Miracle-dz/UniFAR-FTUs huggingface dataset:
Isocitrate dehydrogenase mutations in chondrosarcoma: the crossroads between cellular metabolism and oncogenesis

Purpose of review This article reviews the most recent developments and implications in regard to isocitrate dehydrogenase mutations in chondrosarcoma, a disease in which currently available systemic therapies have proven inefficacious, with an emphasis on how disruption in normal cellular metabolism plays a role in oncogenesis. Recent findings The development of acquired isocitrate dehydrogenase-1/isocitrate dehydrogenase-2 mutations has been described in multiple tumors and more recently in chondrosarcomas. The impact of these mutations has been the focus of multiple research efforts during the last years, allowing us to better understand the impact of the mutation, including its interaction with other proteins, changes in expression of genes involved in tumor genesis, the oncogenic potential of 2-hydroxyglutarate, the impact on cellular proliferation and differentiation, and the influence on the epigenetic state of cells owing to changes in DNA and histone methylation patterns. New compounds targeting the mutation have been developed. Summary This mutation is the first of its kind described in chondrosarcoma, serving as an identifying marker of chondroid differentiation, and becoming the first molecular target with potential anticancer effect, translating into the development of therapies targeting these mutations currently being tested further in preclinical models and clinical trials.
Tacrolimus Inhibits the Revascularization of Isolated Pancreatic Islets

Aims Immunosuppressive drugs could be crucial factors for a poor outcome after islet allotransplantation. Unlike rapamycin, the effects of tacrolimus, the current standard immunosuppressant used in islet transplantation, on graft revascularization remain unclear. We examined the effects of tacrolimus on islet revascularization using a highly sensitive imaging system, and analyzed the gene expression in transplanted islets by introducing laser microdissection techniques. Methods Islets isolated from C57BL/6-Tg (CAG-EGFP) mice were transplanted into the nonmetallic dorsal skinfold chamber on the recipients. Balb/c athymic mice were used as recipients and were divided into two groups: including a control group (n = 9) and tacrolimus-treated group (n = 7). The changes in the newly-formed vessels surrounding the islet grafts were imaged and semi-quantified using multi-photon laser-scanning microscopy and a Volocity system. Gene expression in transplanted islets was analyzed by the BioMark dynamic system. Results The revascularization process was completed within 14 days after pancreatic islet transplantation at subcutaneous sites. The newly-formed vascular volume surrounding the transplanted islets in the tacrolimus-treated group was significantly less than that in the control group (p<0.05). Although the expression of Vegfa (p<0.05) and Ccnd1 (p<0.05) was significantly upregulated in the tacrolimus-treated group compared with that of the control group, no differences were observed between the groups in terms of other types of gene expression. Conclusions The present study demonstrates that tacrolimus inhibits the revascularization of isolated pancreatic islets without affecting the characteristics of the transplanted grafts. Further refinements of this immunosuppressive regimen, especially regarding the revascularization of islet grafts, could improve the outcome of islet allotransplantation.
Asynchronous and Reliable Multimedia Multicast with Heterogeneous QoS Constraints

We present an asynchronous and reliable multicast framework for a scalable multimedia system. An unequal error protection (UEP) transmission scheme employing a layered packetization structure and rateless codes is proposed. With this scheme, asynchronous data reception and guaranteed quality-of-service (QoS) can be achieved at the same time. Furthermore, a novel allocation algorithm is developed within the layered multicast framework, which can minimize the system cost in terms of the number of transmitted packets. Simulation results show that the proposed rateless-codes-based transmission scheme works well for asynchronous multicasting to heterogeneous receivers, and can be applied to a wide range of multimedia applications.
Toward a multiscale modeling framework for understanding serotonergic function

