Miracle-dz/UniFAR-FTUs huggingface dataset:
PITDB: a database of translated genomic elements

Abstract PITDB is a freely available database of translated genomic elements (TGEs) that have been observed in PIT (proteomics informed by transcriptomics) experiments. In PIT, a sample is analyzed using both RNA-seq transcriptomics and proteomic mass spectrometry. Transcripts assembled from RNA-seq reads are used to create a library of sample-specific amino acid sequences against which the acquired mass spectra are searched, permitting detection of any TGE, not just those in canonical proteome databases. At the time of writing, PITDB contains over 74 000 distinct TGEs from four species, supported by more than 600 000 peptide spectrum matches. The database, accessible via http://pitdb.org, provides supporting evidence for each TGE, often from multiple experiments and an indication of the confidence in the TGE’s observation and its type, ranging from known protein (exact match to a UniProt protein sequence), through multiple types of protein variant including various splice isoforms, to a putative novel molecule. PITDB’s modern web interface allows TGEs to be viewed individually or by species or experiment, and downloaded for further analysis. PITDB is for bench scientists seeking to share their PIT results, for researchers investigating novel genome products in model organisms and for those wishing to construct proteomes for lesser studied species.
Role of PLLA plasma surface modification in the interaction with human marrow stromal cells

The effects of oxygen-based radio frequency plasma enhanced chemical vapor deposition (rf PECVD) on the surface of poly(L-lactide) (PLLA) polymers and the influence thereof on protein adsorption and on bone–cell behavior have been studied. Thin films and porous scaffolds based on PLLA polymer were developed, and the role of surface modifications were investigated extensively. PECVD surface treatments were used to alter surface functionality and modulate protein adsorption on the PLLA polymer matrix. In particular, Bovine Serum Albumine fluorescein isothiocyanate (fitc-BSA) conjugate adsorption on patterned surfaces of treated PLLA was analyzed by fluorescence microscopy. Human marrow stromal cells (MSCs) were cultured on scaffolds and cell adhesion and morphology were assessed using fluorescence microscopy. The results indicated that the PLLA surface became hydrophilic and its roughness increased with the treatment time and it had a dominant influence on the adsorption process of the protein. The outcome of the plasma treatment of various PLLA surfaces has been shown to be the up-regulator of the cell-adhesive proteins expression and consequently the improvement of cell adhesion and growth. Oxygen-treated PLLA promoted higher adhesion and proliferation of the MSCs in comparison to the untreated samples. It can be concluded that following plasma treatment, PLLA samples show enhanced affinity for osteoprogenitor cells. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Cellular Uptake of Chloroquine Is Dependent on Binding to Ferriprotoporphyrin IX and Is Independent of NHE Activity in Plasmodium falciparum

Here we provide definitive evidence that chloroquine (CQ) uptake in Plasmodium falciparum is determined by binding to ferriprotoporphyrin IX (FPIX). Specific proteinase inhibitors that block the degradation of hemoglobin and stop the generation of FPIX also inhibit CQ uptake. Food vacuole enzymes can generate cell-free binding, using human hemoglobin as a substrate. This binding accounts for CQ uptake into intact cells and is subject to identical inhibitor specificity. Inhibition of CQ uptake by amiloride derivatives occurs because of inhibition of CQ–FPIX binding rather than inhibition of the Na+/H+ exchanger (NHE). Inhibition of parasite NHE using a sodium-free medium does not inhibit CQ uptake nor does it alter the ability of amilorides to inhibit uptake. CQ resistance is characterized by a reduced affinity of CQ–FPIX binding that is reversible by verapamil. Diverse compounds that are known to disrupt lysosomal pH can mimic the verapamil effect. These effects are seen in sodium-free medium and are not due to stimulation of the NHE. We propose that these compounds increase CQ accumulation and overcome CQ resistance by increasing the pH of lysosomes and endosomes, thereby causing an increased affinity of binding of CQ to FPIX.
Cardiac Hypertrophy Involves Both Myocyte Hypertrophy and Hyperplasia in Anemic Zebrafish

