bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monocyte, Macrophage, and Dendritic Cell Development: the Human Perspective
Authors: Collin Matthew , Bigley Venetia 
Published: October 2016

ABSTRACT
The maintenance of monocytes, macrophages, and dendritic cells (DCs) involves manifold pathways of ontogeny and homeostasis that have been the subject of intense study in recent years. The concept of a peripheral mononuclear phagocyte system continually renewed by blood-borne monocytes has been modified to include specialized DC pathways of development that do not involve monocytes, and longevity through self-renewal of tissue macrophages. The study of development remains difficult owing to the plasticity of phenotypes and misconceptions about the fundamental structure of hematopoiesis. However, greater clarity has been achieved in distinguishing inflammatory monocyte-derived DCs from DCs arising in the steady state, and new concepts of conjoined lymphomyeloid hematopoiesis more easily accommodate the shared lymphoid and myeloid phenotypes of some DCs. Cross-species comparisons have also yielded coherent systems of nomenclature for all mammalian monocytes, macrophages, and DCs. Finally, the clear relationships between ontogeny and functional specialization offer information about the regulation of immune responses and provide new tools for the therapeutic manipulation of myeloid mononuclear cells in medicine.
Coordinated Regulation of Signaling Pathways during Macrophage Activation
Authors: Lawrence Toby 
Published: October 2016

ABSTRACT

The functional and phenotypic diversity of macrophages has long been appreciated, and it is now clear that it reflects a complex interplay between hard-wired differentiation pathways and instructive signals in specific tissues (Lawrence T, Natoli G. 2011,
Nat Rev Immunol
11:
750–761). Recent studies have begun to unravel the molecular basis for the integration of these intrinsic developmental pathways with extracellular signals from the tissue microenvironment that confer the distinct phenotypes of tissue-resident macrophages (Lavin Y et al. 2014.
Cell
159:
1312–1326; Gosselin D et al. 2014.
Cell
159:
1327–1340). Macrophage phenotype and function is particularly dynamic during inflammation or infection, as blood monocytes are recruited into tissues and differentiate into macrophages, and depending on the nature of the inflammatory stimulus, they may acquire distinct functional phenotypes (Xue J et al. 2014.
Immunity
40:
274–288; Murray PJ et al. 2014.
Immunity
41:
14–20). Furthermore, these functional activation states can be rapidly modified in response to a changing microenvironment. Here we will discuss several key signaling pathways that drive macrophage activation during the inflammatory response and discuss how these pathways are integrated to “fine-tune” macrophage phenotype and function.
Murine Monocytes: Origins, Subsets, Fates, and Functions
Authors: Mildner Alexander , Marinkovic Goran , Jung Steffen 
Published: October 2016

ABSTRACT

Monocytes are short-lived mononuclear phagocytes that circulate in the bloodstream and comprise two main subpopulations that in the mouse are best defined by the Ly6C marker. Intravascular functions of “classical” Ly6C
+
monocytes and their interactions with other lymphoid and myeloid leukocytes in the circulation remain poorly understood. Rather, these cells are known to efficiently extravasate into tissues. Indeed, Ly6C
+
monocytes and their descendants have emerged as a third, highly plastic and dynamic cellular system that complements the two classical, tissue-resident mononuclear phagocyte compartments, i.e., macrophages and dendritic cells, on demand. Following recruitment to injured tissue, Ly6C
+
monocytes respond to local cues and can critically contribute to the initiation and resolution of inflammatory reactions. The second main murine monocyte subset, Ly6C
–
cells, derive in steady state from Ly6C
+
monocytes and remain in the vasculature, where the cells act as scavengers. Moreover, a major fraction of Ly6C
–
monocytes adheres to the capillary endothelium and patrols the vessel wall for surveillance. Given the central role of monocytes in homeostasis and pathology, in-depth study of this cellular compartment can be highly informative on the health state of the organism and provides an attractive target for therapeutic intervention.
Screen time of infants in Sydney, Australia: a birth cohort study
Authors: Chandra Meena , Jalaludin Bin , Woolfenden Susan , Descallar Joseph , Nicholls Laura , Dissanayake Cheryl , Williams Katrina , Murphy Elisabeth , Walter Amelia , Eastwood John , Eapen Valsamma 
Published: October 2016

