cssi/SciSciGPT-SciSciNet huggingface dataset:
Metformin Inhibits Migration and Invasion by Suppressing ROS Production and COX2 Expression in MDA-MB-231 Breast Cancer Cells

Background: Several mechanisms of action have been proposed to explain the apparent antineoplastic functions of metformin, many of which are observed at high concentrations that may not be reflective of achievable tissue concentrations. We propose that metformin at low concentrations functions to inhibit ROS production and inflammatory signaling in breast cancer, thereby reducing metastasis. Methods: Using the highly invasive MDA-MB-231 breast carcinoma model, we ascertained the impact of metformin on cell viability by DNA content analysis and fluorescent dye exclusion. Migration and invasion assays were performed using a modified Boyden chamber assay and metastasis was ascertained using the chorioallantoic membrane (CAM) assay. PGE2 production was measured by Enzyme-Linked Immunosorbent Assay (ELISA). COX2 and ICAM1 levels were determined by flow cytometry immunoassay. Results: Metformin acutely decreased cell viability and caused G2 cell cycle arrest only at high concentrations (10 mM). At 100 µM, however, metformin reduced ICAM1 and COX2 expression, as well as reduced PGE2 production and endogenous mitochondrial ROS production while failing to significantly impact cell viability. Consequently, metformin inhibited migration, invasion in vitro and PGE2-dependent metastasis in CAM assays. Conclusion: At pharmacologically achievable concentrations, metformin does not drastically impact cell viability, but inhibits inflammatory signaling and metastatic progression in breast cancer cells.
Neuroprotective Peptide NAPVSIPQ Antagonizes Ethanol Inhibition of L1 Adhesion by Promoting the Dissociation of L1 and Ankyrin-G.

Abstract Background Ethanol causes developmental neurotoxicity partly by blocking adhesion mediated by the L1 neural cell adhesion molecule. This action of ethanol is antagonized by femtomolar concentrations of the neuropeptide NAPVSIPQ (NAP), an active fragment of the activity-dependent neuroprotective protein (ADNP). How femtomolar concentrations of NAP antagonize millimolar concentrations of ethanol is unknown. L1 sensitivity to ethanol requires L1 association with ankyrin-G; therefore, we asked whether NAP promotes the dissociation of ankyrin-G and L1. Methods L1–ankyrin-G association was studied using immunoprecipitation, Western blotting, and immunofluorescence in NIH/3T3 cells transfected with wild-type and mutated human L1 genes. Phosphorylation of the ankyrin binding motif in the L1 cytoplasmic domain was studied after NAP treatment of intact cells, rat brain homogenates, and purified protein fragments. Results Femtomolar concentrations of NAP stimulated the phosphorylation of tyrosine-1229 (L1-Y1229) at the ankyrin binding motif of the L1 cytoplasmic domain, leading to the dissociation of L1 from ankyrin-G and the spectrin-actin cytoskeleton. NAP increased the association of L1 and EphB2 and directly activated EphB2 phosphorylation of L1-Y1229. These actions of NAP were reproduced by P7A-NAP, a NAP variant that also blocks the teratogenic actions of ethanol, but not by I6A-NAP, which does not block ethanol teratogenesis as potently. Finally, knockdown of EPHB2 prevented ethanol inhibition of L1 adhesion in NIH/3T3 cells. Conclusions NAP potently antagonizes ethanol inhibition of L1 adhesion by stimulating EphB2 phosphorylation of L1-Y1229. EphB2 plays a critical role in synaptic development; its potent activation by NAP suggests that ADNP may mediate synaptic development partly by activating EphB2.
Cervical VEMP tuning changes by Meniere's disease stages

Objective To determine if changes in cervical vestibular-evoked myogenic potential (cVEMP) testing reflect the different stages of cochlea-saccular hydrops in Meniere's disease (MD). Methods This is a case-control retrospective series. Forty-seven patients with unilateral MD by American Academy of Otolaryngology-Head and Neck Surgery diagnostic and staging criteria, and 30 with non-MD vertigo as control. Meniere patients were further classified based on symptoms at the time of testing as active or stable. Subsequently, patients underwent cVEMP testing by tone-burst stimuli at 500 and 1,000 Hz. The main outcome measure was to compare the cVEMP 1,000 and 500 Hz amplitude ratio in ears with MD and non-MD vertigo, and in active versus stable MD. Results The cVEMP 1,000/500 Hz amplitude ratio was higher in Meniere's ears (mean = 1.14 μV, SD = 0.25) than in non-Meniere's ears (mean = 0.96 μV, SD = 0.2) (Student's t test, P = .001), and higher in active (mean = 1.22 μV, SD = 0.25) than in stable MD (mean = 1.00 μV, SD = 0.18) (P = .0035). The diagnostic value of cVEMP 1,000/500 Hz amplitude ratio to differentiate MD versus non-MD vertigo was evaluated with a receiver-operating characteristics (ROC) curve and the area under the curve (AUC) was 0.716 (95% confidence interval [CI] [0.591, 0.829]). The ideal cutoff point was 0.9435 with sensitivity and specificity values of 83% and 53%, respectively. The sensitivity and specificity values for this test to differentiate active versus stable MD were 68% and 81%, respectively, with AUC 0.746 (95% CI [0.607, 0.885]) and cutoff value of 1.048. In all ears, the 1,000/500 Hz amplitude ratio increased by a decrease of the 500 Hz amplitude with increasing age. Conclusion The cVEMP 1,000/500 Hz amplitude ratio is elevated in ears with MD but not in those with non-MD vertigo. After corrected by age, this ratio is higher in active but not in stable MD, probably reflecting dynamic changes in saccular membrane motion mechanics in hydrops, and may be a useful marker of disease progression and the effect of therapy. Level of evidence IV.
Patient Safety: Patient Involvement Matters