Background An adult zebrafish heart possesses a high capacity of regeneration. However, it has been unclear whether and how myocyte hyperplasia contributes to cardiac remodeling in response to biomechanical stress and whether myocyte hypertrophy exists in the zebrafish. To address these questions, we characterized the zebrafish mutant tr265/tr265, whose Band 3 mutation disrupts erythrocyte formation and results in anemia. Although Band 3 does not express and function in the heart, the chronic anemia imposes a sequential biomechanical stress towards the heart. Methodology/Principal Findings Hearts of the tr265/tr265 Danio rerio mutant become larger than those of the sibling by week 4 post fertilization and gradually exhibit characteristics of human cardiomyopathy, such as muscular disarray, re-activated fetal gene expression, and severe arrhythmia. At the cellular level, we found both increased individual cardiomyocyte size and increased myocyte proliferation can be detected in week 4 to week 12 tr265/tr265 fish. Interestingly, all tr265/tr265 fish that survive after week-12 have many more cardiomyocytes of smaller size than those in the sibling, suggesting that myocyte hyperplasia allows the long-term survival of these fish. We also show the cardiac hypertrophy process can be recapitulated in wild-type fish using the anemia-inducing drug phenylhydrazine (PHZ). Conclusions/Significance The anemia-induced cardiac hypertrophy models reported here are the first adult zebrafish cardiac hypertrophy models characterized. Unlike mammalian models, both cardiomyocyte hypertrophy and hyperplasia contribute to the cardiac remodeling process in these models, thus allowing the effects of cardiomyocyte hyperplasia on cardiac remodeling to be studied. However, since anemia can induce effects on the heart other than biomechanical, non-anemic zebrafish cardiac hypertrophy models shall be generated and characterized.
An open-source MEteoroLOgical observation time series DISaggregation Tool (MELODIST v0.1.0)

Meteorological time series with 1 h time steps are required in many applications in geoscientific modelling. These hourly time series generally cover shorter periods of time compared to daily meteorological time series. We present an open-source MEteoroLOgical observation time series DISaggregation Tool (MELODIST). This software package is written in Python and comprises simple methods to temporally downscale (disaggregate) daily meteorological time series to hourly data. MELODIST is capable of disaggregating the most commonly used meteorological variables for geoscientific modelling including temperature, precipitation, humidity, wind speed, and shortwave radiation. In this way, disaggregation is performed independently for each variable considering a single site without spatial dependencies. The algorithms are validated against observed meteorological time series for five sites in different climates. Results indicate a good reconstruction of diurnal features at those sites. This makes the methodology interesting to users of models operating at hourly time steps, who want to apply their models for longer periods of time not covered by hourly observations.
Influence of genetic and environmental factors on surface expression and occupancy of IgE receptors and on histamine releasability of mast cells.

The relationship between the IgE load on mast cells and their secretory capacity when challenged with anti-IgE was studied in peritoneal cells obtained from rats of three different strains, Hooded Lister (HL), Wistar Kyoto (WKY) and Sprague-Dawley (SD). IgE was determined cytofluorometrically after labelling with FITC-conjugated anti-IgE before and after the saturation of the IgE receptors to provide a measure of the surface expression of IgE receptors (number of receptors available for bindings) as well as the IgE occupancy of the receptors (native IgE content). The secretory capacity of the mast cells was examined in vitro in terms of histamine release as a function of anti-IgE concentration. Mast cells obtained from HL and WKY rats were found to carry significantly higher levels of IgE receptors and IgE than the mast cells of SD rats bred and raised under the same conventional laboratory conditions. The mast cells of SD rats kept under barrier-maintained conditions carried significantly less IgE than the mast cells obtained from SD rats kept under conventional conditions, but their IgE receptor levels were similar. The IgE-mediated histamine-releasing capacity of the mast cells, evaluated in terms of maximum release or of the slopes of regression lines (histamine release versus anti-IgE concentration), was positively correlated to the levels of native IgE and IgE receptors in the three strains of rat combined. The mast cells obtained from WKY rats showed the highest secretory capacity in the three strains of rat examined, significantly higher than the mast cells of HL rats, even though the latter displayed similar levels of IgE and IgE receptors. (ABSTRACT TRUNCATED AT 250 WORDS)
Secrecy capacity analysis in D2D underlay cellular networks: Colluding eavesdroppers

