Measured proton electromagnetic structure deviates from theoretical predictions.

The visible world is founded on the proton, the only composite building block of matter that is stable in nature. Consequently, understanding the formation of matter relies on explaining the dynamics and the properties of the proton's bound state. A fundamental property of the proton involves the response of the system to an external electromagnetic field. It is characterized by the electromagnetic polarizabilities1 that describe how easily the charge and magnetization distributions inside the system are distorted by the electromagnetic field. Moreover, the generalized polarizabilities2 map out the resulting deformation of the densities in a proton subject to an electromagnetic field. They disclose essential information about the underlying system dynamics and provide a key for decoding the proton structure in terms of the theory of the strong interaction that binds its elementary quark and gluon constituents. Of particular interest is a puzzle in the electric generalized polarizability of the proton that remains unresolved for two decades2. Here we report measurements of the proton's electromagnetic generalized polarizabilities at low four-momentum transfer squared. We show evidence of an anomaly to the behaviour of the proton's electric generalized polarizability that contradicts the predictions of nuclear theory and derive its signature in the spatial distribution of the induced polarization in the proton. The reported measurements suggest the presence of a new, not-yet-understood dynamical mechanism in the proton and present notable challenges to the nuclear theory.

[Knobloch syndrome: a case report].

A 5-year-old girl came to the Tianjin Medical University Eye Hospital in May 2021 because of her poor eyesight after birth. The physical examination showed that she had high myopia, esotropia, horizontal tremor, and high myopia retinopathy of both eyes. After inquiring about her medical history, we found that the baby's occipital cystic mass swelled after birth, and CT examination showed that the occipital skull plate defect with meningocele, but without treatment, at present, the occipital mass had subsided by itself. Considering the eye manifestations and skull changes of the child, it may be conformed to Knobloch syndrome, after the detection of V4 by full exon gene, it was found that the child had the compound heterozygous variation of pathogenic gene COL18A1, and Knobloch syndrome was definite, Knobloch syndrome is a rare autosomal recessive hereditary disease with typical features of high myopia, retinal detachment and occipital encephalocele. At present, there is no clear treatment plan, and gene therapy may be an effective treatment for Knobloch syndrome in the future.

Consistency checks of results from a Monte Carlo code intercomparison for emitted electron spectra and energy deposition around a single gold nanoparticle irradiated by X-rays.

Organized by the European Radiation Dosimetry Group (EURADOS), a Monte Carlo code intercomparison exercise was conducted where participants simulated the emitted electron spectra and energy deposition around a single gold nanoparticle (GNP) irradiated by X-rays. In the exercise, the participants scored energy imparted in concentric spherical shells around a spherical volume filled with gold or water as well as the spectral distribution of electrons leaving the GNP. Initially, only the ratio of energy deposition with and without GNP was to be reported. During the evaluation of the exercise, however, the data for energy deposition in the presence and absence of the GNP were also requested. A GNP size of 50 nm and 100 nm diameter was considered as well as two different X-ray spectra (50 kVp and 100kVp). This introduced a redundancy that can be used to cross-validate the internal consistency of the simulation results. In this work, evaluation of the reported results is presented in terms of integral quantities that can be benchmarked against values obtained from physical properties of the radiation spectra and materials involved. The impact of different interaction cross-section datasets and their implementation in the different Monte Carlo codes is also discussed.

[Occurrence and prediction on post-contrast acute kidney injury following endovascular interventions].

