cssi/SciSciGPT-SciSciNet huggingface dataset:
Molecular mechanisms of OLIG2 transcription factor in brain cancer

Oligodendrocyte lineage transcription factor 2 (OLIG2) plays a pivotal role in glioma development. Here we conducted a comprehensive study of the critical gene regulatory networks involving OLIG2. These include the networks responsible for OLIG2 expression, its translocation to nucleus, cell cycle, epigenetic regulation, and Rho-pathway interactions. We described positive feedback loops including OLIG2: loops of epigenetic regulation and loops involving receptor tyrosine kinases. These loops may be responsible for the prolonged oncogenic activity of OLIG2. The proposed schemes for epigenetic regulation of the gene networks involving OLIG2 are confirmed by patient survival (Kaplan-Meier) curves based on the cancer genome atlas (TCGA) datasets. Finally, we elucidate the Coherent-Gene Modules (CGMs) networks-framework of OLIG2 involvement in cancer. We showed that genes interacting with OLIG2 formed eight CGMs having a set of intermodular connections. We showed also that among the genes involved in these modules the most connected hub is EGFR, then, on lower level, HSP90 and CALM1, followed by three lower levels including epigenetic genes KDM1A and NCOR1. The genes on the six upper levels of the hierarchy are involved in interconnections of all eight CGMs and organize functionally defined gene-signaling subnetworks having specific functions. For example, CGM1 is involved in epigenetic control. CGM2 is significantly related to cell proliferation and differentiation. CGM3 includes a number of interconnected helix-loop-helix transcription factors (bHLH) including OLIG2. Many of these TFs are partially controlled by OLIG2. The CGM4 is involved in PDGF-related: angiogenesis, tumor cell proliferation and differentiation. These analyses provide testable hypotheses and approaches to inhibit OLIG2 pathway and relevant feed-forward and feedback loops to be interrogated. This broad approach can be applied to other TFs.
Growth of a Diffusion Flame in the Field of a Vortex

A simple diffusion flame with fast chemical kinetics is initiated along the horizontal axis between a fuel occupying the upper half-plane and an oxidizer below. Simultaneously a vortex of circulation Γ is established at the origin. As time progresses the flame is extended and “wound up” by the vortex flow field and the viscous core of the vortex spreads, converting the motion in the core to a solid-body rotation.
Selected neuropsychiatric masquerades: a brief review

Multiple neurological conditions can manifest primarily with psychiatric symptoms. The physical signs and symptoms may be much delayed. We have summarized seven clinical presentations of psychiatric symptoms, which were finally diagnosed as neurological conditions, including Huntington’s disease, brain tumors (glioblastoma multiforme, glioma and meningioma), progressive supranuclear palsy (PSP), neurosyphilis and anti-N-Methyl-DAspartate (NMDA) Receptor Encephalitis. These cases highlight that the practicing physician and psychiatrist be cognizant of the differential diagnosis spectrum of presenting symptoms. Conducting appropriate physical examinations, ordering relevant laboratory and imaging tests will clinch an organic versus a psychiatric diagnosis. Such diagnostic acumen will not only improve the quality of life for the patient, but also limit further morbidity.
Science: the slow march of accumulating evidence.

Recent crises over the credibility of research in psychology and the biomedical sciences have highlighted the need for researchers to view and treat replication research as essential to the accumulation of knowledge. In this article, the authors make the case for the utility of replication in medical education research. Specifically, the authors contend that because research in medical education often adopts theories from other disciplines, replication is necessary to gauge the applicability of those theories to the specific medical education context. This article introduces readers to the two major types of replication – direct and conceptual – and provides a primer on conceptual replication. In particular, the article presents key elements of conceptual replication and considers how it can be used to strengthen approaches to knowledge generation, theory testing, and theory development in medical education research.
Loss of IRF-4 Exacerbates the CML-Like Phenotype of IRF-8 Knockout Mice.

Abstract IRF-4 and IRF-8 are related interferon regulatory factors that are required for the development and function of myeloid and lymphoid cells. Mice deficient in IRF-8 develop a myeloproliferative disorder with many similarities to human chronic myeloid leukemia (CML). Our group has shown that in B-lymphocyte development, IRF-4 and 8 function redundantly to control the pre-B to B transition. Though expression of IRF-4 has been demonstrated in myeloid cells, its role in these lineages has not been defined. We hypothesized that, similar to their role in B-cells, IRF-4 and 8 may to some extent function redundantly in myeloid cells. To test this hypothesis, myelopoiesis was analyzed in IRF-4/8 double knockout (DKO) mice. We found that from seven weeks of age, the DKO animals have a more aggressive leukemic phenotype than the IRF-8 KO mice. The white blood cell (WBC) counts of DKO animals were typically in the range of 40,000 to 80,000 cells per microliter, campared to 15,000 to 20,000 for age-matched IRF-8 KO animals. FACS analysis showed that the increased WBCs in the DKO animals was due to a massive expansion of mature granulcytes. The absolute granulocyte counts of DKO animals were typically 7-fold to 10-fold higher than those of IRF-8 KO animals. In addition, histologic preparations showed that by 15 weeks of age the spleens, lymph nodes, and bone marrow of DKO animals were invaded by large numbers of mature granulocytes and pseudo-Gaucher cells, with complete effacement of the normal micro-architecture. Age-matched IRF-8 KO animals showed invasion to a lesser degree, with preservation of many of the normal architectural features. In conclusion, IRF-4 is an important myeloid tumor suppressor, whose loss augments the myeloproliferative disease manifested in IRF-8 deficient mice. This suggests the two transcription factors, similar to their role in B-cell development, function redundantly to control the normal maturation of myeloid-lineage cells.
Highly uniform distribution of Pt nanoparticles on N-doped hollow carbon spheres with enhanced durability for oxygen reduction reaction

