Miracle-dz/UniFAR-FTUs huggingface dataset:
Significance of IDH mutations varies with tumor histology, grade, and genetics in Japanese glioma patients

Mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are found frequently in malignant gliomas and are likely involved in early gliomagenesis. To understand the prevalence of these mutations and their relationship to other genetic alterations and impact on prognosis for Japanese glioma patients, we analyzed 250 glioma cases. Mutations of IDH1 and IDH2 were found in 73 (29%) and 2 (1%) cases, respectively. All detected mutations were heterozygous, and most mutations were an Arg132His (G395A) substitution. IDH mutations were frequent in oligodendroglial tumors (37/52, 71%) and diffuse astrocytomas (17/29, 59%), and were less frequent in anaplastic astrocytomas (8/29, 28%) and glioblastomas (13/125, 10%). The pilocytic astrocytomas and gangliogliomas did not have either mutation. Notably, 28 of 30 oligodendroglial tumors harboring the 1p/19q co‐deletion also had an IDH mutation, and these alterations were significantly correlated (P < 0.001). The association between TP53 and IDH mutation was significant in diffuse astrocytomas (P = 0.0018). MGMT promoter methylation was significantly associated with IDH mutation in grade 2 (P < 0.001) and grade 3 (P = 0.02) gliomas. IDH mutation and 1p/19q co‐deletion were independent favorable prognostic factors for patients with grade 3 gliomas. For patients with grade 3 gliomas and without 1p/19q co‐deletion, IDH mutation was strongly associated with increased progression‐free survival (P < 0.0001) and overall survival (P < 0.0001), but no such marked correlation was observed with grade 2 gliomas or glioblastomas. Therefore, IDH mutation would be most useful when assessing prognosis of patients with grade 3 glioma with intact 1p/19q; anaplastic astrocytomas account for most of these grade 3 gliomas. (Cancer Sci 2012; 103: 587–592)
HUT snow emission model and its applicability to snow water equivalent retrieval

The derivation, testing, and employment to parameter retrieval of the Helsinki University of Technology (HUT) snow microwave emission model is presented. The radiative transfer-based semi-empirical model describes the emission behavior of a homogeneous snowpack as a function of water equivalent (SWE), effective grain size, and density of snow. Additionally, the modeling approach takes into account the influence of soil surface, forest canopy, and atmosphere to spaceborne observed brightness temperature by using empirical and semi-empirical formulas. The comparison of model predictions with independent experimental data shows good correlations, especially in terms of spectral characteristics. This enables the development of a new inversion technique for the SWE retrieval from spaceborne data based on the developed model. The test results using special sensor microwave/imager (SSM/I) data from boreal forest zone showed SWE retrieval accuracies considerably higher than those obtained with conventional algorithms. A discussion and analysis on the feasibility of the new SWE retrieval technique for operational applications is also included.
Design of high-speed bit-serial divider in GF(2m)

In this paper, we reformulated the conventional iterative division algorithm by substituting the pre-defined variable and then updating its initial value accordingly. The reformulated division algorithm allows a restructuring of the divider architecture to further improve its operating speed without increasing latency and area cost. Using the proposed fast algorithm, we developed a high-speed bit-serial GF(2m) divider. Analytical results show that the cost of the initial value update and variable transformation in the reformulated algorithm is almost negligible in the hardware implementation. Our divider reduces the critical path delay. Compared with related divider designs, the proposed design has time and area advantages.
Developing new urban water supplies: investigating motivations and barriers to groundwater use in Cape Town

ABSTRACT Many cities are experiencing increasing water resource stress. In Cape Town, South Africa, surface water supplies are at a record low due to a multi-year drought crisis which began in 2015. This paper analyzes the range of motivations, possibilities and obstacles related to diversifying Cape Town’s water supply system through the upscaling of groundwater resources. Drawing on insights from local experts, it is maintained that uncertainty surrounding groundwater and drought-management practices present significant barriers to Cape Town’s ongoing water diversification efforts. This paper provides further insight and discussion for future water planning in Cape Town, as well as for other urban, water-scarce, regions.
In vitro and in vivo characterization of the dopamine D4 receptor, serotonin 5-HT2A receptor and alpha-1 adrenoceptor antagonist (R)-(+)-2-amino-4-(4-fluorophenyl)-5-[1-[4-(4-fluorophenyl)-4-oxobutyl] pyrrolidin-3-yl]thiazole (NRA0045).

