cssi/SciSciGPT-SciSciNet huggingface dataset:
The Cysteine S-Alkylation Reaction as a Synthetic Method to Covalently Modify Peptide Sequences

Synthetic methodologies to chemically modify peptide molecules have long been investigated for their impact in the field of chemical biology. They allow the introduction of biochemical probes useful for studying protein functions, for manipulating peptides with therapeutic potential, and for structure-activity relationship investigations. The commonly used approach was the derivatization of an amino acid side chain. In this regard, the cysteine, for its unique reactivity, has been widely employed as the substrate for such modifications. Herein, we report on methodologies developed to modify the cysteine thiol group through the S-alkylation reaction. Some procedures perform the alkylation of cysteine derivatives, in order to prepare building blocks to be used during the peptide synthesis, whilst some others selectively modify peptide sequences containing a cysteine residue with a free thiol group, both in solution and in the solid phase.
Hazards in Opportunity

Epidemiology studies have found that immigrants who enter the United States from Mexico have prevalence rates of mental disorder similar to residents of Mexico City. These rates are much lower than rates of mental disorder found in those of Mexican decent who were born in the United States. Prevalence of depression in U.S.-born Mexican-Americans approximates prevalence rates for the general U.S. population and is twice as high as the rates for recent immigrants from Mexico. This paper will discuss hypotheses that might contribute to these findings. These include decrease in family and social support, the need to compete in a more open society, and the inability to satisfy perceived needs and marginal position in society.
Solar Time and Interception of Direct-Beam Solar Radiation

This chapter describes how leaves intercept the Sun's rays. To understand the process, basic principles of astronomy are presented. Sidereal time, solar time, apparent solar time, mean solar time, and standard time are defined. The procedure for determining standard time from apparent solar time is given. Interception of direct-beam solar radiation then is discussed. It is based on the direct-beam solar radiation equation that has been in the literature for over 200 years. It can be used on any sloping surface, but in this chapter we apply it to the sloping surface of a leaf. Four angles need to be known to solve the equation: azimuth and altitude angle of the Sun and azimuth and altitude angle of the leaf. An example is given showing how to use the equation to determine light interception on a leaf. An appendix gives the biography of Kepler, whose work laid the foundation for astronomy.
Fundamental trade-offs between information flow in single cells and cellular populations.

Signal transduction networks allow eukaryotic cells to make decisions based on information about intracellular state and the environment. Biochemical noise significantly diminishes the fidelity of signaling: networks examined to date seem to transmit less than 1 bit of information. It is unclear how networks that control critical cell-fate decisions (e.g., cell division and apoptosis) can function with such low levels of information transfer. Here, we use theory, experiments, and numerical analysis to demonstrate an inherent trade-off between the information transferred in individual cells and the information available to control population-level responses. Noise in receptor-mediated apoptosis reduces information transfer to approximately 1 bit at the single-cell level but allows 3–4 bits of information to be transmitted at the population level. For processes such as eukaryotic chemotaxis, in which single cells are the functional unit, we find high levels of information transmission at a single-cell level. Thus, low levels of information transfer are unlikely to represent a physical limit. Instead, we propose that signaling networks exploit noise at the single-cell level to increase population-level information transfer, allowing extracellular ligands, whose levels are also subject to noise, to incrementally regulate phenotypic changes. This is particularly critical for discrete changes in fate (e.g., life vs. death) for which the key variable is the fraction of cells engaged. Our findings provide a framework for rationalizing the high levels of noise in metazoan signaling networks and have implications for the development of drugs that target these networks in the treatment of cancer and other diseases.
Preclinical efficacy and safety of KCNH2-G628S gene therapy for postoperative atrial fibrillation.

Abstract Background Postoperative atrial fibrillation (POAF) is the most common complication occurring after cardiac surgery. Multiple studies have shown significantly increased risks of stroke, myocardial infarction, and death associated with POAF. Current prophylaxis strategies are inadequate to eliminate this problem. We examined the preclinical efficacy and safety of KCNH2-G628S gene transfer to prevent POAF. Methods Domestic pigs received AdKCNH2-G628S by epicardial atrial gene painting and atrial pacemaker implantation for continuous-burst pacing to induce atrial fibrillation. In an initial dose-ranging evaluation, 3 pigs received 5 × 10 10 to 5 × 10 11 virus particles. In the formal study, 16 pigs were randomized to 3 groups: 5 × 10 11 virus particles of AdKCNH2-G628S with 20% Pluronic P407 in saline, 20% Pluronic P407 in saline with no virus, and saline alone. Animals were followed with daily efficacy and safety evaluations through the period of peak adenovirus-mediated transgene expression. After 14 days, pacing was discontinued, and the animals were followed in sinus rhythm for an additional 14 days to assess any longer-term toxicity. Results In the primary efficacy analysis, the G628S animals exhibited a significant increase in the average time in sinus rhythm compared with the Pluronic control group (59 ± 7% vs 14 ± 6%; P = .009). There was no significant difference between the Pluronic and saline controls (14 ± 6% vs 32 ± 12%; P = .16). Safety assessment showed improved left ventricular function in the G628S animals; otherwise there were no significant differences among the groups in any safety measure. Conclusions These data indicate that KCNH2-G628S gene therapy can successfully and safely reduce the risk of AF.
A phase I/II study of lymphodepletion plus adoptive cell transfer (ACT) with T cells transduced with CXCR2 and NGFR followed by high dose interleukin-2 (IL-2) in patients with metastatic melanoma (MM).

