cssi/SciSciGPT-SciSciNet huggingface dataset:
Localization of amyloid beta peptides to locus coeruleus and medial prefrontal cortex in corticotropin releasing factor overexpressing male and female mice

A culmination of evidence from the literature points to the Locus Coeruleus (LC)-Norepinephrine system as an underappreciated and understudied area of research in the context of Alzheimer's Disease (AD). Stress is a risk factor for developing AD, and is supported by multiple clinical and preclinical studies demonstrating that amplification of the stress system disrupts cellular and molecular processes at the synapse, promoting the production and accumulation of the amyloid beta (Aβ42) peptide. Stress-induced activation of the LC is mediated by corticotropin releasing factor (CRF) and CRF receptors exhibit sex-biased stress signaling. Sex differences are evident in the neurochemical, morphological and molecular regulation of LC neurons by CRF, providing a compelling basis for the higher prevalence of stress-related disorders such as AD in females. In the present study, we examined the cellular substrates for interactions between Aβ and tyrosine hydroxylase a marker of noradrenergic somatodendritic processes in the LC, and Dopamine-β-Hydroxylase (DβH) in the infralimbic medial prefrontal cortex (ILmPFC) in mice conditionally overexpressing CRF in the forebrain (CRFOE) under a Doxycycline (DOX) regulated tetO promoter. CRFOE was sufficient to elicit a redistribution of Aβ peptides in the somatodendritic processes of the LC of male and female transgenic mice, without altering total Aβ42 protein expression levels. DOX treated groups exhibited lysosomal compartments with apparent lipofuscin and abnormal morphology, indicating potential dysfunction of these Aβ42-clearing compartments. In female DOX treated groups, swollen microvessels with lipid-laden vacuoles were also observed, a sign of blood-brain-barrier dysfunction. Finally, sex differences were observed in the prefrontal cortex, as females responded to DOX treatment with increased frequency of co-localization of Aβ42 and DβH in noradrenergic axon terminals compared to vehicle treated controls, while male groups showed no significant changes. We hypothesize that the observed sex differences in Aβ42 distribution in this model of CRF hypersignaling is based on increased responsivity of female rodent CRFR1 in the LC. Aβ42 production is enhanced during increased neuronal activation, therefore, the excitation of DOX treated female CRFOE LC neurons projecting to the mPFC may exhibit more frequent co-localization with Aβ due to increased neuronal activity of noradrenergic neurons.
Simultaneous proton magnetic resonance fingerprinting and sodium MRI

PURPOSE The goal of this work is to demonstrate a method for the simultaneous acquisition of proton multiparametric maps (T1 , T2 , and proton density) and sodium density images in 1 single scan. We hope that the development of such capabilities will help to ease the implementation of sodium MRI in clinical trials and provide more opportunities for researchers to investigate metabolism through sodium MRI. METHODS We developed a sequence based on magnetic resonance fingerprinting (MRF), which contains interleaved proton (1 H) and sodium (23 Na) excitations followed by a simultaneous center-out radial readout for both nuclei. The receive chain of a 7T scanner was modified to enable simultaneous acquisition of 1 H and 23 Na signal. The obtained signal-to-noise ratio (SNR) was evaluated, and the accuracy of both proton T1 , T2 , and B1+ and sodium density maps were verified in phantoms. Finally, the method was demonstrated in 2 healthy subjects. RESULTS The SNR obtained using the simultaneous measurement was almost identical to single-nucleus measurements (<1% change). Similarly, the proton T1 and T2 maps remained stable (normalized root mean square error in T1 ≈ 2.2%, in T2 ≈ 1.4%, and B1+ ≈ 5.4%), which indicates that the proposed sequence and hardware have no significant effects on the signal from either nucleus. In vivo measurements corroborated these results and demonstrated the feasibility of our method for in vivo application. CONCLUSIONS With the proposed approach, we were able to simultaneously acquire sodium density images in addition to proton T1 , T2 , and B1+ maps as well as proton density images.
“Tied to the Land”: Climate Change Activism Among U.S. Hunters and Fishers

This paper investigates climate change activism among sportsmen and sportswomen, or hunters and fishers—a politically conservative group with historically deep roots to environmental conservation. Recently members of this community have created an NGO that focuses solely on climate change action—Conservation Hawks—and several other long-standing organizations have begun to include climate communication and activism within their mission. This article draws on fieldwork conducted throughout the rural western U.S., including ethnographic interviews with sportsmen/sportswomen, participant observation in hunter education courses and conservation events, and publicly-available media produced by hunting-oriented conservation organizations. Using an ethnographic and discourse analytic approach, I find that three primary discursive practices are particularly important within hunting and fishing community—a performed closeness to wildlife and wild places, a privileging of experiential and embodied epistemologies, and a valorization of the past wilderness. In both interviews and sportsmen-oriented media, these discourses can be drawn on when creating doubt and climate skepticism. Increasingly, however, activist groups use the same rhetorical strategies to promote climate change action. I argue that such shared discursive practices can thus mobilize collective identities, challenge political polarization, and create new political subjectivities around climate change in the rural western United States. I also argue that these discursive practices shape the actions portrayed as reasonable responses to the climate crisis within this community. This analysis thus illuminates climate activism within an understudied group, showing the depth of the civic movement on climate change. It also specifically highlights the importance of shared discursive practices to both climate skepticism and climate activism among one politically-conservative group in the United States, rural white hunters and fishers.
Proven Strategies for Increasing Adherence to Colorectal Cancer Screening

