Miracle-dz/UniFAR-FTUs huggingface dataset:
Model‐based analysis of multishell diffusion MR data for tractography: How to get over fitting problems

In this article, we highlight an issue that arises when using multiple b‐values in a model‐based analysis of diffusion MR data for tractography. The non‐monoexponential decay, commonly observed in experimental data, is shown to induce overfitting in the distribution of fiber orientations when not considered in the model. Extra fiber orientations perpendicular to the main orientation arise to compensate for the slower apparent signal decay at higher b‐values. We propose a simple extension to the ball and stick model based on a continuous gamma distribution of diffusivities, which significantly improves the fitting and reduces the overfitting. Using in vivo experimental data, we show that this model outperforms a simpler, noise floor model, especially at the interfaces between brain tissues, suggesting that partial volume effects are a major cause of the observed non‐monoexponential decay. This model may be helpful for future data acquisition strategies that may attempt to combine multiple shells to improve estimates of fiber orientations in white matter and near the cortex. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
Identify predictors of university students’ continuance intention to use online carbon footprint calculator

ABSTRACT An online carbon footprint calculator (CFC) is a Green Information System, which enables individuals to self-estimate carbon footprints, self-manage behaviour, and accordingly self-control carbon emissions. Individuals’ persistent CFC use may help to slow down global warming. Thus, it is vital to establish a model to investigate the motivational predictors of CFC continuance intention. We formulated a model by integrating Expectation-Confirmation Model (ECM) and Theory of Planned Behaviour (TPB), with the former measuring continuance intention and the latter measuring low-carbon behavioural intention. To validate the model and identify significant predictors, a survey was conducted on undergraduate students. The survey results revealed that ECM accounted for 50% of the variance in continuance intention, that TPB accounted for 35% in low-carbon behavioural intention, and that the integrated model accounted for 64% in CFC continuance intention. Plus, direct and significant predictors of CFC continuance intention included low-carbon attitude, low-carbon behavioural intention, low-carbon subjective norm, satisfaction, and usefulness. Findings, implications, and suggestions are accordingly offered.
Stereotactic vacuum‐assisted breast biopsy in 2874 patients: A multicenter study

I read with interest the article by Kettritz et al. regarding the accuracy of stereotactic 11-gauge vacuum-assisted breast biopsy (VAB) for diagnosing breast cancer in nonpalpable breast lesions. Of the 2893 VAB procedures performed, 19 (0.7%) yielded findings that were not representative, whereas 2874 were performed successfully. Atypical ductal hyperplasia (ADH), which was diagnosed in 141 lesions, was upgraded to cancer in 32 of 135 lesions that underwent surgical excision. No followup information was available for lobular carcinoma in situ (LCIS), which was diagnosed in 18 cases. Benign histology was diagnosed in 2090 lesions, with cancer going undetected in 1 of 24 lesions that underwent surgical excision. The false-negative rate was defined as the percentage of lesions diagnosed as being benign on VAB that later proved to be malignant. This rate, which was calculated excluding nonrepresentative lesions and including benign lesions with (n 1438) or without (n 628) follow-up imaging data, was 0.05% (1 of 2090). Although the reported results are impressive, I believe that the analysis may overstate the accuracy of this technique. I prefer an alternative false-negative rate, defined as the percentage of pathologically confirmed malignant lesions that yielded benign stereotactic biopsy findings without findings of atypia or high-risk lesions. This approach requires delineation of atypical and high-risk lesions (including ADH and, variably, LCIS, atypical lobular hyperplasia, radial scar, papilloma, and/or benign phyllodes tumor), knowledge of the total number of cancers found in the study group at any time, and knowledge of how many of those cancers yielded benign (including discordant or nonrepresentative) findings on original biopsy. Falsenegative rates calculated in this manner have been reported for stereotactic 11-gauge VAB and automated 14-gauge large-core needle biopsy. To calculate this alternative false-negative rate for the study conducted by Kettritz et al., more data are needed. For the 19 nonrepresentative lesions and the 18 lesions diagnosed as LCIS, we must know how many of each were rebiopsied and how many cancers subsequently were identified. The total number of cancers among the 2893 lesions evaluated with VAB equals the number of cancers detected on rebiopsy of nonrepresentative lesions and rebiopsy of lesions diagnosed as LCIS plus the number of cancers detected on VAB (n 625), rebiopsy of lesions diagnosed as ADH (n 32), and rebiopsy of lesions found to be benign (n 1). The total number of false-negative lesions equals the number of cancers found on rebiopsy of nonrepresentative lesions plus the one cancer detected on rebiopsy of a lesion that initially was found to be benign.
Regulation of NT‐3 and BDNF levels in guinea pig auditory brain stem nuclei after unilateral cochlear ablation

