cssi/SciSciGPT-SciSciNet huggingface dataset:
Current Status and Future Directions of the Immune Checkpoint Inhibitors Ipilimumab, Pembrolizumab, and Nivolumab in Oncology

Objective To provide the clinician with an update and the current status and future direction of approved immune checkpoint inhibitors (ICIs) in oncology. Data sources A PubMed search from January 1, 1966 to March 13, 2015 was performed using the key terms ipilimumab, pembrolizumab, lambrolizumab, nivolumab, immune checkpoint inhibitor, MDX-010, MDX-101, BMS-734016, MK-3475, SCH 900475, MDX-1106, BMS-936558, ONO-4538, CTLA-4, PD-1, or PD-L1 and cancer, oncology, or neoplasm. Additional references were identified from the investigators(') personal files, recent oncology meetings, review articles, clinical guidelines, and package inserts. Study selection and data extraction All English-language clinical trials assessing the safety and efficacy of ipilimumab, nivolumab, and pembrolizumab in cancer were considered. The PubMed search resulted in 215 trials; 33 met inclusion criteria. A further 28 trials were identified from the above sources; 61 trials from 2005 to 2015 were included. We consolidated and clarified treatment recommendations for the management of immune-related adverse events (irAEs), assessed response criteria, and calculated the clinical utility of leading tumor profiling options. Data synthesis Ipilimumab and nivolumab, but not pembrolizumab, have an overall survival (OS) advantage over chemotherapy first line in unresectable/metastatic melanoma. Nivolumab has an OS advantage versus chemotherapy in second-line squamous non-small-cell lung cancer. Data in other settings are promising. Nivolumab and pembrolizumab are better tolerated than ipilimumab. Further validation of response criteria is needed. Tumor profiling to predict clinical benefit is premature but promising. Conclusions The treatment landscape in oncology is quickly evolving with the advent of ICIs.
Effect of a Selective Decontamination of the Digestive Tract Regimen Including Parenteral Cefepime on Establishment of Intestinal Colonization with Vancomycin-Resistant Enterococcus spp. and Klebsiella pneumoniae in Mice

In mice, a selective decontamination of the digestive tract regimen consisting of orogastric tobramycin, polymyxin E, and amphotericin B in combination with subcutaneous cefepime inhibited gram-negative bacilli, including Klebsiella pneumoniae, and did not promote vancomycin-resistant Enterococcus spp. (VRE) colonization. However, concurrent administration of subcutaneous ampicillin-sulbactam resulted in promotion of VRE.
Chromaticity and Impedance Effect on the Transverse Motion of Longitudinal Bunch Slices in the Tevatron

The Transverse turn-by-turn evolution of a bunch slice are examined considering chromatic and impedance effects. A quasi-analytical approximation is developed using perturbative expansion of Hills equation with a wake field. This approximation is compared to turn-by-turn measurements taken in the Tevatron and from this linear and second order chromaticity, and Impedance are calculated as well as beam stability thresholds.
The Influence of Climate Model Biases on Projections of Aridity and Drought

AbstractGlobal climate models (GCMs) have biases when simulating historical climate conditions, which in turn have implications for estimating the hydrological impacts of climate change. This study examines the differences in projected changes of aridity [defined as the ratio of precipitation (P) over potential evapotranspiration (PET), or P/PET] and the Palmer drought severity index (PDSI) between raw and bias-corrected GCM output for the continental United States (CONUS). For historical simulations (1950–79) the raw GCM ensemble median has a positive precipitation bias (+24%) and negative PET bias (−7%) compared to the bias-corrected output when averaged over CONUS with the most acute biases over the interior western United States. While both raw and bias-corrected GCM ensembles project more aridity (lower P/PET) for CONUS in the late twenty-first century (2070–99), relative enhancements in aridity were found for bias-corrected data compared to the raw GCM ensemble owing to positive precipitation and ne...
Declining frequency of ischemia detection using stress myocardial perfusion imaging.

Nuclear cardiology for detection of myocardial ischemia has a long and proud history that spans many decades ([1][1]). As currently used, stress myocardial perfusion imaging (MPI) using single-photon emission computed tomography has evolved over the years in its use of hardware, software,
Cyclic Oxidation Behavior and Durability of ODS-FeCrAl Alloys in H2O and CO2 Rich Environments

Cyclic oxidation testing was conducted at 1200 C in O2, dry air and in atmospheres rich in H2O and/or CO2 to simulate combustion environments. The oxidation rates were significantly higher in air + 10%H2O and a mixture of O2-buffered 50%H2O-50%CO2, leading to shorter times to breakaway oxidation. Curve fitting using the COSP cyclic oxidation program confirmed that the presence of H2O results in an increase of the alumina spallation rate. The use of specimen mass gain modeling associated with the characterization of pre-oxidized specimens and in particular the determination of the remaining Al content after exposure, will allow to accurately estimate the durability of oxide dispersion-strengthened (ODS) FeCrAl alloys in combustion environments.
Harnessing surface-bound enzymatic reactions to organize microcapsules in solution