Although colorectal cancer (CRC) can be prevented or detected early through screening and surveillance, barriers that lower adherence to screening significantly limit its effectiveness. Therefore, implementation of interventions that address and overcome adherence barriers is critical to efforts to decrease morbidity and mortality from CRC. This article reviews the current available evidence about interventions to increase adherence to CRC screening.
Prevention of Periprosthetic Joint Infection

Periprosthetic joint infection (PJI) has moved into the first place as the cause of failure following total knee arthroplasty (TKA). Recent studies have shown that PJI results in higher mortality in patients than many cancers. The economic burden of treating PJI is likely to exceed $1 billion this year in the US. Thus, it is paramount that all efforts are invested to prevent this dreaded complication after total joint arthroplasty (TJA). This article summarizes some of the most effective and proven strategies for prevention of PJI. It is hoped that the article will be of benefit to the readers of the journal.
Acute Pain in the Chronic Pain Patient

At certain times individuals with chronic pain will experience acute pain either with or without association to their prior complaints. These patients pose unique challenges as they may have been exposed to, or are currently being treated with, various modalities and pharmaceuticals including chronic opioids. In these instances, it is important to elicit an appropriate history, identify barriers, assess morphine equivalency, and develop a multimodal treatment plan that can provide analgesia for both the acute and chronic complaints alike.
P300 latency jitter and its correlates in people with amyotrophic lateral sclerosis.

Abstract Objective People with amyotrophic lateral sclerosis (ALS) can benefit from brain-computer interfaces (BCIs). However, users with ALS may experience significant variations in BCI performance and event-related potential (ERP) characteristics. This study investigated latency jitter and its correlates in ALS. Methods Electroencephalographic (EEG) responses were recorded from six people with ALS and nine neurotypical controls. ERP amplitudes and latencies were extracted. Classifier-based latency estimation was used to calculate latency jitter. ERP components and latency jitter were compared between groups using Wilcoxon rank-sum tests. Correlations between latency jitter and each of the clinical measures, ERP features, and performance measures were investigated using Spearman and repeated measures correlations. Results Latency jitter was significantly increased in participants with ALS and significantly negatively correlated with BCI performance in both ALS and control participants. ERP amplitudes were significantly attenuated in ALS, and significant correlations between ERP features and latency jitter were observed. There was no significant correlation between latency jitter and clinical measures. Conclusions Latency jitter is increased in ALS and correlates with both BCI performance and ERP features. Significance These results highlight the associations of latency jitter with BCI performance and ERP characteristics and could inform future BCI designs for people with ALS.
Impact of the acidic environment on gene expression and functional parameters of tumors in vitro and in vivo

The low extracellular pH (pHe) of tumors resulting from glycolytic metabolism is a stress factor for the cells independent from concomitant hypoxia. The aim of the study was to analyze the impact of acidic pHe on gene expression on mRNA and protein level in two experimental tumor lines in vitro and in vivo and were compared to hypoxic conditions as well as combined acidosis+hypoxia. Gene expression was analyzed in AT1 prostate and Walker-256 mammary carcinoma of the rat by Next Generation Sequencing (NGS), qPCR and Western blot. In addition, the impact of acidosis on tumor cell migration, adhesion, proliferation, cell death and mitochondrial activity was analyzed. NGS analyses revealed that 147 genes were uniformly regulated in both cell lines (in vitro) and 79 genes in both experimental tumors after 24 h at low pH. A subset of 25 genes was re-evaluated by qPCR and Western blot. Low pH consistently upregulated Aox1, Gls2, Gstp1, Ikbke, Per3, Pink1, Tlr5, Txnip, Ypel3 or downregulated Acat2, Brip1, Clspn, Dnajc25, Ercc6l, Mmd, Rif1, Zmpste24 whereas hypoxia alone led to a downregulation of most of the genes. Direct incubation at low pH reduced tumor cell adhesion whereas acidic pre-incubation increased the adhesive potential. In both tumor lines acidosis induced a G1-arrest (in vivo) of the cell cycle and a strong increase in necrotic cell death (but not in apoptosis). The mitochondrial O2 consumption increased gradually with decreasing pH. These data show that acidic pHe in tumors plays an important role for gene expression independently from hypoxia. In parallel, acidosis modulates functional properties of tumors relevant for their malignant potential and which might be the result of pH-dependent gene expression.
Cleaning Zirconia Surface Prior To Bonding: A Comparative Study of Different Methods and Solutions

