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We report the properties of primary cosmic-ray sulfur (S) in the rigidity range 2.15 GV to 3.0 TV based on 0.38 × 106 sulfur nuclei collected by the Alpha Magnetic Spectrometer experiment (AMS). We observed that above 90 GV the rigidity dependence of the S flux is identical to the rigidity dependence of Ne-Mg-Si fluxes, which is different from the rigidity dependence of the He-C-O-Fe fluxes. We found that, similar to N, Na, and Al cosmic rays, over the entire rigidity range, the traditional primary cosmic rays S, Ne, Mg, and C all have sizeable secondary components, and the S, Ne, and Mg fluxes are well described by the weighted sum of the primary silicon flux and the secondary fluorine flux, and the C flux is well described by the weighted sum of the primary oxygen flux and the secondary boron flux. The primary and secondary contributions of the traditional primary cosmic-ray fluxes of C, Ne, Mg, and S (even Z elements) are distinctly different from the primary and secondary contributions of the N, Na, and Al (odd Z elements) fluxes. The abundance ratio at the source for S/Si is 0.167±0.006, for Ne/Si is 0.833±0.025, for Mg/Si is 0.994±0.029, and for C/O is 0.836±0.025. These values are determined independent of cosmic-ray propagation.

ObjectiveLynch Syndrome (LS) carriers have a significantly increased risk of developing colorectal cancer (CRC) during their lifetimes. Further stratification of this patient population may help in identifying additional risk factors that predispose to colorectal carcinogenesis. In most LS patients CRC may arise from adenomas, although an alternative non-polypoid carcinogenesis pathway has been proposed for PMS2 carriers. Using data from our institutional LS cohort, our aim was to describe our current colorectal screening outcomes with a focus on the incidence of adenomas in the context of different MMR genotypes and patient demographics such as gender, race, and ethnicity.DesignWe collected demographics, genetic, colonoscopy, and pathology results from a total of 163 LS carriers who obtained regular screening care at MD Anderson Cancer Center. Data were extracted from the electronic health records into a REDCap database for analysis. Logistic regressions were performed to measure the association between MMR variants and the likelihood of adenomas, advanced adenomas, and CRC. Then, we analyzed the cumulative incidences of these outcomes for the first 36 months following enrollment using Kaplan-Meier incidence curves, and Cox proportional hazard regressions.ResultsOn multivariate analysis, age (≥45 years old) was associated with an increased risk of developing adenomas (P=0.034). Patients with a prior or active cancer status were less likely to develop adenomas (P=0.015), despite of the lack of association between surgical history with this outcome (P=0.868). We found no statistically significant difference in likelihood of adenoma development between MLH1 and MSH2/EPCAM, MSH6, and PMS2 carriers. Moreover, we observed no statistically significant difference in the likelihood of advanced adenomas or CRC for any measured covariates. On Cox proportional hazard, compared to MLH1 carriers, the incidence of adenomas was highest among MSH2/EPCAM carriers during for the first 36-months of follow-up (PP=0.073). No MMR carrier was more likely to develop advanced adenomas. No difference in the incidence of CRC by MMR gene (P=0.198).ConclusionScreening recommendations for CRC in LS patients should be based on specific MMR variants and should also be tailored to consider patient demographics.

Motivation Long-read sequencing methods have considerable advantages for characterizing RNA isoforms. Oxford Nanopore sequencing records changes in electrical current when nucleic acid traverses through a pore. However, basecalling of this raw signal (known as a squiggle) is error prone, making it challenging to accurately identify splice junctions. Existing strategies include utilizing matched short-read data and/or annotated splice junctions to correct nanopore reads but add expense or limit junctions to known (incomplete) annotations. Therefore, a method that could accurately identify splice junctions solely from nanopore data would have numerous advantages. Results We developed ‘NanoSplicer’ to identify splice junctions using raw nanopore signal (squiggles). For each splice junction, the observed squiggle is compared to candidate squiggles representing potential junctions to identify the correct candidate. Measuring squiggle similarity enables us to compute the probability of each candidate junction and find the most likely one. We tested our method using (i) synthetic mRNAs with known splice junctions and (ii) biological mRNAs from a lung-cancer cell-line. The results from both datasets demonstrate NanoSplicer improves splice junction identification, especially when the basecalling error rate near the splice junction is elevated. Availability and implementation NanoSplicer is available at https://github.com/shimlab/NanoSplicer and archived at https://doi.org/10.5281/zenodo.6403849. Data is available from ENA: ERS7273757 and ERS7273453. Supplementary information Supplementary data are available at Bioinformatics online.

