Miracle-dz/UniFAR-FTUs huggingface dataset:
Corticosteroids and the treatment of idiopathic pulmonary fibrosis. Past, present, and future.

Why are corticosteroids used in patients with IPF? There is evidence that corticosteroid therapy is associated with clinical improvement in only a small percentage of IPF patients. This improvement is seen primarily in patients with a cellular histologic pattern on lung biopsy specimens, but no clinical, physiologic, or pathologic finding has been consistently associated with corticosteroid response. For IPF patients with a fibrotic histologic pattern on lung biopsy specimens, there is little evidence that corticosteroids are of any benefit, and available reports suggest that the cost of therapy in terms of both morbidity and mortality may be high. Little is known about the effect of corticosteroids on long-term clinical outcomes, and even less is known about their effects on the overall quality of life. Although current treatment regimens are based on the rationale that IPF is due to alveolar inflammation, which is probably an accurate assumption, the treatment to suppress the alveolitis should have an outcome that patients consider favorable. Data from the New Mexico ILD Registry and from other researchers suggest that the paucity of useful clinical data in IPF has resulted in a hodgepodge of diagnostic approaches and therapeutic criteria, as well as a fatalistic approach to treatment. Medical history is replete with examples of failed therapies. Analogies can be drawn between the history of IPF treatment and other catastrophic illnesses. 67 The common threads in all poorly treatable diseases are a lack of understanding about the cause and pathophysiologic state of the illness, an emphasis on indirect encouraging evidence about therapy instead of direct discouraging evidence, and the physician's ever-present compulsion to “do something. ” What we should learn from these examples is that when clearly effective therapies are not available, we are ethically obligated to give patients full information about the faults and merits of what is available and to assist them in choosing what is best for them. Medicine has advanced in the past only when assumptions about diseases and treatments were examined critically; we must continue to challenge our assumptions about IPF and corticosteroid therapy.
The effect of reduced spectral information on Japanese consonant perception: comparison between L1 and L2 listeners

We investigated how spectral information contributes to the perception of Japanese consonants, using re-synthesised samples that were created by (1) gradually reducing the order of LPC analysis in the residual excited LPC vocoder; and (2) gradually flattening the spectral peak in the frequency domain. The results of native Japanese speakers showed that the information in LPC residuals contributes significantly, if not sufficiently, to Japanese consonant perception, and that the minimum amount of spectral information is sufficient to achieve 90% identification score. It was also found that, although the perceptual error patterns were different, there were striking similarities between Japanese and non-Japanese listeners in their averaged perception scores. The phonological feature analysis of the perceptual results indicated that the residuals provide broad phonotactic information such as major class features.
Identification of a novel mutation in the NTF4 gene that causes primary open-angle glaucoma in a Chinese population

Purpose Neurotrophin-4 protein (NT-4) plays a role in the protection of retinal ganglion cells by activating tyrosine kinase B (TrkB) receptors. A recent study identified mutations within the neurotrophin-4 (NTF4) gene to account for 1.7% of primary open-angle glaucoma (POAG) in Europeans. The aim of this study was to investigate the frequency of NTF4 mutations in Chinese POAG patients. Methods One hundred-seventy-four Chinese subjects with POAG and 91 normal Chinese subjects were recruited. POAG was defined by the presence of glaucomatous optic neuropathy, open angles on gonioscopy, and absence of secondary causes of glaucoma. The single coding exon of NTF4 was PCR amplified and subjected to bidirectional sequencing in all subjects. Results The mean age of POAG patients was 66.0±13.0 years (range 25–96 years) and that of controls was 67.1±4.6 years (range 60–85 years). We identified a novel NTF4 missense mutation substituting leucine by serine at codon 113 (Leu113Ser) caused by a c.338T>C mutation in a single patient with unilateral POAG, who presented with a baseline intraocular pressure of 25 mmHg, a vertical cup-to-disc ratio of 0.9 and an inferior hemifield defect in the affected eye. Structural analysis indicated that the Leu113Ser mutation is likely to alter the NT-4 protein structure near the TrkB binding site and disrupts the formation of the NT-4-TrkB complex required for the activation of TrkB. Conclusions Identification of a single mutation in our study suggests that NTF4 mutations are a rare cause of POAG (0.6%, 95%CI 0.02%–3.16%) in Chinese people.
Shake-n-Shack: Enabling Secure Data Exchange Between Smart Wearables via Handshakes