As the co-chair of Patients for Patient Safety Canada (PFPSC), I have had the opportunity to be a guest editor for this Special Issue of Healthcare Quarterly and, consequently, have reviewed and critiqued each article. I also was a patient partner in the National Patient Safety Consortium, the work of which is the basis for the articles in this issue. Patient safety is a serious issue in Canada. In fact, unintended harm while receiving healthcare is the third leading cause of death in Canada (RiskAnalytica 2017). The papers in this issue describe initiatives that have the potential to and/or have contributed to reducing patient harm if implemented across our system and in such a way that patients and families are an integral part of the process.
Comparison of fluoroscopic cardiovascular measurements from healthy dogs obtained at end-diastole and end-systole.

Abstract Introduction Quantitative measurements are commonly implemented to objectively evaluate heart size in dogs. However, recent studies suggest that the phase of cardiac cycle can impact vertebral heart score, thereby potentially influencing clinical management. This study used fluoroscopy to assess the impact of the cardiac cycle on quantitative cardiovascular measurements in healthy dogs of various breeds. Animals, materials, and methods This was a prospective study. Multiple cardiac and respiratory cycles were recorded fluoroscopically. Peak inspiratory end-systole and end-diastole frames were captured from 49 dogs in right lateral recumbency. Vertebral heart score (VHS), cardiothoracic ratio (CTR), vertebral left atrial size (VLAS), and caudal vena cava diameter ratio (CVCDR) measurements were performed. Mean cardiac measurements were compared between cardiac cycle phases, and the impact of body condition score (BCS), weight, thoracic conformation, sex, and age was evaluated. Results Cardiac cycle had a significant impact on VHS (mean difference: 0.36 ± 0.14 vertebral units between systole and diastole; p Conclusions The cardiac cycle has a significant effect on VHS and CTR but does not impact VLAS or CVCDR. These findings should be taken into consideration during clinical use of these measurements, especially if a patient is being monitored for cardiac changes over time via serial radiographs.
Effects of geographic and economic heterogeneity on the burden of rotavirus diarrhea and the impact and cost-effectiveness of vaccination in Nigeria

Child mortality from rotavirus gastroenteritis remains high in Nigeria, representing 14% of all rotavirus deaths worldwide. Here, we examine the potential impact and cost-effectiveness of national rotavirus vaccine introduction in geographic and economic subpopulations of Nigeria. We projected the health and economic outcomes of rotavirus vaccination in children over the first five years of life using a spreadsheet-based model. We modeled child populations using national survey data on rotavirus mortality risk factors and vaccination coverage to predict burden and impact across regional and wealth quintile subpopulations within Nigeria. Our base case considered introduction of a general rotavirus vaccine, modeled to encompass characteristics of existing vaccines, versus no vaccine. Base case costs were estimated from the government perspective, assuming Gavi subsidies, over the first five years. We also present estimates from the cost of vaccination from the perspective of Gavi. We explored uncertainty in model parameters through probabilistic uncertainty, one-way sensitivity, and scenario analyses. According to our estimates, rotavirus enteritis was responsible for 47,898 [95% Uncertainty Limits: 35,361; 63,703] child deaths per year, with approximately 80% of the national burden concentrated in the three northern regions of Nigeria. Rotavirus vaccination was estimated to prevent 6,454 [3,960; 9,721] deaths, 13% [9%; 18%] of the national annual RV burden. National ICERs for rotavirus vaccination from the Nigerian government and Gavi perspectives were US$47 [$18; $105] and $62 [$29; $130] per DALY averted, respectively. General rotavirus vaccination was projected to reduce rotavirus mortality by only 6% [4%; 9%] in the North West region compared to 35% [24%; 47%] in the South East region. Base case ICERs ranged from US$25 [10; 56] per DALY averted in North West to US$64 [18; 157] per DALY averted in South South. Gavi perspective ICERs ranged from US$33 [$15; $68] in North West to US$88 [35; 191] per DALY averted in South South. According to one-way sensitivity analyses, ICERs were most sensitive to vaccine efficacy, followed by estimated administrative costs and rotavirus mortality. Disparities in mortality reduction were largely driven by inequality in vaccination coverage across regions and between socioeconomic subpopulations. Due to high, persistent, and inequitable burden of rotavirus in Nigeria, routine vaccination with any of these rotavirus vaccines would be an high impact and cost-effective strategy in reducing child mortality.
An Analysis of Requirements-Related Problems that Occurred in an organization Using a Mature Requirements Engineering Process

