Miracle-dz/UniFAR-FTUs huggingface dataset:
CT-planned internal mammary node radiotherapy in the DBCG-IMN study: Benefit versus potentially harmful effects

Abstract Background. The DBCG-IMN is a nationwide population-based cohort study on the effect of internal mammary node radiotherapy (IMN-RT) in patients with node positive early breast cancer. Due to the risk of RT-induced heart disease, only patients with right-sided breast cancer received IMN-RT, whereas patients with left-sided breast cancer did not. At seven-year median follow-up, a 3% gain in overall survival with IMN-RT has been reported. This study estimates IMN doses and doses to organs at risk (OAR) in patients from the DBCG-IMN. Numbers needed to harm (NNH) if patients with left-sided breast cancer had received IMN-RT are compared to the number needed to treat (NNT). Material and methods. Ten percent of CT-guided treatment plans from the DBCG-IMN patients were selected randomly. IMNs and OAR were contoured in 68 planning CT scans. Dose distributions were re-calculated. IMNs and OAR dose estimates were compared in right-sided versus left-sided breast cancer patients. In six left-sided patients, IMN-RT was simulated, and OAR doses were compared to those in the original plan. The NNH resulting from the change in mean heart dose (MHD) was calculated using a published model for risk of RT-related ischemic heart death. Results. In original plans, the absolute difference between right- and left-sided V90% to the IMNs was 38.0% [95% confidence interval (5.5%; 70.5%), p < 0.05]. Heart doses were higher in left-sided plans. With IMN-RT simulation without regard to OAR constraints, MHD increased 4.8 Gy (0.9 Gy; 8.7 Gy), p < 0.05. Resulting NNHs from ischemic heart death were consistently larger than the NNT with IMN-RT. Conclusion. Refraining from IMN-RT on the left side may have spared some ischemic heart deaths. Assuming left-sided patients benefit as much from IMN-RT as right-sided patients, the benefits from IMN-RT outweigh the costs in terms of ischemic heart death.
Response inhibition under alcohol: effects of cognitive and motivational conflict.

OBJECTIVE This experiment tested the effect of cognitive and motivational conflict on response inhibition under alcohol. METHOD Fifty-six male social drinkers were randomly assigned to one of eight groups (n = 8). Four pairs of groups received 0.62 g/kg of alcohol, or a placebo, and each pair performed a go/stop choice reaction time task under one of four conflict conditions. One condition (C) produced cognitive conflict by presenting "go" and "stop" signals in the task. Another condition (IR) added motivational conflict by administering an equal monetary reward for inhibiting responses to stop-signals, and for responding to go-signals. The remaining two conditions resolved the motivational conflict by administering the monetary reward only for inhibitions (I), or only for responses (R). RESULTS Compared with placebo, alcohol reduced inhibitions (i.e., impaired inhibitory control) under cognitive conflict (C; p = .041) and under motivational conflict (IR; p = .012). No significant effect of alcohol on inhibitions was observed in conditions where conflict was resolved (i.e., I and R). CONCLUSIONS The study shows that alcohol can reduce the ability to inhibit a response. However, impaired inhibitory control is not an inevitable outcome of the drug action, because it can be counteracted by the consequences of behavior in the situation.
Assessing the In-Orbit Impact of Cell Cracks - An Electroluminescence Study of Crack Propagation

A set of representative miniature solar arrays was built, featuring triple junction cells with a range of typical production defects. The evolution of these cracks throughout several thousand simulated eclipse phases was studied with the help of electroluminescence imaging and pulsed solar simulator measurements. In addition, the effect of sine vibration and acoustic noise was analyzed by monitoring cell cracks on actual flight panels throughout their testing sequences. A power law dependence was found for the number of crack growth events (CGE) per cycle on the number of thermal cycles and the total number of CGE after 2000 cycles showed a linear dependence on crack size. An unexpected crack growth direction, predominantly parallel to the short cell edge, was found. Sine vibration and acoustic noise testing did not result in crack propagation at all. The electrical impact of propagating cracks originated in most cases from the interruption of the cell front side contact network
The palindromic series I repeats in the simian cytomegalovirus major immediate-early promoter behave as both strong basal enhancers and cyclic AMP response elements