Since ancient Greece, handshaking has been commonly practiced between two people as a friendly gesture to express trust and respect, or form a mutual agreement. In this paper, we show that such physical contact can be used to bootstrap secure cyber contact between the smart devices worn by users. The key observation is that during handshaking, although belonged to two different users, the two hands involved in the shaking events are often rigidly connected, and therefore exhibit very similar motion patterns. We propose a novel Shake-n-Shack system, which harvests motion data during user handshaking from the wrist worn smart devices such as smartwatches or fitness bands, and exploits the matching motion patterns to generate symmetric keys on both parties. The generated keys can be then used to establish a secure communication channel for exchanging data between devices. This provides a much more natural and user-friendly alternative for many applications, e.g., exchanging/sharing contact details, friending on social networks, or even making payments, since it doesn't involve extra bespoke hardware, nor require the users to perform pre-defined gestures. We implement the proposed Shake-n-Shack 1 system on off-the-shelf smartwatches, and extensive evaluation shows that it can reliably generate 128-bit symmetric keys just after around 1s of handshaking (with success rate >99%), and is resilient to real-time mimicking attacks: in our experiments the Equal Error Rate (EER) is only 1.6% on average. We also show that the proposed Shake-n-Shack system can be extremely lightweight, and is able to run in-situ on the resource-constrained smartwatches without incurring excessive resource consumption.
Arabidopsis TFL 2 / LHP 1 Specifically Associates with Genes Marked by Trimethylation of Histone H 3 Lysine 27

TERMINAL FLOWER 2/LIKE HETEROCHROMATIN PROTEIN 1 (TFL2/LHP1) is the only Arabidopsis protein with overall sequence similarity to the HETEROCHROMATIN PROTEIN 1 (HP1) family of metazoans and S. pombe. TFL2/LHP1 represses transcription of numerous genes, including the flowering-time genes FLOWERING LOCUS T (FT) and FLOWERING LOCUS C (FLC), as well as the floral organ identity genes AGAMOUS (AG) and APETALA 3 (AP3). These genes are also regulated by proteins of the Polycomb repressive complex 2 (PRC2), and it has been proposed that TFL2/LHP1 represents a potential stabilizing factor of PRC2 activity. Here we show by chromatin immunoprecipitation and hybridization to an Arabidopsis Chromosome 4 tiling array (ChIP-chip) that TFL2/LHP1 associates with hundreds of small domains, almost all of which correspond to genes located within euchromatin. We investigated the chromatin marks to which TFL2/LHP1 binds and show that, in vitro, TFL2/LHP1 binds to histone H3 dior tri-methylated at lysine 9 (H3K9me2 or H3K9me3), the marks recognized by HP1, and to histone H3 trimethylated at lysine 27 (H3K27me3), the mark deposited by PRC2. However, in vivo TFL2/LHP1 association with chromatin occurs almost exclusively and coextensively with domains marked by H3K27me3, but not H3K9me2 or -3. Moreover, the distribution of H3K27me3 is unaffected in lhp1 mutant plants, indicating that unlike PRC2 components, TFL2/LHP1 is not involved in the deposition of this mark. Rather, our data suggest that TFL2/LHP1 recognizes specifically H3K27me3 in vivo as part of a mechanism that represses the expression of many genes targeted by PRC2.
Validity Estimates for Loopy Belief Propagation on Binary Real-world Networks

We introduce a computationally efficient method to estimate the validity of the BP method as a function of graph topology, the connectivity strength, frustration and network size. We present numerical results that demonstrate the correctness of our estimates for the uniform random model and for a real-world network ("C. Elegans"). Although the method is restricted to pair-wise interactions, no local evidence (zero "biases") and binary variables, we believe that its predictions correctly capture the limitations of BP for inference and MAP estimation on arbitrary graphical models. Using this approach, we find that BP always performs better than MF. Especially for large networks with broad degree distributions (such as scale-free networks) BP turns out to significantly outperform MF.
Graph-model-based dynamic routing and spectrum assignment in elastic optical networks