(R)-(+)-2-Amino-4-(4-fluorophenyl)-5-[1-[4-(4-fluorophenyl)-4-oxobutyl]+ ++pyrrolidin-3-yl]thiazole (NRA0045), a novel thiazole derivative, has high affinities for the human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 2.54, 0.55 and 0.54 nM, respectively. NRA0045 is approximately 91-fold more potent at the dopamine D4.2 receptor, compared with human cloned dopamine D2L receptor. NRA0045 also has high affinities for the serotonin (5-HT)2A receptor (Ki = 1.92 nM) and alpha-1 adrenoceptor (Ki = 1.40 nM) but weak affinities (IC50 values are approximately 1 microM) for six other neurotransmitter receptors (adenosine1, 5-HT1A, 5-HT1C, dopamine transporter, alpha2A and alpha2A) and negligible affinities (IC50 values are over 10(-5) M) for 42 other receptors, including neurotransmitters and hormones, ion channels and second messenger systems. Locomotor hyperactivity induced by methamphetamine (1 mg/kg i.p.) in mice was dose-dependently antagonized by NRA0045 (ED50 = 0.5 mg/kg i.p. and 1.9 mg/kg p.o., respectively). Methamphetamine (10 mg/kg i.p.)-induced stereotyped behavior in mice was dose-dependently antagonized by NRA0045, whereas NRA0045 did not exceed 50% inhibition even at the highest dose given (30 mg/kg i.p.). Catalepsy was dose-dependently and significantly induced by NRA0045 in rats, whereas NRA0045 did not exceed 50% induction even at the highest dose given (30 mg/kg i.p.). Thus NRA0045 blocks behaviors associated with activation of the mesolimbic/mesocortical dopaminergic neurons more selectively than behaviors associated with nigrostriatal dopaminergic neurons. In rats, tryptamine-induced clonic seizure, a 5-HT2 receptor-mediated behavior, was also dose-dependently inhibited by NRA0045 (ED50 = 1.7 mg/kg i.p.). Norepinephrine-induced lethality is regarded as being induced through the alpha-1 adrenoceptor. NRA0045 dose-dependently antagonized norepinephrine-induced lethality in rats (ED50 = 0.2 mg/kg i.p.). Thus NRA0045 may have a unique antipsychotic activity with regard to dopamine D4 and 5-HT2A receptors and alpha-1 adrenoceptor antagonistic activities, without producing the extrapyramidal side effects.
The Complex Role of AR Signaling After Cytotoxic Insult: Implications for Cell Cycle Based Chemotherapeutics

Prostatic adenocarcinomas are dependent on androgen receptor (AR) signaling for growth and progression, in part through the ability of AR to induce G1-S phase cell cycle transition. Hormonal therapies that inhibit AR activity are the first line of intervention for disseminated disease, and are initially quite effective; however, recurrent, incurable tumors ultimately arise with restored AR function. Given the importance of AR in governing the potentiation of this tumor type, there has been a dedicated interest in dissecting the mechanisms by which AR promotes prostate cancer proliferation and survival. Recent studies have challenged the utility of manipulating AR activity to enhance cell death in combination with genotoxic insult. Herein, the role of AR in controlling cell cycle progression and paradoxical roles of AR in survival signals are considered, as are the potential implications of these findings for chemotherapeutic response. Although there is much to be resolved, the present data suggest that knowledge of AR action in promoting cellular proliferation can be utilized for the design of coordinate strategies that maximize cell death in response to cytotoxic chemotherapeutics.
Docosahexaenoic Acid Reduces ER Stress and Abnormal Protein Accumulation and Improves Neuronal Function Following Traumatic Brain Injury