This paper presents an investigation of the secrecy capacity in device-to-device (D2D) enabled cellular network under the collusion of eavesdroppers. We provide the closed-form expressions for the probability of achieving non-zero secrecy capacity of the downlink channel between cellular base-station (BS) and user in the presence of D2D nodes and eavesdroppers. Furthermore, two techniques are used for the simple yet exact evaluation of the average secrecy rate using moment generating functions with and without interference. The impact of transmission factors, path loss exponents, and node density is analysed in numerical results. In contrast to the general notion of interference-aided secure communication, it has been shown that the interference does not impact the secrecy rate under the collusion of eavesdroppers.
Bending of aluminum alloy beams depending on irradiance and repetition rate of UV laser radiation

Aluminum alloy beams having the same width but different lengths were made with semiconductor fabrication methods at the IPMS. The beams are clamped on one end with posts to the underlying plane. They are illuminated with 248 nm UV radiation created by an excimer laser and the bending was investigated in dependence on energy density and repetition rate. This behaviour is important for the development and the operation of MOEMS structures when used in UV applications. Ultraviolet radiation is used for lithography as well as material processing. The light-material interaction is well investigated for high energy densities (Ed) which are used for drilling holes or ablation of materials. In this work the influence of 248 nm low energy pulses (Ed < 200 μJ/cm2) on thin beams of aluminum alloys having a thickness of several hundreds of nanometer is analyzed. The frequency of the laser radiation is varied from 1000 to 2000 Hz. The beams have different lengths and are clamped on one end. Before illumination the beams are planar, after illumination the beams show a curvature which is related to internal stresses. The amount of curvature is dependent on the geometry of the beam, the energy density and the repetition rate of the radiation pulses. Also the relaxation behaviour of the curved beam is examined, i. e. the curvature change after the end of irradiation. The results will help to predict the practicability of materials for MOEMS in UV applications (mirror structures) and to understand their behaviour.
Applying bit-level probabilistically shaped coded modulation for high-throughput communications

We evaluate two architectures for fixed length distribution matching. Distribution matching is essential for probabilistic amplitude shaping, a modulation scheme recently proposed for next generation wireless communications. The parallel architecture, called the bit-level distribution matcher (BL-DM) is compared with the symbol-level constant composition distribution matcher (CCDM). Simulation results confirm higher throughput of the BL-DM without performance loss compared to the symbol-level CCDM, when multiple processors can be used. For single core systems, the symbol-level CCDM achieves higher throughput. We also prove that when the output distributions of the BL-DM and the symbol-level CCDM are the same, i.e., they can be represented as a product of binary distributions, the BL-DM achieves lower or equal rate-loss.
Oncogenic exon 2 mutations in Mediator subunit MED12 disrupt allosteric activation of cyclin C-CDK8/19