A 600-base-pair (bp) enhancer region upstream from the major IE94 gene of simian cytomegalovirus (SCMV) produces very strong basal expression of associated gene products. This domain consists of multiple sets of interspersed repetitive elements, including 11 copies of a conserved 16-bp palindromic sequence with the consensus CCATTGACGTCAATGG. These series I repeats contain an 8-bp core TGACGTCA that resembles the cyclic AMP (cAMP) response element (CRE) of cellular genes. In transient chloramphenicol acetyltransferase assays in K562 human erythroleukemia cells, a set of deleted variants of the IE94 promoter all responded up to 15-fold to induction by cAMP. However, successive removal of most of the SCMV 16-bp motifs reduced basal expression over 20-fold. The cAMP stimulation was also manifested at the steady-state RNA level after SCMV infection of K562 cells and was detectable within 1.5 h after treatment of DNA-transfected cells. Addition of a single 30-bp oligonucleotide encompassing the 16-bp palindrome conveyed up to 10-fold cAMP responsiveness onto a heterologous weak promoter but had no effect on basal expression. In contrast, two or more adjacent copies produced 20- to 40-fold increases in basal expression and provided greater than 200-fold activation in the presence of cAMP. Similar effects were obtained when the oligonucleotides were placed in a downstream location relative to the reporter gene. Studies with mutant oligonucleotides revealed that both the core CRE and the flanking sequence portions of the 16-bp elements were essential for enhancer function. Both components were also important for maximum cAMP responsiveness. Band shift assays with fractionated nuclear extracts from Raji lymphocytes revealed multiple competable complexes with cellular DNA-binding factors that recognized the series I elements. Three distinct CREB-like factors were detected that required only the core 8-bp elements for binding. We conclude that the 16-bp series I repeats provide a major contribution to the constitutive enhancer properties of the IE94 promoter and also act as functional CREs. The cAMP response properties appear likely to play a key role in reactivation of the virus from a latent state in appropriately differentiating cell types.
Electric lead field for a piecewise homogeneous volume conductor model of the head

A new method is presented for computing the electric lead field of a realistic head shape model which has piecewise homogenous conductivity. The basic formulae are derived using the well-known reciprocity theorem. Previously described methods are also based upon this theorem, but these first calculate the electric potential inside the head by a scalar boundary element method (BEM), and then approximate the ohmic current density by some sort of gradient. In contrast, this paper proposes the direct evaluation of the ohmic current density by discretizing the vector Green's second identity which leads to a rector version of BEM. This approach also allows the derivation of the same equations for the three concentric spheres model as obtained by Rush and Driscoll (1969). The results of simulations on a spherical head model indicate that the use of a vector BEM leads to an improvement of accuracy in the computation of the ohmic current density with respect to those reported previously, in term of different measures of error.
Response characteristics of the cells of cortical area 21a of the cat with special reference to orientation specificity.

