Miracle-dz/UniFAR-FTUs huggingface dataset:
Półtawskiego : a parameterized outline font 1 Antykwa Półtawskiego : a parameterized outline font

The question arises whether the complexity of the Computer Modern family reflects the nature of the problem (i. e., type design) or rather Knuth’s personal traits. We would incline to the latter opinion. A herd of 62 parameters may raise doubts, the more so as they control not only dimensions and slanting, but even the presence of serifs. Questionable also is Knuth’s design decision to keep the continuous change of the proportions of glyphs along with the change of font size—it perceivably deteriorates the quality of glyphs in smaller fonts (5–7 pt).
Sequencing of Pooled DNA Samples (Pool-Seq) Uncovers Complex Dynamics of Transposable Element Insertions in Drosophila melanogaster

Transposable elements (TEs) are mobile genetic elements that parasitize genomes by semi-autonomously increasing their own copy number within the host genome. While TEs are important for genome evolution, appropriate methods for performing unbiased genome-wide surveys of TE variation in natural populations have been lacking. Here, we describe a novel and cost-effective approach for estimating population frequencies of TE insertions using paired-end Illumina reads from a pooled population sample. Importantly, the method treats insertions present in and absent from the reference genome identically, allowing unbiased TE population frequency estimates. We apply this method to data from a natural Drosophila melanogaster population from Portugal. Consistent with previous reports, we show that low recombining genomic regions harbor more TE insertions and maintain insertions at higher frequencies than do high recombining regions. We conservatively estimate that there are almost twice as many “novel” TE insertion sites as sites known from the reference sequence in our population sample (6,824 novel versus 3,639 reference sites, with on average a 31-fold coverage per insertion site). Different families of transposable elements show large differences in their insertion densities and population frequencies. Our analyses suggest that the history of TE activity significantly contributes to this pattern, with recently active families segregating at lower frequencies than those active in the more distant past. Finally, using our high-resolution TE abundance measurements, we identified 13 candidate positively selected TE insertions based on their high population frequencies and on low Tajima's D values in their neighborhoods.
A Novel and Effective Chromatographic Approach to the Separation of Isoflavone Derivatives from Pueraria lobata

A novel and effective chromatographic approach to the separation and purification of isoflavone compounds from Pueraria lobata is described. The method is based on flash chromatography (FC), coupled to preparative high performance liquid chromatography (prep-HPLC) via a six-way valve. The FC step comprised tandem reversed phase columns, pre-packed with MCI gel (Mitsubishi Chemical Corp., Tokyo, Japan) and C18 (Fuji Silysia Chemical Ltd, Osaka, Japan) resin, respectively, and was designed to separate a crude Pueraria lobata extract into several preliminary fractions. Fractions containing the target compounds were then directly injected via the six-way valve into prep-HPLC columns, without further treatment, for final isolation and purification. Nine isoflavonoids were successfully isolated, three through an online mode and the other six through an offline mode. The purities of all compounds exceeded 95.0%, as determined by HPLC with an UV-vis photodiode array detector. The convenience, low solvent consumption, and time-saving advantages of this method offer an attractive and promising approach to the isolation of natural products.
ASCOMA: an adaptive hybrid shared memory architecture

Scalable shared memory multiprocessors traditionally use either a cache coherent non-uniform memory access (CC-NUMA) or simple cache-only memory architecture (S-COMA) memory architecture. Recently, hybrid architectures that combine aspects of both CC-NUMA and S-COMA have emerged. We present two improvements over other hybrid architectures. The first improvement is a page allocation algorithm that prefers S-COMA pages at low memory pressures. Once the local free page pool is drained, additional pages are mapped in CC-NUMA mode until they suffer sufficient remote misses to warrant upgrading to S-COMA mode. The second improvement is a page replacement algorithm that dynamically backs off the rate of page remappings from CC-NUMA to S-COMA mode at high memory pressure. This design dramatically reduces the amount of kernel overhead and the number of induced cold misses caused by needless thrashing of the page cache. The resulting hybrid architecture is called adaptive S-COMA (AS-COMA). AS-COMA exploits the best of S-COMA and CC-NUMA, performing like an S-COMA machine at low memory pressure and like a CC-NUMA machine at high memory pressure. AS-COMA outperforms CC-NUMA under almost all conditions, and outperforms other hybrid architectures by up to 17% at low memory pressure and up to 90% at high memory pressure.
Tree-Structured Models for Efficient Multi-Cue Scene Labeling