TPS9594Background: Improving T cell trafficking to tumors may help augment anti-tumor responses in ACT using tumor infiltrating lymphocytes (TILs). mm produces the chemokines CXCL1 and CXCL8, which...
Particle-hole symmetry and composite fermions in fractional quantum Hall states

We study fractional quantum Hall states at filling fractions in the Jain sequences using the framework of composite Dirac fermions. Synthesizing previous work, we write an effective field theory consistent with all symmetry requirements, including Galilean invariance and particle-hole symmetry. Employing a Fermi-liquid description, we demonstrate the appearance of the Girvin-Macdonald-Platzman algebra and compute the dispersion relation of neutral excitations and various response functions. Our results satisfy requirements of particle-hole symmetry. We show that while the dispersion relation obtained from the modified random-phase approximation (MRPA) of the Halperin-Lee-Read (HLR) theory is particle-hole symmetric, correlation functions obtained from this scheme are not. The results of the Dirac theory are shown to be consistent with the Haldane bound on the projected structure factor, while those of the MPRA of the HLR theory violate it.
The durability of operational improvements with rotational patient assignment.

Abstract Introduction Previous work has suggested that Emergency Department rotational patient assignment (a system in which patients are algorithmically assigned to physicians) is associated with immediate (first-year) improvements in operational metrics. We sought to determine if these improvements persisted over a longer follow-up period. Methods Single-site, retrospective analysis focused on years 2–4 post-implementation (follow-up) of a rotational patient assignment system. We compared operational data for these years with previously published data from the last year of physician self-assignment and the first year of rotational patient assignment. We report data for patient characteristics, departmental characteristics and facility characteristics, as well as outcomes of length of stay (LOS), arrival to provider time (APT), and rate of patients who left before being seen (LBBS). Results There were 140,673 patient visits during the five year period; 138,501 (98.7%) were eligible for analysis. LOS, APT, and LBBS during follow-up remained improved vs. physician self-assignment, with improvements similar to those noted in the first year of implementation. Compared with the last year of physician self-assignment, approximate yearly average improvements during follow-up were a decrease in median LOS of 18 min (8% improvement), a decrease in median APT of 21 min (54% improvement), and a decrease in LBBS of 0.69% (72% improvement). Conclusion In a single facility study, rotational patient assignment was associated with sustained operational improvements several years after implementation. These findings provide further evidence that rotational patient assignment is a viable strategy in front-end process redesign.
Fontan-associated liver disease: Monitoring progression of liver fibrosis.

FALD continues to attract much research interest as complications affecting patient morbidity and mortality become increasingly apparent. Currently, there are still no official guidelines for monitoring this population, and multicenter cohort studies have only been published within the past year.1 Guidelines are institution dependent (Fig. ​(Fig.2,2, Table ​Table11).1, 3, 7, 10, 12 Future research will continue to focus on risk stratification of patients for severe sequelae of liver disease and on understanding the role of elastography and noninvasive markers in this population while trying to learn more about the pathophysiological etiology of FALD.
Practical considerations for modeling streamer discharges in air with radiation transport

Two basic challenges limiting the simulation capabilities of the streamer discharge community are the efficient resolution of Poisson's equation and the proper treatment of photoionization. This paper addresses both of these challenges, beginning with a graphics processing unit executed multigrid (MG) algorithm to efficiently solve Poisson's equation on a massively parallel platform. When utilized in a 3D particle-in-cell (PIC) model with radiation transport, the MG solver is demonstrated to reduce the required simulation time by approximately a factor of three over a conventional Jacobi scheme. Next, a fully theoretical photoionization model, based on the basic properties of N2 and O2 molecules is developed as an alternative to widely utilized semi-empirical models. Following a review of N2 emission properties, a total of eight transitions from only three excited states are reported as a base set of transitions for a practical physics-based photoionization model. A 3D PIC simulation of streamer formation is demonstrated with two dominant transitions included in the radiation transport model.
ERM-mediated genetic screens in mammalian cells.

