Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct modes of centromere protein dynamics during cell cycle progression in Drosophila S2R+ cells

Summary Centromeres are specified epigenetically in animal cells. Therefore, faithful chromosome inheritance requires accurate maintenance of epigenetic centromere marks during progression through the cell cycle. Clarification of the mechanisms that control centromere protein behavior during the cell cycle should profit from the relatively simple protein composition of Drosophila centromeres. Thus we have analyzed the dynamics of the three key players Cid/Cenp-A, Cenp-C and Cal1 in S2R+ cells using quantitative microscopy and fluorescence recovery after photobleaching, in combination with novel fluorescent cell cycle markers. As revealed by the observed protein abundances and mobilities, centromeres proceed through at least five distinct states during the cell cycle, distinguished in part by unexpected Cid behavior. In addition to the predominant Cid loading onto centromeres during G1, a considerable but transient increase was detected during early mitosis. A low level of Cid loading was detected in late S and G2, starting at the reported time of centromere DNA replication. Our results reveal the complexities of Drosophila centromere protein dynamics and its intricate coordination with cell cycle progression.
A simplified assay for porphyrins in whole blood.

Recent investigations concerning the significance of porphyrins in erythrocytes indicate a need for a rapid quantitative assay, easily adaptable to routine clinical use. To fill this need, we have developed a simplified procedure for the measurement of porphyrins (essentially protoporphyrin) in whole blood. Blood is stirred with acetone—ethyl acetate and the porphyrins are extracted with formic acid—ether. The porphyrins are then extracted into HCl and measured spectrophotometrically at three wavelengths, a procedure that allows a corrected absorbance to be calculated, to minimize error caused by interfering substances. The assay requires little apparatus, is simple and dependable, and the results correlate well with those obtained by use of a more complex conventional procedure.
Influence of Pseudophakic Lens Capsule Opacification on Spectral Domain and Time Domain Optical Coherence Tomography Image Quality

Abstract Purpose: To evaluate the influence of posterior capsule opacification (PCO) on optical coherence tomography (OCT) acquisition of macular retinal thickness (RT) and volume using time domain OCT (TD-OCT) and spectral domain OCT (SD-OCT). Materials and methods: We studied 37 eyes of 31 patients with PCO. Each patient underwent an evaluation with TD-OCT and with SD-OCT before and after Nd:YAG capsulotomy. We recorded RT and retinal volume in the macular area using only good quality images. Results: Best corrected visual acuity improved in all eyes after Nd:YAG capsulotomy, with the degree of improvement ranging from 0.3 ± 0.7 to 0.1 ±0.7 (p = 0.01). Before the treatment, only 27% of the examinations were valuable with TD-OCT, while using SD-OCT, it was possible to obtain an examination of suitable quality both before and after the Yag laser capsulotomy in 100% of the eyes. We did not observe significant differences between mean preoperative and postoperative RT and total macular volume measurements, neither with TD-OCT nor with SD-OCT. RT and total macular volume values obtained using TD-OCT were always lower than those obtained from the SD-OCT, both before and after capsulotomy. Conclusions: Our study confirmed that with old generation TD-OCT, PCO has a strong negative influence on the quality of OCT acquisition, and examination is reliable only when it is possible to acquire good quality images. With new generation SD-OCT, tomographic acquisitions are always reliable and are not influenced by the presence of PCO.
The multiple sclerosis self-management scale: clinicometric testing.

