Miracle-dz/UniFAR-FTUs huggingface dataset:
Heat Shock Protein 60 or 70 Activates Nitric-oxide Synthase (NOS) I- and Inhibits NOS II-associated Signaling and Depresses the Mitochondrial Apoptotic Cascade during Brain Stem Death*

The cellular and molecular basis of brain stem death remains an enigma. As the origin of a “life-and-death” signal that reflects the progression toward brain stem death, the rostral ventrolateral medulla (RVLM) is a suitable neural substrate for mechanistic delineation of this phenomenon. Here, we evaluated the hypothesis that heat shock proteins (HSPs) play a neuroprotective role in the RVLM during brain stem death and delineated the underlying mechanisms, using a clinically relevant animal model that employed the organophosphate pesticide mevinphos (Mev) as the experimental insult. In Sprague-Dawley rats, proteomic, Western blot, and real-time PCR analyses demonstrated that Mev induced de novo synthesis of HSP60 or HSP70 in the RVLM without affecting HSP90 level. Loss-of-function manipulations of HSP60 or HSP70 in the RVLM using anti-serum or antisense oligonucleotide potentiated Mev-elicited cardiovascular depression alongside reduced nitric-oxide synthase (NOS) I/protein kinase G signaling, enhanced NOS II/peroxynitrite cascade, intensified nucleosomal DNA fragmentation, elevated cytoplasmic histone-associated DNA fragments or activated caspase-3, and augmented the cytochrome c/caspase-3 cascade of apoptotic signaling in the RVLM. Co-immunoprecipitation experiments further revealed a progressive increase in the complex formed between HSP60 and mitochondrial or cytosolic Bax or mitochondrial Bcl-2 during Mev intoxication, alongside a dissociation of the cytosolic HSP60-Bcl-2 complex. We conclude that HSP60 and HSP70 confer neuroprotection against Mev intoxication by ameliorating cardiovascular depression via an anti-apoptotic action in the RVLM. The possible underlying intracellular processes include enhancing NOS I/protein kinase G signaling and inhibiting the NOS II/peroxynitrite cascade. In addition, HSP60 exerts its effects against apoptosis by blunting Mev-induced activation of the Bax/cytochrome c/caspase-3 cascade.
A new communication framework for wide-band cognitive radio networks

Cognitive radio is a promising technology to solve the spectrum scarcity problem. In a cognitive radio network, a secondary user (SU) first senses a specific range of the spectrum to get its available channels and two SUs need to rendezvous on a common available channel to establish a physical link for communications. The spectrum band allocated for existing wireless services is very wide. However, when a SU works in wideband spectrum, the increasing delay and energy consumption in spectrum sensing and the time for two SUs to rendezvous will be a serious problem. All the existing rendezvous papers only focus on designing efficient algorithms for guaranteed rendezvous without considering practical communication issues caused by the wide-band spectrum. In this paper, we propose a novel communication framework for wide-band cognitive radio networks without a common control channel. Our proposed framework can efficiently solve the problems coming from the wide-band spectrum and newly joined SUs. Simulation results show that our proposed scheme can achieve fast rendezvous and a high network throughput. To the best of our knowledge, this is the first work with an effective solution to improve the communications in a wide-band cognitive radio network.
Direct, help‐independent priming of CD8+ T cells by adeno‐associated virus–transduced hepatocytes

Both hepatitis B and C viruses frequently establish chronic infection, raising the question whether T cells are poorly primed in the liver. To determine the role of different cell types in the activation of CD8+ T cells against hepatocellular antigens, we used an Adeno‐associated virus to deliver ovalbumin to hepatocytes. In contrast to CD8+ T cells, CD4+ T cells were not activated. The CD8+ T cells were activated even in the absence of endogenous CD4+ T cells; however, in the liver, these cells were high in the programmed death‐1 protein and low in CD127. Chimera experiments revealed that these CD8+ T cells were activated on a solid tissue cell. Conclusion: Priming of CD8+ T cells directly on nonhematopoietic cells, in the absence of CD4+ T cell help, results in suboptimal T cell activation. This could explain the impaired function of CD8+ T cells seen in chronic liver infection. (HEPATOLOGY 2010)
Towards Optimal Multi-Level Checkpointing

