cssi/SciSciGPT-SciSciNet huggingface dataset:
Nature and the Art Nouveau

THE Art Nouveau is usually approached warily by historians. It is given a place in most recent surveys of architecture, but it is treated as an ornamental style and its influence deprecated. The fact that it was the most widespread expression of the period 1890–1910, which were two of the most experimental and decisive decades in the background of contemporary architecture, must somehow be explained. The style was accepted by dilettantes and by serious designers. The publicity it received was enormous. It formed the basis for much pseudo-philosophizing, and never until perhaps the Bauhaus has an art movement been so thoroughly explained and interpreted by its disciples and so strongly attacked by its critics. Today we are removed from the Art Nouveau by half a century and are perhaps able to judge whether it was a worthless, frivolous interlude or a valid expression which contributed a new viewpoint to the aesthetics of its period and left examples of value to contemporary developments.
Mechanistic studies of the lithium enolate of 4-fluoroacetophenone: rapid-injection NMR study of enolate formation, dynamics, and aldol reactivity.

Lithium enolates are widely used nucleophiles with a complicated and only partially understood solution chemistry. Deprotonation of 4-fluoroacetophenone in THF with lithium diisopropylamide occurs through direct reaction of the amide dimer to yield a mixed enolate-amide dimer (3), then an enolate homodimer (1-Li)2, and finally an enolate tetramer (1-Li)4, the equilibrium structure. Aldol reactions of both the metastable dimer and the stable tetramer of the enolate were investigated. Each reacted directly with the aldehyde to give a mixed enolate-aldolate aggregate, with the dimer only about 20 times as reactive as the tetramer at −120 °C.
The New Art of Structural Engineering: An Introductory Course in Structures

Structural engineers have a rich tradition of creativity, especially since the Industrial Revolution when new materials made possible new forms. This one-semester course seeks to introduce students...
Study on the Effect of Wellhead Back Pressure on POWP Pump Efficiency

The effect of wellhead back pressure on POWP pump efficiency is studied.The elastica collapsing of pump rod-oil tube,pump leaking,pump fluid level were examined on calculating the pump efficiency.By using the calculator program of pump efficiency and wellhead back pressure,the 11 wells of PU-BEI can be calculated.It was found that the pump efficiency and wellhead back pressure could reach linear relationship,the pump efficiency declines 1%～2% by wellhead back pressure increases 1 MPa.
Design Patterns Applied in Optical Transport Integrated NMS

The design patterns are a set of successful designs and system structure.Detailed analyses the application of Builder pattern,Bridge pattern and Command pattern in optical transport integrated NMS.It has been proved that the application of design patterns can enhance the quality and optimize the system structure.
Effect of Trisodium Phosphate on Salmonellae Attached to Chicken Skin.

Processed carcasses from a commercial plant were inoculated with 108 or 102 colony forming units (CFU) of Salmonella typhimurium 14028. Inoculated carcasses were dipped in a 10% trisodium phosphate...
Autologous Hematopoietic Cell Transplantation in Patients With Multiple Myeloma: Effect of Age

Abstract Background In the novel and pre–novel agent era, high-dose therapy, followed by autologous hematopoietic cell transplantation (AHCT), has been shown to prolong survival in patients with multiple myeloma (MM) in randomized trials. However, these trials only included patients aged ≤ 65 years. Given that the median age at diagnosis is 66 years, it is important to know the outcomes of AHCT in older patients. Similarly, definite outcomes of AHCT in very young patients (aged Materials and Methods We analyzed a consecutive cohort of patients with MM receiving AHCT from 2000 to 2015 in 2 different age groups, older (> 70 years) and younger (≤ 50 years), and compared the outcomes. The primary objectives were to assess overall survival, progression-free survival (PFS), and nonrelapse mortality in these 2 groups. Results Of the 191 patients, 86 were young (age ≤ 50 years) and 105 were old (age > 70 years). The younger patients had better performance status and a lower comorbidity index, and most of the older patients had received a melphalan dose of 140 to 180 mg/m 2 . The median follow-up period for the young group was 33 months (range, 2-164 months) compared with 22.5 months (range, 3-133 months) in the old group ( P = .02). The PFS rate at 1 year was 60% (95% confidence interval [CI], 46%-72%) for the young group and 58% (95% CI, 45%-69%) for the old group. The overall survival rate at 1 year was 92% (95% CI, 84%-96%) for the young group and 85% (95% CI, 76%-91%) for the old group. On multivariate analysis, age did not have any effect on survival ( P = .82); however, the patients with high-risk cytogenetics (hazard ratio [HR], 2.2; 95% CI, 1.06-4.6; P = .04) had worse overall mortality. High-risk cytogenetics (HR, 1.2; 95% CI, 1.1-3.5; P = .004) and no disease response or progressive disease at transplantation (HR, 5.0; 95% CI, 1.8-13.5; P = .02) were significantly associated with worse PFS. Conclusion Age should not be a limiting factor in considering the modality of AHCT. However, younger patients might also benefit from additional novel treatment approaches in the setting of clinical trials, given their similar outcomes with the older patients in our study.
Taxation in a Global Economy