Objective: To investigate the incidence, risk factors and prognosis of post-contrast acute kidney injury (PC-AKI) and to evaluate the usefulness of serum cystatin C (sCysC) and serum creatinine (sCr) for the prediction of PC-AKI after endovascular interventions. Methods: The clinical data of 404 patients who underwent endovascular procedures from August 2014 to October 2018 in the Sixth People's Hospital South Campus, Shanghai Jiao Tong University were retrospectively analyzed. All patients received 0.9% sodium chloride through an angiographic catheter during the procedure. Patients with an estimated GFR (eGFR)<60 ml/(min·1.73m2) received a continuous intravenous hydration with isotonic saline from 6 hours before to 12 hours after an endovascular procedure. The level of sCr, eGFR and sCysC were measured at 1-2 days pre-procedure and at 48, 72 h, and 7 days post-procedure. Univariate and multivariate logistic regression analyses were used to identify risk factors of PC-AKI. A receiver operator characteristic (ROC) curve was used to evaluate the usefulness of various factors for the prediction of PC-AKI. Kaplan-Meier method was used for survival analysis. Results: Thirteen patients (3.2%) developed PC-AKI. All patients were divided into PC-AKI group and no PC-AKI group for statistical comparison. Wilcoxon signed rank sum test revealed that sCr levels at 7 days post-procedure [63.0 (56.0, 74.0) µmol/L] were significantly lower than pre-procedure sCr levels [65.6 (56.2, 77.0) µmol/L] in patients without PC-AKI (P<0.05). Meanwhile, eGFR levels were significantly higher at 72 h [114.9 (96.3, 135.0) ml/(min·1.73m2)] and 7 days [116.7 (98.5, 139.9) ml/(min·1.73m2)] post-procedure than eGFR levels before endovascular procedures [112.3 (94.1, 133.5) ml/(min·1.73m2)] in patients without PC-AKI (P<0.05). However, there was an increase in sCysC at 48 h [0.9 (0.8, 1.1) mg/L] after endovascular procedures than pre-operative sCysC [0.9 (0.8, 1.1) mg/L] in patients without PC-AKI (P<0.05). SCr, sCysC, levels were significantly increased at 48 h [108.0 (95.3, 125.0) µmol/L, 1.5 (1.2, 2.0) mg/L] and 72 h [123.4 (91.3, 143.0) µmol/L, 1.6 (1.1, 2.0) mg/L] post-procedure than SCr, sCysC, levels before endovascular procedures [81.6 (63.1, 111.0) µmol/L, 1.1 (1.0,1.7) mg/L] and eGFR levels were significantly decreased at 48 h [55.8 (48.9, 77.6) ml/(min·1.73m2)] and 72 h [52.7 (47.7, 63.9) ml/(min·1.73m2)] after endovascular procedures than eGFR levels before exposure to CM [88.8 (65.6, 100.7) ml/(min·1.73m2)] in patients with PC-AKI (P<0.05). SCr, sCysC and eGFR in PC-AKI group tended to levels before an endovascular procedure within 7 days. The receiver operator characteristic curve (ROC) analysis showed that preoperative sCysC and sCr levels had high discriminatory power for evaluating the risk of PC-AKI after an endovascular procedure. ROC analysis showed that sCysC before endovascular procedures was useful to predict the risk of PC-AKI with a satisfactory sensitivity of 69.2% (9/13), specificity of 77.5% (300/387), positive predictive value (PPV) of 9.3% (9/96) and negative predictive value (NPV) of 98.7% (300/304). The incidence of PC-AKI was low in patients with a pre-procedure sCysC<1.09 mg/L. The sCr was predictive of PC-AKI with a satisfactory sensitivity of 69.2% (9/13), specificity of 76.7% (300/391), PPV of 9.0% (9/100) and NPV of 98.7% (300/304). The incidence of PC-AKI was low in patients with a pre-procedure sCr<77.6 µmol/L. Results of univariate analysis and multiple logistic regression analysis indicated that sCysC before endovascular procedures was an risk factor for PC-AKI (OR=13.917, 95%CI:1.666-116.237, P=0.015). The one-year, three-year and five-year survival rate for patients diagnosed with PC-AKI was 50%, 30% and 30% respectively. The median survival time was 6 (0-26) months. Conclusions: The sCysC before endovascular procedures is an independent risk factor of PC-AKI. SCysC and SCr before an endovascular procedure with a cut-off value of 1.09 mg/L and 77.6 µmol/L may help to rule out patients at lower risk of PC-AKI.

Unique Access to u-Channel Physics: Exclusive Backward-Angle Omega Meson Electroproduction.

