Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of gadolinium nanoparticles and molecular contrast agents for radiation therapy‐enhancement

Purpose: Nanoparticles appear as a novel tool to enhance the effectiveness of radiotherapy in cancer treatments. Many parameters influence their efficacy, such as their size, concentration, composition, their cellular localization, as well as the photon source energy. The current Monte Carlo study aims at comparing the dose‐enhancement in presence of gadolinium (Gd), either as isolated atoms or atoms clustered in nanoparticles (NPs), by investigating the role played by these physical parameters at the cellular and the nanometer scale. In parallel, in vitro assays were performed in presence of either the gadolinium contrast agent (GdCA) Magnevist® or ultrasmall gadolinium NPs (GdNPs, 3 nm) for comparison with the simulations. Methods: PENELOPE Monte Carlo Code was used for in silico dose calculations. Monochromatic photon beams were used to calculate dose enhancements in different cell compartments and low‐energy secondary electron spectra dependence with energy. Particular attention has been placed on the interplay between the X‐ray beam energy, the Gd localization and its distance from cellular targets. Clonogenic assays were used to quantify F98 rat glioma cell survival after irradiation in the presence of GdNPs or GdCA, using monochromatic X‐rays with energies in the 30 keV–80 keV range from a synchrotron and 1.25 MeV gamma photons from a cobalt‐60 source. The simulations that correspond to the experimental conditions were compared with the experimental results. Results: In silico, a highly heterogeneous and clustered Gd‐atom distribution, a massive production of low energy electrons around GdNPs and an optimal X‐ray beam energy, above the Gd K‐edge, were key factors found to increase microscopic doses, which could potentially induce cell death. The different Gd localizations studied all resulted in a lower dose enhancement for the nucleus component than for cytoplasm or membrane compartments, with a maximum dose‐enhancement factor (DEF) found at 65 keV and 58 keV, respectively. In vitro, radiosensitization was observed with GdNPs incubated 5 h with the cells (2.1 mg Gd/mL) at all energies. Experimental DEFs were found to be greater than computational DEFs but follow a similar trend with irradiation energy. However, an important radiosensitivity was observed experimentally with GdNPs at high energy (1.25 MeV), whereas no effect was expected from modeling. This effect was correlated with GdNPs incubation time. In vitro, GdCA provided no dose enhancement at 1.25 MeV energies, in agreement with computed data. Conclusions: These results provide a foundation on which to base optimizations of the physical parameters in Gd radiation‐enhanced therapy. Strong evidence was provided that GdCA or GdNPs could both be used for radiation dose‐enhancement therapy. There in vivo biological distribution, in the tumor volume and at the cellular scale, will be the key factor for providing large dose enhancements and determine their therapeutic efficacy.
MAC1 mediates LPS‐induced production of superoxide by microglia: The role of pattern recognition receptors in dopaminergic neurotoxicity

Microglia‐derived superoxide is critical for the inflammation‐induced selective loss of dopaminergic (DA) neurons, but the underlying mechanisms of microglial activation remain poorly defined. Using neuron‐glia and microglia‐enriched cultures from mice deficient in the MAC1 receptor (MAC1−/−), we demonstrate that lipopolysaccharide (LPS) treatment results in lower TNFα response, attenuated loss of DA neurons, and absence of extracellular superoxide production in MAC1−/− cultures. Microglia accumulated fluorescently labeled LPS in punctate compartments associated with the plasma membrane, intracellular vesicles, and the Golgi apparatus. Cytochalasin D (CD), an inhibitor of phagocytosis, blocked LPS internalization. However, microglia derived from Toll‐like receptor 4 deficient mice and MAC1−/− mice failed to show a significant decrease in intracellular accumulation of labeled LPS, when compared with controls. Pretreatment with the scavenger receptor inhibitor, fucoidan, inhibited 79% of LPS accumulation in microglia without affecting superoxide, indicating that LPS internalization and superoxide production are mediated by separate phagocytosis receptors. Together, these data demonstrate that MAC1 is essential for LPS‐induced superoxide from microglia, implicating MAC1 as a critical trigger of microglial‐derived oxidative stress during inflammation‐mediated neurodegeneration. © 2007 Wiley‐Liss, Inc.
Specific Requirement of Gli Transcription Factors in Hedgehog-mediated Intestinal Development*

