Miracle-dz/UniFAR-FTUs huggingface dataset:
Sequence diversity and haplotype structure in the human ABCB1 (MDR1, multidrug resistance transporter) gene.

OBJECTIVES There is increasing evidence that polymorphism of the ABCB1 (MDR1) gene contributes to interindividual variability in bioavailability and tissue distribution of P-glycoprotein substrates. The aim of the present study was to (1) identify and describe novel variants in the ABCB1 gene, (2) understand the extent of variation in ABCB1 at the population level, (3) analyze how variation in ABCB1 is structured in haplotypes, and (4) functionally characterize the effect of the most common amino acid change in P-glycoprotein. METHODS AND RESULTS Forty-eight variant sites, including 30 novel variants and 13 coding for amino acid changes, were identified in a collection of 247 ethnically diverse DNA samples. These variants comprised 64 statistically inferred haplotypes, 33 of which accounted for 92% of chromosomes analyzed. The two most common haplotypes, ABCB1*1 and ABCB1*13, differed at six sites (three intronic, two synonymous, and one non-synonymous) and were present in 36% of all chromosomes. Significant population substructure was detected at both the nucleotide and haplotype level. Linkage disequilibrium was significant across the entire ABCB1 gene, especially between the variant sites found in ABCB1*13, and recombination was inferred. The Ala893Ser change found in the common ABCB1*13 haplotype did not affect P-glycoprotein function. CONCLUSION This study represents a comprehensive analysis of ABCB1 nucleotide diversity and haplotype structure in different populations and illustrates the importance of haplotype considerations in characterizing the functional consequences of ABCB1 polymorphisms.
PSCAD/EMTDC-based simulations for fault analysis and fault identification in 380V ring DC systems

With an increasing number of DC driven components in power networks, the introduction of 380V DC distribution grids appears to be a valuable option. Besides all positive aspects of DC systems (e.g. high efficiency, the absence of reactive power, etc.), system protection represents the major challenge which needs to be clarified for DC systems. Advanced AC protection equipment's and methodologies are not sufficient in DC environments. In the current research, fault analysis of 380V DC-Microgrid was performed using PSCAD software. Fault behavior was tested with the application of faults at different locations. All components were connected to the grid through two smart switchgears' which incorporated current and voltage sensors. The recorded data were analyzed and current derivatives were identified as the most crucial parameters for fault detection. Based on that, a credit point concept was set up to filter derivative oscillations in regular operating conditions and to standardize fault indicating values.
The tectorial membrane: Anatomical, biomechanical, and histological analysis

There is minimal information in the literature regarding the tectorial membrane. Further, information in the literature regarding the anatomy and function of this structure is often contradictory. We performed the current study to elucidate further this structure's detailed anatomy, function, and histology. Thirteen adult cadavers underwent dissection of their tectorial membranes and detailed observations and measurements were made of them. Ranges of motion of the craniocervical junction were performed before and after transection of this structure. Histological analysis was performed on all membranes. The tectorial membrane was found to attach much more superiorly than previously described and was found to be firmly adherent to the cranial base and body of the axis but not to the posterior aspect of the odontoid process. The mean thickness of this membrane was found to be 1 mm. Flexion of the head made the tectorial membrane fully taut at 15° and extension made it fully taut at 20°; however, there was a buckling effect (redundant tectorial membrane) noted at the level of the odontoid process in extension. With the alar and transverse ligaments cut and with flexion of the head, the middle portion of this membrane was stretched over the odontoid process, thus acting as a “hammock” that inhibited the odontoid process from moving posteriorly. The tectorial membrane did not limit cervical flexion per se but rather helped to insure that the odontoid process did not impinge into the cervical canal. Lateral flexion was not found to be limited by this structure. Histologically, parallel collagen fibers with spindle‐shaped fibrocytes were observed within this membrane and near its attachment to the posterior axis, the collagen fibers were noted to be more homogenous with larger nonspindled fibrocytes. At the cranial attachment of the tectorial membrane, multiple calcified areas were noted that interdigitated with the underlying bone. Also near this cephalic bony attachment, there was an increase in the number of elastic fibers, which were found running parallel with the surrounding Type III collagen fibers. The tectorial membrane was found to attach much more superiorly than previously described. We would propose that the tectorial membrane provides for a second line of defense, preventing the odontoid process from compressing the spinal cord and by doing so, secondarily limits movement of the craniocervical juncture. This hypothesis is strengthened by the finding of many elastic fibers in the tectorial membrane. To our knowledge, our study is the first to perform a detailed histological analysis of the tectorial membrane. We hope that these data are useful to the clinician who investigates this ligament of the craniocervical region. Clin. Anat. 20:382–386, 2007. © 2006 Wiley‐Liss, Inc.
β-Catenin regulates excitatory postsynaptic strength at hippocampal synapses

