Miracle-dz/UniFAR-FTUs huggingface dataset:
Peptide-Nanoparticle Hybrid SERS Probe for Dynamic Detection of Active Cancer Biomarker Enzymes

Real-time in situ detection of protease enzymes is crucial for early-stage cancer screening and cell signaling pathway study; however it is difficult to be realized using fluorescence or radioactive probes. Here we devise a hybrid optical probe by incorporating nanocrescent particle and peptides with artificial tag molecules. The peptides have high specificity to PSA, one of the most prominent prostate cancer markers, and a serine protease present in patients' seminal fluid and serum. The extrinsic Raman spectral signal from the tag molecules is enhanced by the nanocrescent and the signal is monitored as the indicator for the peptide digestion in nanomolar PSA concentration and femtoliter reaction volume. Sensitive detection of cancer-related serine protease activity of PSA proteins in low concentrations and small volumes of biofluid is critical to early cancer diagnosis, clinical staging, and therapy. The high reaction specificity of the peptide and the monitored extrinsic Raman signal also minimizes the false detection of other serine proteases and intrinsic Raman signal, which results in a high-fidelity and high-signal-to-noise-ratio cancer nanoprobe. Peptide-conjugated nanocrescents should also be applicable for measuring the intercellular and intracellular activity of other cancer-related proteases and protease activity profiling-enabled cancer cell identification
An Abscisic Acid-Induced Protein, HVA22, Inhibits Gibberellin-Mediated Programmed Cell Death in Cereal Aleurone Cells1[W][OA]

Plant HVA22 is a unique abscisic acid (ABA)/stress-induced protein first isolated from barley (Hordeum vulgare) aleurone cells. Its yeast homolog, Yop1p, functions in vesicular trafficking and in the endoplasmic reticulum (ER) network in vivo. To examine the roles of plant HVA22, barley HVA22 was ectopically expressed in barley aleurone cells. Overexpression of HVA22 proteins inhibited gibberellin (GA)-induced formation of large digestive vacuoles, which is an important aspect of GA-induced programmed cell death in aleurone cells. The effect of HVA22 was specific, because overexpression of green fluorescent protein or another ABA-induced protein, HVA1, did not lead to the same effect. HVA22 acts downstream of the transcription factor GAMyb, which activates programmed cell death and other GA-mediated processes. Moreover, expression of HVA22:green fluorescent protein fusion proteins showed network and punctate fluorescence patterns, which were colocalized with an ER marker, BiP:RFP, and a Golgi marker, ST:mRFP, respectively. In particular, the transmembrane domain 2 was critical for protein localization and stability. Ectopic expression of the most phylogenetically similar Arabidopsis (Arabidopsis thaliana) homolog, AtHVA22D, also resulted in the inhibition of vacuolation to a similar level as HVA22, indicating function conservation between barley HVA22 and some Arabidopsis homologs. Taken together, we show that HVA22 is an ER- and Golgi-localized protein capable of negatively regulating GA-mediated vacuolation/programmed cell death in barley aleurone cells. We propose that ABA induces the accumulation of HVA22 proteins to inhibit vesicular trafficking involved in nutrient mobilization to delay coalescence of protein storage vacuoles as part of its role in regulating seed germination and seedling growth.
Dried cervical spots for human papillomaviruses identification

Financial and operational constraints limit low‐resource countries in the screening of high‐risk genital human papillomaviruses (HR‐HPV), the etiological agents of cervical cancer. With its simple storage, conservation and shipping, dried cervical sample (DCS) could represent an efficient tool. The aim of the study was to evaluate the reliability of HPV genotyping from DCS. Cervical samples were obtained from 50 women infected with HIV‐1 in Côte d'Ivoire. After DNA extraction from both DCS and matched liquid cervical samples (LCS), HPV genotyping was performed and the concordance of genotyping results was evaluated. HPV prevalence was 88% in LCS and 78% in DCS. Kappa statistic was 0.51 for the presence of any genotype (95% confidence interval, 0.25–0.77) and 0.73 for HR‐HPV (0.45–0.99). Out of 50 samples, 45 were HPV‐positive for DCS and/or LCS, and HR‐HPV were detected in 37 samples (74%) with 36 HR‐HPV multiple infections. Any genotype and HR genotype identification was concordant/compatible in 86% (43/50) and 88% (44/50) of samples, respectively. In most instances, kappa statistics for detection of type‐specific HPV was over 0.6 (including HPV‐16, ‐18, ‐31, ‐33). An excellent agreement (kappa statistic ≥ 0.81) was found for eight genotypes (HPV‐6, ‐31, ‐35, ‐40, ‐56, ‐58, ‐66, and ‐82). In spite of interfering factors (multiple infections, different HPV loads, amplification competition, different inputs), DCS and LCS led to concordant/compatible results in most cases. DCS could represent an efficient tool for epidemiological field studies in resource‐limited settings, and more importantly for improving the screening coverage and care management in women infected with HPV. J. Med. Virol. 85:1222–1228, 2013. © 2013 Wiley Periodicals, Inc.
Fasciola hepatica infection downregulates Th1 responses in mice