Injury to areas of the central nervous system can alter neurotrophin levels, which may influence postlesion neuronal survival and plasticity. To determine if sensorineural hearing loss induces such changes, we used an enzyme‐linked immunosorbent assay (ELISA) to measure neurotrophin‐3 (NT‐3) and brain‐derived neurotrophic factor (BDNF) levels in adult guinea pig brain stem auditory nuclei 3–60 days after a unilateral cochlear ablation (UCA). After UCA, which destroyed the cochlea and cochlear nerve on one side, NT‐3 levels were usually depressed at 3 days by 22–44% but became elevated transiently at 7 days by 28–124%. BDNF levels were elevated transiently by 50% on the ablated side in the anteroventral (AVCN) and posteroventral (PVCN) cochlear nucleus at 3 days and may have signaled support for the survival of deafferented neurons. Coincident elevation at 3 and 7 days of BDNF or NT‐3 and phosphorylated extracellular signal‐regulated protein kinase 2 (ERK2‐P) suggested a relationship to stimulated signal transduction activity. Elevated neurotrophin levels may have contributed to synaptogenesis in the AVCN and the superior olive and to changes in the synaptic biochemistry in the auditory nuclei after UCA. In contrast, deficiencies or failure to elevate neurotrophin levels within several days of the UCA correlated with upregulation of phosphorylated stress‐activated protein kinase (SAPK‐P), suggesting a relationship with stress‐activated signal transduction and with the sparse degeneration of fibers observed in some of the auditory nuclei after UCA. © 2005 Wiley‐Liss, Inc.
Exposure to and recall of violence reduce short-term memory and cognitive control

Significance Research on violence has mainly focused on its consequences on individuals’ health and behavior. This study establishes the effects of exposure to violence on individuals’ short-term memory and cognitive control. These are key factors affecting individual well-being and societal development. We sampled Colombian civilians who were exposed either to urban violence or to warfare. We found that higher exposure to violence significantly reduces short-term memory and cognitive control only in the group actively recalling emotional states linked with such experiences. This finding demonstrates and characterizes the long-lasting effects of violence. Existing studies have found effects of poverty on cognitive control similar to those that we found for violence. This set of findings supports the validity of the cognitive theory underpinning these studies. Previous research has investigated the effects of violence and warfare on individuals' well-being, mental health, and individual prosociality and risk aversion. This study establishes the short- and long-term effects of exposure to violence on short-term memory and aspects of cognitive control. Short-term memory is the ability to store information. Cognitive control is the capacity to exert inhibition, working memory, and cognitive flexibility. Both have been shown to affect positively individual well-being and societal development. We sampled Colombian civilians who were exposed either to urban violence or to warfare more than a decade earlier. We assessed exposure to violence through either the urban district-level homicide rate or self-reported measures. Before undertaking cognitive tests, a randomly selected subset of our sample was asked to recall emotions of anxiety and fear connected to experiences of violence, whereas the rest recalled joyful or emotionally neutral experiences. We found that higher exposure to violence was associated with lower short-term memory abilities and lower cognitive control in the group recalling experiences of violence, whereas it had no effect in the other group. This finding demonstrates that exposure to violence, even if a decade earlier, can hamper cognitive functions, but only among individuals actively recalling emotional states linked with such experiences. A laboratory experiment conducted in Germany aimed to separate the effect of recalling violent events from the effect of emotions of fear and anxiety. Both factors had significant negative effects on cognitive functions and appeared to be independent from each other.
Response of bone turnover biochemical markers to extracorporeal shock wave therapy in the management of long-bone nonunions.

