Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of microRNAs in normal and malignant hematopoiesis

MicroRNAs are small non‐coding RNAs that act at the post‐transcriptional level, regulating protein expression by repressing translation or destabilizing mRNA target. Because of their discovery, microRNAs have been associated with almost every normal cell function, including proliferation, differentiation and apoptosis. Several lines of evidence suggest that they have an important role in normal hematopoiesis as exemplified by the role of mir‐155 and mir‐150 in the differentiation of B and T lymphocytes, the suppressive role of mir‐221 and mir‐222 in erythroid differentiation, the inhibitory effect of mir‐181 on hematopoietic differentiation and the induction of myeloid differentiation by mir‐223. Moreover, they play a role both as oncogenes, probably by a variety of mechanisms, namely through elimination of tumor suppressor proteins, or as tumor suppressor genes by targeting oncogenic mRNAs. Their aberrant expression has been associated with solid tumors and hematopoietic malignancies as suggested by the frequent deletion of mir‐15a and mir‐16‐1 in chronic lymphocytic leukemia, the increased levels of mir‐155 in diffuse large B‐cell lymphomas and the increased levels of mir‐181 in acute myeloid leukemia M1 and M2. The purpose of this review is to summarize current knowledge on the role of microRNAs in normal hematopoiesis and hematopoietic malignancies and, moreover, to highlight their role as potential therapeutic tools.
BRAF V600E Mutated Gene Variant as a Circulating Molecular Marker in Metastatic Melanoma Patients

Cutaneous metastatic melanoma management has recently approached the age of individualized therapy (Romano et al., 2011). The discovery that the 1799T>A point mutation in the BRAF oncogene (BRAFV600E) occurs in ~50% of melanoma lesions and that melanoma cells bearing the mutation are oncogene addicted, i.e., strictly dependent upon BRAFV600E activity for growth and survival, have pointed to BRAFV600E as a promising target for therapy. Drugs targeting BRAF have been developed, and several clinical trials are currently ongoing. Phase I-II results recently reported remarkable tumor regression in the great majority of patients bearing disseminated BRAFV600E mutated melanoma disease after treatment with BRAFV600E-specific inhibitors. In these trials, BRAF mutational status is determined to select patients who may benefit from therapy. However, melanoma specimens are not always available to perform this analysis; moreover, a negative result in a single tumor biopsy may cover the presence of mutation-positive tumor lesions. Because blood has been proven to represent a valuable alternative source of tumor-derived cells as well as of tumor-derived DNA, several technical approaches have been studied to detect BRAFV600E in RNA/DNA extracted from bloodderived circulating tumor cells and in circulating free DNA isolated from plasma or serum. For these reasons, circulating BRAFV600E has the potential as both a specific melanoma molecular marker and a monitoring factor to be used to evaluate clinical response. In this chapter, we summarize the clinical and biological features of BRAF mutation in melanoma. Furthermore, we report a new BRAFV600E detection assay developed in our lab that shows high sensitivity and specificity.
The Role of Sphingosine Kinase in the Signaling Initiated at the High-Affinity Receptor for IgE (FcεRI) in Mast Cells

Over the last few years, sphingolipids have emerged as an additional class of lipids participating in signaling events in various cell types. The best-investigated examples so far are ceramide and sphingosine-1-phosphate. Ceramide-activated protein kinase and sphingosine kinase are two enzymes which respond to and generate these mediators. In particular, sphingosine kinase, its substrate sphingosine and the product sphingosine-1-phosphate have recently been implicated in the signaling cascades initiated at the FcεRI of mast cells. High intracellular levels of sphingosine seem to serve as an ‘intracellular’ inhibitor which is ‘deactivated’ by the action of sphingosine kinase, due to the conversion to sphingosine-1-phosphate. One mode of action of the inhibitory process in this cell type is prevention of the activation of the mitogen-activated protein (MAP) kinase pathway. Sphingosine-1-phosphate itself, the product of this enzymatic reaction, is believed to lead to Ca2+ mobilization and to stimulate the MAP kinase pathway. The existence and function of this second messenger explains the ‘IP3 gap’ described in mast cells after FcεRI activation. Therefore, a picture emerges whereby the balance of these two lipid molecules seems to be decisive for the activation of mast cells by IgE plus antigen, with sphingosine kinase acting as a permissive switch for stimulation.
Long‐term biomechanical properties of rabbit sclera after collagen crosslinking using riboflavin and ultraviolet A (UVA)

