Size and Borrowers’ Salaries Effect on MFI Performance

Most microfinance institutions (MFIs) give small loans to a large number of people, focusing on group lending. Although this has proven to be successful for the MFIs, the impact on long-term povert...
Activity- and Target-Dependent Regulation of Large-Conductance Ca2+-Activated K+ Channels in Developing Chick Lumbar Motoneurons

The functional expression of large-conductance (BK-type) Ca2+-activated K+(KCa) channels was examined in developing chick lumbar motoneurons (LMNs) between embryonic day 6 (E6) and E13 using patch-clamp recording techniques. The macroscopic KCacurrent of E13 LMNs is inhibited by iberiotoxin and resistant to apamin. The average macroscopic KCa density was low before E8 and increased 3.3-fold by E11, with an additional 1.8-fold increase occurring by E13. BK-type KCa channels could not be detected in inside-out patches from E8 LMNs but were readily detected at E11. The density of voltage-activated Ca2+currents did not change between E8 and E11. Surgical ablation of target tissues at E5 caused a significant reduction in average KCadensity in LMNs measured at E11. Conversely, chronic in ovo administration of d-tubocurarine, which causes an increase in motoneuron branching on the surface of the muscle target tissue, evoked a 1.8-fold increase in average LMN KCadensity measured at E11. Electrical activity also contributed to developmental regulation of LMN KCa density. A significant reduction in E11 KCa density was found after chronic in ovo treatment with the neuronal nicotinic antagonist mecamylamine or the GABA receptor agonist muscimol, agents that reduce activation of LMNs in ovo . Moreover, 3 d exposure to depolarizing concentrations of external K+ to LMNs cultured at E8 caused an increase in KCa expression. Conversely, tetrodotoxin caused a decrease in KCaexpression in cultured E8 LMNs developing for 3 d in the presence of neurotrophic factors that promote neuronal survival in the absence of target tissues.
Multiuser transmit beamforming for MIMO uplink with individual SINR targets

For multiuser multiple-input multiple-output (MIMO) uplink communications where the signal-to-interference-plus-noise ratio (SINR) of the k-th user, denoted as SINR k , is expected to achieve the target value γk , we first consider the ideal scenario where multiuser channel matrices are perfectly known to every user and we solve the problem of maximizing min k (SINR k / γk ) over all possible beamformers under individual transmit power constraints via alternating optimization strategies and the generalized eigenvalue problem (GEVP) programming. Then, we study a more realistic situation where only a few number of bits are allowed to feed back to users. We propose to integrate the genetic algorithm into the Lloyd's vector quantization method to design the optimum codebook in terms of maximizing E(min k (SINR k / γk )) with expectation taken with respect to fading channels.
Homodyne generator and detection system

This paper presents a discussion of the operation of a homodyne generator and detection system that can be used to measure high values of attenuation, antenna patterns, etc. from the u.h.f. through the microwave frequency range. The experimental results were obtained with a practical X-band homodyne generator employing readily available commercial components, and using a sawtooth generator in conjunction with a traveling wave tube amplifier as the single side band generator. A brief outline of the operation of the complete system is presented, followed by a discussion of the sensitivity, dynamic range and the magnitude and sources of possible errors. These are illustrated with some experimental results obtained from the actual X-band equipment. In addition, recommendations for improving certain features along with possible modifications of such a system for other purposes are discussed.
Potential benefits of in-vehicle information systems in a real life freeway corridor under recurring and incident-induced congestion

The authors document an initial attempt to ascertain the potential benefits of a real-time in-vehicle traffic information system under recurring and nonrecurring congestion conditions. An actual network in the Santa Monica freeway corridor in Los Angeles was simulated via the FREQ8PC and TRANSYT-7F models. Travel times for both freeway and surface street links from these models were transformed to a network model called PATHNET, which was utilized to determine the travel times for the shortest path between any origin and destination point or for any other path in the network desired. The shortest path is assumed to be the perfect information path. Also considered were freeway-biased paths, arterial-biased paths, and user-defined paths. Comparisons were made for a set of four origin points and three destination points. Under the recurring, non-incident congestion scenario the travel time savings when utilizing the shortest path were generally negligible (less than three minutes for a 20-25 minute trip). Under the nonrecurring, incident congestion scenario (where the incident was created on the freeway and assuming that a small percentage of drivers divert to the surface streets), travel time savings were found to be significant. >
Cost–effectiveness of CYP2b6 genotyping to optimize efavirenz dosing in HIV clinical practice

