In this paper, a unified approach to speech enhancement, feature extraction and feature normalization for speech recognition in adverse recording conditions is presented. The proposed frontend system consists of several different, independent, processing modules. Each of the algorithms contained in these modules has been independently applied to the problem of speech recognition in noise, significantly improving the recognition rates. In this work, these algorithms are merged in a single front-end and their combined performance is demonstrated. Specifically, the proposed advanced front-end extracts noise-invariant features via the following modules: Wiener filtering, voice-activity detection, robust feature extraction (nonlinear modulation or fractal features), parameter equalization and frame-dropping. The advanced front-end is applied to extremely adverse environments where most feature extraction schemes fail. We show that by combining speech enhancement, robust feature extraction and feature normalization up to a fivefold error rate reduction can be achieved for certain tasks. Index Terms: Speech Recognition, Nonlinear Features, Parameter Equalization, Noise Suppression, Noise Invariant Features


Progesterone (P4) is of paramount importance in the establishment and maintenance of pregnancy for mammals. Progesterone stimulates the endometrial secretion of several molecules involved in conceptus growth and development during the peri-implantation period. Indeed, several studies involving ruminants have reported that exogenous P4 supplementation is related to increased early embryo development, higher levels of interferon tau, and improved pregnancy rate. However, there is a lack of information about P4 supplementation during early pregnancy regarding swine embryonic development. Additionally, some of the few studies involving pigs have shown an impaired pregnancy rate when supplementation was performed before Day 6 of pregnancy. Thus, the objective of this study was to evaluate the effects of progesterone/progestin supplementation from Day 6 of pregnancy on total number of embryos (TE), pregnancy rate (PR), embryo development, and maternal serum 17β-oestradiol concentration (17β-E). A total of 31 crossbred, 2 to 6 parity sows were used. All sows were inseminated every 24h through the first oestrus following a 21-day lactation, and ovulation was detected by transrectal real-time ultrasound to determine Day 0 of pregnancy. On Day 6 of pregnancy, animals were randomly allocated to one of the following groups: CON (n=11), non-supplemented sows; RU (n=11), sows supplemented daily with 20mg of Altrenogest-Regumate® from Day 6 to 12 of pregnancy; and PG (n=9), sows supplemented with 2.15 mg/kg of long-acting P4 IM on Day 6 of pregnancy. Sows were treated with altrenogest p.o. as a top dressing over a small portion of feed. Blood samples were collected from 12 sows (4 per group) on Day 12 of pregnancy to measure the level of plasma 17β-E by radioimmunoassay. Sows were slaughtered on Day 28 of pregnancy. The uterus from each sow was collected and embryos were counted to determine TE. Embryos were individually separated from their placentas, weighed, and crown-to-rump length was determined. Data were analysed by the SAS program. All variables were analysed by PROC-MIXED t-test. Statistical difference was considered when P<0.05. The PR did not differ among groups (91, 90, and 88%, for CON, RU, and PG, respectively; P>0.05). No difference was observed among groups for TE and 17β-E level (P>0.05). However, embryonic weight and crown-to-rump length differed among the 3 groups (P<0.001). The RU-treated sows had heavier and bigger embryos when compared with the other groups. In contrast, PG-treated sows had the lowest averages for the same variables (weight: 1.39±0.01, 1.46±0.02, and 1.22±0.01; crown-to-rump: 21.07±0.08, 21.61±0.11, and 20.66±0.11; for CON, RU, and PG, respectively). In conclusion, altrenogest supplementation from Day 6 to 12 of pregnancy increases size and weight of porcine embryos, whereas 2.15mg kg−1 of long-acting P4 on Day 6 of pregnancy decreased these variables when compared with non-supplemented sows.
Research was supported by FAPESP Grant 2017/00290-0.


Objective: To assess the understanding and cultural acceptability of the United States Phar-macopeia Dispensing Information (USP-DI) in a group of elderly Brazilians. Methods: The study participants were individuals between 60 and 90 years old, of both sexes, with different levels of education and income. Fifteen of 81 pictograms from the USP-DI were presented to the elderly subjects, individually, without subtitles and in random order, so that the participants' understanding of the pictograms could be evaluated. Results: The study included 116 participants. Only one of the selected pictograms reached the comprehension criterion established by the International Organization for Standardization 3864. With regard to the relationship between understanding and sociodemographic characteristics, age, wage income, and level of education were all found to be significantly associated with participants' understanding of some of the pictograms. Conclusion: Most of the USP-DI pictograms evaluated were not well understood by the elderly Brazilians. This finding indicates that such pictograms need to be culturally adapted for the Brazilian context if they are to serve their purpose effectively in this country.


Translating idioms is an indispensable part of human life which involves language, thought and action. This study aims to investigate the problems encountered by EFL students in translating English idioms into Arabic or vice versa and set up some solutions. The study hypothesizes that university students are unable to translate idioms from English to Arabic and vice versa. To fulfil this study, the descriptive-analytic method is used and to be followed. A questionnaire is used as data collection instruments. The sample of the study consisted of (20) students from the third and fourth school year at Onaizah Colleges, Qassim, K.S.A. The study found that the differences in the average of the consensus are in favour of the variables that translating idioms is a problematic area for Saudi EFL students. Likewise, EFL students are confused in translating idioms from English to Arabic and vice versa due to poor vocabulary and fixed idiomatic expressions. Moreover, EFL students translate the idioms from English to Arabic and vice versa literally. The study recommends that EFL students should be exposed to a variety of vocabulary, fixed and idiomatic expression in translation tasks. Also, they must be aware of the cultural differences in translation idioms. The study further recommends that deploying fixed and idiomatic expressions in schools' and colleges' aisles could benefit the students in translation.


A general framework is presented which unifies the treatment of wavelet-like, quasidistribution and tomographic transforms. Explicit formulae relating the three types of transforms are obtained. The case of transforms associated with the symplectic and affine groups is treated in some detail. Special emphasis is given to the properties of the scale–time and scale–frequency tomograms. Tomograms are interpreted as a tool to sample the signal space by a family of curves or as the matrix element of a projector.


Delivery of endocytosed macromolecules to lysosomes occurs by means of direct fusion of late endosomes with lysosomes. This has been formally demonstrated in a cell-free content mixing assay using late endosomes and lysosomes from rat liver. There is evidence from electron microscopy studies that the same process occurs in intact cells. The fusion process results in the formation of hybrid organelles from which lysosomes are re-formed. The discovery of the hybrid organelle has opened up three areas of investigation: (i) the mechanism of direct fusion of late endosomes and lysosomes, (ii) the mechanism of re-formation of lysosomes from the hybrid organelle, and (iii) the function of the hybrid organelle. Fusion has analogies with homotypic vacuole fusion in yeast. It requires syntaxin 7 as part of the functional trans-SNARE [SNAP receptor, where SNAP is soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein] complex and the release of lumenal calcium to achieve membrane fusion. Re-formation of lysosomes from the hybrid organelle occurs by a maturation process involving condensation of lumenal content and probably removal of some membrane proteins by vesicular traffic. Lysosomes may thus be regarded as a type of secretory granule, storing acid hydrolases in between fusion events with late endosomes. The hybrid organelle is predicted to function as a 'cell stomach', acting as a major site of hydrolysis of endocytosed macromolecules.


Traditional histological tissue‐based diagnostics have been slow and often require large numbers of sections to interrogate for several different proteins with immunohistochemical stains. Often, due to small biopsy size, there is not sufficient material available to carry out all the desired tests on a patient sample. Mass Spectrometry Imaging (MSI) enables the simultaneous detection of hundreds to thousands of analytes from a single tissue section. In recent years, great strides have been made to standardize MSI workflows and data analysis to make it an accessible tool for clinicians to use in patient diagnoses. This commentary highlights the advances by Janßen et al. toward this goal that are discussed in this issue (Proteomics Clin Appl., https://doi.org/10.1002/prca.202100068).


The reliance of world energy consumption on fossil fuels has produced several major environmental and geopolitical concerns leading to considerable backing for expanding the contribution from of renewable sources of energy. The UK government's target of generating 10% of electricity from renewable resources by 2010, their emphasis on the critical importance of participation at the local level and Portsmouth City Council's currently limited progress, present the overall aim of investigating the potential for individual participation in order to expand renewable energy in Portsmouth. The theoretical context for the study is set within concepts of public understanding and action on environmental issues within a local to global context. A review of the trends and methods used in studies on renewable energy and the public opinion produced the specific objectives of determining the influences from awareness and attitudes of renewable energy, environmental concerns and socio-demographic factors on the willingness to participate in green tariff schemes or micro-renewable home installation. Data was collected by a questionnaire was carried out in two locations in Portsmouth using an extensive predominately quantitative approach. Chi-square and qualitative theme building analysis of results revealed that renewable resource types, age and housing tenure affected participation, while environmental concerns and a lack of knowledge were the most frequently cited incentive and barrier respectively for micro-generation. The lack of impacts from environmental concern reinforces the inconsistencies found in predicting environmental action. Support for renewable energy in Portsmouth is consistent with other regional UK studies and the levels of stated participation are comparatively higher than results found in London. It was concluded that although there is potential for individual contribution towards expansion of renewable energy in Portsmouth, awareness needs to be increased with recommendation of using the effect of demonstration via the use of solar panels.


Diverse plasticity mechanisms are orchestrated to shape the spatiotemporal dynamics underlying brain functions. However, why these plasticity rules emerge and how their dynamics interact with neural activity to give rise to complex neural circuit dynamics remains largely unknown. Here we show that both Hebbian and homeostatic plasticity rules emerge from a functional perspective of neuronal dynamics whereby each neuron learns to encode its own activity in the population activity, so that the activity of the presynaptic neuron can be decoded from the activity of its postsynaptic neurons. We explain how a range of experimentally observed plasticity phenomena with widely separated time scales emerge from learning this encoding function, including STDP and its frequency dependence, and metaplasticity. We show that when implemented in neural circuits, these plasticity rules naturally give rise to essential neural response properties, including variable neural dynamics with balanced excitation and inhibition, and approximately log-normal distributions of synaptic strengths, while simultaneously encoding a complex real-world visual stimulus. These findings establish a novel function-based account of diverse plasticity mechanisms, providing a unifying framework relating plasticity, dynamics and neural computation.


