Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Dynamics Simulations of A27S and K120A Mutated PTP1B Reveals Selective Binding of the Bidentate Inhibitor

Protein tyrosine phosphatase 1B (PTP1B) is considered a potential target for the treatment of type II diabetes and obesity due to its critical negative role in the insulin signaling pathway. However, improving the selectivity of PTP1B inhibitors over the most closely related T-cell protein tyrosine phosphatase (TCPTP) remains a major challenge for inhibitor development. Lys120 at the active site and Ser27 at the second pTyr binding site are distinct in PTP1B and TCPTP, which may bring differences in binding affinity. To explore the determinant of selective binding of inhibitor, molecular dynamics simulations with binding free energy calculations were performed on K120A and A27S mutated PTP1B, and the internal changes induced by mutations were investigated. Results reveal that the presence of Lys120 induces a conformational change in the WPD-loop and YRD-motif and has a certain effect on the selective binding at the active site. Ser27 weakens the stability of the inhibitor at the second pTyr binding site by altering the orientation of the Arg24 and Arg254 side chains via hydrogen bonds. Further comparison of alanine scanning demonstrates that the reduction in the energy contribution of Arg254 caused by A27S mutation leads to a different inhibitory activity. These observations provide novel insights into the selective binding mechanism of PTP1B inhibitors to TCPTP.
Mitochondria-encoded genes contribute to evolution of heat and cold tolerance in yeast

The mitochondrial genome is a hotspot for divergence in thermal growth differences in yeast. Genetic analysis of phenotypic differences between species is typically limited to interfertile species. Here, we conducted a genome-wide noncomplementation screen to identify genes that contribute to a major difference in thermal growth profile between two reproductively isolated yeast species, Saccharomyces cerevisiae and Saccharomyces uvarum. The screen identified only a single nuclear-encoded gene with a moderate effect on heat tolerance, but, in contrast, revealed a large effect of mitochondrial DNA (mitotype) on both heat and cold tolerance. Recombinant mitotypes indicate that multiple genes contribute to thermal divergence, and we show that protein divergence in COX1 affects both heat and cold tolerance. Our results point to the yeast mitochondrial genome as an evolutionary hotspot for thermal divergence.
The Localization Research of Brain Plasticity Changes after Brachial Plexus Pain: Sensory Regions or Cognitive Regions?

Objective Neuropathic pain after brachial plexus injury remains an increasingly prevalent and intractable disease due to inadequacy of satisfactory treatment strategies. A detailed mapping of cortical regions concerning the brain plasticity was the first step of therapeutic intervention. However, the specific mapping research of brachial plexus pain was limited. We aimed to provide some localization information about the brain plasticity changes after brachial plexus pain in this preliminary study. Methods 24 Sprague-Dawley rats received complete brachial plexus avulsion with neuropathic pain on the right forelimb successfully. Through functional imaging of both resting-state and block-design studies, we compared the amplitude of low-frequency fluctuations (ALFF) of premodeling and postmodeling groups and the changes of brain activation when applying sensory stimulation. Results The postmodeling group showed significant decreases on the mechanical withdrawal threshold (MWT) in the bilateral hindpaws and thermal withdrawal latency (TWL) in the left hindpaw than the premodeling group (P < 0.05). The amplitude of low-frequency fluctuations (ALFF) of the postmodeling group manifested increases in regions of the left anterodorsal hippocampus, left mesencephalic region, left dorsal midline thalamus, and so on. Decreased ALFF was observed in the bilateral entorhinal cortex compared to that of the premodeling group. The results of block-design scan showed significant differences in regions including the limbic/paralimbic system and somatosensory cortex. Conclusion We concluded that the entorhinal-hippocampus pathway, which was part of the Papez circuit, was involved in the functional integrated areas of brachial plexus pain processing. The regions in the “pain matrix” showed expected activation when applying instant nociceptive stimulus but remained silent in the resting status. This research confirmed the involvement of cognitive function, which brought novel information to the potential new therapy for brachial plexus pain.
Resmi ve Özel İlköğretim Okullarındaki Eğitici Kol Çalışmalarının Amaçlarına Ulaşma Düzeyine İlişkin Öğrenci Görüşleri (Kayseri İli Örneği)