PURPOSE To evaluate resin cement bond strength after removal of salivary contamination from a zirconia surface using different cleaning solutions and air-borne particle abrasion. MATERIALS AND METHODS One-hundred and twenty zirconia specimens (KATANA STML, Noritake) were prepared and divided into 12 groups (n = 10). Groups were subjected to a notched-edge shear bond strength test (ISO 29022) to analyze the bonding efficiency of a resin cement (Panavia V5, Kuraray Noritake Dental Inc.) before and after contamination with saliva. Group 1 (control) was prepared and cemented without salivary contamination. Group 2 was coated with ceramic primer (Clearfil Ceramic Primer Plus, Kuraray Noritake Dental Inc.) then subjected to salivary contamination then tested. Group 3 was contaminated, cleaned by air-borne particle abrasion, ceramic primer and resin cement applied, and tested. Groups 4 to 12 were contaminated, and then different cleaning solutions (water, 4.5% hydrofluoric acid, 35% phosphoric acid, Ivoclean, KATANA cleaner, Zirclean, sodium hypochlorite 4%, and 7.5%) were used to decontaminate the zirconia surface, followed by ceramic primer, resin cement application, and tested. One-way ANOVA and Tukey post-hoc analysis was used to analyze the data. RESULTS One-way ANOVA showed statistical differences among cleaning procedures (p < 0.001, F = 13.48). Air-borne particle abrasion was the only group which provided a bond strength (21 ± 2.8 MPa) that was not statistically different than the control group in which no contamination occurred (25.3 ± 3.3 MPa) (p = 0.247). The use of hydrofluoric acid and zirconia cleaning solutions resulted in bond strengths values which were not statistically different from each other (17.5-19.1 MPa). CONCLUSION Air-borne particle, zirconia cleaning solutions and hydrofluoric acid are feasible to decontaminate the zirconia surface from saliva prior to bonding the restoration.
IL-17 is expressed on beta and alpha cells of donors with type 1 and type 2 diabetes.

Abstract Purpose IL-17 is an important effector cytokine driving immune-mediated destruction in autoimmune diseases such as psoriasis. Blockade of the IL-17 pathway after the initiation of insulitis was effective in delaying or preventing the onset of type 1 diabetes (T1D) in rodent models. Expression of IL-17 transcripts in islets from a donor with recent-onset T1D has been reported, however, studies regarding IL-17 protein expression are lacking. We aimed to study whether IL-17 is being expressed in the islets of diabetic donors. Methods We stained human pancreatic tissues from non-diabetic (n = 5), auto-antibody positive (aab+) (n = 5), T1D (n = 6) and T2D (n = 5) donors for IL-17, Insulin, and Glucagon, and for CD45 in selected cases. High resolution images were acquired with Zeiss laser scanning confocal microscope LSM780 and analyzed with Zen blue 2.3 software. Cases stained for CD45 were also acquired with widefield slide scanner and analyzed with QuPath software. Results We observed a clear cytoplasmic staining for IL-17 in insulin-containing islets of donors with T1D and T2D, accounting for an average of 7.8 ± 8.4% and 14.9 ± 16.8% of total islet area, respectively. Both beta and alpha cells were sources of IL-17, but CD45+ cells were not a major source of IL-17 in those donors. Expression of IL-17 was reduced in islets of non-diabetic donors, aab+ donors and in insulin-deficient islets of donors with T1D. Conclusion Our finding that IL-17 is expressed in islets of donors with T1D or T2D is quite intriguing and warrants further mechanistic studies in human islets to understand the role of IL-17 in the context of metabolic and immune stress in beta cells.
Predicting ion mobility as a function of the electric field for small ions in light gases.

Abstract High resolution mobility devices such as Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) and Differential Mobility spectrometers (DMS) use strong electric fields to gas concentration ratios, E / N , to separate ions in the gas phase. While extremely successful, their empirical results show a non-linear, ion-dependent relation between mobility K and E / N that is difficult to characterize. The one-temperature theory Mason-Schamp equation, which is the most widely used ion mobility equation, unfortunately, cannot capture this behavior. When the two-temperature theory is used, it can be shown that the K − E / N behavior can be followed quite closely numerically by equating the effect of increasing the field to an increase in the ion temperature. This is attempted here for small ions in a Helium gas environment showing good agreement over the whole field range. To improve the numerical characterization, the Lennard-Jones (L-J) potentials may be optimized. This is attempted for Carbon, Hydrogen, Oxygen and Nitrogen at different degrees of theory up to the fourth approximation, which is assumed to be exact. The optimization of L-J improves the accuracy yielding errors of about 3% on average. The fact that a constant set of L-J potentials work for the whole range of E / N and for several molecules, also suggests that inelastic collisions can be circumvented in calculations for He. The peculiar K − E / N hump behaviors are studied, and whether mobility increases or decreases with E / N is shown to derive from a competition between relative kinetic energy and the interaction potentials.
IPv6 AS Relationships, Cliques, and Congruence