Carbon-supported Pt nanostructures currently exhibit great potential in polymer electrolyte membrane fuel cells. Nitrogen-doped hollow carbon spheres (NHCSs) with extra low density and high specific surface area are a promising carbon support for loading Pt NPs. The doped heteroatom of nitrogen not only contributes to the active activity for the oxygen reduction reaction (ORR), but also shows a strong interaction with Pt NPs for entrapping them to prevent dissolution/migration. This synergetic effect/interaction resulted in the uniform dispersion and strong combination of the Pt NPs on the carbon support and thus plays a significant role in hindering the degradation of the catalytic activities of Pt NPs. As expected, the as-obtained Pt/NHCSs displayed improved catalytic activity and superior durability toward the ORR.
Ultra-compact plasmonic waveguides with high efficiency dipole nanoantennas

We present the design and characterization of ultra-compact plasmonic waveguides incorporating four highly efficient nanoantennas. Free space radiation is coupled into the waveguide from a fiber with high numerical aperture (NA) and the couple-out radiations are measured and compared.
16.7 A 12b 10GS/s interleaved pipeline ADC in 28nm CMOS technology

Software defined radios and wideband instrumentation demand the ability to digitize wide BW RF signals with moderately high dynamic range. A 12b 10GS/s ADC with an input analog bandwidth of 7.4GHz is developed for such applications in 28nm CMOS. The ADC achieves an SNR of 56dB, SNDR of 55dB and SFDR of 64dB with a 4GHz input at 10GS/s, and realizes an NSD of −157dBFS/Hz (i.e. DR = 60dB) while dissipating 2.9W.
Activation of Gαq Signaling Enhances Memory Consolidation and Slows Cognitive Decline

Perhaps the most devastating decline with age is the loss of memory. Therefore, identifying mechanisms to restore memory function with age is critical. Using C. elegans associative learning and memory assays, we identified a gain-of-function Gαq signaling pathway mutant that forms a long-term (cAMP response element binding protein [CREB]-dependent) memory following one conditioned stimulus-unconditioned stimulus (CS-US) pairing, which usually requires seven CS-US pairings. Increased CREB activity in AIM interneurons reduces the threshold for memory consolidation through transcription of a set of previously identified "long-term memory" genes. Enhanced Gαq signaling in the AWC sensory neuron is both necessary and sufficient for improved memory and increased AIM CREB activity, and activation of Gαq specifically in aged animals rescues the ability to form memory. Activation of Gαq in AWC sensory neurons non-cell autonomously induces consolidation after one CS-US pairing, enabling both cognitive function maintenance with age and restoration of memory function in animals with impaired memory performance without decreased longevity.
Public service for all: How a global ethic prepares public administrators for a transnational century

In this moment of populist mistrust of globalization and amid attacks on liberal values of democracy, how can we best train the next generation of public administration professionals to serve a cit...
Low-lying levels in 148Pm.

The /sup 149/Sm(d,/sup 3/He) reaction has been used to populate levels in /sup 148/Pm. Nineteen new excited states have been observed below 1 MeV excitation energy in /sup 148/Pm. The possible astrophysical implications of these results are discussed.
Kidney Blood Flow Changes in Shock

The syndrome of multiple-system organ failure (MSOF) was originally suggested by Baue [1] to be the sequential failure of two or more organ systems in critically ill patients. These initial patients were ill from diverse causes such as pancreatitis, heart disease and a leaking colon anastomosis. This orig inal observation was later confirmed and placed in to better focus by Eiseman [2] and Fry [3] where systemic infection was the identified common ethiologic thread. Although these reports devel oped mostly following multiple trauma, MSOF is currently recognized in a multitude of scenarios such as volume or cardiogenic shock, systemic in fection or the persistent foci of dead tissue. Invasive infection from an identifiable source need not be present for the development of the syndrome, but clearly the circulatory and hypermetabolic state commonly identified in sepsis is a constant feature of MSOF, implying activation of the inflammation cascade as an etiologic factor.
Response to Part IV: Seeing the Whole Iceberg—The Critical Role of Tasks, Inquiry Stance, and Teacher Learning in Lesson Study

Taken together, the three chapters in this part help to illuminate several critical features of lesson study that have not been strongly emphasized in prior accounts of lesson study.
Intellectual Assessment of Deaf and Hard-of-Hearing People: A Quantitative and Qualitative Research Synthesis.

