Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of a Previously Unidentified Viral Protein in Porcine Circovirus Type 2-Infected Cells and Its Role in Virus-Induced Apoptosis

ABSTRACT Porcine circovirus type 2 (PCV2) is the causative agent of postweaning multisystemic wasting syndrome in pigs. In this study, transcription and translation of a novel viral gene (termed ORF3 here) was detected during productive infection of PCV2 in PK15 cells. The results of infection with ORF3-deficient PCV2 by site-directed mutagenesis indicated that the protein is not essential for viral replication. To investigate the underlying mechanism of cell death caused by replication of PCV2, apoptosis characterized by chromosomal condensation and fragmentation, formation of apoptotic bodies, and significant increase in hypodiploids were detected in infected cells. We further demonstrated that PCV2-induced apoptosis required the activation of caspase-8 but not caspase-9. The activation of caspase-8 results in the activation of caspase-3 as shown by an increase in the cleavage of the caspase substrate in the infected cells. To determine whether ORF3 protein could trigger apoptosis, ORF3 as well as ORF1 and ORF2 genes were transiently expressed in PK15 and Cos-7 cells for apoptotic activity assay. Transfection of cells with the ORF3 alone induced apoptosis using a pathway similar to that described in the context of viral infection. This is further confirmed by a significant decrease in apoptotic activity of infected cells in the absence of the ORF3 expression, suggesting that the protein plays a major role in the induction of virus-induced apoptosis. Altogether, these results indicate that ORF3 is a novel PCV2 protein that is not essential for viral replication in cultured cells but is involved in PCV2-induced apoptosis by activating caspase-8 and caspase-3 pathways.
SH2-B Is Required for Nerve Growth Factor-induced Neuronal Differentiation*

Nerve growth factor (NGF) is essential for the development and survival of sympathetic and sensory neurons. NGF binds to TrkA, activates the intrinsic kinase activity of TrkA, and promotes the differentiation of pheochromocytoma (PC12) cells into sympathetic-like neurons. Several signaling molecules and pathways are known to be activated by NGF, including phospholipase Cγ, phosphatidylinositol-3 kinase, and the mitogen-activated protein kinase cascade. However, the mechanism of NGF-induced neuronal differentiation remains unclear. In this study, we examined whether SH2-Bβ, a recently identified pleckstrin homology and SH2 domain-containing signaling protein, is a critical signaling protein for NGF. TrkA bound to glutathione S-transferase fusion proteins containing SH2-Bβ, and NGF stimulation dramatically increased that binding. In contrast, NGF was unable to stimulate the association of TrkA with a glutathione S-transferase fusion protein containing a mutant SH2-Bβ(R555E) with a defective SH2 domain. When overexpressed in PC12 cells, SH2-Bβ co-immunoprecipitated with TrkA in response to NGF. NGF stimulated tyrosyl phosphorylation of endogenous SH2-Bβ as well as exogenously expressed GFP-SH2-Bβ but not GFP-SH2-Bβ(R555E). Overexpression of SH2-Bβ(R555E) blocked NGF-induced neurite outgrowth of PC12 cells, whereas overexpression of wild type SH2-Bβ enhanced NGF-induced neurite outgrowth. Overexpression of either wild type or mutant SH2-Bβ(R555E) did not alter tyrosyl phosphorylation of TrkA, Shc, or phospholipase Cγ in response to NGF or NGF-induced activation of ERK1/2, suggesting that SH2-Bβ may initiate a previously unknown pathway(s) that is essential for NGF-induced neurite outgrowth. Taken together, these data indicate that SH2-Bβ is a novel signaling molecule required for NGF-induced neuronal differentiation.
The UWB Channel in Medical Wireless Body Area Networks (WBANs)

UWB is a technology that has several advantages when considered for a Wireless Body Area Network (WBAN). A WBAN is a network with its communications devices in very close proximity to the human body. In medical applications these devices are connected to sensors that can monitor vital signs such as ECG, temperature, and mobility. A WBAN allows for the remote monitoring of a patient’s health minimizing the number of cables needed. The monitoring of vital signals usually require a relatively low data-rate which in the case of UWB translates into very small transmitting power, long battery life, and less potential side effects caused by electromagnetic radiation. All of these features are very desirable for devices that are close to the body and meant to be used for extended periods of time.
Increases in Thyroid Cancer Incidence and Mortality.