Background: Hedgehog signaling plays important roles during intestinal development. Results: Mesenchymal Gli2 activation, but not Gli3 removal, rescued Hedgehog pathway defects. Screen identified small leucine-rich glycoproteins (SLRPs) downstream of Hedgehog in the gut. Conclusion: Hedgehog activity is mediated by Gli2 and involves SLRP regulation in the developing intestine. Significance: This study uncovers novel genetic and molecular mechanisms underlying Hedgehog function in intestinal development. Hedgehog (Hh) signaling is involved in multiple aspects of embryonic gut development, including mesenchymal growth and smooth muscle differentiation. The Gli family transcription factors is thought to collectively mediate Hh signaling in mammals. However, the function of different Gli proteins in gut development remains uncharacterized. Here, we genetically dissect the contribution of Gli transcriptional activation and de-repression in intestinal growth and patterning. We find that removal of the Gli3 repressor is dispensable for intestinal development and does not play a major role in Hh-controlled gut development. However, Gli2 activation is able to fully rescue the Smoothened (Smo)-null intestinal phenotype, suggesting that the Gli2 transcription factor is the main effector for Hh signaling in the intestine. To understand further the molecular mechanism underlying Hh/Gli function in the developing gut, we identify a subset of small leucine-rich glycoproteins (SLRPs) that may function downstream of Hh signaling in the mesenchyme. We show that osteoglycin, a SLRP, inhibits Hh-induced differentiation toward the smooth muscle lineage in C3H10T1/2 pluripotent mesenchymal cells. Taken together, our study reveals, for the first time, the distinct roles of Gli proteins in intestine development and suggests SLRPs as novel regulators of smooth muscle cell differentiation.
Knowledge gaps in the epidemiology of Toxocara: the enigma remains

SUMMARY Toxocara species infect a wide range of companion, domestic and wild animals as definitive and paratenic hosts, via multiple routes of transmission, producing long-lived tissue-inhabiting larvae and resistant eggs that can survive in the external environment. Therefore Toxocara and the disease it causes in humans, toxocariasis, represents an ideal aetiological agent for the development of the one health approach. However, despite increasing awareness of the public health significance of toxocariasis, gaps in our understanding of certain key aspects of the parasite's biology and epidemiology remain. These gaps hinder our ability to integrate research effort within the veterinary, medical and environmental disciplines. This review will highlight key deficits in our understanding of nine dimensions of Toxocara epidemiology and discuss a potential scenario to develop a more integrated, one health approach to improve our understanding of the prevention and control of this complex and cryptic zoonosis.
Integrated air-filled waveguide antennas in LTCC for G-band operation

In this paper, a new concept in planar transmission lines is introduced, namely the air-filled substrate integrated waveguide. The air-filled guide was fabricated within an LTCC planar circuit. Measurements were made over G-band (140GHz-220GHz) which showed the integrated guide had insertion losses comparable, or slightly less, than other planar transmission lines at these frequencies. To further demonstrate the potential of the new structure a 150GHz slot antenna, using integrated air-filled waveguide, was designed and tested. The principal significance of the new integration technology proposed here is that it will permit the integration of air-filled, high-Q cavity filters and allow the closed integration of efficient slot antennas with front-end circuitry.
"Anergy" of TH0 helper T lymphocytes induces downregulation of TH1 characteristics and a transition to a TH2-like phenotype

Mature CD4+ helper T lymphocytes have been categorized into two major functional phenotypes, TH1 and TH2, which produce distinct arrays of lymphokines and which are thought to arise from a pluripotential precursor cell termed TH0. Clonal anergy can be induced in TH1 clones by stimulating via the T cell receptor (TCR) complex in the absence of a costimulator molecule; however, anergy has been difficult to demonstrate in TH2 clones. We show here that treatment of cloned TH0 lines with anergizing stimuli results in the selective loss of TH1 characteristics and retention of a TH2 phenotype. Treated cells exhibit a substantial reduction in interleukin 2 (IL-2) production and antigen- specific cytolytic activity, but retain comparable IL-4 and IL-5 production in response to restimulation via the TCR complex. TH0 clones exposed to anergizing stimuli also increase in size, thus morphologically resembling TH2 cells. The signaling characteristics of these cells also are altered, in that they exhibit an elevated basal level of intracellular free calcium which fails to increase significantly with subsequent restimulation, reminiscent of the signaling characteristics of TH2 cells. "Anergized" TH0 clones thus share several functional, morphologic, and physiologic properties with cells of the TH2 phenotype, suggesting that TH2 cells may arise when TH0 cells are stimulated via the TCR complex in the absence of a putative costimulator molecule.
Multiple instance learning using visual phrases for object classification

