Miracle-dz/UniFAR-FTUs huggingface dataset:
Recordings of glutamate receptor channels in isolated postsynaptic densities.

We have isolated highly purified rat brain postsynaptic densities (PSDs), that are known to contain glutamate receptors of the AMPA and NMDA types. These PSDs were incorporated into liposomes, and grown, by a cycle of partial de- and rehydration in 5% ethylene glycol, into giant (5-100 microns in diameter) liposomes. These giant liposomes were then made to form Gigaohm (10-20 G omega) seals with conventional patch-clamp electrodes, which, when withdrawn, retain an excised patch in an inside-out configuration. When 5-10 microM L-glutamate (or 10 microM NMDA) plus 1 microM glycine were present inside the patch pipette, but not in the external fluid, a highly complex pattern of currents was seen in about 55% of the cases. This was characterized by very fast kinetics, conductances as high as 460 pS and multiple lower levels of 45, 80, 120, 230 and 340 pS. These currents, when evoked by NMDA plus glycine, were entirely suppressed by the NMDA antagonist 2-amino-5-phosphonovalerate, APV. However, those activated by L-glutamate plus glycine still appeared in the presence of APV in about 18% of the cases, but with lower conductance levels. Current kinetics similar to the latter ones were also induced by the AMPA receptor agonist quisqualate (10 microM) in 16% of the cases. This indicated that both NMDA and AMPA receptors were present, in a functionally well preserved state, in isolated postsynaptic densities. Indirect evidence also suggested that in our experiments, in which 212 seals were studied, only a single postsynaptic density was present in the patches in which channel activity was found. (ABSTRACT TRUNCATED AT 250 WORDS)
Using MRI to evaluate anatomic significance of aortic bifurcation, right renal artery, and conus medullaris when locating lumbar vertebral segments.

OBJECTIVE This study evaluated the anatomic significance and sites of aortic bifurcation, right renal artery, and conus medullaris when locating lumbar vertebral segments on MRI. SUBJECTS AND METHODS. The study group was composed of 210 patients who underwent MRI of the lumbosacral spine. The position of aortic bifurcation was evaluated using MRI. Midline and sagittal MRI were also assessed to identify the proximal portion of the right renal artery and the tip of the conus medullaris. These locations were recorded in relation to the upper or lower half of the adjacent vertebral body or the adjacent intervertebral disk space. RESULTS The most common site of aortic bifurcation was at the L4 vertebra (83%). In most patients two separated iliac arteries were apparent at the level of the L4-L5 disk space (93%), and the right renal artery was located between the lower half of the L1 vertebra and the upper half of the L2 vertebra (92%). The position of the conus medullaris was variably located, and the most frequent site was at the L1 vertebra (56%). CONCLUSION The aortic bifurcation, the right renal artery, and the combination of these structures can be reliable landmarks for determining the lumbar vertebral segments on MRI or CT. However, conus medullaris cannot be considered a good landmark because of its variable locations.
Density-dependent separation of encapsulated cells in a microfluidic channel by using a standing surface acoustic wave.

This study presents a method for density-based separation of monodisperse encapsulated cells using a standing surface acoustic wave (SSAW) in a microchannel. Even though monodisperse polymer beads can be generated by the state-of-the-art technology in microfluidics, the quantity of encapsulated cells cannot be controlled precisely. In the present study, mono-disperse alginate beads in a laminar flow can be separated based on their density using acoustophoresis. A mixture of beads of equal sizes but dissimilar densities was hydrodynamically focused at the entrance and then actively driven toward the sidewalls by a SSAW. The lateral displacement of a bead is proportional to the density of the bead, i.e., the number of encapsulated cells in an alginate bead. Under optimized conditions, the recovery rate of a target bead group (large-cell-quantity alginate beads) reached up to 97% at a rate of 2300 beads per minute. A cell viability test also confirmed that the encapsulated cells were hardly damaged by the acoustic force. Moreover, cell-encapsulating beads that were cultured for 1 day were separated in a similar manner. In conclusion, this study demonstrated that a SSAW can successfully separate monodisperse particles by their density. With the present technique for separating cell-encapsulating beads, the current cell engineering technology can be significantly advanced.
Systematic analysis of biological and physical limitations of proton beam range verification with offline PET/CT scans