By developing new computational models, we examine how enzymatic reactions on an underlying surface can be harnessed to direct the motion and organization of reagent-laden microcapsules in a fluid-filled microchannel. In the presence of appropriate reagents, surface-bound enzymes can act as pumps, which drive large-scale fluid flows. When the reagents diffuse through the capsules’ porous shells, they can react with enzymatic sites on the bottom surface. The ensuing reaction generates fluid density variations, which result in fluid flows. These flows carry the suspended microcapsules and drive them to aggregate into “colonies” on and near the enzyme-covered sites. This aggregation continues until the reagent has been depleted and the convection stops. We show that the shape of the assembled colonies can be tailored by patterning the distribution of enzymes on the surface. This fundamental physicochemical mechanism could have played a role in the self-organization of early biological cells (protocells) and can be used to regulate the autonomous motion and targeted delivery of microcarriers in microfluidic devices.
Donation after cardiac death for lung transplantation: a review of current clinical practice.

Purpose of review This review presents a concise update on clinical donation after cardiac death (DCD or DDCD) lung transplantation. Lung allografts have predominantly been procured from donors after determination of neurologic death but will not meet the existing demand. A steadily increasing need for lungs is evident worldwide, especially in an era of improved outcomes for recipients. Other solid organ utilization from donors after determination of cardiac death has markedly increased internationally, but the utilization rate of lungs from such donors is still considerably less. The multifaceted reasons for this discrepancy are considered, and the recent evidence available supporting DCD for lung transplantation in clinical practice is presented in context. The recent experimental research studies are not within the remit of this appraisal. Recent findings The more recent and markedly increased lung recipient cohorts showed very satisfactory survival outcomes for DCD transplantation in several programs. The overall utilization rate, however, remains low. The background and the rationale of lung donor allograft expansion to proactively include DCD allografts from controlled (Maastricht category III donors) is re-emphasized in this review. The feasibility of other DCD categories for lung transplantation is considered. This is particularly prudent with the advent of the ex-vivo lung perfusion modality in pulmonary procurement. Summary Despite evidence for adequate survival outcomes and reported favorable primary graft dysfunction rates, DCD lung transplantation remains underutilized in most countries. Waiting times could be notably reduced and mortality of lung candidates arguably decreased by a more decided and appropriate implementation of proven DCD lung transplant strategies.
Air Embolism as a Complication of Artificial Pneumothorax

Since the introduction of artificial pneumothorax in the treatment of pulmonary tuberculosis occasional cases of air embolism complicating this form of therapy have been reported in the literature. Bruns reported thirteen cases of air embolism with four deaths, occurring during a nine year period in approximately 12,700 pneumothorax treatments. Reyer and Kohl noted ten cases with five deaths in a "series of many thousand insufflations during a period of about four years." The latter observers believe that many of those cases of pleural shock reported in the literature are, in reality, mild cases of cerebral embolism especially since the sign and symptoms in both conditions are very similar. It is quite probable that this complication is more frequent than is generally recognized. This may be due to the fact that if a fatal termination does not occur, the condition is overlooked or called pleural shock or else this type or case is not reported in the literature. The infrequency of necropsies on cases dying from air embolism and the definite proof of the cause of death warrants the recording of this case.
A Ds Insertional Mutant of a Barley miR172 Gene Results in Indeterminate Spikelet Development

A simple, polymerase chain reaction (PCR) and agarose gel-based system was used to efficiently detect barley (Hordeum vulgare L.) lines with novel transpositions of a modified maize (Zea mays L.) Ds element. One line contained a Ds insertion in a gene critical to barley spike development which appears to be a regulatory component of the ABC model of floral development. This model, elucidated based on studies of dicots, is widely conserved and function of key genes–such as AP2–have been demonstrated in monocots such as rice (Oryza sativa L.) and maize, but significant differences in orthologous gene function exist. This report describes the generation of a Ds-insertional mutant of a putative barley ortholog of miR172. The miR172 family of microRNAs (miRNAs) includes a member shown to control the expression of AP2 and AP2-like orthologs during floral development. The Ds-miR172 mutant contains a 3.6 kb insertion in the mature miRNA sequence, thus abolishing function, and the associated floral abnormalities are consistent with the failure to properly regulate the barley AP2 ortholog. Ds-miR172 mutants show abnormal spikelet development, including the conversion of glumes to partially developed florets in apical regions of spikes. Basal regions of the spike show an abnormal branching phenotype resulting from indeterminate spikelet meristem development, with each branch consisting of multiple, abnormal spikelets and other floral organs in place of a single spikelet. This phenotype is similar to ts4 in maize, the only other known mutation affecting a miR172 ortholog.
Lifetime, Mobility, and Diffusion of Photoexcited Carriers in Ligand-Exchanged Lead Selenide Nanocrystal Films Measured by Time-Resolved Terahertz Spectroscopy