We provide a framework to analyze multi-level checkpointing protocols, by formally defining a <inline-formula> <tex-math notation="LaTeX">$k$</tex-math><alternatives><inline-graphic xlink:href="benoit-ieq1-2643660.gif"/> </alternatives></inline-formula>-level checkpointing pattern. We provide a first-order approximation to the optimal checkpointing period, and show that the corresponding overhead is in the order of <inline-formula> <tex-math notation="LaTeX">$\sum _{\ell =1}^{k}\sqrt{2\lambda _\ell C_\ell}$</tex-math><alternatives> <inline-graphic xlink:href="benoit-ieq2-2643660.gif"/></alternatives></inline-formula>, where <inline-formula> <tex-math notation="LaTeX">$\lambda _\ell$</tex-math><alternatives> <inline-graphic xlink:href="benoit-ieq3-2643660.gif"/></alternatives></inline-formula> is the error rate at level <inline-formula><tex-math notation="LaTeX">$\ell$</tex-math><alternatives> <inline-graphic xlink:href="benoit-ieq4-2643660.gif"/></alternatives></inline-formula>, and <inline-formula> <tex-math notation="LaTeX">$C_\ell$</tex-math><alternatives><inline-graphic xlink:href="benoit-ieq5-2643660.gif"/> </alternatives></inline-formula> the checkpointing cost at level <inline-formula><tex-math notation="LaTeX">$\ell$ </tex-math><alternatives><inline-graphic xlink:href="benoit-ieq6-2643660.gif"/></alternatives></inline-formula>. This nicely extends the classical Young/Daly formula on single-level checkpointing. Furthermore, we are able to fully characterize the shape of the optimal pattern (number and positions of checkpoints), and we provide a dynamic programming algorithm to determine the optimal subset of levels to be used. Finally, we perform simulations to check the accuracy of the theoretical study and to confirm the optimality of the subset of levels returned by the dynamic programming algorithm. The results nicely corroborate the theoretical study, and demonstrate the usefulness of multi-level checkpointing with the optimal subset of levels.
Isolation, identification and growth determination of lactic acid‐utilizing yeasts from the ruminal fluid of dairy cattle

Ruminal organic acid production, especially lactic acid, can be modified by feeding cattle highly concentrated diets, which have been shown to adversely affect dairy cattle health. Therefore, the use of lactic acid‐utilizing organisms is considered to be a potential method for controlling lactic acid levels. This study was conducted to isolate and identify lactic acid‐utilizing yeasts from the ruminal fluid of dairy cattle and to determine the specific growth rate and generation time when using lactic acid as a carbon source instead of glucose. Seventeen yeast isolates were examined in this study. Yeasts isolated from dairy cattle that were fed a high cassava pulp diet (HCP) had higher specific growth rates and shorter generation times than yeasts isolated from dairy cattle that were fed a high‐concentrate diet (HC) and a mixed diet (M). The three most effective yeasts in terms of specific growth rate and generation time were Pichia kudriavzevii, Candida rugosa and Kodamaea ohmeri, with 99, 100 and 99% nucleotide identities, respectively. These three isolates could be used as potential probiotics in dairy cattle diets.
Examining hospice enrollment through a novel lens: Decision time