Backward-angle meson electroproduction above the resonance region, which was previously ignored, is anticipated to offer unique access to the three quark plus sea component of the nucleon wave function. In this Letter, we present the first complete separation of the four electromagnetic structure functions above the resonance region in exclusive ω electroproduction off the proton, ep→e^{'}pω, at central Q^{2} values of 1.60, 2.45 GeV^{2}, at W=2.21 GeV. The results of our pioneering -u≈-u_{min} study demonstrate the existence of a unanticipated backward-angle cross section peak and the feasibility of full L/T/LT/TT separations in this never explored kinematic territory. At Q^{2}=2.45 GeV^{2}, the observed dominance of σ_{T} over σ_{L}, is qualitatively consistent with the collinear QCD description in the near-backward regime, in which the scattering amplitude factorizes into a hard subprocess amplitude and baryon to meson transition distribution amplitudes: universal nonperturbative objects only accessible through backward-angle kinematics.

Pituitary tumor transforming gene binding factor (PBF) is required for androgen-induced prostate cancer proliferation and invasion.

Pituitary tumor transforming gene binding factor (PBF) is a proto-oncogene that plays a role in many cancers; however, its involvement in prostate cancer (PCa) remains unclear. Here, we examined PBF expression in clinical specimens and investigated its regulation and function in human PCa cell lines. Immunohistochemical staining of patient tissues revealed higher PBF expression in PCa than in benign prostatic hyperplasia or adjacent normal prostate specimens. In LNCaP and 22Rv1 cells, PBF expression was upregulated by androgen treatment in a manner partially blocked by the androgen receptor (AR) antagonist bicalutamide. We identified a novel androgen response element in the PBF gene promoter and demonstrated its functional relevance using luciferase reporter assays. Androgen treatment of LNCaP cells induced binding between the endogenous AR and the androgen response element in PBF, as measured by chromatin immunoprecipitation assays. Finally, RNA interference of PBF expression significantly reduced androgen-induced LNCaP cell growth and invasion. Thus, PBF is a novel AR target gene and plays a role in androgen-induced proliferation and metastatic functions in PCa cells.

Evaluation of safety and efficacy of different continuous blood Purification methods in treating infantile sepsis.

The aim of this study was to compare the safety and the efficacy of two methods of continuous blood purification (CBP), continuous veno-venous hemofiltration (CVVH) and high volume hemofiltration (HVHF), for treatment of infantile sepsis. Eighty-six children with sepsis were enrolled in this study and randomly divided into two groups with 47 cases in the CVVH group and 39 cases in the HVHF group. Survival rate, duration of blood filtration, mean arterial pressure (MAP), mean heart rate and SaO2, APACHE II score, procalcitonin, hs-CRP and TXB2 were compared between the two groups. Results showed that survival rate, MAP, mean heart rate and SaO2 in the two groups did not have any significant differences. Duration of blood filtration and APACHE II score in the HVHF group was significantly shorter than that in the CVVH group. After therapy, levels of procalcitonin, hs-CRP and TXB2 declined dramatically in both groups, however this reduction was more significant in the HVHF group. We conclude that HVHF is a safer and more effective method as it produced stable hemodynamics, shorter filtration time, better APACHE II scores and better results in alleviating inflammatory reactions.

[Comparison of the pulmonary function between adolescent patients with Chiari malformation associated scoliosis and idiopathic scoliosis].

Objective: To compare the pulmonary function between adolescent patients with Chiari malformation associated scoliosis (CMS) and adolescent idiopathic scoliosis (AIS). Methods: A retrospective analysis was performed on 52 patients with CMS, and 52 patients with AIS were selected as the control group to match the CMS patients by age, sex, and Cobb angle. Preoperative pulmonary function tests were completed by all the patients, including vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in one second (FEV(1)), maximal mid-expiratory flow (MMEF), and ratio of FEV(1) to FVC. The difference of pulmonary function parameters was analyzed between the two groups; Correlation between pulmonary function and radiographic parameters was analyzed in patients with CMS. Results: There were no significant differences in terms of sex, age, and the main coronal Cobb angle between the two groups. There were 42(80.7%) and 44(84.6%) of patients with restrictive ventilatory dysfunction (the percentage of predicted FVC<80%) in CMS and AIS group respectively. 18(42.8%) and 10 (22.7%) out of these patients were also with obstructive ventilation dysfunction (FEV(1)/FVC<92%) in CMS and AIS group respectively. Types of ventilation dysfunction distributed between the two groups had no significant difference (P>0.05). No significant difference was noted between the two groups in the percentage of predicted VC, FVC, FEV(1) and FEV(1)/FVC (P>0.05). The percentage of predicted MMEF in patients with CMS was lower compared to those with AIS[(57.9±13.3)% vs (67.2±23.3)%, P=0.053]. In patients with CMS, the percentage of predicted VC, FVC, FEV(1) and MMEF had significantly negative correlation with the number of vertebrae involved (P<0.01). Main coronal Cobb angle had negative correlation with the percentage of predicted VC, FVC and FEV(1) (P<0.05). The percentage of predicted VC, FVC and FEV(1) had positive correlation with thoracic kyphosis (P<0.05). Conclusions: There are no significant differences in characteristics of the pulmonary dysfunction between patients with AIS and CMS without obviously neural deficit. Both groups mainly present with restrictive ventilation dysfunction.