There is increasing evidence that IPv6 deployment is maturing as a response to the exhaustion of unallocated IPv4 address blocks, leading to gradual convergence of the IPv4 and IPv6 topologies in terms of structure and routing paths. However, the lack of a fully-connected transit-free clique in IPv6, as well as a different economic evolution than IPv4, implies that existing IPv4 AS relationship algorithms will not accurately infer relationships between autonomous systems in IPv6, encumbering our ability to model and understand IPv6 AS topology evolution. We modify CAIDA’s IPv4 relationship inference algorithm to accurately infer IPv6 relationships using publicly available BGP data. We validate 24.9 % of our 41,589 c2p and p2p inferences for July 2014 to have a 99.3 % and 94.5 % PPV, respectively. Using these inferred relationships, we analyze the BGP-observed IPv4 and IPv6 AS topologies, and find that ASes are converging toward the same relationship types in IPv4 and IPv6, but disparities remain due to differences in the transit-free clique and the influence of Hurricane Electric in IPv6.
Analytical Transmission Electron Microscopy and Scanning Transmission Electron Microscopy Techniques for the Characterization of Nanomaterial Composition, Phase and Crystallinity

Abstract The production and use of manufactured nanomaterials (NMs) have been increasing dramatically for the past few years. Because there are nearly unlimited possibilities for the types of NMs that may be created, heterogeneity and complexity in both composition and structure are expected. In addition, manufactured NMs undergo compositional and structural transformation processes in response to the interaction(s) with their surrounding environment, as well as with that environment as it changes through time. In this chapter, we will introduce and discuss how to identify and characterize chemical composition and crystal structure (and therefore the exact phase or phases) of manufactured NMs (parent forms) as well as their transformed ones (daughter forms) by using analytical transmission electron microscopy (analytical TEM) and scanning transmission electron microscopy (STEM). For this specific purpose, in this chapter, we discuss TEM and STEM techniques for compositional and structural analyses, the applications and limits, the data acquisition and analysis methods, as well as sample preparation procedures in detail. The purpose of this chapter is to make these instruments and techniques much more accessible and familiar to nonexperts in electron microscopy. Manufactured NMs, such as TiO 2 , metals and metal oxides and sulphides will be used for examples throughout this chapter. In addition, examples of naturally occurring NMs will be used for crystal structural analyses, as well as crystal structure refinements.
Fc‐Fusion Protein Expression Technology

Therapeutic Fc-fusion proteins can be categorized loosely, based upon structural design, into two general classes. The first is the classical Fc fusion, whereby an extracellular domain (ECD) of a natural receptor is fused in-frame to the constant domains of human immunoglobulin gamma (see Chapter 1). The targeting moiety of a classical Fc fusion may be an ECD of a receptor, a cytokine receptor, or mimetic, and is generally at the N-terminus of the Fc constant domains (replacing the immunoglobulin variable region domain in most cases). The Fc portion is usually composed of several of the IgG1 constant domains (hinge–CH2–CH3) allowing for dimerization by design in some cases and capable of binding to both effector and neonatal FccR engagement [1]. These fusion proteins differ from true immunoglobulins in that they do not contain a light chain counterpart. The second class of Fc-fusion proteins is composed of novel assembled binding domains. These are not found in nature, but have been created such that protein domains or peptides are fused to the variable domain or attached to the Fc directly to guide the Fc fusion to its target (see Chapter 1). These binding domains vary from simple peptides to genetically engineered domains, all of which have a targeting domain and an effector Fc domain. In both classes of Fc-fusion proteins, this has, to date, been limited to human IgG1 or IgG4 isotype of immunoglobulin. The presence of two biologically active domains, the Fc portion of IgG and a biological ligand, adds to the complexity of Fc fusions as an emergent class of protein therapeutics. The genetic composition of the Fc-fusion proteins is a critical component of intellectual property. The specific molecular sequence is often the difference between obtaining claims in a patent or not. The breadth of patent claims to a specific protein species or to a class of protein (genera) also influences corporate decisions to invest further and/or to seek Food and Drug Administration (FDA) approval on particular indication(s). Intellectual property requires a significant
Some Applications of Modular Forms

Introduction 1. Modular forms 2. Invariant means on L (Sn) 3. Ramanujan graphs 4. Bounds for Fourier coefficients of 1/2-integral weight Bibliogrpahy Index.
Advertising Agency Terminations and Reviews: Stock Returns and Firm Performance

Abstract A key element in generating firm cash flows is the marketing strategy developed by a firm's advertising agency. This study examines both the stock market reaction and selected firm performance measures associated with Wall Street Journal announcements of advertising agency terminations and accounts placed in review (potential terminations). Besides finding a negative investor response to each event type, we report a significant decline in stock market values before such announcements. An examination of time series accounting data reveals a deterioration in firm sales growth before and after the announcement. Declines also occur in both liquidity and operating income. Our evidence is mixed regarding whether industry trends are responsible for these changes in financial position. We do not find an improvement in firm performance following the agency termination or potential termination. Strategic implications and directions for future research are discussed.
Student Research Projects for the New Navy 44 Sail Training Craft