1. Extracellular recording using tungsten‐in‐glass microelectrodes was conducted on 115 neurons in area 21a of fifteen anaesthetized cats. Quantitative analysis using computer‐controlled display and collecting routines were used to investigate the excitatory and inhibitory regions of the receptive field and to see if interaction, within and between these regions, contributed to the response properties of the cells. 2. The responses of the cells in the sample appeared to arise from a single, homogeneous class. All cells had single discharge regions which responded with composite ON/OFF firing to a stationary flashing bar. The same region also responded to moving light and dark bars and edges. There was little evidence of inhibition as measured by the suppression of spontaneous or induced firing. Most cells had relatively small receptive fields (primary width: mean = 2.1 +/‐ 0.9 deg (S.D.); n = 108), all were binocular and were located within 15.0 deg of the visual axes. 3. All cells responded well to slowly moving stimuli but generally failed to respond to stimuli moving faster than 10.0 deg s‐1. All responses were bi‐directional and, although many showed evidence of length summation, there was no sign of linear summation. 4. Despite the absence of significant sideband inhibition many cells were acutely tuned for orientation (half‐width at half‐height: mean = 15.6 +/‐ 5.3 deg; n = 48). To investigate this property further, cells were analysed to assess the effect of changing the length of a moving bar stimulus on the acuteness of the orientation tuning curve. Short bars, of similar length to the width of the receptive field, had orientation tuning curves of equivalent sharpness to those obtained with longer bars. 5. The equivalence of orientation tuning for long and short bars stands in contrast to the results obtained for both simple (S) and complex (C) cells of the striate cortex where tuning for the longer bar is sharper than that for the shorter. The result from area 21a cells is consistent with the absence of sideband inhibition and can be related to an input from the striate cortex that passes through a threshold barrier. 6. The orientation tuning of cells of area 21a can be explained if it is assumed that they receive their major input from C or complex cells of the striate cortex in which firing must reach a threshold frequency to activate the recipient cell.
Implementation of the Simple Endoscopic Activity Score in Crohn's Disease

Simple Endoscopic Score for Crohn's Disease (SES-CD) was developed as an attempt to simplify Crohn's Disease Endoscopic Index of Severity (CDEIS). Since it was constructed from CDEIS, SES-CD performs comparably but also carries similar limitations. Several studies have utilized SES-CD scoring to describe disease severity or response to therapy. Some of them used SES-CD score as a continuous variable while others utilized certain cutoff values to define severity grades. All SES-CD cutoff values reported in published clinical trials were empirically selected by experts. Although in most of the studies that used SEC-CD scoring to define disease severity, a score <3 reflected inactive disease, no study is using score 0 to predefine inactivity. Studies applying SES-CD to define response to treatment used score 0. There is no optimal SES-CD cut-off for endoscopic remission. The quantification of mucosal healing using SES-CD scoring has not been standardized yet. As the definition of mucosal healing by SES-CD is unset, the concept of deep remission is also still evolving. Serum and fecal biomarkers as well as new radiologic imaging techniques are complementary to SES-CD. Current practice as well as important changes in endoscopy should be taken into consideration when defining SES-CD cutoffs. The optimal timing of SES-CD scoring to assess mucosal healing is not defined yet. To conclude, SES-CD represents a valuable tool. However, a consensus agreement on its optimal use is required.
Development of high frequency gyrotrons

An overview of recent experimental and theoretical progess at MIT on the development of high frequency (>100 GHz) gyrotrons will be given. High power oscillators capable of powers in excess of 100 kW, which could be used as rf sources to heat fusion plasmas, are presently being designed and constructed. The operating characteristics of a 200 kW, 140 GHz gyrotron that achieved peak total efficiencies of 41% and single mode emission will be described. A parametric analysis has been completed that indicates that cw gyrotrons capable of powers in excess of 1 MW and high efficiency are consistent with the technological constraints of the device. The design parameters of 1 and 10 MW, 120 GHz monotrons will be reviewed. A 1 MW, 120-140 GHz pulsed gyrotron is presently being constructed at MIT and should be operational by early 1986. In addition to high power operation, gyrotrons are also capable of generating very high frequencies. The harmonic operation of the MIT gyrotron will be reviewed, and the prospects for generating frequencies up to 1 THz will be described.
Detrimental Effect of Class-selective Histone Deacetylase Inhibitors during Tissue Regeneration following Hindlimb Ischemia