Abstract Genetic screens have been proven powerful for the identification of components of various signaling pathways. For mammalian cells, methods for genetic screens are limited. We have developed the ERM (enhanced retroviral mutagen) mutagenesis approach that has been shown to be efficient and amenable to genomewide genetic screens in mammalian cells without the need of cDNA library construction. The ERM method offers several advantages, including conditional gene expression and the flexibility to tag endogenous genes with different epitope‐tag and marker sequences. This chapter will discuss general design, procedures, and applications of the ERM strategy.
Frequency-Dependence of Vegetation Optical Depth-Derived Isohydriciy Estimates

Passive microwave radiometry-derived vegetation optical depth measurements can be used to map how different ecosystems are sensitive to drought. This is quantified using the plant physiological concept of isohydricity. VOD-derived effective ecosystem-scale isohydricity maps have recently become commonly used, but their sensitivity to the underlying VOD datasets is not yet well understood. In this work, the dependence of the isohydricity calculation on assumptions about canopy cover penetration - which depends on frequency - and observation time - which varies by sensor in a manner roughly consistent with the observation frequency - are reviewed, and isohydricity datasets from different VOD datasets are compared and validated.
Structure-based inhibitors halt prion-like seeding by Alzheimer's disease-and tauopathy-derived brain tissue samples

In Alzheimer's disease (AD) and tauopathies, tau aggregation accompanies progressive neurodegeneration. Aggregated tau appears to spread between adjacent neurons and adjacent brain regions by prion-like seeding. Hence, inhibitors of this seeding offer a possible route to managing tauopathies. Here, we report the 1.0 A resolution micro-electron diffraction structure of an aggregation-prone segment of tau with the sequence SVQIVY, present in the cores of patient-derived fibrils from AD and tauopathies. This structure illuminates how distinct interfaces of the parent segment, containing the sequence VQIVYK, foster the formation of distinct structures. Peptide-based fibril-capping inhibitors designed to target the two VQIVYK interfaces blocked proteopathic seeding by patient-derived fibrils. These VQIVYK inhibitors add to a panel of tau-capping inhibitors that targets specific polymorphs of recombinant and patient-derived tau fibrils. Inhibition of seeding initiated by brain tissue extracts differed among donors with different tauopathies, suggesting that particular fibril polymorphs of tau are associated with certain tauopathies. Donors with progressive supranuclear palsy exhibited more variation in inhibitor sensitivity, suggesting that fibrils from these donors were more polymorphic and potentially vary within individual donor brains. Our results suggest that a subset of inhibitors from our panel could be specific for particular disease-associated polymorphs, whereas inhibitors that blocked seeding by extracts from all of the tauopathies tested could be used to broadly inhibit seeding by multiple disease-specific tau polymorphs. Moreover, we show that tau-capping inhibitors can be transiently expressed in HEK293 tau biosensor cells, indicating that nucleic acid-based vectors can be used for inhibitor delivery.
The structure of nearly isothermal, adiabatic shock waves

An explosively generated shockwave with time-dependent radius $R(t)$ is characterized by a phase in which the shocked gas becomes radiative with an effective adiabatic index $\gamma \simeq 1$. Using the result that the post-shock gas is compressed into a shell of width $\Delta R/R \simeq \delta$, where $\delta = \gamma-1$, we show that a choice of self-similar variable that exploits this compressive behavior in the limit that $\gamma \rightarrow 1$ naturally leads to a series expansion of the post-shock fluid density, pressure, and velocity in the small quantity $\delta$. We demonstrate that the leading-order (in $\delta$) solutions, which are increasingly accurate as $\gamma \rightarrow 1$, can be written in simple, closed forms when the fluid is still approximated to be in the energy-conserving regime (i.e., the Sedov-Taylor limit), and that the density declines exponentially rapidly with distance behind the shock. We also analyze the solutions for the bubble surrounding a stellar or galactic wind that interacts with its surroundings, and derive expressions for the location of the contact discontinuity that separates the shocked ambient gas from the shocked wind. We discuss the implications of our findings in the context of the dynamical stability of nearly isothermal shocks.
Association of Adjuvant Chemotherapy With Overall Survival in Patients With Early-Stage Breast Cancer and 21-Gene Recurrence Scores of 26 or Higher.

This cohort study investigates the association of overall survival with receiving chemotherapy among patients with early-stage breast cancer and recurrence scores of 26 to 30 vs those with recurrence scores of 31 or greater.
Quality Assessment of Online Patient Information for Cosmetic Botulinum Toxin.

BACKGROUND In an era of widespread Internet access, patients increasingly look online for health information. Given the frequency with which cosmetic botulinum toxin injection is performed, there is a need to provide patients with high-quality information about this procedure. OBJECTIVES The aim of this study was to examine the quality of printed online education materials (POEMs) about cosmetic botulinum toxin. METHODS An Internet search was performed to identify 32 websites of various authorship types. Materials were evaluated for accuracy and inclusion of key content points. Readability was measured by Flesch Reading Ease and Flesch-Kincaid Grade Level. Understandability and actionability were assessed with the Patient Education Materials Assessment Tool for Printed Materials. The effect of authorship was measured by undertaking analysis of variance between groups. RESULTS The mean [standard deviation] accuracy score among all POEMs was 4.2 [0.7], which represents an accuracy of 76% to 99%. Mean comprehensiveness was 47.0% [16.4%]. Mean Flesch-Kincaid Grade Level and Flesch Reading Ease scores were 10.7 [2.1] and 47.9 [10.0], respectively. Mean understandability and actionability were 62.8% [18.8%] and 36.2% [26.5%], respectively. There were no significant differences between accuracy (P > 0.2), comprehensiveness (P > 0.5), readability (P > 0.1), understandability (P > 0.3), or actionability (P > 0.2) by authorship. CONCLUSIONS There is wide variability in the quality of cosmetic botulinum toxin POEMs regardless of authorship type. The majority of materials are written above the recommended reading level and fail to include important content points. It is critical that providers take an active role in the evaluation and endorsement of online patient education materials.
Reconfigurable construction of all-dielectric chiral metamaterials on solid substrates

