cssi/SciSciGPT-SciSciNet huggingface dataset:
Legionella Becoming a Mutualist: Adaptive Processes Shaping the Genome of Symbiont in the Louse Polyplax serrata.

Legionellaceae are intracellular bacteria known as important human pathogens. In the environment, they are mainly found in biofilms associated with amoebas. In contrast to the gammaproteobacterial family Enterobacteriaceae, which established a broad spectrum of symbioses with many insect taxa, the only instance of legionella-like symbiont has been reported from lice of the genus Polyplax. Here, we sequenced the complete genome of this symbiont and compared its main characteristics to other Legionella species and insect symbionts. Based on rigorous multigene phylogenetic analyses, we confirm this bacterium as a member of the genus Legionella and propose the name Candidatus Legionella polyplacis, sp.n. We show that the genome of Ca. Legionella polyplacis underwent massive degeneration, including considerable size reduction (529.746 bp, 484 protein coding genes) and a severe decrease in GC content (23%). We identify several possible constraints underlying the evolution of this bacterium. On one hand, Ca. Legionella polyplacis and the louse symbionts Riesia and Puchtella experienced convergent evolution, perhaps due to adaptation to similar hosts. On the other hand, some metabolic differences are likely to reflect different phylogenetic positions of the symbionts and hence availability of particular metabolic function in the ancestor. This is exemplified by different arrangements of thiamine metabolism in Ca. Legionella polyplacis and Riesia. Finally, horizontal gene transfer is shown to play a significant role in the adaptive and diversification process. Particularly, we show that Ca. L. polyplacis horizontally acquired a complete biotin operon (bioADCHFB) that likely assisted this bacterium when becoming an obligate mutualist.
Economic Populism and Bandwagon Bigotry: Obama-to-Trump Voters and the Cross Pressures of the 2016 Election:

Through an analysis of validated voters in the 2016 American National Election Study, this article considers the voters who supported Obama in 2012 and Trump in 2016. More than 5.7 million in total...
THE NATURE OF PHYSIOTHERAPY PRACTICE TO PREVENT FALL IN PARKINSON'S DISEASE

Background: One of the main problems in a patient with Parkinson’s disease (PD) is recurrent falls. This paper aims to explore the nature of interventions which target the role of physiotherapy preventing fall in patients with PD.Methods: A scoping review was led dependent on Arksey and O'Malley. This paper-based on this structure to perceive intervention studies have been embraced in physiotherapy to prevent fall after Parkinson disease. The search included various databases. The referencing arrangements of every pertinent paper were additionally filtered for more studies.Results: 173 articles were included, thirty-nine of which met the eligibility criteria. Fifteen studies reported on the direct impact of physiotherapy on fall, while the rest examined the impacts of physiotherapy on factors that are associated with falls. Different outcomes, intervention types, and duration were used in these studies. Findings showed favorable results of physiotherapy on fall and near fall incidence, balance, gait, functional mobility, muscle strength and fear of falling.Conclusion: Physiotherapy can decrease fall incidence and fall risk in people with PD. However, the heterogeneity in the patients’ selection, intervention studies, outcome measures are chosen, time since the onset of disease, variation in intensity and duration of treatment between included studies makes the comparisons difficult. Consequently, more studies are needed on best intervention.
Blood flow patterns during incremental and steady-state aerobic exercise.

BACKGROUND Endothelial shear stress (ESS) is a physiological stimulus for vascular homeostasis, highly dependent on blood flow patterns. Exercise-induced ESS might be beneficial on vascular health. However, it is unclear what type of ESS aerobic exercise (AX) produces. The aims of this study are to characterize exercise-induced blood flow patterns during incremental and steady-state AX. We expect blood flow pattern during exercise will be intensity-dependent and bidirectional. METHODS Six college-aged students (2 males and 4 females) were recruited to perform 2 exercise tests on cycle-ergometer. First, an 8-12-min incremental test (test 1) where oxygen uptake (VO2), heart rate (HR), blood pressure (BP), and blood lactate (La) were measured at rest and after each 2-min step. Then, at least 48-hr. after the first test, a 3-step steady state exercise test (test 2) was performed measuring VO2, HR, BP, and La. The three steps were performed at the following exercise intensities according to La: 0-2 mmol/L, 2-4 mmol/L, and 4-6 mmol/L. During both tests, blood flow patterns were determined by high-definition ultrasound and Doppler on the brachial artery. These measurements allowed to determine blood flow velocities and directions during exercise. RESULTS On test 1 VO2, HR, BP, La, and antegrade blood flow velocity significantly increased in an intensity-dependent manner (repeated measures ANOVA, P<0.05). Retrograde blood flow velocity did not significantly change during test 1. On test 2 all the previous variables significantly increased in an intensity-dependent manner (repeated measures ANOVA, P<0.05). CONCLUSIONS These results support the hypothesis that exercise-induced ESS might be increased in an intensity-dependent way and blood flow patterns during incremental and steady-state exercises include both antegrade and retrograde blood flows.
VASER-Assisted Liposuction of Gynecomastia