Colloidal semiconductor nanocrystals have been used as building blocks for electronic and optoelectronic devices ranging from field-effect transistors to solar cells. Properties of the nanocrystal films depend sensitively on the choice of capping ligand to replace the insulating synthesis ligands. Thus far, ligands leading to the best performance in transistors result in poor solar cell performance, and vice versa. To gain insight into the nature of this dichotomy, we used time-resolved terahertz spectroscopy measurements to study the mobility and lifetime of PbSe nanocrystal films prepared with five common ligand-exchange reagents. Noncontact terahertz spectroscopy measurements of conductivity were corroborated by contacted van der Pauw measurements of the same samples. The films treated with different displacing ligands show more than an order of magnitude difference in the peak conductivities and a bifurcation of time dynamics. Inorganic chalcogenide ligand exchanges with sodium sulfide (Na2S) or ammon...
Abstract 4018: The role of FLI1 in breast cancer development and progression

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Breast cancer is the second most common cancer-related death among women in the US. The majority of the breast cancer-related deaths are due to tumor progression. A multitude of changes in gene expression are required for the cancer cell to acquire the ability to invade and migrate. The transcriptional activation or repression of these cancer-associated genes is not clearly understood, however many ETS family members have been considered good candidates. Friend leukemia virus integration 1 (FLI1) is an ETS protein that is aberrantly expressed in retrovirus-induced hematological tumors, and is found to be rearranged in Ewing's sarcoma and related primitive neuroectodermal tumors characterized by a t(11;22)(q24;q12) translocation. Limited attention has been directed towards elucidating the potential role of FLI1 in epithelial-derived cancers, including breast cancer. Our preliminary immunohistochemical analyses show that FLI1 protein is decreased in human invasive breast tumors compared to normal breast tissue. A decrease of FLI1 mRNA and protein was also demonstrated in breast cell cancer cell lines through Real Time RT-PCR and western blot, respectively. We used adenovirus to examine the effects of FLI1 expression in two invasive breast cancer cell lines (MDA-MB-231 and MDA-MB-157). Re-expression of FLI1 in both MDA-MB-231 and MDA-MB-157 inhibited cell growth, mainly due to a decrease in cellular proliferation. FLI1 expression also inhibited the motility and invasiveness of breast cancer cell lines, determined by the use of Transwell inserts coated with fibronectin or Matrigel, respectively. We hypothesize that the loss of FLI1 is a critical step for breast cancer progression. Loss-of-function studies using shRNA are being performed to complement the above gain-of-function studies. Future studies will investigate potential downstream targets of FLI1. Inhibiting the reduction of FLI1 or regulating its downstream targets may be to be unique targets of breast cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4018. doi:10.1158/1538-7445.AM2011-4018
A theoretical comparison of multifunctional catalyst for sorption-enhanced reforming process

Abstract This work presents the first side-by-side comparison of the two leading multifunctional catalyst designs reported in the literature today for sorption-enhance reforming processes. Two-dimensional unsteady-state models were developed to compare the performance of a core–shell multifunctional catalyst, consisting of a calcium-based sorbent core enclosed in a porous shell of methane steam reforming or water-gas shift catalyst, against an equivalent case of a uniform-distributed multifunctional design in which catalyst and sorbent materials are uniformly distributed within the particle. Additionally, these two multifunctional catalyst designs were compared against the conventional two-pellet approach, where the capture and catalytic properties are distinguished into separate pellets. Both multifunctional catalyst designs (i.e. core-shell and uniform-distributed) had greater adsorbent utilization and higher H 2 outlet concentration up to breakthrough time than the conventional two pellet design. The uniform-distributed multifunctional catalyst design had greater adsorbent utilization up to breakthrough conditions as compared to the core-shell design. This behavior may be attributed to the fact that for the uniform-distributed multifunctional, the active catalyst is constantly producing CO 2 next to an adsorbent active site. For the core-shell multifunctional catalyst design, decreasing catalyst-shell thickness resulted in performance approaching the uniform-distributed case. For the case of exothermic water-gas shift reaction coupled with CO 2 chemisorption, the core-shell design mitigated local bed hot-spot magnitudes by ~40 K.
In vitro and in vivo neuroprotective effects of cJun N-terminal kinase inhibitors on retinal ganglion cells