BACKGROUND The Multiple Sclerosis Self-Management Scale (MSSM) is currently the only measure that was developed specifically to address self-management among individuals with multiple sclerosis (MS). While good internal consistency (α = 0.85) and construct validity have been demonstrated, other psychometric properties have not been established. This study was undertaken to evaluate the criterion validity, test-retest reliability, and face validity of the MSSM. METHODS Thirty-one individuals with MS who met the inclusion criteria were recruited to complete a series of questionnaires at two time points. At Time 1, participants completed the MSSM and two generic self-management tools-the Partners in Health (PIH-12) and the Health Education Impact Questionnaire (heiQ)-as well as a short questionnaire to capture participants' opinions about the MSSM. At Time 2, approximately 2 weeks after Time 1, participants completed the MSSM again. RESULTS The available MSSM factors showed moderate to high correlations with both PIH-12 and heiQ and were deemed to have satisfactory test-retest reliability. Face validity pointed to areas of the MSSM that need to be revised in future work. As indicated by the participants, some dimensions of MS self-management are missing in the MSSM and some items such as medication are redundant. CONCLUSIONS This study provides evidence for the reliability and validity of the MSSM; however, further changes are required for both researchers and clinicians to use the tool meaningfully in practice.
What is IFAP syndrome?

In this issue, Mégarbané et al. [2003] describe two brothers with ‘‘IFAP syndrome’’ (ichthyosis follicularis, alopecia and photophobia). After having studied this interesting paper, I am asking myself whether IFAP syndromecanstillbetakenasonesingleclinicogeneticentity. McLeod [1909] described three cases of ‘‘ichthyosis follicularis’’ associated with baldness. His report fell into oblivion until Zeligman and Fleisher [1959] reported additional cases. Traupe [1989] gave a comprehensive review of IFAP syndrome. A hallmark of this disease is the presence of thorne-like projections of follicular hyperkeratosis, giving the skin a feeling of a ‘‘nutmeg grater’’ [ZeligmanandFleisher, 1959;Eramoetal. , 1985]. In recent years, however, several authors have described atypical patients in whom follicular hyperkeratosis was not a prominent finding. Rather, a generalized lamellar desquamation was present [Boente et al., 2000], or well demarcated psoriasiform lesions involved the gluteal fold, the buttocks or the limbs [Boente et al., 2000, Sato-Matsumura et al., 2000]. In these patients, additional extracutaneous lesions in the form of inguinal hernia or ectrodactyly were present. From a clinical point of view it appears as if we are dealing with two different entities described under the same name. This perspective may be supported by the following argument. In ‘‘classical’’ IFAP syndrome as described by McLeod [1909], only boys show the fullblown syndrome [Keyvani et al., 1998], whereas female carriers may present a linear pattern of involvement reflecting functional X-chromosome mosaicism [König and Happle, 1999]. By contrast, the phenotype characterized by psoriasiform patches can be transmitted from a mother to her daughter who do not show any X-inactivation pattern but, conversely, a rather symmetrical arrangement [Sato-Matsumura et al., 2000]. The cases described by Mégarbané et al. [2003] appear to belong to this ‘‘psoriasiform’’ category. Other reports [Martino et al., 1992; Bibas-Bonet et al., 2001] mention the presence of additional anomalies such as aganglionic megacolon or hypoplasia of corpus callosum, which raises the question whether such cases may represent examples of a contiguous gene syndrome. The issue is becoming even more complicated because Cambiaghi et al. [2002] described ‘‘classical’’ IFAP syndrome in two unrelated girls who were diffusely affected without any sign of functional X-chromosome mosaicism. In these cases, an X-linked ‘‘recessive’’ mode of transmission with lyonization in females can be excluded. Does this mean that there are three different IFAP syndromes? However it may be, the report of Mégarbané et al. [2003] that will give us further food for thought in order to ultimately solve the nosological conundrum of what we presently call ‘‘IFAP syndrome. ’’
Hiroshima: The Origins of Global Memory Culture

We have a sense of living on in our children and their children, an endless biological chain of being. Or in our work, small or large, in our influence upon others; or in something we call spiritual attainment, some sort of religious idea or belief; or in the idea of eternal nature, which all societies symbolize in some way. Or else through the experience of transcendence, the psychic state that Freud called the “oceanic feeling,” one so intense that time and death disappear. Perhaps the most fundamental impact of nuclear weapons on us, without their use (or without their use again), is the break they represent in the great chain of being, the doubt about our still being links in that chain. (1)
Unified nomenclature for the winged helix/forkhead transcription factors.

