Miracle-dz/UniFAR-FTUs huggingface dataset:
Understanding the Care Needs and Profile of People Living at Home With Moderate to Advanced Stage Parkinson Disease

Background: In the United Kingdom, people with Parkinson disease (PD) and atypical parkinsonism will require more support with their care needs as the condition progresses. There are few data on the nature of care input required and the amount of informal and formal care needed by people with PD to enable them to remain within their own home. Method: All people with moderate to advanced stage (Hoehn and Yahr III-V) idiopathic PD and atypical parkinsonism under the care of the Northumbria Healthcare NHS Foundation Trust PD service and living in their own home were invited to take part in The Northumbria Care Needs Project, a 10-year prospective longitudinal study. At baseline, data regarding formal (paid) personal and domestic care input and use of respite care, sitting services, and day centers were collected. We also collected data on patient cognitive disability, functional disability, and disease severity and informal carer tasks. Results: Of 162 people with PD included in the study, only 25.2% accessed formal domestic care and the same proportion formal personal care. In contrast, 80.2% identified an informal carer who helped with these tasks. Despite greater level of functional disability in those with an informal carer, levels of formal personal care input were similar to those with and without a formal carer. Levels of formal domestic carer input were higher in those without an informal carer. Conclusions: Use of formal care services was relatively uncommon in our cohort and much of the burden of caring appears to be being met by informal carers.
Deep mutational analysis reveals functional trade-offs in the sequences of EGFR autophosphorylation sites

Significance Phosphorylation of tyrosine residues in the cytoplasmic tail of the epidermal growth factor receptor (EGFR) by its kinase domain propagates a rich variety of information downstream of growth factor binding. The amino acid sequences surrounding each phosphorylation site encode the extent of phosphorylation as well as the extent of binding by multiple effector proteins. By profiling the kinase activity of EGFR alongside the binding specificities of an SH2 domain and a PTB domain for thousands of defined phosphorylation site sequences, we discovered that the sequences surrounding the phosphorylation sites in EGFR are not optimal and that discrimination against phosphorylation by cytoplasmic tyrosine kinases such as c-Src and c-Abl is likely to have shaped the evolution of these sequences. Upon activation, the epidermal growth factor receptor (EGFR) phosphorylates tyrosine residues in its cytoplasmic tail, which triggers the binding of Src homology 2 (SH2) and phosphotyrosine-binding (PTB) domains and initiates downstream signaling. The sequences flanking the tyrosine residues (referred to as “phosphosites”) must be compatible with phosphorylation by the EGFR kinase domain and the recruitment of adapter proteins, while minimizing phosphorylation that would reduce the fidelity of signal transmission. To understand how phosphosite sequences encode these functions within a small set of residues, we carried out high-throughput mutational analysis of three phosphosite sequences in the EGFR tail. We used bacterial surface display of peptides coupled with deep sequencing to monitor phosphorylation efficiency and the binding of the SH2 and PTB domains of the adapter proteins Grb2 and Shc1, respectively. We found that the sequences of phosphosites in the EGFR tail are restricted to a subset of the range of sequences that can be phosphorylated efficiently by EGFR. Although efficient phosphorylation by EGFR can occur with either acidic or large hydrophobic residues at the −1 position with respect to the tyrosine, hydrophobic residues are generally excluded from this position in tail sequences. The mutational data suggest that this restriction results in weaker binding to adapter proteins but also disfavors phosphorylation by the cytoplasmic tyrosine kinases c-Src and c-Abl. Our results show how EGFR-family phosphosites achieve a trade-off between minimizing off-pathway phosphorylation and maintaining the ability to recruit the diverse complement of effectors required for downstream pathway activation.
T‐cell subset differentiation and antibody responses following antiretroviral therapy during simian immunodeficiency virus infection

Antiretroviral therapy (ART) for the treatment of human immunodeficiency virus (HIV) infection represents a major breakthrough in the treatment of HIV/acquired immune‐deficiency syndrome. However, it remains unclear how ART influences virus‐specific immune responses and understanding this is important for developing novel cure and eradication interventions for HIV‐1. In the present study, we evaluate how ART impacts T‐cell and antibody responses in simian immunodeficiency virus (SIV) ‐infected rhesus macaques. We evaluated CD4 and CD8 T‐cell responses by multiparameter flow cytometry, viral loads by quantitative RT‐PCR by a two‐step process using SIV‐specific primers and antibody neutralization function by luciferase‐based TZM‐bl assays. We demonstrate that macaques treated with ART exhibit phenotypic and qualitative effects on T‐cell and antibody responses. Macaques on ART exhibited low numbers of virus‐specific T‐cell responses, and these responses appeared to be partially biased towards central memory subsets. More importantly, there were significantly reduced neutralizing antibody responses in macaques treated with ART. Collectively, these data improve the understanding of how virus‐specific immune responses are generated during ART, and suggest the potential importance of therapeutic vaccines to maintain adaptive immunity during treated infection.
Contextual influences in decoding pain expressions: effects of patient age, informational priming, and observer characteristics