Aims: To assess the cost–effectiveness of CYP2B6 genotyping to guide efavirenz dosing for initial HIV therapy in the USA. Methods: We used the Cost–Effectiveness of Preventing AIDS Complications (CEPAC) microsimulation model to project quality-adjusted life expectancy and lifetime costs (2014 US dollars) for efavirenz-based HIV therapy with or without CYP2B6 genotyping. We assumed that with genotyping 60% of patients would be eligible to receive lower doses. Results: Current care without CYP2B6 genotyping has an incremental cost–effectiveness ratio >$100,000/QALY compared with genotype-guided dosing, even if lower dosing reduces efficacy. When we assumed generic efavirenz availability, conclusions were similar unless lower dosing reduces efficacy by 6% or more. Conclusion: CYP2B6 genotyping can inform efavirenz dosing and decrease HIV therapy cost.
Effect of oral versus intrauterine progestins on weight in women undergoing fertility preserving therapy for complex atypical hyperplasia or endometrial cancer

Abstract Objective The objective of this analysis was to evaluate weight changes associated with oral progestin therapies versus the levonorgestrel-containing intrauterine device (LNG-IUD) in women undergoing fertility-preserving therapy for complex atypical hyperplasia (CAH) and endometrial cancer (EMC). Methods All patients diagnosed with CAH or EMC managed with fertility-preserving progestin therapy at two institutions from 1998 to 2012 were identified. Those with serial weight measurements before, during and after therapy were included. Patients were categorized according to the type of progestin therapy administered. The rate of weight change over time of patients treated with oral versus intrauterine progestins was compared using the Mann Whitney U test. Results Sixty patients with EMC (35) or CAH (25) were treated during the study period, with 12 patients receiving multiple regimens. These included megestrol acetate (MA, n=42), LNG-IUD (n=22), and other oral progestins (n=11). The median age at diagnosis was 32 and median pre-progestin body mass index (BMI) was 40.4kg/m 2 . The median therapy duration was 11.7months [range: 2.3–118.5]. Median weight change during therapy was greater with MA versus LNG-IUD (+2.95 vs. +0.05kg, P=0.03). Patients with a BMI Conclusion Oral progestin therapy for conservative treatment of young EMC/CAH survivors is associated with increased weight gain, especially when megestrol acetate is utilized. Utilization of LNG-IUD may result in less weight gain.
Transit Fare Affordability: Findings From a Qualitative Study:

Low-income groups use transit in greater numbers than others. There is little scholarship, however, about how they afford the fare. Using interviews with 25 low-income residents and 15 transportati...
Abstract KN01: Updates on engineered T cells as cancer therapies