Despite its importance in regulating emotion and mental wellbeing, the complex structure and function of the serotonergic system present formidable challenges toward understanding its mechanisms. In this paper, we review studies investigating the interactions between serotonergic and related brain systems and their behavior at multiple scales, with a focus on biologically-based computational modeling. We first discuss serotonergic intracellular signaling and neuronal excitability, followed by neuronal circuit and systems levels. At each level of organization, we will discuss the experimental work accompanied by related computational modeling work. We then suggest that a multiscale modeling approach that integrates the various levels of neurobiological organization could potentially transform the way we understand the complex functions associated with serotonin.
Understanding the Molecular Basis of Histologic Grade

Histologic grading in breast cancer is based on the evaluation of 3 morphologic features (tubule formation, nuclear pleomorphism and mitotic count), is essentially describing proliferation and differentiation in breast cancer, and is considered an important prognostic factor for this disease. It has been suggested that histologic grade 1 and 3 breast tumors are 2 different diseases that may have distinct molecular origins, pathogenesis and natural history. Different single markers like Ki-67, thymidine labeling index and S phase fraction/flow cytometry have been studied as markers of proliferation, but none of them, with the possible exception of Ki-67, is currently employed routinely in clinical practice. The advent of the powerful microarray technology has enabled scientists to comprehensively study proliferation in breast cancer on a genome-wide scale. A gene expression grade index (GGI) was developed that challenges the existence and clinical relevance of an intermediate grade 2 classification. The GGI could reclassify patients with histologic grade 2 tumors into 2 groups with high versus low risks of recurrence. GGI has also been used to define 2 clinically relevant subgroups in estrogen receptor-positive breast carcinomas. Finally, in the largest meta-analysis of publicly available gene expression and clinical data, 4 stable molecular subgroups of breast cancer have been identified, namely ER–/HER–, HER2+ and ER+/HER2–, which was divided into 2 subgroups (ER+/low proliferation and ER+/high proliferation). In this same meta-analysis, proliferation was shown to be the common driving force responsible for the performance of various breast cancer prognostic signatures.
Parasite Selection for Immunogenetic Optimality

In vertebrates, genes of the major histocompatibility complex (MHC), with their pronounced polymorphism, potentially represent outstanding examples for the selective advantages of genetic diversity (1). Theoretical models predicted that, within an individual, MHC alleles can be subjected to two opposing selective forces, resulting in an optimal number of genes at intermediate individual MHC diversity (2, 3). Diversifying selection increases heterozygosity and enables wider recognition of pathogens (4). This process is opposed by the need to delete T cells that react with self peptide–MHC combinations (5) from the repertoire, which has been proposed as a possible mechanism constraining expansion of MHC genes. Because too high MHC diversity might delimit T cell diversity, it might also impose limitations on the efficiency of pathogen recognition. However, empirical evidence demonstrating fitness benefits in terms of parasite resistance caused by this type of optimal MHC diversity has been lacking. Therefore, we tested whether three-spined sticklebacks (Gasterosteus aculeatus L.) carrying an intermediate level of individual MHC diversity also displayed the strongest level of resistance against parasite infection. Sticklebacks are particularly suited to test MHC optimality, because MHC class II genotypes can differ markedly in the number of MHC class IIB alleles (6). We caught fish from an outbred population and used these to breed six sibships of immunologically naive fish (i.e., they had no previous contact to parasites). Immunogenetic diversity ranged from three to nine MHC class IIB alleles found in reverse-transcribed messenger RNA (mRNA) [see (6) for details on genotyping]. The MHC genotypes within these sibships segregated above and below the hypothesized optimal number of ∼5 MHC class IIB alleles, which had previously been estimated in an epidemiological field survey (7). In individual infection treatments, fish from all sibships were simultaneously exposed to three of the most abundant parasite species identified in the field (Fig. 1A) (8). After two rounds of infection, separated by an interval of 8 weeks, we found a significant minimal mean infection rate at an intermediate number of individual MHC class IIB variants [i.e., 5.82 expressed alleles (Fig. 1B)]. This result was also confirmed when sibships were considered separately [i.e., 4.96 alleles (Fig. 1C)] (9). The strong pattern only appeared when infection with all three parasites was accounted for simultaneously. This may not be surprising, because single alleles are expected to correlate with single diseases and multiple alleles can contribute to resistance against several infectious agents (2).
Isolation and Characterization of Simian Virus 40 Ribonucleic Acid