stimulus for stalled late-stage development. The assessments of novelty used in this analysis were based on publicly available information and may differ from the FDA’s determination. Companies may not have responded to the voucher incentive because its value is uncertain: the value decreases as more vouchers become available on the market.5 Since 2007, Congress has expanded the number of voucher programs so that vouchers can now also be awarded for new treatments for rare pediatric diseases and medical countermeasures. An improved incentive scheme would reduce the risk of neglected tropical disease product development such as by decreasing the cost of clinical trials to pharmaceutical companies. A publicprivate partnership could provide financial support to sponsors of neglected tropical disease products. The partnership could be actively managed to ensure reasonable cost and access to the end product, unlike the priority review voucher, which does not require companies to make products widely available to patients.
Localization of the 12.6-kDa FK506-binding Protein (FKBP12.6) Binding Site to the NH2-terminal Domain of the Cardiac Ca2+ Release Channel (Ryanodine Receptor)*

The 12.6-kDa FK506-binding protein (FKBP12.6) interacts with the cardiac ryanodine receptor (RyR2) and modulates its channel function. However, the molecular basis of FKBP12.6-RyR2 interaction is poorly understood. To investigate the significance of the isoleucine-proline (residues 2427–2428) dipeptide epitope, which is thought to form an essential part of the FKBP12.6 binding site in RyR2, we generated single and double mutants, P2428Q, I2427E/P2428A, and P2428A/L2429E, expressed them in HEK293 cells, and assessed their ability to bind GST-FKBP12.6. None of these mutations abolished GST-FKBP12.6 binding, indicating that this isoleucine-proline motif is unlikely to form the core of the FKBP12.6 binding site in RyR2. To systematically define the molecular determinants of FKBP12.6 binding, we constructed a series of internal and NH2- and COOH-terminal deletion mutants of RyR2 and examined the effect of these deletions on GST-FKBP12.6 binding. These deletion analyses revealed that the first 305 NH2-terminal residues and COOH-terminal residues 1937–4967 are not essential for GST-FKBP12.6 binding, whereas multiple sequences within a large region between residues 305 and 1937 are required for GST-FKBP12.6 interaction. Furthermore, an NH2-terminal fragment containing the first 1937 residues is sufficient for GST-FKBP12.6 binding. Co-expression of overlapping NH2 and COOH-terminal fragments covering the entire sequence of RyR2 produced functional channels but did not restore GST-FKBP12.6 binding. These data suggest that FKBP12.6 binding is likely to be conformationdependent. Binding of FKBP12.6 to the NH2-terminal domain may play a role in stabilizing the conformation of this region.
Electrostatic discharge test with simulated coverglass flashover for multi-junction GaAs/Ge solar array design

Space Systems/Loral (SS/L) successfully completed electrostatic discharge (ESD) tests of Multi-junction (MJ) GaAs/Ge solar array design in geosynchronous space environment. This ESD test was based on ISO-11221, Space systems - Space solar panels -Spacecraft Charging Induced Electrostatic Discharge Test Methods. In addition to the ISO reference for the test schematic, SS/L implemented modified test circuitry to better simulate the on-orbit operational conditions of our solar array design. The ESD test circuit also included simulated solar array panel coverglass flashover. The ESD test program utilized a 25-cell coupon that had been subjected to 2,000 thermal cycles caused by earth eclipses in GEO orbit and >12,000 thermal cycles caused by the shadow of the spacecraft antennas. Other ESD test coupons are 4-cell coupons that, after baseline ESD experiments, can later be subjected to combined space environmental exposures tests. To demonstrate design robustness, we performed ESD tests to voltages and currents that are higher than that of on-orbit solar array operational voltages and currents. This paper discusses the coverglass flashover simulation, ESD test setup, the importance of the electrical test design in simulating the on-orbit operational conditions, and the test results.
Corrupt Bandits for Privacy Preserving Input