ObjectivesTo determine the amount of daily screen time in children 18 months of age and ascertain correlations that may be contributing to excessive screen use.DesignA birth cohort was followed with telephone interviews at 6, 12 and 18 months of age. Information about screen time was collected at 18 months.SettingParents were recruited from postnatal wards of 2 major public hospitals and at home visits conducted for new mothers within 4 weeks of birth in South Western Sydney (SWS).ParticipantsParents of 500 children with infants 18 months of age residing in SWS.Primary and secondary outcomesScreen time in infants 18 months of age and associated correlations.ResultsA large percentage of children 18 months of age (40%) had screen times >2 hours daily. There were significant associations between more than 2 hours of screen time daily and mothers without a partner (OR 4.32 (95% CI 1.67 to 11.15)); having <3 siblings (no siblings: OR 2.44 (95% CI 1.20 to 4.94); 1–2 siblings: OR 2.08 (95% CI 1.06 to 4.08)); an employed father (OR 1.96 (95% CI 1.09 to 3.52)); no outdoor equipment at home (OR 1.89 (95% CI 1.08 to 3.34)) and fewer than 5 outings per week (OR 2.08 (95% CI 1.37 to 3.17)).ConclusionsThere is emerging evidence that excess screen time in children causes adverse cognitive, developmental and health outcomes. This study has shown that a large proportion of very young children residing in SWS have screen exposures for >2 hours per day. Factors contributing to excess screen time have also been identified in this study; however, a greater understanding of risk factors needs to be ascertained in order to facilitate greater public health efforts to reduce screen exposure.
Funding for cerebral palsy research in Australia, 2000–2015: an observational study
Authors: Herbert D L , Barnett A G , White R , Novak I , Badawi N 
Published: October 2016

ObjectivesTo examine the funding for cerebral palsy (CP) research in Australia, as compared with the National Institutes of Health (NIH).DesignObservational study.SettingFor Australia, philanthropic funding from Cerebral Palsy Alliance Research Foundation (CPARF) (2005–2015) was compared with National Health and Medical Research Council (NHMRC, 2000–2015) and Australian Research Council (ARC, 2004–2015) and CPARF and NHMRC funding were compared with NIH funding (USA).ParticipantsCerebral Palsy researchers funded by CPARF, NHMRC or NIH.ResultsOver 10 years, total CPARF philanthropic funding was $21.9 million, including people, infrastructure, strategic and project support. As competitive grants, CPARF funded $11.1 million, NHMRC funded $53.5 million and Australian Research Council funded $1.5 million. CPARF, NHMRC and NIH funding has increased in real terms, but only the NIH statistically significantly increased in real terms (mean annual increase US$4.9 million per year, 95% CI 3.6 to 6.2, p<0.001). The NHMRC budget allocated to CP research remained steady over time at 0.5%. A network analysis indicated the relatively small number of CP researchers in Australia is mostly connected through CPARF or NHMRC funding.ConclusionsFunding for CP research from the Australian government schemes has stabilised and CP researchers rely on philanthropic funding to fill this gap. In comparison, the NIH is funding a larger number of CP researchers and their funding pattern is consistently increasing.
Front-end genomics: using an alternative approach for the recovery of high-quality DNA from core needle biopsies
Authors: Mojica Wilfrido D , Hou Tieying , Sykes Don , Dey-Rao Rama 
Published: October 2016

AimsDetermine whether a simple prewash step will provide adequate amounts of high-quality DNA from core needle biopsies for molecular sequencing studies.MethodsThe quantitative and qualitative metrics of DNA recovered from core needle biopsies processed either by 1) formalin fixation and paraffin embedding (FFPE), 2) cells recovered after the core needle biopsy was washed, and 3) frozen sections of the core needle biopsy tissue were evaluated and compared to one another.ResultsFairly equivalent amounts of DNA can be obtained from cells recovered from a prewash step relative to the FFPE and frozen section samples. The number of amplifiable DNA in the wash sample was greater than that from the FFPE samples. The average molecular size of DNA in the wash sample was greater than that of both the FFPE and frozen samples.ConclusionsAlthough more starting material in terms of the number of cells was present in both the FFPE and frozen section samples than the wash samples, equivalent to better results were obtained from the latter with regard to quality. This approach may be a means to better aliquot the diminutive amounts of tissue associated with core needle biopsies, allowing dissociated cells to be dedicated for molecular studies while keeping the tissue intact for morphological studies.
Teaching residents: critical appraisal of the literature using a journal club format
Authors: Hohmann Erik , Tetsworth Kevin 
Published: October 2016