Students can examine how international taxation is a system of global tax rules that apply to transactions between two or more countries. They will see how, given differing tax consequences across countries, taxpayers must incorporate tax planning into their strategic decisions to avoid excessive taxation by structuring transactions to limit their additional global tax exposure while taxpayers, seeking to maximize after-tax returns, can structure transactions to chase the lowest tax consequences. Excerpt UVA-C-2328 Nov. 4, 2011 TAXATION IN A GLOBAL ECONOMY International taxation is a system of global tax rules that apply to transactions between two or more countries. While tax planning for purely domestic transactions is subject to a unified country tax code enforced by a single governing body, tax planning for cross-border transactions depends on the interaction of tax laws and enforcement agencies in multiple countries. This interaction can lead to excessive taxation or minimal taxation on cross-border transactions. Given differing tax consequences across countries, taxpayers must incorporate tax planning into their strategic decisions. Taxpayers, fearful of excessive taxation, can simply structure transactions to limit their additional global tax exposure while taxpayers, seeking to maximize after-tax returns, can structure transactions to chase the lowest tax consequences. The Importance of Understanding the Taxation on Foreign Investment and Services During 2010, the United States imported approximately $ 2.34 trillion and exported approximately $ 1.84 trillion of goods and services, both 90% increases since 1999. Today's global marketplace demands that participants have a thorough understanding of the cultural, legal, and financial impacts of cross-border transactions. As businesses pursue cross-border transactions, they will benefit from a general understanding of international taxation, and the benefit will only increase as more transactions span multiple borders in the future. . . .
Socioeconomic and Policy Considerations in the Adoption of Agroforestry Systems: An Ecosystem-based Adaptive Governance Approach

Owing to the shortfalls in conventional approaches to forestry and agriculture, agroforestry has been receiving attention among researchers and policy-makers since the 1970s as an alternative land use strategy in tropical systems. Agroforestry is a promising strategy for deriving a range of benefits, such as food and water security, ecosystem health, energy security, and human health particularly in developing nations. Agroforestry is also posited as a means of producing various ecosystem services necessary for mitigation and adaptation to climate change impacts. In spite of these expected benefits, the adoption of agroforestry policies has been limited, and the potential contributions of agroforestry to resilience and sustainable development remain unrealized. Drawing from theoretical insights in ecosystem management and adaptive governance, this chapter discusses the potential benefits of managing agroforestry systems as complex adaptive social-ecological systems. Ecosystem-based adaptive governance holds promise as a framework for increasing the adoption of agroforestry as a land-use strategy for achieving sustainable development and social-ecological resilience by promoting a more inclusive and dynamic approach to developing locally-based agroforestry models. The modified taungya system in Ghana and other relevant case studies are used to illustrate the argument.
Comprehending visualisations of dense rank order data: a comparison of alternate presentation formats

This study compared two tabular presentations and one graphical presentation of the same rank order data to study differences in participant comprehension. Hypothetical raw voting data by ten different judges ranking ten states on the desirability of each state as a preferred place for retirement was used. Three sets of the data were constructed for the voting scenario with low, high and moderate levels of consensus. The summary data was a table (TABULAR) representing the total count of votes for each rank (first place through tenth place) for all ten states. It was also presented as a 3D cone infographic (GRAPHICAL) and raw voting data (RAW). Participants were asked to estimate the level of agreement (0.00 to 1.00) indicated by each presentation. The results showed that the graphical and tabular presentations differed in participant comprehension for low and moderate levels of agreement but not for high levels of agreement.
A Quick Proof of Fay's Secant Identities

Publisher Summary This chapter presents a proof of Fay's secant identities. The classical view of projective curves relies upon efficient moduli. KdV suggests a very different attitude in which inefficient moduli such as differential operators should be preferred. The inefficiency refers to the fact that these are infinite dimensional objects, as opposed to 3g–3 complex numbers, the trade-off being that efficient machinery is available for computation. The same idea can be expressed in a different form, stating that the restriction to functions of rational character is inefficient, many computations being expedited by use of the exponential function.
The role of host cell death in Salmonella infections.