Abstract We aimed to examine the effects of contextual factors (ie, observers' training background and priming texts) on decoding facial pain expressions of younger and older adults. A total of 165 participants (82 nursing students and 83 nonhealth professionals) were randomly assigned to one of 3 priming conditions: (1) information about the possibility of secondary gain (misuse); (2) information about the frequency and undertreatment of pain in the older adult (undertreatment); or (3) neutral information (control). Subsequently, participants viewed 8 videos of older adults and 8 videos of younger adults undergoing a discomforting physical therapy examination. Participants rated their perception of each patient's pain intensity, unpleasantness, and condition severity. They also rated their willingness to help, sympathy level, patient deservingness of financial compensation, and how negatively/positively they feel towards the patient (ie, valence). Results demonstrated that observers ascribed greater levels of pain and other indicators (eg, sympathy and help) to older compared with younger patients. An interaction between observer type and patient age demonstrated that nursing students endorsed higher ratings of younger adults' pain compared with other students. In addition, observers in the undertreatment priming condition reported more positive valence towards older patients. By contrast, priming observers with the misuse text attenuated their valence ratings towards younger patients. Finally, the undertreatment prime influenced observers' pain estimates indirectly through observers' valence towards patients. In summary, results add specificity to the theoretical formulations of pain by demonstrating the influence of patient and observer characteristics, as well as informational primes, on decoding pain expressions.
Interaction of a Preventative Fungicide Treatment and Root Rot Pathogen on Ambrosia Beetle Attacks during a Simulated Flood Event

Flooding can increase tree susceptibility to root rot pathogens as well as attacks by ambrosia beetles attracted to stress-induced ethanol emissions. The objective of this study was to investigate the interaction of a preventative fungicide treatment and root infection with Phytophthora cinnamomi on ambrosia beetle attacks in flood stressed trees. A fungicide (Pageant® Intrinsic®) was evaluated in two flood trials using Eastern redbud and tulip poplar trees with treatments including the fungicide with or without pathogen or no fungicide with or without pathogen. Fungicide treated trees had fewer ambrosia beetle attacks, particularly in trees without P. cinnamomi co-infection. In a follow-up experiment, ethanol content was evaluated in flooded redbuds to determine if the fungicide treatment reduced stress-induced compounds. All flood stressed trees began producing ethanol within 24 h post flooding, regardless of fungicide treatment or P. cinnamomi infection. We conclude that pre-treatments of a fungicide can provide protection from ambrosia beetle attacks during an extreme flood event, but that protection is reduced if a root rot pathogen is also present. Additionally, rejection of fungicide treated trees was not related to the absence of ethanol, as the fungicide-treated plants released ethanol in quantities similar to non-treated trees.
Implications of AMPK in the Formation of Epithelial Tight Junctions

Tight junctions (TJ) play an essential role in the epithelial barrier. By definition, TJ are located at the demarcation between the apical and baso-lateral domains of the plasma membrane in epithelial cells. TJ fulfill two major roles: (i) TJ prevent the mixing of membrane components; and (ii) TJ regulate the selective paracellular permeability. Disruption of TJ is regarded as one of the earliest hallmarks of epithelial injury, leading to the loss of cell polarity and tissue disorganization. Many factors have been identified as modulators of TJ assembly/disassembly. More specifically, in addition to its role as an energy sensor, adenosine monophosphate-activated protein kinase (AMPK) participates in TJ regulation. AMPK is a ubiquitous serine/threonine kinase composed of a catalytic α-subunit complexed with regulatory β-and γ-subunits. AMPK activation promotes the early stages of epithelial TJ assembly. AMPK phosphorylates the adherens junction protein afadin and regulates its interaction with the TJ-associated protein zonula occludens (ZO)-1, thereby facilitating ZO-1 distribution to the plasma membrane. In the present review, we detail the signaling pathways up-and down-stream of AMPK activation at the time of Ca2+-induced TJ assembly.
TIPE2 inhibits GC via regulation of cell proliferation, apoptosis and inflammation