Abstract : Offshore-capable sail training craft (STC) specifically designed and built for the United States Naval Academy (USNA) have been a cornerstone of its seamanship training program since 1939. Currently the fourth generation of these craft is under development and this paper summarizes research projects performed by eight midshipmen in the areas of parametric design criteria, structures, appendage development and analytical tool evaluation. While the results are oriented toward the new sail training craft, they are general enough to apply to any medium-sized offshore sailing vessel.
Changes in perceptions of transdisciplinary science over time

Abstract Transdisciplinary research teams offer an appropriate alternative to traditional research methods to address today’s complex research problems. However, a lack of common technical language and differing attitudes on collaborative research can create challenges. This paper reports results of an evaluative survey on changes of collaborative capacity within a large transdisciplinary project. Our survey data, collected through pre-assessment (2011) and mid-assessment (2013) evaluation surveys of project participants, measured participants’ attitudes, behaviors, and beliefs regarding transdisciplinary research. Paired samples t-tests were employed to compare measures from the same individuals at two points in time. The key variables were transdisciplinary attitudes, transdisciplinary behaviors, satisfaction with collaboration, perceived impacts of collaboration, and trust and respect. Changes over time were evaluated for the overall project team and by project role subgrouping that included principal investigators, professional and technical staff, graduate students, advisory board members, and extension educators. The analysis examined the following research questions: (1) Do participants’ attitudes and behaviors toward the transdisciplinary process change over the course of the project? (2) Do these changes vary by participant role? Results indicate that while transdisciplinary behaviors did not significantly change for most of the role subgroups, advisory board members showed a decrease in transdisciplinary behaviors from the pre-assessment to the mid-assessment evaluation. Analysis of the other measures consistently showed a positive increase in mean scores from the pre- to the mid-assessment with one exception. Graduate student scores on the transdisciplinary attitude scale decreased over time. Understanding how participant perceptions may change over the course of a project and how project roles may influence these changes is important to managing effective long-term transdisciplinary projects.
Morphing into Shape

Two appendages of the fly, the haltere and the wing, grow to very different sizes. Limited expression and mobility of a growth morphogen is partly responsible for this difference.
Distributed Octree Data Structures and Local Refinement Method for the Parallel Solution of Three-Dimensional Conservation Laws

Conservation laws are solved by a local Galerkin finite element procedure with adaptive space-time mesh refinement and explicit time integration. A distributed octree structure representing a spatial decomposition of the domain is used for mesh generation, and later may be used to correct for processor load imbalances introduced at adaptive enrichment steps. A Courant stability condition is used to select smaller time steps on smaller elements of the mesh, thereby greatly increasing efficiency relative to methods having a single global time step. To accommodate the variable time steps, octree partitioning is extended to use weights derived from element size. Computational results are presented for the three-dimensional Euler equations of compressible flow solved on an IBM SP2 computer. The problem examined is the flow inside a perforated shock tube.
Real-time implementation of distortion corrections for a tiled EMCCD-based Solid State X-ray Image Intensifier (SSXII).

The new Solid State X-ray Image Intensifier (SSXII) is being designed based on a modular imaging array of Electron Multiplying Charge Couple Devices (EMCCD). Each of the detector modules consists of a CsI(Tl) phosphor coupled to a fiber-optic plate, a fiber-optic taper (FOT), and an EMCCD sensor with its electronics. During the optical coupling and alignment of the modules into an array form, small orientation misalignments, such as rotation and translation of the EMCCD sensors, are expected. In addition, barrel distortion will result from the FOTs. Correction algorithms have been developed by our group for all the above artifacts. However, it is critical for the system's performance to correct these artifacts in real-time (30 fps). To achieve this, we will use two-dimensional Look-Up-Tables (LUT) (each for x and y coordinates), which map the corrected pixel locations to the acquired-image pixel locations. To evaluate the feasibility of this approach, this process is simulated making use of parallel coding techniques to allow real-time distortion corrections for up to sixteen modules when a standard quad processor is used. The results of this simulation confirm that tiled field-of-views (FOV) comparable with those of flat panel detectors can be generated in ~17 ms (>30 fps). The increased FOV enabled through correction of tiled images, combined with the EMCCD characteristics of low noise, negligible lag and high sensitivity, should make possible the practical use of the SSXII with substantial advantages over conventional clinical systems. (Support: NIH Grants R01EB008425, R01NS43924, R01EB002873)
Integration of cardiac myofilament activity and regulation with pathways signaling hypertrophy and failure.