We apply a novel optical technique – optothermally-gated photon nudging – to construct all-dielectric chiral metamaterials with silicon nanoparticles (SiNPs) and silicon nanowires (SiNWs). Through coordinating optical heating and radiation-pressure forces, a SiNP is manipulated and delivered to the vicinity of a SiNW to form chiral nanostructures. By dynamically moving the SiNP along the nanowire from one side to the other end, the chirality of the nanostructure can be tailored on-demand. Owing to simultaneous electric and magnetic resonances in dielectric nanostructures, the assembled chiral metamaterials support strong enhancement of optical near-field chirality for high-performance enantiodiscrimination of chiral molecules.
P97. Correlation of UIV and cervical spine surgery to functional outcomes in AIS: a minimum 40-years follow-up

BACKGROUND CONTEXT The long-term impact of Harrington rod instrumentation for AIS and the impact of UIV and future cervical spine fusion on patient reported outcomes is not known. PURPOSE To assess whether cervical spine surgery and high UIV can negatively impact patient reported outcomes in AIS patients. STUDY DESIGN/SETTING Observational. PATIENT SAMPLE We identified 318 patients treated with Harrington instrumentation and fusion between 1961 and 1978. OUTCOME MEASURES Patients were contacted for patient reported outcomes: NDI, SRS-7, PROMIS Physical Function (PF), PROMIS Depression (D), PROMIS Pain Interference (PI). METHODS Bivariate and multivariate analyses were used to compare outcome measures based on UIV and future cervical fusion. RESULTS Fifty-six patients with an average follow-up of 49 years (range 40 - 57) and average age of 64 (range 53 to 73) completed the patient reported outcomes. Four (7%) had T2 UIV, 3 (5%) had T3 UIV, 12 (21%) had T4 UIV, 15 (27%) had T5 UIV, 14 (25%) had T6 UIV, 3 (5%) had T7 UIV, 1 (2%) had T8 UIV, 1 (2%) had T9 UIV and 3 (5%) had T10 UIV. Two patients underwent cervical fusion (3.6%). In patients without cervical spine surgery, those with UIV of T5 and higher had average NDI of 14.6 (p=0.09) and SRS-7 of 22.8 (p=0.45) compared to patients of UIV T6 and below having 10.2 and 22.9. Patients without cervical spine surgery with UIV of T5 and higher had average PROMIS PF (p=0.21) of 43.5, PROMIS D (p=0.24) of 49 and PROMIS PI (p=0.17) of 55.6 compared to UIV T6 and below having 45.5, 51.8 and 53.9. Patients with cervical spine fusion had mean NDI of 23 as compared to NDI of 11.9 in patients without cervical fusion (p=0.09). CONCLUSIONS In long-term follow-up, AIS patients who underwent fusion with UIV of T5 and higher did not have worse outcomes as compared to patients with UIV of T6 and below. Long term follow-up of patients undergoing Harrington Rod Instrumentation (avg. 49 years) did not show a correlation on patient reported outcomes based on UIV and future cervical spine surgery. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.
Cross correlation-based misregistration correction for super resolution T2 -weighted spin-echo images: application to prostate.

Purpose The purpose is to develop a retrospective correction for subtle slice-to-slice positional inconsistencies that can occur when overlapped slices are acquired for super resolution in T2 -weighted spin-echo multislice imaging. Methods Spin-echo acquisition of overlapped slices is typically done using multiple passes. After the passes are assembled into the final slice set, consecutive slices are correlated due to their overlap. Cross correlation was used to measure slice-to-slice displacement. After Z-dependent filtering to preserve true object shape, the displacements were used to correct slice position. The method was tested in a phantom moved slowly (0.16-0.63 mm/pass) under computer control and in vivo in 16 patients having prostate MRI. Results Over the motion range, the correlation method had an accuracy within 0.03 mm/pass and precision ± 0.20 mm (ie, subpixel). Corrected images visually resemble the true object. Over the patient studies, the mean range of motion in the anterior-posterior direction was 1.63 mm. Motion-corrected axial images and the sagittal reformats were evaluated as significantly superior over those formed without motion correction. Conclusion The retrospective correlation-based motion-correction method provides significant improvement in the slice-to-slice registration necessary for effective super resolution using overlapped slices.
The diversity of Maa (Nilotic) adverbs: Speed, Time, Modality, Intensity and Nominal-Tense/Aspect

