cssi/SciSciGPT-SciSciNet huggingface dataset:
The Capillary Circulation

The modern understanding of the capillary circulation represents a fusion of information about structure and function accumulated over the last three hundredyears. The clear definition of structure depended upon the development of increasingly powerful light microscopes and, more recently, upon the great resolving capacity of the electron microscope; the comprehension of function involved the knowledge and techniques of physiology, physics, chemistry, and pathology. Therefore, it is not surprising that the growth of ideas about the capillary circulation has been uneven; often progress was completely arrested because essential information from other fields was not yet available.
Positive emotion infusions of elevation and gratitude: Increasing help-seeking intentions among people with heightened levels of depressive symptomatology

AbstractThree online studies assessed a new approach for increasing help seeking among people with depressive symptomatology (i.e. a positive emotion infusion, PEI). A PEI refers to the induction of positive emotion such that people’s mindsets – including perceptions of help-seeking – are temporarily altered. Study 1 (n = 382) indicated that help-seeking intentions are negatively correlated with depressive symptomatology and positively correlated with elevation and gratitude. Studies 2 and 3 implemented fully randomized experimental designs. In Study 2, two elevation-based (Study 2a, n = 285) and two gratitude-based (Study 2b, n = 338) emotion inductions increased levels of elevation and gratitude, respectively. Results of Study 3a (n = 390) indicate a causal relationship between experiencing the story-based elevation induction and increased help-seeking intentions. The two gratitude-based PEIs (Study 3b, n = 466) were unsuccessful at influencing help-seeking; auxiliary analyses indicate the possibility o...
Lack of dentin acid resistance following 9.3 um CO2 laser irradiation

Previous studies have shown that laser irradiation of dental enamel by specific carbon dioxide laser conditions can inhibit subsequent acid dissolution of the dental enamel surface. The purpose of this study was to determine whether similar carbon dioxide laser conditions would have a protective effect on dentin. Blocks of human dentin roots (3x3 mm 2 ) were irradiated at 9.3 µm wavelength with a 15-18 µs pulse duration laser and fluences of 0.50-1.50 J/cm 2 . A motion controller system was used to ensure uniform irradiation of the entire dentin surface. Surface acid dissolution profiles following irradiation were acquired for the five study groups, control group (Non-irradiated) and four laser-treated groups. Dissolution profiles of low fluence groups (0.50 and 0.75 J/cm 2 ) exhibited similar profiles to the control group. Dissolution profiles of higher fluence groups (1.0 and 1.5 J/cm 2 ) showed an increased dissolution rate over the control group, but these differences were not statistically significant (p>0.05). This study demonstrated that the application of carbon dioxide laser irradiation significantly alters the surface of dentin but did not decrease the acid dissolution rate. Keyword: Acid resistance, CO2 laser, irradiation, dissolution, dissolution.
Need a Change? Try GeTe: A Reconfigurable Filter Using Germanium Telluride Phase Change RF Switches

There is an increasingly high demand for compact, low-loss reconfigurable filters in various advanced wireless applications: cognitive radios, modern transceivers, and antijamming communication systems, to name a few [1]. With reconfigurable filters, wireless communication systems that require multiple operating frequency bands can be implemented in a smaller size and at a reduced cost compared to conventional systems using multiple single-frequency filters. Bandpass filters provide a better RF performance compared to low-pass or high-pass filters, resulting in improved signal-to-noise ratio and out-of-band performance [2].
A World Beyond the Veil: Pursuing Gender Equality in Pakistan

Pakistan has been prominently featured in the media usually with images of angry fundamentalists and submissive veiled women. Although women’s organizations have been functioning in Pakistan since the founding in 1947 and a small but vibrant women’s movement continues today, the voices of women and human rights activists are mostly unheard. This qualitative study explores the experiences of women’s rights activists who are involved with secular human rights-oriented organizations in Lahore, Pakistan. It examines the interface of gender, religion, education, and politics as they promote gender equality and women’s rights to freedom from violence. With a broad view of knowledge as empowerment and a human right framework for action, they have initiated a variety of programs that promote legal literacy, support women’s access to education, and challenge patriarchal ideologies through publication of educational materials that counter intolerance of difference on the basis of religion, gender, and nationality and seek to introduce young people to human rights concepts. This chapter will examine how secular human rights organizations navigate cultural barriers and function within Pakistan’s socio-religious-legal context.
Response to Receiving the John W. Knutson Distinguished Service Award in Dental Public Health

pride of the teacher, and that’s the sort of thing I think Dave has done superlatively. Just tonight, for example, I heard of how he went out to Aberdeen, South Dakota, to help one of his former students achieve approval of a residency in dental public health out in what some would call the boondocks, not your usual academic institution. Today, Dave still gets an enormous number of telephone calls and letters from people all over the world because, when they need help and advice, it seems only natural to them to turn to Dr. Striffler. That must be a source of great satisfaction to him, as it is to the rest of us. People have characterized Dave as having an iron hand in a velvet glove. In fact, it ought to be other way around, because Dave Striffler is basically a softi-veryone knows he’s a soft touch. He is intensely loyal, stands up for people, and is always ready to help. The kinds of things he has accomplished bring credit to The University of Michigan School of Public Health, to the dental profession, to the Dental Health Section of APHA, to all of us here, and in the last analysis to Dave Striffler, himself. I ask you to join me in saluting this year’s John W. Knutson awardee, Dr. David Frank Striffler.
Indoor temperature and humidity in New York City apartments during winter