Plenty has been written on the necessary elements of a requirements engineering (RE) process. When an organization experiences product development problems and is found to lack an effective RE process, it is relatively easy to find potential causes for the problems. For example, changes may not have been managed, or requirements and other artifacts may not have been traced to each other.Nevertheless, what can be said of RE process failures that occur despite an organization’s using a reasonably mature RE process? This paper will examine a set of RE-related problems that occurred in one such organization. It will also describe a solution that has been proposed to avoid such problems in the future.
Ultrasonic Imaging for Evaluating Peri-Implant Diseases

Peri-implant diseases and conditions are prevalent, accounting for approximately 40% of implants. According to the most updated disease classification by the joint effort between the American Academy of Periodontology (AAP) and the European Federation of Periodontology (EFP) in 2017, four categories have been proposed, namely implant health, peri-implant mucositis, peri-implantitis, and soft- and hard-tissue deficiencies. Clinical parameters to differentiate these four diseases and conditions are bleeding upon probing (BOP), radiographic bone loss, probing depth, hard- and soft-tissue dimension, and presence of pus/suppuration. Current methods to measure these clinical parameters have their own limitations and disadvantages, which will be highlighted in this chapter. High-frequency ultrasonography has advantages of being non-ionizing, point-of-care, and cross-sectional; therefore, it can be a first-line tool to evaluate peri-implant tissue health during implant maintenance phase. Recent research efforts by our group suggests ultrasound B-mode is accurate in delineating soft tissue thickness around implants, marginal bone level, and thickness. Additionally, it can also be used to measure peri-implant papilla height, mid-facial soft tissue height, bony fenestration, etc. Besides B-mode imaging, functional ultrasound modes, e.g. color flow and power flow, can estimate blood velocity and volume, currently in 2-dimension. These quantitative ultrasound markers may be related to the degree of inflammation around implants and are under active investigation. Once validated, these functional modes can become objective markers to estimate peri-implant inflammation. This chapter will demonstrate the potential of ultrasound to diagnose peri-implant diseases and conditions by presenting ultrasound images of clinical cases.
Reactivity and increased proliferation of NG2 cells following central nervous system infection with Theiler's murine encephalomyelitis virus.

Neuron-glial antigen 2 (NG2) cells are a glial cell type tiled throughout the gray and white matter of the central nervous system (CNS). NG2 cells are known for their ability to differentiate into oligodendrocytes and are commonly referred to as oligodendrocyte precursor cells. However, recent investigations have begun to identify additional functions of NG2 cells in CNS health and pathology. NG2 cells form physical and functional connections with neurons and other glial cell types throughout the CNS, allowing them to monitor and respond to the neural environment. Growing evidence indicates that NG2 cells become reactive under pathological conditions, though their specific roles are only beginning to be elucidated. While reactive microglia and astrocytes are well-established contributors to neuroinflammation and the development of epilepsy following CNS infection, the dynamics of NG2 cells remain unclear. Therefore, we investigated NG2 cell reactivity in a viral-induced mouse model of temporal lobe epilepsy. C57BL6/J mice were injected intracortically with Theiler’s murine encephalomyelitis virus (TMEV) or PBS. Mice were graded twice daily for seizures between 3 and 7 days post-injection (dpi). At 4 and 14 dpi, brains were fixed and stained for NG2, the microglia/macrophage marker IBA1, and the proliferation marker Ki-67. Confocal z stacks were acquired in both the hippocampus and the overlying cortex. Total field areas stained by each cell marker and total field area of colocalized pixels between NG2 and Ki67 were compared between groups. Both NG2 cells and microglia/macrophages displayed increased immunoreactivity and reactive morphologies in the hippocampus of TMEV-injected mice. While increased immunoreactivity for IBA1 was also present in the cortex, there was no significant change in NG2 immunoreactivity in the cortex following TMEV infection. Colocalization analysis for NG2 and Ki-67 revealed a significant increase in overlap between NG2 and Ki-67 in the hippocampus of TMEV-injected mice at both time points, but no significant differences in cortex. NG2 cells acquire a reactive phenotype and proliferate in response to TMEV infection. These results suggest that NG2 cells alter their function in response to viral encephalopathy, making them potential targets to prevent the development of epilepsy following viral infection.
xGAP: a python based efficient, modular, extensible and fault tolerant genomic analysis pipeline for variant discovery

Motivation Since the first human genome was sequenced in 2001, there has been a rapid growth in the number of bioinformatic methods to process and analyze next generation sequencing (NGS) data for research and clinical studies that aim to identify genetic variants influencing diseases and traits. To achieve this goal, one first needs to call genetic variants from NGS data which requires multiple computationally intensive analysis steps. Unfortunately, there is a lack of an open source pipeline that can perform all these steps on NGS data in a manner which is fully automated, efficient, rapid, scalable, modular, user-friendly and fault tolerant. To address this, we introduce xGAP, an extensible Genome Analysis Pipeline, which implements modified GATK best practice to analyze DNA-seq data with aforementioned functionalities. Results xGAP implements massive parallelization of the modified GATK best practice pipeline by splitting a genome into many smaller regions with efficient load-balancing to achieve high scalability. It can process 30x coverage whole-genome sequencing (WGS) data in approximately 90 minutes. In terms of accuracy of discovered variants, xGAP achieves average F1 scores of 99.37% for SNVs and 99.20% for Indels across seven benchmark WGS datasets. We achieve highly consistent results across multiple on-premises (SGE & SLURM) high performance clusters. Compared to the Churchill pipeline, with similar parallelization, xGAP is 20% faster when analyzing 50X coverage WGS in AWS. Finally, xGAP is user-friendly and fault tolerant where it can automatically re-initiate failed processes to minimize required user intervention. Availability xGAP is available at https://github.com/Adigorla/xgap. Supplementary information Supplementary data are available at Bioinformatics online.
Fisher Information and Uncertainty Principle for Skew-Gaussian Random Variables