Purpose: Scleral crosslinking by the photosensitizer riboflavin and ultraviolet A (UVA) has been shown to increase significantly the scleral biomechanical rigidity and might therefore become a possible sclera‐based treatment modality for progressive myopia. In the present study, the long‐term effect of the new crosslinking method on biomechanical properties was investigated in the rabbit sclera.
A novel compact three-dimensional CMOS branch-line coupler using the meandering ECPW, TFMS, and buried micro coaxial technologies at 60 GHz

This paper proposes a new approach for realizing a compact 3-D 90° hybrid coupler incorporating compact meandered elevated coplanar waveguides (ECPW), thin-film microstrip (TFMS) transmission lines, and micro coaxial shunt stub loading. The design technique has been successfully demonstrated using a multi-layer 90nm CMOS process. The proposed coupler takes advantage of the multi-level metallization processes offered in CMOS technology. The intrinsic area of the fabricated 3-D hybrid coupler is significantly reduced with a size reduction of 81% in circuit area at 60 GHz as compared to that of a conventional hybrid coupler using the ECPW/TFMS configuration. Simulated and experimental results are presented in support of the novel miniature coupler.
Anatomic considerations for electrode implantation into the modiolus

OBJECTIVE: The aim of this study was to assess the anatomic factors that enable successful direct implantation of an electrode into the modiolus. METHODS: We studied the topographic location of the modiolus, including its apical part, to determine an appropriate surgical approach. Ten dissections of human temporal bones were performed. We measured the distance between the apex of the cochlea and the floor of the middle cranial fossa. The length of the modiolar axis was also measured. We used stereomicroscopy to study the modiolus for the possible placement of an electrode along its axis. Finally, via a cochleostomy on the anterior pyramidal surface, we introduced an experimental electrode from the apex to the base of the modiolus, aiming to determine the appropriate length for a modiolar electrode. RESULTS: We found that the appropriate surgical approach to the modiolus is through middle cranial fossa. The cupola (apex) of the cochlea is located medial and anterior to the ganglion geniculi. The greater petrosal nerve served as a landmark. The cupola is about 2 mm below the upper surface of the petrous bone. An 8to 10-mm electrode can be implanted without causing severe damage to the nerve trunk. The results of histologic studies revealed modiolar anatomic structures in detail. CONCLUSIONS: The results of our study suggest that the implantation of an electrode into the modiolus is possible. Modiolar implantation could be an alternative to standard cochlear implantation, especially in patients with severe cochlear ossification and cochlear or middle ear malformation. From the ENT Department, Medical University of Sofia, Sofia (K. Assenova, T. Karchev), ENT Department, Medical Institute, Ministry of Interior, Sofia (S. Stoyanor), Bulgaria
Crystal structure of human heme oxygenase-1 in a complex with biliverdin.

Heme oxygenase oxidatively cleaves heme to biliverdin, leading to the release of iron and CO through a process in which the heme participates both as a cofactor and as a substrate. Here we report the crystal structure of the product, iron-free biliverdin, in a complex with human HO-1 at 2.19 A. Structural comparisons of the human biliverdin-HO-1 structure with its heme complex and the recently published rat HO-1 structure in a complex with the biliverdin-iron chelate [Sugishima, M. , Sakamoto, H. , Higashimoto, Y. , Noguchi, M. , and Fukuyama, K. (2003) J. Biol. Chem. 278, 32352-32358] show two major differences. First, in the absence of an Fe-His bond and solvent structure in the active site, the distal and proximal helices relax and adopt an "open" conformation which most likely encourages biliverdin release. Second, iron-free biliverdin occupies a different position and orientation relative to heme and the biliverdin-iron complex. Biliverdin adopts a more linear conformation and moves from the heme site to an internal cavity. These structural results provide insight into the rate-limiting step in HO-1 catalysis, which is product, biliverdin, release.
A study on prevalence of rifampicin resistance by Gene Xpert with clinico-radiological correlation in previously treated pulmonary tuberculosis patients