In this study, we investigated the development of endoplasmic reticulum (ER) stress after traumatic brain injury (TBI) and the efficacy of post-TBI administration of docosahexaenoic acid (DHA) in reducing ER stress. TBI was induced by cortical contusion injury in Sprague-Dawley rats. Either DHA (16 mg/kg in DMSO) or vehicle DMSO (1 ml/kg) was administered intraperitoneally at 5 min after TBI, followed by a daily dose for 3–21 d. TBI triggered sustained expression of the ER stress marker proteins including phosphorylated eukaryotic initiation factor-2α, activating transcription factor 4, inositol requiring kinase 1, and C/EBP homologous protein in the ipsilateral cortex at 3–21 d after TBI. The prolonged ER stress was accompanied with an accumulation of abnormal ubiquitin aggregates and increased expression of amyloid precursor protein (APP) and phosphorylated tau (p-Tau) in the frontal cortex after TBI. The ER stress marker proteins were colocalized with APP accumulation in the soma. Interestingly, administration of DHA attenuated all ER stress marker proteins and reduced the accumulation of both ubiquitinated proteins and APP/p-Tau proteins. In addition, the DHA-treated animals exhibited early recovery of their sensorimotor function after TBI. In summary, our study demonstrated that TBI induces a prolonged ER stress, which is positively correlated with abnormal APP accumulation. The sustained ER stress may play a role in chronic neuronal damage after TBI. Our findings illustrate that post-TBI administration of DHA has therapeutic potentials in reducing ER stress, abnormal protein accumulation, and neurological deficits.
Can selective digestive decontamination avoid the endotoxemia and cytokine activation promoted by cardiopulmonary bypass?

Objective:To evaluate the effect of selective digestive decontamination on endotoxemia and cytokine activation during the ischemic phase of cardiopulmonary bypass surgery. Design:Prospective, open, randomized, controlled trial. Setting:Two multidisciplinary intensive care units in tertiary care hospitals. Patients:Eighty consecutive patients randomly allocated to two groups: selective digestive decontamination (group 1, n = 40) and controls (group 2, n = 40). Interventions:Preoperative administration of oral antibiotics (polymyxin E, tobramycin, and amphotericin B) vs. untreated controls. Measurements and Main Results:Assessment of decontamination by bacteriologic evaluation of rectal swabs (colony-forming units [cfu]/mL) were made in each group, along with circulating endotoxin, tumor necrosis factor and interleu-kin-6 (IL-6) determinations before surgery, during ischemic and reperfusion phases of bypass, and at 4 hrs and at 24 hrs after surgery. Group 1 patients showed that rectal bacteria decreased ten-fold after treatment for 24 hrs, thousand-fold after 48 hrs, and registered 0 cfu/mL after digestive decontamination was administered for >72 hrs. Endotoxin and IL-6 assays showed significantly lower values in this latter group vs. those circulating concentrations of control patients. On the other hand, both endotoxin and IL-6 concentrations correlated positively with the duration of surgical ischemia. Conclusions:Selective digestive decontamination reduces the gut content of enterobacteria, with complete elimination after 3 days of treatment. This fact could explain the lower endotoxin and cytokine concentrations found in the blood samples of patients who had been fully decontaminated. Duration of aortic cross-clamping is an important factor in generating endotoxemia and in the activation of cytokines. (Crit Care Med 1993; 21:1684–1691)
The Elimination Rate after Clozapine Overdose in Chinese Schizophrenia Patients: A Population Pharmacokinetics Model Study

Abstract 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.
An Improved Support-Vector Network Model for Anti-Money Laundering

The selection of parameters of SVM model will affect the identification effect of suspicious financial transactions, this paper proposes the cross validation method to find the optimal SVM classifier parameters to solve this problem. Cross validation method finds the optimal parameters based on the highest classification accuracy rate through grid search, it can effectively avoid the state of over-learning and less learning, and greatly improves the overall performance of the classifier.
Malignant melanoma: Patterns of metastasis to the small bowel, reliability of imaging studies, and clinical relevance