Fisher information is a measure to quantify information and estimate system-defining parameters. The scaling and uncertainty properties of this measure, linked with Shannon entropy, are useful to c...
B1a and B2 cells are characterized by distinct CpG modification states at DNMT3A-maintained enhancers

The B1 and B2 lineages of B cells contribute to protection from pathogens in distinct ways. The role of the DNA CpG methylome in specifying these two B-cell fates is still unclear. Here we profile the CpG modifications and transcriptomes of peritoneal B1a and follicular B2 cells, as well as their respective proB cell precursors in the fetal liver and adult bone marrow from wild-type and CD19-Cre Dnmt3a floxed mice lacking DNMT3A in the B lineage. We show that an underlying foundational CpG methylome is stably established during B lineage commitment and is overlaid with a DNMT3A-maintained dynamic methylome that is sculpted in distinct ways in B1a and B2 cells. This dynamic DNMT3A-maintained methylome is composed of novel enhancers that are closely linked to lineage-specific genes. While DNMT3A maintains the methylation state of these enhancers in both B1a and B2 cells, the dynamic methylome undergoes a prominent programmed demethylation event during B1a but not B2 cell development. We propose that the methylation pattern of DNMT3A-maintained enhancers is determined by the coincident recruitment of DNMT3A and TET enzymes, which regulate the developmental expression of B1a and B2 lineage-specific genes.
Indirect effects of African megaherbivore conservation on bat diversity in the world's oldest desert

In extreme environments, temperature and precipitation are often the main forces responsible for structuring ecological communities and species distributions. The role of biotic interactions is typically thought to be minimal. By clustering around rare and isolated features, like surface water, however, effects of herbivory by desert-dwelling wildlife can be amplified. Understanding how species interact in these environments is critical to safeguarding vulnerable or data-deficient species. We examined whether African elephants (Loxodonta africana), black rhinoceros (Diceros bicornis), and southern giraffe (Giraffa giraffa) modulate insectivorous bat communities around permanent waterholes in the Namib Desert. We estimated megaherbivore use of sites based on dung transects, summarized vegetation productivity from satellite measurements of the normalized difference vegetation index, and surveyed local bat communities acoustically. We used structural equation models to identify relationships among megaherbivores and bat species richness and dry- (November 2016-January 2017) and wet- (February-May 2017) season bat activity. Site-level megaherbivore use in the dry season was positively associated with bat activity-particularly that of open-air foragers-and species richness through indirect pathways. When resources were more abundant (wet season), however, these relationships were weakened. Our results indicate that biotic interactions contribute to species distributions in desert areas and suggest the conservation of megaherbivores in this ecosystem may indirectly benefit insectivorous bat abundance and diversity. Given that how misunderstood and understudied most bats are relative to other mammals, such findings suggest that managers pursue short-term solutions (e.g., community game guard programs, water-point protection near human settlements, and ecotourism) to indirectly promote bat conservation and that research includes megaherbivores' effects on biodiversity at other trophic levels.
Structural racism and COVID-19 response: Higher risk of exposure drives disparate COVID-19 deaths among Black and Hispanic/Latinx residents of Illinois, USA

Abstract BACKGROUND Structural racism has driven and continues to drive policies that create the social, economic, and community factors resulting in residential segregation, lack of access to adequate healthcare, and lack of employment opportunities that would allow economic mobility. This results in overall poorer population health for minoritized people. In 2020, Black and Hispanic/Latinx communities throughout the United States, including the state of Illinois, experienced disproportionately high rates of COVID-19 cases and deaths. Public health officials in Illinois implemented targeted programs at state and local levels to increase intervention access and reduce disparities. METHODS To quantify how disparities in COVID outcomes evolved through the epidemic, data on SARS-CoV-2 diagnostic tests, COVID-19 cases, and COVID-19 deaths were obtained from the Illinois National Electronic Disease Surveillance System for the period from March 1 to December 31, 2020. Relative risks of COVID-19 cases and deaths were calculated for Black and Hispanic/Latinx vs. White residents, stratified by age group and epidemic interval. Deaths attributable to racial/ethnic disparities in incidence and case fatality were estimated with counterfactual simulations. RESULTS Disparities in case and death rates became less drastic after May 2020, but did not disappear, and were more pronounced at younger ages. From March to May of 2020, the risk of a COVID-19 case for Black and Hispanic/Latinx populations was more than twice that of Whites across all age groups. The relative risk of COVID-19 death reached above 10 for Black and Hispanic/Latinx individuals under 50 years of age compared to age-matched Whites in the early epidemic. In all Illinois counties, relative risk of a COVID-19 case was the same or significantly increased for minoritized populations compared to the White population. 79.3% and 86.7% of disparities in deaths among Black and Hispanic/Latinx populations, respectively, were attributable to differences in age-adjusted incidence compared to White populations rather than differences in case fatality ratios. CONCLUSIONS Racial and ethnic disparities in the COVID-19 pandemic are products of society, not biology. Considering age and geography in addition to race/ethnicity can help to identify the structural factors driving poorer outcomes for certain groups. Studies and policies aimed at reducing inequalities in disease exposure will reduce disparities in mortality more than those focused on drivers of case fatality.
Infrared analysis of the structure of amino acids, polypeptides and proteins.