Sentinel node necrosis is a negative prognostic factor in patients with nasopharyngeal carcinoma: a magnetic resonance imaging study of 252 patients.

PURPOSE: We explored the patterns of sentinel node metastasis and investigated the prognostic value of sentinel node necrosis (snn) in patients with nasopharyngeal carcinoma (npc), based on magnetic resonance imaging (mri). METHODS: This retrospective study enrolled 252 patients at our institution who had metastatic lymph nodes from biopsy-confirmed npc and who were treated with definitive radiation therapy, with or without chemotherapy. All participants underwent mri before treatment, and the resulting images were reviewed to evaluate lymph node status. The patients were divided into snn and non-snn groups. Overall survival (os), tumour-free survival (tfs), regional relapse-free survival (rrfs), and distant metastasis-free survival (dmfs) were calculated by the Kaplan-Meier method, and differences were compared using the log-rank test. Factors predictive of outcome were determined by univariate and multivariate analysis. RESULTS: Of the 252 patients, 189 (75%) had retropharyngeal lymph node metastasis, and 189 (75%) had level iia or iib lymph node necrosis. The incidence of snn was 43.4% (91 of 210 patients with lymph node metastasis or necrosis, or both). After a median follow-up of 54 months, the 5-year rates of os, tfs, rrfs, and dmfs in the snn and non-snn groups were, respectively, 79.4% and 95.3%, 73.5% and 93.3%, 80.4% and 96.6%, and 75.5% and 95.3% (all p < 0.01). Age greater than 40 years, snn, T stage, and N stage were significant independent negative prognostic factors for os, tfs, rrfs, and dmfs. CONCLUSIONS: Metastatic retropharyngeal lymph nodes and necrotic level ii nodes both seem to act as sentinels. Sentinel node necrosis is an negative prognostic factor in patients with npc. Patients with snn have a worse prognosis.

Identification of Genes Associated with Papillary Thyroid Carcinoma (PTC) for Diagnosis by Integrated Analysis.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma, and our understanding of its pathogenesis is incomplete. To elucidate the mechanisms underlying such progression and identify novel diagnostic markers, we aimed to discover the underlying gene associated with PTC. Integrated analysis of microarray datasets was performed to identify differentially expressed genes (DEGs) between PTCs and normal tissues. GO enrichment analysis and KEGG pathway enrichment analysis were then performed to uncover the functions of DEGs. Furthermore, the protein-protein interaction (PPI) network of DEGs was constructed. Five GEO datasets were obtained. Totally, 154 DEGs across the studies were identified, including 26 upregulated and 128 downregulated DEGs. In the PPI network, MLLT1, DLG2, and EFEMP1 were the hub proteins, in which DLG2 and EFEMP1 were involved in tumor progression. Among the top 10 up- and downregulated genes, the dysregulation genes of TPO, CDH16, and MPPED2 may be closely related to the tumorigenesis of PTC. By integrated analysis of multiple gene expression profiles, we propose that the dysregulation genes of TPO and MPPED2 will be the promising diagnostic markers for PTCs.

MOF-derived binary mixed metal/metal oxide @carbon nanoporous materials and their novel supercapacitive performances.