The c-Jun N-terminal kinase (JNK) signaling pathway plays an important role in neuronal pathophysiology. Using JNK inhibitors, we examined involvement of the JNK pathway in cultured rat retinal ganglion cell (RGC) death and in mouse retinal ischemia/reperfusion (I/R) injury of the visual axis. The in vitro effects of JNK inhibitors were evaluated in cultured adult rat retinal cells enriched in RGCs. Retinal I/R was induced in C57BL/6J mice through elevation of intraocular pressure to 120 mmHg for 60 min followed by reperfusion. SP600125 was administered intraperitoneally once daily for 28 days. Phosphorylation of JNK and c-Jun in the retina was examined by immunoblotting and immunohistochemistry. The thickness of retinal layers and cell numbers in the ganglion cell layer (GCL) were examined using H&E stained retinal cross sections and spectral domain optical coherence tomography (SD-OCT). Retinal function was measured by scotopic flash electroretinography (ERG). Volumetric measurement of the superior colliculus (SC) as well as VGLUT2 and PSD95 expression were studied. JNK inhibitors SP600125 and TAT-JNK-III, dose-dependently and significantly (p < 0.05) protected against glutamate excitotoxicity and trophic factor withdrawal induced RGC death in culture. In the I/R model, phosphorylation of JNK (pJNK) in the retina was significantly (p < 0.05) increased after injury. I/R injury significantly (p < 0.05) decreased the thickness of retinal layers, including the whole retina, inner plexiform layer, and inner nuclear layer and cell numbers in the GCL. Administration of SP600125 for 28 days protected against all these degenerative morphological changes (p < 0.05). In addition, SP600125 significantly (p < 0.05) protected against I/R-induced reduction in scotopic ERG b-wave amplitude at 3, 7, 14, 21 and 28 days after injury. SP600125 also protected against the I/R-induced losses in volume and levels of synaptic markers in the SC. Moreover, the protective effects of SP600125 in the retina and SC were also detected even with only 7 days (Days 1–7 after I/R) of SP600125 treatment. Our results demonstrate the important role the JNK pathway plays in retinal degeneration in both in vitro and in vivo models and suggest that JNK inhibitors may be a useful therapeutic strategy for neuroprotection of RGCs in the retina.
Infidelity in romantic relationships

This article summarizes the current state of research on the prediction of infidelity and provides a foundation for advancing knowledge on this topic by offering specific recommendations for future research. The prevalence, terminological diversity, and impact of infidelity on numerous indicators of wellness is first discussed. This is followed by a discussion of the individual, relationship, and contextual factors that have received systematic attention in attempting to predict infidelity. Highlights include various demographics, the closing gender gap, cohabitation, religion, and the role of the internet in facilitating infidelity. The article concludes with 8 recommendations for more informative research to advance understanding of sexual infidelity.
Making data count

Science is built on a foundation of data. The production and publication of that data should be recognized as valuable scholarship, but data lacks an essential prerequisite for modern-day scholarly recognition—accepted metrics of significance. The scientific community has traditionally estimated the impact of a journal article by counting the number of subsequent references to it; more recently, a suite of web-based alternative metrics (‘altmetrics’) offer faster assessment and the chance capture other kinds of impact1. Data can be fit into these article-centered assessment systems by proxy, via data descriptor articles in journals like Earth Systems Science Data or Scientific Data2,3. Another approach is to apply familiar metrics directly to datasets published in online databases or repositories. Complicating matters, the same metric may mean different things with respect to articles versus datasets. A researcher can read an article online closely without downloading the PDF version, but if they view a dataset landing page without downloading the data, their level of engagement is almost certainly low. A better understanding of how to measure data impact is critical if we are to reward data creators and incentivize data publication.
Influence of Disturbance on Japanese Knotweed (Fallopia japonica) Stem and Rhizome Fragment Recruitment Success within Riparian Forest Understory

ABSTRACT Japanese knotweed (Fallopia japonica) is an herbaceous invader in North America and Europe with the ability to recruit via several modes (seeds, rhizome, and stem fragments). Within US riparian forests where Japanese knotweed invades, disturbances are common over space and time in the form of flooding and mowing. It remains unknown how disturbance influences the relative recruitment success of sexual and clonal propagules of this riparian invader. Using an experimental approach, we addressed this topic by planting seeds, and rhizome and stem fragments into riparian forest plots with intact Japanese knotweed subcanopies, and into plots with the Japanese knotweed subcanopy removed, simulating disturbance. We monitored canopy openness and propagule fate (shoot emergence and height) over five months. Regardless of treatment, rhizome fragments had a higher establishment probability (85%) than seeds (3%) or stem fragments (16%). Due to a small sample size, we did not analyze the effect of disturbance o...
The Network Neutrality Battles That Will Follow Reclassification

In 2015, the U.S. Federal Communications Commission (FCC) adopted a new set of network neutrality rules for the Internet. In the process, the FCC declared for the first time that broadband Internet access service is a telecommunications service, which means that the FCC has authority to regulate broadband Internet access services under Title II of the Communications Act. Even if the 2015 Report and Order that reclassifies Internet access withstands the inevitable efforts to overturn it, many of the most important aspects of network neutrality policy have yet to be determined. This paper describes the important next steps in the network neutrality policy debate that will follow the March 2015 Report and Order. The first step is likely to occur in the courts after a legal challenge, and this paper explains why reclassification is consistent with the Telecommunications Act of 1996. The next step will occur at the FCC, because some of the most important policy issues were left unresolved in the 2015 Report and Order. We cannot know the real meaning of network neutrality policy until those issues are decided. Finally, network neutrality policy will be debated in Congress. This paper presents various forms that legislation might take.
Crease-free biaxial packaging of thick membranes with slipping folds