Immune responses induced with helminth parasites have been extensively studied, but there is limited information on those to Fasciola hepatica, especially on the subtype of T cell induced with this parasite. We investigated the local and systemic T cell responses of different strains of mice following oral infection with doses of metacercariae from F. hepatica. Spleen cells from BALB/c and 129Sv/Ev mice given a low‐dose (5 metacercariae) infection exhibited a Th2 response, producing high levels of the cytokines IL‐4 and IL‐5, and low levels of IFN‐γ and IL‐2. In contrast, C57BL/6 mice showed a mixed Th1/Th2 response. A more marked polarization to a Th2 response was observed in BALB/c, 129Sv/Ev exposed to a high‐dose (15 metacercariae) infection and the C57BL/6 mice also exhibited a clear Th2 response. IL‐4 defective (IL‐4−/−) C57BL/6 mice infected with 5 metacercariae produced less IFN‐γ and more IL‐5 compared to their wild‐type C57BL/6 counterparts, suggesting that IL‐4 is important in establishing the Th2 type response in murine fasciolosis. However, the secretion of IFN‐γ and IL‐2 was completely suppressed in the high‐dose infection and this was also observed in IL‐4−/− mice. Thus, liver flukes may secrete molecules that downregulate Th1 responses. T cell responses in the mesenteric (MLN) and hepatic lymph nodes (HLN) were also examined since newly excysted juveniles infect through the intestinal wall of their host before migrating to the hepatic tissue. Cells from both MLN and HLN secreted higher levels of IL‐4 and IL‐5 compared to spleen cells. We also observed a difference in cytokine profiles secreted by the MLN and HLN, which may reflect responses to antigens liberated by newly excysted juveniles and hepatic stage parasites, respectively.
Investimentos na indústria de defesa do Brasil e da Argentina

A partir do seculo XXI os paises latinos americanos tem adotado politicas que visam a modernizacao e inovacao do aparato da industria de defesa. As politicas de defesas dos paises sul-americanos, como Brasil e Argentina, se destacam pelos investimentos e representatividade. Em vista disto, objetivou-se com este trabalho fazer um estudo comparado dos gastos militares e da industria de defesa do Brasil e da Argentina. Onde pretendeu-se conjugar dados de ambos os paises no que tange as despesas militares associando as politicas de desenvolvimento dos paises em questao, atraves de uma revisao historica dos avancos da industria de defesa e suas estrategias. Os dados foram extraidos do Stockholm International Peace Research Institute (SIPRI), ja o recorte temporal compreende de 2000 a 2014. Por meio dos resultados pode-se inferir que o Brasil e a Argentina tem aumentado a quantidade de investimentos nesse ramo industrial, sendo que o Brasil ainda possui niveis superiores ao argentino.
Reconfigurable and tunable efficient power amplifiers for transmitters in telecommunication devices

We summarize the most important results from the first author's PhD dissertation. We primarily address the improvements in power amplifier circuits. We design, fabricate, and validate a reconfigurable amplifier with PIN diode and a tunable amplifier with a varicap diode. In addition, we present a novel theory about the class-J amplifier design confirming that it can sustain high efficiency over relatively wide frequency band — wider than class-B or class-F amplifiers. Measured results of a novel class-J amplifier verify the proposed theory. In addition, we discuss the benefits and shortcomings of circuit-based and full-wave electromagnetic-based analysis. Finally, we present two switchable circuits, based on graphene controlled by either electric or magnetic polarization.
Ethnicity and Polycystic Ovary Syndrome are Associated With Independent and Additive Decreases in Insulin Action in Caribbean-Hispanic Women