We study a variant of the stochastic multi-armed bandit (MAB) problem in which the rewards are corrupted. In this framework, motivated by privacy preservation in online recommender systems, the goal is to maximize the sum of the (unobserved) rewards, based on the observation of transformation of these rewards through a stochastic corruption process with known parameters. We provide a lower bound on the expected regret of any bandit algorithm in this corrupted setting. We devise a frequentist algorithm, KLUCB-CF, and a Bayesian algorithm, TS-CF and give the upper bounds on their regret. We also provide the appropriate corruption parameters to guarantee a desired level of differential privacy and analyze how this impacts the regret. Finally, we present the experimental results which confirm our analysis.
Psychiatric comorbidity and suicide risk in adolescents with chronic daily headache

Objectives: To investigate the prevalence and correlates of comorbid psychiatric disorders and suicidal risk in community-based adolescents with chronic daily headache (CDH). Methods: We identified and recruited 122 adolescents with CDH from a non-referral student sample (n = 7,900). CDH subtypes were classified according to the most updated criteria of the International Classification of Headache Disorders, 2nd edition (ICHD-2). An in-person psychiatric interview was performed with each subject with CDH to assess depressive and anxiety disorders and suicidal risk based on the Mini-International Neuropsychiatric Interview–Kid (MINI-Kid). Clinical correlates and impacts were investigated. Results: A total of 121 subjects (31 male/90 female, mean age 13.8 years) finished the psychiatric interview. Fifty-seven subjects (47%) had ≥1 assessed psychiatric comorbidity with major depression (21%) and panic disorder (19%) as the two most common diagnoses. Current suicidal risk was assessed as high (score ≥ 10) in 20% of subjects. Female gender and older age were associated with depressive disorders. Presence of migraine was associated with psychiatric comorbidities (OR = 3.5, p = 0.002). The associations with psychiatric disorders were stronger for migraine with aura than for migraine without aura. Migraine with aura also independently predicted a high suicidal risk (score ≥ 10) (adjusted OR = 6.0, p = 0.028). In contrast, CDH subtypes, headache frequencies, or medication overuse were not correlated. Comorbid psychiatric disorders were not related to physician consultations or more days of sick leave. Conclusions: This community-based study showed high comorbidity of psychiatric disorders and suicidal risk in adolescents with chronic daily headache. The presence of migraine attacks, especially migraine with aura, was the major predictor for these associations.
Bacterial Decontamination of Water by Bipolar Pulsed Discharge in a Gas&#8211;Liquid&#8211;Solid Three-Phase Discharge Reactor

Inactivation of Escherichia coli by bipolar pulsed discharge in an air-liquid-solid three-phase discharge reactor has been investigated. The effect of several operating parameters on the inactivation efficiency has also been studied. Experimental results showed that bipolar pulsed discharge in the three-phase discharge plasma reactor had good performance in the inactivation of E. coli. Power intensity and gas flow rate had a positive effect on the inactivation, while the initial solution conductivity had little effect. An alkaline solution condition was favorable for the inactivation of E. coli in the reactor. In addition, possible mechanisms of the inactivation were also discussed
Differential aminoacylase expression in neuroblastoma

Neuroblastoma, a cancer of the sympathetic nervous system, is the most common extracranial solid tumor in children. MYCN amplification and increased BDNF/TrkB signaling are features of high‐risk tumors; yet, only ˜25% of malignant tumors display these features. Thus, the identification of additional biomarkers and therapeutic targets is essential. As aminoacylase 1 (ACY1), an amino acid deacetylase, is a putative tumor suppressor in small cell lung and renal cell carcinomas, we investigated whether it or the other family members aspartoacylase (ASPA, aminoacylase 2) or aminoacylase 3 (ACY3) could serve a similar function in neuroblastoma. Aminoacylase expression was examined in TrkB‐positive, MYCN‐amplified (SMS‐KCNR and SK‐N‐BE) and TrkB‐negative, non‐MYCN‐amplified (SK‐N‐AS, SK‐N‐SH, SH‐SY5Y and SH‐EP) neuroblastoma cell lines. Each aminoacylase exhibited distinct spatial localization (i.e., cytosolic ACY1, membrane‐associated ASPA and nuclear ACY3). When SK‐N‐SH cells were treated with neural differentiation agents (e.g., retinoic acid and cAMP) in media containing 10% serum, ACY1 was the only aminoacylase whose expression was upregulated. ASPA was primarily expressed in SH‐EP cells of a glial sublineage. ACY3 was more highly expressed in the TrkB‐positive, MYCN‐amplified lines. All three aminoacylases were expressed in normal human adrenal gland, a common site of neuroblastoma origin, but only ACY1 and ACY3 displayed detectable expression in primary neuroblastoma tumor. Bioinformatics data mining of Kaplan–Meier survival revealed that high ACY3 expression is correlated with poor prognosis, whereas low expression of ACY1 or ASPA is correlated with poor prognosis. These data suggest that aminoacylase expression is dysregulated in neuroblastoma.
Sequential Changes in Cerebral Blood Flow and Distribution of Flow Within the Brain During Hemorrhagic Shock