Publisher Summary This chapter reviews the knowledge obtained on the structure of amino acids, peptides, and proteins from their vibration spectra. Of the two methods employed to investigate vibration spectra, infrared absorption and light scattering, the former proved to be more powerful. The reason for the superiority of the infrared method is the technical difficulties in obtaining Raman spectra of small samples that are rather formidable, whereas the infrared spectrum of almost any material can be observed. Raman spectra are frequently much easier to observe than infrared spectra and the Raman method gives many of the low frequency vibrations, which necessitate especially difficult and tedious techniques in infrared absorption. Ideally, one should obtain both the infrared and the Raman spectrum of each compound, as these two spectra are never wholly identical and are frequently largely complementary for highly symmetrical molecules and for symmetrical groups within larger unsymmetrical molecules.
Innovation and Monopoly Leveraging

This paper, written when Fisher was preparing for his testimony in Microsoft, discusses the circumstances in which monopoly "leveraging" makes sense as an anti-competitive act. Three cases are discussed and contrasted: The IBM case of the 1970's; the Computer Reservation System Cases of the 1980's; and the Microsoft case. Fisher was a principal economic witness in all of them, for the defense in IBM and for plaintiffs in the other two cases.
Occurrence and ecological significance of GTP in the ocean and in microbial cells.

Abstract A comparison between the ATP concentrations based on peak height light emission values (0 to 3 s) and integrated light flux determinations (15 to 75 s) for a variety of seawater samples revealed that the integrated method of light detection consistently yielded higher ATP concentrations, ranging from 1.38 to 2.35 times larger than the corresponding peak ATP values. A significant correlation (r = 0.923) was observed for a plot of ΔADP (i.e., integrated ATP - peak ATP) versus GTP + UTP, suggesting that the analytical interference on the ATP assay was the result of the presence of non-adenine nucleotide triphosphates. Size-fractionation studies revealed an enrichment of the non-adenine nucleotide triphosphates, relative to ATP, in the smallest size fraction analyzed (<10 μm). Investigations were conducted with 20 species of unicellular marine algae to determine their intracellular nucleotide concentrations, and these determinations were compared to the levels measured in lab cultures of the marine bacterium Serratia marinorubra. These results indicated that the intracellular GTP/ATP ratios in S. marinorubra increase in direct proportion to the rate of cell growth, and that the GTP/ATP ratios in bacteria are much greater than in growing algae, presumably due to the differences in rates of cellular biosynthesis. It is concluded that quantitative determinations of GTP/ATP ratios in environmental sample extracts may be useful for measuring microbial growth.
Neutron Scattering in the Analysis of Polymers

The focus of this article is the application of neutron scattering in polymer science, with various examples given to illustrate the types of problems addressed. Neutron scattering is a powerful analytical tool for investigating polymers. Unique aspects such as the capacity to measure thick samples with an absence heating or radiation-induced damage, selective control of the scattering contrast by isotopic substitution, and the measurement of dynamic properties as a function of length scale are among the many attributes that make neutron methods not just complementary to other analytical techniques, but in many cases the only means to address material issues. The information that can be obtained from neutron scattering — the size, form, and orientation of molecular chains, the thermodynamics and phase structure of mixtures, interfaces and interfacial phenomena, the dynamics at both the local and global length scales, details of the structure of complex nanocomposites and biological materials, etc. — has only been surveyed herein. It is a testament to the utility of neutron scattering that even though the application of neutrons to polymers did not begin in earnest until the 1990s, through the past decade, about 325 peer-reviewed publications per year have appeared on the topic. Whether this figure changes in the future will likely depend on the availability of the specialized, costly facilities required for neutron experiments. Certainly there is no expectation of abatement in the number of important problems in polymer science that can be addressed using neutron methods.
Fibrinogen as a therapeutic target for bleeding: a review of critical levels and replacement therapy.