Maa linguistic varieties (Maasai, Parakuyo, Chamus, Samburu, among others), of the Eastern Nilotic family (Nilo-Saharan phylum), have words which can modify a predicate or predication and have the function of what cross-linguistically are called adverbs. While these words can be considered a single class due to this shared function and distribution, there are nevertheless morphosyntactic and usage distinctions. This is partly due to disparate historical origins, but also to semantics and different typical collocations. Among other distinctions, some adverbs can function as nominal tense/aspect markers within a determined nominal phrase (DP). Though the origins of all adverbs cannot be traced, the paper documents sources in oblique prepositional phrases, relational nouns, adjectives, relative clauses, and perhaps infinitive verbs, involving a wide range of lexical roots, such as ‘little’, ‘paint, mark’, ‘be abundant (with grass), be generous’, and others. Some synchronic adverbs do not have evident sources in other word classes, including the ­most frequently used word for ‘previously, before’, and the modal adverb ‘probably not, unlikely’ which is also an attenuative adverb. Maa adjectives and nouns largely overlap in their morphosyntax, but the ability to be modified by certain adverbs distinguishes them.
The Daya Bay antineutrino detector filling system and liquid mass measurement

The Daya Bay Reactor Neutrino Experiment has measured the neutrino mixing angle θ13 to world-leading precision. The experiment uses eight antineutrino detectors filled with 20-tons of gadolinium-doped liquid scintillator to detect antineutrinos emitted from the Daya Bay nuclear power plant through the inverse beta decay reaction. The precision measurement of sin22θ13 relies on the relative antineutrino interaction rates between detectors at near (400 m) and far (roughly 1.8 km) distances from the nuclear reactors. The measured interaction rate in each detector is directly proportional to the number of protons in the liquid scintillator target. A precision detector filling system was developed to simultaneously fill the three liquid zones of the antineutrino detectors and measure the relative target mass between detectors to < 0.02%. This paper describes the design, operation, and performance of the system and the resulting precision measurement of the detectors' target liquid masses.
A Blueprint for Creating Mentored, Collaborative Networks for Early-Career Physician-Scientists.

OBJECTIVES The objective is to improve the high-quality collaborative research of early-career investigators, the American Urogynecologic Society/Pelvic Floor Disorders Foundation funded and developed the Junior Faculty Research Network (JFRN). The purpose of this report is to describe the process of development of the network, discuss barriers, acknowledge accomplishments, and provide a framework for future collaborations. METHODS The development of the JFRN provided sponsorship and mentorship, supported collaboration, and created a network structure for early-career investigators. A request for applications was circulated, requiring a competitive submission process, and 6 physician-scientists were selected to participate in a multicenter trial whose initial focus was on the urinary microbiome and its interaction with sacral neuromodulation. RESULTS The JFRN infrastructure consisted of early-career investigators, senior advisors, and research support staff. Study development and roll-out progressed over monthly conference calls. Initial barriers included the development of institutional participation agreements, logistics of funding disbursement, and coordination of support staff. In addition to the inaugural research project, the network continued to collaborate, and the initial grant provided pilot data for a National Institutes of Health-funded project. CONCLUSIONS The JFRN is a successful mentored collaborative of early-career investigators. The creation of this self-sustaining, independent research network may serve as a blueprint for other early-career physician-scientists to participate in productive multicenter research.
Using Evidence to Frame Problems of Practice

Improvement initiatives crafted based on well-understood problems of practice often stand the greatest chance of leading to sustainable educational improvements. Framing problems of practice using multiple modes of evidence is advisable to fully understand the system of root causes of the problem and its stakeholders. In this study, we used the document analysis method to investigate the types of evidence (e.g., literature, anecdotal, secondary data) that students used to frame problems of practice in EdD dissertations in practice within CPED consortium member institutions (N=53). Results suggest that students predominantly use literature to frame problems of practice with fewer using primary and secondary data.
Caregiver Reports of Physician Risk Counseling for Adolescents with Special Health Care Needs

Abstract Background Research has indicated disagreement between physicians, caregivers, and adolescents with special health care needs regarding appropriate risk counseling. Objective The study examines caregivers’ perceptions of adolescent risk counseling. We hypothesize caregivers of adolescents with special healthcare needs will perceive a lower rate of risk counseling. Methods Data come from the 2016 National Survey of Children’s Health. The sample included 13,542 adolescents. Analysis completed using logistic regression with odds ratios. Results The results indicate no difference in caregiver perceptions of risk counseling for adolescents with special healthcare needs. Gender, race/ethnicity, and relationship between caregiver and provider influenced perception of receipt of risk counseling, regardless of health status. Conclusions Although adolescents with special healthcare needs perceive their risk behavior counseling to be lacking in quantity/quality, caregivers perceive such counseling does occur. These results highlight the need for comprehensive risk counseling for groups at risk of known health disparities. Practice implications Physicians and providers should be provided with the training and resources needed to be comfortable to engage in risk counseling. Adolescents need the opportunity to see their provider privately, and education to advocate for information risky behaviors. Parents, providers, and adolescents should be included in future risk counseling intervention plans.
Comment on Commentaries