Salmonella enterica is an important enteric pathogen of humans and a variety of domestic and wild animals. Infection is initiated in the intestinal tract, and severe disease produces widespread destruction of the intestinal mucosa. Salmonella strains can also disseminate from the intestine and produce serious, sometimes fatal infections with considerable cytopathology in a number of systemic organs. A combination of bacterial genetic and cell biology studies have shown that Salmonella uses specific virulence mechanisms to induce host cell death during infection. Salmonella produces one set of virulence proteins to promote invasion of the intestine and a different set to mediate systemic disease. Significantly, each set of virulence factors mediates a distinct mechanism of host cell death. The Salmonella pathogenicity island-1 (SPI-1) locus encodes a type III protein secretion system (TTSS) that delivers effector proteins required for intestinal invasion and the production of enteritis. The SPI-1 effector SipB activates caspase-1 in macrophages, releasing IL-1β and IL-18 and inducing rapid cell death by a mechanism that has features of both apoptosis and necrosis. Caspase-1 is required for Salmonella to infect Peyer’s patches and disseminate to systemic tissues in mice. Progressive Salmonella infection in mice requires the SPI-2 TTSS and associated effector proteins as well as the SpvB cytotoxin. Apoptosis of macrophages in the liver is found during systemic infection. In cell culture, Salmonella strains induce delayed apoptosis dependent on SPI-2 function in macrophages from a variety of sources. This delayed apoptosis also requires activation of TLR4 on macrophages by the bacterial LPS. Downstream activation of kinase pathways leads to balanced pro- and antiapoptotic regulatory factors in the cell. NF-κB and p38 mitogen-activated protein kinase (MAPK) are particularly important for the induction of antiapoptotic factors, whereas the kinase PKR is required for bacterial-induced apoptosis. The Salmonella SPI-2 TTSS is essential for altering the balance in favor of apoptosis during intracellular infection, but the effectors involved remain poorly characterized. The SpvB cytotoxin has been shown to play a role in apoptosis in human macrophages by depolymerizing the actin cytoskeleton. A model for the role of bacteria-induced host cell death in Salmonella pathogenesis is proposed. In the intestine, the Salmonella SPI-1 TTSS and SipB mediate macrophage death by caspase-1 activation, which also releases IL-1β and IL-18, promoting inflammation and subsequent phagocytosis by incoming macrophages and leading to dissemination to systemic tissues. Intracellular secretion of virulence effector proteins by the SPI-2 TTSS facilitates growth of Salmonella in these macrophages and the delayed onset of apoptosis in extraintestinal tissues. These infected, apoptotic cells are targeted for engulfment by incoming macrophages, thus perpetuating the cycle of cell-to-cell spread that is the hallmark of systemic Salmonella infection.
Effects of the flrA regulatory locus on biosynthesis and excretion of amino acids in EscherichiacoliBr

Abstract We have partially characterized phenotypic effects of an unusual amino acid regulatory locus, flrA , in E . coli B r that alters the expression of the ilv and leu operons [ Kline, E.L (1972) J. Bacteriol. 110:1127–1134]. This study demonstrated that a primary effect of the flrA 7 mutation in haploid strains was overproduction of valine. In diploid strains ( F′ flrA + flrA 7 ) this mutation resulted in excretion of valine, isoleucine, leucine, aspartate, threonine, glutamate, histidine and lysine. Increased excretion of amino acids by mutant strains might be explained by a membrane alteration or by flrA encoding a positive regulatory factor that affects the ilv operon and has pleiotropic effects on other amino acid operons.
Towards Attentive Speed Reading on Small Screen Wearable Devices

Smart watches can enrich everyday interactions by providing both glanceable information and instant access to frequent tasks. However, reading text messages on a 1.5-inch small screen is inherently challenging, especially when a user's attention is divided. We present SmartRSVP, an attentive speed-reading system to facilitate text reading on small-screen wearable devices. SmartRSVP leverages camera-based visual attention tracking and implicit physiological signal sensing to make text reading via Rapid Serial Visual Presentation (RSVP) more enjoyable and practical on smart watches. Through a series of three studies involving 40 participants, we found that 1) SmartRSVP can achieve a significantly higher comprehension rate (57.5% vs. 23.9%) and perceived comfort (3.8 vs. 2.1) than traditional RSVP; 2) Users prefer SmartRSVP over traditional reading interfaces when they walk and read; 3) SmartRSVP can predict users' cognitive workloads and adjust the reading speed accordingly in real-time with 83.3% precision.
Huisarts en POH-GGZ

De POH-GGZ is, na een schoorvoetende start in 2008, inmiddels een belangrijke pijler in de zorg voor mensen met psychische klachten in de huisartsenpraktijk en kan, mits goed opgeleid en ingebed in de organisatie huisartsenpraktijk, veel betekenen bij psychische problematiek. De huisarts dient in de samenwerking rekening te houden met het opleidingsniveau en de specifieke competenties van zijn POH-GGZ. Goede samenwerkingsafspraken zijn, ook vanuit juridisch oogpunt, van belang. De POH-jeugd is een jonge loot aan de tak van de praktijkondersteuning en dit terrein is nog erg in ontwikkeling.
A Broker Architecture, Push-Pull Database System for Intelligence Analysis

Database technology, while quite powerful, is not well suited to Intelligence analysis. One of its drawbacks is the fact that queries are answered as they are posed to the system, and then forgotten. But analysts that are asked to write a report and query the database in order to gather information usually have a certain amount of time to work on such report. If the database is updated and changes are not reported, the analyst may miss relevant, up-to-date information. In this paper, we propose an approach to solve this problem. The approach uses a Broker architecture to develop a push-pull system that allows users to either push documents into the database or pull documents out of the database as needed. Our approach is conceptually simple and can be implemented on top of off-the-shelf relational technology. Also, it can be extended to support more sophisticated functionality.1
Introduction: Inciting Communication Across Queer Migration Studies and Critical Trafficking Studies

While taking a walk in Long Beach, California, an Asian American couple and their child crossed paths with a white woman named Tarin Olson, a professor and counselor in career planning at Golden We...
Water is a Human Right! Grassroots Resistance to Corporate Power