The clinical use of offline positron emission tomography/computed tomography (PET/CT) scans for proton range verification is currently under investigation at the Massachusetts General Hospital (MGH). Validation is achieved by comparing measured activity distributions, acquired in patients after receiving one fraction of proton irradiation, with corresponding Monte Carlo (MC) simulated distributions. Deviations between measured and simulated activity distributions can either reflect errors during the treatment chain from planning to delivery or they can be caused by various inherent challenges of the offline PET/CT verification method. We performed a systematic analysis to assess the impact of the following aspects on the feasibility and accuracy of the offline PET/CT method: (1) biological washout processes, (2) patient motion, (3) Hounsfield unit (HU) based tissue classification for the simulation of the activity distributions and (4) tumor site specific aspects. It was found that the spatial reproducibility of the measured activity distributions is within 1 mm. However, the feasibility of range verification is restricted to a limited amount of positions and tumor sites. Washout effects introduce discrepancies between the measured and simulated ranges of about 4 mm at positions where the proton beam stops in soft tissue. Motion causes spatial deviations of up to 3 cm between measured and simulated activity distributions in abdominopelvic tumor cases. In these later cases, the MC simulated activity distributions were found to be limited to about 35% accuracy in absolute values and about 2 mm in spatial accuracy depending on the correlativity of HU into the physical and biological parameters of the irradiated tissue. Besides, for further specific tumor locations, the beam arrangement, the limited accuracy of rigid co-registration and organ movements can prevent the success of PET/CT range verification. All the addressed factors explain why the proton beam range can only be verified within an accuracy of 1–2 mm in low-perfused bony structures of head and neck patients for which an accurate co-registration of predominant bony anatomy is possible, as shown previously. However, most of the limitations of the current approach are conquerable. By implementing technological and methodological improvements like the use of in-room PET scanners, PET measurements could soon be used to provide proton range verification in clinical routine.
Clinical Outcome after Mechanical Recanalization as Mono- or Adjunctive Therapy in Acute Stroke: Importance of Time to Recanalization

Background: The clinical benefit of mechanical recanalization procedures for acute stroke is still a matter of debate. We report the clinical and imaging results of 34 consecutive patients, focusing on time aspects (i.e. vessel occlusion time and procedure duration). Methods: During a 3-year period, 34 stroke patients with large-vessel occlusion (anterior circulation, n = 19; posterior circulation, n = 15) were treated with several mechanical recanalization devices with (n = 17) or without prior intravenous thrombolysis. Clinical and imaging data before (NIHSS) and after treatment [(mRS) 3 and 6–30 months] were analyzed. The angiographic outcome (TIMI score), complication rates, and procedural issues (i.e. procedure duration and vessel occlusion time) were assessed. Results: The median NIHSS on admission was 17. Successful recanalization (TIMI 2 and 3) was achieved in 23 (68%) patients. The median time from symptom onset to recanalization was 330 min, and the median time from angiography to recanalization was 101 min. Six (18%) patients had a good clinical outcome (3-month mRS ≤2), and 10 (29%) died. The vessel occlusion time was significantly shorter in patients with a good compared to poor clinical outcome (247 vs. 348 min, p = 0.024). In the subgroup of anterior circulation stroke, successful recanalization, and no symptomatic intracranial hemorrhage (n = 11), there was a strong correlation between vessel occlusion time and clinical outcome (r = 0.711, p = 0.014). Conclusions: The rate of vessel recanalization with endovascular therapy is promising. Nevertheless, the long-term clinical outcome is still disadvantageous in the majority of patients, presumably due to too long vessel occlusion times. Better strategies for patient selection and optimization of recanalization strategies (i.e. shorter time intervals to vessel patency) are warranted.
Pulse repetition frequency multiplication with spectral selection in Fabry-Perot filters

We present methods for obtaining high-repetition-rate full duty-cycle RZ optical pulse trains from lower rate laser sources. These methods exploit the memory properties of the Fabry-Perot filter for rate multiplication, while amplitude equalization in the output pulse train is achieved with a semiconductor optical amplifier or with a second transit through the Fabry-Perot filter. We apply these concepts to experimentally demonstrate rate quadruplication from 10 to 40 GHz and discuss the possibility of taking advantage of the proposed methods to achieve repetition rates up to 160 GHz.
The promise of microfinance and women's empowerment: what does the evidence say?