A review of published and unpublished literature (N studies = 285; total N subjects > 171,517) describing the intelligence of deaf and hard-of-hearing people was conducted to determine: (a) assessm...
Duff on Attempts

Antony Duff has had an immense amount to say about crime and punishment. There is hardly any topic within that vast domain on which he hasn’t commented, and commented with great intelligence. Among the doctrinal precincts of criminal law, however, there is only one to which Duff devoted an entire book, and that is the law of attempts. And it is Duff’s elaboration and criticisms of the law of attempts, primarily as they are presented in that book, on which I shall comment in this chapter. My way of presenting Duff’s ideas on attempts will be by contrasting his ideas with my interpretation of orthodox doctrine, particularly as that is reflected in the Model Penal Code. As I proceed through the doctrinal elements of attempts, I shall first give my take on the orthodox doctrine regarding the element in question and then give Duff’s view on how that element should be handled. Near the end of the chapter I shall present my own views about attempts.
Occult blood in faeces: a window into health beyond the colorectum?

After decades of research, testing for occult blood in faeces is firmly established as a method to screen for colorectal cancer (CRC). Such testing is based on the relatively simple premise that asymptomatic CRCs, and some CRC precursors, may lose small amounts of blood into faeces. The provocative study by Libby et al in Gut ,1 which reports the associations between a positive guaiac faecal occult blood test (gFOBT) result and all-cause as well as non-CRC mortality in the National Health Service Tayside Board area of Scotland, suggests that occult blood in faeces may be telling us more than we might have thought. If the eye is the window to the soul, is a faecal test the window to general health? The current study confirms and expands on the observations of Chen et al , who reported a gradient relationship between all-cause mortality and faecal haemoglobin (f-Hb) concentration in population-based screening programmes in Keelung and Tainan, Taiwan.2 Chen et al and Libby et al found associations between occult blood in faeces and CRC mortality, which is not surprising. However, in the study by Chen et al , with median follow-up of 3.5 years and longest follow-up of 8 years, the adjusted HRs for all-cause mortality ranged from 1.15 (95% CI 1.07 to 1.24) to 1.67 (95% CI 1.54 to 2.07) for persons with f-Hb concentrations of 20–49 and ≥450 ng Hb/mL, respectively (trend test p<0.0001), compared with the reference group of 1–19 ng Hb/mL (whose risk did not differ from that of persons with undetectable f-Hb). …
Antibody-Drug Conjugate that Exhibits Synergistic Cytotoxicity with an Endosome-Disruptive Peptide.

Antibody–drug conjugates are an important class of cancer therapeutics. These agents generally bind a specific cell surface receptor, undergo receptor-mediated endocytosis, and enter the endosomal–...
The High Court Rules that Post-Petition Income Taxes on the Sale of Farm Assets Are Not Discharged Pursuant to Chapter 12 of the Bankruptcy Code

In Hall v. U.S., 132 S. Ct. 1882 (2012), the Supreme Court ruled that federal income tax liabilities due to individual debtors’ sales of farm assets during the pendency of a Chapter 12 bankruptcy reorganization are not subject to collection or discharge in the debtors’ plan. The Court opined that the post-petition income taxes are not unsecured claims under Bankruptcy Code §1222(a)(2)(A) as they were not “incurred by the estate” under Bankruptcy Code §503(b). Under Code §1222(a)(2)(A), a Chapter 12 plan must provide for full payment of all claims entitled to priority under Code §507 unless the claim is owed to a governmental unit arising from the sale of any farm asset used in the debtor’s farming operation, in which case it will be treated as an unsecured claim. Code §507(a)(8) gives priority to certain pre-petition taxes while Code §507(a)(2) gives priority to administrative expenses allowed under Code §503(b). Code §503(b)(1)(B)(i) allows for any tax “incurred by the estate” to be treated as an administrative expense. The Court gave the phrase “incurred by the estate” its plain meaning and applied I.R.C. §§1398 and 1399, reasoning that under I.R.C. the Chapter 12 estate was not a separate taxable entity and that the debtor was individually responsible for the tax. In reaching its decision, the Court viewed the statute’s plain language, context, and structure.
Feasibility and acceptability of a structured quality by design approach to enhancing the rigor of clinical studies at an academic health center

Introduction Clinical trials are a critical step in the meaningful translation of biomedical discoveries into effective diagnostic and therapeutic interventions. Quality by design (QbD) is a framework for embedding quality into the design, conduct, and monitoring of clinical trials. Here we report the feasibility and acceptability of a process for implementing QbD in clinical research at an academic health center via multidisciplinary design studios aimed at identifying and prioritizing critical to quality (CTQ) factors. Methods The Clinical Trial Transformation Initiative's Principles Document served as a guide to identify and categorize key CTQ factors, defined as elements of a clinical trial that are critical to patient safety and data integrity. Individual trials were reviewed in CTQ design studios (CTQ-DS) and the feasibility and acceptability of this intervention was examined through post-meeting interviews and surveys. Results Eight clinical research protocols underwent the QbD evaluation process. The protocols ranged from multicenter randomized clinical trials to nonrandomized investigator-initiated studies. A developmental evaluation informed the iterative refinement of the CTQ-DS process, and post-meeting surveys revealed that CTQ-DS were highly valued by principal investigators (PIs) and resulted in multiple protocol changes. Conclusions The present study demonstrated that QbD principles can be implemented to inform the design and conduct of clinical research at an academic health center using multidisciplinary design studios aimed at identifying and prioritizing CTQ elements. This approach was well received by the participants including study PIs. Future research will need to evaluate the effectiveness of this approach in improving the quality of clinical research.
It Was Actually Pretty Easy": COVID-19 Compliance Cost Reductions in the WIC Program."