BACKGROUND & AIMS: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC. METHODS: After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%. RESULTS: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients. CONCLUSIONS: The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC. publishedVersion

Supplemental material, sj-docx-1-jct-10.1177_23800844221109116 for Caries Preventive Interventions and Oral Health Inequalities: A Scoping Review by A.W. van Meijeren-van Lunteren, Y. You, H. Raat, E.B. Wolvius and L. Kragt in JDR Clinical & Translational Research

Background: Guselkumab effectively treats moderate-to-severe psoriasis. Methods: Patients were randomized to guselkumab, placebo with crossover to guselkumab at week 16, or adalimumab. The studies were identical through week 24. VOYAGE 1 evaluated continuous guselkumab treatment (adalimumab-crossover-to-guselkumab at week 52), while VOYAGE 2 assessed randomized withdrawal/retreatment (weeks 28-76). Open-label guselkumab treatment was administered starting at week 52 in VOYAGE 1 and week 76 in VOYAGE 2 and continued through week 252. Pooled safety data were adjusted by exposure and analyzed in the guselkumab groups, including placebo-crossover-toguselkumab (n = 1221) and adalimumab-crossover-to-guselkumab (n = 500), through week 264. Results: Patients were followed for a total of 7166 patient-years (PY). Overall, 1349 of 1721 guselkumab-treated patients (78.4%) continued treatment through week 252. The rates of adverse and serious adverse events were 149/100 PY and 5.01/100 PY, respectively. Rates of adverse events of interest were low: serious infections (0.85/100 PY), nonmelanoma skin cancer (0.34/100 PY), malignancies other than nonmelanoma skin cancer (0.45/100 PY), and major adverse cardiovascular events (0.29/100 PY). Year-to-year variability was evident, but no increasing trend was observed. Limitations: No direct treatment comparisons were possible after week 52. Conclusion: The safety profile remained consistent and favorable during 5 years of continuous guselkumab treatment of psoriasis.

Supplemental material, sj-docx-1-jct-10.1177_23800844221109116 for Caries Preventive Interventions and Oral Health Inequalities: A Scoping Review by A.W. van Meijeren-van Lunteren, Y. You, H. Raat, E.B. Wolvius and L. Kragt in JDR Clinical & Translational Research

BackgroundPostoperative cognitive dysfunction (POCD) is one of the common postoperative complications in the elderly. The main clinical manifestation is memory impairment, which can cause permanent damage and even dementia in severe cases. However, the pathogenesis of POCD is still unknown. Age and neuroinflammation are known to be closely related to its occurrence, while DNA methylation is very important for transcriptional silencing and neuroinflammation. Consequently, this study intended to establish a mouse model of POCD to explore the role of DNA methylation in regulating the expression of interleukin-1β which participated POCD in aged mice.MethodsPOCD model was established by exploratory laparotomy and evaluated by new object experiment and Y maze test. In addition, ELISA, RT-PCR, Western blotting, immunofluorescence, microglia isolation and flow cytometry methods were used to detect the inflammatory state of dorsal hippocampal after surgery. Moreover, MSP, MeDIP and IL-1β promoter DNA methylation sequencing were used to explore the regulation of DNA methylation on IL-1β in this model. Finally, Golgi staining and Western blotting were used to further explore the role of IL-1β in POCD and its possible mechanisms. ResultsCognitive impairment was observed in aged but not adult mice at 1 day after surgery. There was a significant correlation between the level of IL-1β in dorsal hippocampus and the performance of cognitive function. The microglia in the dorsal hippocampus was activated and the IL-1β promoter DNA methylation was decreased in the aged mice. The increased expression of IL-1β impaired synaptic plasticity and hippocampus-dependent memory formation. Intracerebroventricular administration of IL-1β receptor antagonist could prevent the cognitive impairment of aged mice after surgery, reverse the decrease of dendritic spine density and synapse-associated protein expression induced by surgery.ConclusionDNA methylation regulation may be an important mechanism for greater susceptibility to POCD in aged mice by regulating the expression of IL-1β. IL-1β inhibiting prevented surgery-induced cognitive decline and synaptic plasticity dysfunction. The research also provided a new target for the clinical prevention of the occurrence of POCD in the elderly.