AbstractObjectivesCritical appraisal of the literature is an integral and important part of surgical practice, but can this skill be taught to young doctors? The purpose of this study was to investigate the effect of formal instruction regarding critical review and appraisal of journal articles, using junior surgical residents followed over the course of a 10-week long programme.MethodsFirst-year surgical residents who participated in the department of orthopaedic surgery's compulsory journal club evaluated one article per week for 10 weeks, using the reviewer guidelines and a scoring system currently used by Arthroscopy. The article was selected by a senior consultant orthopaedic surgeon and was provided for assessment to each resident the week prior. The scores and evaluation recommendation (accept, revise and reject) of the residents were then compared against the senior surgeon's assessment. A contingency table and Fisher's exact test was used to compare the frequency of agreement between the decisions of the senior surgeon and the residents.ResultsTwenty residents were included. Agreement in overall total assessment scores increased significantly (p=0.0001) from 49.5% at session 1 to 82.5% at session 10. When comparing the mean percentage of agreement of the first five sessions (61%) with the second five sessions (95%), a significant (p=0.03) increase was observed. The percentage of agreement with the senior surgeon (whether the article should be accepted, revised or rejected) improved from 0% for the first session to 60% at the last session (χ2=7.2–11.2, p=0.02–0.04).ConclusionsThe results strongly suggest that a structured approach to the review and appraisal of journal articles using the format of a journal club significantly improves critical reading skills for first-year surgical residents.
Analgesia in the surgical intensive care unit
Authors: Ehieli Eric , Yalamuri Suraj , Brudney Charles S , Pyati Srinivas 
Published: October 2016

ABSTRACTCritically ill patients are a heterogeneous group with diverse comorbidities and physiological derangements. The management of pain in the critically ill population is emerging as a standard of care in the intensive care unit (ICU). Pain control of critically ill patients in the ICU presents numerous challenges to intensivists. Inconsistencies in pain assessment, analgesic prescription and variation in monitoring sedation and analgesia result in suboptimal pain management. Inadequate pain control can have deleterious effects on several organ systems in critically ill patients. Therefore, it becomes incumbent on physicians and nurses caring for these patients to carefully evaluate their practice on pain management and adopt an optimal pain management strategy that includes a reduction in noxious stimuli, adequate analgesia and promoting education regarding sedation and analgesia to the ICU staff. Mechanistic approaches and multimodal analgesic techniques have been clearly demonstrated to be the most effective pain management strategy to improve outcomes. For example, recent evidence suggests that the use of short acting analgesics and analgesic adjuncts for sedation is superior to hypnotic based sedation in intubated patients. This review will address analgesia in the ICU, including opioid therapy, adjuncts, regional anaesthesia and non-pharmacological options that can provide a multimodal approach to treating pain.
Small Depth Proof Systems
Authors: Krebs Andreas , Limaye Nutan , Mahajan Meena , Sreenivasaiah Karteek 
Published: October 2016

A proof system for a language
L
is a function
f
such that Range(
f
) is exactly
L
. In this article, we look at proof systems from a circuit complexity point of view and study proof systems that are computationally very restricted. The restriction we study is proof systems that can be computed by bounded fanin circuits of constant depth (NC
0
) or of
O
(log log
n
) depth but with
O
(1) alternations (poly log AC
0
). Each output bit depends on very few input bits; thus such proof systems correspond to a kind of local error correction on a theorem-proof pair.

We identify exactly how much power we need for proof systems to capture all regular languages. We show that all regular languages have poly log AC
0
proof systems, and from a previous result (Beyersdorff et al. [2011a], where NC
0
proof systems were first introduced), this is tight. Our technique also shows that M
aj
has poly log AC
0
proof system.

We explore the question of whether T
aut
has NC
0
proof systems. Addressing this question about 2TAUT, and since 2TAUT is closely related to reachability in graphs, we ask the same question about Reachability. We show that if Directed reachability has NC
0
proof systems, then so does 2TAUT. We then show that both Undirected Reachability and Directed UnReachability have NC
0
proof systems, but Directed Reachability is still open.