In recent years, scholars have examined the barriers to accessing public assistance benefits. Research identifies learning, compliance, and psychological costs as deterring program use. Compliance costs reflect the burdens of following program rules, which may entail providing documentation, responding to discretionary demands of bureaucrats, or attending appointments to maintain benefits. Studies identify one element of compliance costs-quarterly appointments-as a barrier to continued WIC participation. This article draws on 44 in-depth qualitative interviews with participants in the Special Supplemental Nutrition Assistance Program for Women, Infants, and Children (WIC). We examine how WIC participants perceive the reduction of compliance costs following the implementation of remote appointments in response to the COVID-19 pandemic. WIC participants report satisfaction with remote appointments and a reduction in the compliance costs of accessing and maintaining benefits. We conclude by recommending longer term changes to policy and practices to increase access and continuity in WIC receipt.
The Impact of Managed Care on Residency Training in the Americas

Psychiatric residency training in the United States has been and will continue to be greatly affected by changes in the systems of reimbursement and care, largely, but not exclusively driven by managed care. This paper has summarized some of the changes that reimbursement and care have on residency training and proposed solutions that will benefit the fiscal health of academic departments and the educational integrity of our training programs.1
Does prophylactic treatment of patent ductus arteriosus affect utilization of hospital resources

Introduction: Patent ductus arteriosus (PDA) and its treatment are associated with multiple serious complications in very low birth weight (VLBW) infants. Methods: We retrospectively evaluated the effect of prophylactic PDA treatment with Indomethacin on markers of utilization of hospital resources in a regional neonatal intensive care unit (NICU) between January 1, 2005 and April 30, 2007, including a six month epoch when PDA prophylactic treatment with indomethacin was used in the study site. Infants with gestational ages less than 28 weeks who survived for more than two days were included in the analysis. Results: Twenty infants received Indomethacin prophylactic treatment (treatment group) and 59 received no prophylactic treatment (control group). Infants in the treatment group had similar median gestational age; 26 weeks, but higher birth weights (mean ± SD); 964 ± 247 vs 838 ± 198 grams, p = 0.043 compared to control infants. Prophylactically treated infants needed rescue PDA pharmacologic treatment less frequently (20% vs 63%, p = 0.002) but had similar rates of surgical ligation (30% vs 29%) compared to control infants. Prophylactically treated infants also had significantly higher rates of intestinal perforation (25% vs 7%, p = 0.041) and abdominal surgeries (30% vs 8%, p = 0.03) compared to control infants. The two groups had similar, duration of support with mechanical ventilation and similar duration of supplement with parenteral nutrition. Treatment and control infants had similar rate of survival to discharge to home, 17 (85%) vs 45 (76%). Surviving treated and control infants did not differ statistically in total observed hospital length of stay (LOS in days, mean ± SD); (96 ± 32 vs 89 ± 29; p = 0.43) nor in the difference between observed and predicted LOS (mean observed- predicted ± SD) (10 ±23 vs1 ± 23; p = 0.14). Conclusions: Prophylactic PDA treatment with Indomethacin did not decrease duration of mechanical ventilation or TPN supplementation but was associated with more intestinal perforations and abdominal surgeries. The unfavorable trend in LOS for the treatment group implies that the independent effect of prophylactic PDA treatment on LOS needs to be further explored.
Nanoparticle arrays as model catalysts: Microstructure, thermal stability and reactivity of Pt/SiO2 and Ag/Al2O3 fabricated by electron beam lithography

Electron beam lithography was utilized to produce well-ordered two dimensional arrays of Pt and Ag nanoparticles on silica and alumina. The mean size of the particles was varied between 20 and 50 nm, with interparticle distances of 100 and 200 nm. Due to the narrow size distribution of the particles, these arrays are ideal models for supported metal catalysts. The thermal stability of the arrays and the effect of annealing in different gases were examined by HRTEM and AFM. Pt nanoparticle arrays were stable up to 973 K, which is the onset temperature for recrystallization. Reaction studies of ethylene hydrogenation on Pt nanoparticle arrays yielded rates that are comparable to conventional catalysts. Ag nanoparticles were stable in vacuum and hydrogen up to 773 K, while rapid evaporation occurred above 873 K. In oxygen, the Ag arrays remained intact up to 623 K but sintered at higher temperature.
Donor Cell Leukemia in Umbilical Cord Blood Transplant Patients: A Case Study and Literature Review Highlighting the Importance of Molecular Engraftment Analysis