The precise contribution of the cadherin–β-catenin synapse adhesion complex in the functional and structural changes associated with the pre- and postsynaptic terminals remains unclear. Here we report a requirement for endogenous β-catenin in regulating synaptic strength and dendritic spine morphology in cultured hippocampal pyramidal neurons. Ablating β-catenin after the initiation of synaptogenesis in the postsynaptic neuron reduces the amplitude of spontaneous excitatory synaptic responses without a concurrent change in their frequency and synapse density. The normal glutamatergic synaptic response is maintained by postsynaptic β-catenin in a cadherin-dependent manner and requires the C-terminal PDZ-binding motif of β-catenin but not the link to the actin cytoskeleton. In addition, ablating β-catenin in postsynaptic neurons accompanies a block of bidirectional quantal scaling of glutamatergic responses induced by chronic activity manipulation. In older cultures at a time when neurons have abundant dendritic spines, neurons ablated for β-catenin show thin, elongated spines and reduced proportion of mushroom spines without a change in spine density. Collectively, these findings suggest that the cadherin–β-catenin complex is an integral component of synaptic strength regulation and plays a basic role in coupling synapse function and spine morphology.
Rhabdomyosarcoma of head and neck in children

Embryonal rhabdomyosarcoma is a rare condition that tends to occur in the head and neck in children. This disease carried a very poor prognosis until 10 years ago when a multidisciplinary approach (with surgery, therapy and multiple drug chemotherapy) was instituted. In this article a review of the literature on embryonal rhabdomyosarcoma is given and three rare cases have been reported; the first involved the palate, the second affected the ear and mastoid, and the third was a case originating in the nasopharynx with orbital involvement. Clinical and histopathological descriptions are given and the results of therapy are evaluated.
The impact of climate change policy on the risk of water stress in southern and eastern Asia

The adequacy of freshwater resources remains a critical challenge for a sustainable and growing society. We present a self-consistent risk-based assessment of water availability and use under future climate change and socioeconomic growth by midcentury across southern and eastern Asia (SEA). We employ large ensemble scenarios from an integrated modeling framework that are consistent across the spectrum of regional climate, population, and economic projections. We find socioeconomic growth contributes to an increase in water stress across the entire ensemble. However, climate change drives the ensemble central tendency toward an increase in water stress in China but a reduction in India, with a considerable spread across the ensemble. Nevertheless, the most deleterious unabated climate-change impact is a low probability but salient extreme increase in water stress over China and India. In these outcomes, annual withdrawals will routinely exceed water-storage capacity. A modest greenhouse gas mitigation pathway eliminates the likelihood of these extreme outcomes and also benefits hundreds of millions of people at risk to various levels of water stress increase. Over SEA we estimate an additional 200 million people under threat of facing at least heavily water-stressed conditions from climate change and socioeconomic growth, but the mitigation scenario reduces the additional population-under-threat by 30% (60 million). Nevertheless, there remains a 1-in-2 chance that 100 million people across SEA experience a 50% increase in water stress and a 1-in-10 chance they experience a doubling of water stress. Therefore, widespread adaptive measures may be required over the coming decades to meet these unavoidable risks in water shortfalls.
Are incretin mimetics and enhancers linked to pancreatitis and malignant transformations in pancreas?