Bu arastirma, devlet okullari ile ozel okullarin, Egitici Kol Calismalarinin amaclarina ulasmasinda, yeterlilik duzeylerini karsilastirmali olarak belirlemek amaciyla yapilmistir. Arastirmada soz konusu calismalarin yeterliliginin, ogrenci gozuyle degerlendirilmesi yapilmaya calisilmistir. Bu amacla da toplam 300 ogrenci uzerinde bir anket calismasi gerceklestirilmistir. Verilerin analizi SPSS paket programi ile t-testi uygulanarak yapilmistir. Verilerden elde edilen sonuclara gore; Egitici Kol Calismalarinin hem devlet okullarinda hem de ozel okullarda istenilen duzeyde ve nitelikte yapilmadigi saptanmistir. Ayrica grupla calisma zevki asilama, planli ve duzenli calisma aliskanligi kazandirma, demokratik tutum ve aliskanliklar kazandirma gibi konularda, ozel okullarin devlet okullarindan daha dusuk etkililik duzeyinde oldugu belirlenmistir
The Emerging Role of Estrogens in Thyroid Redox Homeostasis and Carcinogenesis

Reactive oxygen species (ROS) are the most critical class of free radicals or reactive metabolites produced by all living organisms. ROS regulate several cellular functions through redox-dependent mechanisms, including proliferation, differentiation, hormone synthesis, and stress defense response. However, ROS overproduction or lack of appropriate detoxification is harmful to cells and can be linked to the development of several diseases, such as cancer. Oxidative damage in cellular components, especially in DNA, can promote the malignant transformation that has already been described in thyroid tissue. In thyrocyte physiology, NADPH oxidase enzymes produce large amounts of ROS that are necessary for hormone biosynthesis and might contribute to the high spontaneous mutation rate found in this tissue. Thyroid cancer is the most common endocrine malignancy, and its incidence is significantly higher in women than in men. Several lines of evidence suggest the sex hormone estrogen as a risk factor for thyroid cancer development. Estrogen in turn, besides being a potent growth factor for both normal and tumor thyroid cells, regulates different mechanisms of ROS generation. Our group demonstrated that the thyroid gland of adult female rats exhibits higher hydrogen peroxide (H2O2) production and lower enzymatic antioxidant defense in comparison with male glands. In this review, we discuss the possible involvement of thyroid redox homeostasis and estrogen in the development of thyroid carcinogenesis.
Tongue coating microbiome data distinguish patients with pancreatic head cancer from healthy controls

ABSTRACT Background: The microbiota plays a critical role in the process of human carcinogenesis. Pancreatic head carcinoma (PHC)-associated tongue coating microbiome dysbiosis has not yet been clearly defined.Objective: Our aim is to reveal the bacterial composition shifts in the microbiota of the tongue coat of PHC patients.Design: The tongue coating microbiota was analyzed in 30 PHC patients and 25 healthy controls using 16S rRNA gene sequencing technology.Results: The microbiome diversity of the tongue coat in PHC patients was significantly increased, as shown by the Shannon, Simpson, inverse Simpson, Obs and incidence-based coverage estimators. Principal component analysis revealed that PHC patients were colonized by remarkably different tongue coating microbiota than healthy controls and liver cancer patients. Linear discriminant analysis effect size revealed that Leptotrichia, Fusobacterium,Rothia, Actinomyces, Corynebacterium, Atopobium, Peptostreptococcus, Catonella, Oribacterium, Filifactor, Campylobacter, Moraxella and Tannerella were overrepresented in the tongue coating of PHC patients, and Haemophilus, Porphyromonas and Paraprevotella were enriched in the tongue coating microbiota of healthy controls. Strikingly, Haemophilus, Porphyromonas, Leptotrichia and Fusobacterium could distinguish PHC patients from healthy subjects, and Streptococcus and SR1 could distinguish PHC patients from liver cancer patients. Conclusions: These findings identified the microbiota dysbiosis of the tongue coat in PHC patients, and provide insight into the association between the human microbiome and pancreatic cancer.
Monitoring Vaginal Electrical Resistance, Follicular Waves, and Hormonal Profile During Oestrous Cycle in the Transition Period in Bangladeshi Sheep