The microfinance revolution has transformed access to financial services for low-income populations worldwide. As a result, it has become one of the most talked-about innovations in global development in recent decades. However, its expansion has not been without controversy. While many hailed it as a way to end world poverty and promote female empowerment, others condemned it as a disaster for the poor. Female empowerment has often been seen as one of the key promises of the industry. In part, this is based on the fact that more than 80% of its poorest clients, i.e., those who live on less than $1.25/day, are women. This paper discusses what we have learned so far about the potential and limits of microfinance and how insights from research and practice can help inform the industry's current products, policies and future developments.
Mechanisms of radiosensitization in bromodeoxyuridine-substituted cells.

The radiosensitization of exponentially-growing V79-171 cells whose DNA has been substituted by bromodeoxyuridine (BrdU) in place of thymidine is decreased if acetone is present during irradiation. Acetone, at a concentration of 1 mol dm-3, removes the majority of the increase in double-strand breaks (dsbs) caused by BrdU substitution, but only removes approximately half of the increase in cell killing. The decrease in cell radiosensitization coincides with the removal of the additional dsbs. The protection afforded by acetone against dsbs is assumed to be due to its ability to scavenge hydrated electrons, thought to be the active species causing the increased DNA damage in the presence of BrdU. The residual component of BrdU radiosensitization which could not be removed by treatment with acetone may be due to either a subset of nonscavengable, lethal dsbs or the influence of BrdU on the fixation of potentially-lethal damage (Iliakis et al. 1992). Cells substituted with BrdU are not sensitized to hydroxyl radicals (from hydrogen peroxide). Also, the enhanced levels of single-strand break (ssb) and dsb production in cells substituted with BrdU arise from analogous events (i.e. increases in the yield of ssbs). These studies support the locally multiply damaged site theory of lesion (dsb) production (Ward 1981) and, in the case of BrdU-substituted cells, the increase in dsbs appears to be due to the production of additional ssbs by hydrated electrons at sites of multiple damage.
[Lung cancer histological types and diagnostic methods in a tertiary care facility].

OBJECTIVE To describe the histological frequencies, diagnostic methods, gender and age of lung cancer patients in a third level care hospital in western Mexico. METHODS A retrospective and descriptive study (2002 to 2005) was undertaken. From all reviewed cases, 242 patients had a diagnosis compatible with lung cancer. We analyzed the histological type, gender, age group, and diagnostic method. RESULTS The histological type frequencies of lung cancer were as follows: 63.6% adenocarcinoma, 19.0% squamous cell carcinoma, 15.2% small cell carcinoma, and 2.2% large-cell carcinoma. Among these patients, a male-female ratio of 2:1 with a mean age of 63 years was found. Regarding the diagnostic methods followed, the most common included: transthoracic needle aspiration, bronchial biopsy, and bronchial washing. CONCLUSIONS Adenocarcinoma was the most frequent histological type in the sample studied, an association between female gender and risk of developing adenocarcinoma was detected.
Prognostic relevance of NG2/CSPG4, CD44 and Ki-67 in patients with glioblastoma

Neuron-glial antigen 2 (NG2, also known as CSPG4) and hyaluronic acid receptor CD44 are chondroitin sulphate proteoglycans actively involved in brain development and its malignant transformation. Here, we aimed to compare prognostic significances of NG2, CD44 and Ki-67 expression in glioblastoma multiforme patients. Totally, 45 tissue samples and 83 paraffin-embedded tissues for 75 patients were analysed. The prognostic values of the genes were analysed using Kaplan–Meier survival curves. Grade III gliomas showed 2-fold difference in NG2 expression between anaplastic astrocytoma and oligoastrocytoma (10.1 ± 3.5 and 25.5 ± 14.5, respectively). For grade IV gliomas, upregulated NG2 expression (21.0 ± 6.8) was associated with poor glioblastoma multiforme prognosis (overall survival < 12 months) compared with glioblastoma multiforme patients with good prognosis (4.4 ± 3.2; overall survival > 12 months). Multivariate survival analysis using Cox proportional hazards model confirmed that high NG2 expression was associated with low survival of the patients (hazard ratio: 3.43; 95% confidence interval: 1.18–9.93; p = 0.02), whereas age (hazard ratio: 1.02; 95% confidence interval: 0.96–1.09; p = 0.42), tumour resection (hazard ratio: 1.03; 95% confidence interval: 0.98–1.08; p = 0.25) and sex (hazard ratio: 0.62; 95% confidence interval: 0.21–1.86; p = 0.40) did not show significant association with prognosis. Although the positive correlation was shown for NG2 and CD44 expression in the glioblastomas (Pearson coefficient = 0.954), Kaplan–Meier and multivariate survival analyses did not revealed a significant association of the increased CD44 expression (hazard ratio: 2.18; 95% confidence interval: 0.50–9.43; p = 0.30) or high Ki-67 proliferation index (hazard ratio: 1.10; 95% confidence interval: 1.02–1.20; p = 0.02) with the disease prognosis. The results suggest that upregulation of NG2/CSPG4 rather than changes in CD44 or Ki-67 expression is associated with low overall survival in glioblastoma multiforme patients, supporting NG2/CSPG4 as a potential prognostic marker in glioblastoma.
Theoretical model for laser ablation outcome predictions in brain: calibration and validation on clinical MR thermometry images