This study was conducted to determine the impact of polycystic ovary syndrome and ethnicity on insulin action. Thirteen Caribbean-Hispanic and 10 non-Hispanic white polycystic ovary syndrome women were compared with 5 Caribbean-Hispanic and 8 non-Hispanic white normal women matched for age, weight, and body composition. All subjects underwent a 2-h 75 g oral glucose tolerance test and euglycemic glucose clamp study with a 40 mU.m−2 · min−1 insulin dose. Hepatic glucose production was determined basally and throughout the euglycemic clamp study. Polycystic ovary syndrome was associated with significant increases in fasting insulin levels (P < 0.05) and in 2-h postglucose-load glucose and insulin levels (P < 0.001). Ethnicity was not associated with any changes in these parameters. Polycystic ovary syndrome but not ethnicity was also associated with hepatic insulin resistance, because significant (P < 0.05) residual hepatic glucose production occurred during the euglycemic clamp in the polycystic ovary syndrome women. However, significant independent effects existed for both polycystic ovary syndrome (P < 0.01) and ethnicity (P < 0.05) that resulted in decreased insulin-mediated glucose disposal. Similarly, significant independent effects of polycystic ovary syndrome (P < 0.005) and ethnicity (P < 0.05) occurred, resulting in increased steady-state insulin levels during the euglycemic clamp. This appeared to be, in part, secondary to a decrease in the metabolic clearance rate of insulin associated with ethnicity (P < 0.05). We conclude that polycystic ovary syndrome and ethnicity result in independent and additive decreases in insulin sensitivity in Caribbean-Hispanic women. Insulin resistance resulting in hyperinsulinemia may account for the increased prevalence of both polycystic ovary syndrome and of NIDDM in Caribbean-Hispanic women.
High- $Q$  and High-Order Side-Coupled Air-Mode Nanobeam Photonic Crystal Cavities in Silicon

We demonstrate the design, fabrication, and characterization of side-coupled airmode nanobeam photonic crystal cavities in silicon-on-insulator platform. Results show that repeatable devices achieve similar high loaded quality factors (>104) and large optical energy ratio in low refractive region. The unload Q-factors of the fabricated cavities are estimated to exceed 105. With side-coupled configuration, high transmission of through port is achieved with typical insertion loss less than 0.5 dB. Wavelength shifts of the measured resonances with respect to the designed values are observed and well explained by considering the fluctuation of etching depth. The demonstrated side-coupled airmode nanobeam photonic crystal cavities may find their applications in ultracompact integrated photonics, especially for on-chip photonic sensor, notch filter, or optical switch.
Factors linked to transitions in adherence to antiretroviral therapy among HIV-infected illicit drug users in a Canadian setting

HIV-positive people who use illicit drugs typically achieve lower levels of adherence to antiretroviral therapy and experience higher rates of sub-optimal HIV/AIDS treatment outcomes. Given the dearth of longitudinal research into ART adherence dynamics, we sought to identify factors associated with transitioning into and out of optimal adherence to ART in a longitudinal study of HIV-infected people who use illicit drugs (PWUD) in a setting of universal no-cost HIV/AIDS treatment. Using data from a prospective cohort of community-recruited HIV-positive illicit drug users confidentially linked to comprehensive HIV/AIDS treatment records, we estimated longitudinal factors associated with losing or gaining ≥95% adherence in the previous six months using two generalized linear mixed-effects models. Among 703 HIV-infected ART-exposed PWUD, becoming non-adherent was associated with periods of homelessness (adjusted odds ratio [AOR] = 2.52, 95% confidence interval [95% CI]: 1.56–4.07), active injection drug use (AOR = 1.25, 95% CI: 1.01–1.56) and incarceration (AOR = 1.54, 95% CI: 1.10–2.17). Periods of sex work (AOR = 0.51, 95% CI: 0.34–0.75) and injection drug use (AOR = 0.62, 95% CI: 0.50–0.77) were barriers to becoming optimally adherent. Methadone maintenance therapy was associated with becoming optimally adherent (AOR = 1.87, 95% CI: 1.50–2.33) and was protective against becoming non-adherent (AOR = 0.52, 95% CI: 0.41–0.65). In conclusion, we identified several behavioural, social and structural factors that shape adherence patterns among PWUD. Our findings highlight the need to consider these contextual factors in interventions that support the effective delivery of ART to this population.
Quantitative kinetics analysis of BMP2 uptake into cells and its modulation by BMP antagonists