Abstract Introduction: The ovarian follicular dynamics, vaginal electrical resistance (VER), progesterone (P4) and oestrogen (E2) profiles were investigated during the oestrous cycle in four indigenous ewes. Material and Methods: Daily VER values were recorded with a heat detector. The follicles were observed and measured by trans-rectal ultrasonography. Blood was collected daily for hormonal profiles. Results: A significant variation in VER values (P < 0.05) in oestrus by ewes and position in the sequence of cycles was observed. Trans-rectal ultrasonography of ovaries revealed the presence of 2–4 waves of follicular growth. Study of hormonal profiles by ELISA revealed a positive correlation between E2 concentration and development of follicles and a negative correlation between P4 concentration and their development. The concentrations of oestradiol increased in oestrus and then decreased to a basal level. Follicular growth was accompanied by a rise in the concentration of serum oestradiol. Inversely, when follicles received the stimulation for ovulation, concentration of progesterone started to fall, but after ovulation, it climbed back to its peak and remained at this state until next ovulatory follicle reached its maximum diameter. Conclusion: This study could help to set up a manipulative reproductive technique for improving genetic values in indigenous sheep.
Association between angiotensinogen T174M polymorphism and the risk of diabetic nephropathy: A meta-analysis

Objective: Although the angiotensinogen (AGT) gene T174M polymorphism has been implicated in the pathogenesis of diabetic nephropathy (DN), study results have been inconsistent. The present meta-analysis was conducted to determine the correlation of AGT T174M polymorphism with DN. Methods: We retrospectively extracted relevant studies from Embase as well as PubMed databases. Additionally, a fixed- or random-effects model was employed for calculation of pooled odds ratio (OR) along with 95% confidence interval (CI). Results: In total, we identified six studies (1179 cases and 927 controls) regarding the AGT gene T174M polymorphism. The pooled ORs for the association between the AGT T174M polymorphism and DN risk were not statistically significant under all genetic models (M vs T: OR = 1.22, 95% CI = 0.84–1.75; MM vs TT: OR = 1.94, 95% CI = 0.93–4.04; MT vs TT: OR = 1.11, 95% CI = 0.76–1.63; the dominant model: OR =1.19, 95% CI = 0.80–1.77; the recessive model: OR = 1.94, 95% CI = 0.93–4.03). Subgroup analyses based on the type of race showed the M allele of the AGT T174M polymorphism increased DN risk in Asians, but not in Caucasians. Conclusions: Our study indicated that the T174M polymorphism in the AGT gene was associated with DN in Asians.
Occurrence of Reovirus (ARV) Infections in Poultry Flocks in Poland in 2010–2017

Abstract Introduction: Avian reovirus (ARV) infections in poultry populations are reported worldwide. The reovirus belongs to the genus Orthoreovirus, family Reoviridae. The aim of the study was to evaluate the incidence of ARV infections in the poultry population based on diagnostic tests performed in 2010–2017. Material and Methods: Samples of the liver and spleen were collected from sick birds suspected of ARV infection and sent for diagnostics. Isolation was performed in 5–7-day-old SPF chicken embryos infected into the yolk sac with homogenates of internal organs of sick birds. Four primer pairs were used to detect the σNS, σC, σA, and µA ARV RNA gene fragments. A nested PCR was used for the detection of the σNS and σC genes. Results: In 2010–2017, ARV infection was found in birds from 81 flocks of broiler chickens and/or layers, 8 flocks of slaughter turkeys, and in 4 hatchery embryos at 17–20 days of incubation. The primers used in RT-PCR and nested PCR did not allow effective detection of ARV RNA in all virus-positive samples. Conclusion: The problem of ARV infections in the poultry population in Poland still persist. The primers used for various ARV segments in RT-PCR and nested PCR did not allow effective detection of RNA in the visceral organs of sick birds. The presented results confirm the necessity of using classical diagnostic methods (isolation in chicken embryos, AGID).
Tumor Treating Fields for Glioblastoma Treatment: Patient Satisfaction and Compliance With the Second-Generation Optune® System