Fibrinogen plays a critical role in achieving and maintaining hemostasis and is fundamental to effective clot formation. There is increasing awareness of the important role of fibrinogen as a key target for the treatment and prevention of acquired bleeding. Fibrinogen is the first coagulation factor to fall to critically low levels (<1.0 g/L) during major hemorrhage (normal plasma fibrinogen levels range from 2.0 to 4.5 g/L), and current guidelines recommend maintaining the plasma fibrinogen level above 1.5 g/L. Fibrinogen supplementation can be achieved using plasma or cryoprecipitate; however, there are a number of safety concerns associated with these allogeneic blood products and there is a lack of high-quality evidence to support their use. Additionally, there is sometimes a long delay associated with the preparation of frozen products for infusion. Fibrinogen concentrate provides a promising alternative to allogeneic blood products and has a number of advantages: it allows a standardized dose of fibrinogen to be rapidly administered in a small volume, has a very good safety profile, and is virally inactivated as standard. Administration of fibrinogen concentrate, often guided by point-of-care viscoelastic testing to allow individualized dosing, has been successfully used as hemostatic therapy in a range of clinical settings, including cardiovascular surgery, postpartum hemorrhage, and trauma. Results show that fibrinogen concentrate is associated with a reduction or even total avoidance of allogeneic blood product transfusion. Fibrinogen concentrate represents an important option for the treatment of coagulopathic bleeding; further studies are needed to determine precise dosing strategies and thresholds for fibrinogen supplementation.
Silicon quantum-dot transistors operating above 100 K

Reports the fabrication and characterization of unique silicon quantum-dot transistors (QDTs) that demonstrate quantum as well as single-electron Coulomb blockade effects at temperatures above 100 K. They are also the first Si transistors that show interference between different modes of quantum waves in a cavity. The transistors were fabricated on SIMOX (separation by implanted oxygen) silicon wafer with the top silicon layer 70 nm thick.
Occurrence of glucuronokinase in various plant tissues and comparison of enzyme activity of seedlings and green plants

Abstract Glucuronokinase (EC 2.7.1.43) activity was detected in etiolated seedlings of corn, mung bean and soybean. Biosynthesis of glucuronokinase is not limited to seedlings, because expanding green leaves of corn produced almost as much glucuronokinase activity as etiolated seedlings when data were expressed on the basis of soluble protein. The enzyme was also present in extracts of tobacco callus and Lilium longiflorum pollen, with more enzyme activity obtained from pollen than any other source. Detection of glucuronokinase in green leaves of of mung bean was precluded by the presence of an enzyme inhibitor.
Modern Hebrew in American Colleges and Universities

IN AN article entitled, "The Teaching of Hebrew in American Universities,"' the writer discussed the development of the study of Hebrew from the early colonial days to 1946. The present article deals with more data brought out in a recent study2 on the subject. The book reveals that out of 1,025 colleges and universities, 206 or 20% teach Hebrew. A total of 7,206 students are enrolled in 415 courses taught in the 206 schools. 169 of these schools including 44 colleges, 39 universities, 86 theological schools, offer courses in Hebrew as an ancient tongue, in which they stress the minute details of grammar and the technical language aspect, as if Hebrew had not progressed beyond the Biblical stage, and had no present or future. Fully 75% of the 415 courses are based on the classical approach. Some 3,802 students are enrolled in theseclasses. There is a visible decline in interest in this type of study, which is reflected in the fact that at least 12 schools have indicated that they are suffering from a gradual decline in student enrollment. The attempts made by Weingreen, Yates, Seller and others to modernize texts and instruction and improve on Davidson and the other Hebrew textbooks commonly used in these Semitic departments, have proved to be of little avail.
The role of the inter-heavy chain disulfide bond in modulating the flexibility of immunoglobulin G antibody.

Comparison of the time dependent fluoresecence anisotropies of intact and reduced rabbit anti-dansyl antibodies showed that reduction of the inter-heavy chain disulfide bond significantly increased the internal flexibility of the antibody molecules.
Hydrocortisone-dependent alterations of transcriptional activity in WI38 cells

Abstract The effect of hydrocortisone on the transcriptional activity of exponentially and parasynchronously growing WI38 cells was measured using E. coli RNA polymerase or endogenous chromatinbound RNA polymerase to catalyse RNA synthesis in vitro. Results indicated that the transcriptional activity of cells was increased 8 h after hydrocortisone addition to exponentially growing cultures and 3–5 h after hormone addition to parasynchronously growing cultures. The hydrocortisone-induced alteration of transcriptional activity was not an artifact induced by different rates of RNA or DNA, degradation. These findings indicate that the hormone-dependent alteration of transcriptional activity is an early event in the hydrocortisone-mediated stimulation of WI38 cell proliferation.
Citizens of sound: negotiations of race and diaspora in the anthems of the UNIA and NAACP

Abstract The development of large-scale black protest organizations in the early decades of the twentieth century precipitated an unparalleled amount of communication and exchange between African descended populations. This paper argues the centrality of black organization anthems to the enterprise of black diaspora formation and solidarity. Through the composition and ritualization of their anthems, black organizations defined and announced an agenda for their membership, who similarly constructed their identities through the performance of the song. Anthems were central to the efforts to solidify and mobilize these organizations yet they also contained important contests that highlighted the differences in access and experience amongst the membership. The anthems of the Universal Negro Improvement Association (UNIA) and National Association for the Advancement of Colored People (NAACP) are central to an examination of these complicated processes. The organizations’ sonic histories are highlighted here i...
Method for enlarging the dynamic aperture of accelerator lattices

A method for finding four-dimensional symplectic maps with an enlarged nearly integrable region is described. The method relies on solving for parameter values at which the linear stability factors of the fixed points (periodic orbits) of the map have the values corresponding to integer island tunes. This method is applied to accelerator lattices in order to increase dynamic aperture. The result shows a significant increase of the dynamic aperture after correction.
A new synthon for the regiospecific γ-alkylation of 2-cyclohexenones. Application to the synthesis of zingiberenol and oxygenated bicycle[3.3.1] nonanes