Introduction: Dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists are new options in the treatment of type 2 diabetes mellitus. However, due to accumulating reports on the occurrence of acute pancreatitis (AP), a suspicion of an association between incretin-based therapies and pancreatic disease has arisen. Areas covered: A review of the literature on the safety of incretin-based therapies in regard to AP and pancreatic cancer was undertaken with discussion of potential mechanisms as well as limitations. Expert opinion: Until now, several preclinical and clinical studies have been published; however, they present conflicting results. Common risk factors, low incidence rates, long latency periods (in regard to pancreatic malignancy), lack of availability of human pancreatic tissues during lifetime among others hamper the confirmation or exclusion of a causal association. The results of the ongoing large randomized controlled trials will add further data. In line with current recommendations by European Medicines Agency and FDA, incretin-based therapies should be discontinued in patients with suspicion of AP, and incretin mimetics should not be administered to patients with a history of AP. However, based on current knowledge, there is no sound reason for depriving type 2 diabetic patients in general of a beneficial and effective therapy. However, this conclusion cannot be final and should be subject to constant reevaluation and, if necessary, change.
Immunogenicity and efficacy of an anthrax/plague DNA fusion vaccine in a mouse model.

The efficacy of multi-agent DNA vaccines consisting of a truncated gene encoding Bacillus anthracis lethal factor (LFn) fused to either Yersinia pestis V antigen (V) or Y . pestis F1 was evaluated. A/J mice were immunized by gene gun and developed predominantly IgG1 responses that were fully protective against a lethal aerosolized B. anthracis spore challenge but required the presence of an additional DNA vaccine expressing anthrax protective antigen to boost survival against aerosolized Y. pestis.
APOBEC3G Inhibits Elongation of HIV-1 Reverse Transcripts

APOBEC3G (A3G) is a host cytidine deaminase that, in the absence of Vif, restricts HIV-1 replication and reduces the amount of viral DNA that accumulates in cells. Initial studies determined that A3G induces extensive mutation of nascent HIV-1 cDNA during reverse transcription. It has been proposed that this triggers the degradation of the viral DNA, but there is now mounting evidence that this mechanism may not be correct. Here, we use a natural endogenous reverse transcriptase assay to show that, in cell-free virus particles, A3G is able to inhibit HIV-1 cDNA accumulation not only in the absence of hypermutation but also without the apparent need for any target cell factors. We find that although reverse transcription initiates in the presence of A3G, elongation of the cDNA product is impeded. These data support the model that A3G reduces HIV-1 cDNA levels by inhibiting synthesis rather than by inducing degradation.
Role of ornithine decarboxylase in epidermal tumorigenesis.

Ornithine decarboxylase (ODC) plays a key role in the biosynthesis of polyamines, which are necessary for cell growth and differentiation. ODC expression is very tightly controlled in all normal cells; however, regulation of its expression is altered in many tumor cells resulting in much higher basal levels of ODC in tumors. To investigate the potential role of ODC overexpression in epidermal tumorigenesis, we constructed a replication-defective retroviral vector to overexpress a truncated ODC protein in epidermal cells. Stable viral infection of mouse epidermal cells dramatically increases not only the basal ODC activity but also the basal putrescine and spermidine levels. In all infected epidermal cells with high polyamine levels, DNA synthesis is increased as measured by [3H]thymidine incorporation into DNA as well as increased bromodeoxyuridine staining in the nuclei of ODC-infected epidermal cells. ODC viral infection of nontumorigenic BK-1 epidermal cells and primary cultures of mouse keratinocytes and fibroblasts from newborn mouse skin yields no tumors when injected s.c. into athymic nude mice or when transplanted as skin grafts onto nude mice. Epidermal cell lines SP-1 and 308 (which possess an activated rasHa gene) are not tumorigenic when injected s.c. into nude mice. However, following infection with the ODC virus, they form tumors filled with keratin and papilloma-like projections of hyperplastic epidermal cells displaying dysplasia and many mitotic figures. These data indicate that ODC overexpression by itself is not sufficient to induce tumors in normal cells but that increased expression of ODC enhances tumor development in initiated premalignant epidermal cells.
Accelerated transepithelial corneal cross-linking for progressive keratoconus: a prospective study of 12 months