Surgery for the correction of gynecomastia is relatively common. It is currently listed as the third most common surgical procedure in men, with over 20,000 cases reported by board certified plastic surgeons in the latest procedural statistics of the American Society of Plastic Surgeons. There is still significant controversy in the literature regarding the incidence of the condition. A prevalence of 32–65% has been reported in adult males and in adolescents the reported range is 4–69%. A number of treatment options have been suggested for cases in which skin resection is not required. The most common approach to these cases involves some technique of liposuction combined with some technique of gland resection. Lately the pull-through technique has become a popular method for addressing the glandular tissue. The adipose tissue is currently addressed by any of the following: traditional liposuction (SAL), power-assisted liposuction (PAL), ultrasound-assisted liposuction (UAL), or VASER-assisted liposuction (VAL).
Analysis of TRPA1 antagonist, A-967079, in plasma using high-performance liquid chromatography tandem mass-spectrometry

Abstract The noxious effects from exposure to toxic inhalation hazards (TIHs, such as isocyanates, chlorine, etc.) are known to be triggered by the activation of transient receptor potential ankyrin 1 (TRPA1) ion channel. Antagonists of TRPA1 have shown near complete attenuation of the noxious effects from TIH exposure. One of the TRPA1 antagonists, (1E,3E)-1-(4-fluorophenyl)-2-methyl-1-pentene-3-one oxime (A-967079), has shown impressive efficacy, high selectivity, high potency, and oral bioavailability. Although a validated method to quantify A-967079 in biological matrices is vital for the further development of A-967079 as a therapeutic agent, no method for its analysis from any matrix is currently available. Hence, a rapid and simple HPLC-MS/MS method was developed and validated to quantify A-967079 in rabbit plasma. The method presented here features an excellent LOD of 25 nM and a wide linear range (0.05–200 μM), with good accuracy and precision (100 ± 10.5% and
Production behavior and performance predictions

Abstract CBM reservoirs exhibit a very different gas production profile as compared to conventional gas reservoirs. Initially, they may produce only water followed by a period of decreasing water rates and increasing gas rates until the gas rate reaches the peak value. The period before the peak gas rate production is reached, is referred to as dewatering stage. The cost to treat and dispose the produced water can be a critical factor in the economics of a CBM project. After dewatering, the gas production rates experience a declining trend similar to conventional gas reservoirs. CBM production behavior is complex and difficult to predict or analyze especially during the dewatering stage. The complex nature of gas production from CBM reservoirs requires significantly more reservoir parameters than conventional reservoirs. The key parameters for evaluation of CBM prospects are the gas resources, reserves, and deliverability. The acquisition and analysis of the core and well test data are indispensable in evaluating any CBM project. Several approaches, both analytical and numerical, have been presented to predict the production performance for coalbed methane reservoirs.
Does Use of Neoadjuvant Chemotherapy Affect the Decision to Pursue Fertility Preservation Options in Young Women with Breast Cancer

The American Society of Clinical Oncology guidelines recommend early referral to reproductive endocrinology and infertility (REI) specialists for young women diagnosed with breast cancer. Current practice patterns demonstrate an increased utilization of neoadjuvant chemotherapy (NAC). We evaluated premenopausal women with breast cancer after consultation with a Fertility Nurse Specialist (FNS) and determine factors associated with referral to REI specialists. This retrospective review included all premenopausal women diagnosed at our institution with stage 0–III unilateral breast cancers between 2009 and 2015 who completed an FNS consultation. Clinicopathologic features and factors associated with referral to REI after FNS consultation were analyzed. A total of 334 women were identified. Median age was 35 years (interquartile range 32–38). The majority of women were single (n = 198, 59.3%) and nulliparous (n = 239, 71.6%). REI referrals were common (n = 237, 71.0%). The Breast Surgery service was the most frequent referring service (n = 194, 58.1%), with significantly more REI referrals compared to Breast Medicine and Genetics services (p = 0.002). Nulliparity was associated with REI referral (p < 0.0001). Adjuvant chemotherapy (p = 0.003) was associated with pursuing REI referral, whereas NAC (p < 0.001) was associated with declining REI referral. Most women elected to consult with an REI specialist, confirming strong interest in fertility preservation among premenopausal women with breast cancer. However, women receiving NAC more frequently declined referral to REI, suggesting that the need to start NAC may influence decisions regarding fertility preservation. With increasing utilization of NAC, our study supports the need for further counseling and education regarding fertility preservation for women undergoing NAC.
You Say You Want an Antitrust Revolution? The Paradox of Modern Merger Control:

Over the past twenty years, merger control has made what appear to be substantial advances in concepts and methodology, claiming the mantle of a “revolution.” This essay observes, however, that ove...
Where there's smoke, there's fuel: predicting Great Basin rangeland wildfire