The field of adoptive cell transfer (ACT) is currently comprised of chimeric antigen receptor (CAR T) and TCR engineered T cells and has emerged from principles of basic immunology to paradigm-shifting clinical immunotherapy. ACT of T cells engineered to express artificial receptors that target cells of choice is an exciting new approach for cancer, and it holds equal promise for chronic infection and autoimmunity. Using principles of synthetic biology, advances in immunology, and genetic engineering have made it possible to generate human T cells that display desired specificities and enhanced functionalities. Clinical trials in patients with advanced B cell leukemias and lymphomas treated with CD19-specific CAR T cells have induced durable remissions in adults and children. The prospects for the widespread availability of engineered T cells have changed dramatically given the recent entry of the pharmaceutical industry to this arena. In this presentation, I will discuss some of the challenges and opportunities that face the field of ACT. References: 1. Maude S, Frey N, Shaw P, Aplenc R, Barrett D, Bunin N, Chew A, Gonzalez V, Zheng Z, Lacey S, Mahnke Y, Melenhorst J, Rheingold S, Shen A, Teachey D, Levine B, June C, Porter D, and Grupp SA. Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia. N Engl J Med. 2014;371(16):1507-17. 2. Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, Grupp SA, and Mackall CL. How I treat: current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124(2):188-95. 3. Rapoport AP, Stadtmauer EA, Binder-Scholl GK, Goloubeva O, Vogl DT, Lacey SF, Badros AZ, Garfall A, Weiss B, Finklestein J, Kulikovskaya I, Sinha SK, Kronsberg S, Gupta M, Bond S, Melchiori L, Brewer JE, Bennett AD, Gerry AB, Pumphrey NJ, Williams D, Tayton-Martin HK, Ribeiro L, Holdich T, Yanovich S, Hardy N, Yared J, Kerr N, Philip S, Westphal S, Siegel DL, Levine BL, Jakobsen BK, Kalos M, and June CH. NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nature Medicine. 2015;21(8):914-21. 4. Garfall AL, Maus MV, Hwang WT, Lacey SF, Mahnke YD, Melenhorst JJ, Zheng Z, Vogl DT, Cohen AD, Weiss BM, Dengel K, Kerr ND, Bagg A, Levine BL, June CH, and Stadtmauer EA. Chimeric Antigen Receptor T Cells against CD19 for Multiple Myeloma. N Engl J Med. 2015;373(11):1040-7. Citation Format: Carl H. June. Updates on engineered T cells as cancer therapies. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr KN01.
Sucrose as a sweetener for activated charcoal

The efficacy of sucrose as a flavor for activated charcoal was studied. In vitro adsorption of sucrose (in Simulated Gastric Fluid, USP, without pepsin) to activated charcoal, and of a 1-g/liter sodium salicylate solution to a 1:1 mixture of sucrose and activated charcoal and to plain activated charcoal, was measured spectrophotometrically. In vitro adsorption of sucroses to activated charcoal was minimal. Sucrose reduced in vitro adsorption of sodium salicylate to activated charcoal by only small amounts. For example, at a ratio of 4 g activated charcoal to 1 g sodium salicylate, sucrose reduced salicylate adsorption to activated charcoal from 99% to 95%. A 1:1 sucrose-activated charcoal preparation provides sufficient flavor without substantial loss of adsorbance.
Was macht die Pflege von demenzkranken alten Menschen so schwierig

Unsere Patientinnen leben in ihrer Welt und drucken ihre Bedurfnisse in ihrer Art und Weise aus. Unsere Aufgabe ist es, jeder einzelnen von ihnen auf ihre Gefuhlsebene zu folgen, mit ihr in Beziehung zu treten, darauf zu achten, sie nicht zu verletzen, ihre korperlichen Schmerzen und qualenden Beschwerden zu erkennen und moglichst zu lindern. Daruber hinaus mussen wir ihre seelischen Bedurfnisse und ihre Ressourcen wahrnehmen und ihr dabei helfen, sich als wertvolles Mitglied der Gemeinschaft zu fuhlen. Dies alles fordert uns ununterbrochen sowohl in unserer fachlichen als auch in unserer menschlichen Kompetenz und ist daher von niemandem vollstandig zu erbringen. Zum Gluck verzeihen uns unsere Patientinnen unser Fehlverhalten, wenn sie spuren, dass wir ihnen ehrlich zugewandt sind. Dieses Zugewandtsein erklart auch, warum wir trotz aller Belastungen gerne unserem Beruf nachgehen
Body Mass Index at 3 Years of Age: Cascading Effects of Prenatal Maternal Depression and Mother-Infant Dynamics.