In this short piece, I seek to explore two main questions: 1) How can communities take control over local governance and shape local economic futures?and2) How can local communities effectively band together to support world-system transformation? I examine examples of transnational organizing around water and, specifically, the National Summit on the Human Right to Water held in Abuja, Nigeria in January 2019. A repeated theme at the Summit was the idea that privatization is a threat because the narrative of the profit-based solution of privatization is at odds with the idea that people—and their human right to basic needs like water—come before profit. Privatization is a threat to human rights everywhere,and as climate change progresses resources will become even more scarce, with more of a push from corporations seeking to control and commodify water. One of the most powerful short-term results of this summit, therefore, was how it served as a space forglobalsolidarity buildingaround the human right to water.
A two-zone reaction-based combustion model for a spark-ignition engine:

This article presents a control-oriented two-zone reaction-based zero-dimensional model to accurately describe the combustion process of a spark-ignited engine for real-time simulations, and the de...
Dynamics of Mycobacterium Tuberculosis Ag85B Revealed by a Sensitive Enzyme-Linked Immunosorbent Assay

ABSTRACT Secretion of specific proteins contributes to pathogenesis and immune responses in tuberculosis and other bacterial infections, yet the kinetics of protein secretion and fate of secreted proteins in vivo are poorly understood. We generated new monoclonal antibodies that recognize the Mycobacterium tuberculosis secreted protein Ag85B and used them to establish and characterize a sensitive enzyme-linked immunosorbent assay (ELISA) to quantitate Ag85B in samples generated in vitro and in vivo. We found that nutritional or culture conditions had little impact on the secretion of Ag85B and that there is considerable variation in Ag85B secretion by distinct strains in the M. tuberculosis complex: compared with the commonly used H37Rv strain (lineage 4), Mycobacterium africanum (lineage 6) secretes less Ag85B, and two strains from lineage 2 secrete more Ag85B. We also used the ELISA to determine that the rate of secretion of Ag85B is 10- to 100-fold lower than that of proteins secreted by Gram-negative and Gram-positive bacteria, respectively. ELISA quantitation of Ag85B in lung homogenates of M. tuberculosis H37Rv-infected mice revealed that although Ag85B accumulates in the lungs as the bacterial population expands, the amount of Ag85B per bacterium decreases nearly 10,000-fold at later stages of infection, coincident with the development of T cell responses and arrest of bacterial population growth. These results indicate that bacterial protein secretion in vivo is dynamic and regulated, and quantitation of secreted bacterial proteins can contribute to the understanding of pathogenesis and immunity in tuberculosis and other infections. IMPORTANCE Bacterial protein secretion contributes to host-pathogen interactions, yet the process and consequences of bacterial protein secretion during infection are poorly understood. We developed a sensitive ELISA to quantitate a protein (termed Ag85B) secreted by M. tuberculosis and used it to find that Ag85B secretion occurs with slower kinetics than for proteins secreted by Gram-positive and Gram-negative bacteria and that accumulation of Ag85B in the lungs is markedly regulated as a function of the bacterial population density. Our results demonstrate that quantitation of bacterial proteins during infection can reveal novel insights into host-pathogen interactions.
Examining Overparenting and Child Gender in Adolescence

Overparenting research has been primarily confined to parents of adult, college-aged children. Few studies have examined overparenting among parents of early adolescent children, particularly in non-academic out-of-school time settings. The present study examined the relation between overparenting, commonly associated parental behaviors, and child gender, to determine if, in a sample of 169 parents of youth ages 11–17 (M = 15.49), the same relations would be present as in prior overparenting research with emerging adult samples. Data were collected using a cross-sectional design with a questionnaire administered to parents following their child’s participation in a one-week university-based residential summer camp. The initial seven-factor scale included items related to overparenting, affect management, parental monitoring, digital limit setting, psychological control, risk aversion, and autonomy granting. The final seven-factor 22-item measure was validated through confirmatory factor analysis and study hypotheses were tested through a structural equation model. Consistent with much of the overparenting literature involving parents of emerging adults, overparenting had a significant positive direct effect on affect management, parental monitoring, parental digital limit setting, psychological control, and risk aversion, and a significant negative direct effect on autonomy granting. No relation was found between child gender and affect management, parental monitoring, parental digital limit setting, overparenting, risk aversion, psychological control, or autonomy granting. The findings were partly consistent with prior studies of emerging adults and have implications for our understanding of overparenting during adolescence as well as within the out-of-school time contexts in which overparenting research is emerging.
Who innovates with whom and why? Evidence from international collaboration in energy patenting

The use of renewable and alternative energy technologies, which have the potential to reduce carbon emissions worldwide, is limited. Common environmental policy environments may encourage inventors...
Review of: Great Debates in Criminology

Not everybody writes good books, but Chad Posick and Michael Rocque sure have. Their Great Debates in Criminology is poised to be a staple of criminology classrooms in the coming years. This is not...
Does an association exist between liver fibrosis and non-HCC cancers.

e16594Background: The association between liver fibrosis and hepatocellular cancer (HCC) is well established, however there is limitation of data on liver fibrosis and non-HCC cancers. The aim of t...
User concept pattern discovery using relevance feedback and multiple instance learning for content-based image retrieval

Understanding and learning the subjective aspect of humans in Content-Based Image Retrieval has been an active research field during the past few years. However, how to effectively discover users' concept patterns when there are multiple visual features existing in the retrieval system still remains a big issue. In this paper, we propose a multimedia data mining framework that incorporates Multiple Instance Learning into the user relevance feedback in a seamless way to discover the concept patterns of users, especially where the user's most interested region and how to map the local feature vector of that region to the high-level concept pattern of users. This underlying mapping can be progressively discovered through the feedback and learning procedure. The role user plays in the retrieval system is to guide the system mining process to his/her own focus of attention. The retrieval performance is tested under a couple of conditions.
Mitigation Interventions in the United States: An Exploratory Investigation of Determinants and Impacts

Purpose:To examine the determinants and impacts of implementing the mitigation interventions to combat the COVID-19 disease in the United States during the first 5 weeks of the pandemic.Method:A co...
Yttrium-90 dosimetry and implications on tumour response and survival after radioembolisation of chemo-refractory hepatic metastases from breast cancer.