Wildfires are a growing management concern in western US rangelands, where invasive annual grasses have altered fire regimes and contributed to an increased incidence of catastrophic large wildfires. Fire activity in arid, non-forested regions is thought to be largely controlled by interannual variation in fuel amount, which in turn is controlled by antecedent weather. Thus, long-range forecasting of fire activity in rangelands should be feasible given annual estimates of fuel quantity. Using a 32 yr time series of spatial data, we employ machine learning algorithms to predict the relative probability of large (>400 ha) wildfire in the Great Basin based on fine-scale annual and 16-day estimates of cover and production of vegetation functional groups, weather, and multitemporal scale drought indices. We evaluate the predictive utility of these models with a leave-one-year-out cross-validation, building spatial forecasts of fire probability for each year that we compare against actual maps of large wildfires. Herbaceous vegetation aboveground biomass production, bare ground cover, and long-term drought indices were the most important predictors of fire probability. Across 32 fire seasons, >80% of the area burned in large wildfires coincided with predicted fire probabilities [≥]0.5. At the scale of the Great Basin, several metrics of fire season severity were moderately to strongly correlated with average fire probability, including total area burned in large wildfires, number of large wildfires, and average and maximum fire size. Our findings show that recent years of exceptional fire activity in the Great Basin were predictable based on antecedent weather and biomass of fine fuels, and reveal a significant increasing trend in fire probability over the last three decades driven by widespread changes in fine fuel characteristics.
The discovery of indolone GW5074 during a comprehensive search for non-polyamine-based polyamine transport inhibitors

The native polyamines putrescine, spermidine, and spermine are essential for cell development and proliferation. Polyamine levels are often increased in cancer tissues and polyamine depletion is a validated anticancer strategy. Cancer cell growth can be inhibited by the polyamine biosynthesis inhibitor difluoromethylornithine (DFMO), which inhibits ornithine decarboxylase (ODC), the rate-limiting enzyme in the polyamine biosynthesis pathway. Unfortunately, cells treated with DFMO often replenish their polyamine pools by importing polyamines from their environment. Several polyamine-based molecules have been developed to work as polyamine transport inhibitors (PTIs) and have been successfully used in combination with DFMO in several cancer models. Here, we present the first comprehensive search for potential non-polyamine based PTIs that work in human pancreatic cancer cells in vitro. After identifying and testing five different categories of compounds, we have identified the c-RAF inhibitor, GW5074, as a novel non-polyamine based PTI. GW5074 inhibited the uptake of all three native polyamines and a fluorescent-polyamine probe into human pancreatic cancer cells. GW5074 significantly reduced pancreatic cancer cell growth in vitro when treated in combination with DFMO and a rescuing dose of spermidine. Moreover, GW5074 alone reduced tumor growth when tested in a murine pancreatic cancer mouse model in vivo. In summary, GW5074 is a novel non-polyamine-based PTI that potentiates the anticancer activity of DFMO in pancreatic cancers.
Membrane bound Peroxiredoxin-1 serves as a biomarker for in vivo detection of sessile serrated adenomas.

Aim Sessile serrated adenomas (SSAs) are pre-malignant lesions driven by the BRAFV600E mutation to give rise to colorectal cancers (CRCs). They are often missed during white light colonoscopy because of their subtle appearance. Previously, a fluorescently-labeled 7mer peptide KCCFPAQ was shown to detect SSAs in vivo. We aim to identify the target of this peptide. Results Peroxiredoxin-1 (Prdx1) was identified as the binding partner of the peptide ligand. In vitro binding assays and immunofluorescence staining of human colon specimens ex vivo supported this result. Prdx1 was overexpressed on the membrane of cells with the BRAFV600E mutation, and this effect was dependent on oxidative stress. RKO cells harboring the BRAFV600E mutation and human SSA specimens showed higher oxidative stress as well as elevated levels of Prdx1 on the cell membrane. Innovation and Conclusions: These results suggest that Prdx1 is overexpressed on the cell surface in the presence of oxidative stress, and can serve as an imaging biomarker for in vivo detection of SSAs.
Laser-acceleration of quasi mono-energetic and low-divergence Titanium ion beams

Ion acceleration by a high intensity (> 1018 W/cm2) laser pulse interacting with a solid target has been an active research area. The major interest stems from the prospects of designing and building a novel laser-driven ion source that is significantly more compact in size and shorter in duration than conventional ion accelerators, to enable applications requiring high power such as isochoric heating.
Building an agile data analytics environment to support university decision-making: A case study of Ohio State University's rapid development of a COVID-19 dashboard system

Abstract Data analytics is increasingly important to the operations and strategic growth of higher education institutions. In September 2019, three higher education professional associations issued a rare joint statement calling for the accelerated investment and intensified efforts to develop and deploy data analytics in support of campus decision making. COVID-19 disrupted the momentum generated by the joint statement. However, during the pandemic, many universities recognized data analytics as a critical asset to their response to the crisis. In this case study of Ohio State University's COVID-19 dashboard development process, the authors demonstrate that the principles advocated by the joint statement are exactly the reasons that a successful and nationally recognized dashboard effort was possible. The case study shows that senior leadership support, strategic investment in the right technologies, and close collaboration among campus data analytics professionals are among the key factors of success.
Ratification of Human Rights Treaties: The Beginning, Not the End

Instead of examining ratiﬁcation and outcomes, researchers should probe the full range of human rights indicators, as clariﬁed by the UN Special Rapporteur on the Right to Health. Human rights indicators for health — derived from treaty language, selected by state parties, and legitimised through monitoring bodies — can better assess whether states’ domestic policy implementation is in accordance with human rights obligations.
Social Impression of Faces: From Prediction to Modification