OBJECTIVES:The aims of this study were to determine the frequency of different patterns of melanoma metastases to small bowel on radiological examination, and to assess the reliability of the most commonly used radiological methods for detecting these lesions.METHODS:The records of cases archived as melanoma metastatic to the small bowel of the Armed Forces Institute of Pathology were reviewed. The clinical information, type of imaging procedure performed, and radiological features were analyzed and compared to the findings at surgery and at autopsy.RESULTS:A total of 32 patients had clinical and surgical data with pathological confirmation. Seven patients had metastasis involving the duodenum, 22 had jejunal involvement, and 11 had ileal involvement. Metastases were categorized as polypoid, cavitary, infiltrating, or exoenteric. The polypoid pattern was seen in 20 patients (63%), six of whom showed multiple polypoid lesions (>10), referred to as polyposis. The “target lesion,” a discrete polypoid mass with a central ulceration, was observed in only three (9%) of the 32 patients. Eight patients (25%) demonstrated a cavitary pattern, a circumferential mass with inner marginal necrosis, and five (16%) showed an infiltrating pattern. One patient (3%) had an exoenteric lesion with a fistulous tract. The small bowel follow-through demonstrated 32 of 55 metastases (sensitivity 58%). Contrast-enhanced CT demonstrated 32 of 48 masses (sensitivity 66%). Of the six cases of malignant polyposis, none were identified using CT, and only two were diagnosed by small bowel follow-through.CONCLUSIONS:The polypoid pattern, equally distributed between the jejunum and ileum, is the most common manifestation of metastatic melanoma to the small bowel. The target lesion was infrequently seen in this series. Small bowel follow-through and conventional CT seem to be unreliable in demonstrating melanoma metastases to the small bowel.
Nonautonomous Apoptosis Is Triggered by Local Cell Cycle Progression during Epithelial Replacement in Drosophila

ABSTRACT Tissue remodeling involves collective cell movement, and cell proliferation and apoptosis are observed in both development and disease. Apoptosis and proliferation are considered to be closely correlated, but little is known about their coordinated regulation in physiological tissue remodeling in vivo. The replacement of larval abdominal epidermis with adult epithelium in Drosophila pupae is a simple model of tissue remodeling. During this process, larval epidermal cells (LECs) undergo apoptosis and are replaced by histoblasts, which are adult precursor cells. By analyzing caspase activation at the single-cell level in living pupae, we found that caspase activation in LECs is induced at the LEC/histoblast boundary, which expands as the LECs die. Manipulating histoblast proliferation at the LEC/histoblast boundary, either genetically or by UV illumination, indicated that local interactions with proliferating histoblasts triggered caspase activation in the boundary LECs. Finally, by monitoring the spatiotemporal dynamics of the S/G2/M phase in histoblasts in vivo, we found that the transition from S/G2 phases is necessary to induce nonautonomous LEC apoptosis at the LEC/histoblast boundary. The replacement boundary, formed as caspase activation is regulated locally by cell-cell communication, may drive the dynamic orchestration of cell replacement during tissue remodeling.
The epidemiology of women's rugby injuries.

OBJECTIVE The purpose of this study was to identify all injuries to members of an elite women's rugby team and to compare these injuries with published data on injuries in other women's contact and collision sports. DESIGN This was a prospective cohort observational study conducted using a monthly log completed by the team's certified athletic therapist to closely monitor attendance at practices and games along with the type and severity of injuries. SETTING Rugby games and practices held in Ontario, Quebec, and the Netherlands. PARTICIPANTS Forty members of the Ontario Women's Senior Provincial Rugby Team over the 1997 season and the 1998 World Championships. MAIN OUTCOME MEASURES An injury was defined as a rugby-related event that kept a player out of practice or competition for >24 hours or required the attention of a physician (e.g., suturing lacerations) and in addition included all dental, eye, and nerve injuries and concussions. RESULTS There were a total of 35 injuries in 4,958 player-hours and 2,926 athletic exposures. This resulted in a rugby injury rate of 7.1+/-0.4 per 1,000 player-hours and 12.0+/-2 per 1,000 athletic exposures. CONCLUSION The incidence of injuries in women's rugby is comparable with that in other women's contact and collision sports, indicating that the sport may be safer than stated in the literature and media.
Regulation of COX‐2 Mediates Acid‐Induced Bone Calcium Efflux in Vitro