Summary Bone morphogenetic proteins (BMPs) are members of the TGF&bgr; family of signaling proteins and play an important role during development and in tissue formation. BMP signaling is a well-studied process, which is initiated through binding of cognate receptors and processed through activation of Smad downstream mediators. A hallmark of BMP signaling is its modulation at the extracellular level through specific antagonists. Although it had been shown that BMP and TGF&bgr; receptors are internalized following activation, little is known about the fate of BMP ligands. We prepared biologically active fluorescently labeled BMP2 and quantitatively analyzed its binding and uptake in cells using flow cytometry and confocal microscopy. Exogenous BMP2 was rapidly bound to the cell surface and subsequently internalized in a time-dependent manner and accumulated in the cell center. Although binding to the cell surface was limited by binding sites at the beginning, internalization continously increased with time, after a short delay. Using different inhibitors we found that internalization of BMP2 through endosomal particles occurred in a clathrin-dependent pathway. Furthermore, uptake of BMP2 was modulated in strikingly different ways by BMP2 antagonists. Although Noggin and Gremlin increased BMP2 uptake, Chordin blocked BMP2 uptake, which was concentration dependent in both cases. In conclusion, our findings present interesting mechanisms for the modulation of BMP signaling by concentration gradients of BMP ligands and antagonists in a dose- and time-dependent manner, which can provide an explanation of some properties of the BMP regulatory network.
NF-κB Signaling Pathways

Intracellular pathways related to cell survival regulate neuronal physiology during development and neurodegenerative disorders. One of the pathways that have recently emerged with an important role in these processes is nuclear factor-κB (NF-κB). The activity of this pathway leads to the nuclear translocation of the NF-κB transcription factors and the regulation of anti-apoptotic gene expression. Different stimuli can activate the pathway through different intracellular cascades (canonical, non-canonical, and atypical), contributing to the translocation of specific dimers of the NF-κB transcription factors, and each of these dimers can regulate the transcription of different genes. Recent studies have shown that the activation of this pathway regulates opposite responses such as cell survival or neuronal degeneration. These apparent contradictory effects depend on conditions such as the pathway stimuli, the origin of the cells, or the cellular context. In the present review, the authors summarize these findings and discuss their significance with respect to survival or death in the nervous system.
Purification and Characterization of an Extracellular Protease from Xenorhabdus nematophila Involved in Insect Immunosuppression

ABSTRACT Xenorhabdus nematophila, a bacterium pathogenic for insects associated with the nematode Steinernema carpocapsae, releases high quantities of proteases, which may participate in the virulence against insects. Zymogram assays and cross-reactions of antibodies suggested that two distinct proteases were present. The major one, protease II, was purified and shown to have a molecular mass of 60 kDa and an estimated isoelectric point of 8.5. Protease II digested the chromogenic substrate N-tosyl-Gly-Pro-Arg-paranitroanilide (pNA) with Vmax and Km values of 0.0551 μM/min and 234 μM, respectively, and the substrate dl-Val-Leu-Arg-pNA with Vmax and Km values of 0.3830 μM/min and 429 μM, respectively. Protease II activity was inhibited 93% by Pefabloc SC and 45% by chymostatin. The optimum pH for protease II was 7, and the optimum temperature was 23°C. Proteolytic activity was reduced by 90% at 60°C for 10 min. Sequence analysis was performed on four internal peptides that resulted from the digestion of protease II. Fragments 29 and 45 are 75 and 68% identical to alkaline metalloproteinase produced by Pseudomonas aeruginosa. Fragment 29 is 79% identical to a metalloprotease of Erwinia amylovora and 75% identical to the protease C precursor of Erwinia chrysanthemi. Protease II showed no toxicity to hemocytes but destroyed antibacterial activity on the hemolymph of inoculated insects' larvae and reduced 97% of the cecropin A bacteriolytic activity.
Toxicity of tributyltin and triphenyltin to early life‐stages of Paracentrotus lividus (Echinodermata: Echinoidea)

Sperm cell and embryo toxicity tests using the Mediterranean sea urchin Paracentrotus lividus were performed to assess the toxicity of tributyltin chloride, bis(tributyltin)oxide, triphenyltin acetate, and triphenyltin hydroxide. Toxicity values (mean effective concentration [EC50]) ranged from 2.97 to 18.5 μg/L for sperm cells and from 1.11 to 2.62 μg/L for embryos. For sperm cells, the toxicity of the two tributyl compounds was significantly greater than that of two triphenyl compounds; for embryos, the triphenyl compounds appeared to be more toxic. Study of embryotoxic effects highlighted closely concentration‐dependent damages, the most sensitive stages corresponding to the crucial phases of differentiation (gastrula and prisma). Both EC50 and no‐observed‐effect concentration values for the four organotin compounds are similar to those reported in the literature for early life stages of other marine organisms.
mcl-1 Is an Immediate-Early Gene Activated by the Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Signaling Pathway and Is One Component of the GM-CSF Viability Response