Abstract Purpose: Neurosurgical laser ablation is experiencing a renaissance. Computational tools for ablation planning aim to further improve the intervention. Here, global optimisation and inverse problems are demonstrated to train a model that predicts maximum laser ablation extent. Methods: A closed-form steady state model is trained on and then subsequently compared to N = 20 retrospective clinical MR thermometry datasets. Dice similarity coefficient (DSC) is calculated to provide a measure of region overlap between the 57 °C isotherms of the thermometry data and the model-predicted ablation regions; 57 °C is a tissue death surrogate at thermal steady state. A global optimisation scheme samples the dominant model parameter sensitivities, blood perfusion (ω) and optical parameter (μeff) values, throughout a parameter space totalling 11 440 value-pairs. This represents a lookup table of μeff–ω pairs with the corresponding DSC value for each patient dataset. The μeff–ω pair with the maximum DSC calibrates the model parameters, maximising predictive value for each patient. Finally, leave-one-out cross-validation with global optimisation information trains the model on the entire clinical dataset, and compares against the model naïvely using literature values for ω and μeff. Results: When using naïve literature values, the model’s mean DSC is 0.67 whereas the calibrated model produces 0.82 during cross-validation, an improvement of 0.15 in overlap with the patient data. The 95% confidence interval of the mean difference is 0.083–0.23 (p < 0.001). Conclusions: During cross-validation, the calibrated model is superior to the naïve model as measured by DSC, with +22% mean prediction accuracy. Calibration empowers a relatively simple model to become more predictive.
Association of NASP with HSP90 in Mouse Spermatogenic Cells

NASP (nuclear autoantigenic sperm protein) is a linker histone-binding protein found in all dividing cells that is regulated by the cell cycle (Richardson, R. T., Batova, I. N., Widgren, E. E., Zheng, L. X., Whitfield, M., Marzluff, W. F., and O'Rand, M. G. (2000) J. Biol. Chem. 275, 30378-30386), and in the nucleus linker histones not bound to DNA are bound to NASP (Alekseev, O. M., Bencic, D. C., Richardson R. T., Widgren E. E., and O'Rand, M. G. (2003) J. Biol. Chem. 278, 8846-8852). In mouse spermatogenic cells tNASP binds the testis-specific linker histone H1t. Utilizing a cross-linker, 3,3′-dithiobissulfosuccinimidyl propionate, and mass spectrometry, we have identified HSP90 as a testis/embryo form of NASP (tNASP)-binding partner. In vitro assays demonstrate that the association of tNASP with HSP90 stimulated the ATPase activity of HSP90 and increased the binding of H1t to tNASP. HSP90 and tNASP are present in both nuclear and cytoplasmic fractions of mouse spermatogenic cells; however, HSP90 bound to NASP only in the cytoplasm. In vitro nuclear import assays on permeabilized HeLa cells demonstrate that tNASP, in the absence of any other cytoplasmic factors, transports linker histones into the nucleus in an energy and nuclear localization signal-dependent manner. Consequently we hypothesize that in the cytoplasm linker histones are bound to a complex containing NASP and HSP90 whose ATPase activity is stimulated by binding NASP. NASP-H1 is subsequently released from the complex and translocates to the nucleus where the H1 is released for binding to the DNA.
Driving-Related Cognitive Performance in Older Adults with Pharmacologically Treated Cardiovascular Disease