This paper presents a novel scheme to biaxially package and deploy flat membranes, in which the thickness of the membrane is accounted for through the novel concept of slipping folds. The membrane is divided into parallel strips connected by slipping folds, and specially chosen wrapping profiles that require zero slip along the edges of the membrane are identified. This packaging scheme avoids the kinematic incompatibilities that in other schemes result in local buckles and wrinkles that increase the deployment force and permanently deform the membrane. The paper also presents a scheme to apply uniform uniaxial prestress to the deployed membrane, as well as a two-stage deployment scheme. Packaging efficiencies of up to 83% have been demonstrated for meter-scale models, although for large membranes the packaging efficiency approaches 100%.
Abstract 4046: Interleukin-10 and programmed death-1 cooperate to regulate tumor antigen-specific CD8+ T cells in melanoma patients

With the recent success of immune checkpoint blockade in the clinic, it is expected that strategies aimed at counteracting the negative immunoregulatory networks in the tumor microenvironment will develop into potent therapy for melanoma. Here, we report that programmed death-1high (PD-1high) tumor antigen (TA)-specific CD8+ T cells present at periphery and at tumor sites in patients with advanced melanoma upregulate IL-10 receptor (IL-10R) expression. IL-10 is produced by multiple PBMC subsets in melanoma patients and acts directly on IL-10R+ TA-specific CD8+ T cells to impede proliferation and increase apoptosis. PD-1 blockade augments IL-10R expression by TA-specific CD8+ T cells, suggesting that PD-1 blockade renders PD-1+ TA-specific CD8+ T cells more sensitive to the immunosuppressive effects of endogenous IL-10. As a result, we show that IL-10 blockade adds to PD-1 blockade to increase the expansion and functions of TA-specific CD8+ T cells. Collectively, our findings support dual IL-10 and PD-1 blockade to counteract melanoma-induced T cell dysfunction and enhance TA-specific CD8+ T cell responses in patients with advanced melanoma. Citation Format: Zhaojun Sun, Julien Fourcade, Ornella Pagliano, Joe-Marc Chauvin, Cindy Sander, John M. Kirkwood, Hassane M. Zarour. Interleukin-10 and programmed death-1 cooperate to regulate tumor antigen-specific CD8+ T cells in melanoma patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4046. doi:10.1158/1538-7445.AM2015-4046
e-Business and e-Commerce

e-business uses information and communication technologies (ICT) to improve and expand the operation and functions of an organization. It is a recent phenomenon, with online commerce dating from the commercialization of the Internet in the early 1990s. e-business has many dimensions, including its relationships between business, government, and consumers, as well as in terms of intermediate and final goods and services. The global nature of the network society, combined with changing production locations and different economic, cultural, linguistic, and legal norms creates a complex set of geographies for each element of e-business.
Performance evaluation of 3D vision-based semi-autonomous control method for assistive robotic manipulator

We developed a 3D vision-based semi-autonomous control interface for assistive robotic manipulators. It was implemented based on one of the most popular commercially available assistive robotic manipulator combined with a low-cost depth-sensing camera mounted on the robot base. To perform a manipulation task with the 3D vision-based semi-autonomous control interface, a user starts operating with a manual control method available to him/her. When detecting objects within a set range, the control interface automatically stops the robot, and provides the user with possible manipulation options through audible text output, based on the detected object characteristics. Then, the system waits until the user states a voice command. Once the user command is given, the control interface drives the robot autonomously until the given command is completed. In the empirical evaluations conducted with human subjects from two different groups, it was shown that the semi-autonomous control can be used as an alternative control method to enable individuals with impaired motor control to more efficiently operate the robot arms by facilitating their fine motion control. The advantage of semi-autonomous control was not so obvious for the simple tasks. But, for the relatively complex real-life tasks, the 3D vision-based semi-autonomous control showed significantly faster performance. Implications for Rehabilitation A 3D vision-based semi-autonomous control interface will improve clinical practice by providing an alternative control method that is less demanding physically as well cognitively. A 3D vision-based semi-autonomous control provides the user with task specific intelligent semiautonomous manipulation assistances. A 3D vision-based semi-autonomous control gives the user the feeling that he or she is still in control at any moment. A 3D vision-based semi-autonomous control is compatible with different types of new and existing manual control methods for ARMs.
Amino acid sequence of an immunogenic corneal stromal protein.