Background: No information is available about the effect of class-selective histone deacetylase inhibitors (DIs) following hindlimb ischemia. Results: Class I and class IIa DIs prevent/delay ischemic muscle reconstruction at different stages. Conclusion: Evidence is provided about a detrimental effect of DIs during normal muscle regeneration. Significance: The therapeutic relevance of class-selective DIs in hindlimb ischemia may be limited by adverse effects. Histone deacetylase inhibitors (DIs) are promising drugs for the treatment of several pathologies including ischemic and failing heart where they demonstrated efficacy. However, adverse side effects and cardiotoxicity have also been reported. Remarkably, no information is available about the effect of DIs during tissue regeneration following acute peripheral ischemia. In this study, mice made ischemic by femoral artery excision were injected with the DIs MS275 and MC1568, selective for class I and IIa histone deacetylases (HDACs), respectively. In untreated mice, soon after damage, class IIa HDAC phosphorylation and nuclear export occurred, paralleled by dystrophin and neuronal nitric-oxide synthase (nNOS) down-regulation and decreased protein phosphatase 2A activity. Between 14 and 21 days after ischemia, dystrophin and nNOS levels recovered, and class IIa HDACs relocalized to the nucleus. In this condition, the MC1568 compound increased the number of newly formed muscle fibers but delayed their terminal differentiation, whereas MS275 abolished the early onset of the regeneration process determining atrophy and fibrosis. The selective DIs had differential effects on the vascular compartment: MC1568 increased arteriogenesis whereas MS275 inhibited it. Capillarogenesis did not change. Chromatin immunoprecipitations revealed that class IIa HDAC complexes bind promoters of proliferation-associated genes and of class I HDAC1 and 2, highlighting a hierarchical control between class II and I HDACs during tissue regeneration. Our findings indicate that class-selective DIs interfere with normal mouse ischemic hindlimb regeneration and suggest that their use could be limited by alteration of the regeneration process in peripheral ischemic tissues.
Detection of Submicroscopic Lymph Node Metastases with Polymerase Chain Reaction in Patients with Malignant Melanoma

BackgroundThe presence or absence of lymph node metastases in patients with malignant melanoma is the most powerful prognostic factor for predicting survival. If regional nodal metastases are found, the 5-year survival for the patient decreases approximately 50%. If the presence or absence of regional nodal metastases will determine which patients receive formal dissections or which patients enter adjuvant trials, then a technique is needed to accurately screen lymph node samples for occult disease. Routine histopathologic examination routinely underestimates the number of patients with metastases. This study was initiated to develop a highly sensitive clinically applicable method to detect micrometastases by examining lymph nodes for the presence of tyrosinase messenger RNA (mRNA). The hypothesis was that if mRNA for tyrosinase is found in the lymph node preparation, that finding is good evidence that metastatic melanoma cells are present. MethodsThe assay is accomplished using the combination of reverse transcription and double-round polymerase chain reaction (RT-PCR). The amplified samples are examined on a 2% agarose gel and tyrosinase cDNA is seen as a 207 base pair fragment. Lymph node preparations from 29 patients who were clinically stage I and II and undergoing elective node dissections were analyzed both by standard pathologic staining and RT-PCR. ResultsEleven of 29 lymph node (38%) samples from 29 patients with intermediate thickness melanoma were pathologically positive. Nineteen of the 29 lymph node preparations (66%) were RT-PCR-positive, and these included all of the pathologically positive samples, so that the false-negative rate was 0. In a spiking experiment, one SK-Mel-28 melanoma cell in a background of one million normal lymphocytes could be detected, thus indicating the sensitivity of this method. In addition, analysis by restriction enzyme mapping showed that the amplified 207-bp PCR product produced is part of the tyrosinase gene sequence.
Development of the Facial Midline