Although extracorporeal shock-wave therapy (ESWT)1 has been used extensively for treatment of nonunions of bone fractures (1), this treatment fails in many patients. Plain radiography remains the gold-standard approach for monitoring nonunion healing. Biochemical bone markers, however, may provide information regarding the effects of treatment earlier than radiography. Osteocalcin (OC) and bone-specific alkaline phosphatase (bALP) are used to monitor normal and delayed fracture healing (2). We investigated whether these biochemical bone markers can be used to distinguish between nonunions that respond to ESWT treatment and those that do not and to provide this information earlier than radiographic findings. Study participants were 34 patients [26 men and 8 women, mean (SD) age 42.5 (5.9) years] with tibial (22 patients) or femoral (12 patients) hypertrophic nonunions. This study was approved by our local ethics committee, and all subjects gave their written informed consent. All the patients underwent the same ESWT treatment, which consisted of 4 separate ESWT sessions at 1-week intervals, with 4000 impulses per session with an energy-flux density (EFD) of 0.40 mJ/mm2, provided by a an electromagnetic ESWT generator (Modulith SLK Storz Medical AG). The nonunion healing process was assessed …
Phosphorylation of an HP1-like protein is a prerequisite for heterochromatin body formation in Tetrahymena DNA elimination

Significance In various eukaryotes, heterochromatin is cytologically visible because multiple heterochromatic loci are assembled into higher order structures called heterochromatin bodies. Although heterochromatin bodies are dynamically assembled and disassembled during development, aging, and carcinogenesis, their role and the mechanism of formation remain to be clarified. In this report, by investigating the role of the heterochromatin body component Jub4p in the de novo heterochromatin body formation process in the ciliated protozoan Tetrahymena, we reveal that the phosphorylation and subsequent dephosphorylation of the Heterochromatin Protein 1-like protein Pdd1p are prerequisites for heterochromatin body formation and the following programmed DNA elimination. This study demonstrates the biochemical and biological importance of a temporally ordered phosphorylation–dephosphorylation cycle of a heterochromatin component in heterochromatin body formation. Multiple heterochromatic loci are often clustered into a higher order nuclear architecture called a heterochromatin body in diverse eukaryotes. Although phosphorylation of Heterochromatin Protein 1 (HP1) family proteins regulates heterochromatin dynamics, its role in heterochromatin bodies remains unknown. We previously reported that dephosphorylation of the HP1-like protein Pdd1p is required for the formation of heterochromatin bodies during the process of programmed DNA elimination in the ciliated protozoan Tetrahymena. Here, we show that the heterochromatin body component Jub4p is required for Pdd1p phosphorylation, heterochromatin body formation, and DNA elimination. Moreover, our analyses of unphosphorylatable Pdd1p mutants demonstrate that Pdd1p phosphorylation is required for heterochromatin body formation and DNA elimination, whereas it is dispensable for local heterochromatin assembly. Therefore, both phosphorylation and the following dephosphorylation of Pdd1p are necessary to facilitate the formation of heterochromatin bodies. We suggest that Jub4p-mediated phosphorylation of Pdd1p creates a chromatin environment that is a prerequisite for subsequent heterochromatin body assembly and DNA elimination.
High Resolution Structure and Double Electron-Electron Resonance of the Zebrafish Voltage-dependent Anion Channel 2 Reveal an Oligomeric Population*