First impressions are influential in shaping our personal, economic, and political decisions. We develop a computational framework that can model and modify impressions of faces. First, we use a state-of-the-art predictive model of facial impressions (such as facial attractiveness, trustworthiness, and intelligence) and apply it to a large-scale natural face dataset in order to create a robust facial impression dataset. We validate the augmented dataset with respect to human judgments. Second, we use the new dataset to train a model, ModifAE, that changes face smoothly and effectively in multiple social dimensions. This modification model offers social scientists the ability to manipulate impressions as needed, and it sheds light on both the biases and the visual features underlying first impression formation.
Towards a Computerized Materials Characterization Expert System

The feasibility of using logic programming for materials characterization in connection with an information base on materials is demonstrated. The previously described LOGLISP knowledge base for materials selection, which contains properties and rules commonly used in materials science, served as the basis for the present study. It is shown that the laboratory notebook format presented in the earlier study can readily be adapted for use in materials characterization. Characterization requirements are obtained as a response to simple LOGLISP inquiries for the conditions to meet a certain set of (unique) properties.
On the Relation Between Grammars and Automata

Since the early 1950’s, the digital computer has become a familiar object. The use of such machines has become widespread, in part because of the availability of higher-level languages, which make computers rather easy to use. In the early 1960’s, when computer science began to develop as an academic discipline, a number of researchers began to ask deeper questions.
James M. Buchanan and Gordon Tullock: A Reflection on Two Disruptive Economists

This chapter offers the author’s personal reflections on encounters with James Buchanan and Gordon Tullock as individuals, as intellectuals, and as providers of major unsettling ideas that formed new chapters in the history of economic thought. The story includes personal encounters as a graduate student, faculty member, and government economist and tells how these two unusual men and their ideas contributed to the author’s professional growth. Buchanan’s and Tullock’s major insights are described as being as powerful as they were disruptive to the intellectual status quo. In short, the more disruptive, the more powerful. Together and separately, the two scholars laid some of the largest stones in the foundation on which modern political economy has been erected.
Photo-induced carrier generation and recombination dynamics probed by combining time-resolved microwave conductivity and transient absorption spectroscopy

We examined photoinduced charge-generation dynamics of the poly(3-hexylthiophene) (P3HT)/titanyl phthalocyanine (TiOPc) bilayer and the P3HT/TiOPc/C60 trilayer using the combination of flash-photolysis time-resolved microwave conductivity experiments (fp-TRMC) and classic pump-probe transient absorption (TA) spectroscopy following dominant excitation of the P3HT layer. The superlinear increase of φΣμ for the P3HT/TiOPc bilayer, compared to the φΣμ sum of each P3HT and TiOPc layer suggest photoinduced carrier-generation. Furthermore, the superlinear increase of φΣμ of the P3HT/TiOPc/C60 trilayer with respect to the each P3HT/TiOPc and TiOPc/C60 bilayers evinces charge migration from one interface to the other interface. In addition, with selective photoexcitation on the P3HT layer, both amorphous and H-aggregated P3HT domains participate in electron transfer ([P3HT*/TiOPc]→[P3HT•+/TiOPc•-]), contrasting to the previous observation where with selective excitation of the TiOPc layer, only the H-aggregated P3HT domain involves in hole transfer ([P3HT/TiOPc→[P3HT•+/TiOPc•-]) to produce P3HT•+/TiOPc•- in J. Phys. Chem. B 119(24), 7729—7739 (2015). These results under different excitation conditions are consistent with calculated energetic driving force (ΔECS) for charge generation which is -0.58 eV and -0.73 eV for amorphous and H-aggregated P3HT domains under the P3HT layer excitation, while 0.04 eV and -0.11 eV for amorphous and H-aggregated P3HT domains under the TiOPc layer excitation.
Principles of turbomachinery in air-breathing engines

1. Introduction to gas turbine engines 2. Overview of turbomachinery nomenclature 3. Aerothermodynamics of turbomachines 4. Energy transfer between a fluid and a rotor 5. Dimensional analysis, maps and specific speed 6. Radial equilibrium theory 7. Polytropic (small-stage) efficiency 8. Axial-flow turbines 9. Axial-flow compressors 10. Radial inflow turbines 11. Centrifugal compressors 12. Turbine-compressor matching.
Co-Morbidity between Cardiovascular Pathology and Depression: Role of Inflammation