Single-cell RNA sequencing (scRNA-seq) technologies and associated analysis methods have undergone rapid development in recent years. This includes methods for data preprocessing, which assign sequencing reads to genes to create count matrices for downstream analysis. Several packaged preprocessing workflows have been developed that aim to provide users with convenient tools for handling this process. How different preprocessing workflows compare to one another and influence downstream analysis has been less well studied.Here, we systematically benchmark the performance of 9 end-to-end preprocessing workflows (Cell Ranger, Optimus, salmon alevin, kallisto bustools, dropSeqPipe, scPipe, zUMIs, celseq2 and scruff) using datasets with varying levels of biological complexity generated on the CEL-Seq2 and 10x Chromium platforms. We compare these workflows in terms of their quantification properties directly and their impact on normalization and clustering by evaluating the performance of different method combinations. We find that lowly expressed genes are discordant between workflows and observe that some workflows have systematic biases towards particular classes of genomics features. While the scRNA-seq preprocessing workflows compared varied in their detection and quantification of genes across datasets, after downstream analysis with performant normalization and clustering methods, almost all combinations produced clustering results that agreed well with the known cell type labels that provided the ground truth in our analysis.In summary, the choice of preprocessing method was found to be less influential than other steps in the scRNA-seq analysis process. Our study comprehensively compares common scRNA-seq preprocessing workflows and summarizes their characteristics to guide workflow users.

BackgroundLow-dose antibiotic contamination in animal food is still a severe food safety problem worldwide. Penicillin is one of the main classes of antibiotics being detected in food. Previous studies have shown that transient exposure of low-dose penicillin (LDP) during early life resulted in metabolic syndrome (MetS) in mice. However, the underlying mechanism(s) and efficient approaches to counteracting this are largely unknown.MethodsWild-type (WT) or secretory IgA (SIgA)-deficient (Pigr-/-) C57BL/6 mice were exposed to LDP or not from several days before birth to 30 d of age. Five times of FMT or probiotics (a mixture of Lactobacillus bulgaricus and L. rhamnosus GG) treatments were applied to parts of these LDP-treated mice from 12 d to 28 d of life. Bacterial composition from different regions (mucosa and lumen) of the colon and ileum were analyzed through 16S rDNA sequencing. Intestinal IgA response was analyzed. Multiple parameters related to MetS were also determined. In addition, germ-free animals and in vitro tissue culture were also used to determine the correlations between LDP, gut microbiota (GM) and intestinal IgA response.ResultsLDP disturbed the intestinal bacterial composition, especially for ileal mucosa, the main inductive and effective sites of IgA response, in 30-d-old mice. The alteration of early GM resulted in a persistent inhibition of the intestinal IgA response, leading to a constant reduction of fecal and caecal SIgA levels throughout the 25-week experiment, which is early life-dependent, as transfer of LDP-GM to 30 d germ-free mice only resulted in a transient reduction in fecal SIgA. LDP-induced reduction in SIgA led to a decrease in IgA+ bacteria and a dysbiosis in the ileal mucosal samples of 25 week wild-type but not Pigr-/- mice. Moreover, LDP also resulted in increases in ileal bacterial encroachment and adipose inflammation, along with an enhancement of diet-induced MetS in an intestinal SIgA-dependent manner. Furthermore, several times of FMT or probiotic treatments during LDP treatment are efficient to fully (for FMT) or partially (for probiotics) counteract the LDP-effect on both GM and metabolism.ConclusionsEarly-life LDP-induced enhancement of diet-induced MetS is mediated by intestinal SIgA, which could be (partially) restored by FMT or probiotics treatment.

SUMMARYRecent studies have characterized the single-cell immune landscape of host immune response of coronavirus disease 2019 (COVID-19), specifically focus on the severe condition. However, the immune response in mild or even asymptomatic patients remains unclear. Here, we performed longitudinal single-cell transcriptome sequencing and T cell/B cell receptor sequencing on 3 healthy donors and 10 COVID-19 patients with asymptomatic, moderate, and severe conditions. We found asymptomatic patients displayed distinct innate immune responses, including increased CD56briCD16−NK subset, which was nearly missing in severe condition and enrichment of a new Th2-like cell type/state expressing a ciliated cell marker. Unlike that in moderate condition, asymptomatic patients lacked clonal expansion of effector CD8+T cells but had a robust effector CD4+T cell clonal expansion, coincide with previously detected SARS-CoV-2-reactive CD4+T cells in unexposed individuals. Moreover, NK and effector T cells in asymptomatic patients have upregulated cytokine related genes, such asIFNGandXCL2. Our data suggest early innate immune response and type I immunity may contribute to the asymptomatic phenotype in COVID-19 disease, which could in turn deepen our understanding of severe COVID-19 and guide early prediction and therapeutics.