The growth of the United Auto Workers in Canada dramatically improved the lives of thousands of workers. Not only did it achieve impressive bargaining gains, but the UAW was regarded as one of the most democratic and socially progressive of the major industrial unions in North America. However, workers in the automotive sector, who constituted the largest segment of the UAW membership, witnessed blatant gender inequalities. From 1937 to 1979, UAW leaders did little to challenge these inequalities. Both the union and the workplace remained highly masculine settings in which male workers and bosses played out the gender politics of the times. Pamela Sugiman draws on archival materials and in-depth interviews with workers and union representatives to explore the ways in which the small groups of women in southern Ontario auto plants fought for dignity, respect, and rights within this restrictive context. During the Second World War, women auto workers formed close bonds with one another - bonds that rested largely around their identification as a sex. By the late 1960s, they were drawing on a growing union consciousness, the modern women's movement, and their gender identity, to launch an organized collective struggle for sexual equality. In describing the women's experiences, Sugiman employs the concept of a 'gendered strategy.' A gendered strategy incorporates both reasoned decisions and emotional responses, calculated interests and compromises. Within a context of gender and class divisions, workers developed strategies of coping, resistance, and control. Labour's Dilemma reveals how people may be simultaneously agents and victims, compliant and resistant.


The Australian social security system has undergone a major transformation in the last decade. "Social Security Law and Policy," published by Federation Press in 2006, provides a thorough discussion of legislation and case law, and sets out the legal principles and concepts, which underpin recent welfare reforms. This book reviews the history and transformation of the welfare state, ideas about the nature of poverty, and the policy changes that need to be made. Detailed case studies examine current welfare issues and consider the changes affecting key groups including: • the replacement of passive unemployment benefits with requirements to "actively seek work" and completion of "activity tests;" • the expectation for sole parents, and the ill and the disabled to join the workforce; • the increasingly grey area between work and retirement for our ageing population; • the changing nature of access to family payments for children which is now largely governed by the taxation system; and • the workings of income and means tests.


Background: Hyaluronic acid (HA) is the most common intra-articular therapy used to treat mild to moderate osteoarthritis (OA). However, the mechanism involved in this treatment is still not fully understood. The aim of the present study was to examine the effect and the possible mechanism of intra-articular HA (IAHA) injection in patients with knee osteoarthritis (OA).Methods: Twenty-eight patients with Kellgren–Lawrence scale II to III were enrolled in this study. All patients underwent ultrasound-guided injection using three consecutive weekly IAHA. Functional ability and pain were determined by the Western Ontario and McMaster University Index (WOMAC) questionnaire and visual analog scale (VAS). Further, the levels of HA, metalloproteinase (MMP)-1, MMP-3, MMP-13, interleukin (IL)-1β and IL-6 in synovial fluid were determined weekly before HA injection. Results: Functional improvement and pain relief were observed 4 weeks after treatment. At week 4, a significant increase of HA concentration was found, and the concentration of inflammatory cytokines including IL-1β, and IL-6, as well as matrix MMP-3 and MMP-13 significantly decreased. However, no significant difference was observed in MMP-1 level. Conclusion: These results suggest that increasing HA accumulation in synovial fluid may be associated with disease relief after weekly IAHA injection in patients with knee OA.


Background: Although approximately 20% of adults are eligible, adult cancer clinical trial (CCT) accrual in the U.S. lingers around 3%. Participation rates are significantly lower among racial/ethnic minorities and the medically underserved, who are likely to have poorer outcomes than the larger population. CCT participation is increasingly a concern of healthy equity and social justice among racial/ethnic minorities. This study proposes a promising strategy for engaging physician-oncologists and communities to stream-line CCT awareness, access and accrual of racial/ethnic minorities. Methods: Study recruited 40 community and academic-research institutions to provide CCT education days at a local, pre-dominantly African American mega-church, (N = 253) participants, during one-year. There was pre/post-testing of general clinical trial knowledge each-day. Education included a 3-patient panel-discussion of their trial experiences. Four physician-oncologists provided expertise on the significance of minority representation in CCTs. The physician-oncologists discussed the types of CCTs that were locally available for specific-types of cancer. Anticipated outcome was provision of recruitment opportunity of potentially-eligible participants while addressing any gaps in CCT knowledge. Results: The (N = 253) participants: (75%) African American, (13%) Hispanic/Latino, (2%) American Indian/Alaskan Native, (6%) Asian, and (2%) Hawaiian/Pacific Islander. Pre-survey (N = 104) included: How much do you know about clinical research?; a lot (23%), general sense (51%), very-little (21%), never heard of it, (3%). Thirty-eight percent were past participants in some type of trial. Post survey (N = 171), participants indicated: would very likely(51%) and somewhat likely(41%) participate in a CCT if invited by doctor. An additional (3%) were somewhat-unlikely or very-unlikely (6%) to participate in CCT if invited by doctor. Post-survey, most-notable reasons for lack of participation: never invited (28.5%); lack of information (16.5%); didn9t know who to talk to about trials (6.5%); worried about my rights (1%); hassle of participation (2%); insurance (2%); worried about health risk (6.5%); other (6.5%); no reply (30.5%). Conclusions: Physician-engagement in direct community CCT recruitment strategies demonstrates a hopeful mechanism for reaching diverse, interested, potentially-eligible cancer subjects, in a culturally-appropriate and timely manner. Citation Format: Jameisha B. Brown. Physician-engagement in cancer clinical trial recruitment: Leveraging partnerships among community-academic research institutions for direct accrual of racial/ethnic minorities and the medically underserved. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-142.


We systematically review the literature linking health to economic activity, particularly education and labor market outcomes, over the lifecycle. In the first part, we review studies that link childhood health to later-life outcomes. The main themes we focus on are in-utero exposures, birthweight, physical health and nutrition, mental health, and the environment. In the second part, we review studies of the impact of health on labor market success for adults. The main themes we focus on are the environment, disability, physical health shocks, within-household spillovers, cancer, and mental health.


In a context of growing attention to the benefits of the arts in peacebuilding, this article reports on the findings of a small scoping study that aimed to identify how the arts are perceived and supported by international development agencies. Based on a 2012 analysis of five international aid agencies working in the South East Asia and Pacific region, the study found that arts and creative practices are not, as yet, afforded a significant role in current policy or strategy, although arts activity is recognised as a social development tool by agencies working in partnership with local organisations. Resulting from an analysis of participating agencies' publicly available documentation, and interviews with staff, arts practitioners and volunteers working in field-based arts projects, this article argues that the value of arts-based interventions in peacebuilding and development is yet to be fully realised. Bringing field experience as well as policy and research backgrounds to the analysis, the authors consider why this might be the case and pose broader questions about the communication, role and influence of evaluation as one factor in this. They argue for a better acknowledgment of the diverse applications and implications of the "use" of the arts within complex social, political, and cultural systems by linking this call with evaluation methodologies that may better reveal the ways in which such projects "raise possibilities" rather than "confirm probabilities." This article suggests a four-question schema for augmenting the documentation and evaluation of arts-based work to more authentically capture "the good" that may arise from the emergent nature of artmaking itself. Abstract In a context of growing attention to the benefits of the arts in peacebuilding, this article reports on the findings of a small scoping study that aimed to identify how the arts are perceived and supported by international development agencies. Based on a 2012 analysis of five international aid agencies working in the South East Asia and Pacific region, the study found that arts and creative practices are not, as yet, afforded a significant role in current policy or strategy, although arts activity is recognised as a social development tool by agencies working in partnership with local organisations. Resulting from an analysis of participating agencies' publicly available documentation, and interviews with staff, arts practitioners and volunteers working in field-based arts projects, this article argues that the value of arts-based interventions in peacebuilding and development is yet to be fully realised. Bringing field experience as well as policy and research backgrounds to the analysis, the authors consider why this might be the case and pose broader questions about the communication, role and influence of evaluation as one factor in this. They argue for a better acknowledgment of the diverse applications and implications of the "use" of the arts within complex social, political, and cultural systems by linking this call with evaluation methodologies that may better reveal the ways in which such projects "raise possibilities" rather than "confirm probabilities." This article suggests a four-question schema for augmenting the documentation and evaluation of arts-based work to more authentically capture "the good" that may arise from the emergent nature of artmaking itself.


Mesenchymal stem cells (MSCs) represent a valuable cell source in regenerative medicine, and large numbers of MSCs can be isolated from the amnion noninvasively. Sclerosing cholangitis is a chronic cholestatic disease and characterized by progressive biliary destruction leading to cirrhosis. Many factors are involved in the development of sclerosing cholangitis; however, effective medical therapy is not established. We investigated the effects of human amnion-derived MSCs (hAMSCs) and conditioned medium (CM) obtained from hAMSC cultures in rats with sclerosing cholangitis. Sclerosing cholangitis was induced via the intragastric administration of 100 mg/kg alpha-naphthylisothiocyanate (ANIT) twice weekly for 4 weeks. One million hAMSCs or 200 μL of CM were intravenously administered on days 15 and 22. Rats were sacrificed on day 29 and evaluated via histological, immunohistochemical, and mRNA expression analyses. hAMSC transplantation and CM administration significantly improved the histological score. In addition, these two interventions significantly improved biliary hyperplasia, peribiliary fibrosis, and inflammation in Glisson's sheath. Accordingly, CK19, MMP-9, and TNF-α, and MCP-1 expression in the liver was also decreased by hAMSC and CM administration. In conclusion, hAMSC and CM administration ameliorated biliary hyperplasia, peribiliary fibrosis, and inflammation in a rat model of sclerosing cholangitis. hAMSCs and CM may represent new modalities for treating sclerosing cholangitis.