The syndrome of congestive heart failure (CHF) is an entity of ever increasing clinical significance. CHF is characterized by a steady decrease in cardiac pump function, which is eventually lethal. The mechanisms that underlie the decline in cardiac function are incompletely understood. A central theme in solving the mystery of heart failure is the identification of mechanisms by which the myofilament contractile machine of the myocardium is altered in CHF and how these alterations act in concert with pathways that signal cell growth and death. The cardiac myofilaments are a point of confluence of signals that promote the hypertrophic/failure process. Our hypothesis is that a prevailing hemodynamic stress leads to an increased strain on the myocardium. The increased strain in turn leads to miscues of the normal physiological pathway by which heart cells are signaled to match and adapt the intensity and dynamics of their mechanical activity to prevailing hemodynamic demands. These miscues result in a maladaptation to the stressor and failure of the heart to respond to hemodynamic loads at optimal end diastolic volumes. The result is a vicious cycle exacerbating the failure. Cardiac myofilament activity, the ultimate determinant of cellular dynamics and force, is a central player in the integration and regulation of pathways that signal hypertrophy and failure. © 2000 Biomedical Engineering Society.
Anisotropic Interference of Three-Wave and Double Two-Wave Frequency Mixing in GaAs

It is shown that two-step, two-wave mixing makes a substantial contribution to the total three-wave mixing process in a noncentrosymmetric crystal. The efficiency of generating $2{\ensuremath{\omega}}_{1}\ensuremath{-}{\ensuremath{\omega}}_{2}$ was observed as a function of the difference frequency ${\ensuremath{\omega}}_{1}\ensuremath{-}{\ensuremath{\omega}}_{2}$, the electric polarization vector, and the propagation direction. This method allowed the determination of the true third-order susceptibility ${\ensuremath{\chi}}^{(3)}$, in both sign and magnitude, in terms of ${[{\ensuremath{\chi}}^{(2)}]}^{2}$.
The 1.1-Å resolution crystal structure of DJ-1, the protein mutated in autosomal recessive early onset Parkinson's disease

Mutations in DJ-1, a human gene with homologues in organisms from all kingdoms of life, have been shown to be associated with autosomal recessive, early onset Parkinson's disease (PARK7). We report here the three-dimensional structure of the DJ-1 protein, determined at a resolution of 1.1 A by x-ray crystallography. The chain fold of DJ-1 resembles those of a bacterial protein, PfpI, that has been annotated as a cysteine protease, and of a domain of a bacterial catalase whose role in the activity of that enzyme is uncertain. In contrast to PfpI, a hexameric protein whose oligomeric structure is essential for its putative proteolytic activity, DJ-1 is a dimer with completely different intersubunit contacts. The proposed catalytic triad of PfpI is absent from the corresponding region of the structure of DJ-1, and biochemical assays fail to detect any protease activity for purified DJ-1. A highly conserved cysteine residue, which is catalytically essential in homologues of DJ-1, shows an extreme sensitivity to radiation damage and may be subject to other forms of oxidative modification as well. The structure suggests that the loss of function caused by the Parkinson's-associated mutation L166P in DJ-1 is due to destabilization of the dimer interface. Taken together, the crystal structure of human DJ-1 plus other observations suggest the possible involvement of this protein in the cellular oxidative stress response and a general etiology of neurodegenerative diseases.
Recognition of tRNA Backbone for Aminoacylation with Cysteine: Evolution from Escherichia coli to Human

The underlying basis of the genetic code is specific aminoacylation of tRNAs by aminoacyl-tRNA synthetases. Although the code is conserved, bases in tRNA that establish aminoacylation are not necessarily conserved. Even when the bases are conserved, positions of backbone groups that contribute to aminoacylation may vary. We show here that, although the Escherichia coli and human cysteinyl-tRNA synthetases both recognize the same bases (U73 and the GCA anticodon) of tRNA for aminoacylation, they have different emphasis on the tRNA backbone. The E. coli enzyme recognizes two clusters of phosphate groups. One is at A36 in the anticodon and the other is in the core of the tRNA structure and includes phosphate groups at positions 9, 12, 14, and 60. Metal-ion rescue experiments show that those at positions 9, 12, and 60 are involved with binding divalent metal ions that are important for aminoacylation. The E. coli enzyme also recognizes 2'-hydroxyl groups within the same two clusters: at positions 33, 35, and 36 in the anticodon loop, and at positions 49, 55, and 61 in the core. The human enzyme, by contrast, recognizes few phosphate or 2'-hydroxy groups for aminoacylation. The evolution from the backbone-dependent recognition by the E. coli enzyme to the backbone-independent recognition by the human enzyme demonstrates a previously unrecognized shift that nonetheless has preserved the specificity for aminoacylation with cysteine.
Chronic inflammation and bladder cancer

The relation between Schistosomiasis and bladder cancer is well-established and accounts for the high rates of bladder cancer in a number of developing countries, including Egypt. In developed countries, transitional cell carcinoma is the predominant type of bladder cancer, whereas in Schistosomiasis-endemic regions, squamous cell carcinoma is the most common type. In this review, experimental and observational data on infection, inflammation, and bladder cancer are summarized with special emphasis on transitional cell carcinoma. Findings from numerous studies suggest that inflammation is likely to have an important role in bladder carcinogenesis in developed countries. Future studies need to focus in greater detail on risk factors that increase inflammation of the bladder, examine genetic susceptibility to inflammatory pathways, and include markers of inflammation measured prior to cancer diagnosis. Understanding the role of inflammation on transitional cell carcinogenesis may provide important insights on how to prevent the sixth most common cancer in the United States.
The agouti-related protein and body fatness in humans