Recently, bag of words (BoW) model has led to many significant results in visual object classification. However, due to the limited descriptive and discriminative ability of visual words, the resulting performance of visual object classification is still incomparable to its analogy in text domain, i.e. document categorization. Furthermore, for weakly labeled image data, where we only know whether an object is present or not, traditional learning based methods may suffer from background clutters and large appearance variations. To address these issues, we propose a novel visual phrase based Multiple Instance Learning (MIL) method. In this method, the visual phrase is first generated from over-segmented image regions of homogeneous appearance and visual words within each region, which may provide enhanced descriptive ability by enforcing the spatial coherency. Then a MIL algorithm is applied to efficiently learn from the weakly labeled image data. The experiments on benchmark datasets show that our proposed method always significantly outperforms several state-of-the-art algorithms, such as Spatial Pyramid Matching (SPM) [5] and Spatial-LTM [8].
Sesquicentennial Tribute to Emil Redlich (1866-1930), The ‘Embodied Conscience of Neurology'

Professor Emil Redlich (1866-1930) of the University of Vienna was born 150 years ago. Raised in a humble environment, he became an eminent researcher and neurology scholar, and succeeded in laying some of the key foundations of neuroanatomy and neuropathology. His name is linked to medical eponyms that define the dorsal root entry zone into the spinal cord, epidemic disseminated encephalomyelitis, narcolepsy, senile plaques and dementia. As its first director, he managed to organize the Maria-Theresien-Schlössel into a first-class neuropsychiatric hospital. The one attribute that his colleagues constantly recognized was his inexorable scientific demeanor, always insisting on a critical checking of the facts before formulating any hypothesis.
Free Cortisol in Sepsis and Septic Shock

BACKGROUND:Severe sepsis activates the hypothalamopituitary axis, increasing cortisol production. In some studies, hydrocortisone substitution based on an adrenocorticotropic hormone-stimulation test or baseline cortisol measurement has improved outcome. Because only the free fraction of cortisol is active, measurement of free cortisol may be more important than total cortisol in critically ill patients. We measured total and free cortisol in patients with severe sepsis and related the concentrations to outcome. METHODS:In a prospective study, severe sepsis was defined according the American College of Chest Physicians/Society of Critical Care Medicine criteria. Blood samples were drawn within 24 h of study entry. Serum cortisol was analyzed by electrochemiluminescence immunoassay. The Coolens method was used for calculating serum free cortisol concentrations. RESULTS:Blood samples were collected from 125 patients, of whom 62 had severe sepsis and 63 septic shock. Hospital mortality was 21%. Calculated free serum cortisol correlated well with serum total cortisol (r = 0.90, P < 0.001). There was no difference in the total cortisol concentrations in patients with sepsis and septic shock (728 ± 386 nmol/L vs 793 ± 439 nmol/L, P = 0.44). Nonsurvivors had higher calculated serum free (209 ± 151 nmol/L) and total (980 ± 458 nmol/L) cortisol concentrations than survivors (119 ± 111 nmol/L, P = 0.002, and 704 ± 383 nmol/L, P = 0.002). Depending on the definition, the incidence of adrenal insufficiency varied from 8% to 54%. CONCLUSIONS:Clinically, calculation of free cortisol does not provide essential information for identification of patients who would benefit from corticoid treatment in severe sepsis and septic shock.
Sphingosine 1‐phosphate receptor agonist FTY720‐phosphate causes marginal zone B cell displacement