Abstract Objective: No prior studies on hospice utilization have captured information about the amount of time between when one first learns of hospice as a potential option for care and when he/she actually enrolls. Little is in fact known about this decision-making process. The present study examines hospice enrollment by exploring relationships between hospice decision time and known barriers to care. Method: This was an exploratory cross-sectional study. Pearson's r was employed to identify bivariate relationships between barriers to care and decision time for hospice care. Independent-sample t tests and ANOVA were utilized to consider differences in decision time across key variables. Results: Some 90 hospice patients, or their primary decision maker, participated in the study from a not-for-profit hospice located in the southern United States. Decision time was correlated with referral source, use of disease-directed treatment, functional status (on the Palliative Performance Scale [PPS]), age, diagnosis, income, race, and spirituality—suggesting that decision time is a pertinent variable when examining hospice utilization. Differences in decision time were found across diagnosis, race, income, and referral source. Significance of results: This study provides implications for policy and practice, particularly for clinicians faced with initial conversations about hospice care. Differences in decision time highlight ongoing needs related to overcoming healthcare disparities, the important role of including families in initial conversations, and the potential need for varied approaches to talking about hospice care based upon diagnosis. Results also highlight the need for policies supportive of concurrent care, where hospice can be accessed alongside curative care.
Wave Activity for Large-Amplitude Disturbances Described by the Primitive Equations on the Sphere

AbstractPseudomomentum and pseudoenergy are both measures of wave activity for disturbances in a fluid, relative to a notional background state. Together they give information on the propagation, growth, and decay of disturbances. Wave activity conservation laws are most readily derived for the primitive equations on the sphere by using isentropic coordinates. However, the intersection of isentropic surfaces with the ground (and associated potential temperature anomalies) is a crucial aspect of baroclinic wave evolution. A new expression is derived for pseudoenergy that is valid for large-amplitude disturbances spanning isentropic layers that may intersect the ground. The pseudoenergy of small-amplitude disturbances is also obtained by linearizing about a zonally symmetric background state. The new expression generalizes previous pseudoenergy results for quasigeostrophic disturbances on the β plane and complements existing large-amplitude results for pseudomomentum.The pseudomomentum and pseudoenergy diag.
A Comprehensive Microarray-Based DNA Methylation Study of 367 Hematological Neoplasms

Background Alterations in the DNA methylation pattern are a hallmark of leukemias and lymphomas. However, most epigenetic studies in hematologic neoplasms (HNs) have focused either on the analysis of few candidate genes or many genes and few HN entities, and comprehensive studies are required. Methodology/Principal Findings Here, we report for the first time a microarray-based DNA methylation study of 767 genes in 367 HNs diagnosed with 16 of the most representative B-cell (n = 203), T-cell (n = 30), and myeloid (n = 134) neoplasias, as well as 37 samples from different cell types of the hematopoietic system. Using appropriate controls of B-, T-, or myeloid cellular origin, we identified a total of 220 genes hypermethylated in at least one HN entity. In general, promoter hypermethylation was more frequent in lymphoid malignancies than in myeloid malignancies, being germinal center mature B-cell lymphomas as well as B and T precursor lymphoid neoplasias those entities with highest frequency of gene-associated DNA hypermethylation. We also observed a significant correlation between the number of hypermethylated and hypomethylated genes in several mature B-cell neoplasias, but not in precursor B- and T-cell leukemias. Most of the genes becoming hypermethylated contained promoters with high CpG content, and a significant fraction of them are targets of the polycomb repressor complex. Interestingly, T-cell prolymphocytic leukemias show low levels of DNA hypermethylation and a comparatively large number of hypomethylated genes, many of them showing an increased gene expression. Conclusions/Significance We have characterized the DNA methylation profile of a wide range of different HNs entities. As well as identifying genes showing aberrant DNA methylation in certain HN subtypes, we also detected six genes—DBC1, DIO3, FZD9, HS3ST2, MOS, and MYOD1—that were significantly hypermethylated in B-cell, T-cell, and myeloid malignancies. These might therefore play an important role in the development of different HNs.
Extractors for the Real World 1