Mixed cobalt and manganese oxides embedded in the nanoporous carbon framework (M/MO@C) were synthesized by the direct carbonization of a binary mixed-metal organic framework (CoMn-MOF-74) for the first time. The unique M/MO@C carbon materials maintained the primary morphology of CoMn-MOF-74, and showed a uniform dispersibility of Co, MnO and CoO nanoparticles in the carbon matrix, and therefore greatly increased the conductivity of the M/MO@C materials. A series of M/MO@C samples were tested as the electrode materials for supercapacitors, and a remarkable specific capacitance of 800 F g(-1) was obtained using the M/MO@C-700 sample at a current density of 1 A g(-1) in 6 M KOH electrolyte. Moreover, the M/MO@C sample showed a good cycling stability with a capacitance retention of 85% after 1000 cycles. It is also found that the optimized carbonization temperature is a critical parameter to obtain such a M/MO@C nanoporous carbon framework with the best capacitive performances. The present approach is convenient and reproducible, which could be easily extended to the preparation of other M/MO@C composites with excellent electrochemical performances.

Rod-like CuMnOx transformed from mixed oxide particles by alkaline hydrothermal treatment as a novel catalyst for catalytic combustion of toluene.

Rod-like copper manganese mixed oxides (CuMnx-NR) have been synthesized from copper manganese mixed oxide particles by sodium hydroxide hydrothermal treatment, and a higher BET surface area of 221 m(2) g(-1) is obtained on the nanorod-like sample, which exhibits superior catalytic activity toward toluene combustion at 210 °C due to the increase in its oxygen mobility of the chemisorbed oxygen species as well as the increase in surface concentrations of higher valance cations, Cu(2+), Mn(3+) and Mn(4+), in the samples.

Ectopic expression of Arabidopsis thaliana Na+(K+)/H+ antiporter gene, AtNHX5, enhances soybean salt tolerance.

Drought and salt stresses are the two major factors influencing the yield and quality of crops worldwide. Na(+)(K(+))/H(+) antiporters (NHXs) are ubiquitous membrane proteins that play important roles in maintaining the cellular pH and Na(+)(K(+)) homeostasis. The model plant Arabidopsis potentially encodes six NHX genes, namely AtNHX1 to 6. In the present study, AtNHX5, a comparatively less well-studied NHX, was cloned and transferred into a soybean variety, Dongnong-50, via Agrobacterium-mediated cotyledonary node transformation to assess its role in improving salt tolerance of the transgenic plants. The transgenic soybean plants were tolerant to the presence of 300 mM NaCl whereas the non-transgenic plants were not. Furthermore, after NaCl treatment, the transgenic plants had a higher content of free proline but lower content of malondialdehyde compared to the non-transgenic plants. Our results revealed that that AtNHX5 possibly functioned by efficiently transporting Na(+) and K(+) ions from the roots to the leaves. Overall, the results obtained in this study suggest that soybean salt tolerance could be improved through the over expression of Arabidopsis AtNHX5.

[Effect of hyperbaric oxygen therapy on antioxidant capacity in brains of rats after acute carbon monoxide poisoning].

OBJECTIVE: This study was designed to observe the antioxidant effects of hyperbaric oxygen (HBO) on brains of rats after acute carbon monoxide (CO) poisoning. METHODS: Sixty-six Sprague-Dawley (SD) male rats were divided into three groups including control group, CO group and HBO group.Morris water maze experiments were used for monitoring cognitive function.Antioxidant capacities were evaluated by detecting T-AOC, GSH-PX, GR and CAT activities in the brain. RESULTS: Compared with the control group (45±17, 43±14, 35±12, 34±11, 29±13) s and the HBO group (40±10, 39±6, 35±9, 31±11, 21±10) s, the CO group (57±5, 54±8, 52±8, 52±10, 46±8) s had the longer escape latency (P<0.05). Compared with the control group (51±6) s and the HBO group(40±10) s, the CO group (8±5) s had the shorter swimming time in I quadrant (P<0.05). Compared with the control group (1.25±0.40) U/mg and the HBO group(0.97±0.31, 0.97±0.39, 1.45±0.15, 1.40±0.25, 1.20±0.20) U/mg, the CO group (0.68±0.09, 0.45±0.17, 0.71±0.18, 0.69±0.29, 0.48±0.29) U/mg had the lower T-AOC activity of brain tissue.The GSH-PX activity (42±13, 106±46, 197±49, 173±42, 429±58) U/mg in the CO group decreased compared with the control group (182±53) U/mg and the HBO group (203±63, 325±86, 389±29, 385±100, 453±32) U/mg.GR activity (4.3±0.7, 2.6±0.5, 3.0±1.2, 1.8±0.8, 3.2±1.9) U/mg in the CO group decreased compared with the control group(14.5±3.0) U/mg and the HBO group (13.9±3.3, 4.3±1.0, 3.9±0.7, 4.8±0.9, 4.6±0.9) U/mg.CAT activity (1.6±0.8, 4.3±1.6, 3.9±1.0, 8.5±2.6, 5.4±1.7) U/mg in the CO group decreased compared with the control group(5.2±1.3) U/mg and the HBO group (5.2±2.2, 8.8±2.8, 5.3±1.0, 9.2±2.1, 14.1±3.8) U/mg. CONCLUSIONS: HBO can improve the behavior of rats after acute CO poisoning.The antioxidant capacity in rat brain tissue after acute CO poisoning decreases, while after the HBO therapy, the antioxidant capacity in rat brain tissue can increase.