Objective To investigate the effects of mothers' prenatal depression on parenting during infancy, ensuing childhood regulation, and body mass index (BMI) at age 3 years. Study design The sample (N = 284) included teen mothers (n = 157), adult mothers with low education (n = 69), and adult mothers with high education (n = 58), and their first-born children. Maternal depressive symptoms were assessed prenatally through self-report; observational methods and self-report were used to assess mothers' parenting at 4, 6, and 8 months and children's regulation at 18, 24, and 30 months of age. Child BMI was measured at 36 months of age in the laboratory. Results Structural equation modeling supported mediating processes such that mothers who reported more depressive symptoms prenatally exhibited less positive parenting during infancy. In turn, less positive parenting predicted lower levels of child regulation during toddlerhood, which predicted higher child BMIs at 36 months of age, even after controlling for infant birth weight and concurrent maternal BMI. Models comparing groups (teen mothers, adult low-educated mothers, and adult-high educated mothers) indicated mean differences in maternal depression, parenting, and child regulation, but similar patterns of prediction across groups. Conclusions The present study provides evidence of cascading psychosocial processes beginning prenatally and continuing through infancy, toddlerhood, and into early childhood. Results have implications for family-wide intervention strategies to help lower the risk for early onset obesity in children.
The Distribution of Intensity Associated With the Great 1897 Assam Earthquake and Bounds on the Extent of the Rupture Zone

The great 1897 Assam earthquake probably was associated with underthrusting of the Indian subcontinent beneath the Shillong Plateau, and as such it absorbed part of India's convergence with the Himalaya. Seeber and Armbruster (1981) concluded that slip occurred on a fault that extended north beneath the Himalaya and south beneath much of what is now Bangladesh and that the east-west dimension of the rupture was 550 km. A reassessment of the information given by Oldham (1899) leads me to favor Oldham's inference that the length of the rupture was only about 200 km. The southern edge of the rupture was more likely at the southern edge of the Shillong Plateau than south of it. The possibility that the rupture extended beneath the Himalaya seems to be permissible but not provable from Oldham's observations. Thus, it would be unwise to assume that the 1897 earthquake released the strain that had accumulated east and west of the Shillong Plateau since the last earthquakes in those areas. Although the risk of a large earthquake in the near future in the segment north of the Shillong Plateau is probably less than that in the segments of the range to the east or west, the 1897 earthquake may not have relieved the strain in that segment as well. Given the evidence that the 1897 earthquake was a very large earthquake, however, it seems unlikely that there will be a repeat of such an event in the next hundred years, or more.
Some Present-Day Asylum Seekers in the U.S.: Machismo and "Women on the Run"

Following a brief review of international asylum law (The Geneva Conventions), and the role of American mental health professionals in the asylum process, this paper attempts to understand the ways in which the often trauma-creating custom of machismo is transferred across generations in Central American families. Using as background the work of self psychologist Alan Roland (1989,1996, 2005), I have described families from these areas as so powerfully father-centric that children develop a sense of themselves based largely on their ability to sustain their father’s positive regard. In addition, without discussion, they present a positive image of him to the outside world, even when his behavior at home is brutal. To do otherwise would be humiliating. Having no place to reflect on these customs, often they are acted upon/acted out in the next generation. Note:We publish thi paper also tranlated in italian by Francesca Tessitore (Francesca Tessitore, Psychologist, PhD Student in Mind, Gender and Languages, her research fields are the processes of female immigration and motherhood at risk through a psychodynamic framework. francitessitore@gmail.com ).
Surface Engineered Nanoparticles: Considerations for Biomedical Applications

The development of reproducible methods for the fabrication of nanoparticles in the 21st century is a major scientific achievement. Currently, there are many well-established methods for the production of nanoparticles of different shapes, sizes, and compositions. Along with these advancements in nanotechnology, nanoparticles have emerged as excellent tools for a diverse range of applications and have become a focus of research globally. With fundamental research being established, efforts are now being directed toward intelligently designed nanoparticles in which the properties of the nanomaterial are finely tuned depending on the application of interest. Usually, this involves the functionalization of the nanoparticle surface with a ligand. In this review, the impact of nanoparticle surface chemistry is discussed as it applies to biological systems.
UV plasmonic enhancement through three dimensional nano-cavity antenna array in aluminum