Somatic mutations in exon 2 of the RNA polymerase II transcriptional Mediator subunit MED12 occur at high frequency in uterine fibroids (UFs) and breast fibroepithelial tumors as well as recurrently, albeit less frequently, in malignant uterine leimyosarcomas, chronic lymphocytic leukemias, and colorectal cancers. Previously, we reported that UF-linked mutations in MED12 disrupt its ability to activate cyclin C (CycC)–dependent kinase 8 (CDK8) in Mediator, implicating impaired Mediator-associated CDK8 activity in the molecular pathogenesis of these clinically significant lesions. Notably, the CDK8 paralog CDK19 is also expressed in myometrium, and both CDK8 and CDK19 assemble into Mediator in a mutually exclusive manner, suggesting that CDK19 activity may also be germane to the pathogenesis of MED12 mutation–induced UFs. However, whether and how UF-linked mutations in MED12 affect CDK19 activation is unknown. Herein, we show that MED12 allosterically activates CDK19 and that UF-linked exon 2 mutations in MED12 disrupt its CDK19 stimulatory activity. Furthermore, we find that within the Mediator kinase module, MED13 directly binds to the MED12 C terminus, thereby suppressing an apparent UF mutation–induced conformational change in MED12 that otherwise disrupts its association with CycC-CDK8/19. Thus, in the presence of MED13, mutant MED12 can bind, but cannot activate, CycC-CDK8/19. These findings indicate that MED12 binding is necessary but not sufficient for CycC-CDK8/19 activation and reveal an additional step in the MED12-dependent activation process, one critically dependent on MED12 residues altered by UF-linked exon 2 mutations. These findings confirm that UF-linked mutations in MED12 disrupt composite Mediator-associated kinase activity and identify CDK8/19 as prospective therapeutic targets in UFs.
Overexpression of Coiled-Coil Domain-Containing Protein 34 (CCDC34) and its Correlation with Angiogenesis in Esophageal Squamous Cell Carcinoma

Background The coiled-coil domain-containing proteins have been shown to have a series of functions in biological synthesis. Recent studies have found that CCDC34 is highly expressed in bladder cancer, but the underlying molecular mechanisms still remain unclear. Therefore, we performed the present study to assess the expression of the coiled-coil domain-containing protein 34 (CCDC34) in esophageal squamous cell carcinoma (ESCC) patients. We also explored the relationships between CCDC34 expression and clinicopathologic characteristics, tumor angiogenesis, and prognosis. Material/Methods We detected the expressions of CCDC34, VEGF, and MVD by immunohistochemical technique in 100 cases of ESCC and 80 cases of corresponding paracarcinomatous normal tissues. The relationship between CCDC34 expression and clinicopathologic characteristics, tumor angiogenesis, and prognosis were also explored. Results The expression of CCDC34 protein was obviously increased in ESCC tissues, which was significantly correlated with sex (p=0.038), TNM stage (p=0.003), and lymphatic metastasis (p=0.024). In addition, we found that the expression of CCDC34 was an independent prognostic factor for ESCC patients. The overexpression of CCDC34 protein in ESCC was associated with tumor progression, angiogenesis, and poor survival. Conclusions Our results demonstrate that CCDC34 is overexpressed in ESCC and can be used as an independent parameter for indicating the poor prognosis of ESCC patients, suggesting that CCDC34 might be a new potential therapeutic target for ESCC patients in the future.
Acute renal thrombosis induced by angiotensin-converting enzyme inhibitors in patients with renovascular hypertension.

Acute reversible renal failure is a widely recognized potential complication of angiotensin-converting enzyme inhibitor (ACEI) administration in renovascular hypertension, particularly in bilateral artery stenosis or stenosis involving a solitary kidney. We report herein 2 cases of a rare but severe complication, i.e., acute renal artery thrombosis. Whereas marked hypotension does not seem to be necessary to trigger acute renal failure following ACE inhibition, by contrast, the fall in blood pressure could play an important role in our patients. Since single-dose ACEI has been advocated in order to improve the predictive value of renal scintigraphy or plasma renin activity measurements in the diagnosis of renovascular hypertension, the potential risk of this approach should be stressed.
Subclinical cardiomyopathy and long QT syndrome: an echocardiographic observation.