Objective We assessed whether in-depth messaging delivered via a smoking cessation quitline results in participants: (1) speaking to their physician, or (2) insurance company regarding lung cancer screening (LCS). MethodsEligible participants lived in New York State and met the United States Preventive Services Task Force eligibility criteria for LCS (N = 1000). A randomized trial was conducted among New York State Smokers' Quitline participants to assess the impact of a brochure containing information on risks, benefits, and costs associated with LCS (control group) versus the brochure supplemented with phone-based in-depth messaging (treatment group). ResultsAfter a 4-month telephone survey (N = 431), associations between the study groups were examined for: (1) speaking with a physician regarding LCS, and (2) speaking with an insurance company about LCS coverage. Multivariate logistic regression models adjusted for demographics, insurance status, emphysema/COPD, and past 30-day cigarette use found no significant associations. However, sensitivity analyses among control participants found significant associations, including for speaking with a physician (p < .05) by receipt of the study brochure. Analyses repeated in the treatment group also had statistically significant findings emerge, including for speaking with insurance company (p < .05). ConclusionsThe educational brochure may be an effective and low-cost way to deliver information about LCS.


Background: Altered white matter connectivity, as evidenced by pervasive microstructural changes in myelination and axonal integrity in neuroimaging studies, has been implicated in the development of autism spectrum disorder (ASD) and related neurodevelopmental conditions such as schizophrenia. Despite an increasing appreciation that such white matter disconnectivity is linked to social behavior deficits, virtually no etiologically meaningful myelin-related genes have been identified in oligodendrocytes, the key myelinating cells in the CNS, to furnish an account on the causes. The impact of neurodevelopmental perturbations during pregnancy such as maternal immune activation (MIA) on these genes in memory-related neural networks has not been experimentally scrutinized. Methods: In this study, a mouse model of MIA by the viral dsRNA analog poly(I:C) was employed to mimic the effects of inflammation during pregnancy. Transcriptional expression levels of selected myelin- or oligodendroglia-related genes implicated in schizophrenia or ASD development were analyzed by in situ hybridization (ISH) and quantitative real-time PCR (qRT-PCR) with brain samples from MIA and control groups. The analysis focused on SOX-10 (SRY-related HMG-box 10), MAG (myelin-associated glycoprotein), and Tf (transferrin) expression in the hippocampus and the surrounding memory-related cortical regions in either hemisphere. Results: Specifically, ISH reveals that in the brain of prenatal poly(I:C)-exposed mouse offspring in the MIA model (gestation day 9), mRNA expression of the genes SOX10, MAG and Tf were generally reduced in the limbic system including the hippocampus, retrosplenial cortex and parahippocampal gyrus on either side of the hemispheres. qRT-PCR further confirms the reduction of SOX10, MAG, and Tf expression in the medial prefrontal cortex, sensory cortex, amygdala, and hippocampus. Conclusions: Our present results provide direct evidence that prenatal exposure to poly(I:C) elicits profound and long-term changes in transcript level and spatial distribution of myelin-related genes in multiple neocortical and limbic regions, notably the hippocampus and its surrounding memory-related neural networks. Our work demonstrates the potential utility of oligodendroglia-related genes as biomarkers for modeling neurodevelopmental disorders, in agreement with the hypothesis that MIA during pregnancy could lead to compromised white matter connectivity in ASD.


The importance of the ubiquitin-proteasome pathway to cellular function has brought it to the forefront in the search for new anticancer therapies. The ubiquitin-proteasome pathway has proven promising in targeting various human cancers. The approval of the proteasome inhibitor bortezomib for clinical treatment of relapsed/refractory multiple myeloma and mantle cell lymphoma has validated the ubiquitin-proteasome as a rational target. Bortezomib has shown positive results in clinical use but some toxicity and side effects, as well as resistance, have been observed, indicating that further development of novel, less toxic drugs is necessary. Because less toxic drugs are necessary and drug development can be expensive and time-consuming, using existing drugs that can target the ubiquitin-proteasome pathway in new applications, such as cancer therapy, may be effective in expediting the regulatory process and bringing new drugs to the clinic. Toward this goal, previously approved drugs, such as disulfiram, as well as natural compounds found in common foods, such as green tea polyphenol (-)-EGCG and the flavonoid apigenin, have been investigated for their possible proteasome inhibitory and cell death inducing abilities. These compounds proved quite promising in preclinical studies and have now moved into clinical trials, with preliminary results that are encouraging. In addition to targeting the catalytic activity of the proteasome pathway, upstream regulators, such as the 19S regulatory cap, as well as E1, E2, and E3, are now being investigated as potential drug targets. This review outlines the development of novel proteasome inhibitors from preclinical to clinical studies, highlighting their abilities to inhibit the tumor proteasome and induce apoptosis in several human cancers.


Site- and season-specific regressions of particulates less than 10 mu in diameter (PM10) on total suspended particulates (TSPs) were formed throughout California during years when both were monitored. The regressions were then applied to monitored TSPs for the years 1973 to 1987, and indirect estimates of PM10 were formed. These estimates of PM10 were validated by interpolating them to other monitoring stations. The split-halves correlation between the estimated and monitored mean concentrations, obtained when both were first cumulated for a 2-y period, was .86. Indirect estimates of PM10 at monitoring stations were interpolated, by month, to zip code centroids of home and work location and were cumulated for a cohort of 3,914 California Seventh-day Adventist (SDA) nonsmokers. Multivariate analyses, adjusted for several covariates, showed statistically significant (p < .05), but small, positive associations between PM10 and development of (a) definite symptoms of overall airway obstructive disease, (b) chronic productive cough, and (c) increased severity of airway obstructive disease and asthma. The relative risk (RR) associated with 1,000 h/y (42 d) exposure to concentrations of PM10 that exceeded 100 micrograms/m3 for development of airway obstructive disease was 1.17 (95% confidence interval [CI]: 1.02, 1.33); for development of productive cough, the RR was 1.21 (CI 1.02, 1.44); and for development of asthma, the RR was 1.30 (CI, 0.97, 1.73). Stronger associations were observed for those who were exposed occupationally to dusts and fumes. The RR of developing airway obstructive disease as an adult for those who had airway obstructive disease as a child was 1.66 (CI 1.15, 2.33).


For years, Substance Abuse has annually published a communication regarding the annual conference of the International Society of Addiction Medicine (ISAM). These pieces have highlighted the important events of the conference and the work of the organization, as reflected in part by selected abstracts from the conference. This editorial communicates the events of the 2020 conference, the third to be held in conjunction with the Canadian Society of Addiction Medicine (CSAM) and the first virtual conference. The conference was attended by over 800 participants and covered a wide range of topics, including addiction medicine during the COVID-19 pandemic. Despite the challenges of not being able to meet physically in Victoria, British Columbia as had been planned, the virtual event provided an opportunity to share current information in order to help advance prevention, treatment, policy and public helath efforts relating to addressing addictions and helping those impacted by these often devastating conditions.


Background. The aim of the study was to correlate clinical factors (disease‐free interval/survival) with growth pattern in terms of structural entropy of patients with primary colorectal carcinomas and secondary lung lesions. Methods. Proliferation and apoptosis markers as well as determinants involved in information transfer by protein‐carbohydrate interactions were monitored. The clinical history, surgical and histopathological reports, tumor load, survival of the patients with a maximum follow‐up of 14 years, and sections of paraffin blocks of 60 colorectal carcinoma specimens and their pulmonary metastases were examined. Measurements of the staining intensities after processing sections of primary and secondary carcinomas with the marker panel and calculations of syntactic structure and stereological parameters were performed. Results. The majority of primary tumors (80%, 49/60) were surgically treated at advanced tumor stages (pT3/pT4), with detectable lymph node involvement (34/60). Lung metastases were resected after a median disease‐free interval of 30.5 months, an average of 3.0 metastases adding up to a mean intrapulmonary tumor load of 9.98 ccm. The median survival was calculated to be 82 months after resection of the colon/rectal carcinomas and 40 months after that of intrapulmonary metastases. It was correlated with certain structural and vascular features such as vascular circumference. The proliferation index and several textural features were strongly associated with vascularization in primary and secondary tumors. Conclusions. Despite intra‐ and interindividual variations, vascularization properties and features such as bcl‐2 positivity and CEA‐ and galectin‐3‐associated structural entropy in primary tumors or metastases are described as independent prognostic features. Absence of lymph node involvement or limited tumor stages of colon/rectal carcinomas should not exclude patients from thorough postsurgical scrutiny to detect lung metastases.


We argue that operads provide a general framework for dealing with
polynomials and combinatory completeness of combinatory algebras, including the
classical $\mathbf{SK}$-algebras, linear $\mathbf{BCI}$-algebras, planar
$\mathbf{BI}(\_)^\bullet$-algebras as well as the braided $\mathbf{BC^\pm
I}$-algebras. We show that every extensional combinatory algebra gives rise to
a canonical closed operad, which we shall call the internal operad of the
combinatory algebra. The internal operad construction gives a left adjoint to
the forgetful functor from closed operads to extensional combinatory algebras.
As a by-product, we derive extensionality axioms for the classes of combinatory
algebras mentioned above.


Abstract This paper explores the role of co-presence in the emergence of collectives with reference to corporeal communication in online conferences and seminars. It emphasizes the importance of feelings of togetherness and demarcates them from feelings of mere affiliation. The emergence of shared feelings depends on corporeal communication, and specifically on the solidary form of corporeal communication as opposed to its antagonistic counterpart. Under online conditions, both forms tend to generate illusions, since a genuine exchange of glances, which opens up corporeal communication in the first place, is not possible. The missing exchange of glances must therefore be compensated online by imagination and the concentration on linguistic meanings.


Dietary T-2 toxin (0, 1, 2, 4, 8, and 16 mug./g.) was fed to 4 groups of 10 chickens at each treatment level from hatching until 3 weeks of age. Growth inhibitory levels (4, 8, and 16 mug./g.) caused abnormal feathering which appeared dose related. The chickens were sparsely covered with short feathers protruding at odd angles in comparison to controls. There were few feathers on the base of the neck, on the anterior dorsal surface of the wing, and on the side and back adjacent to the tail. Feather tips frequently were constricted and bent downward while the quill could have a reverse curve. A literature survey suggests that T-2 toxin may cause this effect through a nutritional imbalance.