After savoring the commentaries which inaugurate the March 1975 issue of Pediatrics, I am moved to respond. These parsimonious but learned callings of attention to important issues in pediatrics provide a very useful service, and I wish to cast an enthusiastic vote for this increasingly important section. Keep up the good work. Editor9s Note: It is nice to have compliments. We will continue to try harder.
Cardiac Telemetry, Natality and Genetics of a Recolonized Population of Bighorn Sheep at a Wild Horse Range

Data were collected from 05-88 to 12-88 in continued research to aid in the development of a management program for Rocky Mountain bighorn Sheep (Ovid c. canadensis) at Bighorn Canyon National Recreation Area (BICA). A principle goal of the management program at BICA is to promote the continued expansion of a recolonized population throughout ancestral habitat in the area (BICA 1984). In previous research at BICA (Coates and Schemnitz, 1988), we identified 3 factors as potentially limiting to herd expansion: visitor and (or) vehicular disturbance of bighorns (esp. reproductive ewes), competition with horses for grasses, and possible genetic constraints on recruitment resulting from small founder-group size.
Respiratory syncytial virus (RSV) and its propensity for causing bronchiolitis

Infants and young children with acute onset of wheezing and reduced respiratory airflows are often diagnosed with obstruction and inflammation of the small bronchiolar airways, ie bronchiolitis. The most common aetological agents causing bronchiolitis in young children are the respiratory viruses, and of the commonly encountered respiratory viruses, respiratory syncytial virus (RSV) has a propensity for causing bronchiolitis. Indeed, RSV bronchiolitis remains the major reason why previously healthy infants are admitted to hospital. Why RSV infection is such a predominant cause of bronchiolitis is the subject of this review. By reviewing the available histopathology of RSV bronchiolitis, both in humans and relevant animal models, we identify hallmark features of RSV infection of the distal airways and focus attention on the consequences of columnar cell cytopathology occurring in the bronchioles, which directly impacts the development of bronchiolar obstruction, inflammation and disease. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Chapter 7. Molecular imaging of tumor vasculature.

Cancer, with more than 10 million new cases a year worldwide, is the third leading cause of death in developed countries. One critical requirement during cancer progression is angiogenesis, the formation of new blood vessels. Structural and functional imaging of tumor vasculature has been studied using various imaging modalities such as magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound. Molecular imaging, a key component of the 21st‐century cancer‐patient management strategy, takes advantage of these traditional imaging techniques and introduces molecular probes to determine the expression of indicative molecular markers at different stages of cancer development. In this chapter, we will focus on two tumor vasculature–related targets: integrin αvβ3 and vascular endothelial growth factor receptor (VEGFR). For imaging of integrin αvβ3 on the tumor vasculature, only nanoparticle‐based probes will be discussed. VEGFR imaging will be discussed in depth, and we will give a detailed example of positron emission tomography (PET) imaging of VEGFR expression using radio‐labeled VEGF121 protein. Future clinical translation will be critical for maximum patient benefit from these agents. To achieve this goal, multidisciplinary approaches and cooperative efforts from many individuals, institutions, industries, and organizations are needed to quickly translate multimodality tumor vasculature imaging into multiple facets of cancer patient management.
Then and Now: America's New Immigrant Entrepreneurs, Part VII

The period of unprecedented expansion of immigrant-led entrepreneurship that characterized the 1980s and 1990s has come to a close. Today, the growth rate of immigrant-founded companies nationwide, at 24.3 percent, has plateaued. In the high-tech hub of Silicon Valley, the proportion of immigrant-founded companies has dropped from 52.4 percent during 1995-2005 to 43.9 percent during 2006-2012.Immigrant founders of engineering and technology companies have employed roughly 560,000 workers and generated an estimated $63 billion dollars in sales during this time. While the rate of growth of immigrant entrepreneurship has stagnated, these numbers nonetheless underscore the continuing importance of high-skilled immigrants to the maintenance and expansion of the national economy. These findings are interestingly complex, since the two major skilled-immigrant groups — Indian and Chinese — are starting companies at higher rates than they did previously. Historically and today, the United States continues to benefit directly from the contributions of such immigrants. Far from expendable, high-skilled immigrants will remain a critical asset for maintaining U.S. competitiveness in the global economy.
Membrane-bound protein kinase C modulates receptor affinity and chemotactic responsiveness of Lewis lung carcinoma sublines to an elastin-derived peptide.