Gastric cancer (GC), a type of gastric mucosal epithelium disease caused by common malignant tumors, has become a major threat to human health and survival. Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2) is a negative immune regulatory factor that is selectively expressed in immune organs, immune cells and various epithelial cells and serves an important role in the maintenance of human physiological immune homeostasis. In our preliminary study, we found that the expression of TIPE2 was downregulated or absent in GC tissues compared with normal gastric mucosa tissues, indicating that TIPE2 may play a significant role in the development of GC. To clarify the role of TIPE2 in the progression of human GC and to elucidate the underlying mechanism, the association between TIPE2 and phosphatidylinositol 3-kinase (PI3K)/AKT, the cell cycle, the caspase-related apoptosis pathway and the NF-κB signaling pathway were investigated through western blot and flow cytometric analysis. It was determined that TIPE2 inhibited GC cell proliferation mainly by reducing the expression of phosphorylated AKT and ERK, which caused subsequent inhibition of the PI3K-AKT and Ras-Raf-MEK-ERK1/2 signaling pathways. Additionally, we investigated the relationship between TIPE2 and GC and discovered that TIPE2 inhibited tumor progression via growth, apoptosis and inflammatory pathways. The results of the present study provided a theoretical basis for the development and application of TIPE2 as an antitumor agent.
Transferred electron amplifiers and oscillators

In some semiconductors the conduction band system has two minima separated by only a small energy, and the lower minimum has associated with it a smaller electron effective mass than the upper minimum. At high electric fields it should be possible to transfer electrons to the upper minimum where they will have a lower mobility. The conductivity of a homogeneous crystal bar can therefore decrease as the field is increased, and it is conceivable that a differential negative resistance could be obtained. The conditions needed for obtaining negative resistance are examined, and calculations made for GaSb and semi-insulating GaAs. It appears that negative resistances should be observable in both these materials.
Overexpression of HES6 has prognostic value and promotes metastasis via the Wnt/β-catenin signaling pathway in colorectal cancer

HES6 is a member of the hairy-enhancer of the split homolog family, which has been implicated in oncogenesis and cancer progression in a variety of human cancers, including prostate and breast cancer. However, its clinical significance and biological role in colorectal cancer (CRC) remain unclear. In the present study, the expression of HES6 was significantly upregulated in CRC cell lines and CRC tissues at both the mRNA and protein levels. The present study also reported high expression of HES6 in 138/213 (64.8%) paraffin-embedded archived CRC specimens. HES6 expression was significantly correlated with T classification (P<0.001), N classification (P=0.020), and distant metastasis (P<0.001). Patients with higher HES6 expression levels exhibited a reduced overall survival (P<0.001). In addition, a multivariate analysis revealed that the expression of HES6 may be a novel prognostic marker for the survival of patients with CRC. Furthermore, the present study demonstrated that ectopic expression of HES6 enhanced the migration and invasive abilities of CRC cells. These abilities were significantly inhibited upon knockdown of endogenous HES6 expression by specific short hairpin RNAs. Additionally, the present study reported that the effects of HES6 on metastasis may be associated with the activation of the Wnt/β-catenin signaling pathway. Collectively, the findings of the present study revealed that overexpression of HES6 played a key role in the progression of CRC, leading to a poor prognosis and clinical outcome.
Quantization distortion in pulse-count modulation with nonuniform spacing of levels

It is shown that the distortion introduced in a pulse-count-modulation system due to quantization can be minimized by nonuniform spacing of levels. Equations are derived for an arrangement of nonuniform level spacing that produces minimum distortion. It is also shown that minimum distortion is significantly less than distortion resulting from uniform quantization when the crest factor of the signal is greater than four.
Associations Between Hand Hygiene Education and Self-Reported Hand-Washing Behaviors Among Korean Adults During MERS-CoV Outbreak

Background. Hand washing is an effective way to prevent transmission of infectious diseases. Education and promotional materials about hand washing may change individuals’ awareness toward hand washing. Infectious disease outbreak may also affect individuals’ awareness. Aims. Our study aimed to examine associations between hand-washing education and self-reported hand-washing behaviors among Korean adults during the year of the Middle East respiratory syndrome (MERS) outbreak. Methods. Data from the 2015 Community Health Survey were used for this study. The total study population comprised 222,599 individuals who were older than 20 years of age. A multiple linear regression model was used to investigate associations between hand hygiene education and self-reported hand-washing behaviors. Subgroup analyses stratified by age, sex, income, and MERS outbreak regions were also performed. Results. Individuals who received hand-washing education or saw promotional materials related to hand washing had significantly higher scores for self-reported use of soap or sanitizer (β = 0.177, P < .0001) and self-reported frequency of hand washing (β = 0.481, P < .0001) than those who did not have such experiences. The effect of hand-washing education on self-reported behavior change was greater among older adults, women, and lower income earners. The effect of hand hygiene education on self-reported use of soap or sanitizer was similar regardless of whether the participants lived in MERS regions. Conclusion. Our findings emphasize the importance of education or promotions encouraging hand washing, especially for older adults, women, and lower income earners. In addition, MERS outbreak itself affected individuals’ awareness of hand-washing behaviors. Well-organized campaigns that consider these factors are needed to prevent infectious diseases.
Arecoline inhibits the growth of 3T3-L1 preadipocytes via AMP-activated protein kinase and reactive oxygen species pathways