“Intellectual excellence lies in having faith in the observation of apparently nontranscendental and unimportant facts. To observe an anatomic element calmly, with an open, analytical spirit, and with spiritual freedom, can lead to an explosive vortex of new knowledge. ” –Miguel Orticochea, M.D. 1Traditional descriptive embryology based upon the interaction of frontonasal, lateral nasal, and medial nasal prominences is incapable of explaining the three-dimensional development of the facial midline. The internal structure of the nose and that of the oronasal midline can best be explained by the presence of paired A fields originating from the prechordal mesendoderm, associated with the nasal and optic placodes, supplied by the internal carotid artery, and sharing a common genetic coding with the prosomeres of the forebrain. Mesial drift of these fields leads to fusion of their medial walls; this in turn provides bilateral functional matrics within which form the orbits ethmoids, lacrimals, turbinates, premaxillae, vomerine bones, and the cartilages of the nose. This two-part paper reports six lines of evidence supporting the field theory model of facial development: (1) An apparent watershed exists in the midline of the base between the territories of the internal and external carotid systems. Isolation of the ICA in injected fetal specimens confirmed that the demarcation was distinct and restricted to the embryonic nasal capsule. (2) Field theory explains the developmental anatomy of the contents of the nasal capsule. (3) The neuromeric model of CNS development provides a genetic basis for the anatomy and behavior of fields. (4) Mutants for the Dlx5 gene demonstrate A field deletion patterns. These experiments relate the nasal placode to the structures of the A fields. (5) Separate regions of the original nasal placodes give rise to neurons, which are dedicated to separate sensory and endocrine systems. The A fields constitute the pathways by which these neurons reach the brain. (6) Non–cleft lip-related cleft palate, holoprosencephaly, and the Kallmann syndrome are clinical models that demonstrate the effects of anatomic disturbances within the A fields.
Results of a prospective pilot trial on mobility after whole body vibration in children and adolescents with osteogenesis imperfecta

Objective: To evaluate the effect of whole body vibration on the mobility of long-term immobilized children and adolescents with a severe form of osteogenesis imperfecta. Osteogenesis imperfecta is a hereditary primary bone disorder with a prevalence from 1 in 10000 to 1 in 20000 births. Most of these children are suffering from long-term immobilization after recurrent fractures. Due to the immobilization they are affected by loss of muscle (sarcopenia) and secondary loss of bone mass. Subjects: Whole body vibration was applied to eight children and adolescents (osteogenesis imperfecta type 3, N=5; osteogenesis imperfecta type 4, N=3) over a period of six months. Interventions and results: Whole body vibration was applied by a vibrating platform (Galileo Systems) constructed on a tilting-table. Success of treatment was assessed by measuring alterations of the tilting-angle and evaluating the mobility (Brief Assessment of Motor Function). All individuals were characterized by improved muscle force documented by an increased tilting-angle (median = 35 degrees) or by an increase in ground reaction force (median at start=30.0 [N/kg] (14.48—134.21); median after six months = 146.0 [N/kg] (42.46—245.25). Conclusions: Whole body vibration may be a promising approach to improve mobility in children and adolescents severely affected with osteogenesis imperfecta.
Verification of protein structures: Patterns of nonbonded atomic interactions

A novel method for differentiating between correctly and incorrectly determined regions of protein structures based on characteristic atomic interactions is described. Different types of atoms are distributed nonrandomly with respect to each other in proteins. Errors in model building lead to more randomized distributions of the different atom types, which can be distinguished from correct distributions by statistical methods.
Flexible parametric models for random‐effects distributions

It is commonly assumed that random effects in hierarchical models follow a normal distribution. This can be extremely restrictive in practice. We explore the use of more flexible alternatives for this assumption, namely the t distribution, and skew extensions to the normal and t distributions, implemented using Markov Chain Monte Carlo methods. Models are compared in terms of parameter estimates, deviance information criteria, and predictive distributions. These methods are applied to examples in meta‐analysis and health‐professional variation, where the distribution of the random effects is of direct interest. The results highlight the importance of allowing for potential skewing and heavy tails in random‐effects distributions, especially when estimating a predictive distribution. We describe the extension of these random‐effects models to the bivariate case, with application to a meta‐analysis examining the relationship between treatment effect and baseline response. We conclude that inferences regarding the random effects can crucially depend on the assumptions made and recommend using a distribution, such as those suggested here, which is more flexible than the normal. Copyright © 2007 John Wiley & Sons, Ltd.