Miracle-dz/UniFAR-FTUs huggingface dataset:
Confocal Raman data analysis enables identifying apoptosis of MCF-7 cells caused by anticancer drug paclitaxel

Abstract. Confocal Raman microscopy is a noninvasive, label-free imaging technique used to study apoptosis of live MCF-7 cells. The images are based on Raman spectra of cells components, and their apoptosis is monitored through diffusion of cytochrome c in cytoplasm. K-mean clustering is used to identify mitochondria in cells, and correlation analysis provides the cytochrome c distribution inside the cells. Our results demonstrate that incubation of cells for 3 h with 10 μM of paclitaxel does not induce apoptosis in MCF-7 cells. On the contrary, incubation for 30 min at a higher concentration (100 μM) of paclitaxel induces gradual release of the cytochrome c into the cytoplasm, indicating cell apoptosis via a caspase independent pathway.
Fracture resistance of Resilon filled roots following different re-treatment techniques

The aim of this study was to investigate whether endodontically retreated teeth filled with Resilon are more resistant to fracture than those filled with guttapercha following hand or rotary removal techniques. Seventy-two upper anterior human teeth were selected, decoronated and reduced to 12 mm. The canals were shaped using rotary ProTaper files and randomly assigned into two groups (n=36). Obturation was performed using guttapercha/AH-Plus in Group 1 and Resilon/RealSeal in Group 2. The roots were stored for one week at 37°C. The roots were then randomly allocated into three subgroups: A (n=10), no further treatment was performed. In B (n=13), the filling was removed using hand K-files and in C (n=13) using ProTaper retreatment files. Subgroups B and C were refilled using the same materials as used in the primary treatment and stored for one week. Three roots from each of the four subgroups were left unfilled to act as a control (n=12). All the roots were embedded in resin and subjected to fracture in a universal testing machine. Data were analysed using Kruskal-Wallis with multiple pairwise comparisons. Resilon-refilled roots showed no significance difference in fracture resistance compared with guttapercha-refilled roots regardless of the retreatment technique. There was no significant difference in fracture resistance between the two retreatment techniques. When used as a root filling material, Resilon was found not to increase the fracture resistance of primarily and previously root filled teeth regardless of the retreatment technique.
Anti-tumor efficacy and biodistribution of intravenous polymeric micellar paclitaxel

The purpose of this study was to evaluate the diblock copolymer poly(DL-lactide)-block-methoxy polyethylene glycol as an i.v. delivery vehicle for paclitaxel. Nude mice were implanted s.c. with fragments of MV-522 lung carcinomas and treated with paclitaxel on a daily x 5 schedule when tumors were approximately 5x5 mm in size. Cremophor paclitaxel or polymeric micellar paclitaxel were given i.p. or i.v. at the maximum tolerated dose (Cremophor paclitaxel MTD: 20 mg/kg/day i.v. or i.p.; micellar paclitaxel MTD: 25 mg/kg/day i.v. or 100 mg/kg/day i.p.). The tumors were measured using callipers during the experiment and accurately weighted at the end. Two biodistribution studies were carried out. In one study, the nude mice were given micellar paclitaxel at a dose of 25 mg/kg i.v. or 100 mg/kg i.p. In another study, BDF-1 mice were given either micellar paclitaxel or Cremophor paclitaxel at a dose of 20 mg/kg i.v. The mice were sacrificed after a given time and the organs were harvested. Paclitaxel in the organs was extracted with acetonitrile and analyzed using HPLC. Tumor growth inhibitions of 98.5 and 98.7% were obtained from i.v. administered micellar paclitaxel and Cremophor paclitaxel at their MTDs, respectively. Micellar paclitaxel was more efficacious i.p. (98.7% tumor growth inhibition) than Cremophor paclitaxel i.p. (83.0% tumor growth inhibition) at their MTDs. The highest concentrations of paclitaxel were found in the liver after administration of paclitaxel formulations. Paclitaxel was also found in spleen, kidney, lung and blood, in order of decreasing concentration. The preliminary results indicate that polymeric micellar paclitaxel could be a clinically useful chemotherapeutic formulation
THE POPULATION OF TINY NEAR-EARTH OBJECTS OBSERVED BY NEOWISE