OBJECTIVE Long QT syndrome (LQTS) is a cardiac channelopathy predisposing to syncope and sudden death secondary to LQT-triggered ventricular arrhythmias. Long QT syndrome has been regarded as a purely electrical disease. Recent reports have shown by echocardiography that LQTS patients have contraction abnormalities that are associated with cardiac arrhythmias. The purpose of this study was to determine the spectrum and prevalence of echocardiographic anomalies in a large cohort of patients diagnosed genetically and/or clinically with LQTS. OUTCOME MEASURES Two-dimensional and Doppler echocardiographic studies performed during medical evaluation in Mayo's LQTS Clinic were reviewed for 216 LQTS patients. Echocardiograms were evaluated for morphologic abnormalities and atrial and ventricular size and function. Left atrial volume was indexed by body mass. Arrhythmic events were defined as a history of aborted cardiac arrest, documented ventricular tachycardia or fibrillation, and syncope. RESULTS While 75% of patients had normal standard echocardiograms, 54 patients (25%) had at least one abnormal echocardiographic finding. Most common were subclinical cardiomyopathic changes, including increased left atrial volume index (n = 25), left or right ventricular enlargement (n = 7), and grade I-II diastolic dysfunction (n = 7). Left atrial volume index was higher in LQTS patients with arrhythmic events compared with those without (24.4 ± 5.5 mL/m(2) vs. 22.3 ± 6.1 mL/m(2) , P =. 02). Corrected QT intervals and left atrial volume index correlated significantly albeit weakly (r(2) = 0.04, P <. 01). Concomitant congenital heart disease was found in two patients. CONCLUSIONS Subclinical cardiomyopathic changes were found in nearly 20% of LQTS patients. Left atrial enlargement was the most common finding and was associated with prolonged corrected QT and arrhythmic events. These changes may stem from underlying contraction abnormalities caused by ion channel dysfunction.
Microstructural refinement and deformation twinning during severe plastic deformation of 316L stainless steel at high temperatures

The present work focuses on the severe plastic deformation and deformation twinning of 316L austenitic stainless steel deformed at high temperatures (700 and 800 °C) using equal channel angular extrusion (ECAE). Very high tensile and compressive strength levels were obtained after ECAE without sacrificing toughness with relation to microstructural refinement and deformation twinning. The occurrence of deformation twinning at such high temperatures was attributed to the effect of high stress levels on the partial dislocation separation, i.e., effective stacking fault energy. High stress levels were ascribed to the combined effect of dynamic strain aging, high strain levels (∈ ∼ 1.16) and relatively high strain rate (2 s^−1). At 800 °C, dynamic recovery and recrystallization took place locally leading to grains with fewer dislocation density and recrystallized grains, which in turn led to lower room temperature flow strengths than those from the samples processed at 700 °C but higher strain hardening rates. Apparent tension-compression asymmetry in the 700 °C sample was found to be the consequence of the directional internal stresses.
Biting mechanics and niche separation in a specialized clade of primate seed predators

We analyzed feeding biomechanics in pitheciine monkeys (Pithecia, Chiropotes, Cacajao), a clade that specializes on hard-husked unripe fruit (sclerocarpy) and resistant seeds (seed predation). We tested the hypothesis that pitheciine crania are well-suited to generate and withstand forceful canine and molar biting, with the prediction that they generate bite forces more efficiently and better resist masticatory strains than the closely-related Callicebus, which does not specialize on unripe fruits and/or seeds. We also tested the hypothesis that Callicebus-Pithecia-Chiropotes-Cacajao represent a morphocline of increasing sclerocarpic specialization with respect to biting leverage and craniofacial strength, consistent with anterior dental morphology. We found that pitheciines have higher biting leverage than Callicebus and are generally more resistant to masticatory strain. However, Cacajao was found to experience high strain magnitudes in some facial regions. We therefore found limited support for the morphocline hypothesis, at least with respect to the mechanical performance metrics examined here. Biting leverage in Cacajao was nearly identical (or slightly less than) in Chiropotes and strain magnitudes during canine biting were more likely to follow a Cacajao-Chiropotes-Pithecia trend of increasing strength, in contrast to the proposed morphocline. These results could indicate that bite force efficiency and derived anterior teeth were selected for in pitheciines at the expense of increased strain magnitudes. However, our results for Cacajao potentially reflect reduced feeding competition offered by allopatry with other pitheciines, which allows Cacajao species to choose from a wider variety of fruits at various stages of ripeness, leading to reduction in the selection for robust facial features. We also found that feeding biomechanics in sympatric Pithecia and Chiropotes are consistent with data on food structural properties and observations of dietary niche separation, with the former being well-suited for the regular molar crushing of hard seeds and the latter better adapted for breaching hard fruits.