Morbidity and mortality of cardiovascular disease is exceedingly high worldwide. Depressive illness is a serious psychiatric illness that afflicts a significant portion of the population worldwide. Epidemiological studies have confirmed the high co-morbidity between these two entities and the co-morbidity is bidirectional. Systems that are involved in and accountable for this co-morbidity in a major, complex and interactive way include the central and autonomic nervous systems, the neuroendocrine system, the immune system, and the vascular and hematologic systems. Specific pathophysiologic factors across these systems include homeostatic imbalance between the sympathetic and the parasympathetic systems with loss of heart rate variability in depression, sympathoadrenal activation, hypothalamic-pituitary-adrenal axis activation resulting in hypercortisolemia, immune system dysregulation with release of pro-inflammatory cytokines and chemokines, platelet activation and hypercoagulability. All of these abnormalities have been demonstrated in most individuals diagnosed with major depressive disorder. This chapter will focus on inflammatory processes. Inflammation occurs in cardiac and cardiovascular pathology independent of the presence or absence of depression. A chronic pro-inflammatory status has been documented in numerous studies of depression. Inflammation is closely associated with endothelial dysfunction which is a preamble to atherosclerosis and atherothrombosis. Endothelial dysfunction has been detected in depression and may prove to be a trait marker for this illness. Thus, understanding vascular biology in conjunction with psychiatric co-morbidity will be of critical importance. A likely common instigator underlying the co-morbidity between cardiovascular pathology and depression is mental stress. Chronic stress shifts the homeostatic balance in the autonomic nervous system with sustained sympathetic overdrive and diminished vagal tone. Diminished vagal tone contributes to a pro-inflammatory status which affects neurotransmitter regulation, specifically serotonergic transmission. Antidepressant drug therapy is of definite benefit to patients with medical and psychiatric co-morbidity and may reverse the pro-inflammatory status associated with depression.
Fluorinated Pyrimidines: XXXIX. Effects of 5-Trifluoromethyl-2'-deoxyuridine on the Replication of Vaccinia Viral Messenger Ribonucleic Acid and Proteins

The mechanism of the antiviral activity of 5-trifluoromethyl-29-deoxyuridine (F 3 TdR) has been studied in vaccinia virus-infected HeLa cells. When normal virions are used to infect the cells in the presence of the analogue, sucrose gradient sedimentation has shown that the early messenger RNA is normal and associates normally with polyribosomes. However, any late mRNA that may be produced under those conditions has abnormal sedimentation properties and does not associate normally with polyribosomes. When the cells are infected with purified virions containing F 3 TdR in their DNA, they adsorb to the cells and are uncoated normally. However, early mRNA is not transcribed normally. Studies of viral protein synthesis with polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate suggest that a major virus-induced protein is not synthesized in the presence of F 3 TdR, and that another protein is formed instead.
Electron Transport Engineering by Nanostructures for Efficient Thermoelectrics

We theoretically investigate nanoscale structures such as nanoparticles embedded in bulk materials as a means of improving the thermoelectric energy conversion efficiency. We focus on the impact of such nanostructures on the electron transport in the host material, and discuss the enhancement of the thermoelectric power factor and thus the figure of merit. Nanostructures embedded in thermoelectric materials can create potential variations at the nanoscale due to the hetero-interfaces, which can alter the transport of charge carriers in the host material to enhance the Seebeck coefficient and the power factor. The energy-dependent electron scattering times induced by nanoparticles are calculated using the partial wave method. Thermoelectric transport properties are then calculated based on the linearized Boltzmann transport theory with the relaxation time approximation for various thermoelectric materials such as ErAs:InGaAs, PbTe, and Mg2Si. The effects of different kinds of nanoparticles including single-phase ionized metallic nanoparticles and core–shell nanoparticles embedded in semiconductors are investigated in these semiconductors. Finally the electron energy filtering scheme is discussed to further enhance the thermoelectric energy conversion efficiency.
Childhood Maltreatment, Shame-Proneness and Self-Criticism in Social Anxiety Disorder: A Sequential Mediational Model.

Previous research has shown a robust link between emotional abuse and neglect with social anxiety symptoms. However, the mechanisms through which these links operate are less clear. We hypothesized a model in which early experiences of abuse and neglect create aversive shame states, internalized into a stable shame-based cognitive–affective schema. Self-criticism is conceptualized as a safety strategy designed to conceal flaws and prevent further experiences of shame. However, self-criticism maintains negative self-perceptions and insecurity in social situations. To provide preliminary, cross-sectional support for this model, a nonclinical community sample of 219 adults from Israel (110 females, mean age = 38.7) completed measures of childhood trauma, shame-proneness, self-criticism and social anxiety symptoms. A sequential mediational model showed that emotional abuse, but not emotional neglect, predicted shame-proneness, which in turn predicted self-criticism, which in turn predicted social anxiety symptoms. These results provide initial evidence supporting the role of shame and self-criticism in the development and maintenance of social anxiety disorder. The clinical implications of these findings are discussed Copyright © 2014 John Wiley & Sons, Ltd. Key Practitioner Message Previous research has shown that histories of emotional abuse and emotional neglect predict social anxiety symptoms, but the mechanisms that underlie these associations are not clear. Using psycho-evolutionary and emotion-focused perspectives, the findings of the current study suggest that shame and self-criticism play an important role in social anxiety and may mediate the link between emotional abuse and symptoms. These findings also suggest that therapeutic interventions specifically targeting shame and self-criticism should be incorporated into treatments for social anxiety, especially with socially anxious patients with abuse histories.
Release of simian virus 40 virions from epithelial cells is polarized and occurs without cell lysis.