The winged helix/forkhead class of transcription factors is characterized by a 100-amino-acid, monomeric DNAbinding domain. The structure of the DNA-binding domain of one of the class members, hepatocyte nuclear factor 3 g (HNF3g), in a complex with a DNA target has been solved (Clark et al. 1993). The DNA-binding domain folds into a variant of the helix–turn–helix motif and is made up of three a helices and two characteristic large loops, or “wings. ” Therefore, the DNA-binding motif has been named the winged helix DNA-binding domain. Over the past 9 years since the identification of the first member of this class, the Drosophila melanogaster gene Fork head, >100 members of this gene family have been identified (for review, see Kaufmann and Knöchel 1996) in species ranging from yeast to human. The rapid accumulation of sequences by many different laboratories has led to the use of multiple names and classification systems, making it very difficult to follow the literature and to name newly characterized winged helix/ forkhead transcription factors. This problem was recognized and discussed at the first International Meeting on Forkhead/Winged Helix Proteins, held in La Jolla, California, in November 1998. At that time a proposal was developed to standardize the nomenclature for these proteins. Fox (Forkhead box) was adopted as the unified symbol for all chordate winged helix/forkhead transcription factors. A winged helix/forkhead nomenclature committee was elected to implement this proposal, in consultation with the community at large. This final proposal has been endorsed by >20 scientists as well as the Human and Mouse Gene Nomenclature Committees.
Effect of hormone replacement therapy on the pathological stage of breast cancer: population based, cross sectional study

Hormone replacement therapy is being used increasingly. Although it is known that the risk of developing breast cancer is slightly increased with long term use,1 hormone replacement does not seem to adversely affect mortality from breast cancer.2 Studies have suggested that users of hormone replacement who get breast cancer develop tumours with “favourable” pathological features compared with non-users. One study included women who had been detected at screening and women who had presented with symptoms, with more screen detected women in the study group (users) than in the controls (non-users). 2 Another study compared type of tumour in users and non-users in a screen detected population alone3 and showed that grade 1, node negative tumours were more common in the users. Women with breast cancer who have used hormone replacement, however, may be more likely to have a cancer that was missed at screening; we have shown that women who develop such cancers (interval cancers) within …
A speaker classification framework for non-intrusive user modeling: speech-based personalization of in-car services

The human voice is a very efficient communication medium that we depend on each day to transfer messages. By taking a closer look, it turns out that the speech we produce is never just a message, but always contains additional, more unconsciously perceived cues about the speaker, the so-called paralinguistic information. The field of Speaker Classification, a sub-field of artificial intelligence, computational linguistics, signal processing, and others, is concerned with the extraction of this information from the speech signal. Examples of such speaker characteristics that manifest themselves in the voice are the person’s age, gender, physics, emotion, personality, attention, cognitive load, or even identity. The main goal of this dissertation is to develop a novel Speaker Classification system for automatic age and gender recognition that allows this information be used in applications for various purposes. One particular motivation is drawn from the aim to utilize the nonintrusively obtained knowledge for personalization of functions and services in the automotive context, which is a very active domain for human-machine interaction research. One aspect of this thesis deals with the question of how current Speaker Classification systems can be improved. The methodology consequently follows a principled approach, motivating the investigation through analyses of how the speech apparatus is affected by age and gender, instead of looking only at the decision problem. An extensive study and comparison of several recent and early approaches points out where research is heading, what the most promising leads are, and where the culprits are located. Based on this survey, an approach named Frisc is developed and presented in detail. It combines the promising GMM-SVM supervector pattern recognition system with frame-based cepstral voice features (MFCCs) and applies further optimizations to source, feature, and score domain. To be a suitable choice for time-critical on-line application, the system was further designed to process incoming data and update knowledge in incremental manner and with real-time efficiency. A further focus of this principled approach lies in the way the evaluation of the system is performed. As part of the contribution of this work, a carefully designed parameter space exploration experiment is conducted to discover the impact of each of a large number of different parameters to the overall classification performance. Parameters include MFCC extraction settings, GMM training parameters, SVM kernel function, background model impact, feature and silence filtering ratio, and more. Best practices with respect to data set generation and balancing are particularly emphasized. In spite of the complexity introduced, the procedure ensures that the complete system is always tested using a large number of samples, and only a single parameter is changed between any two experiments. It is believed that the very specific results presented in this thesis are more valuable in the long run than an unstructured or less
4D subharmonic aided pressure estimation for monitoring neoadjuvant chemotherapy response of breast cancer