Metallic nanostructure can enhance fluorescence through excited surface plasmons which increase the local field as well as improve its quantum efficiency. When coupling to cavity resonance with proper gap dimension, gap hot spots can be generated to interact with fluorescence at their excitation/emission region in UV. A 3D nano-cavity antenna array in Aluminum has been conducted to generate local hot spot resonant at fluorescence emission resonance. Giant field enhancement has been achieved through coupling fundamental resonance modes of nanocavity into surface plasmons polaritons (SPPs). In this work, two distinct plasmonic structure of 3D resonant cavity nanoantenna has been studied and its plasmonic response has been scaled down to the UV regime through finite-difference-time-domain (FDTD) method. Two different strategies for antenna fabrication will be conducted to obtain D-coupled Dots-on-Pillar Antenna array (D2PA) through Focus Ion Beam (FIB) and Cap- Hole Pair Antenna array (CHPA) through nanosphere template lithography (NTL). With proper optimization of the structures, D2PA and CHPA square array with 280nm pitch have achieved distinct enhancement at fluorophore emission wavelength 350nm and excitation wavelength 280nm simultaneously. Maximum field enhancement can reach 20 and 65 fold in the gap of D2PA and CHPA when light incident from substrate, which is expected to greatly enhance fluorescent quantum efficiency that will be confirmed in fluorescence lifetime measurement.
The Interaction Between Storage and Computation in Morphosyntactic Processing

The term morphology derives from the Greek word “morphe” meaning “form,” and is generally used to refer to the study of the physical forms of entities in many scientific disciplines. In linguistics and psycholinguistics, morphology is the study of the internal structure of words which are the linguistic units that provide the main mapping between form and meaning. Word recognition has had a long and distinguished history in psycholinguistics, yet few models of lexical processing have included morphology as a level of linguistic representation. This may be because despite the ubiquity of multi-morphemic words, many current models of visual word recognition have been developed to model the mapping of orthography and phonology onto semantics—and thus have focused on morphologically simple words. Expanding the focus of research to include multi-morphemic words will significantly advance our understanding of reading by allowing us to evaluate the contribution of morphological analysis to the process of word recognition.
Identification of an amphipathic helix within IFITM3 that promotes inhibition of influenza virus

Interferon-induced transmembrane protein 3 (IFITM3) inhibits influenza virus fusion with endosomes by altering cellular membrane properties through mechanisms that are largely uncharacterized. In order to identify regions of secondary structure within IFITM3 that may contribute to its mechanism of action, we performed structural predictions using the I-TASSER and PSSpred algorithms. Insterestingly, we identified a 10-amino acid region of likely helicity that possesses an amphipathic distribution of amino acids. Consistent with the known role of amphipathic helices in altering membrane properties, we observed that cells expressing a helix-deleted mutant of IFITM3 were infected with influenza virus at a 4-fold higher rate than cells expressing WT IFITM3. Confirming that the amphipathicity of this helix contributes to antiviral activity, single, double and triple alanine mutations of the three residues making up the hydrophilic face of the helix progressively decreased antiviral activity of IFITM3, as did single polar mutations in the hydrophobic face of the helix, or single amino acid insertions that disrupted amphipathicity. Amino acid sequence alignments suggest that amphipathicity in this region is highly conserved in IFITMs throughout evolution. Overall, we utilized bioinformatics methods coupled with functional infectivity assays to provide the first evidence that IFITM3 utilizes an amphipathicity-based mechanism for inhibition of viruses.
Relationship between individual and family characteristics and psychosocial factors in persons with familial pancreatic cancer.