Background/aims To evaluate the clinical results of accelerated transepithelial corneal cross-linking (CXL) in Japanese patients with progressive keratoconus (KCN). Methods Thirty eyes of 19 patients (16 male, 3 female patients) with progressive KCN were included. The mean age was 24.9±7.0 (range 16–38) years. All patients received ultraviolet A radiation for 3 min at an irradiance of 30 mW/cm2. Patients were followed up on the first day, at 1 week and 2 weeks, and at 1 month, 3 months, 6 months and 12 months postoperatively. Clinical examinations included measures of uncorrected visual acuity, best corrected visual acuity (BCVA), average keratometry (AveK), maximum keratometry (Kmax), central corneal thickness, thinnest corneal thickness (TCT), endothelial cell density, intraocular pressure and non-mydriatic indirect fundus examination. Patients were asked to report any pain or discomfort at each visit. Results There were no intraoperative or postoperative complications. All 30 eyes finished the follow-up. After 12 months, there was a significant decrease in Kmax (p<0.0001), AveK (p=0.003) and TCT (p=0.002), and a significant improvement in BCVA (p=0.001). There were no other significant changes. Pain or foreign-body sensation following CXL appeared in the first 2 days, but lasted no more than 1 week in all cases. Conclusions There were no complications associated with accelerated transepithelial corneal CXL, and the clinical outcomes were appraisable in a 12-month follow-up. Trial registration number UMIN000009372.
Thiazolidinediones: a new class of antidiabetic drugs

Thiazolidinediones (TZDs) are a new class of oral antidiabetic agents. They selectively enhance or partially mimic certain actions of insulin, causing a slowly generated antihyperglycaemic effect in Type 2 (noninsulin dependent) diabetic patients. This is often accompanied by a reduction in circulating concentrations of insulin, triglycerides and nonesterified fatty acids. TZDs act additively with other types of oral antidiabetic agents (suphonylureas, metformin and acarbose) and reduce the insulin dosage required in insulin‐treated patients. The glucose‐lowering effect of TZDs is attributed to increased peripheral glucose disposal and decreased hepatic glucose output. This is achieved substantively by the activation of a specific nuclear receptor – the peroxisome proliferator‐activated receptor‐gamma (PPARγ), which increases transcription of certain insulin‐sensitive genes. To date one TZD, troglitazone, has been introduced into clinical use (in Japan, USA and UK in 1997). This was suspended after 2 months in the UK pending further investigation of adverse effects on liver function. TZDs have been shown to improve insulin sensitivity in a range of insulin‐resistant states including obesity, impaired glucose tolerance (IGT) and polycystic ovary syndrome (PCOS). In Type 2 diabetes, the TZDs offer a new type of oral therapy to reduce insulin resistance and assist glycaemic control.
Expression of the neural RNA‐binding protein Musashi1 in human gliomas

Tumor cells arising from a particular tissue may exhibit the same gene expression patterns as their precursor cells. To test this proposition, we have analyzed the expression of a neural RNA‐binding protein, Musashi1, in primary human central nervous system (CNS) tumors. In rodents, Musashi1 is expressed predominantly in proliferating multipotent neural precursor cells, but not in newly generated postmitotic neurons. The expression of Musashi1 is downregulated with the successive progression of neurogenesis. In normal adult human tissues, we detected low levels of Musashi1 expression in brain and testis by RT‐PCR analysis. In an RNA panel of 32 cancer tissues and cell lines, elevated expression of Musashi1 was seen in all five malignant gliomas studied, in contrast to the slight expression seen in other tumor cells, including those in several melanomas and a prostate cancer. Western blot analysis showed strong Musashi1 expression in malignant gliomas compared with nonneoplastic brain tissue. Glioblastomas, the most malignant form of glioma, showed higher Musashi1 expression than less malignant gliomas by immunohistochemical analysis. Tumors with strong Musashi1 expression tended to have high proliferative activity. Thus, the expression of Musashi1 correlated with the grade of the malignancy and proliferative activity in gliomas. These results suggest that primary CNS tumors may share gene expression patterns with primitive, undifferentiated CNS cells and that Musashi1 may be a useful marker for the diagnosis of CNS tumors. GLIA 34:1–7, 2001. © 2001 Wiley‐Liss, Inc.
Toward the Deployment of an Ultra-Wideband Localization Test Bed