Abstract Background Concerns about indoor residential humidity have largely centered on dampness prevention. Overly dry air, however, may favor the survival of some viruses and hence respiratory infections. Many residents employ portable humidifiers to humidify their home environment, yet the effect of these humidifiers on indoor humidity is not known. Methods We monitored indoor temperature and humidity in 34 apartments in New York City during winter 2014–2015. We combined information from the monitors with surveyed information on building, household, and apartment-level factors and with information on household humidifier use. Using multilevel regression models, we investigated the role of these factors on indoor absolute humidity levels during the winter. Results Mean indoor vapor pressure (a measure of absolute humidity) was 6.7 mb in the surveyed homes during the winter season. Ownership of a humidifier was not associated with higher indoor humidity levels; however, larger building size (above 100 units) was significantly associated with lower humidity. The presence of a radiator heating system was non-significantly associated with higher humidity. Conclusions The wintertime indoor environment in this sample of New York City apartments is dry. Future research is needed to evaluate the effectiveness of portable humidifiers in the home and to clarify the relationship between dry indoor air and the transmission of viral infections.
Endogenous Two-Photon Excited Fluorescence Imaging Characterizes Neuron and Astrocyte Metabolic Responses to Manganese Toxicity

As neurodegenerative conditions are increasingly linked to mitochondrial dysfunction, methods for studying brain cell metabolism at high spatial resolution are needed to elucidate neurodegeneration mechanisms. Two-photon excited fluorescence (TPEF) imaging is a non-destructive, high-resolution technique for studying cell metabolism via endogenous fluorescence of reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD). We employed TPEF to study the metabolism of primary rat astrocyte and neuronal cultures under normal growth conditions and in response to manganese (Mn) treatment. Histograms of pixel-wise optical redox ratio, defined as FAD/(FAD + NAD(P)H), revealed three distinct redox distributions and significant differences in their relative weights between astrocytes and neurons. When treated with Mn, both cell types exhibited redox ratio shifts consistent with increased oxidative stress. However, the manner in which the redox distributions was affected was distinct for the two cell types. Furthermore, NAD(P)H fluorescence lifetime imaging revealed an increase in bound NAD(P)H fraction upon Mn treatment for neurons, consistent with enhanced apoptosis. Astrocytes showed a decrease in bound fraction, possibly due to a shift towards glycolytic metabolism in response to impaired respiration. These results exhibit TPEF’s utility for characterizing detailed metabolic changes of different brain cell types in response to neurotoxins.
Medical residents' circadian preferences across specialties.

Objective Circadian preference refers to the tendency of individuals to be more alert and effective in the morning (larks) or the evening (owls). Given the rigors of medical residency training and perceived lifestyle differences among specialties, circadian preference may play a role in choice of medical specialty and subsequent job satisfaction during training. This study aimed to determine the circadian preferences of residents across specialties and correlations with specialty choice and job satisfaction. Study Design Single-institution, cross-sectional survey. Methods The Horne-Ostberg Morningness-Eveningness questionnaire, the standard to identify circadian preference, was modified to include demographic and job satisfaction variables and administered to residents at our tertiary care hospital in 2014. Independent t tests were used to correlate circadian preference and specialty choice, and Spearman's correlations were used to correlate circadian preference and job satisfaction. Results A total of 160 residents from postgraduate years 1 through 7 and 10 specialties responded. The mean chronotype scores from all specialties met the category of “neither” morning nor evening type. A significant difference occurred between emergency medicine residents and residents from anesthesiology (P = 0.0007), surgery (P < 0.0001), and medicine (P = 0.0005). Residents in the surgical specialties trended toward the morning chronotype, whereas emergency medicine trended toward evening chronotype. There was no significant correlation between chronotype and job satisfaction. Conclusion Although preliminary because of the low response rate, this study points to the potential of considering circadian preference in choice of specialty training and for designing resident on-call schedules. Level of Evidence NA. Laryngoscope, 2017
Successful Management of Early Peri-Implant Infection and Bone Loss Using a Multidisciplinary Treatment Approach.