Chronic metabolic acidosis induces net Ca efflux from bone; this osteoclastic bone resorption is mediated by increased osteoblastic prostaglandin synthesis. Cyclooxygenase, the rate‐limiting enzyme in prostaglandin synthesis, is present in both constitutive (COX‐1) and inducible (COX‐2) forms. We report here that acidosis increases both osteoblastic RNA and protein levels for COX‐2 and that genetic deficiency or pharmacologic inhibition of COX‐2 significantly reduces acid‐induced Ca efflux from bone.
Stage Transfer Effect on Impairment Forecasts

With the introduction of expected credit loss based impairment methodology banks stress testing programs need to include forecasts of stressed impairment losses as an important component in the firmwide stress testing programs. The forecasts of stressed impairment losses are comprised of incurred loss up to the forecasting horizon of the stress test, and, the regular expected credit loss after the stress test horizon. In this paper we analyze the effect of IFRS 9 stage transfer on the stressed impairment forecasts. For a sample state transition model, portfolio and stage transfer rules it is shown that the stage transfer can have significant effects on the staged impairment forecast compared to the IFRS 9 actuals (current expected credit loss). Specifically, stage 1 dominated initial portfolios can have significantly increased stressed impairments forecasts compared to the IFRS 9 actuals impairment calculation under stressed scenario. This reflects their downside in terms of stage transfer potential to stage 2 up until forecast time. Recently downgraded or lower quality portfolios in stage 2 can have the opposite effect of decreased stressed impairments forecasts compared to the IFRS 9 actuals impairment calculation under stressed scenario. This reflects their upside in terms of stage transfer potential to stage 1 up until forecast time. A lifetime measurement only approach for all assets (as in US CECL) ensures a direct link between actuals stressed impairment amounts and stressed impairment forecast amounts. Their difference can be attributed to the forecast new business assumptions and natural decay due to run-off. Taking into account stage transfer in impairment forecasts we find it is more natural to analyze the stressed impairment forecast relative to a baseline scenario impairment forecast benchmark. Such an approach focus more specifically on the macroeconomic stress effect and its impact.
Benzo[a]pyrene Uptake by Serum Lipids: Correlation with Triglyceride Concentration 1

Abstract An in vitro study of the relationship between benzo[a]pyrene (BaP) association with serum lipoproteins (LP) and LP composition was conducted using human subjects. BaP partitioning into different serum LP ranged from 53 to 71% of available BaP. Efficiency of BaP partitioning was examined for the relationship with lipid components of different sera. The data indicate that triglyceride (TG) concentrations were more directly correlated with BaP uptake than were concentrations of other LP components. Adjusting sera to a uniform TG concentration (96.5 mg/dl) resulted in the same BaP uptake for each serum type, while adjusting sera to contain a uniform cholesteryl ester concentration (104.6 mg/dl) did not result in similar BaP uptake among serum types. Analysis of serum LP composition suggested that marked differences in both BaP uptake and serum TG concentrations among the subjects were due mainly to differences in serum very low density lipoprotein (VLDL) concentrations. A correlation study using 14 human subjects showed that serum TG concentration was the best predictor (r = 0.973, P < 0.001) for BaP uptake by serum, followed by phospholipid (r = 0.658, P < 0.01) and total cholesterol (r = 0.514, P < 0.05) concentrations. The results indicate that serum TG concentration (typically VLDL-TG) may be the primary factor affecting BaP uptake by serum LP, and suggest that a small change in serum TG concentration could cause a significant increase in BaP uptake by serum LP, contributing to an increased level of circulating carcinogen.