BACKGROUND: The drug resistant tuberculosis is a great threat to mankind. The rifampicin resistance is a good predictor of multidrug resistant tuberculosis. The Gene Xpert is an excellent diagnostic tool for rapid detection of Mycobacterium tuberculosis and rifampicin resistance. AIMS & OBJECTIVES: The aims & objectives of the study were to find out the prevalence of rifampicin resistance among smear positive and smear negative previously treated pulmonary tuberculosis patients and to correlate clinico-radiological profile with rifampicin resistance. MATERIALS & METHODS: The prospective analytic study was conducted in 200 presumptive TB patients with past history of anti-tuberculosis treatment for one month or more. The Gene Xpert test (CBNAAT) was performed. The results were analysed using appropriate statistical tests. RESULTS: Out of 200 study population, Mycobacterium tuberculosis was detected in 159 (79.5%) cases by Gene Xpert. Rifampicin resistance was detected in 36 (22.64%) out of 159 cases. The prevalence of rifampicin resistance among sputum positive previously treated pulmonary tuberculosis was 25.21% (31/123) whereas the prevalence among previously treated sputum negative pulmonary tuberculosis was 13.8% (5/36). Out of 57 relapse cases, 26 failure cases, 40 treatment after default cases and 36 other cases, rifampicin resistance was detected in 9 (15.79%), 12 (46.15%), 10 (25%) and 5 (13.88%) patients respectively. The statistically significant correlation was found between failure cases and rifampicin resistance (P<0.05). CONCLUSION: The overall prevalence of rifampicin resistance is 22.64% among previously treated pulmonary tuberculosis. The failure case is significantly associated with rifampicin resistance.
Relative fitness of females and hermaphrodites in a natural gynodioecious population of wild radish, Raphanus sativus L. (Brassicaceae): comparison based on molecular genotyping

In many gynodioecious species, sex determination involves both cytoplasmic male‐sterility (CMS) genes and nuclear genes that restore male function. Differences in fitness among genotypes affect the dynamics of those genes, and thus that of gynodioecy. We used a molecular marker to discriminate between hermaphrodites with and without a CMS gene in gynodioecious Raphanus sativus. We compared fitness through female function among the three genotypes: females, hermaphrodites with the CMS gene and those without it. Although there was no significant difference among the genotypes in seed size, hermaphrodites without the CMS gene produced significantly more seeds, and seeds with a higher germination rate than the other genotypes, suggesting no fitness advantage for females and no benefit to bearing the CMS gene. Despite the lack of fitness advantage for females in the parameter values we estimated, a theoretical model of gynodioecy shows it can be maintained if restorer genes impose a cost paid in pollen production. In addition, we found that females invest more resources into female reproduction than hermaphrodites when they become larger. If environmental conditions enable females to grow larger this would facilitate the dynamics of CMS genes.
Localized field enhancement in slow-wave modes of modified Bragg waveguide

Modified scheme of Bragg reflection waveguide with additional layers between the hollow core and cladding is considered. Dispersion diagrams are calculated on the base of dispersion equations solutions for ordinary and modified Bragg waveguides. Slow-wave regimes are considered for both kinds of structure. Electric field spatial distributions for localized slow-wave modes of Bragg reflection waveguide are obtained. It is shown that modified scheme of Bragg waveguide provides the enhanced localization of the surface modes field in the hollow core. Therefore modified Bragg waveguide is the promising electrodynamic system not only for laser-driven accelerators but also for the vacuum electron devices where usual slow-wave structures are unconvenient.
Subtyping of Listeria monocytogenes on the basis of plasmid profiles and arsenic and cadmium susceptibility

The susceptibilities to arsenic and cadmium together with the detection of plasmid DNA were evaluated for use as epidemiological markers for the subtyping of Listeria monocytogenes. Plasmid DNA was detected in 34% of 322 apparently unrelated isolates of L. monocytogenes. The resistance to cadmium and arsenic differentiated 565 apparently unrelated cultures into four groups, the smallest being 5% of cultures resistant to both agents, and the largest (53%) being sensitive to cadmium and resistant to arsenic. The resistance patterns to these agents and the presence of plasmid DNA varied markedly between the serotypes of the cultures. The detection of plasmid DNA was strongly associated with cadmium resistance in serogroup 1/2 cultures, but not within those of serogroup 4. Arsenic resistance was not associated with plasmid DNA. All methods were sufficiently stable to be useful for epidemiological investigations. The techniques described here offer simple methods which can be easily utilized in laboratories without a specialized expertise for this bacterium.
Does deprivation index modify the acute effect of black smoke on cardiorespiratory mortality?