Abstract The M27 and H59 variants of Lewis lung carcinoma differ in their responsiveness to the chemotactic elastin peptide Val-Gly-Val-Ala-Pro-Gly (VGVAPG). M27 cells, selected for metastasis to lung, are highly responsive to a positive gradient of VGVAPG. H59 cells, selected for metastasis to liver, do not migrate in response to VGVAPG. Although both cell types bind radiolabeled VGVAPG, Scatchard analysis of 125I-Tyr-VGVAPG binding reveals that M27 cells bind the chemoattractant with a Kd of 2.7 nM, whereas nonresponsive H59 cells bind the peptide with a Kd of 67 nM. These findings indicate that the failure of H59 cells to migrate in response to VGVAPG may be due to the reduced affinity of their VGVAPG receptors. Both receptor affinity and chemotactic responsiveness to VGVAPG can be modulated in each of these two tumor cell lines by the levels of active membrane-associated protein kinase C. Treatment of nonresponsive H59 cells with 12-O-tetradecanoylphorbol 13-acetate increases the level of membrane-bound protein kinase C activity with a concomitant increase in VGVAPG binding affinity and induction of chemotactic responsiveness to VGVAPG. Treatment of M27 cells with the protein kinase C inhibitor, staurosporine, reduces VGVAPG binding affinity and abrogates the chemotactic response. We conclude that chemotactic responsiveness of M27 and H59 tumor cells is dependent upon high VGVAPG receptor affinity, which is strongly correlated to high levels of membrane-bound protein kinase C activity.
The verb, past and perfect tenses (weak)

The verbs in all Germanic languages can be divided into two major classes according to whether the past tense is formed by the addition of a suffix to the stem, e.g.
Language and sexuality in Spanish and English dating chats

Three half-hour conversations each from five English and four Spanish dating chat rooms were analyzed following conversation analytic methodologies. Participants in the chats often engaged in playful and humorous erotic conversations, using a set of interactionally negotiated conventions about chatting that constitute a play frame, characterized linguistically by graphemic representations of laughter, appropriations, reproduction of a humorous pronunciation, and interactions through alter personae. Such playfulness enhances participants' pleasure while allowing them to maintain critical distance, and balances the constraints of public interaction with the pursuit of private erotic pleasures. This study contributes to our understanding of the social and discursive dimension of sexuality, going beyond issues of sexual identity and focusing on the conversational negotiation of eroticism and desire.
The Treatment of Osteonecrosis in the Hip

Osteonecrosis of the femoral head is both a debilitating disease and a very difficult clinical condition to treat. There are a wide variety of treatment options and an incomplete understanding of the pathophysiological cause. Research and treatment algorithms are based on the concepts of decompression, supplementation, and reconstruction. As our understanding of osteonecrosis continues to advance, our treatments continue to evolve on a technical and biologic front. This paper highlights some of these treatments and areas for future development.
An analysis of printed breast cancer information for African American women

Abstract Background. The 1995‐1998 Delta Project was designed to increase breast cancer screening among disadvantaged African American women with limited literacy skills by educating their health care professionals about breast health. The research team intended to provide on‐site training and appropriate educational materials; however, they found no suitable materials. This article presents the results of an assessment of available materials and defines the need for suitable materials. Methods. Nineteen organizations that develop cancer‐related publications submitted materials intended for African American audiences. Sixty‐one documents were examined for readability and cultural sensitivity. The Flesch Reading Ease (FRE), Flesch‐Kincaid (F‐K), and Cultural Sensitivity Assessment Tools (CSAT) were used in testing. Results. The mean FRE score of 65 yielded a F‐K mean grade level of 7.5 (desired level: 3.5). Using CSAT, 16 documents (26%) were eliminated because they had no visuals. Twenty‐two publications ...
Incentive Conflicts and Contracting: Evidence from Franchising

This paper develops cross-sectional implications about the assignment of rights in franchise contracts. These implications are tested using a large sample of franchise agreements. The tests support the predictions and suggest that restrictive provisions (such as mandatory advertising, passive-ownership restrictions and area development plans) are used when title to unit profits provide insufficient incentives for optimal investment by the franchisee. The evidence also suggests that the incentive instruments used in franchise contracts are complements. While the study focuses on franchising, the results provide insights into related provisions in other contracts, such as the common restriction that an employee must report to work (even when the work could be performed at home). The evidence is also consistent with the hypothesis that vertical restraints are included in distribution contracts to help control horizontal free-rider problems.
Information technology as a component of system engineering education

The growth of information technology over the last several decades and the prospects for continued rapid growth in this field have precipitated the need for systems engineers who can design and integrate large-scale information systems for enterprises. The demand in this area is so large that in some schools more than half of the undergraduates find employment in information technology. Hence, engineering education in general and systems engineering in particular must provide programs to accommodate this growing need for engineers who have an education relevant to a career in this area. This paper describes our approach to combining formal instruction in information technology with other more traditional topics in systems engineering. The paper emphasizes the contribution of the capstone or senior design program to our educational goals in the area of information technology. It also provides a description of an exemplary student project in this area.
A bactericidal antibody to Borrelia burgdorferi is directed against a variable region of the OspB protein.