Only a very small fraction of the asteroid population at size scales comparable to the object that exploded over Chelyabinsk, Russia has been discovered to date, and physical properties are poorly characterized. We present previously unreported detections of 105 close approaching near-Earth objects (NEOs) by the Wide-field Infrared Survey Explorer (WISE) mission's NEOWISE project. These infrared observations constrain physical properties such as diameter and albedo for these objects, many of which are found to be smaller than 100 m. Because these objects are intrinsically faint, they were detected by WISE during very close approaches to the Earth, often at large apparent on-sky velocities. We observe a trend of increasing albedo with decreasing size, but as this sample of NEOs was discovered by visible light surveys, it is likely that selection biases against finding small, dark NEOs influence this finding.
Use of Machine Learning Methods to Reduce Predictive Error of Groundwater Models

Quantitative analyses of groundwater flow and transport typically rely on a physically‐based model, which is inherently subject to error. Errors in model structure, parameter and data lead to both random and systematic error even in the output of a calibrated model. We develop complementary data‐driven models (DDMs) to reduce the predictive error of physically‐based groundwater models. Two machine learning techniques, the instance‐based weighting and support vector regression, are used to build the DDMs. This approach is illustrated using two real‐world case studies of the Republican River Compact Administration model and the Spokane Valley‐Rathdrum Prairie model. The two groundwater models have different hydrogeologic settings, parameterization, and calibration methods. In the first case study, cluster analysis is introduced for data preprocessing to make the DDMs more robust and computationally efficient. The DDMs reduce the root‐mean‐square error (RMSE) of the temporal, spatial, and spatiotemporal prediction of piezometric head of the groundwater model by 82%, 60%, and 48%, respectively. In the second case study, the DDMs reduce the RMSE of the temporal prediction of piezometric head of the groundwater model by 77%. It is further demonstrated that the effectiveness of the DDMs depends on the existence and extent of the structure in the error of the physically‐based model.
Detection and Typing of Human Herpesvirus 6 by Molecular Methods in Specimens from Patients Diagnosed with Encephalitis or Meningitis

ABSTRACT Human herpesvirus 6 (HHV-6) was detected in specimens from patients hospitalized with symptoms of encephalitis or meningitis. A real-time PCR assay was developed which has a linear dynamic range of 5 to 5 × 106 copies of HHV-6 and a sensitivity of five gene copies per reaction. While the assay detects both subtypes, HHV-6A and HHV-6B, it is specific and does not cross-react with a selected specificity panel. A total of 1,482 patient specimens, which were collected between 2003 and 2007, were tested; 26 specimens from 24 patients were found to be positive for HHV-6 by real-time PCR. The HHV-6 detection rate in this population was therefore 1.75%. The majority of the specimens tested (>95%) were cerebrospinal fluid (CSF) specimens. We were able to type 20 of the 26 positive specimens by conventional PCR and sequence analysis; all were HHV-6B. Forty-two percent of the patients were 3 years of age or younger, which may indicate a primary infection in these patients. Given the ages of the remaining patients (from 4 to 81 years), their infections were most probably due to virus reactivations. Where information was available, symptoms of patients included fever (71%), altered mental status (67%), and abnormal CSF profile (75%). Fifty percent of patients of 3 years of age or younger suffered from seizures. The detection of HHV-6 in specimens from patients diagnosed with encephalitis or meningitis, in the absence of a positive PCR result for other agents, strongly suggests a role for HHV-6 in the pathogenesis of these central nervous system diseases.
The unconventional P-loop NTPase OsYchF1 and its regulator OsGAP1 play opposite roles in salinity stress tolerance.

YchF proteins are a group of mysterious but ubiquitous unconventional G-proteins found in all kingdoms of life except Archaea. Their functions have been documented in microorganisms, protozoa and human, but those of plant YchF homologues are largely unknown. Our group has previously shown that OsYchF1 and its interacting protein, OsGAP1, play opposite roles in plant defense responses. OsGAP1 was found to stimulate the GTPase/ATPase activities of OsYchF1 and regulate its subcellular localization. In this report, we demonstrate that both OsYchF1 and OsGAP1 are localized mainly in the cytosol under NaCl treatment. The ectopic expression of OsYchF1 in transgenic Arabidopsis thaliana leads to reduced tolerance towards salinity stress, while the ectopic expression of OsGAP1 has the opposite effect. Similar results were also obtained with the Arabidopsis homologues, AtYchF1 and AtGAP1, by using AtGAP1 overexpressors and underexpressors, as well as an AtYchF1-knockdown mutant. OsYchF1 and OsGAP1 also exhibit highly significant effects on salinity-induced oxidative stress tolerance. The expression of OsYchF1 suppresses the anti-oxidation enzymatic activities and increases lipid peroxidation in transgenic Arabidopsis, and leads to the accumulation of reactive oxygen species (ROS) in tobacco BY-2 cells, while the ectopic expression of OsGAP1 has the opposite effects in these two model systems.
Back pain in pregnancy