Neoadjuvant chemotherapy is standard of care for localized breast. The patient response to neoadjuvant chemotherapy correlates with survival and early response assessment is therefore beneficial. The purpose of this study was to determine if 4D subharmonic aided pressure estimation (SHAPE) can predict the response of breast cancer to neoadjuvant chemotherapy based on changes in interstitial fluid pressure and breast tumor vascularity. Seventeen patients scheduled for neoadjuvant therapy of a breast cancer underwent 4 ultrasound exams: prior to therapy, at 10%, 60%, and 100% completion of chemotherapy. Ultrasound exams were performed using a modified Logiq 9 scanner with a 4D10L probe (GE Healthcare, Milwaukee, WI, USA). Modified software enabled the collection of radiofrequency data from 4D pulse inversion subharmonic imaging (transmitting at 5.8 MHz and receiving at 2.9 MHz) before and during a continuous infusion of Definity (Lantheus Medical Imaging, N Billerica, MA, USA) at acoustic settings optimized for SHAPE. The ratios of maximum subharmonic magnitude acquired during infusion relative to unenhanced signals were calculated offline in the tumor and surrounding areas for all 4 exams. The difference between ratios in the tumor and the surrounding area were then compared to the final tumor treatment response. Four patients left the study and 2 patients' data were discarded. Patients' clinical outcomes consisted of 6 responders (tumor volume reduction > 90%) and 5 partial/non responders. The results from 10% completion of therapy showed the subharmonic signal increased more in the tumor than in the surrounding area for responders compared to partial/non responders (3.23 ± 1.41 dB vs. -0.88 ± 1.46 dB; p = 0.001). Moreover, 3 patients whose tumor size initially increased during therapy were correctly predicted by SHAPE to be responders. In conclusion, SHAPE has the potential to predict the neoadjuvant chemotherapy response of breast cancer as early as at 10% completion of the therapy; albeit based on a small sample size.
Micromechanical modeling of the multiphysical behavior of smart materials using the variational asymptotic method

A multiphysics micromechanics model is developed to predict the effective properties as well as the local fields of periodic smart materials responsive to fully coupled electric, magnetic, thermal and mechanical fields. This work is based on the framework of the variational asymptotic method for unit cell homogenization (VAMUCH), a recently developed micromechanics modeling scheme. To treat the general microstructure of smart materials, we implemented this model using the finite element technique. Several examples of smart materials are used to demonstrate the application of the proposed model for prediction of multiphysical behavior.
Synergistic Activation of Interleukin-12 p35 Gene Transcription by Interferon Regulatory Factor-1 and Interferon Consensus Sequence-binding Protein*