Abstract Borrelia burgdorferi, an agent of Lyme disease, is killed by some monoclonal antibodies in the absence of complement or phagocytes. In the present study, the bactericidal action of monoclonal antibodies against B. burgdorferi and B. hermsii, a cause of relapsing fever, was further characterized. H6831, an antibody recognizing the OspB proteins of some B. burgdorferi strains, and H4825, an antibody specific for one serotype of B. hermsii, were purified, and Fab fragments of the antibodies were prepared. In time-kill studies, more than 99.9% of strain B31 B. burgdorferi cells were killed after 30 min of exposure to H6831 Fab fragments. The MBC of the Fab fragments was 10 micrograms/ml. Electron microscopy revealed that the bactericidal Fab fragments produced numerous blebs and cell lysis of the borrelias for which they were specific. To identify the epitope for H6831, the OspB sequences of H6831-susceptible and -resistant strains and mutants were determined. The deduced OspB proteins of all H6831-resistant strains and mutants differed from the strain B31 OspB at residue 253. Murine antisera raised against a 21-mer synthetic peptide representing the region around residue 253 were specific for strain B31 by Western blot (immunoblot) and growth inhibition assays. Furthermore, the antipeptide serum inhibited the binding of H6831 to whole borrelias. These findings indicated that the linear component of the bactericidal antibody's epitope was located at or near residue 253.
The MIRRORS/II simulator

MIRRORS/II is a software system for developing connectionist models. This paper discusses the unique features of MIRRORS/II: application independence, specification language, multiple target languages, extensibility, and accumulative resources. A detailed example of the use of MIRRORS/II is given. Finally, MIRRORS/II is compared with other existing connectionist modelling systems and future plans are discussed.
Optical latches using optical amplifiers

Optical latches are important for a wide range of applications including communication systems, optical logic systems, optical random access memory (RAM) and encryption. All optical logic operations using quantum dot (QD) based semiconductor optical amplifier (SOA) and Mach-Zehnder interferometer (MZI) have been studied. The building block of an optical latch such as NAND gate has been fabricated and their operation experimentally demonstrated at ~ 80 GHz. A rate equation model has been developed for the QD-SOA-MZI and it has been used to analyze the Boolean logic operation. The model has been used to analyze the Set-Reset (S-R) latch and the D-Flip-Flop (DFF) devices. The DFF is the basic device for building larger logic circuits. The results show that the latches would work to speeds of ~ 250 Gb/s.
The impact of local black residents’ socioeconomic status on white residents’ racial views

This paper extends the study of contextual influences on racial attitudes by asking how the SES of the local black community shapes the racial attitudes of local whites. Using responses to the 1998–2002 General Social Surveys merged with year 2000 census data, we compare the influences of black educational and economic composition on white residents’ attitudes. Finally, the independence of these effects from the impact of white contextual SES is assessed. Across three dimensions of racial attitudes, white residents’ views are more positive in localities where the black population contains more college graduates. However, such localities tend also to have highly educated white populations, as well as higher incomes among blacks and whites, and the multiple influences are inseparable. In contrast, many racial attitude measures show an independent effect of black economic composition, white residents reporting more negative views where the local African American community is poorer.
Comparative Nutritive Value of Silages Made from High-Sugar Male Sterile Hybrid Corn and Regular Starchy Corn

Abstract Comparable seedings of high-sugar male sterile hybrid seed corn and of typical starchy dent corn were made in May, 1967. The starchy dent corn was harvested for silage in late September and that from the high-sugar corn in late October, based on apparent optimal times of harvest. Under equal rates of seeding (56,800 seeds per hectare) high-sugar corn yielded 30,819 kg of 78.5% moisture whole plant silage per hectare (6,626 kg dry matter) and starchy dent corn yielded 40,418 kg of 65.3% moisture whole plant silage (14,025 kg dry matter) per hectare. Chemical analyses of the two types of silage showed greater crude protein, crude fiber, and ether extract and lesser nitrogen-free extract and ash in the silage made from the male sterile corn. Digestion trial technique showed the digestibility of crude protein and crude fiber fractions of silage made from male sterile corn was significantly (P
Glucuronide formation in the transport of estradiol by rat intestine in vitro.

Abstract When [14C]-17-β-estradiolis incubated with everted sacs of rat intestine net transport of radioactivity to the serosal medium is accomplished by oxidation of the estradiol to estrone followed by conjugation of the estrone as a glucuronide. The conjugated estrone is accumulated in the serosal medium. Relative impermeability of the mucosa to the conjugate offers a reasonable basis for the accumulation of radioactivity in the serosal fluid.
Augmented nuclease activity during cellular senescence in vitro

The molecular correlates of the limited proliferative potential of normal human diploid fibroblasts and extensive single-strand braks in the genomic DNA of these cells were examined by transfection analyses in which DNA replication could be uncoupled from DNA damage and repair. Both supercoiled (fmI), and restriction endonuclease-cleaved, linear (fmIII) molecules of a well-defined bacterial plasmid DNA, pBR322, were transfected into, and subsequently recovered from, early and late passage fibroblasts. Southern blot analysis revealed that fmI DNA was converted by random nicks into fmII DNA slightly more rapidly in late passage cells compared with cells at early passage. Similarly, fmII and fmIII DNAs also sustained multiple random nicks and no appreciable net religation of free ends of fmIII DNA could be detected at either passage. In addition, the efficiency of in vitro ligation of fmIII DNA recovered from late passage cells was also reduced, compared with that from early passage cells, as determined by Southern blotting. These data suggest that in the absence of DNA replication, a putative nuclease activity may contribute to DNA damage observed in senescent cells, which, in turn, may be causally related to their limited replicative potential.