OBJECTIVE Describe relationships between self-reported personal demographics or familial characteristics and psychosocial outcomes (Patient Reported Outcome Measurement Information System Global Health, Impact of Event Scale-Revised [pancreatic cancer risk-related distress], cancer risk perception, and cancer worry) in participants with inherited or familial pancreatic cancer risk. METHODS A multisite cross sectional survey of adults with elevated pancreatic cancer risk based on family history. All variables were summarized with descriptive statistics. To assess univariate associations, t test and chi-square/Fisher's exact test were used, and backward model selection was used in multivariable analysis. RESULTS Respondents (N = 132) reported moderate to high frequency of cancer worry and 59.3% perceived a 50% or more perceived lifetime risk for pancreatic cancer, which far exceeds objective risk estimates. Cancer worry was associated with female gender (P = .03) and pancreatic cancer risk specific distress (P = .05). Higher-risk perception was associated with having a high school education or less (P = .001), higher distress (P = .02), and cancer worry (P = .008) and family cancer death experience (P = .02). Higher distress was associated with experience as a caregiver to a seriously ill family member in the past 5 years (P = .006). CONCLUSIONS Individuals with inherited or familial pancreatic cancer risk experience cancer worry, distress, and have increased risk perception, particularly in the period following caring for a loved one with cancer. Routine evaluation of distress in this setting, as well as the development of supportive care resources, will help support patients living with risk for pancreatic cancer.
The role of macrophages in THC-induced alteration of the cytokine network.

Delta-9-tetrahydrocannabinol (THC) has been shown to decrease Thl responses (cell mediated immunity) while increasing Th2 responses (humoral immunity), both in vitro and in vivo. The addition of THC to murine splenocytes stimulated for 72 hrs with pokeweed mitogen (PWM) increased the detection of IL-4 and IL-10, cytokines associated with Th2 responses, and decreased IFNγ, IL-15 and IL-12, cytokines associated with Thl responses. To investigate the cellular molecular basis for these effects of THC, cell depletion studies were performed. Removal of macrophages from the cell cultures eliminated the increase in IL-4 activity. This effect was observed when the macrophages were depleted during the first few hours but not after 24 hrs. Thus, it appears that the macrophages were producing an early factor responsible for the IL-4 increase. To examine the direct effect of THC on macrophages, peritoneal macrophages were cultured with various stimulators in the presence of THC. It was found that THC suppressed IL-12, IL-15 and IL-6 and increased IL-lα, IL-lβ, and TNFα in all of the stimulated cultures. IL-12 and IL-15 are known to induce IFNγ production from T cells and NK cells and to be involved in the induction a Thl response, while IL-1 is considered a growth factor for Th2 cells. Thus, the effects of THC on macrophages reflects the basic observation that THC decreases Thl responses and increases Th2 responses. The data obtained adds to the understanding of the THC-induced Thl/Th2 shift, but the mechanisms still must be determined. However, the results of these studies do suggest that, in addition to lymphocytes, THC affects macrophages in splenocyte cultures and that the macrophages are involved in the alternation of the cytokines. Furthermore, the data demonstrate the diversity of the immunomodulatory effects THC exerts.
Extracting Relations from XML Documents

XML is becoming a prevalent format for data exchange. Many XML documents have complex schemas that are not always known, and can vary widely between information sources and applications. In contrast, database applications rely mainly on the flat relational model. We propose a novel, partially supervised approach for extracting user-defined relations from XML documents with unknown schema. The extracted relations can be directly used by an RDBMS, or utilized for information integration or data mining tasks. Our method attempts to automatically capture the lexical and structural features that indicate the relevant portions of the input document, based on a few user-annotated examples. This information can then be used to extract the relation of interest from documents with schemas potentially different from the training examples. We present preliminary experiments showing that our method could be capable of extracting the target relation from XML documents even in the presence of significant variations in the document schemas.
Power Management for Multicore Processors via Heterogeneous Voltage Regulation and Machine Learning Enabled Adaptation