My career developed very differently from those of most academic researchers. After school I worked for six years in industries that employed yeast to manufacture ethanol and beer. At university I was trained as a microbiologist with very little training in molecular biology. I retrained in 1987 in molecular yeast genetics and focused on genetic engineering of industrial yeasts to minimise the production of spoilage compounds in wine and ethyl carbamate, a carcinogen, in wine. The malolactic yeast ML01 and the urea-degrading yeast were the first genetically enhanced yeasts that obtained US FDA approval for commercial applications. Apart from applied research, I was fascinated by classic molecular yeast genetic studies using sophisticated techniques such as transcriptomics, proteomics, and metabolomics. Doing research at the University of British Columbia was stimulating and exciting, we established a core microarray and metabolomics facilities that were used by many scientists at UBC and hospitals in Vancouver. I also established a state-of-the-art Wine Library that was used to study aging of wines produced in British Columbia. Finally, I have been fortunate to know and collaborate with leading yeast scientists who motivated me.


The macroeconomic effects of capital account liberalization in Korea are examined. Simple data analysis suggests that capital account liberalization substantially changed the nature and composition of capital flows. Based on the VAR model, the authors find the following stylized facts. First, after capital market liberalization, capital flows become less driven by current account imbalances and therefore become more autonomous. Second, capital account liberalization significantly changes the effects of capital flows on macroeconomic variables. Third, capital account liberalization is highly related to consumption and investment booms, and subsequent appreciation of nominal and real exchange rates, which leads to the current account worsening. Finally, there is strong evidence of sterilized foreign exchange market intervention in response to capital inflows.


The entry of an antibiotic into phagocytes is a prerequisite for its intracellular bioactivity against susceptible facultative or obligatory intracellular microorganisms. AF 3013 is a new fluoroquinolone, and its uptake into and elimination from mouse peritoneal macrophages, together with its effects on phagocytic and antimicrobial mechanisms against Klebsiella pneumoniae, were investigated. AF 3013 efficiently penetrated into phagocytic cells at all concentrations tested. The uptake proceeded rapidly and was energy independent, since it was not affected by cell viability, environmental temperature or the addition of a metabolic inhibitor. Therefore, a possible passive transmembrane diffusion mechanism might be proposed. The elution of AF 3013 from macrophages occurred relatively slowly; in fact, 60 min after the removal of extracellular AF 3013, nearly 40% of the drug still remained in the phagocytes. Exposure to 1 MIC of AF 3013 significantly enhanced macrophages phagocytosis and increased intracellular bactericidal activity against K. pneumoniae. Following preexposure of macrophages to 1 MIC of AF 3013, there was a significant increase in both phagocytosis and killing, compared with the controls, indicating the ability of AF 3013 to interact with biological membranes and remain active within phagocytes. Preexposure of Klebsiella to AF 3013 made the bacteria more susceptible to the bactericidal mechanisms of macrophages than untreated organisms.


Objectives Although there are increasing data suggesting that patients could get survival advantage from the recanalising procedure of coronary chronic total occlusion (CTO) as compared with optimal medical treatment (OMT) alone, it still remains unclear whether diabetic patients could get similar benefits from this procedure. Methods A total of 239 diabetic patients with CTO who underwent percutaneous coronary intervention (PCI group, n = 97) or OMT alone (OMT group, n = 142) from Jan 2004 to Dec 2010 were enrolled into this study. All patients received OMT as per existing guidelines. Various clinical outcomes at 2 years were compared between the two groups. Results The baseline clinical characteristics didn't differ significantly between the two groups. But, OMT group had a higher rate of multi-vessel disease as compared with PCI group (84.5% vs. 43.2%, P < 0.001). Two-year clinical outcomes showed that PCI group had significantly lower rates of all cause death and major adverse cardiac events (composite of all cause death, myocardial infarction and revascularisation) as compared with OMT alone group. However, multivariable logistic analysis revealed that OMT alone (vs. PCI) was not an independent predictor for all cause death [odds ratio (OR) 2.35, confidential interval (CI) 0.44-12.4, P = 0.314) or MACE (OR 1.99, CI 0.85-4.64, P = 0.110). Conclusions The current data failed to show significant advantages of recanalising coronary CTO over OMT alone in diabetic patients, suggesting this aggressive recanlisation might be a thankless job in this subset of patients.


Sensitivity degradation trend is analyzed for ASTER: Advanced Spaceborne Thermal Emission and Reflection radiometer/Visible and Near-Infrared Radiometer: VNIR onboard Terra satellite. Fault Tree Analysis is made for sensitivity degradation. Firstly, it is confirmed that the VNIR detectors are stable enough through dark current and shot noise behavior analysis. Then it is also confirmed that radiance of calibration lamp equipped VNIR is stable enough through lamp monitor of photodiode output data analysis. It is confirmed that radiance at the front of VNIR optics is, on the other hand, degraded in conjunction with sensitivity degradation of VNIR through an analysis of another photodiode output data which is equipped at the front of VNIR optics, photodiode output is scale-off at around one year after the launch though. VNIR optics transparency might not be so degraded due to the fact that VNIR output and the later photodiode output show almost same degradations. Consequently, it may say that one of possible causes of VNIR sensitivity degradation is thruster plume.


Behavior prediction based on historical behavioral data have practical real-world significance. It has been applied in recommendation, predicting academic performance, etc. With the refinement of user data description, the development of new functions, and the fusion of multiple data sources, heterogeneous behavioral data which contain multiple types of behaviors become more and more common. In this paper, we aim to incorporate heterogeneous user behaviors and social influences for behavior predictions. To this end, this paper proposes a variant of Long-Short Term Memory (LSTM) which can consider context information while modeling a behavior sequence, a projection mechanism which can model multi-faceted relationships among different types of behaviors, and a multi-faceted attention mechanism which can dynamically find out informative periods from different facets. Many kinds of behavioral data belong to spatio-temporal data. An unsupervised way to construct a social behavior graph based on spatio-temporal data and to model social influences is proposed. Moreover, a residual learning-based decoder is designed to automatically construct multiple high-order cross features based on social behavior representation and other types of behavior representations. Qualitative and quantitative experiments on real-world datasets have demonstrated the effectiveness of this model.


BACKGROUND: Inhalation injury increases morbidity and mortality in burn patients. Patients with inhalation injury present with large differences between end-tidal CO2 pressure and PaCO2, an indirect measure of dead space. We aimed to investigate the relationships between increased dead space and inhalation injury outcomes. METHODS: This retrospective study included 51 adult subjects with burns and inhalation injuries. Demographics, size of burns, length of stay, ventilator days, blood gas results, end-tidal CO2 pressure, presence of ventilator-associated pneumonia, and mortality data were collected. Modified Baux scores and ratios of alveolar dead space to alveolar tidal volume (VDalv/VTalv) were calculated. Independent t tests were used to compare mean VDalv/VTalv of survivors to that of subjects who died and between subjects with and without pneumonia. The relationships between VDalv/VTalv and ventilator days or modified Baux score were assessed with bivariate correlation analysis. RESULTS: Our population had a mean age of 52 y and an average burn size of 17.5%. The average length of stay and ventilator days were 12 d and 3.8 d, respectively. The mean modified Baux score was 87. The mean VDalv/VTalv was 0.38. Ten subjects died, and 6 subjects had pneumonia. The VDalv/VTalv of survivors was significantly smaller for survivors than for subjects who died (0.34 vs 0.52, P = .03). No significant difference was observed between subjects with and without pneumonia (0.36 vs 0.47, P = .26). VDalv/VTalv correlated significantly with modified Baux score (r = .524, P < .001). CONCLUSIONS: Alveolar dead space (VDalv/VTalv) is easily calculated from PaCO2 and end-tidal CO2 pressure and may be useful in assessing severity of inhalation injury, the patient's prognosis, and the patient's response to treatment.


Although cytokines are known to be involved in the regulation of ACTH secretion, their effects, along with the molecular mechanisms, on POMC gene expression are not thoroughly characterized. In this study we examined the effects of representative cytokines on transcription of the POMC gene in corticotrophs in vitro using AtT20PL, a clone of the AtT20 cell line stably transfected with approximately 0.7 kilobase of the rat POMC 5'-promoter-luciferase fusion gene. In each experiment, cells were incubated with the cytokine tested, and the changes in POMC 5'-promoter activity were determined by a luciferase assay. The results showed that interleukin-1beta (IL-1beta) stimulated promoter activity in a biphasic manner [weak short term effects (2-3 h) followed by potent long term effects (>12-16 h)]. Tumor necrosis factor-alpha had similar effects, but much less potency. IL-6 showed a profound stimulatory, but only a long term (>20 h), effect. IL-2 did not influence POMC expression. In contrast, interferon-alpha (IFN alpha) and IFN-gamma showed acute stimulatory effects (approximately 4 h) followed by marked inhibitory effects (>8 h). Although the acute effects of IL-1beta, IL-6, and tumor necrosis factor-alpha alone were minimal, they significantly potentiated the stimulatory effect of CRH on POMC expression. Finally, pretreatment of the cells with a broad spectrum tyrosine kinase inhibitor, genistein, abolished or significantly diminished the effects of all cytokines except IFNs. Our results suggest that 1) each cytokine tested has a distinct effect on POMC gene expression; 2) there are positive cross-talk effects between CRH and cytokines at the corticotroph level; and 3) tyrosine phosphorylation cascades are involved in the intracellular signaling mechanisms of some cytokines.