Abstract The regiospecific γ-alkylation of γ-sulfonycyclohexone ketals is described and applied to variuos synthetic objectives.
Routine Habitat Change: A Source of Unrecognized Transient Alteration of Intestinal Microbiota in Laboratory Mice

The mammalian intestine harbors a vast, complex and dynamic microbial population, which has profound effects on host nutrition, intestinal function and immune response, as well as influence on physiology outside of the alimentary tract. Imbalance in the composition of the dense colonizing bacterial population can increase susceptibility to various acute and chronic diseases. Valuable insights on the association of the microbiota with disease critically depend on investigation of mouse models. Like in humans, the microbial community in the mouse intestine is relatively stable and resilient, yet can be influenced by environmental factors. An often-overlooked variable in research is basic animal husbandry, which can potentially alter mouse physiology and experimental outcomes. This study examined the effects of common husbandry practices, including food and bedding alterations, as well as facility and cage changes, on the gut microbiota over a short time course of five days using three culture-independent techniques, quantitative PCR, terminal restriction fragment length polymorphism (TRFLP) and next generation sequencing (NGS). This study detected a substantial transient alteration in microbiota after the common practice of a short cross-campus facility transfer, but found no comparable alterations in microbiota within 5 days of switches in common laboratory food or bedding, or following an isolated cage change in mice acclimated to their housing facility. Our results highlight the importance of an acclimation period following even simple transfer of mice between campus facilities, and highlights that occult changes in microbiota should be considered when imposing husbandry variables on laboratory animals.
778 CEREBROSPINAL FLUID AND SERUM ANTIBODY IN RABBITS WITH HERPES SIMPLEX ENCEPHALITIS

The development of effective chemotherapy for Herpes Simplex Virus Encephalitis (HSE)with adenine arabinoside has stimulated interest in pathogenesis and the need for rapid diagnosis. To evaluate pathogenesis we have characterized herpes simplex virus (HSV)antibody in CSF and serum during the course of the illness in rabbits. The rabbit model of HSE is produced by corneal inoculation with HSV-1. Seven days post inoculation they have encephalitis with inflammatory cells in CSF and HSV in brain tissue. CSF and sera were collected prior to and days 5,7,9,and 12 post inoculation. Antibody was measured with radioimmune precipitation assay. The HSV-1 and control antigens were prepared in media containing C14 amino acids. The antigen-antibody precipitate was solubilized and C14 labeled HSV antigens were characterized with SDS acrylamide gel electrophoresis and autoradiography. HSV-1 antibody appeared in CSF 5 days after inoculation and serum antibody appeared on day 7. The HSV antigens precipitated from CSF and serum collected on day 12 were the same for the predominant high molecular weight group but showed differences in lesser molecular weight ranges. In this model of primary HSV-1 encephalitis antibody is detected in CSF before serum and qualitative differences are noted. These measurements better define the pathogenesis of HSE, and clinical studies are now underway characterizing antibody in human CSF and serum.
Electrochemical oxidation of H2O2 on Pt and Pt + Ir electrodes in physiological buffer and its applicability to H2O2-based biosensors

Abstract The electrochemical oxidation of hydrogen peroxide on Pt disk and Pt + Ir wire electrodes was studied in physiological buffer at pH 7.40 in order to establish a practical protocol for H 2 O 2 -based biosensors. The electrode reaction is a two-electron irreversible process. The oxidation of H 2 O 2 on Pt and Pt+Ir electrode surfaces is a catalytic reaction which is H 2 O 2 concentration dependent but O 2 pressure independent at low H 2 O 2 concentration. Amperometric detection of H 2 O 2 is strongly affected by pH, temperature and electrode surface conditioning. An oxidized surface is required to obtain a stable H 2 O 2 response, and reductive pretreatment of the electrode always yields prolonged stabilization times. The application of a cellulose acetate membrane to the surface can protect the oxidized surface and therefore substantially reduce the stabilization time for H 2 O 2 measurements.
Enzymatic treatment of peanut kernels to reduce allergen levels

Abstract This study investigated the use of enzymatic treatment to reduce peanut allergens in peanut kernels as affected by processing conditions. Two major peanut allergens, Ara h 1 and Ara h 2, were used as indicators of process effectiveness. Enzymatic treatment effectively reduced Ara h 1 and Ara h 2 in roasted peanut kernels by up to 100% under optimal conditions. For instance, treatment of roasted peanut kernels with α-chymotrypsin and trypsin for 1–3 h significantly increased the solubility of peanut protein while reducing Ara h 1 and Ara h 2 in peanut kernel extracts by 100% and 98%, respectively, based on ELISA readings. Ara h 1 and Ara h 2 levels in peanut protein extracts were inversely correlated with protein solubility in roasted peanut. Blanching of kernels enhanced the effectiveness of enzyme treatment in roasted peanuts but not in raw peanuts. The optimal concentration of enzyme was determined by response surface to be in the range of 0.1–0.2%. No consistent results were obtained for raw peanut kernels since Ara h 1 and Ara h 2 increased in peanut protein extracts under some treatment conditions and decreased in others.
COMPARISON OF THE ISOELECTRIC AND MOLECULAR WEIGHT PROPERTIES OF TUBULIN SUBUNITS