The design, development, and deployment of Ultra-Wideband (UWB) localization systems involves digital and Radio-Frequency (RF) hardware, embedded software, localization algorithms, security and reliability aspects, electromagnetics, and others. Design and integration decisions affect the performance of an UWB system, in particular the most important metrics: localization accuracy and position update rate. To facilitate further development of UWB localization systems and to analyze some of the major trade-offs we share our experience in deploying the EPFL UWB-Lite test bed (U-Lite). We describe an approach to numerical simulation modeling that can help in the design and evaluation of UWB localization systems. To validate our approach we show experimental results with one transmitter and one receiver. Our UWB test bed includes a mobile robot platform, so we can study and evaluate the UWB performance trade-offs in real-world conditions.
An Association Between Glatiramer Acetate and Malignant Melanoma

A 43-year-old female receiving immunomodulatory therapy with glatiramer acetate (copaxone, GA) for relapsing, remitting multiple sclerosis was diagnosed with stage IIIB melanoma that recurred <7 months after resection and lymphadenectomy. In preparation for systemic therapy the patient discontinued GA, and shortly thereafter experienced spontaneous and complete clinical and radiographic resolution of her disease. The development and subsequent regression of melanoma in this patient may be due to the use and subsequent discontinuation of GA, and our discussion of the case includes the potential immunologic mechanisms that may provide an explanation for our findings. To the best of our knowledge, this case represents the first reported association between the immunomodulatory agent GA and malignant melanoma.
Role of the Promoter in Maintaining Transcriptionally Active Chromatin Structure and DNA Methylation Patterns In Vivo

ABSTRACT Establishment and maintenance of differential chromatin structure between transcriptionally competent and repressed genes are critical aspects of transcriptional regulation. The elements and mechanisms that mediate formation and maintenance of these chromatin states in vivo are not well understood. To examine the role of the promoter in maintaining chromatin structure and DNA methylation patterns of the transcriptionally active X-linked HPRT locus, 323 bp of the endogenous human HPRT promoter (from position −222 to +102 relative to the translation start site) was replaced by plasmid sequences by homologous recombination in cultured HT-1080 male fibrosarcoma cells. The targeted cells, which showed no detectable HPRT transcription, were then assayed for effects on DNase I hypersensitivity, general DNase I sensitivity, and DNA methylation patterns across the HPRT locus. In cells carrying the deletion, significantly diminished DNase I hypersensitivity in the 5′ flanking region was observed compared to that in parental HT-1080 cells. However, general DNase I sensitivity and DNA methylation patterns were found to be very similar in the mutated cells and in the parental cells. These findings suggest that the promoter and active transcription play a relatively limited role in maintaining transcriptionally potentiated epigenetic states.
Electromyographic activity of the longissimus dorsi muscles in horses during trotting on a treadmill.

OBJECTIVE To use electromyography (EMG) to measure physiologic activity of the longissimus dorsi muscles of horses during trotting on a treadmill. ANIMALS 15 adult horses (5 to 20 years old that weighed 450 to 700 kg) that did not have clinical signs of back pain. PROCEDURE Data were recorded for each horse during trotting on a treadmill at speeds of 2.6 to 4.4 m/s. Surface electromyography was recorded bilaterally from the longissimus dorsi muscles at the levels of T12, T16, and L3. RESULTS In each motion cycle, 2 EMG maxima were found at the end of the diagonal stance phases. The EMG activity peaked slightly later at L3 than at T12 and T16. Maximum EMG amplitudes were highest at T12 and decreased caudally, with mean +/- SD values of 4.51 +/- 1.20 mV at T12, 3.00 +/- 0.83 mV at T16, and 1.78 +/- 0.67 mV at L3. Mean minimum EMG activity was 1.30 +/- 0.63 mV at T12, 0.83 +/- 0.35 mV at T16, and 0.80 +/- 0.39 mV at L3. The relative amplitudes (ie, [maximum - minimum]/maximum) were 67 +/- 11% at T12, 66 +/- 8% at T16, and 71 +/- 8% at L3. CONCLUSIONS AND CLINICAL RELEVANCE Activity of the longissimus dorsi muscles is mainly responsible for stabilization of the vertebral column against dynamic forces. The difference between minimum and maximum activity may allow application of this method as a clinical tool. Data reported here can serve as reference values for comparison with values from clinically affected horses.