Donor cell neoplasms are rare complications of treatment regimens that involve stem cell transplantation for hematological malignancies, myelodysplastic processes, or certain genetic or metabolic disorders. We report a case of donor cell leukemia in a pediatric patient with a history of acute myeloid leukemia that manifested as recurrent AML FAB type M5 fourteen months after umbilical cord blood transplantation. Although there was some immunophenotypic drift from the patient's original AML and their posttransplant presentation, the initial pathological impression was of recurrent disease. Bone marrow engraftment analysis by multiplex PCR of short tandem repeat markers performed on the patient's diagnostic specimen showed complete engraftment by donor cells, with a loss of heterozygosity in the donor alleles on chromosome 7. This led to the reinterpretation of this patient's disease as donor-derived leukemia. This interpretation was supported by a routine karyotype and fluorescence in situ hybridization analysis showing loss of chromosome 7 and a male (donor) chromosome complement in this female patient. Also noted was a loss of the patient's presenting chromosomal abnormality, t(11;19)(q23;p13). This case highlights the need for close coordination between all aspects of clinical testing for the transplant patient, including molecular engraftment studies, when distinguishing the very common complication of recurrent disease from the exceedingly rare complication of donor cell leukemia.
Prenatal development of retinocollicular projections in the cat: an anterograde tracer transport study

The retinal projection to the superior colliculus of the cat was examined at four gestational ages, embryonic days 38, 46, 56, and 61, using the antegrade transport of horseradish peroxidase and tritiated leucine. Gestation in the cat averages 65 days. By the 38th day of gestation (E38), the anlage of the entire superior colliculus, both ipsilateral and contralateral to an injection, was labeled intensely. The peroxidase label had an extremely coarse grained texture. As late as E46, the ipsilateral retinal projection extended to the presumed caudal border of the colliculus, while by E56, as in the mature cat, the ipsilateral terminal field was largely excluded from the rostral and caudal tectal poles. The contralateral terminal field at E56, as in younger fetal material, extended across the entire tectal mantle. By E61, clear gaps of label were observed in the contralateral stratum griseum superficiale. At this age, patches or bands of label were accentuated on the ipsilateral side. In double labeled tissue, it could be demonstrated that the ipsilateral patches corresponded quite closely to the gaps in the contralaterally derived label. Thus, a few days before birth, the retinal projection to the superior colliculus has a pattern which resembles that of the adult.
Human thymidylate synthetase—III: Effects of methotrexate and folate analogs

Abstract The structure-activity relationship of human thymidylate synthetase (EC 2.1.1.45) was studied with two groups of folate analogs: (1) methotrexate (MTX) analogs modified at the glutamate residue and N 10 ; and (2) tetrahydrofolate (H 4 PteGlu) analogs modified at N 5 and N 10 . With respect to MTX analogs, it was found that: (1) substitution of the glutamate side chain by α-aminoadipic acid. α-aminopimelic acid or β-aminoglutaric acid slightly affects its K i ; (2) a free α-carboxyl group on the amino acid side chain of MTX, or any free carboxyl group in that vicinity plays an important role in the inhibitory potency of MTX analogs to the enzyme; (3)esterification or amidation of the α-carboxyl group of MTX decreases the inhibitory potency; and (4) free aspartyl or glutamyl conjugation through a peptide linkage to the γ-carboxyl group of the glutamate side chain decreases its K i to the enzyme by 5- and 8-fold respectively. Tetrahydrofolate analogs formed by inserting an ethylene, iminyl or a carbonyl bridge between the nitrogen at N 5 and N 10 or by substitution at the N 5 position were found to be poor inhibitors under our assay conditions.
Effect of inhaled crystalline silica in a rat model: time course of pulmonary reactions.

Numerous investigations have been conducted to elucidate mechanisms involved in the initiation and progression of silicosis. However, most of these studies involved bolus exposure of rats to silica, i.e. intratracheal instillation or a short duration inhalation exposure to a high dose of silica. Therefore, the question of pulmonary overload has been an issue in these studies. The objective of the current investigation was to monitor the time course of pulmonary reactions of rats exposed by inhalation to a non-overload level of crystalline silica. To accomplish this, rats were exposed to 15 mg/m3silica, 6 h/day, 5 days/week for up to 116 days of exposure. At various times (5-116 days exposure), animals were sacrificed and silica lung burden, lung damage, inflammation, NF-KB activation, reactive oxygen species and nitric oxide production, cytokine production, alveolar type II epithelial cell activity, and fibrosis were monitored. Activation of NF-KB/DNA binding in BAL cells was evident after 5 days of silica inhalation and increased linearly with continued exposure. Parameters of pulmonary damage, inflammation and alveolar type II epithelial cell activity rapidly increased to a significantly elevated but stable new level through the first 41 days of exposure and increased at a steep rate thereafter. Pulmonary fibrosis was measurable only after this explosive rise in lung damage and inflammation, as was the steep increase in TNF-a and IL-1 production from BAL cells and the dramatic rise in lavageable alveolar macrophages. Indicators of oxidant stress and pulmonary production of nitric oxide exhibited a time course which was similar to that for lung damage and inflammation with the steep rise correlating with initiation of pulmonary fibrosis. Staining for iNOS and nitrotyrosine was localized in granulomatous regions of the lung and bronchial associated lymphoid tissue. Therefore, these data demonstrate that the generation of oxidants and nitric oxide, in particular, is temporally and anatomically associated with the development of lung damage, inflammation, granulomas and fibrosis. This suggests an important role for nitric oxide in the initiation of silicosis. (Mol Cell Biochem 234/235: 177–184, 2002)
Beating the Grog