Deoxyribonucleic acid-ribonucleic acid (RNA) hybridization in formamide was used to isolate simian virus 40-specific RNA. Early in the lytic cycle, a 19S viral RNA species was observed. Late in the lytic cycle, 16S and 19S viral species were found. The 16S and 19S species of viral RNA were localized in the cytoplasm. High-molecular-weight heterogeneous RNA, containing viral sequences, was isolated from the nuclear fraction of infected cells late in the lytic cycle. This RNA may contain non-viral sequences linked to viral sequences. The formamide hybridization technique can be used to isolate intact late lytic viral RNA which is at least 99% pure.
Occupational Therapists’ Beliefs and Involvement with Secondary Transition Planning

ABSTRACT The purpose of the study was to investigate the involvement and beliefs toward possible involvement of occupational therapy in one geographical area of the United States in regard to secondary transition planning for students with disabilities. Secondary transition planning is mandated by federal legislature and occurs while the student is attending high school. This planning process is to assist high school students with preparation for successful living after graduation. The types and frequency of occupational therapy services being included in the planning were explored along with the specific factors that might facilitate and/or hinder occupational therapy involvement. The results revealed generally low involvement of occupational therapists in the planning for the students as they plan and prepare for adult roles. In contrast, majority of the respondents indicated positive beliefs in regard to whether occupational therapy could play a role in secondary transition planning. Factors that encourage occupational therapy involvement in the planning process and factors that hinder involvement were reported. A lack of knowledge of possible contributions that occupational therapy can provide to enhance the planning for the student appeared to be a major factor for both the therapists and school personnel. In conclusion, the results of the study indicate minimal involvement of the school-based therapists but positive beliefs toward their possible involvement. These results clearly indicate the need for greater communication between disciplines and increased understanding of each discipline's role in providing secondary transition services.
Factors Influencing Booster Seat Use in a Multiethnic Community: Lessons for Program Implementation

Based on the local incidence and severity of motor vehicle occupant injuries, the authors' community and hospital injury prevention partnership identified child passenger safety for 4-to-8-year-old children as a priority. They designed a booster seat promotion campaign using an integrated social cognition model of health behavior. A series of focus groups were held with low-income African American, Somali, and Vietnamese parents to understand determinants of booster seat use in these communities. Deficits in understanding about the purpose of booster seats were seen in all groups, and concerns about cost and self-efficacy varied in important ways. Although legislation is an important tool in motivating child passenger restraint, most families saw safety as the prime reason to use booster seats with their children. These results illustrate the use of qualitative data to adapt a theory-based intervention to the needs of specific communities.
Threshold spectra for random graphs

Let G = G(n, p) be the random graph with n vertices and edge probability p and ƒ(n, p, A) be the probability that G has A, where A is a first order property of graphs. The evolution of the random graph is discussed in terms of a spectrum of p = p(n) where ƒ(n, p, A) changes. A partial characterization of possible spectra is given. When p = n-a, a irrational, and A is any first order statement, it is shown that lim ƒ(n, p, A) = 0 or 1.
World Health Organization Grade II Oligodendroglioma Occurring after Successful Treatment for Childhood Acute Lymphoblastic Leukemia

When treating childhood acute lymphoblastic leukemia (ALL), secondary neoplasms are a significant long term problem. Radiation is generally accepted to be a major cause of the development of secondary neoplasms. Following treatment for ALL, a variety of secondary tumors, including brain tumors, hematologic malignancies, sarcomas, thyroid cancers, and skin cancers have been reported. However, oligodendroglioma as a secondary neoplasm is extremely rare. Herein we present a case of secondary oligodendroglioma occurring 13 years after the end of ALL treatment.
MCE-based training of subspace distribution clustering HMM