In recent years, the concept of the elastic optical network (EON) was proposed and very quickly became an attractive solution for flexible channel bandwidth utilization. Analogous to the routing and wavelength assignment (RWA) problem in traditional wavelength-routed networks, routing and spectrum assignment (RSA) is the most basic and critical resource management issue in EONs. In this work, we exploit and modify the layered graph model, which is a well-known RWA model, to design two RSA heuristic algorithms named LG-FF and LG-SP. Additionally, we also derive an analytical model to estimate the number of required layered graphs. Numerical results demonstrate that LG-SP can achieve the same blocking performance level with significant time complexity reduction as compared to the near-optimal solution. Whether we care about blocking performance or aim at saving computational time, the layered graph is an important representation model of resource utilization status to efficiently solve the RSA problem.
Glucose sensing by carotid body glomus cells: potential implications in disease

The carotid body (CB) is a key chemoreceptor organ in which glomus cells sense changes in blood O2, CO2, and pH levels. CB glomus cells have also been found to detect hypoglycemia in both non-primate mammals and humans. O2 and low-glucose responses share a common final pathway involving membrane depolarization, extracellular calcium influx, increase in cytosolic calcium concentration, and neurotransmitter secretion, which stimulates afferent sensory fibers to evoke sympathoadrenal activation. On the other hand, hypoxia and low glucose induce separate signal transduction pathways. Unlike O2 sensing, the response of the CB to low glucose is not altered by rotenone, with the low glucose-activated background cationic current unaffected by hypoxia. Responses of the CB to hypoglycemia and hypoxia can be potentiated by each other. The counter-regulatory response to hypoglycemia by the CB is essential for the brain, an organ that is particularly sensitive to low glucose. CB glucose sensing could be altered in diabetic patients, particularly those under insulin treatment, as well as in other medical conditions such as sleep apnea or obstructive pulmonary diseases, where chronic hypoxemia presents with plastic modifications in CB structure and function. The current review will focus on the following main aspects: (1) the CB as a low glucose sensor in both in vitro and in vivo models; (2) molecular and ionic mechanisms of low glucose sensing by glomus cells, (3) the interplay between low glucose and O2 sensing in CB, and (4) the role of CB low glucose sensing in the pathophysiology of cardiorespiratory and metabolic diseases, and how this may serve as a potential therapeutic target.
Molecular Dynamics Simulation of the Influenza A(H3N2) Hemagglutinin Trimer Reveals the Structural Basis for Adaptive Evolution of the Recent Epidemic Clade 3C.2a

Influenza A(H3N2) has been a major cause of seasonal influenza in humans since 1968, and has evolved by antigenic drift under the constantly changing human herd immunity. Increasing evidence suggests that the antigenic change occasionally occurred concomitant with the alterations of the N-glycosylation site profile and hemagglutination activity of the virion surface protein hemagglutinin (HA). However, the structural basis of these changes remains largely unclear. To address this issue, we performed molecular dynamics simulations of the glycosylated HA trimers of the A(H3N2), which has a novel pattern of Asn-X-Ser/Thr sequons unique in the new A(H3N2) epidemic clade 3C.2a and is characterized by attenuated ability to agglutinate nonhuman erythrocytes. Comparison of the equilibrated structures of the glycosylated HA trimers with and without the 3C.2a-specific mutations reveals that the mutations could induce a drastic reduction in the apical space for the ligand binding via glycan-shield rearrangement. The results suggest that the 3C.2a strain has evolved an HA structure that is advantageous for evading pre-existing antibodies, while also increasing the ligand binding specificity. These findings have structural implications for our understanding of the phenotypic changes, evolution, and fate of influenza A(H3N2).
Social cohesion among kin, gene flow without dispersal and the evolution of population genetic structure in the killer whale (Orcinus orca)