Purpose The aim of the study was to evaluate the effects of tumour dose on tumour response and overall survival (OS) in patients with chemo-refractory metastatic breast cancer (MBC) to the liver undergoing yttrium-90 radioembolisation (Y90 RE). Materials and methods In 20 consecutive patients with chemo-refractory MBC to the liver undergoing 33 total Y90 RE resin treatments, volumes of interest were drawn around the five largest tumours of the targeted liver lobe on post-Y90 RE Bremsstrahlung single-photon emission computed tomography/computed tomography using MIM software v.6.9 (MIM Software, Cleveland, Ohio, USA) and dose-volume histograms were calculated. Response Evaluation Criteria in Solid Tumours (RECIST) was used to determine tumour response at 3 months. Receiver operating characteristics (ROC) curves were used to determine thresholds for various dosimetry parameters. Kaplan-Meier estimation was used to determine OS. Results Overall, 11 of 33 (33%) Y90 RE treatments resulted in complete or partial response according to RECIST criteria with a median OS of 20.97 months compared to 11.73 months for nonresponders (P = 0.003). Mean tumour dose, defined as the aggregate tumour dose of up to the five largest tumours in the targeted lobe, was the most predictive of tumour response with the highest area under the ROC curve of 0.967. Mean tumour dose >70 Gy had 91% sensitivity and 100% specificity for predicting tumour response. Patients with mean tumour dose >70 Gy experienced a median OS of 16.1 months vs. 12.8 months for those who did not (P = 0.008). Conclusion For patients with chemo-refractory breast cancer with liver metastases, achieving a mean tumour dose >70 Gy is a significant predictor of tumour response and prolonged OS.
Reinscribing gender: social media, algorithms, bias

This article reflects on an apparent paradox – in light of cultural shifts in gender, as well as a growing understanding of the multiplicity of gender, internet algorithms tend to reinforce dualist...
Lessons from an “Oops” at Consumer Reports: Consumers Follow Experts and Ignore Invalid Information:

Abstract In 2007, Consumer Reports released, and two weeks later retracted, a flawed report on the safety of infant car seats. Analyzing data from 5471 online auctions for car seats ending before, during, and after the information was considered valid, this article shows that (1) consumers responded to the new information and, more surprisingly, (2) they promptly ceased to do so when it was retracted. Because of the random nature of the flawed ratings, this first finding demonstrates that expert advice has a causal effect on consumer demand. The second finding suggests that people's inability to willfully ignore information is not as extreme as the experimental evidence in the psychological literature suggests.
Nature and the Rivers of Life: William L. Graf, 1947–2019

I came to know rivers throughout the United States, ranging from the Canning in Alaska to the Everglades in Florida, from the wilderness Colorado River to the artificial Los Angeles River. Like a r...
Colonizing Air: British Colonial Meteorology and the Building of an East African Climate

From 1929 to 1963 the colonial British East African Meteorological Service-- the forerunner to the East African Community Meteorological Service-- collaborated with the Uganda Protectorate Forestry Office to measure, record, and interpret the climate of Uganda. During this period, Ugandan forest rangers and guards were charged with the tasks of measuring rainfall, wind, temperature, soil moisture, and light intensity (sunshine) at forestry stations throughout the country. At an infrastructural level, this paper traces how the building of a meteorological network that spanned from Kenya to Uganda, Tanganyika (Tanzania), Northern Rhodesia (Zambia), and Zanzibar contributed to the idea of a cohesive, regional "East African Climate." On a micro-level, this paper examines the relationships that Ugandan forest workers forged with the technologies of this new infrastructure through the practice of daily scientific measurement and data collection, with an attention especially to the pleasures and frustrations that this work afforded. Rather than view forestry and meteorology fieldworkers solely as exploited local actors at the whim of western scientists, this paper argues that Ugandan researchers contributed to the coproduction of cultural and scientific knowledge about the East African Climate in ways that were mediated by their own attachments to the technology.
232 INCB090244, a potent small molecule that inhibits the PD-L1/PD-1 axis and functions similarly to PD-L1 antibodies