Background : Cataracts are defects of the lens that cause progressive visual impairment and ultimately blindness in many vertebrate species. Most cataracts are age-related, but up to one third have an underlying genetic cause. Cataracts are common in captive zoo animals, but it is often unclear whether these are congenital or sporadic (age-related) lesions.Results: Here we used a functional candidate gene-screening approach to identify mutations associated with cataracts in a captive giant panda ( Ailuropoda melanoleuca ). We identified a novel missense mutation ( c.686G>A) in the MIP gene encoding major intrinsic protein, which is expressed in the lens and normally accumulates in the plasma membrane of lens fiber cells, where it plays an important role in fluid transport and cell adhesion. The mutation causes the replacement of serine with asparagine ( p.229S>N ) in the C-terminal tail of the protein, and modeling revealed that mutation-induced conformational changes may interfere with lens permeability and cell–cell interactions.Conclusions: The mutation was not found in healthy pandas, suggesting it could serve as a new informative marker to predict the risk of congenital cataracts in captive giant pandas.

Background Patients treated with tumour necrosis factor (TNF) inhibitors are at risk of new-onset tuberculosis (TB) or reactivation of latent tuberculosis infection (LTBI). Association between TB/LTBI and interleukin (IL)-23 inhibitors for psoriasis is unclear. Patients with LTBI typically initiate LTBI therapy before receiving biologics. Objectives Safety in moderate-to-severe psoriasis patients with LTBI treated with guselkumab (IL-23 inhibitor) and LTBI treatment was evaluated. Methods In the VOYAGE 1 & VOYAGE 2 studies, patients screened for LTBI were randomized to guselkumab, placebo, or adalimumab (TNF inhibitor) at baseline. Placebo -> guselkumab crossover occurred at week 16 and adalimumab -> guselkumab at week 52 (VOYAGE 1), or at week 28 or later (VOYAGE 2). Incidence of active TB, adverse events (AEs), serious AEs (SAEs), and markedly abnormal liver function tests [alanine aminotransferase test (ALT); aspartate aminotransferase test (AST)] were evaluated using pooled data through week 100 in guselkumab-treated patients receiving and not receiving LTBI treatment. Results At baseline, 130 randomized patients (guselkumab: n = 69; adalimumab: n = 36; placebo: n = 25) tested positive for LTBI and received concomitant LTBI treatments (LTBI+). No active TB was reported among guselkumab-treated patients without LTBI (LTBI-) through week 100. Two cases of active TB occurred in LTBI- patients treated with adalimumab. Through week 16, across all treatment groups, greater proportions of LTBI+ patients reported ALT and AST elevations compared with LTBI- patients. Through week 100, proportions of patients experiencing AEs and SAEs were comparable between LTBI+ and LTBI- patients. Conclusions No cases of active TB, including reactivation of LTBI, were reported in patients with or without LTBI treated with guselkumab through up to 2 years. LTBI treatment was effective across all treatment groups in preventing reactivation of LTBI. Long-term treatment with guselkumab was generally well-tolerated through up to 2 years in patients receiving LTBI medications.

Objective. Evaluate enthesitis, physical function, and health-related quality of life (HRQOL) among patients with psoriatic arthritis (PsA) who are naive to anti-tumor necrosis factor agents. Methods. In PSUMMIT 1 and 2, patients with PsA were randomized to placebo or ustekinumab 45 mg or 90 mg. Enthesitis was assessed at weeks 0 and 24 (Maastricht Ankylosing Spondylitis Enthesitis Score). Assessments included Health Assessment Questionnaire-Disability Index (HAQ-DI), Medical Outcomes Study Short Form-36 (SF-36) physical component summary/mental component summary (PCS/MCS), and American College of Rheumatology 20 (ACR20). Results. At Week 24, 21 had worsened enthesitis, 158 had improved enthesitis, and 412 had unchanged enthesitis. Improved enthesitis was associated with improvements in HAQ-DI and SF-36 MCS. Results were similar for ACR20 responders and nonresponders. Conclusion. Improvement in enthesitis at Week 24 was associated with improvements in physical function/HRQOL regardless of ACR20 response.