Dr Ashkan and colleagues describe the case of a woman with compression of the cauda equina due to prolapse of the lumbosacral invertebral disc (February 1998 JRSM, pp 88-90). Because the back pain was attributed to her pregnancy, referral was delayed and she was left with a residual neurological deficit after surgical decompression. We have lately been involved in a similar case of a young woman who developed back pain and signs of lumbar radiculopathy in the third month of her second pregnancy. Postpartum, magnetic resonance imaging (MRI) of the lumbar spine showed no abnormality and she was diagnosed as having obstetric palsy with secondary sympathetic dystrophy. Two years passed before the diagnosis was established by pelvic MRI, which revealed a mass adjacent to the greater sciatic foramen (Figure 1) which on biopsy proved to be a malignant peripheral nerve sheath tumour a locally aggressive tumour whose prognosis is related to size at diagnosis1 2. This is another example of the serious consequences of failing to investigate pregnant patients with back pain and neurological signs. We agree with Dr Ashkan and colleagues that detailed history-taking and neurological examination are essential, and suggest that MRI of the pelvis should be considered especially in those with normal lumbar spine imaging.
Self‐assessment and learning through GOSCE (group objective structured clinical examination)

Summary. The objective structured clinical examination (OSCE) was modified to serve as a means of self‐assessment and learning, rather than as an examination. The main modifications were to adapt it for use by small groups instead of individuals, and to provide a correct answer or other feedback at each station. The resulting group OSCE (GOSCE) was used as an introductory session in two residential refresher courses for general practitioners. The 300 participants rated it highly as a method of self‐assessment and as an enjoyable social event. Four potential applications of the GOSCE are suggested: as an assessment instrument for formative and informal summative assessment, as a resource for learning about interpersonal and interprofessional relationships, and as a framework for problem‐based short courses.
Lack of evidence from HPLC 32P-post-labelling for tamoxifen-DNA adducts in the human endometrium.

Tamoxifen is associated with an increased incidence of endometrial cancer in women. It is also a potent carcinogen in rat liver and forms covalent DNA adducts in this tissue. A previous study exploring DNA adducts in human endometria, utilizing thin layer chromatography 32P-postlabelling, found no evidence for adducts in tamoxifen-treated women [Carmichael,P.L. , Ugwumadu,A.H. N. , Neven,P., Hewer,A.J., Poon,G.K. and Phillips,D.H. (1996) Cancer Res., 56, 1475-1479]. However, subsequent work utilizing HPLC 32P-post-labelling [Hemminki,K. , Ranjaniemi,H. , Lindahl,B. and Moberger,B. (1996) Cancer Res., 56, 4374-4377] suggested that very low levels could be detected. We have sought to investigate this question further by reproducing the HPLC methodology at two centres, and analysing endometrial DNA from 20 patients treated with 20 mg/day tamoxifen for between 22 and 65 months. Liver DNA isolated from tamoxifen-treated rats was used as a positive control. We found no convincing evidence for tamoxifen-derived DNA adducts in human endometrium. HPLC elution profiles of post-labelled DNA from tamoxifen-treated women were indistinguishable from those obtained with DNA from 14 untreated women and from six women taking toremifene, an analogue of tamoxifen.
Voltage Loss Analysis for Bifacial Silicon Solar Cells: Case for Two-Dimensional Large-Area Modeling

While it is relatively easy to analyze the optical and recombination losses contributing to a solar cell's short-circuit current, there are many nuanced effects that lead to the solar cell's voltage at the maximum power point and at open circuit. This paper analyzes the impact of some commonly considered factors, such as series resistance, as well as some hard-to-discern factors, like localized recombination at the wafer periphery and metal busbars, on the solar cell's open-circuit voltage, maximum power point, and fill factor. A series of samples related to an n-type bifacial solar cell are chosen as an example.
The effect of providing a warning about the lie scale in a personality inventory.