Background Blocking the PD-L1 immune checkpoint axis with therapeutic antibodies against either the ligand or PD-1 has proven to be an effective treatment modality for multiple cancer histologies. Small molecules targeting the PD-L1/PD-1 axis represent an alternate modality of blocking this pathway. INCB090244 is a small molecule that blocks the PD-L1/PD-1 interaction and restores T cell function similar to the clinical stage PD-L1 inhibitor INCB086550. Methods MDA-MB-231 or CHO cells overexpressing PD-L1 were used to investigate effects of INCB090244 on PD-L1 dimerization, and intracellular trafficking. In vivo, CD34+ humanized mice harboring MDA-MB-231 tumors or C57Bl/6 mice bearing GL261 subcutaneous or orthotopic tumors were used to investigate the efficacy, biodistribution, and pharmacodynamic effects of INCB090244. Human specific gene expression changes in tumors from MDA-MB-231 bearing humanized mice were analyzed by RNA sequencing. Results In vitro, INCB090244 potently disrupted the PD-L1:PD-1 interaction, induced PD-L1 dimerization, and inhibited PD-1-mediated negative signaling, resulting in enhanced IFN gamma and IL-2 production in primary human immune cells. Following dimerization, INCB090244 induced internalization of PD-L1 resulting in co-localization with the Golgi apparatus and partial localization in the nucleus. After cell treatment and washing, full restoration of PD-L1 at the cell surface was observed after 5 days of culture in vitro. In vivo, INCB090244 reduced tumor growth in CD34+ humanized mice bearing MDA-MB-231 tumors, to similar levels as atezolizumab. Antitumor activity was completely abrogated in immunodeficient mice, confirming the pharmacologic dependency on a competent immune system. RNA sequencing analysis on tumors from these mice demonstrated similar T cell activation gene signatures as clinical checkpoint blockade antibodies. Biodistribution studies in mice bearing both subcutaneous and orthotopically implanted GL261 glioma tumors demonstrated higher accumulation of INCB090244 in tumor tissue compared to PD-L1 antibodies. Conclusions INCB090244 effectively disrupted the PD-L1/PD-1 interaction, induced dimerization and internalization of PD-L1, restored immunity in in vitro and in vivo tumor models, and is a suitable surrogate for the clinical candidate INCB086550. RNA sequencing demonstrated T cell activation signatures similar to those observed in patients receiving checkpoint blockade antibodies. Biodistribution studies demonstrated higher subcutaneous and brain tumor penetration by INCB090244 compared to PD-L1 antibodies, suggesting a potential advantage of small molecule PD-L1 inhibitors in accessing intratumoral regions. These data further support the clinical evaluation of small molecule PD-L1 inhibitors as an alternative approach to immune therapy.
Zoledronic Acid Induces the Proliferation of Human Cord Blood Gamma Delta T Cells Ex Vivo

Cord blood (CB) T cells are known to be naive cells, but can be activated to respond similar to adult peripheral blood (PB) T cells. Reports indicate that culture with aminobisphosphonate (NBP) stimulates CB gamma delta T cell proliferation ex vivo, specifically the TCRγ9δ2 subset, which has been extensively studied in PB gamma delta T cells. As CB gamma delta T cells are not well described, we compared CB gamma delta T cell proliferation, phenotype and genotype to PB gamma delta T cells when culturing cells with the NBP, Zometa (zoledronic acid), and IL-2. Fourteen days in culture resulted in significant fold increase in the proliferation of gamma delta T cells and in the percent of lymphocytes in both sample types. PB gamma delta T cells proliferated more robustly than CB with a 288.60 versus 21.32 fold increase, respectively. Additionally, in freshly isolated samples, CB gamma delta T cells comprised an average of 1.404% of the lymphocyte population, which was similar to PB gamma delta T cells, with an average of 2.319%. However, by day 14, PB gamma delta T cells increased to 70.15% of lymphocytes whereas CB gamma delta T cells increased to 12.49%. Phenotypically, both CB and PB had similar percent of CD45RA+ and CD45RO+ gamma delta T cell memory subsets in freshly isolated samples. Following culture, PB gamma delta T cells were mostly CD45RO+ memory cells, with significantly fewer CD45RA+ naive cells, whereas more CB gamma delta T cells were of the intermediate CD45RA+CD45RO+ subset. Further phenotypic analysis of the memory subsets indicated that cultured PB gamma delta T cells were either effector memory cells (CD27-CD45RA-) or central memory cells (CD27+CD45RA-), while CB gamma delta T cells were mostly naive (CD27+CD45RA+). The cytokines secreted by these cells were also assessed and the culture of PB and CB gamma delta T cells resulted in differing cytokine secretion profiles. After 14 days of culture, PB gamma delta T cells secreted more IFNγ and TNFα, while CB gamma delta T cells secreted more IL-10 and RANTES. We also examined TCRγ9 and TCRδ2 phenotypic expression and found that the TCRγ9δ2 was a common clone in freshly isolated PB gamma delta T cells, which predominated after 14 days in culture. However, while the TCRγ9δ2 variant was expressed in CB gamma delta T cells, it was low before and after culture, suggesting that Zometa may not stimulate gamma delta T cells in CB the same as PB. As limited TCRγδ phenotypic reagents are available, we developed a single cell PCR assay for genotypic analysis of the TCRγδ repertoire. PCR analysis suggests that the TCRγδ repertoire is diverse in both samples, yet TCRγ9δ2 is most prevalent. Further analysis of the variant subsets is warranted and may give insight into how each of these receptor pairings affects function. Disclosures No relevant conflicts of interest to declare.
Triple therapy for Helicobacter pylori infection: clinical observation of 36 cases.