In Indigenous communities across Australia, alchol misuse has had devastating social and health consequences. To date, there have been multiple strategies enacted by both the Australian government and local communities. However, the government legislation has been critized for being culturally insensitive and draconian; additionally, Aboriginal communities have not been able to achieve much success combating alcohol on their own. The majority of successful restrictions have a combination of local community intervention as well as strong legislature.
Aspects of Data Base Systems for Computer Aided Design

This paper is intended to familiarize with data base system technology. In its first part it describes the objectives and structure of data base management systems and discusses important concepts. Special emphasis is put on the aspects of interactive usage. In the second part data base management systems are reviewed with respect to requirements of computer aided design. In the third part a proposal for an interactive problem solving environment is discussed to give further insight to the interactive design process. Textbooks and surveys may serve for additional information on data base systems, e.g. /DATE75, WEDE74, ACM76, BLAS76/.
Steady progress and recent breakthroughs in the accuracy of automated genome annotation

The sequencing of large, complex genomes has become routine, but understanding how sequences relate to biological function is less straightforward. Although much attention is focused on how to annotate genomic features such as developmental enhancers and non-coding RNAs, there is still no higher eukaryote for which we know the correct exon-intron structure of at least one ORF for each gene. Despite this uncomfortable truth, genome annotation has made remarkable progress since the first drafts of the human genome were analysed. By combining several computational and experimental methods, we are now closer to producing complete and accurate gene catalogues than ever before.
Phylogenetic relationships among species groups of the virilis-repleta radiation of Drosophila.

r nae is the virilis–repleta radiation, as evaluated by the umber of species and species groups (Throckmorton, 962, 1975). The virilis and repleta species groups have een extensively used as model systems in the studies f mechanisms of speciation, mapping genes, and chroosomal rearrangements (Patterson and Stone, 1952; owell, 1997). Drosophila virilis is a prominent refernce species for comparison with D. melanogaster in regard to patterns and mechanisms of molecular and genomic evolution (Nurminsky et al., 1996; Hartl and ozovskaya, 1995). The Drosophila repleta group ithin this radiation is potentially very promising for he study of speciation mechanisms, because it dislays a range of different degrees of reproductive isoation among its members (Patterson and Stone, 1952). t also provides an example of a very rapid and sucessful radiation in the deserts. The phylogenetic relationships of species groups in he virilis–repleta radiation are largely unresolved in hrockmorton’s classifications. Moreover, there are ome discrepancies between his earlier (1962) and ater (1975) schemes. Improvement in the understandng of the phylogenetic relationships among the species roups and subgroups of the virilis–repleta radiation as come from cytological studies (reviewed in Wasseran, 1982, 1992; Powell, 1997), but there were few olecular studies considering intergroup and subroup relationships of the radiation. In a study based n 28S rRNA genes, Pelandakis and Solignac (1993) ncluded representatives of many groups of the virilis– epleta radiation. With the exception of D. polychaeta, hese groups form a monophyletic lineage, but with low ootstrap support (less than 50%) for the clade as a hole and for the relationships among species groups. ecently, Durando et al. (2000) have conducted a deailed phylogenetic analysis of the repleta species roup, which also includes three other groups of the
Tanshinone IIA reduces macrophage death induced by hydrogen peroxide by upregulating glutathione peroxidase.

Abstract Aims Tanshinone IIA is an important ingredient in the herb danshen ( Salvia miltiorrhiza ), which has been used to treat cardiovascular diseases such as atherosclerosis and angina for hundreds of years in China. There are numerous reports that TIIA has anti-oxidant properties but the chemical structure indicates that TIIA is fully oxidized. Here, we test the hypothesis that TIIA alters the expression and/or activity of specific anti-oxidation enzymes to protect cells from oxidant damage. Main methods We utilized J774 macrophages to model cellular responses to TIIA when challenged with H 2 O 2 . Expression and activity levels of several anti-oxidation enzymes were investigated and the only system modulated by TIIA was glutathione peroxidase (GPx). Key findings GPx-1 mRNA levels were significantly increased by TIIA but not the vitamin E analogue, Trolox. GPx activities were also significantly increased by TIIA. Mercaptosuccinic acid inhibited GPx activity and the protective effect of TIIA was attenuated. Thus, TIIA protects cultured macrophages from H 2 O 2 -induced cell death and protection is mediated in large part by TIIA induction of GPx gene expression and activity. Significance Because of the importance of GPx in health and because TIIA is able to modulate GPx activity to some extent in cell culture, we suggest that TIIA is a worthwhile candidate for further study in animal models of atherosclerosis and eventually in human prospective trials.
Small-molecule inhibition of a depalmitoylase enhances Toxoplasma host-cell invasion