In social species, breeding system and gregarious behavior are key factors influencing the evolution of large‐scale population genetic structure. The killer whale is a highly social apex predator showing genetic differentiation in sympatry between populations of foraging specialists (ecotypes), and low levels of genetic diversity overall. Our comparative assessments of kinship, parentage and dispersal reveal high levels of kinship within local populations and ongoing male‐mediated gene flow among them, including among ecotypes that are maximally divergent within the mtDNA phylogeny. Dispersal from natal populations was rare, implying that gene flow occurs without dispersal, as a result of reproduction during temporary interactions. Discordance between nuclear and mitochondrial phylogenies was consistent with earlier studies suggesting a stochastic basis for the magnitude of mtDNA differentiation between matrilines. Taken together our results show how the killer whale breeding system, coupled with social, dispersal and foraging behaviour, contributes to the evolution of population genetic structure.
Fast Algorithms for the Approximation of the Pseudospectral Abscissa and Pseudospectral Radius of a Matrix

The $\varepsilon$-pseudospectral abscissa and radius of an $n\times n$ matrix are, respectively, the maximal real part and the maximal modulus of points in its $\varepsilon$-pseudospectrum, defined using the spectral norm. Existing techniques compute these quantities accurately, but the cost is multiple singular value decompositions and eigenvalue decompositions of order $n$, making them impractical when $n$ is large. We present new algorithms based on computing only the spectral abscissa or radius of a sequence of matrices, generating a sequence of lower bounds for the pseudospectral abscissa or radius. We characterize fixed points of the iterations, and we discuss conditions under which the sequence of lower bounds converges to local maximizers of the real part or modulus over the pseudospectrum, proving a locally linear rate of convergence for $\varepsilon$ sufficiently small. The convergence results depend on a perturbation theorem for the normalized eigenprojection of a matrix as well as a characterization of the group inverse (reduced resolvent) of a singular matrix defined by a rank-one perturbation. The total cost of the algorithms is typically only a constant times the cost of computing the spectral abscissa or radius, where the value of this constant usually increases with $\varepsilon$, and may be less than 10 in many practical cases of interest.
Natural history and treatment of chronic delta hepatitis

Summary. Chronic delta hepatitis (CDH) represents a severe form of chronic viral hepatitis, induced by the hepatitis delta virus (HDV) in conjunction with the hepatitis B virus (HBV). Delta hepatitis may lead to disease in humans through co‐infection. The former leads to acute hepatitis which clinically can range from mild hepatitis to fulminant hepatitis and death. Severe or fulminant hepatitis is more often observed with HBV‐HDV co‐infection compared to HBV mono‐infection. Chronic infection after acute hepatitis B + D co‐infection is infrequent and similar to the rate in mono‐infected patients. CDH develops in 70–90% of patients with superinfection. CDH runs a more progressive course than chronic hepatitis B and may lead to cirrhosis within 2 years in 10–15% of patients. However, as with any immune‐mediated disease, different patterns of progression, ranging from mild to severe progressive disease, are observed. Active replication of both HBV and HDV may be associated with a more progressive disease pattern. Further, different HDV and HBV genotypes may contribute to various disease outcomes. CDH may be frequently associated with hepatocellular carcinoma development although recent studies provided conflicting results. The only established therapy for CDH is treatment with interferons for a duration of at least 1 year. On treatment, 6 month HDV RNA assessment may give clues as to whether to stop treatment at 1 year or continue beyond 1 year. New approaches to treatment of CDH are an urgent need of which the use of prenylation inhibitors appears the most promising.
The Effect of Converting Enzyme Inhibition with SQ20,881 on Plasma and Urinary Kinins, Prostaglandin E, and Angiotensin II in Hypertensive Man