The evidences for the influence of thermonuclear (type-I) X-ray bursts upon the surrounding environments in neutron star low-mass X-ray binaries (LMXB) were detected previously via spectral and timing analyses. Benefitting from a broad energy coverage of Insight-HXMT, we analyze one photospheric radius expansion (PRE) burst, and find an emission excess at soft X-rays. Our spectral analysis shows that, such an excess is not likely relevant to the disk reflection induced by the burst emission and can be attributed to an enhanced pre-burst/persistent emission. We find that the burst and enhanced persistent emissions sum up to exceed Eddington luminosity by $\sim$ 40 percentages. We speculate that the enhanced emission is from a region beyond the PRE radius, or through the Comptonization of the corona., Comment: accepted by JHEA(Journal of High Energy Astrophysics)

Apparent molar volumes (VΦ) of hexane-1,2,3,4,5,6-hexol in aqueous solutions of 1- and 2-propanols were obtained from densities of ternary solutions, accurately measured with a quartz vibrating-tube densimeter at several temperatures in the range from (293.15 to 313.15) K. Refractive indexes (nD) measurements were also made for hexane-1,2,3,4,5,6-hexol + propanol + water at T = 298.15 K. The data of VΦ have been used to deduce the limiting partial molar volumes of hexane-1,2,3,4,5,6-hexol (V0Φ) and limiting partial molar volumes of transfer (ΔtrsV0Φ) from water to different alcohol solutions at different concentrations. From the values of nD, molar refractive indexes (RD) were calculated. Then the changes of these parameters were discussed in the light of interaction between solute and solvent and the different locations of the hydroxyl group in propanol isomers.

Eighty-seven methanol extracts of medicinal plants, most of them are currently used in Vietnamese oriental medicine, were screened for NF-κB inhibitory activity. Seven methanol extracts showed strong to moderate inhibitory activity. These include the extracts of Crinum latifolium (leaves), Evodia rutaecarpa (fruits), Polygonum cuspidatum (rhizoma), Perilla ocymoides (leaves), Rubia cordifolia (leaves), Scutellaria barbata (leaves) and Sparganium stenophyllum (leaves). The NF-κB inhibitory activities of several metabolites isolated from some of these plants were also reported.

Brain-derived neurotrophic factor (BDNF) stimulation of its high-affinity receptor TrkB results in activation of pro-survival cell-signalling pathways that can afford neuroprotection to the retina. Reduction in retrograde axonal transport of neurotrophic factors such as BDNF from the brain to the neuronal cell bodies in the retina has been suggested as a critical factor underlying progressive and selective degeneration of ganglion cell layer and optic nerve in glaucoma. We investigated the role of BDNF in preserving inner retinal homeostasis in normal and glaucoma states using BDNF+/- mice and compared it with wild type controls. This study demonstrated that BDNF+/- animals were more susceptible to functional, morphological and molecular degenerative changes in the inner retina caused by age as well as upon exposure to experimental glaucoma caused by increased intraocular pressure. Glaucoma induced a down regulation of BDNF/TrkB signalling and an increase in levels of neurotoxic amyloid β 1-42 in the optic nerve head which were exacerbated in BDNF+/- mice. Similar results were obtained upon analysing the human optic nerve head tissues. Our data highlighted the role of BDNF in maintaining the inner retinal integrity under normal conditions and the detrimental effects of its insufficiency on the retina and optic nerve in glaucoma. © 2014 Elsevier B.V.

Traditional information extraction methods mainly rely on visual feature assisted techniques; but without considering the hierarchical dependencies within the paragraph structure, some important information is missing. This paper proposes an integrated approach for extracting academic information from conference Web pages. Firstly, Web pages are segmented into text blocks by applying a new hybrid page segmentation algorithm which combines visual feature and DOM structure together. Then, these text blocks are labeled by a Tree-structured Random Fields model, and the block functions are differentiated using various features such as visual features, semantic features and hierarchical dependencies. Finally, an additional post-processing is introduced to tune the initial annotation results. Our experimental results on real-world data sets demonstrated that the proposed method is able to effectively and accurately extract the needed academic information from conference Web pages. © 2013 Springer-Verlag.