The present study was designed to investigate the pathways involved in the effect of betel nut arecoline on cell viability in 3T3-L1 preadipocytes. Arecoline, but not arecaidine or guvacine, inhibited preadipocyte viability in a concentration- and time-dependent manner. Arecoline arrested preadipocyte growth in the G2/M phase of the cell cycle; decreased the total levels of cyclin-dependent kinase 1 (CDK1), p21, and p27 proteins; increased p53 and cyclin B1 protein levels; and had no effect on CDK2 protein levels. These results suggested that arecoline selectively affected a particular CDK subfamily. Arecoline inhibited AMP-activated protein kinase (AMPK) activity; conversely, the AMPK activator, AICAR, blocked the arecoline-induced inhibition of cell viability. Pre-treatment with the antioxidant, N-acetylcysteine, prevented the actions of arecoline on cell viability, G2/M growth arrest, reactive oxygen species (ROS) production, and the levels of CDK1, p21, p27, p53, cyclin B1, and phospho-AMPK proteins. These AMPK- and ROS-dependent effects of arecoline on preadipocyte growth may be related to the mechanism underlying the modulatory effect of arecoline on body weight.
Modified contra-wound helix circuits for high-power traveling-wave tubes

Experiments performed on modified forms of the Chodorow-Chu contra-wound helix circuit are presented with emphasis on those properties useful in the design of high voltage, high power traveling-wave tubes. Velocity and impedance measurements are shown for a fair range of pitches, crossover angles, wire widths, and wire thicknesses. Impedances are compared with those of a circuit having ideal fields (and the same phase and group velocities) and are found to be very good. Loading effects of glass and metal cylinders (envelopes), current paths, a second mode, and transitions from helix to waveguide are described. It is shown that periodic supports (stubs), used to make the structure much more rugged mechanically and capable of large heat dissipation, also increase the (already high) impedance almost as much as they decrease the group velocity, implying that the stubs add but little stored energy.
The Philosophy of PCM

Recent papers describe experiments in transmitting speech by PCM (pulse code modulation). This paper shows in a general way some of the advantages of PCM, and distinguishes between what can be achieved with PCM and with other broadband systems, such as large-index FM. The intent is to explain the various points simply, rather than to elaborate them in detail. The paper is for those who want to find out about PCM rather than for those who want to design a system. Many important factors will arise in the design of a system which are not considered in this paper.
ROS-mediated autophagy through the AMPK signaling pathway protects INS-1 cells from human islet amyloid polypeptide-induced cytotoxicity

Oligomerization of human islet amyloid polypeptide (hIAPP) is toxic and contributes to progressive reduction of β cell mass in patients with type 2 diabetes mellitus. Autophagy is a highly conserved homeostatic mechanism in eukaryotes. Previous studies have confirmed that hIAPP can promote autophagy in β cells, but the underlying molecular mechanism and cellular regulatory pathway of hIAPP-induced autophagy remains not fully elucidated. Accumulation of reactive oxygen species (ROS) causes hIAPP induced-β cell death. At present, little is known about the association between hIAPP-induced oxidative stress and autophagy in β cells. Therefore, the present study investigated the underlying molecular mechanism and regulatory pathway of hIAPP-induced autophagy. Transmission electron microscopy was used to observe the number of autophagosome in cells. Cell viability was determined by an MTT test. A 2′,7′-dichlorofluorescin diacetate assay was used to measure the relative levels of reactive ROS. Western blotting was used to detect expression of adenosine monophosphate-activated protein kinase (AMPK) and autophagic markers p62 and microtubule associated protein 1 light chain 3. The results demonstrated that hIAPP induces autophagy through ROS-mediated AMPK signaling pathway in INS-1 cells. Upregulation of autophagy by AMPK activator 5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside decreased ROS and malondialdehyde generation, whereas inhibition of autophagy by 3-methyladenine and AMPK inhibitor compound C aggravated hIAPP-induced oxidative stress and toxicity in INS-1 cells. Taken together, the present study suggested that hIAPP induces autophagy via a ROS-mediated AMPK signaling pathway. Furthermore, autophagy serves as a cell-protective mechanism against hIAPP-induced toxicity and chemical promotion of autophagy through AMPK signaling pathway attenuates hIAPP induced cytotoxicity and oxidative stress in INS-1 cells.