OBJECTIVE: The objective of this study was to examine the impact of a single nucleotide polymorphism (SNP) (−38C>T) in the promoter of the human agouti-related protein (hAgRP) gene on promoter affinity for transcription factors (TFs) and its possible association with body composition phenotypes. DESIGN: Electrophoretic mobility shift assays for the functional studies and association analyses for the population studies. SUBJECTS AND METHODS: Nuclear extracts were isolated from the mouse hypothalamus cell line GT1-7 and subjected to binding assays using oligonucleotide probes corresponding to the −38C>T region and an antibody for the E12/E47 TFs. Individuals (n?=?259) from the HERITAGE Family Study were genotyped for the −38C>T SNP and used in the association studies. RESULTS: Electrophoretic mobility shift and supershift assays confirmed binding of the E12/E47 TF to the −38C>T site in a genotype-dependent manner. The T allele was found exclusively in the black subjects while the genotype with the higher binding affinity, CC, was significantly associated with high BMI, fat mass, and percent body fat in the black subjects of the HERITAGE Family Study. CONCLUSIONS: The E12/E47 TF could play a role in the regulation of hAgRP expression while the population studies suggest that the TT genotype of the −38C>T SNP could play a protective role against the development of obesity in the black population of the HERITAGE Family Study.
Effect of salts on the physical and kinetic properties of human placental choline acetyltransferase.

— The effects of salt on the properties of human placental choline acetyltransferase have been examined. Increases in enzyme activity, thermal denaturation and susceptibility to proteolysis can be related to increases in ionic strength, rather than to specific salt effects. Increased ionic strength increases the maximal velocity (Km) of the reaction, with no change in the kinetic parameter Vmax/Km (choline). The pH-Km profile, measured over the range of 6.5–8.0, indicates the requirement of a dissociated acidic residue whose pKa is below 7.5 at high ionic strength, and a protonated residue whose pKa is above 7.5 at low ionic strength. It is proposed that the conformation of the enzyme is different at high ionic strength and at low ionic strength, and that these different conformational states of the enzyme result in different rate-determining steps of the reaction.
Further studies on the protein conjugation of hydroxamic acid bifunctional chelating agents: group-specific conjugation at two different loci.

A procedure utilizing an activated ester approach for conjugation of unprotected hydroxamic acids to antibodies and peptides was recently reported. Here, an alternative method with advantages over the activated ester strategy is described. This protocol utilizes the hydrazone formation between a hydrazide derivative of the trihydroxamate ligand trisuccin and either a ketone derivative of antibody or the aldehyde groups, generated by oxidation of the carbohydrate residues. Thus, the trisuccin carboxylic acid (1) was derivatized with tert-butyl carbazate to the hydrazide 2, and the protecting groups were removed by catalytic hydrogenation and acidolysis with TFA to afford the hydroxamate hydrazide 4. Conjugation of 4 to monoclonal antibody CC49 was effected by two approaches: attachment through the amine (e.g., lysine) residues of the antibody or oxidation of the carbohydrate residues. The extent of conjugations were monitored by MALDI, through evaluation of the increases in molecular weights of the conjugates compared to the unconjugated antibody. The first approach utilizing a ketone linker (6-oxoheptanoic acid, OHA) which served as a hydrazide anchor, is being introduced in this report as a new technique for conjugation of hydrazide derivatives to proteins. The OHA approach proved to be a superior strategy over the aldehyde approach in the ease of the procedure and yield of protein recovery. It also had the advantage of yielding more control in adjusting the ligand-to-protein ratio and was therefore selected for protocol optimization. All conjugates resulting from both approaches were radiolabeled with 125I and screened for their immunoreactivity. Furthermore, the conjugates prepared through the optimized OHA protocol were radiolabeled with both 99mTc and 125I for which the radiolabeling yields and immunoreactivities are reported.
Stresses in some anisotropic materials due to indentation and sliding

Abstract This paper is concerned with the stress field in Hertzian contact of parallel cylinders composed of some general anisotropic materials, and of the Hertzian contact of transversely isotropic spherical bodies. Explicit analytical expressions are found for the stress components in each case. Numerical results indicate that the maximum shear stress distribution may deviate significantly from that of the isotropic case.
Dentist's Ratings and Adolescents' Perceptions of Oral Health

The extent to which adolescents' self-appraisals of dental status agree with the dentist's evaluation is analyzed. The dentist's evaluation was expressed in standard dental status indicators (DMF, OHI-S. Russell Index) and in a rating of overall status as "excellent," "good," "fair," "poor." The relationship between the adolescents' self-reported dental care practices and the dentist's evaluation is also examined.
Direct Evidence of Active-Site Reduction and Photodriven Catalysis in Sensitized Hydrogenase Assemblies