Purpose. A unique cornea-associated antigen (CO-Ag) has been purified previously from stromal extracts. The protein is the target for autoantibodies in patients with Mooren's ulcer. In this study, the amino acid sequence of CO-Ag was analyzed and the structure-function properties of CO-Ag was determined. Methods. Purified CO-Ag was subjected to N-terminal sequencing by automated Edman degradation. Binding of calcium (Ca 2+ ) to CO-Ag was measured by a direct 45 Ca 2+ -binding assay. Results. The complete amino acid sequence of CO-Ag has been determined. The protein contains 70 amino acids in a single chain and lacks cysteine, tryptophan, and methionine residues. A computerized data base search of protein and nucleic acid sequences revealed strong homology to the Ca 2+ -binding proteins of the S-100 family. The sequence of CO-Ag shows a high homology with calgranulin C (CaG-C) previously purified from pig granulocytes. The functional Ca 2+ -binding sites of CO-Ag and CaG-C were different based on homology with known Ca 2+ -binding domains and their Ca 2+ -binding properties. There are three amino acid substitutions in the N-terminal Ca 2+ -binding domain. Differences were functionally conserved and compatible, with minimum single-base changes in the codon structures. The greatest difference was located in the C-terminal Ca 2+ binding domain. Five consecutive amino acid changes from D 63 -K-K-G-A 67 in Co-Ag to M 63 -Q-D-E-Q 67 occurred in CaG-C. These differences alter the structure of CO-Ag, which no longer can bind Ca 2+ ions. The existence of this nonfunctional Ca 2+ -binding site was corroborated by its Ca 2+ -binding properties. The number of Ca 2+ -binding sites for the CO-Ag subunit is approximately half that of the CaG-C monomer, although these two proteins have a similar low binding constant of approximately 2 X 10 -4 M. Conclusions. These results suggest that CO-Ag is a new member of the Ca 2+ -binding protein of the S-100 family heretofore undescribed in the cornea. Sequence data provide an important framework to search for sequence similarity with microbial proteins as possible substrates for molecular mimicry and for the identification of possible pathogenic epitopes in CO-Ag.
Structured Residuals for Fault Isolation, Disturbance Decoupling and Modelling Error Robustness

Abstract Isolation of additive and multiplicative faults and decoupling from disturbances and modelling errors are presented in a unified residual structuring framework. For additive faults and disturbances, the structured residuals are obtained via the off-line transformation of a primary parity equation set. For multiplicative faults and modelling errors, they are computed online as time-varying combinations of the primary residuals. While the number of single faults that can be isolated is unrestricted, complete decoupling is possible only from a limited number of disturbances or parameter uncertainties.
Synthesis, Characterization, and Adsorption Properties of a Graphene Composite Sand (GCS) and Its Application in Remediation of Hg(II) Ions

In this study, graphene-based adsorbent was successfully prepared following a thermal treatment method. The prepared material, named as graphene-coated sand (GCS), was used as an adsorbent for the removal of Hg(II) ions from aqueous solutions. Structure, composition, and morphology of the GCS were characterized by Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), X-ray diffractometer (XRD), Raman spectroscopy, electron diffraction (ED) measurements, energy dispersive X-ray spectroscopy (EDX), surface area measurements, particle size, and zeta potential measurements, respectively. A batch adsorption method was used to assess the ability of GCS towards removal of Hg(II) ions from aqueous solutions. The results of batch studies revealed that the GCS required a pH value 6.0, contact time 120 min, and adsorbent dose of 200 mg to attain adsorption equilibrium. Langmuir, Freundlich, Temkin, and D-R adsorption isotherm models were employed to evaluate the isotherm constants and other parameters related to the adsorption process. The Hg(II) ions uptake by the GCS was found to follow Freundlich isotherm model with R 2 value of 0.97695, under optimized conditions and at 40 °C with a maximum adsorption capacity of 299.40 mg/g. The adsorption process followed the second-order kinetic path. The thermodynamic parameters such as ΔH°, ΔS°, and ΔG° were also calculated which suggested that the adsorption processes of Hg(II) ions onto the GCS was endothermic and entropy favored. The values of ΔG° at 283, 303, and 313 K were − 1.10, − 0.025, and − 4.55 kJ, respectively, and ΔH°, ΔS° were calculated to be 26.60 kJ mol−1 and ΔS° 1.35 J mol−1 K−1, respectively. The obtained results revealed that the prepared materials could be effectively and economically beneficial.
Influence of Reclaimed Asphalt Pavement on Performance-Related Properties of Gap-Graded Rubberized Hot-Mix Asphalt

Rubberized hot-mix asphalt (RHMA) has been widely used in construction projects by the California Department of Transportation (Caltrans) for the environmental benefits of its recycled waste tires and for its improved fatigue and reflective cracking resistance. Currently, Caltrans does not permit the use of reclaimed asphalt pavement (RAP) in any gap- or open-graded rubberized asphalt mixes. However, given the cost and environmental benefits of RAP to replace portions of required virgin binder and aggregates in conventional mixes, interest is growing in the addition of some RAP to RHMA mixes as well. This study investigated concerns about this proposed practice. Three phases of laboratory testing (i.e., asphalt binder testing, fine aggregate matrix mix testing, and full-graded mix testing) were conducted to evaluate the effects of the addition of RAP into new RHMA mixes. The results indicated that the gap-graded aggregate structure of RHMA might limit the amount of RAP that could be used in the mix. Only ...
Pericyte ALK5/TIMP3 Axis Contributes to Endothelial Morphogenesis in the Developing Brain