Abstract We have investigated the process of release of simian virus 40 (SV40) virions from several monkey kidney cell lines. High levels of virus release were observed prior to any significantly cytopathic effects in all cell lines examined, indicating that SV40 utilizes a mechanism for escape from the host cell which does not involve cell lysis. We demonstrate that SV40 release was polarized in two epithelial cell types (Vero C1008 and primary African green monkey kidney cells) grown on permeable supports; release of virus occurs almost exclusively at apical surfaces. In contrast, equivalent amounts of SV40 virions were recovered from apical and basal culture fluids of nonpolarized CV-1 cells. SV40 virions were observed in large numbers on apical surfaces of epithelial cells and in cytoplasmic smooth membrane vesicles. The sodium ionophore monensin, an inhibitor of vesicular transport, was found to inhibit SV40 release without altering viral protein synthesis or infectious virus production.
Consistency of Pharmaceutical Products: An FDA Perspective on Hot-Melt Extrusion Process

Hot-melt extrusion represents an efficient technology to formulate drugs with poor aqueous solubility into safe and effective drug delivery systems. The interest in this technology continues to grow as it is suitable for both high dose and potent low dose compounds. It is amenable to real-time monitoring and control of the consistency of the product with respect to content uniformity and crystalline conversion. Quality-by-design (QbD) has become an essential part of modern pharmaceutical quality systems since it incorporates an enhanced product and process understanding. It encourages real-time monitoring and control of critical material attributes and process parameters. The QbD paradigm can be easily incorporated into hot-melt processes. It has the potential to replace traditional batch processes due to its continuous nature and ease of scale-up from laboratory scale to commercial scale.
High-mobility ions in cyclohexane. A transient absorption study

Transient absorption kinetics in radiolysis of N2O-saturated cyclohexane has been studied (0.1−100 ns; 300−800 nm). The spectra indicate the involvement of at least three cations (ions I, II, and III), only one of them having abnormally high mobility. Ion II is probably the cyclohexene radical cation, and ion III might be the dimer olefin ion. These two ions absorb as much as ion I at 450−500 nm. While ion II and ion III are scavenged by ethanol and triethylamine with a rate constant of ≈1010 mol-1 dm3 s-1, the scavenging of ion I proceeds with rate constants of ≈9 × 1010 and 2.3 × 1011 mol-1 dm3 s-1, respectively. The spectrum of ion I is similar to the spectrum of the radical cation of cyclohexane isolated in low-temperature matrices. We were not able to observe the absorption from ion I at delay times longer than 50 ns. A corresponding fast growth of the absorption from solute radical cations of pyrene and perylene was observed. The data (simulated using continuum-diffusion and Monte Carlo approaches) ...
Substrate Binding Protein SBP2 of a Putative ABC Transporter as a Novel Vaccine Antigen of Moraxella catarrhalis

Moraxella catarrhalis is a common respiratory tract pathogen that causes otitis media in children and infections in adults with chronic obstructive pulmonary disease. Since the introduction of the pneumococcal conjugate vaccines with/without protein D of nontypeable Haemophilus influenzae, M. catarrhalis has become a high-priority pathogen in otitis media. For the development of antibacterial vaccines and therapies, substrate binding proteins of ATP-binding cassette transporters are important targets. In this study, we identified and characterized a substrate binding protein, SBP2, of M. catarrhalis. Among 30 clinical isolates tested, the sbp2 gene sequence was highly conserved. In 2 different analyses (whole-cell enzyme-linked immunosorbent assay and flow cytometry), polyclonal antibodies raised to recombinant SBP2 demonstrated that SBP2 expresses epitopes on the bacterial surface of the wild type but not the sbp2 mutant. Mice immunized with recombinant SBP2 showed significantly enhanced clearance of M. catarrhalis from the lung compared to that in the control group at both 25-μg and 50-μg doses (P < 0.001). We conclude that SBP2 is a novel, attractive candidate as a vaccine antigen against M. catarrhalis.
An optimized method to detect influenza virus and human rhinovirus from exhaled breath and the airborne environment

Respiratory viruses are difficult to characterize in the airborne environment due to their low concentration and the presence of a wide range of inhibitors. As a first step in studying airborne viruses, we optimized molecular biology methods to quantify influenza viruses and human rhinovirus. Quantitative PCR was used as an endpoint to evaluate RNA extraction techniques and reverse transcription protocols. We found that a Trizol-chloroform extraction and MultiScribe RT increased virus detection 10-fold compared to methods used in published field studies of airborne respiratory viruses. Virus was recovered without inhibition from samples contaminated with up to 50 microg/sample of particulate matter. The methods developed can be used in studies of airborne respiratory viruses.
Pore and continuum scale study of the effect of subgrid transport heterogeneity on redox reaction rates