Background: Biochemical characterization of voltage-dependent anion channel 2 (VDAC2) is limited due to an inability to obtain functional protein. Results: The crystal structure of VDAC2 suggests a dimer interface that is confirmed by double electron-electron resonance and cross-linking. Conclusion: zfVDAC2 has a fractional dimeric population. Significance: VDAC isoforms are structurally similar, but this study has identified a number of hot spots that require further exploration. In recent years, there has been a vast increase in structural and functional understanding of VDAC1, but VDAC2 and -3 have been understudied despite having many unique phenotypes. One reason for the paucity of structural and biochemical characterization of the VDAC2 and -3 isoforms stems from the inability of obtaining purified, functional protein. Here we demonstrate the expression, isolation, and basic characterization of zebrafish VDAC2 (zfVDAC2). Further, we resolved the structure of zfVDAC2 at 2.8 Å resolution, revealing a crystallographic dimer. The dimer orientation was confirmed in solution by double electron-electron resonance spectroscopy and by cross-linking experiments disclosing a dimer population of ∼20% in lauryldimethine amine oxide detergent micelles, whereas in lipidic bicelles a higher population of dimeric and higher order oligomers species were observed. The present study allows for a more accurate structural comparison between VDAC2 and its better-studied counterpart VDAC1.
Hypermethylation of the MLH1 Promoter With Concomitant Absence of Transcript and Protein Occurs in Small Patches of Crypt Cells in Unaffected Mucosa From Sporadic Colorectal Carcinoma

Hypermethylation of the MLH1 promoter is present in most sporadic colorectal cancers and leads to the abrogation of MLH1 transcription. The significance of the hypermethylation of the promoter that can be detected in rare foci of cells in the normal colonic epithelium adjacent to the carcinoma is unclear. The purpose of this study was to determine the distribution of hypermethylation of the MLH1 promoter DNA with MLH1 RNA expression by RT in situ PCR and MLH1 protein expression by immunohistochemistry in normal colonic tissues. Hypermethylation of the MLH1 promoter DNA was not evident in sections of normal colon from 10 people with no history of colon cancer. MLH1 RNA and protein were detected diffusely throughout the colonic epithelium in these 10 controls. In comparison, hypermethylation of either of 2 regions of the promoter was evident in the normal mucosa from cases adjacent to adenocarcinoma of the colon. In situ analysis of the DNA methylation showed that there were rare foci that involved small groups of cells, typically toward the middle and surface area of a given crypt. In these areas, small foci of colonic epithelial cells, typically in groups of 5 to 10, were found to lack MLH1 RNA and protein in adjacent serial sections, consistent with silencing of the gene by hypermethylation that may play a role in the origin of these neoplasms. It is concluded that the rare foci of hypermethylation of the MLH1 promoter in normal colon epithelium from people with colorectal cancer is associated with silencing of the gene that may play a role in the early evolution of these neoplasms. A combination of methylation-specific in situ PCR with in situ RNA and protein analysis can assist in documenting rare foci of promoter hypermethylation-induced gene silencing.
A cohort study of fat intake and risk of breast cancer.

Between 1982 and 1987, 519 newly incident, histologically confirmed cases of breast cancer were identified in a cohort of 56,837 women enrolled in the Canadian National Breast Screening Study. These women had completed a dietary questionnaire before the occurrence of their breast cancer, and this has been used to estimate their intake of dietary fat and several other nutrients. There is evidence of a positive association between breast cancer and total fat intake, with a relative risk of 1.35 (95% confidence interval, 1.00-1.82) per 77 g per day, and some evidence of a dose-response relationship (P = .052).
Don't get the message: the effect of a warning text before visiting a proanorexia website.

OBJECTIVE This study examined the effect of the placement of a warning text before visiting proanorexia websites on actual access of these websites. METHOD A separate webpage with a warning text aiming at first-time visitors was placed before each proanorexia website hosted by a Dutch Internet provider. During the research period of 1 year, the numbers of hits at the warning webpage were registered together with the numbers of hits at the underlying proanorexia website. RESULTS Of the total number of hits registered at the warning webpage, about two-third of the visitors were registered at the underlying proanorexia website. This indicates that about one-third of the visitors did not continue their visit to a proanorexia website after being exposed to the warning text. DISCUSSION Placement of a warning text before proanorexia websites appears a promising strategy in holding back potential visitors.
Three Small Nucleolar RNAs Identified from the Spliced Leader-Associated RNA Locus in Kinetoplastid Protozoans