This work is based on the vision that the ultimate power integrity and efficiency may be best achieved via a heterogeneous chain of voltage processing starting from onboard switching voltage regulators (VRs), to on-chip switching VRs, and finally to networks of distributed on-chip linear VRs. As such, we propose a heterogeneous voltage regulation (HVR) architecture encompassing regulators with complimentary characteristics in response time, size, and efficiency. By exploring the rich heterogeneity and tunability in HVR, we develop systematic workload-aware power management policies to adapt heterogeneous VRs with respect to workload change at multiple temporal scales to significantly improve system power efficiency while providing a guarantee for power integrity. The proposed techniques are further supported by hardware-accelerated machine learning (ML) prediction of nonuniform spatial workload distributions for more accurate HVR adaptation at fine time granularity. Our evaluations based on the PARSEC benchmark suite show that the proposed adaptive three-stage HVR reduces the total system energy dissipation by up to 23.9% and 15.7% on average compared with the conventional static two-stage voltage regulation using off-chip and on-chip switching VRs. Compared with the three-stage static HVR, our runtime control reduces system energy by up to 17.9% and 12.2% on average. Furthermore, the proposed ML prediction offers up to 4.1% reduction of system energy.
Polynomially bounded error estimates for Trapezoidal Rule Convolution Quadrature

Abstract We clarify the dependence with respect to the time variable of some estimates about the convergence of the Trapezoidal Rule based Convolution Quadrature method applied to hyperbolic problems. This requires a careful investigation of the article of Lehel Banjai where the first convergence estimates were introduced, and of some technical results from a classical paper of Christian Lubich.
What Consumers Say About Hospices in Online Reviews.

Background: Until recently, consumers have had limited resources to assess quality of hospices agencies, contributing to growing numbers of consumers turning to online review sites, such as Yelp. However, little is known about the content of hospice Yelp reviews and how these relate to recently available Center for Medicare and Medicaid Services' Hospice Compare (HC) site data. Objective: To better understand what consumers report on Yelp about hospice care and explore how these areas relate to HC data. Design: We examined 692 consumer Yelp reviews of 67 hospices in California and compared identified themes with quality measures presented on the HC site. Setting/Subjects: We used a purposive sample of California Hospice's with Yelp reviews. Measurements: Qualitative consumer comments about their experience with hospice care were analyzed by using a grounded theory approach. Results: We found that overall Yelp comments were positive, however Yelp themes were more extensive and diverse than those on HC. Conclusion: We recommend that consumers consider both HC and online review sites such as Yelp when evaluating a hospice.
Charge Nurses Taking Charge, Challenging the Culture of Culture-Negative Sepsis, and Preventing Central-Line Infections to Reduce NICU Antibiotic Usage

Objective We aimed to reduce our monthly antibiotic usage rate (AUR, days of treatment per 1,000 patient-days) in the neonatal intensive care unit (NICU) from a baseline of 330 (July 2015–April 2016) to 200 by December 2018. Study Design We identified three key drivers as follows: (1) engaging NICU charge nurses, (2) challenging the culture of culture-negative sepsis, and (3) reducing central-line associated bloodstream infections (CLABSI). Our main outcome was AUR. The percentage of culture-negative sepsis that was treated with antibiotics for >48 hours and CLABSI was our process measure. We used hospital cost/duration of hospitalization and mortality as our balancing measures. Results After testing several plan-do-study-act (PDSA) cycles, we saw a modest reduction in AUR from 330 in the year 2016 to 297 in the year 2017. However, we did not find a special-cause variation in AUR via statistical process control (SPC) analysis (u'-chart). Thereafter, we focused our efforts to reduce CLABSI in January 2018. As a result, our mean AUR fell to 217 by December 2018. Our continued efforts resulted in a sustained reduction in AUR beyond the goal period. Importantly, cost of hospitalization and mortality did not increase during the improvement period. Conclusion Our sequential quality improvement (QI) efforts led to a reduction in AUR. We implemented processes to establish a robust antibiotic stewardship program that included antibiotic time-outs led by NICU charge nurses and a focus on preventing CLABSI that were sustained beyond the QI period. Key Points
Choriocapillaris flow loss in center-involving retinitis pigmentosa: a quantitative optical coherence tomography angiography study using a novel classification system