Sequential changes in cerebral blood flow as well as in regional blood flow to the brain (brain stem, cerebellum, hypothalamus, white matter and grey matter) were measured in unanesthetized dogs subjected to gradual prolonged hemorrhage according to a protocol which stimulates the most commonly encountered type of clinical hemorrhagic shock. Microspheres labeled with five different radioactive isotopes were injected into a left atrial catheter at five different times: control, early hypotension (immediately after hemorrhage), late hypotension (just before reinfusion of the shed blood), as well as one and eight hours after reinfusion of the shed blood. Immediately after hemorrhage, the total cerebral blood flow decreased slightly, but increased when calculated as a percent of the cardiac output. In the late hypotensive, hypovolemic stage, there was decreased flow calculated both as percentages of cardiac output and absolute flow as compared with the initial response to hemorrhage. Immediately after reinfusion of the shed blood, there were further reductions of flow. Eight hours subsequently, flow rose to values slightly above control. The patterns of each region was almost identical to that of the total cerebral flow. Since each of the major regions of the brain are approximately equally affected, changes in the level of consciousness and other cerebral functions occurring with hypovolemic shock may reflect circulation of the white matter as well as that of the whole brain.
Human Cytomegalovirus Activates Inflammatory Cytokine Responses via CD14 and Toll-Like Receptor 2

ABSTRACT Human cytomegalovirus (CMV) is a ubiquitous opportunistic pathogen that causes significant morbidity and mortality in immuncompromised people. An understanding of how CMV induces and circumvents host immunity is of critical importance in efforts to design effective therapeutics. It was recently discovered that mere cell contact by CMV particles leads to profound modulation of cellular gene expression, including induction of inflammatory cytokines and interferon-stimulated genes characteristic of innate immune detection. These findings suggest that a membrane receptor recognizes a CMV envelope protein(s), leading to innate immune activation. Here, we show that the pattern recognition receptors Toll-like receptor 2 (TLR2) and CD14 recognize CMV virions and trigger inflammatory cytokine production. Induction of inflammatory cytokines is mediated via TLR2-dependent activation of NF-κB. Since many of the pathological processes associated with CMV disease are facilitated or directly mediated by inflammatory cytokines, identification of the host membrane detection machinery may ultimately lead to improved therapeutics.
MALE MATE CHOICE AND THE EVOLUTION OF FEMALE PLUMAGE COLORATION IN THE HOUSE FINCH

The house finch (Carpodacus mexicanus) is a sexually dichromatic passerine in which males display colorful plumage and females are generally drab brown. Some females, however, have a subdued version of the same pattern of ornamental coloration seen in males. In previous research, I found that female house finches use male coloration as an important criterion when choosing mates and that the plumage brightness of males is a reliable indicator of male nest attentiveness. Male house finches invest substantially in the care of young and, like females, stand to gain by choosing high‐quality mates. I therefore hypothesized that a female's plumage brightness might be correlated with her quality and be the basis for male mate choice. In laboratory mate choice experiments, male house finches showed a significant preference for the most brightly plumaged females presented. Observations of a wild population of house finches, however, suggest that female age is the primary criterion in male choice and that female plumage coloration is a secondary criterion. In addition, yearling females tended to have more brightly colored plumage than older females, and there was no relationship between female plumage coloration and overwinter survival, reproductive success, or condition. These observations fail to support the idea that female plumage coloration is an indicator of individual quality. Male mate choice for brightly plumaged females may have evolved as a correlated response to selection on females to choose brightly colored males.
The preferred response slopes and two-channel compression ratios in twenty listening conditions by hearing-impaired and normal-hearing listeners and their relationship to the acoustic input