Introduction: Peri-implant infections can occur any time post-loading. Although management of peri-implant infections has been described extensively in the literature, no consensus exists on the best approach to its treatment. Infections and bone loss can also occur around implants prior to loading, leading to early implant loss. Little has been reported on management of peri-implant infections occurring prior to loading. This report describes the identification, surgical and restorative management of infection and bone loss around a pre-loaded dental implant.Case Presentation: A 52 year old systemically healthy, non-smoking white female had severe inflammation with bleeding on probing and bone loss around implant #28 seven weeks after placement and augmentation with autogenous and deproteinated bovine bone and a resorbable collagen membrane (RCM). Surgical exposure revealed a deep bony crater around the entire implant. The implant was cleaned for 4-5 minutes with a tetracycline and saline slurry. Guided ...
Acoustic differences in morphologically-distinct homophones

ABSTRACTPrevious work demonstrates that a word's status as morphologically-simple or complex may be reflected in its phonetic realisation. One possible source for these effects is phonetic paradigm uniformity, in which an intended word's phonetic realisation is influenced by its morphological relatives. For example, the realisation of the inflected word frees should be influenced by the phonological plan for free, and thus be non-homophonous with the morphologically-simple word freeze. We test this prediction by analysing productions of forty such inflected/simple word pairs, embedded in pseudo-conversational speech structured to avoid metalinguistic task effects, and balanced for frequency, orthography, as well as segmental and prosodic context. We find that stem and suffix durations are significantly longer by about 4–7% in fricative-final inflected words (frees, laps) compared to their simple counterparts (freeze, lapse), while we find a null effect for stop-final words. The result suggests that wordfo...
Comparing best-first search and dynamic programming for optimal multiple sequence alignment

Sequence alignment is an important problem in computational biology. We compare two different approaches to the problem of optimally aligning two or more character strings: bounded dynamic programming (BDP), and divide-and-conquer frontier search (DCFS). The approaches are compared in terms of time and space requirements in 2 through 5 dimensions with sequences of varying similarity and length. While BDP performs better in two and three dimensions, it consumes more time and memory than DCFS for higher-dimensional problems.
Biosimilars for Immune-Mediated Chronic Diseases in Primary Care: What a Practicing Physician Needs to Know

The introduction of biologics has revolutionized the treatment of immune-mediated diseases, but high cost and limited patient access remain hurdles, and some physicians are concerned that biosimilars are not similar enough. The purpose of this narrative review is to describe biosimilar safety, efficacy, nomenclature, extrapolation and interchangeability. In the United States, the Biologics Price Competition and Innovation Act created an abbreviated pathway for licensing of a biologic that is biosimilar to another licensed product (i.e., the reference product). This approval pathway differs from that of generic small-molecule drugs because biologics are too complex to be perfectly duplicated, and follows a process designed to demonstrate that any differences between the biosimilar and its reference product have no significant impact on safety and efficacy. The US approval process requires extensive analytical assessments, animal studies and clinical trials, assuring that biosimilar products provide clinical results similar to those of the reference product.
A 5–15 GHz stacked I/Q modulator with 15–19 dBm OP 1dB and 26–30 dBm OIP3 in 45 nm SOI CMOS

In this paper, a 5–15 GHz I/Q modulator implemented in 45 nm SOI CMOS is presented, which shares DC current through biasing branch, I/Q mixers and stacked-FET power amplifier (PA) to provide high output power and linearity. Stacked SOI transistors are used to isolate the modulator from high voltage swing at the load and mitigate device break-down. The proposed architecture results in an OP 1db and OIP3 of 15.6–19.5 dBm and 26–30 dBm at 5–15 GHz, respectively. The circuit occupies only 0.46 rnrn2 including pads. Application areas are in the 5G high-linearity IF circuity for high data-rate modulations.
THE REPRODUCTIVE EFFECTS OF HORMONALLY ACTIVE ENVIRONMENTAL AGENTS

Efforts during the past 50 or more years to improve agricultural productivity and manufacturing processes have led to the introduction of numerous man-made chemicals into the environment. In the course of this chapter, these chemicals, generally, will be referred to as environmental toxicants or xenobiotics. It is now known that many of these chemicals have unexpected effects on the animal populations of the planet and one expects that such effects have occurred or will occur in the human population. The untoward effects that are of particular interest to us in the context of reproductive biology are effects that interfere with the normal development and function of the male and female reproductive systems and which lead to reduced fertility, infertility, or sterility. Although the mechanisms by which environmental toxicants cause their disruptive effects on reproduction were at first elusive, it is now clear that many act by interfering with the physiological regulation of reproductive processes by sex-steroid hormones. Other environmental toxicants act through other mechanisms, such as the thyroid hormone receptor and through the aryl hydrocarbon receptor (1, 2). This chapter will concentrate exclusively on xenobiotics that act through the sex-steroid hormone pathway since these hormones are known to be intimately involved in regulating reproductive processes.
Pharmacy contributions to improving care and sustaining change in a comprehensive cancer center.