Objective:To investigate the effets of amoxicillin-clavulanate potassium,clarithromycin and omeprazole-based triple therapy on Helicobacter pylori (Hp) infection. Methods: Treatment for the treatment group are: clarithromycin 10-15 mg/(kg·d) (divided into two postprandial dosages P.O.;amoxicillin-clavulanate potassium granules: for 3 to 7-year old patients,228.5 mg/time;for 7 to 14-year old patients,457 mg/time,postprandial oral,twice per day;omeprazole tablets: 10 mg/time,for 3 ~ 7-year old patients,once per day;for 7 to 14-year old patients,twice per day,fasting oral. Treatment for the control group are: amoxicillin-clavulanate potassium granules: for 3 to 7-year old patients,228.5 mg/time;for 7 to 14-year old patients,457 mg/time,postprandial oral,twice per day;colloidal bismuth subcitrate: 9 mgkg / (kg·d) (divided into three dosages). No other treatments were given for both the treatment group and the control group. After 14 days of treatment,gastroscopy were performed on each patients for Hp detection. Results: Hp eradication were shown in 30 cases (83.33%) of the treatment group and 24 cases (60%) of the control group,pain were relieved in 29 cases (80.56%) of the treatment group and 22 cases of the control group (55%) after 3 days of treatment (P0.05). Conclusion: Clarithromycin and amoxicillin-clavulanate potassium,omeprazole-based triple therapy is not only good for initial treatment but also for re-treatment of HP infection.
Microscopic model for heavy‐ion nonrelativistic collisions

A microscopic model for nuclear dynamics has been formulated and applied to the collisions between heavy ions. It may be viewed as an extension of the collisionless time-dependent Hartree–Fock (TDHF) method to include nucleon-nucleon collisions. The collision term is written in the form of a time relaxation. The relaxation time is obtained from separate calculations. Some results are shown for the collisions between two 16O nuclei. The computations require a storage of several million words and require a super-computer. Calculations have been done on the John von Neumann Center (JVNC) CYBER-205. Future calculations are planned on the JVNC ETA-10.
Single-Dose CpG Immunization Protects Against a Heterosubtypic Challenge and Generates Antigen-Specific Memory T Cells

Despite extensive research, influenza A virus (IAV) remains a major cause of morbidity, mortality, and healthcare expenditure. Emerging pandemics from highly pathogenic IAV strains such as H5N1 and pandemic H1N1 highlight the need for universal, cross-protective vaccines. Current vaccine formulations generate strain-specific neutralizing antibodies primarily against the outer coat proteins hemagglutinin and neuraminidase. In contrast to these highly mutable proteins, internal proteins of IAV are more conserved and are a favorable target for developing vaccines that induce strong T cell responses in addition to humoral immunity. Here, we found that intranasal administration with a single dose of CpG and inactivated x31 (H3N2) reduced viral titers and partially protected mice from a heterosubtypic challenge with a lethal dose of PR8 (H1N1). Early after immunization, vaccinated mice showed increased innate immune activation with high levels of MHCII and CD86 expression on dendritic cells in both the draining lymph nodes and lungs. Three days after immunization, CD4 and CD8 cells in the lung upregulated CD69, suggesting that activated lymphocytes are present at the site of vaccine administration. The ensuing effector Th1 responses were capable of producing multiple cytokines and were present at least 30 days after immunization. Furthermore, functional memory responses were observed, as antigen specific IFN-γ+ and GrB+ cells were detected early after lethal infection. Together, this work provides evidence for using pattern recognition receptor agonists as a mucosal vaccine platform for inducing robust T cell responses capable of protecting against heterologous IAV challenges.
The Utility of Strains of Morphological Group II Bacillus

Publisher Summary The chapter illustrates the utility of many of the morphological group II strains of Bacillus. In morphological group II, the endospore is centrally or subterminally located with the endospore seemingly swelling the cell, causing a spindle-like shape. The general considerations that establish the background for the chapter are examined. The bacteria/targets discussed in the chapter are presented in the order in which they were examined. After briefly examining the utility of the morphological group II strains of Bacillus according to target, the bacterial biology of the strains and their utility according to strain and species is discussed. In the following subsections, a brief introduction, the systematics of the specific strains, specifics of their fermentation process, and their biological events and effects are discussed. Two major components to be considered when examining a fermentation process are the bacterial candidate cultures being used and the process itself. The chapter consists of a more general discussion comparing the strains and species across the four species in terms of their fermentation processes, their “toxins,” and their potential for products. The chapter also discusses the utility of the morphological group II strains of Bacillus in terms of useful products and in terms of bacterial biology. However there has been a calamitous reduction by both industry and the federal funding agencies in support of the search for these new agents.
Stable expression of blood group H determinants and GDP-L-fucose:β-D-galactoside 2-α-L-fucosyltransferase in mouse cells after transfection with human DNA