[The application value of two-dimensional image technology and three-dimensional visualization technology in hepatocellular carcinoma treated by associating liver partition and portal vein ligation for staged hepatectomy: a preliminary study].

OBJECTIVE: To preliminarily explore the application value of two-dimensional image technology and three-dimensional visualization technology in hepatocellular carcinoma(HCC) treated by associating liver partition and portal vein ligation for staged hepatectomy(ALPPS). METHODS: Clinical data of nineteen HCC patients treated by ALPPS were retrospectively analyzed in Sun-Yat-Sen Memorial Hospital of Sun Yat-Sen University from August 2013 to May 2015.Preoperative assessment, surgical planning and intraoperative guidance were assisted by traditional two-dimensional imaging technology(group 2D) in 15 cases, and the rest 4 cases were assisted by three-dimensional visualization technology(group 3D). RESULTS: Three-dimensional visualization technology offered precise, visual, and distinct images, calculated the liver volume precisely, achieved virtual simulation operations, and assisted the formulation of intraoperative decisions.The mean operation time of the first stage were(331.3±61.7)minutes and (261.3±21.4)minutes in group 2D and group 3D, and the mean volume of intraoperative bleedings were (360.7±51.9)ml and (300.0±40.8)ml, respectively.The mean operation time of the second stage were (199.3±41.0)minutes and (170.0±29.4)minutes in group 2D and group 3D, and the mean volume of intraoperative bleedings were (285.3±132.6)ml and (257.5±99.5)ml, respectively.The mean interval time between two stages of operations were (15.3±6.5)d and (13.8±5.1)d in group 2D and group 3D, and the mean hospital stays were (39.3±5.8)d and (31.5±7.5)d, respectively.There were 4 cases and 12 cases who accepted the second stage operation in group 2D and group 3D respectively.There were 7 cases(4 with grade A, 2 with grade B, 1 with grade C) and 2 cases(1 with grade A, 1 with grade B) with post-hepatectomy liver failure and 9 cases(4 with grade Ⅰ, 2 with grade Ⅱ, 1 with grade Ⅲ, 2 with grade Ⅳ) and 3 cases (1 with grade Ⅰ, 1 with grade Ⅱ, 1 with grade Ⅲ)with postoperative complications in group 2D and group 3D respectively.There were 2 cases and 0 case died after operation in group 2D and group 3D respectively.There were 3 cases and 1 case who were recurrent and 4 cases and 1 case died 6 months after surgery in group 2D and group 3D respectively. CONCLUSION: Three-dimensional visualization technology assisted the formulation of preoperative assessments and surgical planning individually and precisely, which displayed potential application value in HCC treated by ALPPS.

The Elimination Rate after Clozapine Overdose in Chinese Schizophrenia Patients: A Population Pharmacokinetics Model Study.