150Background: Delivery of care in an outpatient hematology/oncology clinic is complex and requires the coordination of numerous services for timely and efficient treatment of patients. The Norris Cotton Cancer Center in Lebanon, NH, began a comprehensive assessment of clinic and infusion operations in 2012 and developed a system-wide initiative to address inconsistent performance in infusion, clinic and pharmacy services. Methods: Cancer center staff and leadership were trained on lean six-sigma methodology to initiate system-wide improvements through targeted project work. We collaborated with quality improvement experts and our analytics team to obtain and analyze data from our EMR. Then we established process measures for all operational areas and a key performance indicator (KPI) for hem/onc infusion: “on time performance.” The pharmacy contributed to on-time performance by focusing improvement initiatives on turn-around time (TAT) for clinical reviews and order verification, TAT for drug preparation...
Important Plant Parasitic Nematodes of Row Crops in Arkansas, Lousiana and Mississippi

This chapter’s focus is on the important plant parasitic nematodes and their management on row crops in Arkansas, Louisiana and Mississippi. This region is referred to as the Mid-South. Agronomic crops, production practices and nematode management practice are similar throughout the region.
Controlling Peptide Conformation Using Tungsten Alkyne Coordination

Abstract Tungsten can coordinate one, two, or three alkyne ligands, and certain of its bis-alkyne complexes are air stable. This chemistry has been explored as a means for constraining peptides to either β-turns or β-sheets. To determine whether two peptides coordinated to tungsten would hydrogen-bond in the manner of a β-sheet, peptides bearing a single alkyne at either the N- or C-terminus were used to form tungsten bis-alkynylpeptide complexes (3, 4a-b, 5a-b, 6 and 7). It was found that in these complexes the two peptides do not hydrogen-bond with each other to form a β-sheet; rather at 23°C the two alkynylpeptide ligands rotate about the tungsten center to generate syn- and anti-orientations that are in equilibrium. Similarly, symmetrical peptide derivatives incorporating 1,4-dihydroxy-2-butyne, when coordinated to tungsten as mono-alkyne complexes (11a-c, 12 and 13), did not hydrogen-bond with each other or with themselves to generate a β-sheet structure. However, coordination of peptides incorporating 2-amino-2′-carboxydiphenylacetylene (14 and 15), which are known to adopt a β-sheet conformation, to tungsten as mono-alkyne complexes (16a-b and 17a-b), did maintain the β-sheet structure. Current work to generate β-sheet structures revolves around a recently discovered cyclic ferrocene tungsten bis-alkyne complex (25), that limits the two alkyne ligands to only the syn orientation. Peptide derivatives of 25, where the peptides are linked to the two alkyne ligands (27a-b–31a-b, and 32 and 33), are under investigation. The ability of tungsten alkyne coordination to induce turn conformations was explored using metallacyclicpeptides, where coordination of a single tungsten to two alkynes positioned at two different locations on a single peptide was used to form a ring system incorporating the tungsten metal; such molecules are called metallacyclicpeptides. Cyclization of dipeptides bearing an alkyne on each amino acid (22–24), failed to limit the peptide to a turn conformation, but cyclization of tri- and tetrapeptides bearing alkynes at their N- and C-termini (20 and 21), did generate turn structures.
Investigating the role of temporal fine structure in everyday hearing

Human listeners can derive substantial masking release when there are discrepancies in pitch or spatial location between the target and masking sounds. While the temporal fine-structure (TFS) in low-frequency sounds can convey information about both pitch and location, a nuanced debate exists in the literature about the role of these TFS cues in masking release. The long-term goal of the present study is to leverage individual differences to understand the role of TFS in everyday hearing. As a first step, we sought to measure individual TFS sensitivity using monaural frequency modulation (FM) and binaural interaural time difference (ITD) detection tasks. Preliminary data show large individual differences in these measures. Moreover, individual differences in ITD sensitivity were correlated with monaural FM sensitivity suggesting that monaural TFS coding can be a primary bottleneck determining binaural sensitivity. Alternately, both FM and ITD sensitivity variations could be reflecting common non-sensory factors (e.g., attention). To disambiguate between these hypotheses, we designed two passive EEG metrics of TFS coding. Follow-up experiments will compare individual differences in these perceptual and EEG measures to each other, and to speech-in-noise perception in complex environments.
Parental Validation, College Experiences, and Institutional Commitment of First-Generation and Low-Income Students

This study examines how a specific form of parental support—parental validation—is related to students’ college experiences and institutional commitment. Results based on a survey of first-generati...
Corporate-Led Environmental Governance: A Theoretical Model:

The growing reliance on non-state environmental governance (EG) coupled with the current U.S. political environment portends an increasing salience of governing efforts from non-state actors. Among...
Parallel Trajectories of Proactive and Reactive Aggression in Middle Childhood and Their Outcomes in Early Adolescence

This study used an accelerated longitudinal design to investigate trajectories of proactive and reactive aggression in middle childhood and their outcomes in early adolescence. Children (N = 1420; ages 5–12; 48% female) were assessed biannually over 6 school years. Classroom teachers rated students’ proactive and reactive aggression throughout grades K-5; and multi-method (teacher-report, self-report, school records) measures of peer problems, depressive symptoms, academic performance, disciplinary actions, and school absenteeism were collected throughout grades 3–5. Latent class growth models were estimated to differentiate parallel-process trajectories of proactive-reactive aggression. Class membership was then examined as a predictor of outcomes at the end of 5th grade. The best-fitting solution had four trajectory classes: (1) low aggression, 76.7%; (2) high proactive-reactive aggression, 4.7%; (3) declining aggression, 4.9%; and (4) predominantly reactive aggression, 13.7%. Most classes showed seasonal upticks in aggressive behavior in the spring semester relative to fall; these were especially pronounced for proactive aggression, both as a variable and for the proactive-reactive class. Relative to their low-aggression peers, children in any elevated-aggression class had higher levels of peer problems, depressive symptoms, and disciplinary actions and lower GPAs at the end of 5th grade. The reactive class—which on no occasion had the highest total aggression—exhibited the most consistently unfavorable pattern of outcomes across methods and measures. Findings offer new insights concerning the multifinality and heterogeneity of aggressive behavior in childhood. Research, theory, and practice could benefit from adopting person-centered conceptualizations that consider the long-term trajectories, short-term variations, and proactive vs. reactive functions of youth aggression.
Experimental and theoretical assessment of protonated Hoogsteen 9-methylguanine-1-methylcytosine base-pair dissociation: kinetics within a statistical reaction framework.