Although there have been numerous advances in our understanding of how apicomplexan parasites such as Toxoplasma gondii enter host cells, many of the signaling pathways and enzymes involved in the organization of invasion mediators remain poorly defined. We recently performed a forward chemical-genetic screen in T. gondii and identified compounds that markedly enhanced infectivity. Although molecular dissection of invasion has benefited from the use of small-molecule inhibitors, the mechanisms underlying induction of invasion by small-molecule enhancers have never been described. Here we identify the Toxoplasma ortholog of human APT1, palmitoyl protein thioesterase-1 (TgPPT1), as the target of one class of small-molecule enhancers. Inhibition of this uncharacterized thioesterase triggered secretion of invasion-associated organelles, increased motility and enhanced the invasive capacity of tachyzoites. We demonstrate that TgPPT1 is a bona fide depalmitoylase, thereby establishing an important role for dynamic and reversible palmitoylation in host-cell invasion by T. gondii.
Up-conversion single-photon detector using multi-wavelength sampling techniques

The maximum achievable data-rate of a quantum communication system can be critically limited by the efficiency and temporal resolution of the system’s single-photon detectors. Frequency up-conversion technology can be used to increase detection efficiency for IR photons. In this paper we describe a scheme to improve the temporal resolution of an up-conversion single-photon detector using multi-wavelength optical-sampling techniques, allowing for increased transmission rates in single-photon communications systems. We experimentally demonstrate our approach with an up-conversion detector using two spectrally and temporally distinct pump pulses, and show that it allows for high-fidelity single-photon detection at twice the rate supported by a conventional single-pump up-conversion detector. We also discuss the limiting factors of this approach and identify important performance-limiting trade offs.
Young Children's Discourse Strategies During Block Play: A Bakhtinian Approach

Abstract This study describes the application of Bakhtin's theories of dialogism to nineteen 5-year-old preschool children's communication strategies and the ways children appropriate meaning in block play. The observed frequency of communication strategies used in three different naturally emerging social relationships–1) individuals, 2) dyads, and 3) groups of three or more children–in a culturally diverse preschool program was investigated. Both quantitative and qualitative data were collected and analyzed. Using Corsaro's (1986) coding system for types of utterances, results indicated significant differences in the communication strategies of 5-year-old children engaged in block play. Significant differences were also found in the communication strategies with regard to social groupings. This study suggests that 5-year-old preschool children use communication strategies and appropriate shared meaning in block play, and is important in that it has implications for encouraging language development.
1H Nuclear Magnetic Resonance Metabolomics Analysis Identifies Novel Urinary Biomarkers for Lung Function

Chronic obstructive pulmonary disease (COPD), characterized by chronic airflow limitation, is a serious public health concern. In this study, we used proton nuclear magnetic resonance ((1)H NMR) spectroscopy to identify and quantify metabolites associated with lung function in COPD. Plasma and urine were collected from 197 adults with COPD and from 195 without COPD. Samples were assayed using a 600 MHz NMR spectrometer, and the resulting spectra were analyzed against quantitative spirometric measures of lung function. After correcting for false discoveries and adjusting for covariates (sex, age, smoking) several spectral regions in urine were found to be significantly associated with baseline lung function. These regions correspond to the metabolites trigonelline, hippurate and formate. Concentrations of each metabolite, standardized to urinary creatinine, were associated with baseline lung function (minimum p-value = 0.0002 for trigonelline). No significant associations were found with plasma metabolites. Urinary hippurate and formate are often related to gut microflora. This could suggest that the microbiome varies between individuals with different lung function. Alternatively, the associated metabolites may reflect lifestyle differences affecting overall health. Our results will require replication and validation, but demonstrate the utility of NMR metabolomics as a screening tool for identifying novel biomarkers of pulmonary outcomes.
Road traffic fatalities and economic development: National and Sub-National longitudinal analysis in China

Background Road Traffic Injury (RTI) is a global health problem. In China, 4 million traffic crashes occurred in 2010, led to 65 225 deaths, 254 075 injuries, and direct property loss of 140 million US dollars. Previous studies found that road traffic safety is closely associated with economic development, which is accompanied with motorisation and road construction. Communities usually do not realise the necessity to take actions to prevent traffic crashes until significant loss occurred. Aims/Objectives/Purpose To test a priori hypothesis of an inversed U-shaped relationship between economic development and traffic crashes/deaths/injuries rates in China. Methods Longitudinal regression models using RTI-related data, GDP, and population from Statistical Yearbooks of China 1996–2011. (data source?). Results/Outcome A consistent inversed U-shaped relationship was identified at both national and provincial level. At national level, the traffic fatality rate began to decline as GDP per capita grew from 2004, when China released its first national traffic law. Traffic fatality rate decreased significantly by 1.22 per 100 000 people (95% CI 0.90 to 1.53) with every $1000 increase of GDP per capita. Most provinces experienced the similar turning points also around 2004. Some provinces had higher traffic fatality rates than other provinces did. Provincial disparity is projected to increase in the absence of targeted intervention in high-risk provinces. Significance/Contribution to the Field This study is the first to focus on investigating the relationship between RTI and economic development in China. Other developing countries could learn from the experience of China to improve traffic safety by making and strengthening traffic laws.
Petrogenesis of isotopically unusual Pliocene olivine leucitites from Deep Springs Valley, California