We propose a novel approach to semantic scene labeling in urban scenarios, which aims to combine excellent recognition performance with highest levels of computational efficiency. To that end, we exploit efficient tree-structured models on two levels: pixels and superpixels. At the pixel level, we propose to unify pixel labeling and the extraction of semantic texton features within a single architecture, so-called encode-and-classify trees. At the superpixel level, we put forward a multi-cue segmentation tree that groups superpixels at multiple granularities. Through learning, the segmentation tree effectively exploits and aggregates a wide range of complementary information present in the data. A tree-structured CRF is then used to jointly infer the labels of all regions across the tree. Finally, we introduce a novel object-centric evaluation method that specifically addresses the urban setting with its strongly varying object scales. Our experiments demonstrate competitive labeling performance compared to the state of the art, while achieving near real-time frame rates of up to 20 fps.
Renal structure in early autosomal-dominant polycystic kidney disease (ADPKD): The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) cohort.

BACKGROUND Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by gradual renal enlargement and cyst growth prior to loss of renal function. Standard radiographic imaging has not provided the resolution and accuracy necessary to detect small changes in renal volume or to reliably measure renal cyst volumes. The Consortium for Radiologic Imaging Studies in Polycystic Kidney Disease (CRISP) is longitudinally observing ADPKD individuals using high-resolution magnetic resonance (MR) imaging to determine if change in renal and cyst volumes can be detected over a short period of time, and if they correlate with decline in renal function early in disease. METHODS Standardization studies were conducted in phantoms and four subjects at each participating clinical center. After, in the full-scale protocol, healthy ADPKD individuals 15 to 45 years old with creatinine clearance>70 mL/min underwent standardized MR renal imaging, renal iothalamate clearance, comprehensive clinical evaluation, and determination of 24-hour urinary albumin and electrolyte excretion. Stereology was used from T1-weighted images to quantify renal volume, and region-growing thresholding was used from T2-weighted images to determine cyst volume. Renal structures were evaluated in relation to demographic, clinical, and biochemical variables using means/medians, standard deviations, and Pearson correlations. RESULTS Reliability coefficients for MR renal and cyst volume measurements in phantoms were 99.9% and 89.2%, respectively. In the full-scale protocol, 241 ADPKD individuals (145 women and 96 men) were enrolled. Total renal, cyst, and % cyst volume were significantly greater in each decade group. Hypertensive individuals demonstrated greater renal, cyst, and % cyst volume than normotensive subjects. Age-adjusted renal (r = -0.31, P < 0.0001), cyst (r = -0.36, P < 0.0001), and % cyst volume (r = -0.35, P < 0.0001) were inversely related to glomerular filtration rate (GFR). Age-adjusted renal volume (r = 0.42, P < 0.0001), cystic (r = 0.39, P < 0.0001, and % cyst volume (r = 0.41, P < 0.0001) were related with urinary albumin excretion. CONCLUSION MR measures of renal and cyst volume are reliable and accurate in patients with ADPKD. ADPKD is characterized by significant cystic involvement that increases with age. Structure (renal and cyst volume) and function (GFR) are inversely related and directly related with the presence of hypertension and urinary albumin excretion in individuals with normal renal function.
Diet Quality Scores and Risk of Nasopharyngeal Carcinoma in Chinese Adults: A Case-Control Study