In the context of how much power is needed for proof systems for languages in NP, we observe that proof systems for a good fraction of languages in NP do not need the full power of AC
0
; they have SAC
0
or coSAC
0
proof systems.
Inherited Chromosomally Integrated Human Herpesvirus 6 and Breast Cancer
Authors: Gravel Annie , Dubuc Isabelle , Brooks-Wilson Angela , Aronson Kristan J. , Simard Jacques , Velásquez-García Héctor A. , Spinelli John J. , Flamand Louis 
Published: October 2016

Abstract
Background: Inherited chromosomally integrated human herpesvirus 6 (iciHHV-6) is a condition observed in approximately 1% of the population. Whether such a genetic alteration predisposes to cancer development in currently unknown. Two studies were conducted to determine whether iciHHV-6 is associated with cancer development.
Methods: First, a screen of 19,597 people from the province of Quebec (Canada) was conducted. A replication test, using data from a population-based case–control study of 1,090 women with incident breast cancer and 1,053 controls from British Columbia and Ontario (Canada) was conducted. DNA samples were analyzed by qPCR and droplet digital PCR to identify iciHHV-6+ carriers.
Results: In the initial study, a potential association between iciHHV-6 positivity and breast cancer was identified [OR = 2.66; 95% confidence interval (CI), 0.95–7.44]. In the replication dataset, no association was found between iciHHV-6 positivity in women and breast cancer (OR = 0.87; 95% CI, 0.35–2.15).
Conclusions: We found no statistically significant associations between inherited chromosomally integrated HHV-6 and breast cancer in women.
Impact: These results do not provide evidence to suggest that iciHHV-6 is a risk factor for breast cancer. Cancer Epidemiol Biomarkers Prev; 26(3); 425–7. ©2016 AACR.
Cabozantinib Is Active against Human Gastrointestinal Stromal Tumor Xenografts Carrying Different KIT Mutations
Authors: Gebreyohannes Yemarshet K. , Schöffski Patrick , Van Looy Thomas , Wellens Jasmien , Vreys Lise , Cornillie Jasmien , Vanleeuw Ulla , Aftab Dana T. , Debiec-Rychter Maria , Sciot Raf , Wozniak Agnieszka 
Published: October 2016

Abstract
In the majority of gastrointestinal stromal tumors (GIST), oncogenic signaling is driven by KIT mutations. Advanced GIST is treated with tyrosine kinase inhibitors (TKI) such as imatinib. Acquired resistance to TKI is mainly caused by secondary KIT mutations, but can also be attributed to a switch of KIT dependency to another receptor tyrosine kinase (RTK). We tested the efficacy of cabozantinib, a novel TKI targeting KIT, MET, AXL, and vascular endothelial growth factor receptors (VEGFR), in patient-derived xenograft (PDX) models of GIST, carrying different KIT mutations. NMRI nu/nu mice (n = 52) were bilaterally transplanted with human GIST: UZLX-GIST4 (KIT exon 11 mutation, imatinib sensitive), UZLX-GIST2 (KIT exon 9, imatinib dose-dependent resistance), or UZLX-GIST9 (KIT exon 11 and 17 mutations, imatinib resistant). Mice were grouped as control (untreated), imatinib (50 mg/kg/bid), and cabozantinib (30 mg/kg/qd) and treated orally for 15 days. Cabozantinib resulted in significant tumor regression in UZLX-GIST4 and -GIST2 and delayed tumor growth in -GIST9. In all three models, cabozantinib inhibited the proliferative activity, which was completely absent in UZLX-GIST4 and significantly reduced in -GIST2 and -GIST9. Increased apoptotic activity was observed only in UZLX-GIST4. Cabozantinib inhibited the KIT signaling pathway in UZLX-GIST4 and -GIST2. In addition, compared with both control and imatinib, cabozantinib significantly reduced microvessel density in all models. In conclusion, cabozantinib showed antitumor activity in GIST PDX models through inhibition of tumor growth, proliferation, and angiogenesis, in both imatinib-sensitive and imatinib-resistant models. Mol Cancer Ther; 15(12); 2845–52. ©2016 AACR.
Interference with the HSF1/HSP70/BAG3 Pathway Primes Glioma Cells to Matrix Detachment and BH3 Mimetic–Induced Apoptosis
Authors: Antonietti Patrick , Linder Benedikt , Hehlgans Stephanie , Mildenberger Iris C. , Burger Michael C. , Fulda Simone , Steinbach Joachim P. , Gessler Florian , Rödel Franz , Mittelbronn Michel , Kögel Donat 
Published: October 2016