Abstract— Brain tubulin subunits were separated by a combination of isoelectric focusing and electrophoresis in the presence of sodium dodecyl sulfate (SDS) using a two-dimensional polyacrylamide slab gel technique. Isoelectric focusing separated tubulin subunits into two major groups of bands, such that the more acidic group corresponded to the α subunit and the less acidic group corresponded to the β subunit. In addition, isoelectric focusing resolved the β subunit into two subspecies which differed slightly in isoelectric properties but were the same apparent molecular weight. The a subunit was resolved into many subspecies that appear to differ from each other by both apparent molecular weight and isoelectric properties.
Growth and Characterization of Hard Nitrides Films Prepared by Pulsed Laser Deposition

Transition metal of nitrides have many desirable properties for application at elevated temperatures because of extremely high melting point, hardness, high temperature strength, good thermal shock resistance, and high thermal conductivity. We have investigated the thin film coatings of nitrides (titanium nitride, and composite carbon nitride) on various commercial useful substrates by the pulsed laser deposition (PLD) method. The PLD method is unique process for depositing high quality thin films with novel microstructure and properties. The laser parameters: energy density, pulse rate, target/substrate distance and substrate temperature have been optimized to improve the quality of thin films. The mechanical properties of the films have been evaluated at different processed conditions by nanoindentation technique. The films were characterized by X-ray diffraction, scanning electron microscope and FTIR techniques. Optimization of laser deposition parameters to obtain high quality thin films will be discussed in detail.
PROPERTIES OF FLAGELLAR "RIGOR WAVES" FORMED BY ABRUPT REMOVAL OF ADENOSINE TRIPHOSPHATE FROM ACTIVELY SWIMMING SEA URCHIN SPERM

Sea urchin sperm were demembranated and reactivated with a solution containing 0.04% Triton X-100 and 0.03 mM ATP. The ATP concentration was then lowered abruptly by diluting the sperm suspension 50-fold into reactivating solution containing no ATP. The flagella of the sperm in the diluted suspension were not motile, but they were bent into a variety of stationary rigor wave forms closely resembling the wave forms occurring at different stages of the flagellar bending cycle during normal movement. The form of these rigor waves was unchanged upon storage for several hours in the presence of dithiothreitol and EDTA. Addition of 1 µM ATP induced slow relaxation of the waves, with most of the sperm becoming partially straightened over a period of about 30 min; somewhat higher concentrations gave a more rapid and complete relaxation. Concentrations of ATP above 10 µM induced resumption of normal beating movements. Addition of ITP, GTP, or GDP (up to 1 mM) produced no relaxation of the rigor waves. Digestion with trypsin to an extent sufficient to disrupt the radial spokes and the nexin links caused no change in the rigor wave forms, suggesting that these wave forms could be maintained by the dynein cross-bridges between the outer doublet tubules of the flagellar axoneme. Study of the effects of viscous shear on the rigor wave axonemes has shown that they are resistant to distortion by bending, although they can be twisted relatively easily.
Empathy in Leadership: Appropriate or Misplaced? An Empirical Study on a Topic that is Asking for Attention

Leadership has become a more popular term than management, even though it is understood that both phenomena represent important organizational behaviors. This paper focuses on empathy in leadership, and presents the findings of a study conducted among business students over the course of 3 years. Finding that empathy consistently ranked lowest in the ratings, the researchers set out to discover the driving motives behind this invariable trend, and conducted a second study to obtain opinions about possible underlying factors. The paper presents the findings of both studies, as well as literature reviews on the differences between management and leadership, a historical overview of leadership, a reflection of 21st century leadership, the ongoing debate on the effects of corporate psychopaths on ethical performance, and scholars’ perception on empathy in corporate leadership. The findings indicate the need for a paradigm shift in corporations as well as business schools in regards to leaders’ required skills, and suggest a proactive approach from business faculty to change the current paradigm.
On piecewise-linear classification

The authors make use of a real data set containing 9-D measurements of fine needle aspirates of a patient's breast for the purpose of classifying a tumor's malignancy for which early stopping in the generation of the separating hyperplanes is not appropriate. They compare a piecewise-linear classification method with classification based on a single linear separator. A precise methodology for comparing the relative efficacy of two classification methods for a particular task is described and is applied to the comparison on the breast cancer data of the relative performances of the two versions of the piecewise-linear classifier and the classification based on an optimal linear separator. It is found that for this data set, the piecewise-linear classifier that uses all the hyperplanes needed to separate the training set outperforms the other two methods and that these differences in performance are significant at the 0.001 level. There is no statistically significant difference between the performance of the other two methods. The authors discuss the relevance of these results for this and other applications. >
Computer-Controlled Cycle Ergometer

This communication describes a computer-controlled cycle ergometer that generates any dynamic work rate stimulus between 0 and 350 W. The ergometer system features true "zero" watt pedaling and a response time less than 0.5 s. The work rate stimulus is generated via computer software.