We report the observation by angle-resolved photoemission spectroscopy of an impurity state located inside the superconducting gap of Ba$_{0.6}$K$_{0.4}$Fe$_2$As$_2$ and vanishing above the superconducting critical temperature, for which the spectral weight is confined in momentum space near the Fermi wave vector positions. We demonstrate, supported by theoretical simulations, that this in-gap state originates from weak non-magnetic scattering between bands with opposite sign of the superconducting gap phase. This weak scattering, likely due to off-plane Ba/K disorders, occurs mostly among neighboring Fermi surfaces, suggesting that the superconducting gap phase changes sign within holelike (and electronlike) bands. Our results impose severe restrictions on the models promoted to explain high-temperature superconductivity in these materials., Comment: 8 pages, 5 figures. Accepted for publication in Physical Review X

A new glycosaminoglycan has been isolated from the giant African snail Achatina fulica. This polysaccharide had a molecular weight of 29,000, calculated based on the viscometry, and a uniform repeating disaccharide structure of --4)-2-acetyl,2-deoxy-alpha-D-glucopyranose (1--4)-2-sulfo-alpha-L-idopyranosyluronic acid (1--. This polysaccharide represents a new, previously undescribed glycosaminoglycan. It is related to the heparin and heparan sulfate families of glycosaminoglycans but is distinctly different from all known members of these classes of glycosaminoglycans. The structure of this polysaccharide, with adjacent N-acetylglucosamine and 2-sulfo-iduronic acid residues, also poses interesting questions about how it is made in light of our current understanding of the biosynthesis of heparin and heparan sulfate. This glycosaminoglycan represents 3-5% of the dry weight of this snail's soft body tissues, suggesting important biological roles for the survival of this organism, and may offer new means to control this pest. Snail glycosaminoglycan tightly binds divalent cations, such as copper(II), suggesting a primary role in metal uptake in the snail. Finally, this new polysaccharide might be applied, like the Escherichia coli K5 capsular polysaccharide, to the study of glycosaminoglycan biosynthesis and to the semisynthesis of new glycosaminoglycan analogs having important biological activities.

Optical variability occurs in the near-surface and upper ocean on very short time and space scales (e.g., milliseconds and millimeters and less) as well as greater scales. This variability is caused by solar, meteorological, and other physical forcing as well as biological and chemical processes that affect optical properties and their distributions, which in turn control the propagation of light across the air-sea interface and within the upper ocean. Recent developments in several technologies and modeling capabilities have enabled the investigation of a variety of fundamental and applied problems related to upper ocean physics, chemistry, and light propagation and utilization in the dynamic near-surface ocean. The purpose here is to provide background for and an introduction to a collection of papers devoted to new technologies and observational results as well as model simulations, which are facilitating new insights into optical variability and light propagation in the ocean as they are affected by changing atmospheric and oceanic conditions.

Proxy data constraining land and ocean surface paleo-temperatures indicate that the Middle Miocene Climate Optimum (MMCO), a global warming event at ∼15 Ma, had a global annual mean surface temperature of 18.4°C, about 3°C higher than present and equivalent to the warming predicted for the next century. We apply the latest National Center for Atmospheric Research (NCAR) Community Atmosphere Model CAM3.1 and Land Model CLM3.0 coupled to a slab ocean to examine sensitivity of MMCO climate to varying ocean heat fluxes derived from paleo sea surface temperatures (SSTs) and atmospheric carbon dioxide concentrations, using detailed reconstructions of Middle Miocene boundary conditions including paleogeography, elevation, vegetation and surface temperatures. Our model suggests that to maintain MMCO warmth consistent with proxy data, the required atmospheric CO2 concentration is about 460–580 ppmv, narrowed from the most recent estimate of 300–600 ppmv.

Utilizing general circulation models (GCMs) for paleoclimate study requires the construction of appropriate model boundary conditions. We present a middle Miocene paleotopographic and paleobathymetric reconstruction geographically constrained at 15 Ma for use in GCMs. Paleotopography and paleogeography are reconstructed using a published global plate rotation model and published geological data. Paleobathymetry is reconstructed through application of an age-depth relationship to a middle Miocene global digital isochron map, followed by the overlay of reconstructed sediment thickness and large igneous provinces. Adjustments are subsequently made to ensure our reconstruction may be utilized in GCMs.