Background: Tumor treating fields (TTFields) are a non-invasive antimitotic therapy that delivers alternating electric fields via the Optune® system. The Phase III EF-14 trial in newly diagnosed glioblastoma multiforme (GBM) showed significantly improved progression-free, overall and long-term survival when Optune was used together with maintenance temozolomide (TMZ) compared with TMZ alone. Compliance (average monthly use) was associated with better clinical outcome. The first-generation Optune system weighed approximately 6 pounds (~2.7 kg). The second-generation redesigned Optune system weighs 2.7 pounds (~1.2 kg). We tested and compared GBM patient experience with the second-generation system versus the first-generation system. Methods: Ten newly diagnosed and recurrent GBM patients in Germany (median age: 52.9 years [31-79]) were prospectively monitored over the first month of transitioning from the first-generation to the second-generation Optune system. Questionnaires using a numerical analog scale assessed feedback at baseline (first generation) and after 1 month of second-generation use. Results: After transitioning to the second-generation system, compliance improved by more than 10% in four patients, was maintained in five patients and decreased by more than 10% in one patient. Following transition, eight out of nine patients reported a reduction in the triggering of malfunction alarms. Self-reported patient feedback showed improved handling and portability (weight, mobility) of the second- versus the first-generation Optune system. Conclusions: This patient user survey suggests that patient satisfaction with the second-generation Optune system is improved versus the first-generation system. Improved features of the new system help patients achieve and maintain a higher rate of treatment compliance.
Urinary Neurotransmitter Anaiysis as a Biomaricer for Psychiatric Disorders

In a recent article by Cook (2008), an outline of desirable characteristics of biomarkers in psychiatry was described. Cook (2008) stated that certain criteria must be met for a biomarker to be considered for psychiatric management. First, the biomarker must be timely, clinically useful, and cost-effective. Second, the technology needed to assess the biomarker must be well tolerated by the target patient population. Third, methods that can be easily integrated into the practitioner's current practice patterns are more likely to be accepted than those that require a major change in the delivery of care. These criteria are mentioned here as a prelude for an innovative technology that both satisfies psychiatric biomarker requirements and significantly
Bank Runs and Moral Hazard: A Review of Deposit Insurance

Deposit insurance is a widely adopted policy to promote financial stability in the banking sector. Deposit insurance helps ensure depositor confidence in the financial system and prevents contagious bank runs, but it also comes with an unintended consequence of encouraging banks to take on excessive risk. In this chapter, we begin with a review of the economic costs and benefits associated with deposit insurance. Drawing on the recent literature, we then review and discuss optimal deposit insurance design and risk-based pricing of insurance premiums. Finally, we discuss the impact of the larger institutional environment on how well deposit insurance schemes work in practice.
Behavioural context regulates dual function of ultrasonic hearing in lesser waxmoths : bat avoidance and pair formation

Ultrasonic hearing in moths evolved to detect bat echolocation cries and has been co-opted into the mating system of some species. Some moths evade or approach ultrasonic stimuli that overlap in their spectral and temporal features. The present study addressed the evaluation of ultrasonic stimuli by lesser waxmoths, a species in which ultrasonic hearing functions in bat evasion and pair formation. Playback experiments show that the role of different stimulus features varies with behavioural context. Flying moths have a single evasive response, which is performed mainly on the basis of pulse length and stimulus power: they dive upon hearing loud pulses 1ms in length, and respond more strongly to high-power stimuli above that pulse length. Female moths walking on the ground respond with positive phonotaxis mainly on the basis of pulse rate by orienting toward pulses delivered at rates 30 pulses s . Consequently, moths on the ground approach stimuli that elicit evasion when detected in flight. However, the different responses given to stimulus features by flying and walking moths match the distinguishing features of bat cries and conspecific males in both contexts. Stimulus evaluation, modified by behavioural context, gives lesser waxmoths the flexibility to show appropriate evasion or approach responses to stimuli that overlap in their features.
Towards the Use of Cultural Indicators in Planning for Vibrant Activity Centres

Across Australia, capital cities are developing strategies for Activity Centres where increased housing density and improved employment opportunities are supported by high-quality public services and facilities. The recent Moreland Activity Centre and Housing Strategy (MACHS) identified the need for Activity Centre planning to consider economic, social, environmental and cultural benefits, and sought to develop indicators across these domains. In recognising the importance of cultural vitality within Activity Centres, Moreland City Council's cross-functional working group and consultant team considered the interplay between cultural factors and planning considerations, including the correlation between cultural vitality, built form and particular place conditions. This paper touches on some of the questions that council staff and consultants engaged with during the development of the Moreland Activity Centre and Housing Strategy. It includes some key challenges and possible solutions for planning and enlivening Activity Centres in order to meet cultural as well as social, economic and environmental aims.
Universal coefficient theorems for generalized homology and stable cohomotopy.