This paper presents the results from two experiments in which normal-hearing and hearing-impaired listeners used an adaptive procedure to select their preferred frequency response slope and two-channel compression ratios in twenty listening conditions. Whereas the preferred response slope mostly depended on the difference in SNR between frequency bands, the preferred output levels in two channels depended highly on the intensity level entering each band. In both cases, subjects preferred less gain in frequency bands where noise was more intrusive and they preferred less gain for listening comfort than for speech understanding. The preferred response slope also depended on the slope of the audiogram. Relative to the prescribed NAL-RP response, the preferred gain variations improved the broadband SNR and hence listening comfort, but not the estimated speech intelligibility index. Overall, the findings confirm the approach used in many commercial products of applying wide dynamic range compression in multiple bands with additional gain reductions in bands where the noise is estimated to be dominant. Sumario Este trabajo presenta los resultados de dos experimentos en los cuales un grupo los sujetos normo-oyentes y otro de hipoacúsicos usaron un procedimiento adaptativo para seleccionar su perfil de respuestas de frecuencia y dos relaciones de compresión de dos canales en 20 condiciones de escucha. Mientras que el perfil de respuesta preferida dependió sobre todo de la diferencia en la relación señal/ruido entre bandas de frecuencia, los niveles de salida en dos canales dependieron altamente del nivel de intensidad que entra en cada banda. En ambos casos, los sujetos prefirieron menor ganancia en bandas de frecuencia en las que el ruido era más molesto y prefirieron también menor ganancia para tener mayor comodidad que mejor comprensión del lenguaje. El perfil de respuesta preferida también dependió del perfil del audiograma. En relación con la respuesta prescrita NAL-RP, las variaciones de ganancia preferida mejoraron la relacion S/R de banda ancha y la comodidad de la escucha pero no el índice estimado de inteligibilidad del lenguaje. Por lo general, los hallazgos confirman la forma usada en muchos productos comerciales de aplicar un amplio rango dinámico de compresión en bandas múltiples con reducciones adicionales de ganancia en bandas en las que el ruido se estima como lo dominante.
Comparison of the effects of bisphenol a alone and in a combination with X‐irradiation on sperm count and quality in male adult and pubescent mice

Bisphenol A (BPA) is employed in the manufacturing of epoxy, polyester‐styrene, and polycarbonate resins, which are used for the production of baby and water bottles and reusable containers, food and beverage packing, dental fillings and sealants. The study was designed to examine the effects of 8‐week exposure (a full cycle of spermatogenesis) to BPA alone and in a combination with X‐irradiation on the reproductive organs and germ cells of adult and pubescent male mice. Pzh:Sfis male mice were exposed to BPA (5, 10, and 20 mg/kg) or X‐rays (0.05 Gy) or to a combination of both (0.05 Gy + 5 mg/kg bw BPA). The following parameters were examined: sperm count, sperm motility, sperm morphology, and DNA damage in male gametes. Both BPA and X‐rays alone diminished sperm quality. BPA exposure significantly reduced sperm count in pubescent males compared to adult mice, with degenerative changes detected in seminiferous epithelium. This may suggest a higher susceptibility of germ cells of younger males to BPA action. Combined BPA with X‐ray treatment enhanced the harmful effect induced by BPA alone in male germ cells of adult males, whereas low‐dose irradiation showed sometimes protective or additive effects in pubescent mice. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1301–1313, 2014.
Adaptation to Deep-Sea Hydrothermal Vents: Some Molecular and Developmental Aspects

Alvinella pompejana is a polychaetous annelid inhabiting the surface of deep sea hydrothermal chimneys along the ridge of the east part of the Pacific ocean. The main characteristic of this emblematic species is its habitat, which is very aggressive considering its temperature. The exceptional thermotolerance of this species (up to 80℃) has been the subject of much controversy. This review is focused on the thermal adaptation of this worm regarding molecular data relative to its extracellular matrix and life history traits.