High-K mafic alkalic lavas (5.4 to 3.2 wt% K2O) from Deep Springs Valley, California define good correlations of increasing incompatible element (e.g., Sr, Zr, Ba, LREE) and compatible element contents (e.g., Ni, Cr) with increasing MgO. Strontium and Nd isotope compositions are also correlated with MgO; 87Sr/86Sr ratios decrease and ɛNd values increase with decreasing MgO. The Sr and Nd isotope compositions of these lavas are extreme compared to most other continental and oceanic rocks; 87Sr/86Sr ratios range from 0.7121 to 0.7105 and ɛNd values range from −16.9 to −15.4. Lead isotope ratios are relatively constant, 206Pb/204Pb ∼17.2, 207Pb/204Pb ∼15.5, and 208Pb/204Pb ∼38.6. Depleted mantle model ages calculated using Sr and Nd isotopes imply that the reservoir these lavas were derived from has been distinct from the depleted mantle reservoir since the early Proterozoic. The Sr-Nd-Pb isotope variations of the Deep Springs Valley lavas are unique because they do not plot along either the EM I or EM II arrays. For example, most basalts that have low ɛNd values and unradiogenic 206Pb/204Pb ratios have relatively low 87Sr/86Sr ratios (the EM I array), whereas basalts with low ɛNd values and high 87Sr/86Sr ratios have radiogenic 206Pb/204Pb ratios (the EM II array). High-K lavas from Deep Springs Valley have EM II-like Sr and Nd isotope compositions, but EM I-like Pb isotope compositions. A simple method for producing the range of isotopic and major- and trace-element variations in the Deep Springs Valley lavas is by two-component mixing between this unusual K-rich mantle source and a more typical depleted mantle basalt. We favor passage of MORB-like magmas that partially fused and were contaminated by potassic magmas derived from melting high-K mantle veins that were stored in the lithospheric mantle. The origin of the anomalously high 87Sr/86Sr and 208Pb/204Pb ratios and low ɛNd values and 206Pb/204Pb ratios requires addition of an old component with high Rb/Sr and Th/Pb ratios but low Sm/Nd and U/Pb ratios into the mantle source region from which these basalts were derived. This old component may be sediments that were introduced into the mantle, either during Proterozoic subduction, or by foundering of Proterozoic age crust into the mantle at some time prior to eruption of the lavas.
Schistosome genetic diversity: the implications of population structure as detected with microsatellite markers

Blood flukes in the genus Schistosoma are important human parasites in tropical regions. A substantial amount of genetic diversity has been described in populations of these parasites using molecular markers. We first consider the extent of genetic variation found in Schistosoma mansoni and some factors that may be contributing to this variation. Recently, though, attempts have been made to analyze not only the genetic diversity but how that diversity is partitioned within natural populations of schistosomes. Studies with non-allelic molecular markers (e.g. RAPDs and mtVNTRs) have indicated that schistosome populations exhibit varying levels of gene flow among component subpopulations. The recent characterization of microsatellite markers for S. mansoni provided an opportunity to study schistosome population structure within a population of schistosomes from a single Brazilian village using allelic markers. Whereas the detection of population structure depends strongly on the type of analysis with a mitochondrial marker, analyses with a set of seven microsatellite loci consistently revealed moderate genetic differentiation when village boroughs were used to define parasite subpopulations and greater subdivision when human hosts defined subpopulations. Finally, we discuss the implications that such strong population structure might have on schistosome epidemiology.
Effects of the conformation of single-stranded DNA on renaturation and aggregation

Abstract Sedimentation behavior is used to follow strand combination in T7 DNA and to analyze the nature of the product formed. Complementary single strands of DNA apparently combine under any condition where the DNA double helix is stable. The rate of strand combination is most strongly influenced by the ionic strength and the degree of folding of the single strands; the nature of the product formed is determined by the degree of folding of the reactants. Temperature affects the reaction primarily through its influence on folding, except at temperatures near T m , where its effect on the stability of base pairing becomes dominant. Folding of the single strands (Studier, 1969) can decrease the rate of strand combination by orders of magnitude, by reducing the possibilities for pairing between complementary strands. Folding also inhibits the zippering up of joined strands, thus leading to multiple nucleations and consequent aggregation, as well as to the formation of complexes containing part native and part folded regions. If such nucleated complexes are placed under conditions which disrupt folding but do not separate strands, extensive zippering up occurs, but at least some aggregates do not dissociate. Perfect renaturation, that is, strand combination which produces perfectly native DNA, requires only that the single strands be unfolded and the native structure stable. Under such conditions, only those associations which put the two strands in register are stable, and once joined, the strands zipper up completely. No stable intermediates are detected. For unfolded molecules, the rate of renaturation increases with approximately the cube of the ionic strength, at least until 0.2 m -NaCl. The implications of these findings for the preparation and storage of singlestranded DNA and for studies of hybridization and homology are discussed. Perfect renaturation is found under quasi-physiological conditions; it seems only logical that the same factors which affect this reaction in vitro will also apply in vivo .