For resource-limited platforms, the subspace distribution clustering hidden Markov model (SDCHMM) is better than the continuous density hidden Markov model (CDHMM) for its smaller storage and lower computations while maintaining a decent recognition performance. But the normal SDCHMM obtaining method does not ensure optimality in classifier design. In order to obtain an optimal classifier, a new SDCHMM training algorithm that adjusts the parameters of SDCHMM according to the minimum classification error (MCE) criterion is proposed in this paper. Our experimental results on TiDigits and RM tasks show the MCE-based SDCHMM training algorithm provides 15-80% word error rate reduction (WERR) compared with the normal SDCHMM that is converted from CDHMM.
Comparison of sialylated N‐glycopeptide levels in serum of pancreatic cancer patients, acute pancreatitis patients, and healthy controls

Serum protein glycosylation is known to be affected by pathological conditions, including cancer and inflammatory diseases. Pancreatic cancer patients would benefit from early diagnosis, as the disease is often detected in an advanced stage and has poor prognosis. Searching for changes in serum protein site‐specific glycosylation could reveal novel glycoprotein biomarkers. We used Sambucus nigra lectin affinity chromatography to enrich α‐2,6 sialylated tryptic N‐glycopeptides from albumin‐depleted sera of pancreatic cancer patients, acute pancreatitis patients, and healthy individuals, and compared their relative abundance using ultra performance LC‐MS. Relative quantitation was done using the spectrum processing software MZmine. Identification was performed on the web‐based tool GlycopeptideID, developed for in silico analysis of intact N‐glycopeptides. Seventeen high‐abundance serum proteins, mainly acute‐phase proteins, and immunoglobulins, with total 27 N‐glycosylation sites, and 62 glycoforms, were identified. Pancreatitis patient sera contained 38, and pancreatic cancer patients sera contained 13 glycoform changes with statistical significance (p < 0.05). In pancreatitis, up to tenfold changes were found in some glycoforms, and in pancreatic cancer, threefold. Analysis showed that the changes often concerned one or two, but not all, N‐glycosylation sites in a specific glycoprotein. In conclusion, the analysis shows that pancreatic cancer, and acute pancreatitis are associated with changes in concentrations of intact sialylated N‐glycopeptides derived from acute‐phase proteins, and immunoglobulins, and that changes are site specific.
BASIC PENTACYSTEINE Proteins Repress ABSCISIC ACID INSENSITIVE4 Expression via Direct Recruitment of the Polycomb-Repressive Complex 2 in Arabidopsis Root Development

Plant transcription factors generally act in complex regulatory networks that function at multiple levels to govern plant developmental programs. Dissection of the interconnections among different classes of transcription factors can elucidate these regulatory networks and thus improve our understanding of plant development. Here, we investigated the molecular and functional relationships of the transcription factors ABSCISIC ACID INSENSITIVE 4 (ABI4) and members of the BASIC PENTACYSTEINE (BPC) family in lateral root (LR) development of Arabidopsis thaliana. Genetic analysis showed that BPCs promote LR development by repressing ABI4 expression. Molecular analysis showed that BPCs bind to the ABI4 promoter and repress ABI4 transcription in roots. BPCs directly recruit the Polycomb Repressive Complex 2 (PRC2) to the ABI4 locus and epigenetically repress ABI4 expression by catalyzing the trimethylation of histone H3 at Lys27. In addition, BPCs and ABI4 co-ordinate their activities to fine-tune the levels of PIN-FORMED1, a component of the auxin signaling pathway, and thus modulate LR formation. These results establish a functional relationship between two universal and multiple-role transcription factors, and provide insight into the mechanisms of the transcriptional regulatory networks that affect Arabidopsis organogenesis.
Simulation of Acupuncture Skin Deformation Using Mathematical-Physical Model

In order to simulate the whole process of acupuncture treatment, we put forward a methodology based on improved mass-spring model to simulate the skin rotation by using method of Mathematical Physics. Firstly, we simulate the subsidence of skin when the acupuncture needle exerts external force on the skin by using the improved mass-spring model. And then, we adopt Verlet integration to update mass points' position and draw dynamic deformation of the skin when the skin mesh re-gains balance. Finally, we implement the simulation experiments in the OpenGL environment. Experimental results show that the methodology we present can simulate the skin rotation deforma-tion realistically and well meet the requirement of real-time.
Shiftwork and Metabolic Dysfunction