ABSTRACT First characterized in Trypanosoma brucei, the spliced leader-associated (SLA) RNA gene locus has now been isolated from the kinetoplastids Leishmania tarentolae and Trypanosoma cruzi. In addition to the T. brucei SLA RNA, bothL. tarentolae and T. cruzi SLA RNA repeat units also yield RNAs of 75 or 76 nucleotides (nt), 92 or 94 nt, and ∼450 or ∼350 nt, respectively, each with significant sequence identity to transcripts previously described from the T. brucei SLA RNA locus. Cell fractionation studies localize the three additional RNAs to the nucleolus; the presence of box C/D-like elements in two of the transcripts suggests that they are members of a class of small nucleolar RNAs (snoRNAs) that guide modification and cleavage of rRNAs. Candidate rRNA-snoRNA interactions can be found for one domain in each of the C/D element-containing RNAs. The putative target site for the 75/76-nt RNA is a highly conserved portion of the small subunit rRNA that contains 2′-O-ribose methylation at a conserved position (Gm1830) in L. tarentolae and in vertebrates. The 92/94-nt RNA has the potential to form base pairs near a conserved methylation site in the large subunit rRNA, which corresponds to position Gm4141 of small rRNA 2 in T. brucei. These data suggest that trypanosomatids do not obey the general 5-bp rule for snoRNA-mediated methylation.
Solid dispersions, Part II: new strategies in manufacturing methods for dissolution rate enhancement of poorly water-soluble drugs

Introduction: The absorption of poorly water-soluble drugs, when presented in the crystalline state to the gastrointestinal tract, is typically dissolution rate-limited, and according to BCS these drugs belong mainly to class II. Both dissolution kinetics and solubility are particle size dependent. Nowadays, various techniques are available to the pharmaceutical industry for dissolution rate enhancement of such drugs. Among such techniques, nanosuspensions and drug formulation in solid dispersions are those with the highest interest. Areas covered: This review discusses strategies undertaken over the last 10 years, which have been applied for the dissolution enhancement of poorly water-soluble drugs; such processes include melt mixing, electrospinning, microwave irradiation and the use of inorganic nanoparticles. Expert opinion: Many problems in this field still need to be solved, mainly the use of toxic solvents, and for this reason the use of innovative new procedures and materials will increase over the coming years. Melt mixing remains extremely promising for the preparation of SDs and will probably become the most used method in the future for the preparation of solid drug dispersions.
Signaling Mechanisms Regulating Self-Renewal and Differentiation of Pluripotent Embryonic Stem Cells

An ability to propagate pluripotent embryonic cells in culture is the foundation both for defined germline modification in experimental rodents and for future possibilities for broad-based cellular transplantation therapies in humans. Yet, the molecular basis of the self-renewing pluripotent phenotype remains ill-defined. The relationship between factors that influence embryonic stem cell propagation in vitro and mechanisms of stem cell regulation operative in the embryo is also uncertain. In this article we discuss the role of intracellular signalling pathways in the maintenance of pluripotency and induction of differentiation in embryonic stem cell cultures and the mammalian embryo.
A power sharing scheme for series connected offshore wind turbines in a medium voltage DC collection grid

This work introduces a new method for connecting offshore wind turbine generators (WTGs) in series when interfaced to a medium voltage DC (MVDC) collection grid. Limiting the series stacking to pairs of WTGs and introducing a power sharing converter (PSC) stage between them allows series connected WTGs to operate at independent power levels in a voltage sourced collection grid. This allows for reduced collection grid losses compared to previously proposed series connected current sourced approaches when operating below nominal power. Simulation results demonstrate system operation during a 1:2 power unbalance between series connected WTGs. A 100 W, 100 Vdc three-phase lab-scale prototype input rectifer stage demonstrates proper WTG current shaping with >0.97 displacement power factor magnitude, as well as balanced DC link voltages.