NASA has awarded Computer Sciences Corporation (CSC) of Falls Church, Va., a modification to exercise the first option year under its existing contract. This is a one-year option period for the continuation of financial management, human resources, procurement and information technology support services to NASA. The one-year option increases the existing NASA Shared Services Center support contract by more than $38 million and provides services through Sept. 30, 2011. The center is a partnership among NASA, CSC, and the states of Mississippi and Louisiana. The center performs selected business activities for all 10 NASA centers. For more information about the NASA Shared Services Center, visit: http://www.nssc.nasa.gov


The hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate is a key reaction of carbohydrate metabolism. The enzyme that catalyzes this reaction, fructose-1,6-bisphosphatase, appears to be present in all forms of living organisms. Regulation of the enzyme activity, however, occurs by a variety of distinct mechanisms. These include AMP inhibition (most sources), cyclic AMP-dependent phosphorylation (yeast), and light-dependent activation (chloroplast). In this short review, we have analyzed the function of several fructose-1,6-bisphosphatases and we have made a comparison of partial amino acid sequences obtained from the enzymes of the yeast Saccharomyces cerevisiae, Escherichia coli, and spinach chloroplasts with the known entire amino acid sequence of a mammalian gluconeogenic fructose-1,6-bisphosphatase. These results demonstrate a very high degree of sequence conservation, suggesting a common evolutionary origin for all fructose-1,6-bisphosphatases.


GABAA-mediated miniature IPSCs (mIPSCs) were recorded from layer V pyramidal neurons of the visual cortex using whole-cell patch-clamp recording in rat brain slices. At room temperature, the benzodiazepine site agonist zolpidem enhanced both the amplitude (to 138 ± 26% of control value at 10 μm) and the duration (163 ± 14%) of mIPSCs. The enhancement of mIPSC amplitude was not caused by an increase of the single-channel conductance of the postsynaptic receptors, as determined by peak-scaled non-stationary fluctuation analysis of mIPSCs. The effect of zolpidem on fast, synaptic-like (1 msec duration) applications of GABA to outside-out patches was also investigated. The EC50 for fast GABA applications was 310 μm. In patches, zolpidem enhanced the amplitude of currents elicited by subsaturating GABA applications (100–300 μm) but not by saturating applications (10 mm). The increase of mIPSC amplitude by zolpidem provides evidence that the GABAA receptors are not saturated during miniature synaptic transmission in the recorded cells. By comparing the facilitation induced by 1 μm zolpidem on outside-out patches and mIPSCs, we estimated the concentration of GABA seen by the postsynaptic GABAA receptors to be ∼300 μm after single vesicle release. We have estimated a similar degree of receptor occupancy at room and physiological temperature. However, at 35°C, zolpidem did not enhance the amplitude of mIPSCs or of subsaturating GABA applications on patches, implying that, in these neurons, zolpidem cannot be used to probe the degree of receptor occupancy at physiological temperature.


Many spatial analysis techniques rely on the ability to geocode individual locations based on addresses or other descriptive information. The quality of geocoding and its effect on spatial analysis have received some attention in the literature, in particular in the field of health. This article reviews the foundation of geocoding and presents a framework for evaluating geocoding quality. Errors introduced by street gecoding include incompleteness, positional error, and incorrect assignment to geographic units. A review of empirical studies suggests that these errors are neither small nor random in nature and that substantial bias may be introduced in spatial analysis that employs the results of geocoding. Several alternatives have also emerged, including the use of address points and parcels, and these are gradually becoming more widely used. Several areas for future research on geocoding have been identified: (i) refinements of address data models to incorporate complex addressing situations; (ii) development of error propagation techniques to determine the level of geocoding quality required for a particular analysis scenario; (iii) development of measures of reliability for geocoding results; (iv) comparative analysis of geocoding quality across different jurisdictions; and (v) validation of online geocoding services and volunteered geographic information.


Recrystallization and structural recovery in -decay damage in zircon samples have been studied using Raman spectroscopy. Fifteen zircon samples with different degrees of radiation damage have been thermally annealed between 600 K and 1800 K for up to 28 days and 8 hours. The experimental results from this study reveal that recrystallization in the damaged zircon samples is a multi-stage process that depends on the degree of initial damage of the samples. In partially damaged samples the lattice recovery of damaged crystalline ZrSiO4 takes place at temperatures as low as about 700 K, as shown by a remarkable band-sharpening and a significant increase in the frequencies of 1 and 3 Si-O stretching vibrations together with the external band near 357 cm-1 with increasing temperature. A dramatic increase of Raman scattering intensity of ZrSiO4 occurs in partially damaged samples near 1000 K due to a recrystallization process involving epitaxial growth. Heavily damaged samples tend to decompose into ZrO2 and SiO2 at high temperatures. Tetragonal ZrO2 has been observed under annealing between 1125 K and about 1600 K in heavily damaged samples while monoclinic ZrO2 appears above 1600 K. Weak signals from ZrSiO4 were detected at 1125 K in highly metamict zircon although the main recrystallization appears to occur near 1500 K accompanied by a decrease of the volumes of ZrO2 as well as SiO2 . This suggests that this recrystallization is associated with the reaction of ZrO2 with SiO2 to form ZrSiO4 . A possible intermediate phase has been observed, for the first time, by Raman spectroscopy in damaged zircons annealed at temperatures between 800 K and 1400 K. This phase is characterized by strong, broad Raman signals near 670, 798 and 1175 cm-1 . Prolonged isothermal annealing at 1050 K results in a decrease of these characteristic bands and eventually the disappearance of this intermediate phase.


Abstract The most obvious lesson from the recent crisis is that today's version of unfettered capitalism is unable to selfcorrect. For the past 30 years and more, perhaps, the neoliberal model of capitalism has ruled supreme, promoting ultimate freedom in markets and the globalisation of finance to apparently deliver endless prosperity to all through consumption-led growth. The result has been massive environmental damage, depletion of natural resources and a growing gap between rich and poor. The model is unravelling, as the hidden costs are surfacing everywhere. Asian governments are being called upon to wake up and understand that to rely on the market to correct the inefficiencies in the allocation of resources is at best futile and naive and at worst plain dishonest.


Wireworms of Agriotes spp. are severe and widespread agricultural pests affecting especially maize, potatoes and numerous vegetable crops. Within the framework of a national cooperation project on pest management strategies against soil insects, special emphasis was placed on evaluating alternative wireworm control methods for vegetable production. Therefore, the potential of calcium cyanamide and Metarhizium anisopliae was investigated. Calcium cyanamide showed a repellent but no lethal effect on late instars of Agriotes ustulatus. A Swiss Metarhizium anisopliae strain revealed promising crop protection effects requiring further investigations concerning treatment reliability and commercialisation.


Although the skin constitutes the first line of defense against waterborne pathogens, there is a great lack of information regarding the skin associated lymphoid tissue (SALT) and whether immune components of the skin are homogeneously distributed through the surface of the fish is still unknown. In the current work, we have analyzed the transcription of several immune genes throughout different rainbow trout (Oncorhynchus mykiss) skin areas. We found that immunoglobulin and chemokine gene transcription levels were higher in a skin area close to the gills. Furthermore, this skin area as well as other anterior sections also transcribed significantly higher levels of many different immune genes related to T cell immunity such as T cell receptor α (TCRα), TCRγ, CD3, CD4, CD8, perforin, GATA3, Tbet, FoxP3, interferon γ (IFNγ), CD40L and Eomes in comparison to posterior skin sections. In agreement with these results, immunohistochemical analysis revealed that anterior skin areas had a higher concentration of CD3+ T cells and flow cytometry analysis confirmed that the percentage of CD8+ T lymphocytes was also higher in anterior skin sections. These results demonstrate for the first time that T cells are not homogeneously distributed throughout the teleost skin. Additionally, we studied the transcriptional regulation of these and additional T cell markers in response to a bath infection with viral hemorrhagic septicemia virus (VHSV). We found that VHSV regulated the transcription of several of these T cell markers in both the skin and the spleen; with some differences between anterior and posterior skin sections. Altogether, our results point to skin T cells as major players of teleost skin immunity in response to waterborne viral infections.


Wild animals are faced with many stressors from starvation to infections, which will affect individual survival and population dynamics. Free radicals and reactive oxygen species are involved in many of these processes, from cell signalling and immunity, to potentially being a causal factor in ageing. Oxidative stress is posited as a major factor in population dynamics, ultimately driving the evolution of life-history traits in wild species, acting as the 'currency' through which various trade-offs operate. In this thesis, I present a series of studies on the Wytham population of European badgers ( Meles meles ) focussed on dissecting the effects of host responses to stressors and pathogen recognition on life-history success. The first part of this thesis investigates intrinsic and extrinsic factors affecting oxidative stress and antioxidant defences, linked to population-dynamic effects and life-history traits. I model the crucial intrinsic (development, ageing, reproduction) and one important extrinsic (weather conditions) factors affecting oxidative stress levels in a wild mammal, in relation to survival and reproductive investment. Benefitting from a long term study with marked individuals of a known age, I found that cubs trade-off the development of antioxidant defences against growth, and that juvenile survival is dependent on levels of oxidative damage. These factors are interactive with prevailing yearly weather conditions; investment in antioxidant defences has the greatest survival benefit for young cubs in harsh years (dry, cold spring). I also show that weather affects age-classes in different ways, but I did not find any link between higher oxidative damage and ageing, even following individual responses. The second major focus for the thesis is to explore the immune capability of badgers, focussing on macrophage function and the initial recognition of pathogens. Wildlife immunology represents a "neglected area" of ecology that has potential for large impacts in terms of conservation and disease management. Indeed, wildlife can be a reservoir for infections that affect humans (zoonotic infections) and their livestock. The badger is a classic example of this effect being considered an important reservoir for Mycobacterium bovis , the cause of bovine tuberculosis (bTB). I employed molecular immunology methodologies to develop a methodological tool box to assess immune responses in badgers, which are then employed to investigate the response of blood monocyte-derived macrophages to microbial agonists that stimulate Toll-like receptors. The major findings are that badger macrophages fail to produce nitric oxide or meaningfully upregulate inducible nitric oxide synthase mRNA after exposure to TLR agonists, bacterial lysates and / or recombinant badger Interferon gamma. The TLR system is demonstrated to be largely intact in badger macrophages since exposure to TLR agonists did induce upregulation of cytokine mRNA. The only agonists that stimulated very low responses are those that target TLR9, but this was due to very low levels of expression of TLR9 mRNA. Both nitric oxide and TLR9 are implicated in responses to bTB and these deficiencies would significantly impact on the susceptibility of badgers to infection. There are numerous wider implications of my work: My thesis foremost highlights the importance of taking an integrated approach to eco-physiology and eco-immunology, as these processes are heavily intertwined. The weather correlates of oxidative stress not only highlight the potential vulnerability of all species to human induced rapid environmental change, but provide a stark warning especially for less resilient specialists. The immunology work confirms the importance of carefully analysing immune responses of wildlife species, especially in the context of designing effective species management strategies for diseases such as bTB, providing indicators of why a species may be susceptible to infection and indicating potential ways to improve vaccination.