Abstract A micromodel system, which corresponds to one or part of a numerical grid in the continuum model, was used to investigate the effect of subgrid transport heterogeneity on redox reaction rates. Hematite reductive dissolution by injecting a reduced form of flavin mononucleotide (FMNH2) at variable flow rates was used as an example to probe the variations of redox reaction rates in different subgrid transport domains. Experiments, pore-scale simulations, and macroscopic continuum modeling were performed to measure and simulate in-situ hematite reduction and to evaluate the scaling behavior of the redox reaction rates from the pore to continuum scales. The results indicated that the measured pore-scale rates of hematite reduction were consistent with the predictions from a pore-scale reactive transport model. A general trend is that hematite reduction followed reductant transport pathways, starting from the advection-dominated pores toward the interior of diffusion-dominated domains. Two types of diffusion domains were considered in the micromodel: a micropore diffusion domain, which locates inside solid grains or aggregates where reactant transport is limited by diffusion; and a macropore diffusion domain, which locates at wedged, dead-end pore spaces created by the grain-grain contacts. The rate of hematite reduction in the advection-dominated domain was faster than those in the diffusion-controlled domains, and the rate in the macropore diffusion domain was faster than that in the micropore domain. The reduction rates in the advection and macropore diffusion domains increased with increasing flow rate, but were affected by different mechanisms. The rate increase in the advection domain was controlled by the mass action effect as a faster flow supplied more reactants, and the rate increase in the macropore domain was more affected by the rate of mass exchange with the advection domain, which increased with increasing flow rate. The hematite reduction rate in the micropore domain was, however, not affected by the flow rate because molecular diffusion limits reductant supply to the micropore domain interior. Domain-based macroscopic models were evaluated to scale redox reaction rates from the pore to continuum scales. Simulation results from the single domain model, which ignores subgrid transport heterogeneity, deviated significantly from the pore-scale results. Further analysis revealed that the rate expression for hematite reduction was not scalable from the pore to porous media using the single domain model. A three-domain model, which effectively considers subgrid reactive diffusion in the micropore and macropore domains, significantly improved model description. Overall this study revealed the importance of subgrid transport heterogeneity in the manifestation of redox reaction rates in porous media and in scaling reactions from the pore to porous media. The research also supported that the domain-based scaling approach can be used to directly scale redox reactions in porous media with subgrid transport heterogeneity.
Mechanisms involved in fibrin formation.

That the role of thrombin in the conversion of fibrinogen to fibrin is essentially enzymatic, is established not only by the minute amounts of thrombin which are effective but also by the complete independence of fibrin yields and thrombin concentrations over a very wide range of thrombin dilutions and clotting times. The thrombin-fibrinogen reaction, in the phase beyond the "latent period" at least, seems fundamentally "first order." Technical requirements of the experiments leading to these conclusions include: (1) a highly purified ( e.g . 97 per cent "clottable") fibrinogen, (2) absence of traces of thrombic impurities in the fibrinogen, (3) absence of fibrinolytic protease contaminant of the thrombin and the fibrinogen, and (4) sufficient stability of the thrombin even at very high dilutions. Four conditions affecting thrombin stability have been investigated. Fibrin yields are not significantly modified by numerous experimental circumstances that influence the clotting time, such as (1) temperature, (2) pH, (3) non-specific salt action due to electrical (ionic) charges, which alter the Coulomb forces involved in the fibrillar aggregation, (4) specific ion effects, whether clot-accelerating ( e.g . Ca ++ ) or clot-inhibitory ( e.g . Fe(CN) 6 9999), (5) occluding (adsorptive) colloids, which have a "fibrinoplastic" action, e.g . ( a ) acacia and probably ( b ) fibrinogen which has been mildly "denatured" by salt-heating, acidification, etc. The data with which several European workers have attempted to substantiate the idea of a two-stage thrombin-fibrinogen reaction with an intermediary "profibrin" (allegedly partly "denatured") have been reanalyzed with controls which lead us to very different conclusions, viz . (1) denaturation and fibrin formation are independent; (2) partial denaturation is "fibrinoplastic" (see above); and (3) conditions of strong salinity and acid pH (5.1) usually do not completely prevent the thrombin-fibrinogen reaction but merely prolong the "latent" phase and lessen the time required for completion of essentially the same reaction (fibrin polymerization) when more favorable clotting conditions are restored. Thus, our experiments advance the modern concepts concerning the coagulation mechanisms along lines that, for the most part, agree with those of the Harvard physical chemists, and we oppose the European views concerning a two-stage reaction, "profibrin," and "the denaturase theory" of clotting.
Abstract A51: Disruption of Abi1/Hssh3bp1 expression induces prostatic intraepithelial neoplasia in the conditional Abi1/Hssh3bp1 KO mice

