682 research outputs found

    Can Deep Learning Improve Technical Analysis of Forex Data to Predict Future Price Movements?

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    The foreign exchange market (Forex) is the world's largest market for trading foreign money, with a trading volume of over 5.1 trillion dollars per day. It is known to be very complicated and volatile. Technical analysis is the observation of past market movements with the aim of predicting future prices and dealing with the effects of market movements. A trading system is based on technical indicators derived from technical analysis. In our work, a complete trading system with a combination of trading rules on Forex time series data is developed and made available to the scientific community. The system is implemented in two phases: In the first phase, each trading rule, both the AI-based rule and the trading rules from the technical indicators, is tested for selection; in the second phase, profitable rules are selected among the qualified rules and combined. Training data is used in the training phase of the trading system. The proposed trading system was extensively trained and tested on historical data from 2010 to 2021. To determine the effectiveness of the proposed method, we also conducted experiments with datasets and methodologies used in recent work by Hernandez-Aguila et al., 2021 and by Munkhdalai et al., 2019. Our method outperforms all other methodologies for almost all Forex markets, with an average percentage gain of 20.2%. A particular focus was on training our AI-based rule with two different architectures: the first is a widely used convolutional network for image classification, i.e. ResNet50; the second is an attention-based network Vision Transformer (ViT). The results provide a clear answer to the main question that guided our research and which is the title of this paper

    The regions of the sequence most exposed to the solvent within the amyloidogenic state of a protein initiate the aggregation process.

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    Formation of misfolded aggregates is an essential part of what proteins can do. The process of protein aggregation is central to many human diseases and any aggregating event needs to be prevented within a cell and in protein design. In order to aggregate, a protein needs to unfold its native state, at least partially. The conformational state that is prone to aggregate is difficult to study, due to its aggregating potential and heterogeneous nature. Here, we use a systematic approach of limited proteolysis, in combination with electrospray ionisation mass spectrometry, to investigate the regions that are most flexible and solvent-exposed within the native, ligand-bound and amyloidogenic states of muscle acylphosphatase (AcP), a protein previously shown to form amyloid fibrils in the presence of trifluoroethanol. Seven proteases with different degrees of specificity have been used for this purpose. Following exposure to the aggregating conditions, a number of sites along the sequence of AcP become susceptible to proteolytic digestion. The pattern of proteolytic cleavages obtained under these conditions is considerably different from that of the native and ligand-bound conformations and includes a portion within the N-terminal tail of the protein (residues 6-7), the region of the sequence 18-23 and the position 94 near the C terminus. There is a significant overlap between the regions of the sequence found to be solvent-exposed from the present study and those previously identified to be critical in the rate-determining steps of aggregation from protein engineering approaches. This indicates that a considerable degree of solvent exposure is a feature of the portions of a protein that initiate the process of aggregation

    Heat Sensing Receptor TRPV1 Is a Mediator of Thermotaxis in Human Spermatozoa

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    The molecular bases of sperm thermotaxis, the temperature-oriented cell motility, are currently under investigation. Thermal perception relies on a subclass of the transient receptor potential [TRP] channels, whose member TRPV1 is acknowledged as the heat sensing receptor. Here we investigated the involvement of TRPV1 in human sperm thermotaxis. We obtained semen samples from 16 normozoospermic subjects attending an infertility survey programme, testis biopsies from 6 patients with testicular germ cell cancer and testis fine needle aspirates from 6 patients with obstructive azoospermia undergoing assisted reproductive technologies. Expression of TRPV1 mRNA was assessed by RT-PCR. Protein expression of TRPV1 was determined by western blot, flow cytometry and immunofluorescence. Sperm motility was assessed by Sperm Class Analyser. Acrosome reaction, apoptosis and intracellular-Ca2+ content were assessed by flow cytometry. We found that TRPV1 mRNA and protein were highly expressed in the testis, in both Sertoli cells and germ-line cells. Moreover, compared to no-gradient controls at 31°C or 37°C (Ctrl 31°C and Ctrl 37°C respectively), sperm migration towards a temperature gradient of 31-37°C (T gradient) in non-capacitated conditions selected a higher number of cells (14,9 ± 4,2×106 cells T gradient vs 5,1± 0,3×106 cells Ctrl 31°C and 5,71±0,74×106 cells Ctrl 37°C; P = 0,039). Capacitation amplified the migrating capability towards the T gradient. Sperms migrated towards the T gradient showed enriched levels of both TRPV1 protein and mRNA. In addition, sperm cells were able to migrate toward a gradient of capsaicin, a specific agonist of TRPV1, whilst capsazepine, a specific agonist of TRPV1, blocked this effect. Finally, capsazepine severely blunted migration towards T gradient without abolishing. These results suggest that TRPV1 may represent a facilitating mediator of sperm thermotaxis

    Genetic and molecular diagnostics of male infertility in the clinical practice.