We investigated the collision-induced dissociation (CID) reactions of a protonated Hoogsteen 9-methylguanine–1-methylcytosine base pair (HG-[9MG·1MC + H]+), which aims to address the mystery of the literature reported “anomaly” in product ion distributions and compare the kinetics of a Hoogsteen base pair with its Watson-Crick isomer WC-[9MG·1MC + H]+ (reported recently by Sun et al.; Phys. Chem. Chem. Phys., 2020, 22, 24986). Product ion cross sections and branching ratios were measured as a function of center-of-mass collision energy using guided-ion beam tandem mass spectrometry, from which base-pair dissociation energies were determined. Product structures and energetics were assessed using various theories, of which the composite DLPNO-CCSD(T)/aug-cc-pVTZ//ωB97XD/6-311++G(d,p) was adopted as the best-performing method for constructing a reaction potential energy surface. The statistical Rice–Ramsperger–Kassel–Marcus theory was found to provide a useful framework for rationalizing the dominating abundance of [1MC + H]+ over [9MG + H]+ in the fragment ions of HG-[9MG·1MC + H]+. The kinetics analysis proved the necessity for incorporating into kinetics modeling not only the static properties of reaction minima and transition states but more importantly, the kinetics of individual base-pair conformers that have formed in collisional activation. The analysis also pinpointed the origin of the statistical kinetics of HG-[9MG·1MC + H]+vs. the non-statistical behavior of WC-[9MG·1MC + H]+ in terms of their distinctively different intra-base-pair hydrogen-bonds and consequently the absence of proton transfer between the N1 position of 9MG and the N3′ of 1MC in the Hoogsteen base pair. Finally, the Hoogsteen base pair was examined in the presence of a water ligand, i.e., HG-[9MG·1MC + H]+·H2O. Besides the same type of base-pair dissociation as detected in dry HG-[9MG·1MC + H]+, secondary methanol elimination was observed via the SN2 reaction of water with nucleobase methyl groups.
My Old World chap, this α-gal is not for you.

30 million years ago, ancestors of Old World primates lost the ability to produce α-gal. In this issue of Cell Host & Microbe, Singh et al. (2021) show that the loss is associated with increased resistance to sepsis, but that this advantage comes alongside a cost of accelerated reproductive senescence.
The commercialization of bias in cashless India

Abstract The Digital India initiative is a sweeping set of reformative policies and programs set by the Indian government to bring communications technology to the masses in an effort to bridge the digital divide in the country and equalize underlying economic conditions among Indian citizens. The government has met these challenges by setting forth a series of initiatives that involve the foundation of new physical infrastructures and the creation of novel digital products – some of which are designed to promote the drive toward cashlessness across the country. Layered atop the creation of these new policies and programs will eventually be increased collection of data and implementation of automated decision-making processes to enable full utility from these new installations. The principal purpose of this paper is to examine the changes to technology infrastructure proposed in the Digital India initiative, conduct a policy analysis thereof with respect specifically to its impact on individual privacy, and identify policy interventions through which possible adverse impacts in these areas for segments of the Indian population could be diminished. We find that several critical policy questions remain unaddressed by the initiative, and that it can promote further bias in the absence of certain equity-promoting interventions and adjustments. We conclude by suggesting areas for policy focus that may require consideration by the government to maintain and promote normative fairness.
Anti-Inflammatory Effects of Conditioned Medium of Periodontal Ligament-Derived Stem Cells on Chondrocytes, Synoviocytes, and Meniscus Cells.

Osteoarthritis (OA) is the most common type of arthritis, afflicting millions of people in the world. Elevation of inflammatory mediators and enzymatic matrix destruction is often associated with O...
Moderate levels of 5-fluorocytosine cause the emergence of high frequency resistance in cryptococci.