Summary The murine embryonic blood-brain barrier (BBB) consists of endothelial cells (ECs), pericytes (PCs), and basement membrane. Although PCs are critical for inducing vascular stability, signaling pathways in PCs that regulate EC morphogenesis during BBB development remain unexplored. Herein, we find that murine embryos lacking the transforming growth factor β (TGF-β) receptor activin receptor-like kinase 5 (Alk5) in brain PCs (mutants) develop gross germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH). The germinal matrix (GM) is a highly vascularized structure rich in neuronal and glial precursors. We show that GM microvessels of mutants display abnormal dilation, reduced PC coverage, EC hyperproliferation, reduced basement membrane collagen, and enhanced perivascular matrix metalloproteinase activity. Furthermore, ALK5-depleted PCs downregulate tissue inhibitor of matrix metalloproteinase 3 (TIMP3), and TIMP3 administration to mutants improves endothelial morphogenesis and attenuates GMH-IVH. Overall, our findings reveal a key role for PC ALK5 in regulating brain endothelial morphogenesis and a substantial therapeutic potential for TIMP3 during GMH-IVH.
Comparison of Trace Mineral Repletion Strategies in Beef Cattle to Overcome a High Antagonist Diet

It was observed that diets with high sulfur and molybdenum decreased markers of copper, selenium, and manganese after 90 d. In a 62-d trace mineral repletion period, steers receiving an injection of Multimin90 had the most rapid improvement of copper and selenium status by d 14, while it took 28 d and 42 d for copper and selenium status to improve in steers supplemented with 150% of national recommended concentrations from either an inorganic and organic blend, or only inorganic trace minerals. Further research is needed to understand the optimal trace mineral supplementation strategy to overcome dietary antagonisms without creating economic loss for producers.
Prediction of imipenem-resistant microorganisms among the nosocomial critically ill patients with Gram-negative bacilli septicemia: a simple risk score.

Objectives The increasing number of reports on infections due to carbapenem-resistant Gram-negative bacilli (GNB) has raised concerns, because they have complicated empiric or guided antibiotic therapy for critically ill patients. We aimed to develop a scoring system to predict nosocomial imipenem-resistant GNB (IR-GNB) septicemia among the critically ill patients. Materials and methods The study included critically ill adult patients with nosocomial GNB septicemia at Kaohsiung Chang Gung Memorial Hospital (CGMH) in 2013-2015, and the scoring system for predicting IR-GNB septicemia was developed, followed by prospective validation conducted among patients at Linkou CGMH and Kaohsiung CGMH between January and June, 2016. Results In the development of the scoring system, 748 patients were included. The independent factors associated with IR-GNB septicemia were prior exposure (days) to carbapenems (adjusted odds ratio [aOR] per 1-day increase, 1.1; 1-3 days: 2 points, 4-6 days: 5 points, 7-9 days: 8 points, and ≥10 days: 13 points), use of mechanical ventilation (aOR 3.7; 5 points), prior colonization with IR-GNB strains (aOR 3.5; 5 points) within 30 days before the onset of GNB septicemia, and comorbid condition with chronic kidney disease (aOR 2.1; 3 points). The internal validation showed an area under the receiver operating characteristic curve (ROC) of 0.75; and an external validation among 314 patients showed similarly good performance (ROC 0.77). Youden's index indicated the score of ≥6 as the best cutoff value with sensitivity of 75% and specificity of 79%. Conclusion This scoring system might help clinicians stratify the risk for developing IR-GNB septicemia among critically ill patients and combined antibiotics may be used until antimicrobial de-escalation/adjustment is clearly indicated by the subsequently identified GNB and its susceptibility profile.
Comparing Clinical Perimetry and Population Receptive Field Measures in Patients with Choroideremia.

Purpose Choroideremia (CHM) is an X-linked recessive form of hereditary retinal degeneration, which, at advanced stages, leaves only small central islands of preserved retinal tissue. Unlike many other retinal diseases, the spared tissue in CHM supports excellent central vision and stable fixation. Such spared topography in CHM presents an ideal platform to explore the relationship between preserved central retinal structure and the retinotopic organization of visual cortex by using functional magnetic resonance imaging (fMRI). Methods fMRI was conducted in four participants with CHM and four healthy control participants while they viewed drifting contrast pattern stimuli monocularly. A single ∼3-minute fMRI run was collected for each eye separately. fMRI data were analyzed using the population receptive field (pRF) modeling approach. Participants also underwent ophthalmic evaluations of visual acuity and static automatic perimetry. Results The spatial distribution and strength of pRF estimates correlated positively and significantly with clinical outcome measures in most participants with CHM. Importantly, the positive relationship between clinical and pRF measurements increased with increasing disease progression. A less consistent relationship was observed for control participants. Conclusions Although reflecting only a small sample size, clinical evaluations of visual function in participants with CHM were well characterized by the spatial distribution and strength of pRF estimates by using a single ∼3-minute fMRI experiment. fMRI data analyzed with pRF modeling may be an efficient and objective outcome measure to complement current ophthalmic evaluations. Specifically, pRF modeling may be a feasible approach for evaluating the impact of interventions to restore visual function.
Affect, Mood, Emotions: Depressive Disorders and Bipolar and Related Disorders