Many experimental studies use the quantification of aerobic and anaerobic ability as performance indicators and as injury rehabilitative measures. The measurement of aerobic performance can be quantified by the volume of oxygen consumed while exercising sub-maximally or at maximum capacity or intensity. Recently, high intensity interval training (HIIT) has emerged as a sustainable and effective method for improving cardiorespiratory fitness (CRF). HIIT has been proven to produce equal or greater improvements in cardio respiratory fitness (CRF) when compared to moderate intensity continuous exercise. HIIT has been described as an intermittent exercise period of short intense training bouts interspersed by different recovery periods. Whether using continuous aerobic or intermittent anaerobic training protocols to develop increased exercise capacity, the quantification of the active muscle mass contributing to the measurement outcome is important. Here we suggest that outcome measures should be based on lean tissue mass and not total body composition when examining individual responses to aerobic and anaerobic training protocols.


BACKGROUND: DLBCL is the most common and a potentially curable non-Hodgkin lymphoma. Multiple previous studies have shown that minority populations have worse outcomes compared to Caucasians (Tao L, Blood 2014; Griffiths R, BMC Cancer 2010; Koroukian et al, Cancer, 2010, Shenoy PJ Cancer 2010). Moreover, it has been reported that uninsured and Medicaid insured patients with DLBCL have inferior survival compared to privately insured patients (Han X, Cancer 2014; Koroukian et al, Cancer 2010;). It has also been well established that minorities are underrepresented in clinical trials (Gerrero S, Sci Rep 2018; Kwiatkowski K, Cancer 2013). We present the baseline characteristics, treatment paradigms and outcomes of Caucasian (C) and non-Caucasian (NC) patients with de novo DLBCL treated at a single academic hybrid cancer center.
 METHODS: We collected demographic, disease, insurance coverage, treatment characteristics, and treatment outcomes for patients with de novo DLBCL who presented between January 2016 and January 2019 at Levine Cancer Institute, Charlotte, North Carolina. Patient race, C or NC were self-reported. Insurance was categorized as Government (Medicaid or Medicare), Private, or Uninsured. We used the Revised International Prognostic Index (R-IPI) to risk stratify patients. Double-hit lymphomas (DHL) were defined as having the MYC translocation with either BCL2 or BCL6 translocation on fluorescent in situ hybridization. Treatments included standard chemoimmunotherapies, stem cell transplantation and clinical trials including chimeric antigen receptor therapies (CART). Outcomes of overall survival (OS) and progression free survival (PFS) were calculated using the Kaplan Meier method and compared with log rank test. Demographic data was compared using Fisher's Exact tests.
 RESULTS: One hundred and ninety-six consecutive patients with de novo DLBCL were included in the analysis [155 (79%) = C, 41 (21%) = NC] (Table). The NC group was predominantly African American (71%) followed by Hispanic (15%). Prognostic scores (R-IPI) and the incidence of DHL were similar between C and NC. The median age at diagnosis in the NC group was lower than in C. There were significant differences in insurance coverage between the 2 groups (p=0.012). The C group did not have any uninsured patients and had more patients with private insurance (33%) compared to the NC group (7% uninsured and 27% with private insurance). The most common frontline treatment was RCHOP (C=66%, NC=70%) followed by dose adjusted REPOCH (C=12%, NC=15%). Median follow up was 31.6 months. There was no difference in OS and PFS between the 2 groups (Figure 1). OS at 2 years from date of diagnosis was 81% for C and 84% for NC, p=0.852. Two-year PFS from time of diagnosis were similar for both groups: 61% for C and 63% for NC, p=0.999.
 Similar numbers of patients in both groups developed relapsed or refractory (R/R) disease after frontline therapy. Median number of treatments was 2 for both groups, p=0.582. For patients who developed R/R DLBCL, the 2-year OS was 60% for C and 63% for NC, p=0.590. Similar proportions underwent stem cell transplantation: 11% for C and 20% for NC, p= 0.186. Clinical trial enrollment was comparable: 11% for C and 12% for NC, p=0.785.
 CONCLUSION: Unlike previous population-based studies that have shown racial disparities with superior outcomes for Caucasians and for patients with private insurance, our single center experience demonstrates similar survival outcomes between Caucasians and non-Caucasians diagnosed with de novo DLBCL, despite differences in insurance coverage favoring Caucasians. In the R/R setting, similar proportions of both groups underwent stem cell transplantation and enrolled on clinical trials. The likely explanation is that our safety net cancer center, with extensive nurse navigator support and access to standard treatments, stem cell transplants and cutting-edge clinical trials may abrogate the inferior outcomes in minority populations that have been previously reported.

 Symanowski: Immatics: Consultancy; Eli Lilly: Consultancy; Carsgen Therapeutics: Consultancy; Boston Biomedical: Consultancy. Park:Rafael Pharma: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Research Funding; Gilead: Speakers Bureau; Teva: Consultancy, Research Funding; G1 Therapeutics: Consultancy; Seattle Genetics: Research Funding, Speakers Bureau. Avalos:Juno: Membership on an entity's Board of Directors or advisory committees; Best Practice-Br Med J: Patents & Royalties: receives royalties from a coauthored article on evaluation of neutropenia. Jacobs:Genentech: Speakers Bureau; AstraZeneca: Speakers Bureau; TG Therapeutics: Honoraria, Research Funding; AbbVie: Consultancy, Speakers Bureau; JUNO: Consultancy; Gilead: Consultancy; Pharmacyclics LLC, an AbbVie Company: Research Funding, Speakers Bureau. Ghosh:TG Therapeutics: Consultancy, Honoraria, Research Funding; SGN: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Research Funding; Genentech: Research Funding; AstraZeneca: Honoraria, Speakers Bureau; Forty Seven Inc: Research Funding.


Abstract : This thesis examines the effect of transitions to peace in Nicaragua, El Salvador and Guatemala on internal security forces. It reveals how the influence of the military affected the implementation of internal security reforms, influencing the professionalism and effectiveness of police forces in the fight against violence and gangs today. The research shows Sandinista influence allowed Nicaragua to maintain an experienced core of security personnel that has confronted the present challenges more effectively. Reforms in El Salvador yielded a new, highly restructured and reduced security force of which only one-fifth some policing experience, reducing the short-term effectiveness of the force in the fight against insecurity, but increasing the probability for long term consolidation of a professional and effective police institution. In Guatemala, the transitions resulted in the creation of a new police force mostly manned by former security personnel, perpetuating the corruption that permeated the force prior to the transitions--a fact reflected in the high levels of crime in the country today. The thesis proposes that the effect of the transitions on the current forces is a pivotal factor on their effectiveness, and must be addressed in order to improve security for citizens and democracy.


Abstract. Some strong natural fluctuations of climate in the Eastern Mediterranean (EM) region are shown to be connected to the major tropical systems. Potential relations between EM rainfall extremes to tropical systems, e.g. El Nino, Indian Monsoon and hurricanes, are demonstrated. For a specific event, high resolution modelling of the severe flood on 3-5 December 2001 in Israel suggests a relation to hurricane Olga. In order to understand the factors governing the EM climate variability in the summer season, the relationship between extreme summer temperatures and the Indian Monsoon was examined. Other tropical factors like the Red-Sea Trough system and the Saharan dust are also likely to contribute to the EM climate variability.


At the northern edge of their North American range, moose (Alces alces) occupy treeline and shrub tundra environments characterized by extreme seasonality. Here we describe aspects of the seasonal ecology of a northern Yukon moose population that summers in Old Crow Flats, a thermokarst wetland complex, and winters in surrounding alpine habitat. We collared 19 moose (10 adult males and 9 adult females) fitted with GPS radio-collars in Old Crow Flats during summer, and monitored their year-round habitat use, associated environmental conditions, and movements for 2 years. Seventeen of 19 moose were classified as migratory, leaving Old Crow Flats between August and November and returning in April to July, and spent winter in alpine habitats either northwest (n = 8), west (n = 4), or southeast (n = 5) of Old Crow Flats. The straight-line migration distance between summer and winter ranges ranged from 59 to 144 km, averaging 27 km further for bulls than cows. In summer, 18 of 19 moose situated their home ranges in and around drained lake basins and shallow lake habitats within Old Crow Flats. In winter, moose at elevations < 400 m selected for river, shrub, or drained lake habitats, whereas those at elevations >600 m selected for shrubby valley bottoms near lakes and rivers within home ranges dominated by alpine tundra. Moose at high elevations marginally reduced their exposure to cold extremes due to the prevalence of thermal inversions, but cold avoidance was not a strong driver of habitat selection, including for moose at low elevations. Stable isotope signatures of moose hair, aquatic plants, and terrestrial plants were consistent with a year-round, shrub-dominated diet characterized by slight habitatand season-associated dietary differences. Local knowledge of the Vuntut Gwitchin First Nation predicted several of our major results, including 1) summer home range fidelity, 2) selection of lakeshore habitats, 3) use of drained lake basins, 4) dietary reliance on shrubs and emergent vegetation, and 5) responses to contemporary environmental changes. Although the core habitat of this moose population, including the winter ranges of its 3 subpopulations, is well protected by a variety of special management units, parks, and protected areas in Yukon and Alaska, pronounced climate warming is dramatically impacting this thermokarst wetland. Coordinated monitoring, management, and conservation of this unique landscape, moose population, and socio-ecological system is warranted. ALCES VOL. 55: 105–130 (2019)


In live streaming applications, a fixed set of bitrate-resolution pairs (known as bitrate ladder) is used for simplicity and efficiency to avoid the additional encoding run-time required to find optimum resolution-bitrate pairs for every video content. However, an optimized bitrate ladder may result in (i) decreased storage or delivery costs or/and (ii) increased Quality of Experience (QoE). This paper introduces a perceptually-aware per-title encoding (PPTE) scheme for video streaming applications. In this scheme, optimized bitrate-resolution pairs are predicted online based on Just Noticeable Difference (JND) in quality perception to avoid adding perceptually similar representations in the bitrate ladder. To this end, Discrete Cosine Transform (DCT)-energy-based low-complexity spatial and temporal features for each video segment are used. Experimental results show that, on average, PPTE yields bitrate savings of 16.47% and 27.02% to maintain the same PSNR and VMAF, respectively, compared to the reference HTTP Live Streaming (HLS) bitrate ladder without any noticeable additional latency in streaming accompanied by a 30.69% cumulative decrease in storage space for various representations.