The antifungal agent 5-fluorocytosine (5-FC) is used for the treatment of several mycoses, but is unsuitable for monotherapy due to the rapid development of resistance. Here, we show that cryptococci develop resistance to 5-FC at a high frequency when exposed to concentrations several fold above the minimal inhibitory concentration. The genomes of resistant clones contain alterations in genes relevant as well as irrelevant for 5-FC resistance, suggesting that 5-FC may be mutagenic at moderate concentrations. Mutations in FCY2 (encoding a known permease for 5-FC uptake), FCY1, FUR1, UXS1 (encoding an enzyme that converts UDP-glucuronic acid to UDP-xylose) and URA6 contribute to 5-FC resistance. The uxs1 mutants accumulate UDP-glucuronic acid, which appears to down-regulate expression of permease FCY2 and reduce cellular uptake of the drug. Additional mutations in genes known to be required for UDP-glucuronic acid synthesis (UGD1) or a transcriptional factor NRG1 suppress UDP-glucuronic acid accumulation and 5-FC resistance in the uxs1 mutants. Pathogenic fungi rapidly develop resistance to the antifungal agent 5-fluorocytosine (5-FC). Here, Chang et al. explore the mechanisms by which Cryptococcus develops 5-FC resistance at a high frequency, including mutations in several genes and altered levels of key metabolites.
Immunogenicity and safety of concomitant inoculation of Measles and rubella combined live vaccine and Japanese encephalitis attenuated live vaccine

Objective: To evaluate the immunogenicity and safety of concomitant inoculation of Measles and Rubella Combined Live-attenuated Japanese encephalitis vaccine. Methods: Healthy children aged 8 months in selected cities in Zhejiang Province were randomly assigned to the MR and JVE-L combined vaccination group (the experimental group), and the MR single vaccination group (the control group) was taken before the exemption and 6 weeks after the exemption. Peripheral venous blood 1 ml was used as serum antibody test for measles and rubella, and the levels of measles and rubella antibodies before and after vaccination were evaluated. The safety of combined vaccination was evaluated. Measles and rubella IgG antibodies were detected by enzyme-linked immunosorbent assay (ELISA). Data were double-entry with Epidata and statistical analysis was performed using Epi Info epidemiological statistical analysis software. Results: The results showed that no severe adverse event occurred in two groups, clinical reactions in each inoculation group were mild.The seroconversion rate of measles antibody and rubella antibody were 96.43% and 88.49% in the experimental group after vaccination, the geometrical mean concentrations(GMC) of measles antibody was 1 526.45 mIU/ml and the GMC of rubella antibody was 47.70 mIU/ml after concomitant inoculation; the seroconversion rate of measles antibody and rubella antibody were 97.62% and 86.11% in the control group, the GMC of Measles antibody was 1 392.28 mIU/ml and the GMC of Rubella antibody was 45.72 mIU/ml after MV inoculation. No difference were detected in two groups of seroconversion rate of measles antibody and rubella antibody and GMC after vaccination. Conclusion: The immunogenicity and safety is equivalent when MR and JVE-L were simultaneous inoculation.
Deficiency of CC chemokine ligand 2 and decay-accelerating factor causes retinal degeneration in mice

CC chemokine ligand 2 (CCL2) recruits macrophages to reduce inflammatory responses. Decay-accelerating factor (DAF) is a membrane regulator of the classical and alternative pathways of complement activation. In view of the link between complement genes and retinal diseases, we evaluated the retinal phenotype of C57BL/6J mice and mice lacking Ccl2 and/or Daf1 at 12 months of age, using scanning laser ophthalmoscopic imaging, electroretinography (ERG), histology, immunohistochemistry, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis. In comparison to C57BL/6J mice, mutant mice had an increased number of autofluorescent foci, with the greatest number in the Ccl2−/−/Daf1−/− retina. ERG amplitudes in Ccl2−/−/Daf1−/−, Ccl2−/− and Daf1−/− mice were reduced, with the greatest reduction in Ccl2−/−/Daf1−/− mice. TUNEL-positive cells were not seen in C57BL/6J retina, but were prevalent in the outer and inner nuclear layers of Ccl2−/−Daf1−/− mice and were present at reduced density in Ccl2−/− or Daf1−/− mice. Cell loss was most pronounced in the outer and inner nuclear layers of Ccl2−/−/Daf1−/− mice. The levels of the endoplasmic reticulum chaperone GPR78 and transcription factor ATF4 were significantly increased in the Ccl2−/−/Daf1−/− retina. In comparison to the C57BL/6J retina, the phosphorylation of NF-κB p65, p38, ERK and JNK was significantly upregulated while SIRT1 was significantly downregulated in the Ccl2−/−/Daf1−/− retina. Our results suggest that loss of Ccl2 and Daf1 causes retinal neuronal death and degeneration which is related to increased endoplasmic reticulum stress, oxidative stress and inflammation.
MODE SPECIFIC VIBRATIONAL PREDISSOCIATION DYNAMICS IN FRAGILE MOLECULES

State resolved vibrational dynamics in weakly bound complexes is investigated via high resolution IR absorption spectroscopy in a slit supersonic jet expansion. The tunable frequency near IR source can readily excite the high frequency intramolecular vibrations of the subunits, as well as the low frequency, intermolecular vibrations via combination band excitations built on the high frequency modes. These upper state energies lie far above the van der Waals binding energy limit, and yet predissociate typically on the nsec time scale or longer (i.e. many millions of vibrational periods). This exceptional metastability in such small systems is highly non-statistical, and proves to be a rich arena of vibrational mode mixing and mode-specific predissociation behavior. We select recent examples from our group effort to illustrate these concepts.
Gestalt: From Phenomena to Laws