Abstract
Malignant gliomas exhibit a high intrinsic resistance against stimuli triggering apoptotic cell death. HSF1 acts as transcription factor upstream of HSP70 and the HSP70 co-chaperone BAG3 that is overexpressed in glioblastoma. To specifically target this resistance mechanism, we applied the selective HSF1 inhibitor KRIBB11 and the HSP70/BAG3 interaction inhibitor YM-1 in combination with the pan-Bcl-2 inhibitor AT-101. Here, we demonstrate that lentiviral BAG3 silencing significantly enhances AT-101–induced cell death and reactivates effector caspase-mediated apoptosis in U251 glioma cells with high BAG3 expression, whereas these sensitizing effects were less pronounced in U343 cells expressing lower BAG3 levels. KRIBB11 decreased protein levels of HSP70, BAG3, and the antiapoptotic Bcl-2 protein Mcl-1, and both KRIBB11 and YM-1 elicited significantly increased mitochondrial dysfunction, effector caspase activity, and apoptotic cell death after combined treatment with AT-101 and ABT-737. Depletion of BAG3 also led to a pronounced loss of cell–matrix adhesion, FAK phosphorylation, and in vivo tumor growth in an orthotopic mouse glioma model. Furthermore, it reduced the plating efficiency of U251 cells in three-dimensional clonogenic assays and limited clonogenic survival after short-term treatment with AT-101. Collectively, our data suggest that the HSF1/HSP70/BAG3 pathway plays a pivotal role for overexpression of prosurvival Bcl-2 proteins and cell death resistance of glioma. They also support the hypothesis that interference with BAG3 function is an effective novel approach to prime glioma cells to anoikis. Mol Cancer Ther; 16(1); 156–68. ©2016 AACR.
Invention into the AC Voltage Regulator with V/F Technique for Induction Motor Starting Applications
Authors: Kollipara Mahesh , Kolluru V N Srinivasa Rao 
Published: October 2016

Modern electrical motors are available in many different forms with different mounting arrangements. To ensure a long life for the motor it is important to select it with correct degree of protection when operating under heavy duty conditions in a severe environment. Smooth starting is also one of major considerations to get long life and optimum efficiency. The conventional method to start an asynchronous motor with a soft starter is by reducing the voltage of the motor by varying the voltage “off time”. The “off time” could for example be controlled to achieve a desired maximum current level or a constant driving torque. Even if the voltage is reduced the fundamental frequency of the voltage is equal to the supply voltage frequency. That gives a large difference between angular speed of supply voltage and angular speed of the rotor during start. Due to the large difference in angular speed the motor flux will be low and thereby also the ability to produce torque. Instead of using the conventional control method with a reduced voltage it is possible to use a method with controlled flux similar to frequency inverters for soft-starters. As the soft-starter does not have the intermediate DC energy storage the applied voltage vector has to be directly modulated from the mains supply.
Regime Analysis of Critical Raindrop Diameters for Rainfall Attenuation in Southern Africa
Authors: Adetan O , Obiyemi OO 
Published: October 2016

The influence of critical raindrop diameters on the specific rainfall attenuation in Durban (29o52'S, 30o58'E), South Africa using various rainfall regimes is analyzed in this paper. Different rain rate values representing drizzle, widespread, shower and thunderstorm are selected for the purpose of analysis over the measured raindrop size distribution. The three-parameter lognormal and gamma DSD models with shape parameter of 2 are used to estimate the parameters required to investigate the drop sizes which produce a major contribution to the total specific rainfall attenuation for the selected rain rate values. The computed total specific attenuation increases with increasing frequencies and rain rates. The highest and prevailing contribution to the specific attenuation occurs at for the stratiform (drizzle or widespread) and convective (shower or thunderstorm) rain types for the models considered. The total percentage fraction formed by drops in the diameter range 0.5 mm ≤ D ≤ 2.5 mm and 1.0 mm ≤ D ≤ 3.0 mm are found to be most critical for the specific rain attenuation for the stratiform (drizzle and widespread) and convective (shower and thunderstorm) rainfall types especially at higher frequencies.
Leakage Immune 9T-SRAM Cell in Sub-threshold Region
Authors: Gupta Priya , Gupta Anu , Asati Abhijit 
Published: October 2016

The paper presents a variability-aware modified 9T SRAM cell. In comparison to 6T SRAM cell the proposed cell achieves 1.3× higher read-SNM and 1.77× higher write-SNM with 79.6% SINM (static current noise margin) distribution at the expense of 14.7× lower WTI (write trip current) at 0.4 V power supply voltage, while maintaining similar stability in hold mode. Thus, comparative analysis exhibits that the proposed design has a significant improvement, thereby achieving high cell stability at 45nm technology.