Summary. A new method of encouraging truthful answers to a questionnaire was investigated. 262 school pupils aged 12 and 13 years completed a revised version of the Junior Eysenck Personality Inventory. The scale was administered to half the group (controls) with the normal instructions while the others (experimental group) were, in addition, given information drawing attention to the existence of a ‘lie’ scale. The experimental group obtained a lower L score, and a higher score on psychoticism, and neuroticism (boys only); the effect on extraversion was not significant. The results from the experimental instructions were found to compare favourably with those from alternative ‘correction’ procedures, such as eliminating individuals with high L scores from the group analysis, or statistically adjusting scores on the basis of their correlation with L. It is thus suggested that the procedure of warning subjects about the presence of a ‘lie’ scale may prove useful as a standard practice in personality assessment.
Impaired Production of Proinflammatory Cytokines and Host Resistance to Acute Infection with Trypanosoma cruzi in Mice Lacking Functional Myeloid Differentiation Factor 881

Studies performed in vitro suggest that activation of Toll-like receptors (TLRs) by parasite-derived molecules may initiate inflammatory responses and host innate defense mechanisms against Trypanosoma cruzi. Here, we evaluated the impact of TLR2 and myeloid differentiation factor 88 (MyD88) deficiencies in host resistance to infection with T. cruzi. Our results show that macrophages derived from TLR2 −/− and MyD88−/− mice are less responsive to GPI-mucin derived from T. cruzi trypomastigotes and parasites. In contrast, the same cells from TLR2−/− still produce TNF-α, IL-12, and reactive nitrogen intermediates (RNI) upon exposure to live T. cruzi trypomastigotes. Consistently, we show that TLR2−/− mice mount a robust proinflammatory cytokine response as well as RNI production during the acute phase of infection with T. cruzi parasites. Further, deletion of the functional TLR2 gene had no major impact on parasitemia nor on mortality. In contrast, the MyD88−/− mice had a diminished cytokine response and RNI production upon acute infection with T. cruzi. More importantly, we show that MyD88−/− mice are more susceptible to infection with T. cruzi as indicated by the higher parasitemia and accelerated mortality, as compared with the wild-type mice. Together, our results indicate that T. cruzi parasites elicit an alternative inflammatory pathway independent of TLR2. This pathway is partially dependent on MyD88 and necessary for mounting optimal inflammatory and RNI responses that control T. cruzi replication during the early stages of infection.
CMV infection following nonmyeloablative allogeneic stem cell transplantation using Campath.

We would like to comment on the recent report by Chakrabarti et al[1][1] on the risk of cytomegalovirus (CMV) infection following nonmyeloablative allogeneic transplantation. The conditioning regimen utilized by the authors consisted of fludarabine, melphalan, and a total dose of 100 mg of
Changes in Regional Blood–Brain Transfer of l‐Leucine Elicited by Arginine‐Vasopressin

Abstract: Arginine‐vasopressin (AVP), injected into the carotid artery in physiological concentration together with L‐leucine, changed kinetic constants of the blood—brain barrier (BBB) transport of this neutral amino acid without changing the cerebral blood flow (CBF). The maximum velocity of transport (Vmax), the half‐saturation constant (Km), the nonsaturable transport constant (KD), and CBF were estimated in nine brain regions of male Wistar rats anesthetized with ether. In cerebral hemisphere, Vmax decreased from 21 nmol min−1. g−1 (control) to 7.6 nmol. min−1. g−1 (AVP). Km decreased from 0.11 to 0.029 mM. Regional differences of the kinetic constants were found in controls as well as in AVP‐treated animals. In all regions, the calculated constants Vmax and Km of animals coinjected with AVP were significantly decreased when compared to controls. A direct or indirect interaction of AVP with the transport system of large neutral amino acids is suggested.
Mechanism of β-Adrenergic Receptor Desensitization in Cardiac Hypertrophy Is Increased β-Adrenergic Receptor Kinase*

Pressure overload cardiac hypertrophy in the mouse was achieved following 7 days of transverse aortic constriction. This was associated with marked β-adrenergic receptor (β-AR) desensitization in vivo, as determined by a blunted inotropic response to dobutamine. Extracts from hypertrophied hearts had ≈3-fold increase in cytosolic and membrane G protein-coupled receptor kinase (GRK) activity. Incubation with specific monoclonal antibodies to inhibit different GRK subtypes showed that the increase in activity could be attributed predominately to the β-adrenergic receptor kinase (βARK). Although overexpression of a βARK inhibitor in hearts of transgenic mice did not alter the development of cardiac hypertrophy, the β-AR desensitization associated with pressure overload hypertrophy was prevented. To determine whether the induction of βARK occurred because of a generalized response to cellular hypertrophy, βARK activity was measured in transgenic mice homozygous for oncogenic ras overexpression in the heart. Despite marked cardiac hypertrophy, no difference in βARK activity was found in these mice overexpressing oncogenic ras compared with controls. Taken together, these data suggest that βARK is a central molecule involved in alterations of β-AR signaling in pressure overload hypertrophy. The mechanism for the increase in βARK activity appears not to be related to the induction of cellular hypertrophy but to possibly be related to neurohumoral activation.
Evaluation of Pharmacokinetic Interaction between PA-824 and Midazolam in Healthy Adult Subjects