Choriocapillaris insufficiency may play a role in centripetal retinitis pigmentosa (RP) progression involving the fovea. However, the relationship between choriocapillaris integrity and foveal damage in RP is unclear. We examined the relationship between choriocapillaris flow and the presence of foveal photoreceptor involvement in RP. We categorized the severity of central involvement in RP by the occurrence of foveal ellipsoid zone (EZ) disruption: present (severe RP) or absent (mild RP). Using optical coherence tomography angiography (OCTA, AngioVue, Optovue) in cases and unaffected age-matched controls, we compared vessel density (VD) between the groups using the generalized linear mixed model, controlling for age, gender, and scan quality. Fifty-seven eyes (20 severe RP, 18 mild RP, and 19 controls) were included. Foveal and parafoveal mean outer retinal thickness (µm) were lower in severe RP (fovea: 101.3 ± 14.5; parafovea: 68.4 ± 11.7) than controls (fovea: 161.2 ± 8.9; parafovea: 142.1 ± 11.8; p ≤ 0.001) and mild RP (fovea: 162.0 ± 14.7; parafovea: 116.8 ± 29.4; p ≤ 0.0001). Foveal choriocapillaris VD (%) was lower in severe RP (56.7 ± 6.8) than controls (69.9 ± 4.6; p = 0.008) and mild RP (65.3 ± 5.3; p = 0.01). The parafoveal choriocapillaris VD was lower in severe RP than controls (64.4 ± 5.9 vs. 68.3 ± 4.1; p = 0.04) but no different than in mild RP (p = 0.4). Choriocapillaris flow loss was associated with fovea-involving photoreceptor damage in RP. Further research is warranted to validate this putative association and clarify causation. Choriocapillaris imaging using OCTA may provide information to supplement structural OCT findings when evaluating subjects with RP in neuroprotective or regenerative clinical trials.
Stabilizing and Strengthening the Affordable Care Act: Opportunities for a New Administration

For the past decade, the Affordable Care Act (ACA) has successfully reduced uninsurance and improved access to and affordability of health care services for millions of Americans. But the law was weakened when the Trump administration shortened the open enrollment period in the federal Marketplace, reduced outreach and enrollment funding, and revised the public charge rule, among other actions. The Biden administration will have the chance to reverse some of these changes and further strengthen the law to improve health care access and affordability. In this article, the author explores options for expanding access to affordable coverage and care for those who do not qualify for Medicaid or marketplace financial assistance and further discusses opportunities for increasing enrollment among those who are already eligible. The author also examines opportunities for expanding access to specific services, including reproductive health care, among those with insurance. Any attempts to modify or build on the ACA will likely be complicated by the ongoing coronavirus pandemic as well as slim Democratic majorities in the House and Senate, but regulatory solutions will likely be easier to achieve than those that require changes to federal law or state policy.
Stimulated Electron Radiation in a Medium due to Wiggled Magnetic Field

The PDECC (partial differential equations respect to coupling constants) formalism [1,2] is used to derive the S matrix suitable for treating the stimulated radiation when an electron interacts with a static wiggled magnetic field in a dielectric medium. The power spectrum, P(w), of emitted radiation is calculated from the vacuum to vacuum S matrix transition, , through the relation
Greater trochanter osteotomy as a component of cementless total hip replacement: Five cases in four dogs

OBJECTIVE To describe the surgical technique and report the long-term outcome of greater trochanteric osteotomy (GTO) as a component of cementless total hip replacement (THR) in dogs with severe medialization of the greater trochanter or chronic craniodorsal hip luxation. STUDY DESIGN Short case series. ANIMALS Four dogs treated with five THRs. METHODS Data collected from medical records included signalment, indication for THR, duration of clinical signs, body weight, pre- and post-operative radiographic assessment, surgical templating, osteotomy technique, THR implant selection, surgical time, complications, and long-term clinical and radiographic follow-up. Clinical outcomes were determined based on in-hospital history, orthopedic examination, and radiographic evaluation. RESULTS All five surgical procedures resulted in satisfactory long-term clinical results at follow-up a median of 48.2 months (range, 34-56 months) after THR. There were no minor complications and one major complication. One dog experienced post-operative luxation unrelated to the GTO and was successfully treated with a cup revision. CONCLUSION AND CLINICAL RELEVANCE GTO was effective in facilitating cementless THR in dogs with either severe medialization of the greater trochanter or chronic craniodorsal luxation.