Extractors are a special type of binary graphs that can be utilized to improve the quality of randomness sources that generate strings with small entropy. The paper explores constructions of extractors that are practical and easy to implement. Randomized and deterministic constructions are presented and compared with some previously known constructions that achieve very good asymptotical performances. One of our methods is shown to have a better behavior for reasonable values of the involved parameters.
Potential therapeutic strategies for non - muscle invasive bladder cancer based on association of intravesical immunotherapy with P-MAPA and systemic administration of cisplatin and doxorubicin

ABSTRACT The present study describes the histopathological and molecular effects of P-MAPA (Protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride) intravesical immunotherapy combined with systemic doxorubicin or cisplatin for treatment of non-muscle invasive bladder cancer (NMIBC) in an appropriate animal model. Our results showed an undifferentiated tumor, characterizing a tumor invading mucosa or submucosa of the bladder wall (pT1) and papillary carcinoma in situ (pTa) in the Cancer group. The histopathological changes were similar between the combined treatment with intravesical P-MAPA plus systemic Cisplatin and P-MAPA immunotherapy alone, showing decrease of urothelial neoplastic lesions progression and histopathological recovery in 80% of the animals. The animals treated systemically with cisplatin or doxorubicin singly, showed 100% of malignant lesions in the urinary bladder. Furthemore, the combined treatment with P-MAPA and Doxorubicin showed no decrease of urothelial neoplastic lesions progression and histopathological recovery. Furthermore, Akt, PI3K, NF-kB and VEGF protein levels were significantly lower in intravesical P-MAPA plus systemic cisplatin and in intravesical P-MAPA alone treatments than other groups. In contrast, PTEN protein levels were significantly higher in intravesical P-MAPA plus systemic cisplatin and in intravesical P-MAPA alone treatments. Thus, it could be concluded that combination of intravesical P-MAPA immunotherapy and systemic cisplatin in the NMIBC animal model was effective, well tolerated and showed no apparent signs of antagonism between the drugs. In addition, intravesical P-MAPA immunotherapy may be considered as a valuable option for treatment of BCG unresponsive patients that unmet the criteria for early cystectomy.
Encoding variable cortical states with short-term spike patterns

Neurons in the primary somatosensory cortex (S1) respond to peripheral stimulation with synchronised bursts of spikes, which lock to the macroscopic 600 Hz EEG waves. The mechanism of burst generation and synchronisation in S1 is not yet understood. Using models of single-neuron responses fitted to unit recordings from macaque monkeys, we show that these synchronised bursts are the consequence of correlated synaptic inputs combined with a refractory mechanism. In the presence of noise these models reproduce also the observed trial-to-trial response variability, where individual bursts represent one of many stereotypical temporal spike patterns. When additional slower and global excitability fluctuations are introduced the single-neuron spike patterns are correlated with the population activity, as demonstrated in experimental data. The underlying biophysical mechanism of S1 responses involves thalamic inputs arriving through depressing synapses to cortical neurons in a high-conductance state. Our findings show that a simple feedforward processing of peripheral inputs could give rise to neuronal responses with non-trivial temporal and population statistics. We conclude that neural systems could use refractoriness to encode variable cortical states into stereotypical short-term spike patterns amenable to processing at neuronal time scales (tens of milliseconds).
Parallel random number generators for sequences uniformly distributed over any range of integers

A VLSI design methodology is proposed for the efficient generation of multiple pseudorandom number sequences based on a simplification of Cauwenberghs' counterpropagation technique. We demonstrate that the counterpropagation of two sequences can be replaced by one propagating and one nonpropagating sequence, requiring as few as half the number of flip-flops, while still allowing new circuits to be added to the system without additional calculations-there is no need to keep track of random starting values, tap combinations, or time shifts. Moreover we extend our method from multiple bit sequences to multiple random number sequences that are uniformly distributed over any range of integers. In particular we address the more general problem of generating sequences over the range [0,K] where K+1 is any desired integer, including a power of two or a prime number. To this end we demonstrate that the simple concatenation of random bits to form random bytes is a special case of a more general concept whereby random integers distributed over prime number ranges are concatenated to form random integers distributed over any range. We find that the proposed design compares favorably with design strategies based on cellular automata, both in terms of statistical properties and implementation efficiencies.
Pharmacokinetics and Absorption of Posaconazole Oral Suspension under Various Gastric Conditions in Healthy Volunteers