ABSTRACT mcl-1, a bcl-2 family member, was originally identified as an early gene induced during differentiation of ML-1 myeloid leukemia cells. In the present study, we demonstrate that Mcl-1 is tightly regulated by the granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling pathway. Upon deprivation of survival factor from TF-1 myeloid progenitor cells, Mcl-1 levels quickly dropped prior to visible detection of apoptosis of these cells. Upon restimulation of these deprived cells with GM-CSF, themcl-1 mRNA was immediately induced and its protein product was accordingly resynthesized. Analysis with Ba/F3 cells expressing various truncation mutants of the GM-CSF receptor revealed that the membrane distal region between amino acids 573 and 755 of the receptor β chain was required for mcl-1 induction. Transient-transfection assays with luciferase reporter genes driven by various regions of the mcl-1 promoter demonstrated that the upstream sequence between −197 and −69 is responsible for cytokine activation of the mcl-1 gene. Overexpression ofmcl-1 delayed but did not completely prevent apoptosis of cells triggered by cytokine withdrawal. Its down regulation by antisense constructs overcame, at least partially, the survival activity of GM-CSF and induced the apoptosis of TF-1 cells. Taken together, these results suggest that mcl-1 is an immediate-early gene activated by the cytokine receptor signaling pathway and is one component of the GM-CSF viability response.
Sevelamer Hydrochloride and Calcium Bicarbonate Reduce Serum Fibroblast Growth Factor 23 Levels in Dialysis Patients

Abstract: Fibroblast growth factor 23 (FGF23) is a member of the fibroblast growth factor superfamily which displays a strong phosphaturic action and an inhibition of vitamin D 1‐α hydroxylase activity. Fourty‐six patients undergoing maintenance hemodialysis therapy participated in the study. They were randomly divided into 2 groups, and treated with either 3 g sevelamer hydrochloride + 3 g of calcium bicarbonate (CaCO3), or 3 g of CaCO3 alone. Serum FGF23 levels were determined by a sandwich enzyme‐linked immunosorbent assay (ELISA) system that detects the intact form of FGF23 molecules. Although the serum inorganic phosphate (Pi) levels were comparable before treatment, the levels were significantly lower in the patients treated with sevelamer hydrochloride + CaCO3 than those with CaCO3 alone after 4 weeks of treatment (P < 0.05). Serum FGF23 levels significantly decreased after 4 weeks of the treatment with sevelamer hydrochloride + CaCO3 from the pretreatment levels (P < 0.05), while no changes were found in the patients treated with CaCO3 alone. Thus, the use of sevelamer hydrochloride and CaCO3 reduced serum FGF23 levels in dialysis patients presumably through inhibiting phosphate load into the intestine.
Dietary Na and baroreflex modulation of blood pressure and RSNA in normotensive vs. spontaneously hypertensive rats.

Different changes in baroreflex control of the circulation have been postulated to play a role in the different blood pressure (BP) effects of dietary sodium in normotensive vs. genetically hypertensive rats. We therefore evaluated in young Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR), with or without chronic sinoaortic denervation (SAD), the effects of low, regular, and high dietary sodium intake from 4 to 8 wk of age on BP and baroreflex function. The latter was assessed by changes in renal sympathetic nerve activity (RSNA) and heart rate in response to (de)pressor agents. In SHR, the above range of sodium caused a marked change in resting BP, somewhat more in intact (48 mmHg) vs. SAD (36 mmHg) rats. In contrast, in WKY this range of sodium intake caused only a minor (7 mmHg) change in resting BP of intact WKY but a significant (16 mmHg) change in WKY with SAD, mainly due to an increase in BP on high sodium. In intact WKY increasing dietary sodium from low to regular to high caused stepwise increases in the gain of the RSNA-BP reflex, whereas in intact SHR only an increase from low to regular sodium intake increased the gain. After SAD, the gain of the RSNA-BP reflex was very low, and no longer affected by dietary sodium in either strain. These data suggest that in WKY a sensitization in arterial baroreflex control of RSNA prevents a sodium-induced increase in BP. (ABSTRACT TRUNCATED AT 250 WORDS)