FTY720 is an immunosuppressive agent that modulates lymphocyte trafficking. It is phosphorylated in vivo to FTY720‐phosphate (FTY‐P) and binds to a family of G protein‐coupled receptors recognizing sphingosine 1‐phosphate (S1P) as the natural ligand. It has previously been reported that FTY‐P blocks egress of lymphocytes from the thymus and lymph nodes, resulting in peripheral blood lymphopenia. We now report that FTY‐P also causes displacement of marginal zone (MZ) B cells to the splenic follicles, an effect that is similar to that observed after in vivo administration of lipopolysaccharide. This effect is specific to B cells in the MZ, as treatment with FTY‐P does not cause redistribution of the resident macrophage population. A small but statistically significant decrease in the expression of β1 integrin on MZ B cells was observed with FTY‐P treatment. The redistribution of MZ B cells from the MZ sinuses does not abolish the ability of these cells to respond to the T‐independent antigen, trinitrophenol‐Ficoll. It has been proposed that the displacement of MZ B cells to the follicles is an indication of cell activation. Consistent with this, FTY‐P caused an increase in percentage of MZ B cells expressing activation markers CD9, CD1d, and CD24. These results suggest that S1P receptors on MZ B cells are responsible for their mobilization to follicles.
Characterization of the Conserved Interaction between GATA and FOG Family Proteins* 210

The N-terminal zinc finger (ZnF) from GATA transcription factors mediates interactions with FOG family proteins. In FOG proteins, the interacting domains are also ZnFs; these domains are related to classical CCHH fingers but have an His → Cys substitution at the final zinc-ligating position. Here we demonstrate that different CCHC fingers in the FOG family protein U-shaped contact the N-terminal ZnF of GATA-1 in the same fashion although with different affinities. We also show that these interactions are of moderate affinity, which is interesting given the presumed low concentrations of these proteins in the nucleus. Furthermore, we demonstrate that the variant CCHC topology enhances binding affinity, although the His → Cys change is not essential for the formation of a stably folded domain. To ascertain the structural basis for the contribution of the CCHC arrangement, we have determined the structure of a CCHH mutant of finger nine from U-shaped. The structure is very similar overall to the wild-type domain, with subtle differences at the C terminus that result in loss of the interaction in vivo. Taken together, these results suggest that the CCHC zinc binding topology is required for the integrity of GATA-FOG interactions and that weak interactions can play important roles in vivo.
Care-related distress: a nationwide study of parents who lost their child to cancer.

PURPOSE Palliative care is an important part of cancer treatment. However, little is known about how care-related factors affect bereaved intimates in a long-term perspective. We conducted a population-based, nationwide study addressing this issue, focusing on potential care-related stressors in parents losing a child to cancer. METHODS In 2001, we attempted to contact all parents in Sweden who had lost a child to cancer in 1992 to 1997. The parents were asked, through an anonymous postal questionnaire, about their experience of the care given and to what extent these experiences still affect them today. RESULTS Information was supplied by 449 (80%) of 561 eligible parents. Among 196 parents of children whose pain could not be relieved, 111 (57%) were still affected by it 4 to 9 years after bereavement. Among 138 parents reporting that the child had a difficult moment of death, 78 (57%) were still affected by it at follow-up. The probability of parents reporting that their child had a difficult moment of death was increased (relative risk = 1.4; 95% CI, 1.0 to 1.8) if staff were not present at the moment of death. Ten percent of the parents (25 of 251 parents) were not satisfied with the care given during the last month at a pediatric hematology/oncology center; the corresponding figure for care at other hospitals was 20% (33 of 168 parents; P = .0163). CONCLUSION Physical pain and the moment of death are two important issues to address in end-of-life care of children with cancer in trying to reduce long-term distress in bereaved parents.
Performance Analysis of Hybrid STBC in MIMO-OFDM-Based Wireless LANs

In this paper, we present a detailed study of the performance of hybrid STBC wireless LAN systems. In particular, we look at the performances of hybrid STBC systems with two different antenna configurations. We analyze the performance and advantages of using hybrid STBC over spatial multiplexing and of using "even" and "uneven" modulation and coding sets.
Absolute and attributable risks of cardiovascular disease incidence in relation to optimal and borderline risk factors: comparison of African American with white subjects--Atherosclerosis Risk in Communities Study.