The ND1 subunit gene of the mitochondrial NADH-ubiquinone oxidoreductase (complex I) is a hot spot for mutations causing Leber hereditary optic neuropathy and several mutations causing the mitochondrial encephalopathy, lactic acidosis and stroke-like episodes syndrome (MELAS). We have used Escherichia coli and Paracoccus denitrificans as model systems to study the effect of mutations 3946 and 3949, which change conserved residues in ND1 and cause MELAS. The vicinity of these mutations was also explored with a series of mutations in charged residues. The 3946 mutation results in E214K substitution in human ND1. Replacement of the equivalent residue in E. coli with lysine or glutamine detracted from enzyme assembly and the assembled enzyme was inactive. However, the equivalent E234Q mutant enzyme in P. denitrificans failed to assemble completely (or was rapidly degraded). Also the corresponding substitution with aspartate decreased the enzyme activity in P. denitrificans and E. coli. The 3949-equivalent substitution, Y229H in E. coli, lowered the catalytic activity by 30%. In addition, an activation of the enzyme during catalytic turnover was seen in this bacterial NDH-1, something that was even more pronounced in another mutant in the same loop, D213E. Several other mutations in this region decreased the enzyme activity. The studied MELAS mutations are situated in a matrix-side loop, which appears to be highly sensitive to structural perturbations. The results provide new information on the function of the region affected by the MELAS mutations 3946 and 3949 that is not obtainable from patient samples or current eukaryote models.


Carbon quantum dots (CQDs) have recently emerged as innovative theranostic nanomaterials, enabling fast and effective diagnosis and treatment. In this study, a facile hydrothermal approach for N-doped biomass-derived CQDs preparation from Citrus clementina peel and amino acids glycine (Gly) and arginine (Arg) has been presented. The gradual increase in the N-dopant (amino acids) nitrogen content increased the quantum yield of synthesized CQDs. The prepared CQDs exhibited good biocompatibility, stability in aqueous, and high ionic strength media, similar optical properties, while differences were observed regarding the structural and chemical diversity, and biological and antioxidant activity. The antiproliferative effect of CQD@Gly against pancreatic cancer cell lines (CFPAC-1) was observed. At the same time, CQD@Arg has demonstrated the highest quantum yield and antioxidant activity by DPPH scavenging radical method of 81.39 ± 0.39% and has been further used for the ion sensing and cellular imaging of cancer cells. The obtained results have demonstrated selective response toward Fe3+ detection, with linear response ranging from 7.0 µmol dm−3 to 50.0 µmol dm−3 with R2 = 0.9931 and limit of detection (LOD) of 4.57 ± 0.27 µmol dm−3. This research could be a good example of sustainable biomass waste utilization with potential for biomedical analysis and ion sensing applications.


In the framework of the CLIC/CTF3 studies, a numerical study of the couplingbetween an electron beam bunched at 12 GHz and a nearly confocal resonator(NCR) with spherical mirrors is presented in this paper. The geometry of theNCR pick-up was chosen to have a large quality factor for the diffraction lossesat 12 GHz, and thus a weak coupling to parasitic external TE and TM modesthat may propagate in the wake of the electron bunches. The simulated shuntimpedance shows the presence of undesired resonances at low frequencies, whichcan however be significantly damped, e.g. by placing bricks of absorbing materialalong the side walls of the beam pipe. The power spectrum induced by a singleelectron bunch in an extraction waveguide connected to the upper mirror of theNCR pick-up was computed. Another simulation was performed, this time withoutthe NCR cavity on the beam pipe. A comparison of the power induced by a bunchtrain at 12 GHz in these two cases shows that the presence of the NCR cavityreduces the available signal by at least three orders of magnitude, as a result ofthe transit time factor for the NCR eigen-mode at 12 GHz. Since this reduction isabout the same as for the parasitic modes propagating in the wake of the bunches,we conclude that no significant improvement of the signal-to-noise ratio can beobtained with the NCR pick-up.


Pancreatic cancer is a particularly challenging malignancy, given its usually advanced stage at diagnosis and its rather limited treatment options. Gemcitabine has been standard therapy for advanced pancreatic cancer for well over a decade. The addition of capecitabine or erlotinib to gemcitabine has resulted in modestly improved, although still poor, overall survival. The majority of the recently completed randomized trials, however, have failed to demonstate an improvement of newer treatments over single-agent gemcitabine. Efforts currently underway center on new cytotoxic chemotherapy drugs, as well as novel targeted agents inhibiting various molecular pathways. Newly discovered proteins and cellular elements involved in tumor growth and invasion are potential therapeutic targets, and have become the focus of current trials, as well as future clinical trials. A better understanding of the biology of the disease at the basic science level, and epidemiology and risk factors from a public-health perspective, are needed. Continued research is clearly warranted with the goal of improving survival and optimizing treatment outcomes in locally advanced and metastatic pancreatic cancer.


Drug discovery research based on marine organisms is a big challenge. However, lack of facilities and competent human resources stand as a barrier on the way of research. More in-depth study especially on deep-sea natural products needs to be carried out to solidify the research on the potential for marine organisms to contribute to the future of drug discovery. The total drug discovery processes including collection of marine organisms, extraction, isolation, structure elucidation, biological assay and experimental screening as well as clinical trials is a very long journey and big challenge. Therefore, researchers pay a big attempt to design and discovery of synthetic congeneric leads by derivatizing the natural potent compounds. Therefore, In-silico High throughput screening based on QSAR and molecular docking has been attempted in the present study for the design and discovery of promising anticancer compounds considering existed marine sponge-derived hymenialdisine analogs which are protein kinase inhibitors having nanomolar activities against CDKs, Mek1, GSK 3β and CK1. It may crystallize crucial features for the design and discovery of promising anticancer HMD compounds which could be proposed for further synthesis and testing. QSAR and molecular docking analysis of HMD analogs are being carried out by freely accessible open source software which are very economical and potential in drug discovery attempt.


Abstract. The short-tailed shearwater (Ardenna tenuirostris) is one of the abundant marine top predators in the Pacific; this seabird spends its non-breeding period in the northern North Pacific during May–October and many visit the southern Chukchi Sea in August–September. We examined potential factors affecting this seasonal pattern of distribution by counting short-tailed shearwaters from boats. Their main prey, krill, was sampled by net tows in the southeastern Bering Sea/Aleutian Islands and in the Bering Strait/southern Chukchi Sea. Short-tailed shearwaters were mainly distributed in the southeastern Bering Sea/Aleutian Islands (60 ± 473 birds km−2) in July 2013, and in the Bering Strait/southern Chukchi Sea (19 ± 91 birds km−2) in September 2012. In the Bering Strait/southern Chukchi Sea, krill size was greater in September 2012 (9.6 ± 5.0 mm in total length) than in July 2013 (1.9 ± 1.2 mm). Within the Bering Strait/southern Chukchi Sea in September 2012, short-tailed shearwaters occurred more frequently in cells (50  ×  50 km) where large-sized krill were more abundant. These findings, and information previously collected in other studies, suggest that the seasonal northward movement of short-tailed shearwaters might be associated with the seasonal increase in krill size in the Bering Strait/southern Chukchi Sea. We could not, however, rule out the possibility that large interannual variation in krill abundance might influence the seasonal distribution of shearwaters. This study highlights the importance of krill, which is advected from the Pacific, as an important prey of top predators in the Arctic marine ecosystem.


This Diploma paper is exploring the contribution of Advanced Management Services and Digital Technologies to cultural communication as well as the use and educational utilization of technological applications in Cultural Institutions. In the globalized and competitive environment of the 21st century, Cultural Organizations are called upon to respond to the challenges of the digital age and integrate new technologies into their operation. Digital communication replaces traditional forms of communication and Cultural Institutions are considered as places to promote non-conventional education and learning in the field of Culture.In this paper, the historical evolution of Culture and Cultural Industry is presented, Virtual Museums and new trends in Museology are explored in relation to the expanding role of Museum Institutions, in which the incorporation and use of innovative technologies have become educational instruments in the field of culture. Relevant research topics and issues are also discussed. Thus, digitization projects of cultural heritage and policies pursued by the European Union and our country for the protection and promotion of cultural goods are mentioned. The Digital Exhibition of the History of the Ancient Olympic Games is presented at the Old Museum of Ancient Olympia, which is a pioneer in the use of new technologies. The research section of this diploma paper is based on a research conducted in 2019 at Ancient Olympia and addressed to the visitors of the Digital Exhibition. The main focus of the Research was to identify their views on innovative technologies as tools of education and learning in the Cultural Foundations, as a means of promoting Greek Culture and their contribution to the increase of visitors to cultural institutions' programs using new technologies. The most appropriate method that was followed in this research, was the quantitative one, using three types of questionnaires designed specifically for the school community, teachers and adults. The final conclusions of the research are formulated precisely and the proposals related to the survey's objectives are documented.