Many studies show that dietary factors may affect the risk of nasopharyngeal carcinoma (NPC). We examined the association between overall diet quality and NPC risk in a Chinese population. This case-control study included 600 NPC patients and 600 matched controls between 2009 and 2011 in Guangzhou, China. Habitual dietary intake and various covariates were assessed via face-to-face interviews. Diet quality scores were calculated according to the Healthy Eating Index-2005 (HEI-2005), the alternate Healthy Eating Index (aHEI), the Diet Quality Index-International (DQI-I), and the alternate Mediterranean Diet Score (aMed). After adjustment for various lifestyle and dietary factors, greater diet quality scores on the HEI-2005, aHEI, and DQI-I—but not on the aMed—showed a significant association with a lower risk of NPC (p-trends, <0.001–0.001). The odds ratios (95% confidence interval) comparing the extreme quartiles of the three significant scores were 0.47 (0.32–0.68) (HEI-2005), 0.48 (0.33–0.70) (aHEI), and 0.43 (0.30–0.62) (DQI-I). In gender-stratified analyses, the favorable association remained significant in men but not in women. We found that adherence to the predefined dietary patterns represented by the HEI-2005, aHEI, and DQI-I scales predicted a lower risk of NPC in adults from south China, especially in men.
Junctionless Nanosheet (3 nm) Poly-Si TFT: Electrical Characteristics and Superior Positive Gate Bias Stress Reliability

In this letter, a junctionless (JL) poly-Si thin-film transistor (TFT) with a 3-nm-thick nanosheet channel is successfully fabricated using the low-temperature atomic level etching process. An inversion-mode (IM) TFT is also prepared for performance comparison and reliability investigation of positive gate bias stress (PGBS). In comparison with the IM-TFT, the JL-TFT exhibits superior PGBS reliability. The origin of the difference in degradation rates between the JL and IM-TFTs is ascribed to the different transport mechanisms and different gate dielectric fields under the same gate over-drive stress. Nanosheet JL-TFTs with a 3-nm channel thickness show excellent S.S (69 mV/decade) and extremely low off-current (1.93 fA). Results indicate that it is a promising candidate for low-power 3-D integrated circuits.
Effect of physical exercise on workplace social capital: Cluster randomized controlled trial

Aims: While workplace health promotion with group-based physical exercise can improve workers’ physical health, less is known about potential carry-over effects to psychosocial factors. This study investigates the effect of physical exercise on social capital at work. Methods: Altogether, 200 female healthcare workers (nurses and nurse’s aides) from 18 departments at three hospitals were randomly allocated at the department level to 10 weeks of (1) group-based physical exercise at work during working hours or (2) physical exercise at home during leisure time. At baseline and follow-up, participants replied to a questionnaire concerning workplace social capital: (1) within teams (bonding); (2) between teams (bridging); (3) between teams and nearest leaders (linking A); (4) between teams and distant leaders (linking B). Results: At baseline, bonding, bridging, linking A and linking B social capital were 74 (SD 17), 61 (SD 19), 72 (SD 22) and 70 (SD 18), respectively, on a scale of 0–100 (where 100 is best). A group by time interaction was found for bonding social capital (P=0.02), where physical exercise at work compared with physical exercise during leisure time increased 5.3 (95% confidence interval 2.3– 8.2)(effect size, Cohen’s d = 0.31) from baseline to follow-up. For physical exercise at home during leisure time and exercise at work combined, a time effect (P=0.001) was found for linking A social capital, with a decrease of 4.8 (95% confidence interval 1.9–7.6). Conclusions: Group-based physical exercise at work contributed to building social capital within teams at the workplace. However, the general decrease of social capital between teams and nearest leaders during the intervention period warrants further research.
The Resilience and Resistance of an Ecosystem to a Collapse of Diversity