INTRODUCTION: The prescribing of clozapine in China is common because of its outstanding efficacy and low price. There have been many cases of clozapine overdose in China. However, studies about the pharmacokinetics after overdose in the Chinese have rarely been reported. Population pharmacokinetics (PopPK) can analyze sparse data, and it is appropriate to compute clozapine pharmacokinetics after overdose. METHODS: There were 47 clozapine overdose cases. We constructed a single-compartment first-order elimination PopPK model. We also considered some covariates that can influence the pharmacokinetics parameters. RESULTS: 21 cases were included in the analysis. When the reported toxic dosage was 3,740 mg, the elimination rate constant of the population was 0.0258(h(-1)). The elimination half-life was 26.9 h. The coefficient of random variation was 17%. DISCUSSION: PopPK can solve the problem of sparse data after overdose. The area under the concentration-time curve after clozapine overdose exhibited the "two peaks phenomenon." The reported toxic dosage could impact clozapine elimination after overdose. Delayed absorption of clozapine is the best explanation for this finding.

Calculation of internal dose from ingested soil-derived uranium in humans: Application of a new method.

The aim of the present study was to determine the internal dose in humans after the ingestion of soil highly contaminated with uranium. Therefore, an in vitro solubility assay was performed to estimate the bioaccessibility of uranium for two types of soil. Based on the results, the corresponding bioavailabilities were assessed by using a recently published method. Finally, these bioavailability data were used together with the biokinetic model of uranium to assess the internal doses for a hypothetical but realistic scenario characterized by a daily ingestion of 10 mg of soil over 1 year. The investigated soil samples were from two former uranium mining sites of Germany with (238)U concentrations of about 460 and 550 mg/kg. For these soils, the bioavailabilities of (238)U were quantified as 0.18 and 0.28 % (geometric mean) with 2.5th percentiles of 0.02 and 0.03 % and 97.5th percentiles of 1.48 and 2.34 %, respectively. The corresponding calculated annual committed effective doses for the assumed scenario were 0.4 and 0.6 µSv (GM) with 2.5th percentiles of 0.2 and 0.3 µSv and 97.5th percentiles of 1.6 and 3.0 µSv, respectively. These annual committed effective doses are similar to those from natural uranium intake by food and drinking water, which is estimated to be 0.5 µSv. Based on the present experimental data and the selected ingestion scenario, the investigated soils-although highly contaminated with uranium-are not expected to pose any major health risk to humans related to radiation.

Construction and analysis of a suppression subtractive hybridization library of regeneration-related genes in soybean.

The development of a genetic transformation system is needed to address the problem of the low efficiency associated with soybean regeneration. To contribute to the enhancement of the soybean regenerative capacity, we explored the developmental mechanisms of soybean regeneration at the molecular level using a suppression subtractive hybridization cDNA library constructed from cotyledonary nodes of soybean cultivar DN50. A total of 918 positive clones were identified and screened, with most inserted fragments ranging from 100 to 750 bp. Of these, 411 differentially expressed functional expressed sequence tags were identified and annotated based on their similarity to orthologs and paralogs detected in GenBank using the nucleotide and translated nucleotide Basic Local Alignment Search Tools. Functional analysis revealed that the associated genes were involved in signal transduction, synthesis, and metabolism of macromolecules, glucose and protein synthesis and metabolism, light and leaf morphogenesis, regulation of apoptosis, cell defense, cell wall differentiation, and a variety of hormone and cytokinin-mediated signaling pathways. The information uncovered in our study should serve as a foundation for the establishment of an efficient and stable genetic transformation system for soybean regeneration.

Estimating the absorption of soil-derived uranium in humans.

The aim of the present study was to improve the estimation of soil-derived uranium absorption in humans. For this purpose, an in vitro solubility assay was combined with a human study by using a specific edible soil low in uranium. The mean bioaccessibility of the soil-derived uranium, determined by the solubility assay in artificial gastrointestinal fluid, was found to be 7.7% with a standard deviation of 0.2%. The corresponding bioavailability of the soil-derived uranium in humans was assumed to be log-normal distributed with a geometric mean of 0.04% and a 95% confidence interval ranging from 0.0049% to 0.34%. Both results were used to calculate a factor, denoted as fA(sol), which describes the relation between the bioaccessibility and the bioavailability of soil-derived uranium. The geometric mean of fA(sol) was determined to be 0.53% with a 95% confidence interval ranging from 0.06% to 4.43%. Based on fA(sol), it is possible to estimate more realistic values on the bioavailability of uranium for highly uranium-contaminated soils in humans by just performing the applied solubility assay. The results of this study can be further used to obtain more reliable results on the internal dose assessment of ingested highly uranium-contaminated soils.