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    Male infertility represents one of the clearest examples of complex phenotype with substantial genetic basis. It is indeed well established that genetic causes account for 10-15% of infertility cases, including chromosomal abnormalities and single-gene mutations. However, a large proportion of infertile males does not receive a clear diagnosis and thus they are reported as idiopathic or unexplained. Male (in)fertility is commonly based on standard semen analysis, which, however, cannot clearly distinguish fertile from infertile populations and therefore fails to detect any abnormality in many cases. Abnormal sperm function or specific molecular defects can be hypothesized in these cases. This review considers practical genetic and molecular diagnostic tests for male infertility, reporting on the most frequent genetic causes of male infertility and on the pros and cons of most commonly used techniques for genetic, molecular and functional sperm evaluation. Finally, this review will discuss recent advances in pharmacogenetics and new developments on sperm analysis that will form the basis for future research

    Is there any clinical relevant difference between non mosaic Klinefelter Syndrome patients with or without Androgen Receptor variations?

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    Klinefelter Syndrome (KS) is the most common chromosomal disorder in men leading to non-obstructive azoospermia. Spermatozoa can be found by TESE in about 50% of adults with KS despite severe testicular degeneration. We evaluated AR variations and polymorphism length in 135 non-mosaic KS patients, aimed to find possible correlation with clinical features, sex hormones and sperm retrieval. Among 135 KS patients we found AR variations in eight subjects (5.9%). All variations but one caused a single amino acid substitution. Four variations P392S, Q58L, L548F, A475V found in six patients had been previously described to be associated with different degrees of androgen insensitivity. Moreover we observed in two patients Y359F and D732D novel variations representing respectively a missense variation and a synonymous variation not leading to amino acid substitution. All the Klinefelter patients with AR gene variations were azoospermic. Spermatozoa were retrieved with TESE for two men (40%), sperm retrieval was unsuccessful in other 3 patients. This is the only study reporting AR variations in KS patients. Relevant clinical differences not emerged between AR mutated and not AR mutated KS patients, but does each variation play an important role in the trasmission to the offspring obtained by ART in this patients

    Spontaneous fertility and in vitro fertilization outcome: New evidence of human papillomavirus sperm infection

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    Objective To evaluate the reproductive outcome of infertile couples undergoing assisted reproduction techniques (ART) with or without human papillomavirus (HPV) semen infection. Design Cross-sectional clinical study. Setting Units of andrology, reproductive medicine, and gynecology. Patient(s) A total of 226 infertile couples. Intervention(s) Male partners were evaluated by means of fluorescence in situ hybridization (FISH) for HPV on semen. After a diagnostic period, female partners underwent intrauterine insemination (IUI) or intracytoplasmic sperm injection (ICSI). Main Outcome Measure(s) Seminal parameters and FISH analysis for HPV in sperm head. Spontaneous or assisted pregnancies, live births, and miscarriages were recorded. Statistical analysis included unpaired Student t test and chi-square test. Result(s) Fifty-four male partners (23.9%) had HPV semen infection confined to sperm, confined to exfoliated cells, or in both cells. During the diagnostic period, noninfected couples showed spontaneous pregnancies. IUI and ICSI treatments were performed in, respectively, 60 and 98 noninfected and in 21 and 33 infected couples, with 38.4% and 14.2% cumulative pregnancy rates, respectively. The follow-up of pregnancies showed a higher miscarriage rate in infected couples (62.5% vs. 16.7%). Ongoing pregnancies of the latter group were characterized by HPV infection confined to exfoliated cells. Conclusion(s) A reduction in natural and assisted cumulative pregnancy rate and an increase in miscarriage rate are related to the presence of HPV at sperm level. Although the exact mechanism by which sperm infection is able to impair fertility remains unclear, this aspect is worthy of further investigations. If confirmed, these results could change the clinical and diagnostic approach to infertile couples
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