Many of the health problems that are more prevalent among shiftworkers are thought to be linked to their heightened susceptibility to metabolic syndrome, i.e., the association of even moderate degrees of visceral obesity, dyslipidemia, abnormal blood pressure, and serum glucose levels in the same individual. Although previous studies have identified associations between shiftwork and metabolic syndrome, there is relatively little evidence to date of how the risk of developing it varies as a function of exposure to shiftwork. The current study seeks to confirm earlier findings of an association between shiftwork exposure and metabolic dysfunction, and to examine the impact of exposure duration, while adjusting for a number of covariates in the analyses. The analyses were based on data from VISAT, a study involving the measurement of physiological, behavioral, and subjective outcomes from 1757 participants, 989 being current or former shiftworkers. The sample comprised employed and retired wage earners, male and female, who were 32, 42, 52, and 62 yrs old. The first analysis sought to confirm previous findings of an association between exposure to shiftwork and the risk of developing metabolic syndrome. It indicated that participants who were or who had previously been shiftworkers (i.e., working schedules that involved rotating shifts; not being able to go to bed before midnight; having to get up before 05:00 h; or being prevented from sleeping during the night) were more likely to exhibit symptoms of metabolic syndrome, after adjusting for age, sex, socioeconomic status, smoking, alcohol intake, perceived stress, and sleep difficulty (odds ratio [OR] 1.78; 95% confidence interval [CI] 1.03–3.08). The results suggest the association between shiftwork and metabolic syndrome cannot be fully accounted for by either higher levels of strain or increased sleep difficulty among shiftworkers, although it remains a possibility that either one or both of these factors may have played a contributing role. The second analysis addressed the issue of duration of exposure to shiftwork. Participants with >10 yrs' experience of working rotating shifts were more likely to exhibit symptoms of metabolic syndrome than participants without exposure to shiftwork, i.e., dayworkers, even after adjusting for age and sex (OR 1.96; 95% CI 1.03–3.75). Thus, the current study confirms the association between shiftwork exposure and metabolic syndrome. It also provides new information regarding the time course of the development of the illness as function of exposure duration, although this was only examined in relation to rotating shiftwork. It is concluded that those responsible for monitoring workers' health should pay particular attention to indices of metabolic dysfunction in workers who have been exposed to shiftwork for >10 yrs. (Author correspondence: p.t.tucker@swansea.ac.uk)
The Amorphous Fixation Measure Revisited : with Applications to Autism

The analysis of eye-tracking data hinges on the ability of automated algorithms to separate rapid saccadic eye movements from stable eye fixations. However, though it has long been known that changing the parameters of fixationidentification algorithms can lead to very different qualitative impressions, less is known about how algorithmic parameters interact with quantitative eye-tracking measures. In this study we show that by manipulating aspects of fixation identification, we can completely reverse the patterns of observed results for mean fixation duration, a measure traditionally associated with cognitive load. However, by linearly mapping mean fixation duration over its parameter space, we obtain a new formulation which addresses many of the deficits of the standard analysis. We use our methods to analyze the gaze patterns of toddlers with autism spectrum disorder and control populations and discuss the observed differences in terms of the physical and cognitive ramifications of our methodology.
Kirchhoff modeling for attenuative anisotropic media using Gaussian beams

ABSTRACTSeismic wave propagation in attenuative media can be efficiently modeled with ray-based methods. We present a methodology to generate reflection data from attenuative anisotropic media using the Kirchhoff scattering integral and summation of Gaussian beams. The Green’s functions are computed in the reference elastic model by Gaussian-beam summation, and the influence of attenuation is incorporated as a perturbation along the central ray. The reflected P-wave is obtained by substituting the approximate Green’s functions into the Kirchhoff scattering integral. Numerical examples for a transversely isotropic medium above a horizontal reflector and for a structurally complex acoustic model with a salt body confirm the accuracy of the method.