Abstract. This paper provides an analysis of the combined theory of gravity-inertial-Rossby waves on a β-plane in the Boussinesq approximation. The wave equation for the system is fifth order in space and time and demonstrates how gravity-inertial waves on the one hand are coupled to Rossby waves on the other through the combined effects of β, the stratification characterized by the Vaisala-Brunt frequency N, the Coriolis frequency f at a given latitude, and vertical propagation which permits buoyancy modes to interact with westward propagating Rossby waves. The corresponding dispersion equation shows that the frequency of a westward propagating gravity-inertial wave is reduced by the coupling, whereas the frequency of a Rossby wave is increased. If the coupling is sufficiently strong these two modes coalesce giving rise to an instability. The instability condition translates into a curve of critical latitude Θc versus effective equatorial rotational Mach number M, with the region below this curve exhibiting instability. "Supersonic" fast rotators are unstable in a narrow band of latitudes around the equator. For example Θc~12° for Jupiter. On the other hand slow "subsonic" rotators (e.g. Mercury, Venus and the Sun's Corona) are unstable at all latitudes except very close to the poles where the β effect vanishes. "Transonic" rotators, such as the Earth and Mars, exhibit instability within latitudes of 34° and 39°, respectively, around the Equator. Similar results pertain to Oceans. In the case of an Earth's Ocean of depth 4km say, purely westward propagating waves are unstable up to 26° about the Equator. The nonlinear evolution of this instability which feeds off rotational energy and gravitational buoyancy may play an important role in atmospheric dynamics.


Bycatch—the incidental capture of non-targeted species in fishing gear—threatens many different marine species. Fisheries bycatch threatens the continued survival of several sea turtle species, which have experienced population declines over the past several decades. New devices and gear modifications such as acoustic pingers, turtle excluder devices, and circle hooks have reduced the bycatch of marine mammals and sea turtles. Because sea turtles use visual cues to aid in foraging habits, methods that use visual deterrents to reduce incidental sea turtle capture in gillnets are an emerging research area. Past experiments have found that attaching light sources to gillnets reduces sea turtle bycatch without affecting target catch rates or catch market value; however, these methods were too costly and time-intensive to the fishers to be practical. This project will test the effectiveness of using illuminated nets to reduce sea turtle bycatch. Portions of the nets will be composed of a phosphorescent material that absorbs wavelengths of light and glows in the dark. The experiment will be carried out in summer 2010 in Punta Abreojos and Bahia de los Angeles, Baja California, Mexico. Students from underserved communities in San Diego will assist in data collection and analysis as part of the Ocean Leaders Initiative with the non-profit Ocean Discovery Institute.


The Senate takes up measures under procedures set in Senate rules and by long-standing customs, thereby giving it flexibility in setting its floor agenda. This report first treats those processes or customs most often used by the Senate and then discusses some procedures less often used to call up measures.


Background There is increasing recognition of sex/gender differences in health and the importance of identifying differential effects of interventions for men and women. Yet, to whom the research evidence does or does not apply, with regard to sex/gender, is often insufficiently answered. This is also true for systematic reviews which synthesize results of primary studies. A lack of analysis and reporting of evidence on sex/gender raises concerns about the applicability of systematic reviews. To bridge this gap, this pilot study aimed to translate knowledge about sex/gender analysis (SGA) into a user-friendly 'briefing note' format and evaluate its potential in aiding the implementation of SGA in systematic reviews. Methods Our Sex/Gender Methods Group used an interactive process to translate knowledge about sex/gender into briefing notes, a concise communication tool used by policy and decision makers. The briefing notes were developed in collaboration with three Cochrane Collaboration review groups (HIV/AIDS, Hypertension, and Musculoskeletal) who were also the target knowledge users of the briefing notes. Briefing note development was informed by existing systematic review checklists, literature on sex/gender, in-person and virtual meetings, and consultation with topic experts. Finally, we held a workshop for potential users to evaluate the notes. Results Each briefing note provides tailored guidance on considering sex/gender to reviewers who are planning or conducting systematic reviews and includes the rationale for considering sex/gender, with examples specific to each review group's focus. Review authors found that the briefing notes provided welcome guidance on implementing SGA that was clear and concise, but also identified conceptual and implementation challenges. Conclusions Sex/gender briefing notes are a promising knowledge translation tool. By encouraging sex/gender analysis and equity considerations in systematic reviews, the briefing notes can assist systematic reviewers in ensuring the applicability of research evidence, with the goal of improved health outcomes for diverse populations.


Summary Pyruvate kinase (PK) (EC 126.96.36.199) isozymes were assayed in normal rat liver and a series of transplantable rat hepatomas ranging widely in growth rate and degree of differentiation, with the use of gradient elution by chloride ion from columns of DEAE-cellulose. In agreement with other studies, three noninterconvertible forms were found in rat tissues: isozyme I, the major form in adult rat liver; isozyme II, the sole form in heart and skeletal muscle; and isozyme III, the sole form in poorly differentiated hepatomas, the major form in normal kidney and lung, and the minor form in adult liver. In normal adult rat liver, PK I makes up 90% of the total activity at 57 units/g tissue, and is decreased to 30 units/g after a 48-hr fast. Carbohydrate refeeding restores the normal PK I level in 24 hr and increases its activity to twice the normal level after 72 hr. Little or no change occurs in PK III, which remains at 3 to 6 units/g. In regenerating liver after partial hepatectomy, PK I was slightly below the normal fasted level, but PK III at 72 hr had about twice the normal activity. Fetal liver of 19 to 21 days had equal PK I and PK III levels, whereas early fetal liver or whole fetus contained almost entirely PK III. Although one highly differentiated hepatoma, 9618A, has a PK isozyme pattern similar to that of liver, other well- and highly differentiated hepatomas had much lower total activities than liver, with a preponderance of PK III. In contrast, the rapidly growing, poorly differentiated hepatomas had extremely high total PK activity, virtually all consisting of PK III. These results provide further evidence of a profound alteration of gene expression in hepatomas resulting in the loss of a specific liver-marker isozyme with loss of differentiation and its replacement in poorly differentiated hepatomas by high activities of an isozyme normally very low in the normal liver.


Abstract Objective Circular RNAs (circRNAs) involve in the development and progression of tumour. The mechanism of circRNAs in oral squamous cell carcinoma (OSCC) has remained unclear. This study aimed to investigate the role of circular Yes-associated protein (circYap) in OSCC. Methods Quantification reverse transcription-polymerase chain reaction (qRT-PCR) was applied to measure circYap expression in patients with OSCC tissues and cells. Flow cytometry was performed to evaluate cell cycle. circYap interaction with CDK4 was detected by RNA immunoprecipitation (RIP) and RNA pull-down. The interaction of Cyclin D1 and CDK4 was determined using co-immunoprecipitation (co-IP). Results We showed that circYap expression was downregulated in OSCC tissues. Using small interfering circular (Si-circYap) and overexpression plasmid, we found that circYap overexpression inhibited proliferation and arrested cell cycle in OSCC cells, while, circYap knockdown yielded the opposite result. Cyclin D1/CDK4 complexes and nuclear translocation is essential for cell cycle progression. We found that CDK4 interacted with circYap was increased when circYap overexpression, meanwhile, Cyclin D1/CDK4 complexes and of nuclear distribution were decreased. Conclusions Our findings suggest that circYap impedes progression of OSCC. Overexpression of circYap suppresses proliferation and cell cycle through binding to CDK4 to block formation and nuclear translocation of Cyclin D1/CDK4 complexes. Thus, circYap may serves as a valuable therapeutic target for OSCC.


Fulminant hepatic failure may develop as a complication of liver disease of various etiology. Infectious agents, drugs and liver toxins represent the major causes of fulminant hepatitis. The function of many organ systems may be impaired during acute hepatic failure because of the crucial role of the liver in intermediary metabolism. The mortality of 50% or more is mainly due to cerebral edema, bleeding from the gastrointestinal tract or disseminated infections. In this review the causes, complications and pathophysiology of fulminant hepatitis are discussed, with particular reference to the prevention of complications and to therapeutic strategies. Moreover, criteria for assessment of prognosis are discussed. A case report illustrates the complex clinical picture and frequently fatal outcome of the disease.


Abstract Pyozia mesenensis, gen et sp. nov. is the second varanopid synapsid from the Middle Permian Krasnoschelsk Formation of Russia. Pyozia is a basal varanopid similar to Archaeovenator in having teeth that lack lateral compression or serration, lacking a caniniform tooth or region on the maxilla, and possessing four premaxillary teeth. Pyozia uniquely possesses a medial contact of the maxilla with the quadratojugal with no lateral exposure allowing the jugal to form part of the skull's ventral margin, and rounded interpterygoid vacuities just anterior to the basipterygoid articulations. Phylogenetic analysis places Pyozia as sister taxon to the terminal dichotomy of Mycterosaurinae and Varanodontinae. The newly described Upper Carboniferous Archaeovenator is again found to be the most basal varanopid. The Permian saw a large-scale changeover of the synapsid fauna, with derived, but ecologically similar, taxa, replacing more primitive "pelycosaurs." Leaf-shaped tooth-bearing caseids were replaced in the Middle and Late Permian by herbivorous pareiasaurs with similar dentition, and Edaphosaurus was replaced by therapsids capable of processing plant material. The large predators of Sphenacodontidae were similarly replaced by therapsid predators. The small to medium sized predator niche, however, was continuously occupied by varanopids. The discovery of the basal Pyozia suggests that varanopids maintained their diversity in the Middle Permian.


Long-term sensory conflict protocols are a valuable means of studying motor learning. The presented protocol produces a persistent sensory conflict for experiments aimed at studying long-term learning in mice. By permanently wearing a device fixed on their heads, mice are continuously exposed to a sensory mismatch between visual and vestibular inputs while freely moving in home cages. Therefore, this protocol readily enables the study of the visual system and multisensory interactions over an extended timeframe that would not be accessible otherwise. In addition to lowering the experimental costs of long-term sensory learning in naturally behaving mice, this approach accommodates the combination of in vivo and in vitro experiments. In the reported example, video-oculography is performed to quantify the vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) before and after learning. Mice exposed to this long-term sensory conflict between visual and vestibular inputs presented a strong VOR gain decrease but exhibited few OKR changes. Detailed steps of device assembly, animal care, and reflex measurements are hereby reported.