Interferon regulatory factor-1 (IRF-1) and interferon consensus sequence-binding protein (ICSBP or IRF-8) are two members of the IRF family of transcription factors that play critical roles in interferon signaling in a wide range of host responses to infection and malignancy. Interleukin-12 (IL-12) is a key factor in the induction of innate resistance and generation of T helper type 1 cells and cytotoxic T lymphocytes. In this work, we find that ICSBP-deficient macrophages are highly defective in the production of IL-12. The defect is also observed at the level of IL-12 p40 and p35 mRNA expression. Transcriptional analyses revealed that ICSBP is a potent activator of the IL-12 p35 gene. It acts through a site localized to –226 to –219, named ICSBP-response element (ICSBP-RE), in the human IL-12 p35 promoter through physical association with IRF-1 both in vitro and in vivo. Co-expression of ICSBP and IRF-1 synergistically stimulates the IL-12 p35 promoter activity. Mutations at the ICSBP-RE results in the loss of protein binding as well as transcriptional activation by ICSBP alone or together with IRF-1. This study provides novel mechanistic information on how signals initiated during innate and adaptive immune responses synergize to yield greater IL-12 production and sustained cellular immunity.
Exploring a post-traumatic stress disorder paradigm in Flinders sensitive line rats to model treatment-resistant depression II: response to antidepressant augmentation strategies

Objective Post-traumatic stress disorder (PTSD) displays high co-morbidity with major depression and treatment-resistant depression (TRD). Earlier work demonstrated exaggerated depressive-like symptoms in a gene×environment model of TRD and an abrogated response to imipramine. We extended the investigation by studying the behavioural and monoaminergic response to multiple antidepressants, viz. venlafaxine and ketamine with/without imipramine. Methods Male Flinders sensitive line (FSL) rats, a genetic model of depression, were exposed to a time-dependent sensitisation (TDS) model of PTSD and compared with stress naive controls. 7 days after the TDS procedures, immobility and coping (swimming and climbing), behaviours in the forced swim test (FST) as well as hippocampal and cortical 5-hydroxyindoleacetic acid (5HIAA) and noradrenaline (NA) levels were analysed. Response to imipramine, venlafaxine and ketamine treatment (all 10 mg/kg×7 days) alone and in combination were subsequently studied. Results TDS exacerbated depressive-like behaviour of FSL rats in the FST. Imipramine, venlafaxine and ketamine were ineffective as monotherapy in TDS-exposed FSL rats. However, combining imipramine with either venlafaxine or ketamine resulted in significant anti-immobility effects and enhanced coping behaviours. Only ketamine+imipramine (frontal-cortical 5HIAA and NA), ketamine alone (frontal-cortical and hippocampal NA) and venlafaxine+imipramine (frontal-cortical NA) altered monoamine responses versus untreated TDS-exposed FSL rats. Conclusion Exposure of FSL rats to TDS inhibits antidepressant response at behavioural and neurochemical levels. Congruent with TRD, imipramine plus venlafaxine or ketamine overcame treatment resistance in these animals. These data further support the hypothesis that exposure of FSL rats to a PTSD-like paradigm produces a valid animal model of TRD and warrants further investigation.
A multi-station proprioceptive exercise program in patients with ankle instability.

PURPOSE The aim of the present study was to investigate the effects of a 6-wk multi-station proprioceptive exercise program that is easy to integrate in normal training programs. METHODS Patients with chronic ankle instability were used, and results of three testing procedures before and afterward were compared: joint position sense, postural sway, and muscle reaction times to sudden inversion events on a tilting platform. A total of 30 subjects with 48 unstable feet were evaluated (exercise group: N = 31; control group: N = 17). RESULTS In the exercise group, the results showed a significant improvement in joint position sense and postural sway as well as significant changes in muscle reaction times. CONCLUSION Based on the present results, a multi-station proprioceptive exercise program can be recommended for prevention and rehabilitation of recurrent ankle inversion injuries.
Spin dynamics of nearly localized electrons.

Etude RPE de Si:P metallique au voisinage de la transition metal-isolant, entre 100 K et 30 mK. Analyse des variations de la susceptibilite de spin paramagnetique et de la largeur de raie RPE en fonction de la temperature; relations avec l'amplification des fluctuations de spin et le ralentissement de la diffusion de spin au voisinage de la transition