We report photocatalytic H2 production by hydrogenase (H2ase)–quantum dot (QD) hybrid assemblies. Quenching of the CdTe exciton emission was observed, consistent with electron transfer from the quantum dot to H2ase. GC analysis showed light-driven H2 production in the presence of a sacrificial electron donor with an efficiency of 4%, which is likely a lower limit for these hybrid systems. FTIR spectroscopy was employed for direct observation of active-site reduction in unprecedented detail for photodriven H2ase catalysis with sensitivity toward both H2ase and the sacrificial electron donor. Photosensitization with Ru(bpy)32+ showed distinct FTIR photoreduction properties, generating all of the states along the steady-state catalytic cycle with minimal H2 production, indicating slow, sequential one-electron reduction steps. Comparing the H2ase activity and FTIR results for the two systems showed that QDs bind more efficiently for electron transfer and that the final enzyme state is different for the two se...
Design and implementation of real-time off-grid detection tool based on FNET/GridEye

Real-time situational awareness tools are of critical importance to power system operators, especially during emergencies. The availability of electric power has become a linchpin of most post disaster response efforts as it is the primary dependency for public and private sector services, as well as individuals. Knowledge of the scope and extent of facilities impacted, as well as the duration of their dependence on backup power, enables emergency response officials to plan for contingencies and provide better overall response. Based on real-time data acquired by Frequency Disturbance Recorders (FDRs) deployed in the North American power grid, a real-time detection method is proposed. This method monitors critical electrical loads and detects the transition of these loads from an on-grid state, where the loads are fed by the power grid to an off-grid state, where the loads are fed by an Uninterrupted Power Supply (UPS) or a local backup generation system. The details of the proposed detection algorithm are presented, and some case studies and off-grid detection scenarios are also provided to verify the effectiveness and robustness. Meanwhile, how to implement the detection tool in real-time environment and its achievements in detecting off-grid situations are discussed in this paper.
SH-SY5Y cells as a model for sigma receptor regulation of potassium-stimulated dopamine release

Abstract Previous studies in our laboratory using rat brain tissue have shown that neuropeptide Y (NPY) can enhance NMDA- and potassium-stimulated dopamine release from various brain regions and that this enhancement is reversed by sigma (σ) receptor antagonists. In the current study, we sought to determine whether SH-SY5Y cells are suitable for investigating σ receptor effects and whether any σ receptors present are of the subtype responsive to NPY. We compare mechanisms by which the prototypical σ receptor agonist (+)-pentazocine, and the proposed endogenous σ receptor ligand NPY regulate potassium-stimulated [ 3 H]dopamine release from SH-SY5Y cells. Both (+)-pentazocine and NPY inhibit potassium-stimulated [ 3 H]dopamine release. Unlike our studies in rat brain tissue, the effect of NPY on [ 3 H]dopamine release is not reversed by σ receptor antagonists. SH-SY5Y cells appear to be an appropriate model to study the regulation of dopamine release by σ receptors or by NPY receptors, but this population is not identical to that population identified in brain slices.
From molecules to societies: mechanisms regulating swarming behavior in honey bees (Apis spp.)

Reproduction by colony fission, or swarming, is a spectacular example of a behavior that requires the simultaneous coordination of the activities of thousands of honey bee workers and their queen. The successful execution of this collective phenomenon relies on the appropriate response of individuals in swarms to a myriad of signals that are produced by workers and queens to synchronize their nest exodus, subsequent house hunting, and eventual relocation to a new nest site. In this review, we describe our current understanding of the social factors that trigger swarming in colonies and the nonchemical and chemical signals that mediate a coordinated transition between its stages. We also highlight emerging work on the physiological and genomic mechanisms underpinning swarming behavior. Finally, we discuss the possible evolutionary origins of swarming behavior, through comparisons with related behaviors of migration, overwintering, estivation, and diapause in honey bees and other insects.
Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: Role of bone marrow-derived myelomonocytic cells

Tumor vasculature is derived from sprouting of local vessels (angiogenesis) and bone marrow (BM)-derived circulating cells (vasculogenesis). By using a model system of transplanting tumors into an irradiated normal tissue to prevent angiogenesis, we found that tumors were unable to grow in matrix metalloproteinase-9 (MMP-9) knockout mice, but tumor growth could be restored by transplantation of wild-type BM. Endothelial progenitor cells did not contribute significantly to this process. Rather, CD11b-positive myelomonocytic cells from the transplanted BM were responsible for tumor growth and the development of immature blood vessels in MMP-9 knockout mice receiving wild-type BM. Our results suggest that MMP-9 could be an important target for adjunct therapy to enhance the response of tumors to radiotherapy.
Fourier transform infrared spectroscopic studies of atmospheric chemistry

Abstract Recent advances in the Fourier transform IR absorption spectroscopic method make it a powerful tool for quantitative analysis of gaseous molecules present in the air at low concentrations. As a result, its use in laboratory studies of atmospheric chemistry has led to better spectroscopic characterization of “difficult-to-handle” gases and observation of new atmospheric compounds. These recent findings are highlighted to illustrate its potential for studies of molecular spectroscopy.