Mood is a continuum, with one end representing feeling down, blue, sad, miserable, depressed, or down in the dumps; the middle representing euthymia; and the other end representing feeling happy, high, joyous, euphoric, elated, exulted, ecstatic, or manic. All of us experience varying gradations of moods, and they are necessary and adaptive experiences for survival and emotional maturation. The extremes of moods, the depressive syndrome and the manic syndrome, are final common pathway brain dysfunctions. The diagnosis and treatment of mood disorders are discussed in this chapter.
Vacuum Tunneling in Minkowski Space

The recent discovery of classical Euclidean solutions to non-abelian gauge theories1–5 and their possible interpretation as tunnelings among vacua with different winding numbers6–10 stimulate much excitement and speculation. However, the interpretation of a classical Euclidean solution as a realization of vacuum tunneling is not completely transparent. Since the tunneling process is well understood in a quantum mechanical potential scattering theory, it is conceptually satisfactory to reduce a vacuum tunneling process in a quantum field theory to an effective one particle quantum mechanical potential scattering problem. In these lectures, I shall present the vacuum tunneling in Minkowski Space10 as a change of field configurations from one ground state to another. By properly choosing the intermediate field configurations, we obtain an effective one parameter quantum mechanical system in which the tunneling between two different vacua take place. In the first lecture (Sec. 2 below), I shall work out a simple example describing the vacuum tunneling in a two-dimensional ϕ4 field theory. In the next lecture (Sees. 3 and 4), I shall work out the vacuum tunneling associated with the simplest one-instanton solution in a Yang-Mills theory.
Eusocial evolution and the recognition systems in social insects.

Eusocial species, animals which live in colonies with a reproductive division of labor, typically have closed societies, in which colony members are allowed entry and nonmembers, including animals of the same species, are excluded. This implies an ability to discriminate colony members (“self”) from nonmembers (“nonself”). We draw analogies between this type of discrimination and MHC-mediated cellular recognition in vertebrates. Recognition of membership in eusocial colonies is typically mediated by differences in the surface chemistry between members and nonmembers and we review studies which support this hypothesis. In rare instances, visual signals mediate recognition. We highlight the need for better understanding of which surface compounds actually mediate recognition and for further work on how differences between colony members and nonmembers are perceived.
Protecting the Religious Liberty of Religious Institutions

This article is a preliminary inquiry into the question of whether the freedom of the Church, as a distinct religious institution, can be justified from an American legal perspective. The first part of the article identifies respect for the individual dignity and autonomy of the person as a primary justification for providing distinctive legal protection to religious liberty. It goes on to discuss whether distinctive religious liberty protection for religious institutions can be derived from the dignitary interests of the institution’s members – and if so, whether there is some limit beyond which institutional religious liberty claims cannot be grounded in the individual dignitary interests of congregants or constituents.The second and longer part of the Article examines whether an argument for protecting and accommodating the autonomy of religious institutions can be grounded in American history during the 1700’s and early 1800’s. The history of this period includes multiple cross currents of values and interests that very by time and region – making it difficult to reach more than tentative conclusions. However, the Protestant commitment by religious liberty proponents to the belief that each man must judge for himself on matters relating to religion, the virulent anti-Catholicism of the period, at least some of which may be attributed to fear of and antipathy toward top down ecclesiastical hierarchy, and the prevalence of anti-clerical attitudes suggest some limits to the American commitment to the freedom of the Church as an institution. Clearly, a sphere of religious liberty extended to the local congregation and to a considerable extent to democratically created and accountable ecclesiastical decision-making bodies. It may be argued, however, that Americans of this period viewed non-democratic, hierarchical religious institutional structures – that challenged the intrinsic right of individual conscience in matters of faith – to be much less deserving of respect and protection.
Basic Principles of Nanotechnology

The book allows the reader to have a basic understanding of the structure and properties of nanoscale materials routinely used in nanotechnology-based research and industries. To add, the book describes the operation of nanoscale transistors and the processes used to fabricate the devices. Additionally, it presents research involving the use of carbon nanotubes, graphene, and molecules to create non-silicon based electronic devices. It aims to provide an understanding of the operation of the most frequently used fabrication and characterization procedures, such as scanning electron microscopy, atomic force microscopy, etch, e-beam lithography, and photolithography. Provides explanations of the common techniques used in nanofabrication. Focuses on nanomaterials that are almost exclusively used in academic research and incorporated in consumer materials, such as carbon nanotubes, graphene, metal nanoparticles, quantum dots, and conductive polymers. Each chapter begins with a list of key objectives describing major content covered. Includes end-of-chapter questions to reinforce chapter content.