The Gestalt phenomena of grouping in space and in space-time (proximity, similarity, good continuation, common fate, apparent motion and so on) are an essential foundation of perception. Yet they have remained fairly vague, experimentally intractable, and unqualified. We describe progress we made in the quest for clarity, lawfulness and precision in the formulation of these phenomena.
Data-driven prediction of therapeutic efficacy and optimization of de novo drug combinations on the human protein-protein interaction network (842.11)

Combination therapy is a promising direction for cancer research as it is shown to eradicate drug-resistant cancer more effectively than monotherapy. The challenge, however, in creating a successful combinatorial treatment lies in the inability to screen through a huge number of possible combinations. We introduce PROPHECY (Predictive Optimization of Pharmaceutical Efficacy), a data-driven search engine for the selection of drugs in combination therapy. The user provides a genetic profile, e.g. mutations in cancer cell lines or primary cells, and PROPHECY will select optimal drug combinations from a comprehensive library of existing drugs to meet clinical objectives. The decision is made by comparing the efficacy of drug combinations with in silico screening, in which a predictive machine is trained with a large-scale database of drug screening experiments to recognize high-order target-gene interactions in the human protein-protein interaction network (PPI). The predictive module in the machine incorpora...
Modulation of the IgE immune response to BSA by fragments of the antigen: I. Suppression by free fragments and by fragments conjugated to homologous γ-globulin

Abstract Nonimmunogenic peptic fragments of bovine serum albumin (BSA), Fraction Ia, suppressed immune response to BSA in mice. Splenic T lymphocytes from mice treated with these fragments suppressed the anti-DNP response in irradiated mice reconstituted with DNP-BSA-primed cells, indicating carrier-specific suppression. The conjugate of Fraction Ia with mouse γ-globulin (MGG) was found to be an effective suppressive substance but it did not induce suppressor T cells. B cells from mice given Ia-MGG were unresponsive to BSA when transferred to irradiated recipients along with either normal or BSA-primed T cells. Thus, unresponsiveness to BSA was mediated by either T or B lymphocytes, depending whether the inducing substance was a free fragment of the antigen or fragments conjugated to homologous γ-globulin.
Tyrosinase of the goldfish Carassius auratus L. II. Correlation of tyrosinase activity with pigmentation.

1. 1. It has been demonstrated that during stress-induced melanogenesis in the goldfish, Carassius auratus L, the level of tyrosinase in the skin is increased several fold and that this increase precedes pigmentation. 2. 2. The increase in tyrosinase activity is more pronounced in the particulate fraction than in the soluble fraction. 3. 3. In three varieties of the goldfish (xanthic, wild-type grey and black moor), the tyrosinase activity parallels the degree of pigmentation of the skin. This is due to a higher level of particulate tyrosinase in the pigmented fish. 4. 4. Considerable tyrosinase activity is present in skin homogenates prepared from totally xanthic fish. Therefore, in addition to the level of tyrosinase activity, other factors may regulate melanogenesis.
What Is a Postmodern Constitutionalism

I begin with a puzzle. It must certainly strike one as odd that the subject of postmodern constitutional law arises at a time when the actual arbiters of the Constitution the federal judiciary and in particular the Supreme Court of the United States appear to be more conservative than they have been for many years, and indeed, are likely to remain so for the foreseeable future. Postmodernism is often associated with what is new, innovative, and on the cutting edge of cultural development. Yet if we were to define the elements of a postmodern constitutional culture, it would be clear that one of the most central features of the present period if the expression "central" still has any remaining currency in an era of postmodernism is a judiciary which has no intention of being new or innovative in anything. Its intellectual leader, Justice Scalia, has even called for a constitutional jurisprudence of tradition, coupled with a return to an interpretive theory of plain meanings for statutes and original intention with respect to the Constitution.1 To be sure, some might be tempted to explain away this phenomenon as an anomaly or an exception. The federal judiciary, they will say, is behind the times, much as the Lochner-era justices were. Eventually, when a different administration comes to power, and appoints new judges, the judiciary will catch up with the breathtaking developments we now discuss under the name of "postmodern" jurisprudence. Indeed, all about us we see, in the works of legal commentators and scholars, and even in the speeches of a few enlightened political leaders, the harbingers of a new dawn of constitutional postmodernism.
Self-Insured Health Plans: State Variation and Recent Trends by Firm Size, 1996-2013