The objective of this study was to determine if older drivers with pharmacologically treated hypertension and/or heart disease demonstrate impaired performance on established driving-related cognitive measures. Data regarding self-reported demographic variables (i.e., age, sex, race, income, mental and physical health diagnoses, and prescription drug use) and performance on driving-related measures of cognitive function (i.e., Trail Making Test B and Useful Field of View [UFOV®] subtest 2) were gathered from 865 licensed drivers. No group cognitive performance differences were found among the treated hypertensive group and the healthy control group, thus underscoring the importance of effective hypertension management. However, older adults with pharmacologically treated heart disease demonstrated poorer performance than did older adults without heart disease on Trails B and UFOV® subtest 2. Although it is generally agreed that assessment and early intervention with regard to heart disease risk factors (i.e., cholesterol, tobacco smoking, obesity, etc.) beneficially affect physical health, the current results also indicate that addressing such risk factors prior to the development of heart disease may benefit cognitive function as well.
Evaluation of the prototype Anaesthetic Non‐technical Skills for Anaesthetic Practitioners (ANTS‐AP) system: a behavioural rating system to assess the non‐technical skills used by staff assisting the anaesthetist

This study tested the reliability, validity and usability of a prototype behavioural rating system for the non‐technical skills of assistants working with the anaesthetist. Anaesthetic nurses and operating department practitioners (n = 48) used the prototype Anaesthetic Non‐technical Skills for Anaesthetic Practitioners (ANTS‐AP) system to rate the non‐technical skills of anaesthetic assistants in 12 videos of simulated theatre work. Test–retest reliability was assessed with a sub‐sample (n = 12). The skill categories assessed were ‘situation awareness’, ‘teamwork and communication’ and ‘task management’. The internal consistency for the ratings of elements in categories was acceptable (Cronbach's α of 0.78, 0.77 and 0.69, respectively), with more modest inter‐rater reliability (intraclass correlations for categories 0.54, 0.70, 0.86), test–retest reliability (intraclass correlations 0.68, 0.58, 0.38) and accuracy (weighted kappa 0.39). Most participants considered the system complete (n = 42, 87%), the wording clear (n = 48, 100%) and the system useful for structuring observation (n = 48, 100%).
Genomic Landscape of Colorectal Mucosa and Adenomas

The molecular basis of the adenoma-to-carcinoma transition has been deduced using comparative analysis of genetic alterations observed through the sequential steps of intestinal carcinogenesis. However, comprehensive genomic analyses of adenomas and at-risk mucosa are still lacking. Therefore, our aim was to characterize the genomic landscape of colonic at-risk mucosa and adenomas. We analyzed the mutation profile and copy number changes of 25 adenomas and adjacent mucosa from 12 familial adenomatous polyposis patients using whole-exome sequencing and validated allelic imbalances (AI) in 37 adenomas using SNP arrays. We assessed for evidence of clonality and performed estimations on the proportions of driver and passenger mutations using a systems biology approach. Adenomas had lower mutational rates than did colorectal cancers and showed recurrent alterations in known cancer driver genes (APC, KRAS, FBXW7, TCF7L2) and AIs in chromosomes 5, 7, and 13. Moreover, 80% of adenomas had somatic alterations in WNT pathway genes. Adenomas displayed evidence of multiclonality similar to stage I carcinomas. Strong correlations between mutational rate and patient age were observed in at-risk mucosa and adenomas. Our data indicate that at least 23% of somatic mutations are present in at-risk mucosa prior to adenoma initiation. The genomic profiles of at-risk mucosa and adenomas illustrate the evolution from normal tissue to carcinoma via greater resolution of molecular changes at the inflection point of premalignant lesions. Furthermore, substantial genomic variation exists in at-risk mucosa before adenoma formation, and deregulation of the WNT pathway is required to foster carcinogenesis. Cancer Prev Res; 9(6); 417–27. ©2016 AACR.
Netbank: The Conservative Internet Entrepreneurs

NetBank is a successful Internet startup. In late 2001 it was the only Internet Bank that really succeeded in the U.S. By the end of 2001, Netbank operated nation wide with nearly a quarter of a million customers. The number of accounts grew at 275 percent per annum compounded since incorporation. This case describes the development of NetBank and addresses the issues it faced in handling rapid growth as it implemented Internet banking.