Objectives To investigate whether deprivation index modifies the acute effect of black smoke on cardiorespiratory mortality. Methods Generalised linear Poisson regression models were used to investigate whether deprivation index (as measured by the Carstairs deprivation index) modified the acute effect of black smoke on mortality in two largest Scottish cities (Glasgow and Edinburgh) between January 1981 and December 2001. Lag periods of up to 1 month were assumed for the effects of black smoke. Results Deprivation index significantly modified the effect of black smoke on mortality, with black smoke effects generally increasing as level of deprivation increased. The interaction coefficient from a parametric model assuming a linear interaction between black smoke (μg/m−3) and deprivation in their effect on mortality—equivalent to a test of ‘linear trend’ across Carstairs categories—was significant for all mortality outcomes. In a model where black smoke effects were estimated independently for each deprivation category, the estimated increase in respiratory mortality over the ensuing 1-month period associated with a 10 μg/m3 increase in the mean black smoke concentration was 8.0% (95% CI 5.1 to 10.9) for subjects residing in the ‘most’ deprived category (Carstairs category 7) compared to 3.7% (95% CI −0.7 to 8.4) for subjects residing in the ‘least’ deprived category (Carstairs category 1). Conclusions The results suggest a stronger effect of black smoke on mortality among people living in more deprived areas. The effect was greatest for respiratory mortality, although significant trends were also seen for other groups. If corroborated, these findings could have important public health implications.
Growth inhibition and induction of apoptosis in MCF-7 breast cancer cells by oridonin nanosuspension

The mechanism for anti-tumor activity of oridonin (ORI) nanosuspension, prepared by the high pressure homogenization method, was studied using MCF-7 human breast carcinoma cells in vitro. MTT assay, observation of morphologic changes, flow cytometric analysis, and western blot analysis indicated that ORI nanosuspension could significantly intensify the in vitro anti-tumor activity to MCF-7 cells, as compared with ORI solution. Furthermore, ORI nanosuspension induced G2/M stage proliferation arrest and apoptosis in MCF-7 cells depending on its concentration. In addition, western blot analysis indicated that the pro-caspase-3 protein was not cleaved into the activated form and the expression of anti-apoptotic Bcl-2 protein decreased, on the contrary, the expression of pro-apoptotic Bax protein increased in a dose-dependent manner in ORI nanosuspension-treated cells. These observations indicated that the anti-tumor activity of ORI nanosuspension was intensified by cell-cycle arrest and apoptosis induction.
Distribution of yellowhead virus in selected tissues and organs of penaeid shrimp Penaeus vannamei

The distribution of yellow-head virus (YHV) in 9 different tissues and organs Including the branchial portion of the gill, nerve cord, lymphoid organ (Oka), heart, midgut, hepatopancreas, head soft tissues (HST), abdominal muscle, and eyestalk of experimentally infected moribund white shrunp Penaeus vannamei (Boone) was examined by bioassay using penaeid shrimp indicators and by quantal assay (TCIDSO) in primary shrimp Oka organ cell cultures. Infectious YHV was demonstrated in all the tissues and organs tested; inoculation of each of the tissue and organ filtrates into experimental shrimp resulted In 100% mortality within 6 to 9 d postinfection. The TCID,, assay in primary Oka organ cells revealed that Oka, gill and HST contained 10to 800-fold higher titers of YHV than the other tissues and organs tested and suggested that they are apparently the primary target tissues and organs for YHV infection.
Dislocated acromioclavicular joint: follow-up study of 35 unreduced acromioclavicular dislocations

no difficulty until the muscular support of the shoulder weakens, most likely by aging, is shown by a 55-year-old right-handed tennis player whose entire right clavicle was removed at age 14. He had been playing regularly without difficulty, but sought medical advice for drooping of the shoulder and aching pain in the same arm. One of us concluded that he was experiencing a brachial plexus stretch from this shoulder droop. Treatment consisted of a support brace and he continued to play tennis. This he did, without untoward manifestation, for 5 more years until he died from an unrelated cause.
Antibiotic susceptibility of group A streptococci: a 6-year follow-up study