Experimental study using nude mice human hepatocellular carcinoma (HCC) xenograft indicated that the combination treatment with iodine 131 (131I)-anti-human HCC isoferritin (131I-isoFtAb), cisplatin, and mixed bacterial vaccine (MBV) yielded better inhibition rate as compared with double combination or 131I-isoFtAb alone. Based on these findings, 25 patients with surgically proven nonresectable and pathologically proven HCC have been treated by radioimmunotherapy using 131I-isoFtAb intrahepatic arterial infusion as a part of multimodality treatment. Of the 25 patients, seven (28.0%) received second-look resection after marked shrinkage of tumor. The 1-year survival was 52.5% (12/23) and 2-year survival 27.7% (five of 18) in the entire series. Of the five patients with 2-year survival, four were in the second-look resection group. Patients with tumor less than or equal to 8 cm showed higher second-look resection rate (62.5% versus 11.8%) and 1-year survival (85.7% versus 37.5%) as compared with tumor greater than 8 cm. Mixed bacterial vaccine as adjuvant immunotherapy seemed effective to prolong survival. The 2-year survival was higher in patients with second-look resection as compared with those without (75.0% versus 14.3%). Thus, radioimmunotherapy using 131I-isoFtAb might be one of the modalities of choice, particularly in the conversion of nonresectable to resectable HCC in a well-designed multimodality treatment regimen.

Four Chinese patients with xeroderma pigmentosum (XP), who had different degrees of skin symptoms, were tested for their genetic complementation groups. Skin fibroblasts obtained from the patients were used for complementation analysis done by a cell-fusion technique. Three of the patients belonged to group C and one, who had the mildest cutaneous manifestations, to group E. This is the first report of a group E XP patient in China. Our present findings together with previous reports suggest that group C XP is more common in China, similar to the distribution among Caucasian XP patients but markedly different from the Japanese distribution.

A total of 1344 children, 3-5 yr old, from two rural counties, Haidian and Miyun, close to Beijing, China, were examined in 1992. A modified DDE Index was employed in this study, and a pre-designed formula was used to calculate an enamel defect score (EDS) for each individual in the study. Oral examination was performed by one dentist under natural light using a standard mouth mirror and dental probe. Developmental enamel lesions were diagnosed without drying or cleaning the teeth prior to examination. Results from this study showed that primary teeth with defective enamel were seen in 23.9% of the children examined, opacity in 1.6%, and hypoplasia in 22.2%. Among the teeth, maxillary central and lateral incisors were affected by enamel hypoplasia most often (40.8% and 39.2%), followed by maxillary canines (25.7%), maxillary 1st molars (22.1%), and mandibular 1st molars (18.5%). The enamel defects occurred more frequently on the buccal surfaces of teeth than on any other surface. The study did not find a significant association of the children's age, family socioeconomic status, and anthropometric measurements with the distribution of enamel defects. However, there was a significantly higher prevalence of teeth with defects in males compared to females (P < 0.001), as well as mean tooth surfaces with defects (P < 0.05), and mean EDS (P < 0.05). Children born prematurely were shown to have four times more enamel lesions than children who were full term (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

1. 1. The effects of prostaglandins (PGs) E1 and E2, testosterone, 17β-estradiol and indomethacin on the intestinal zinc transport rates of male and female rats were compared. 2. 2. pge1 stimulated ms (the zinc flux rate from mucosa-to-serosa) of jejunal segments from male rats but inhibited ms of those from female rats in Ussing chamber experiments. 3. 3. 17β-Estradiol inhibited ms of jejunal segments from male rats, while testosterone stimulated it in those from female rats. However, testosterone inhibited ms of segments isolated from male rats and 17β-estradiol that of those from female rats, while in segments from ovariectomized rats, both of these steroid hormones stimulated ms. 4. 4. When PGE2 was added to an indomethacin containing medium, ms significantly increased whereas Jsm (the zinc flux rate from serosa-to-mucosa) decreased further.

An efficient Euler and full Navier–Stokes solver based on a flux splitting scheme is presented. The original Van Leer flux vector splitting form is extended to arbitrary body-fitted co-ordinates in the physical domain so that it can be used with a finite volume scheme. The block matrix is inverted by Gauss–Seidel iteration. It is verified that the often used reflection boundary condition will produce incorrect flux crossing the wall and cause too large numerical dissipation if flux vector splitting is used. To remove such errors, an appropriate treatment of wall boundary conditions is suggested. Inviscid and viscous steady transonic internal flows are analysed, including the case of shock-induced boundary layer separation.