We show that if h is a nice (e.g. representable) homology functor and G is an Abelian group, then there is a cohomology functor k(X; G) which is a "quasi-functor" of G and a short exact sequence 0 —•> Ext (h(ΣX), G) —•> k(X; G) —> Horn (h(X), G) —> 0 which is natural in X, "strongly quasi-natural" in G, and split if two additional conditions are satisfied. If, for example, h(X) = H n{X), then k(X; G) = Hn(X; G), and we obtain a proof of the ordinary Universal Coefficient Theorem which does not descend to the chain level but which does make heavy use of Brown's Representability Theorem [2]. After setting up the machinery and proving some technical results in § 1, we derive in § 2 quasinaturality and, with suitable restrictions, splitting of the sequence. The construction of k(X; G) involves an injective resolution of G. We show (2.8) that k(X; G) is independent (up to non-canonical isomorphism) of the resolution chosen and we remark (in 2.12) that there is a particular injective resolution Γ(G) which is even functorial. In § 3 we prove a corresponding Universal Coefficient Theorem for stable cohomotopy. We construct (3.8) the following short exact sequence for finitely generated G and finite dimensional X
Design and development of a small scale 12S-14P outer rotor HEFSM

Simulation, prototype experimental, and mathematical modelling is an essential process to provide sufficient evidence before a full-scale development or mass production. Hence, this study focuses on validating a small scale of 12S-14P outerrotor hybrid excitation flux switching motor (OR-HEFSM) through simulation, experimental, and mathematical modelling. The JMAG-Designer software as finite element solver is used to design and analyse the designed geometry structure. Throughout simulation process, the rotor design with direct drive structure as illustrated in Appendix A is chosen based on optimisation process. Thus, the generated back EMF, torque, and power through simulation at a speed of 1,200 r/min is 6.58 V, 16.4 Nm, and 12.4 kW, correspondingly. The designed model has been fabricated using actual prototype analysis (APA) approach, which is involves five stages, namely 3-D design, material selection, fabrication, assembly, and experimental test. The computer-aided software of SolidWorks is used to implement the first stage of APA while the prototype structure is fabricated using a computer numerical control (CNC) machine. The prototype has been tested experimentally using a measurement tool such as Fluke Analyser and oscilloscope. The back EMF showed a good agreement between simulation and preliminary experimental results with percentage differences approximately 5.1% at a speed of, 1,200 r/min. In contrast with the prediction results based on mathematical modelling using sizing equation, the calculated back EMF, torque, and power is 7.58%, 8.6%, and 8.4% higher than simulation results, respectively. Even so, the results had proven that the concept of three-phase working principle for small-scale 12S-14P OR-HEFSM with direct drive structure remained the same for simulation, experiment, and prediction.
Late to the parade

We undertake an examination of southern state legislators who changed their party affiliation between 1992 and 2012. Not surprisingly, the vast majority went from being Democrats to Republicans, and this change has fuelled the dynamics at the national level by pulling the Republican Party further to the right and Democrats to the left. Hence, these are the incumbent party switchers we evaluate. With the use of constituency, electoral and contextual data on both switchers and non-switchers, we assess which factors influence the likelihood that a Democratic office-holder will switch to the GOP (Grand Old Party). We find that the typical demographic correlates of southern Republicanism, such as race and education, do indeed have a significant effect on the probability of the GOP label being adopted. In addition, the disruptive effect of redistricting induces switches, as does a change in the party of the elected governor. However, electoral pressure does not have an independent effect on party switching. Our results suggest that party switching is a response to several district-level factors as well as the broader political context within the state. We conclude with a discussion of why increasing partisan polarization and the maturation of the southern GOP is likely to forestall future party switching.