The susceptibility patterns of group A streptococci over the last 6 years in our hospital were determined. Since our last study, carried out in 1987, all isolates have remained very susceptible in vitro to penicillin and all of the other beta-lactam agents tested. We observed resistance to erythromycin, clindamycin, tetracycline, and ofloxacin. The prevalence of erythromycin-resistant group A streptococci did not change appreciably throughout the study period.
Comparative genomic hybridization reveals genetic progression of oral squamous cell carcinoma from dysplasia via two different tumourigenic pathways

To clarify the genetic pathway(s) involved in the development and progression of oral squamous cell carcinoma (OSCC), as well as the relationship between genetic aberrations and biological characteristics of OSCC tumours, comparative genomic hybridization was used to analyse genetic alterations in both primary OSCCs and adjacent dysplastic lesions of the same biopsy specimens from 35 patients. Gain of 8q22–23 was the most frequent alteration in both OSCC and mild dysplasia, and was considered the earliest event in the process of oral tumourigenesis. The average number of DNA sequence copy number aberrations (DSCNAs) increased with progression from mild dysplasia to invasive carcinoma (r = 0.737, n = 70, p < 0.001). OSCC samples were classified as having a large or small number of DSCNAs (OSCC‐L, 21.4 ± 4.7 DSCNAs or OSCC‐S, 10.0 ± 1.7 DSCNAs, respectively; p < 0.0001). Gains of 3q26‐qter, 8q, 11q13, 14q, and 20q and losses of 4q, 5q12–22, 6q, 8p, 13q, and 18q22‐qter were common to OSCC‐L and OSCC‐S. Gains of 5p15, 7p, 17q11–22, and 18p and losses of 3p14–21, 4p, and 9p were detected exclusively in OSCC‐L. The average number of DSCNAs depended on whether the samples showed OSCC‐ L or dysplasia plus OSCC‐L, or showed OSCC‐S or dysplasia plus OSCC‐S (p = 0.001). Gain of 5p15 and losses of 4p and 9p were detected even in dysplastic lesions adjacent to OSCC‐L samples. Loss of 4p was associated with node metastasis by multivariate analysis (p = 0.013). OSCC‐L tumours were more often T3–T4 stage tumours than T1–T2 stage tumours (p = 0.03). These findings suggest that two different types of OSCC, OSCC‐L associated with high‐stage cancer and OSCC‐S associated with low‐stage cancer, arise from different types of dysplasia via different genetic pathways. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Load That Maximizes the Average Mechanical Power Output During Jump Squats in Power‐Trained Athletes

Three studies that used rugby league players experienced in power training methods as subjects were performed to investigate the resistance (percentage of 1 repetition maximum [1RM]) that maximized the average mechanical power output (Pmax) during the jump squat exercise. Maximum strength was assessed via 1RM (studies 2 and 3) or 3RM (study 1) during the full-squat exercise. Pmax was assessed during barbell jump squats, using resistances of 40, 60, 80, and 100 kg within the Plyometric Power System. All studies found that power output was maximized by resistances averaging circa 85–95 kg, representing 55–59% of 1RM full-squat strength. However, loads in the range of 47–63% of 1RM were often similarly effective in maximizing power output. The results of this investigation suggest that athletes specifically trained via both maximal strength and power training methods may generate their maximal power outputs at higher percentages of 1RM than those previously reported for solely strength-trained athletes and that there would appear to be an effective range of resistances for maximizing power output.
INTERSECTION NUMBERS OF SPECIAL CYCLES

Let G /Q be a connected semisimple algebraic group defined over Q, and let a, r be two Q-rational automorphisms of finite order of G which commute with each other. We assume that the group G(R) of real points of G is noncompact. Let i be a torsionfree arithmetic subgroup of G(Q) which is stable under the group (a, r) generated by a and r. Then a and r act on the space X of maximal compact subgroups of G(R) and on the locally symmetric space X/I in a natural way. If G(f.l) denotes the reductive algebraic Q-group of fixed points of f.l = a , r acting on G, then the corresponding symmetric space X(f.l) is acted upon by the arithmetic group 1(f.l) of fixed points of f.l acting on i. These give rise to nonempty closed immersed submanifolds C(a) = X(a)/1(a) and C(r) = X(r)/1(r) of X/i. They are called special cycles. We assume that X/i, C(a), and C ( r) are oriented and that the intersection C (a) n C ( r) is compact. Then, if dim C(a) + dim C(r) = dim X, the intersection number