This paper examines recent trends in self-insurance. Data come from the Medical Expenditure Panel Survey (MEPS) and are presented by establishment size among only private-sector employers. State-level data are also presented. In 2013, 37.6 percent of private-sector establishments self-insured at least one of their health plans, up from 26.5 percent in 1999. All of the growth in self-insurance in recent years has been confined to larger firms. In 2013, 83.9 percent of employers with 500 or more employees self-insured at least one health plan, up from 66.2 percent in 1999. The percentage of employers offering a self-insured health plan with fewer than 100 employees has bounced around between 10.7 percent and 14.7 percent between 1996 and 2013. Furthermore, the percentage of employers offering a self-insured health plan with 100-499 employees fell from 35.3 percent in 1996 to 25 percent in 2006, and has been between 25.2 percent and 29.2 percent since. Large employers (with 1,000 or more workers) have driven the upward trend in overall self-insurance. Understanding the trend in self-insurance for employers with 50 or more workers and those with fewer than 50 workers is important because the employer mandate in the Patient Protection and Affordable Care Act (PPACA) affects only employers with at least 50 workers. To the degree small employers are concerned about the rising cost of providing health coverage, self-insurance may become a more attractive means to mitigate any expected regulatory cost increases. However, as of 2013, there is no evidence that smaller firms were increasingly self-insuring their health plans. In 2013, 64.6 percent of firms with 50 or more employees offered at least one self-insured plan, compared with 13.2 percent among firms with fewer than 50 employees. This analysis finds that the percentage of workers in self-insured plans has been increasing. In 2013, 58.2 percent of workers with health coverage were in self-insured plans, up from 40.9 percent in 1998. The percentage of workers in self-insured plans in firms with fewer than 50 employees has been close to 12 percent in most years examined in this analysis. The estimates in this analysis should serve as a baseline to gauge the potential impact of rising health insurance costs on self-insurance in the future.
A Fibonacci-like sequence of composite numbers.

In 1964, Ronald Graham proved that there exist relatively prime natural numbers $a$ and $b$ such that the sequence $\{A_n\}$ defined by $$ {A}_{n} =A_{n-1}+A_{n-2}\qquad (n\ge 2;A_0=a,A_1=b)$$ contains no prime numbers, and constructed a 34-digit pair satisfying this condition. In 1990, Donald Knuth found a 17-digit pair satisfying the same conditions. That same year, noting an improvement to Knuth's computation, Herbert Wilf found a yet smaller 17-digit pair. Here we improve Graham's construction and generalize Wilf's note, and show that the 12-digit pair $$(a,b)= (407389224418,76343678551)$$ also defines such a sequence.
Statics: Analyses of Systems in Equilibrium

Statics is an area within the field of applied mechanics that is concerned with the analysis of rigid bodies in equilibrium. In mechanics, the term equilibrium implies that the body of concern is either at rest or moving with a constant velocity. A rigid body is one that is assumed to undergo no deformation under the effect of externally applied forces. In reality, there is no rigid material and the concept is an approximation. For some applications, the extent of deformations involved may be so small that the inclusion of the deformation characteristics of the material may not influence the desired analysis. In such cases, the material may be treated as a rigid body.
Relative Contribution of Purkinje Fibers to CA2+-Dependent Arrhythmias in a Murine Model of CPVT

Background. Purkinje fibers (PFs) are critical for coordinated electrical excitation of the ventricles and thought to play a key role in abnormal impulse formation and ventricular arrhythmias. However, the arrhythmogenic properties of PFs as compared to ventricular tissue remain to be elucidated and were the focus of the present study.Results. To examine the arrhythmic potential of PFs vs ventricular tissue we performed Ca2+ and membrane potential (MP) imaging in PFs and ventricular tissue preparations derived from both wild-type (WT) mice and genetically modified mice prone to Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). PFs and trabeculae dissected from the right ventricles were loaded with the voltage- and Ca2+-sensing dyes RH237 and Rhod-2, respectively. PFs were identified by the characteristic long, narrow shape and lack of T-tubules of Purkinje cells, as evidenced by membrane staining with RH237. In PFs and trabeculae preparations isolated from CPVT but not WT mice, exposure to the beta-adrenergic agonist isoproterenol resulted in frequent diastolic Ca2+ releases both spontaneous and triggered, that were associated with corresponding MP signals. Consistent with their ability to lead to triggered events, diastolic spontaneous Ca2+ releases showed high synchronicity between adjacent cells in both tissues. Overall spontaneous Ca2+ release synchronicity and the rates of occurrence of spontaneous and triggered Ca2+ release events were similar between PFs and trabeculae.Conclusion. These results suggest that the Purkinje system and ventricular tissue possess similar arrhythmic potentials in a setting of CPVT, consistent with a diffuse nature of the genesis of Ca2+-dependent ventricular arrhythmias.
Analysis of symmetric and asymmetric nanoscale slab slot waveguides

Nanoscale slab slot waveguides provide for high optical confinement and have found abundant applications in silicon photonics. After developing an analytical mode solver for general asymmetric slot waveguides, the confinement performance of symmetric as well as asymmetric geometries was systematically analyzed and compared. For symmetric structures, 2D confinement optimization by varying both low-index slot and high-index slab width revealed a detailed saturation trend of the confinement factor with the increase of the studied width. Furthermore, simple design rules on how to choose the slot and slab width for achieving optimal confinement was obtained. For asymmetric structures, we demonstrated that the confinement performance was always lower than the 2D optimized confinement of the symmetric structures providing the two high-index slab layers and the two cladding layers have same refractive indices, respectively. In addition, the sensitivity of the confinement to the degree of asymmetry was studied, and we found that the fabrication tolerance on the material and structural parameters may be reasonably large for symmetric structures designed at optimal confinement.