BACKGROUND Among white Americans, a large proportion of cardiovascular disease (CVD) events is explained by borderline or any elevated CVD risk factor levels. The degree to which this is true among African American subjects is unclear. METHODS The Atherosclerosis Risk in Communities Study included 14 162 middle-aged adults who were free of recognized stroke or coronary heart disease and had baseline information on risk factors. Based on national guidelines, we categorized risk factors (blood pressure, cholesterol levels, diabetes, and smoking) into 3 categories, ie, optimal, borderline, and elevated. Incidence of CVD (composite of stroke and coronary heart disease) (n = 1492) and CVD mortality (n = 612) were identified for a 13-year period. RESULTS The proportion of subjects with all optimal risk factor levels was lower in African American (3.8%) than in white (7.5%) subjects. Conversely, the proportion of subjects with at least 1 elevated risk factor was higher in African American (approximately 80%) than in white (approximately 60%) subjects. After adjustment for these risk factor differences and education level, African American and white subjects had virtually identical rates of CVD (relative hazard for African American subjects, 1.01; 95% confidence interval, 0.90-1.14). The proportion of CVD events explained by elevated risk factors was high in African American subjects (approximately 90%) compared with approximately 65% in white subjects. CONCLUSIONS The higher CVD incidence rate in African American than in white subjects seems largely attributable to a high frequency of elevated CVD risk factors in African American subjects. Primary prevention of elevated CVD risk factors in African American subjects might greatly reduce CVD occurrence as much as it has for white subjects.
1,N6-etheno-2'-deoxytubercidin hemihydrate.

The title compound [systematic name: 7-(2-deoxy-β-D-erythro-pentofuranosyl)-7H-imidazo[1,2-c]pyrrolo[2,3-d]pyrimidine hemihydrate], 2C(13)H(14)N(4)O(3)·H(2)O or (I)·0.5H(2)O, shows two similar conformations in the asymmetric unit. These two conformers are connected through one water molecule by hydrogen bonds. The N-glycosylic bonds of both conformers show an almost identical anti conformation with χ = -107.7 (2)° for conformer (I-1) and -107.0 (2)° for conformer (I-2). The sugar moiety adopts an unusual N-type (C3'-endo) sugar pucker for 2'-deoxyribonucleosides, with P = 36.8 (2)° and τ(m) = 40.6 (1)° for conformer (I-1), and P = 34.5 (2)° and τ(m) = 41.4 (1)° for conformer (I-2). Both conformers and the solvent molecule participate in the formation of a three-dimensional pattern with a `chain'-like arrangement of the conformers. The structure is stabilized by intermolecular O-H.O and O-H.N hydrogen bonds, together with weak C-H.O contacts.
The Evolution of a Teacher Professional Learning Network for Digital Literacy

This case study describes the evolution of a teacher professional development project for digital literacy. The goal of this teacher professional development project is to support teachers’ effective use of technology and professional learning in an ICT-based learning environment by creating a professional learning network (PLN). The case suggests that the situated, collaborative learning environment of this PLN provided supportive affordance to improve teachers’ use of technology and professional learning. In addition, we highlight teachers’ voice as an important element to sustain the effectiveness of the PLN.
Selection of Enzymes for Terminal Restriction Fragment Length Polymorphism Analysis of Fungal Internally Transcribed Spacer Sequences

ABSTRACT Terminal restriction fragment length polymorphism (TRFLP) profiling of the internally transcribed spacer (ITS) ribosomal DNA of unknown fungal communities is currently unsupported by a broad-range enzyme-choosing rationale. An in silico study of terminal fragment size distribution was therefore performed following virtual digestion (by use of a set of commercially available 135 type IIP restriction endonucleases) of all published fungal ITS sequences putatively annealing to primers ITS1 and ITS4. Different diversity measurements were used to rank primer-enzyme pairs according to the richness and evenness that they showed. Top-performing pairs were hierarchically clustered to test for data dependency. The enzyme set composed of MaeII, BfaI, and BstNI returned much better results than randomly chosen enzyme sets in computer simulations and is therefore recommended for in vitro TRFLP profiling of fungal ITSs.