SUMMARY The relationship between levels of angiotensin II, kinins, and prostaglandin E and the depressor response to 1 or 3 mg/kg of the conrerting enzyme inhibitor SQ20.88I was studied in recumbent hypertensive subjects during 109 mEq and 9 mEq/day sodium intake. In 13 sodium-replete patients, SQ20,881 decreased angiotensin II from 46.7 ± 9.2 (mean ± SEM) to 31.7 ± 5.1 pg/ml and plasma aldosterone from 6.8 ± 0.9 to 2.9 ± 0.6 ng/dl (p < 0.003) without compensatory elevations of plasma renin activity and angiotensin I. Administration of SQ20.881 had no effect on plasma bradyklnin but it increased mean immunoreactive prostaglandin E from 143 ± 17 to 302 ± 75 pg/ml (p < 0.02) and in some patients it increased urinary kinin excretion. The distribution of the mean 2-hour depressor response was bimodal as four patients had a fall in diastollc pressure of at least 11 torr (mean 14 ± 1 torr) and nine had a minimal depressor response £ 4 torr, (−1 ± 1 torr); patients with a greater decrease in blood pressure showed an increase in urinary kinin excretion rate, whereas the other patients showed a fall (471 ± 121 vs − 99 ± 106 ng/hr; p < 0.005); both had similar control levels and responses of plasma angiotensin II, aldosterone, immunoreactive prostaglandin E, and brad} kinin. In nine sodium-depleted patients, SQ20.881 slightly decreased mean angiotensin II from 30.5 ± 4.5 to 22.4 ± 4.3 pg/ml early after drug administration, but because this was accompanied by rapid compensatory elevations of angiotensin I (which increased from < 14 pg/ml to levels as high as 513 pg/ml) and mean plasma renin activity from 43 ± 1.6 to 13.9 ± 43 ng/ml/hr, levels of angiotensin II returned toward control soon after drug administration. We found that SQ20381 had no effect on plasma bradykinin but increased urinary kinin excretion by 203 ± 63 ng/hr (p < 02) and in some patients increased plasma prostaglandin E. The distribution of the mean 2-hour depressor response in these nine sodium-depleted patients was also bimodal as flve sodium-depleted patients had a depressor response to drug of at least 7 torr (10 ± 1 torr) while four sodium-depleted patients had a minimal response (−1 ± 1 torr). The patients with a greater decrease in blood pressure showed a greater (p < 0.05) increase in both immunoreactive prostaglandin E (248 ± 99 vs 20 ± 12 pg/ml) and urinary kinin excretion (270 ± 69 vs 83 ± 75 ng/hr) whereas decrements in plasma angiotensin II and aldosterone were similar. Thus, the depressor response to SQ20,881 correlated better with alterations in urinary kinins and plasma prostaglandin E than with changes in plasma levels of angiotensin II.
Linking of Microorganisms to Phenanthrene Metabolism in Soil by Analysis of 13C-Labeled Cell Lipids

ABSTRACT Phenanthrene-metabolizing soil microbial communities were characterized by examining mineralization of [14C]phenanthrene, by most-probable-number (MPN) counting, by 16S-23S spacer DNA analysis of the numerically dominant, culturable phenanthrene-degrading isolates, and by examining incorporation of [13C]phenanthrene-derived carbon into sterols and polar lipid fatty acids (PLFAs). An unpolluted agricultural soil, a roadside soil diffusely polluted with polycyclic aromatic hydrocarbons (PAHs), and two highly PAH-polluted soils from industrial sites were analyzed. Microbial phenanthrene degraders were not detected by MPN counting in the agricultural soil and the roadside soil. In the industrial soils, phenanthrene degraders constituted 0.04 and 3.6% of the total number of CFU. 16S-23S spacer DNA analysis followed by partial 16S DNA sequencing of representative isolates from one of the industrial soils showed that one-half of the isolates belonged to the genus Sphingomonas and the other half were closely related to an unclassified beta-proteobacterium. The 13C-PLFA profiles of the two industrial soils were relatively similar and resembled the profiles of phenanthrene-degrading Sphingomonas reference strains and unclassified beta-proteobacterium isolates but did not match the profiles of Pseudomonas, Mycobacterium, or Nocardia reference strains. The 13C-PLFA profiles of phenanthrene degraders in the agricultural soil and the roadside soil were different from each other and different from the profiles of the highly polluted industrial soils. Only in the roadside soil were 10me/12me18:0 PLFAs enriched in 13C, suggesting that actinomycetes metabolized phenanthrene in this soil. The 13C-PLFA profiles of the unpolluted agricultural soil did not resemble the profiles of any of the reference strains. In all of the soils investigated, no excess 13C was recovered in the 18:2ω6,9 PLFA, suggesting that fungi did not contribute significantly to assimilation of [13C]phenanthrene.