Abstract Prostate cancer is one of the leading causes of cancer-related deaths in the United States and a leading diagnosed non-skin cancer in American men. Genetic mutations underlying prostate cancer tumorigenesis include alterations of tumor suppressor genes. We previously proposed that ABI1/hSSH3BP1 acts as a tumor suppressor gene (Macoska, et al. 2001 Neoplasia 3, 99-104). Here, we tested this hypothesis by searching for ABI1 gene mutations in primary prostate tumors from patients, and by analyzing the consequences of prostate-specific disruption of the mouse Abi1/Hssh3bp1 orthologue. We sequenced the ABI1/hSSH3BP1 gene and identified mutations in 15 out of 44 prostate tumors. Moreover, complementation growth-, proliferation- and xenograft- assays using the LNCaP cell line, which contains the loss-of-function Abi1 mutation, and stably expressed wt ABI gene, were consistent with the tumor suppressor hypothesis. To test the hypothesis further, we disrupted the gene in the mouse prostate by breeding the Abi1 floxed strain with the probasin promoter-driven Cre recombinase strain. Histopathological evaluation of mice indicated development of prostatic intraepithelial neoplasia (PIN) in Abi1/Hssh3bp1 KO mouse as early as the 8th month, but no progression beyond PIN was observed in mice as old as 12 months. Observed decreased levels of E-cadherin, β-catenin, and WAVE2 in mouse prostate suggest abnormal cellular adhesion as the mechanism underlying PIN development due to Abi1 disruption. In summary, this study provides further evidence for the hypothesis that Abi1 down-regulation plays a role in the development of prostate cancer and warrants further investigations of Abi19s role in prostate cancer tumorigenesis. Citation Format: Xiaoling Xiong, Leszek Kotula, Anna Chorzalska, Patrycja Dubielecka, Julie White, Yogindra Vedvyas, Cyrus V. Hedvat, Adriana Haimovitz-Friedman, Jason A. Koutcher, Janet A. Sawicki. Disruption of Abi1/Hssh3bp1 expression induces prostatic intraepithelial neoplasia in the conditional Abi1/Hssh3bp1 KO mice [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A51.
Vegetable oil based fatty amide as hydrophobes in associative thickener

A vegetable oil based high performance associative thickener has been designed and synthesized from a hydroxyl functional soybean oil derivative (hydroxyl value 159 mg KOH/g). An isocyanate-terminated prepolymer was synthesized from polyethylene glycol (PEG) and isophorone diisocyanate (IPDI), and end-capped with the hydroxyl functional soybean oil derivative to prepare a hydrophobically modified ethoxylated polyurethane (HEUR) thickener. The synthesis was monitored by infrared spectroscopy via the isocyanate peak at 2258–2270 cm−1. Thickener efficiency was tested with a commercial styrene–acrylic latex UCAR™ 443, an acrylic latex Acronal® Optive 130 and an alkyd emulsion WorleeSol® E 150W. High thickening efficiency was noted in the low shear region, e.g., 0.5 wt % HEUR loading with UCAR 443 increased viscosity from 0.66 P to 3.06 P at a shear rate of 1333 s−1. The effect of soybean oil fatty amide based rheology modifier as additive in coating was evaluated in terms of gloss, viscosity, sag resistance, and flow and leveling properties. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 1530–1538, 2013
Cross-reactivity between human and murine lymphocyte antigens. IV. Reactivity of H-2 alloantisera with HLA-A, B antigens.

The anti-H-2 alloantiserum D-32 [(BlO.A(2R) × C3H.SW) anti-C3H] is cytolytic to human lymphocytes. Fab2 blocking assays, indirect immunoprecipitation and sequential immunoprecipitation experiments showed that the anti-H-2 alloantiserum D-32 recognizes antigenic determinants which are expressed on the heavy chain of subpopulations of HLA-A, B antigens. These determinants are different from those defining the serological polymorphism of the HLA-A, B, C system, are the same as or spatially close to those recognized by the anti-HLA-A, B monoclonal antibody Q6/64 and are expressed on rabbit, rat or guinea pig lymphocytes.
Acyclic N-Halamine Polymeric Biocidal Films

Low concentrations of acyclic amide monomers, methacrylamide (MAM) and acrylamide (AM), were copolymerized with vinyl acetate (VAc). No significant differences between the synthesized copolymers and poly(VAc) were seen by 1H-NMR, FTIR, and DSC analysis. Biocidal films, formed by coating the copolymers onto polyester transparency slides and polyester fabric swatches, were chlorinated by exposure to sodium hypochlorite solutions. Both S. aureus and E. coli O157: H7 were completely inactivated within 1 min on the transparency slides and polyester fabric swatches derived from poly(VAc-co-MAM). The chlorine on the films was stable under UVA irradiation and the surfaces were rechargeable upon chlorine loss.
Role of convection in global‐scale transport in the troposphere

[1] The role of convection in global-scale transport in the troposphere is studied by using climatological Green's functions of the mass conservation equation for a conserved, passive tracer. The Green's functions are calculated from long-term atmospheric trajectory calculations based on three-dimensional winds from a 19-year simulation by Version 3 of the NCAR Community Climate Model (CCM3). Two trajectory calculations are compared: one that includes the effects of the model's parameterized convection and one that neglects the convective transport. The global transport properties of the two cases are qualitatively similar. The global troposphere can be divided into three parts: the tropics, and the Northern and Southern Hemisphere extratropics. Transport within each region is rapid, while the exchange of air between the regions is comparatively slow. Semipermeable barriers to transport exist in the subtropics in both cases. Convection slightly suppresses transport across the subtropical barriers. Convective transport enhances the vertical dispersion of air parcels, particularly in the rising branch of the Hadley circulation. Localized differences between the two runs can reach 50–80%. The differences are largest in the upper troposphere. Interannual transport variations related to the El Nino–Southern Oscillation (ENSO) phase can be detected in both cases, with the vertical transport being enhanced in the presence of convection.