Abstract We report here the application of a genetic approach to identify and isolate human DNA sequences controlling the expression of a GDP-L-fucose: beta-D-galactoside 2-alpha-L-fucosyltransferase [alpha-1,2)fucosyltransferase). Mouse L cells were chosen as host cells for this scheme since they express the necessary substrate and acceptor molecules for surface display of blood group H Fuc alpha 1----2 G al linkages constructed by (alpha-1,2) fucosyltransferases. However, they do not express cell surface blood group H structures nor detectable (alpha-1,2)fucosyltransferase activity. We therefore asked if (alpha-1,2)fucosyltransferase activity could be expressed and detected in these cells after transfection with human DNA sequences. These cells were transfected with genomic DNA isolated from a human cell line (A431) that expresses (alpha-1,2)fucosyltransferase. A panning procedure and fluorescence-activated cell sorting were used to isolate a mouse transfectant cell line that expresses cell surface H Fuc alpha 1----2 Gal linkages and a cognate (alpha-1,2)fucosyltransferase. Southern blot analysis showed that the genome of this cell line contains several hundred kilobase pairs of human DNA. Genomic DNA from this primary transfectant was used to transfect mouse L cells, and several independent, H-expressing secondary transfectants were isolated by immunological selection. Each expresses an (alpha-1,2)fucosyltransferase. Southern blot analysis demonstrated that the genome of each secondary transfectant contains common, characteristic human DNA restriction fragments. These results show that transfected human DNA sequences determine expression of the (alpha-1,2)fucosyltransferases in the mouse transfectants, that these sequences represent a single locus, and that they are within or linked to specific human restriction fragments identifiable in each secondary transfectant. These sequences may represent a human (alpha-1,2)fucosyltransferase gene.
V antigen of Yersinia pestis inhibits neutrophil chemotaxis

Abstract V antigen (V), a secreted protein encoded by the 70 kb low-calcium response plasmid of Yersinia pestis , is an essential virulence factor. In animal models, it inhibits the early host inflammatory response to infection which is associated with decreased blood and tissue levels of proinflammatory cytokine synthesis. To elucidate further the pathogenetic mechanism(s) of V, in vitro systems are needed to measure and analyse relevant functional activities of V. We studied the effect of V on the migration of neutrophils to a chemoattractant both in vivo and in vitro . Peripheral injection of V was associated with a reduction in the number of PMN migrating into s.c. sponges and i.p. exudates. Similarly, pre-incubating human peripheral blood neutrophils with ≥ng/ml V significantly inhibited the in vitro chemotactic response to the peptide chemoattractant FMLP. The inhibitory activity of V was inactivated by heat and was neutralized by rabbit polyclonal anti-V IgG as well as by sera from mice surviving infection with Y. pestis . Recombinant polyhistidine-tagged V fusion proteins retained biological activity compared to V proteins lacking the tag. Inhibition of chemotaxis appears to be the first demonstration of an in vitro biological effect of V and may be a useful model to elucidate its molecular mechanism of action.
Spreadable media: Creating value and meaning in a networked culture, by Henry Jenkins, Sam Ford, and Joshua Green

Review of Henry Jenkins, Sam Ford, and Joshua Green. Spreadable Media: Creating Value and Meaning in a Networked Culture. New York: NYU Press, 2013, $29.95 (352p) ISBN 978-0814743508.
Residual Gas Measurements in a Utility Engine

The residual gas fraction was measured in an air-cooled single-cylinder utility engine by directly sampling the trapped cylinder charge during a programmed misfire. Tests were performed for a range of fuel mixture preparation systems, cam timings, ignition timings, engine speeds and engine loads. The residual fraction was found to be relatively insensitive to the fuel mixture preparation system, but was, to a moderate degree, sensitive to the ignition timing. The residual fraction was found to be strongly affected by the amount of valve overlap and engine speed. The effects of engine speed and ignition timing were, in part, due to the in-cylinder conditions at EVO, with lower temperatures favoring higher residual fractions. The data were compared to existing literature models, all of which were found to be lacking. The effect of the threshold value used to define lift was investigated, and a modified form of the Yun and Mirsky correlation, which was relatively insensitive to lift threshold, was proposed.
State-wide information center for handicapped children

Reported is the experience of a 2 year pilot program established to provide information concerning available facilities for handicapped children in the Commonwealth of Massachusetts. A total of 697 inquiries were studied. The majority of the callers (52 per cent) were parents, and only 26 (3.7 per cent) physicians utilized the service. Calls were concerned mainly about home programs for the handicapped. Eighty-three per cent of the callers acted on the information, and 70 per cent had attempted to find the information elsewhere and were unsuccessful. A computerized national information center is the next logical step.
Effect of Alkali Metal Hydroxides on the Dissolution Behavior of a Zinc Phosphate Conversion Coating on Steel and Pertinence to Cathodic Delamination

Abstract Raman microprobe spectroscopy, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and wet chemical methods of analysis were successfully used to determine the effects of high-pH environments on zinc phosphate conversion coatings. The more rapid dissolution of phosphate ions from the phosphate coating was pH dependent. At a pH of 12.5, phosphate ions were more rapidly dissolved from the phosphate coating while at 11.5 and 13.5 pH, zinc ions were more rapidly dissolved from the coating. Raman spectra confirmed the more rapid dissolution of the phosphate ions was a result of zinc oxide formation on the surface of the original phosphate conversion coating. The cation of the alkaline environment also proved to be an important factor in the dissolution of the phosphate conversion coating. Sodium hydroxide dissolved the phosphate coating at the greatest rate followed by hydroxides of potassium, cesium, and lithium. This cation dependence was related to the number of precipitation ...