ABSTRACT A four-part, randomized, crossover study with healthy subjects evaluated the effects of gastric pH, the dosing frequency and prandial state, food consumption timing, and gastric motility on the absorption of posaconazole. In part 1, a single dose (SD) of posaconazole (400 mg) was administered alone or with an acidic beverage or a proton pump inhibitor (PPI), or both. In part 2, posaconazole (400 mg twice daily and 200 mg four times daily) was administered for 7 days with and without a nutritional supplement (Boost). In part 3, an SD of posaconazole (400 mg) was administered while the subjects were fasting and before, during, and after a high-fat meal. In part 4, an SD of posaconazole (400 mg) and the nutritional supplement were administered alone, with metoclopramide, and with loperamide. Compared to the results obtained with posaconazole alone, administration with an acidic beverage increased the posaconazole maximum concentration in plasma (Cmax) and the area under the concentration-time curve (AUC) by 92% and 70%, respectively, whereas a higher gastric pH decreased the posaconazole Cmax and AUC by 46% and 32%, respectively. Compared to the results obtained with posaconazole alone, posaconazole at 400 mg or at 200 mg plus the nutritional supplement increased the posaconazole Cmax and AUC by 65% and 66%, respectively, and by up to 137% and 161%, respectively. Administration before a high-fat meal increased the Cmax and the AUC by 96% and 111%, respectively, while administration during and after the meal increased the Cmax and the AUC by up to 339% and 387%, respectively. Increased gastric motility decreased the Cmax and the AUC by 21% and 19%, respectively. Strategies to maximize posaconazole exposure in patients with absorption difficulties include administration with or after a high-fat meal, with any meal or nutritional supplement, with an acidic beverage, or in divided doses and the avoidance of proton pump inhibitors.
Differentially Methylated Regions of Imprinted Genes in Prenatal, Perinatal and Postnatal Human Tissues

Epigenetic plasticity in relation to in utero exposures may mechanistically explain observed differences in the likelihood of developing common complex diseases including hypertension, diabetes and cardiovascular disease through the cumulative effects of subtle alterations in gene expression. Imprinted genes are essential mediators of growth and development and are characterized by differentially methylated regulatory regions (DMRs) that carry parental allele-specific methylation profiles. This theoretical 50% level of methylation provides a baseline from which endogenously- or exogenously-induced deviations in methylation can be detected. We quantified DNA methylation at imprinted gene DMRs in a large panel of human conceptal tissues, in matched buccal cell specimens collected at birth and at one year of age, and in the major cell fractions of umbilical cord blood to assess the stability of methylation at these regions. DNA methylation was measured using validated pyrosequencing assays at seven DMRs regulating the IGF2/H19, DLK1/MEG3, MEST, NNAT and SGCE/PEG10 imprinted domains. DMR methylation did not significantly differ for the H19, MEST and SGCE/PEG10 DMRs across all conceptal tissues analyzed (ANOVA p>0.10). Methylation differences at several DMRs were observed in tissues from brain (IGF2 and MEG3-IG DMRs), liver (IGF2 and MEG3 DMRs) and placenta (both DLK1/MEG3 DMRs and NNAT DMR). In most infants, methylation profiles in buccal cells at birth and at one year of age were comparable, as was methylation in the major cell fractions of umbilical cord blood. Several infants showed temporal deviations in methylation at multiple DMRs. Similarity of inter-individual and intra-individual methylation at some, but not all of the DMRs analyzed supports the possibility that methylation of these regions can serve as useful biosensors of exposure.