ABSTRACT This study assessed the safety, tolerability, and pharmacokinetic interaction between PA-824, a novel antitubercular nitroimidazo-oxazine, and midazolam, a CYP3A4 substrate, in 14 healthy adult male and female subjects. The study followed up on observations in vitro that PA-824 caused weak and time-dependent inhibition of CYP3A4. Subjects received a single oral dose of midazolam (2 mg), followed by a 2-day washout. After the washout, all subjects received PA-824 (400 mg) once daily for 14 consecutive days. On day 14, all subjects received the final PA-824 dose coadministered with a 2-mg oral dose of midazolam. The pharmacokinetic endpoints AUC0–t, AUC0–∞, and Cmax for midazolam and 1-hydroxy midazolam were compared between midazolam administered alone versus midazolam coadministered with PA-824. Statistical analysis demonstrated that the mean midazolam values of Cmax, AUC0–t, and AUC0–∞ parameters were reduced by ca. 16, 15, and 15%, respectively, when PA-824 was coadministered with midazolam. The total exposure (AUC) of 1-hydroxy midazolam was 13 to 14% greater when coadministered with PA-824 compared to midazolam administered alone. The Cmax of 1-hydroxy midazolam was similar between treatments. Based on these results, PA-824 does not inhibit or induce CYP3A4 to a clinically meaningful extent and is not likely to markedly affect the pharmacokinetics of CYP3A4 metabolized drugs.
Damage to the cytoskeleton of large diameter sensory neurons and myelinated axons in vincristine‐induced painful peripheral neuropathy in the rat

Vincristine, along with other antimitotic chemotherapeutic drugs, produces a peripheral neuropathy in humans that is accompanied by painful paresthesias, dysesthesias, and occasionally hypoesthesia, and by hyporeflexia (Holland et al. [ 1973 ] Cancer Res. 33:1258–1264; McLeod and Penny [ 1969 ] J Neurol Neurosurg Psychiatry 32:297–304; Postma et al. [1993] J Neurooncol. 15:23–27; Sandler et al. [ 1969 ] Neurology 19:367–374). Systemic administration of vincristine causes swelling of unmyelinated axons and disorientation of axonal microtubules (Tanner et al. [ 1998a 1998a] J Comp Neurol. 395:481–492) at a time when it also produces allodynia and mechanical hyperalgesia (Aley et al. [ 1996 ] Neuroscience 73:259–265; Authier et al. [1999] Neuroreport 10:965–968) and enhanced responsiveness in C‐fibers in the rat (Tanner et al. [ 1998b ] J Neurosci. 18:6480–6491). Because slowing of A‐fiber conduction velocities had also been demonstrated (Tanner et al. [ 1998b ] J Neurosci. 18:6480–6491), and mechanical hyperalgesia can occur secondary to damage to large diameter sensory afferents (Basbaum et al. [ 1991 ] Can J Physiol Pharmacol. 69:647–651; Coggeshall et al. [ 1993 ] Pain 52:233–242; Woolf and Mannion [ 1999 ] Lancet 353:1959–1964), we sought to determine whether vincristine also induced ultrastructural changes in myelinated A‐fibers. Moreover, since systemic treatment with vincristine did not cause profound microtubule depolymerization in the unmyelinated axons of the peripheral nerve, we hypothesized that the drug's effects may be more extensive in the cell body, because in the spinal ganglion, the blood‐nerve barrier is less restrictive. We used quantitative ultrastructural methods to analyze the microtubule cytoskeleton in myelinated axons in the mid‐shaft of the saphenous nerve and in the sensory ganglion cells. Vincristine induced swelling of the whole nerve and an increase in the cross‐sectional areas of myelinated axons but no loss of myelinated axons. There was a significant decrease in axonal microtubules, as well as microtubule disorganization, in myelinated fibers from vincristine‐treated rats. In the spinal ganglion, vincristine induced swelling of large diameter sensory neurons and a build‐up of neurofilaments in the cell bodies and proximal axons, suggestive of impaired anterograde axonal transport. J. Comp. Neurol. 424:563–576, 2000. © 2000 Wiley‐Liss, Inc.