Diversity is expected to increase the resilience of ecosystems. Nevertheless, highly diverse ecosystems have collapsed, as did Lake Victoria’s ecosystem of cichlids or Caribbean coral reefs. We try to gain insight to this paradox, by analyzing a simple model of a diverse community where each competing species inflicts a small mortality pressure on an introduced predator. High diversity strengthens this feedback and prevents invasion of the introduced predator. After a gradual loss of native species, the introduced predator can escape control and the system collapses into a contrasting, invaded, low-diversity state. Importantly, we find that a diverse system that has high complementarity gains in resilience, whereas a diverse system with high functional redundancy gains in resistance. Loss of resilience can display early-warning signals of a collapse, but loss of resistance not. Our results emphasize the need for multiple approaches to studying the functioning of ecosystems, as managing an ecosystem requires understanding not only the threats it is vulnerable to but also pressures it appears resistant to.
Modulation of the NF-κB Pathway by Bordetella pertussis Filamentous Hemagglutinin

Background Filamentous hemagglutinin (FHA) is a cell-associated and secreted adhesin produced by Bordetella pertussis with pro-apoptotic and pro-inflammatory activity in host cells. Given the importance of the NF-κB transcription factor family in these host cell responses, we examined the effect of FHA on NF-κB activation in macrophages and bronchial epithelial cells, both of which are relevant cell types during natural infection. Methodology/Principal Findings Exposure to FHA of primary human monocytes and transformed U-937 macrophages, but not BEAS-2B epithelial cells, resulted in early activation of the NF-κB pathway, as manifested by the degradation of cytosolic IκBα, by NF-κB DNA binding, and by the subsequent secretion of NF-κB-regulated inflammatory cytokines. However, exposure of macrophages and human monocytes to FHA for two hours or more resulted in the accumulation of cytosolic IκBα, and the failure of TNF-α to activate NF-κB. Proteasome activity was attenuated following exposure of cells to FHA for 2 hours, as was the nuclear translocation of RelA in BEAS-2B cells. Conclusions These results reveal a complex temporal dynamic, and suggest that despite short term effects to the contrary, longer exposures of host cells to this secreted adhesin may block NF-κB activation, and perhaps lead to a compromised immune response to this bacterial pathogen.
Massive Telomere Loss Is an Early Event of DNA Damage-induced Apoptosis*

Chromosomal stability and cell viability require a proficient telomeric end-capping function. In particular, telomere dysfunction because of either critical telomere shortening or because of mutation of telomere-binding proteins results in increased apoptosis and/or cell arrest. Here, we show that, in turn, DNA damage-induced apoptosis results in a dramatic telomere loss. In particular, using flow cytometry for simultaneous detection of telomere length and apoptosis, we show that cells undergoing apoptosis upon DNA damage also exhibit a rapid and dramatic loss of telomeric sequences. This telomere loss occurs at early stages of apoptosis, because it does not require caspase-3 activation, and it is induced by loss of the mitochondrial membrane potential (Δψm) and production of reactive oxygen species. These observations suggest a direct effect of mitochondrial dysfunction on telomeres.
Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer

Significance Increasing evidence suggests that extracellular vesicles (EVs) can transfer genetic material to recipient cells. However, the mechanism and role of this phenomenon are largely unknown. Here we have made a remarkable discovery: EVs can harbor the full mitochondrial genome. These extracellular vesicles can in turn transfer their mtDNA to cells with impaired metabolism, leading to restoration of metabolic activity. We determined that hormonal therapy induces oxidative phosphorylation-deficient breast cancer cells, which can be rescued via the transfer of mtDNA-laden extracellular vesicles. Horizontal transfer of mtDNA occurred in cancer stem-like cells and was associated with increased self-renewal potential of these cells, leading to resistance to hormonal therapy. We propose that mtDNA transfer occurs in human cancer via EVs. The horizontal transfer of mtDNA and its role in mediating resistance to therapy and an exit from dormancy have never been investigated. Here we identified the full mitochondrial genome in circulating extracellular vesicles (EVs) from patients with hormonal therapy-resistant (HTR) metastatic breast cancer. We generated xenograft models of HTR metastatic disease characterized by EVs in the peripheral circulation containing mtDNA. Moreover, these human HTR cells had acquired host-derived (murine) mtDNA promoting estrogen receptor-independent oxidative phosphorylation (OXPHOS). Functional studies identified cancer-associated fibroblast (CAF)-derived EVs (from patients and xenograft models) laden with whole genomic mtDNA as a mediator of this phenotype. Specifically, the treatment of hormone therapy (HT)-naive cells or HT-treated metabolically dormant populations with CAF-derived mtDNAhi EVs promoted an escape from metabolic quiescence and HTR disease both in vitro and in vivo. Moreover, this phenotype was associated with the acquisition of EV mtDNA, especially in cancer stem-like cells, expression of EV mtRNA, and restoration of OXPHOS. In summary, we have demonstrated that the horizontal transfer of mtDNA from EVs acts as an oncogenic signal promoting an exit from dormancy of therapy-induced cancer stem-like cells and leading to endocrine therapy resistance in OXPHOS-dependent breast cancer.
In Vitro and In Vivo Studies of the Yrp1 Protease from Yersinia ruckeri and Its Role in Protective Immunity against Enteric Red Mouth Disease of Salmonids

ABSTRACT Yersinia ruckeri, the etiological agent of the enteric red mouth disease (ERM) of salmonids, produces Yrp1, a serralysin metalloprotease involved in pathogenesis. We describe here the hydrolytic and immunogenic properties of Yrp1. The protease was able to hydrolyze different matrix and muscle proteins as laminin, fibrinogen, gelatine, actin, and myosin but not type II and IV collagens. In addition, the Yrp1 protein, when inactivated by heat and used as an immunogen, was able to elicit a strong protection against the development of ERM. The analysis of different Y. ruckeri strains with (Azo+) or without (Azo−) Yrp1 activity showed that all of them contained the yrp1 operon. By using yrp1::lacZ operon fusions, protease production analysis, and complementation studies, it was possible to show that an Azo− strain was blocked at the transcription level. The transcriptional study of the yrp1 operon under different environmental conditions showed that it was regulated by osmolarity and temperature, without pH influence. Finally, when β-galactosidase activity was used as a probe in vivo, the progression of the disease in the fish could be visualized, and the tropism of the bacterium and affected organs could be defined. This system opens a vast field of study not only with regard to fish disease progression but also in pathogen interactions, temporal gene expression, carrier stages, antibiotic resistance selection, etc.
Pulmonary rehabilitation and exercise in pulmonary arterial hypertension: An underutilized intervention

Pulmonary arterial hypertension (PAH) is a rare and devastating disease characterized by progressive increases in pulmonary arterial pressure and pulmonary vascular resistance which eventually leads to right ventricular failure and death. Early thought process was that exercise and increased physical activity may be detrimental to PAH patients however many small cohort trials have proven otherwise. In addition to the many pharmaceutical options, exercise and pulmonary rehabilitation have also been shown to increase exercise capacity as well as various aspects of psychosomatic health. As pulmonary and exercise rehabilitation become more widely used as an adjuvant therapy patient outcomes improve and physicians should consider this in the therapeutic algorithm along with pharmacotherapy.
Transcript Profiling and Inference of Escherichia coli K-12 ArcA Activity across the Range of Physiologically Relevant Oxygen Concentrations*

Oxygen availability is the major determinant of the metabolic modes adopted by Escherichia coli. Although much is known about E. coli gene expression and metabolism under fully aerobic and anaerobic conditions, the intermediate oxygen tensions that are encountered in natural niches are understudied. Here, for the first time, the transcript profiles of E. coli K-12 across the physiologically significant range of oxygen availabilities are described. These suggested a progressive switch to aerobic respiratory metabolism and a remodeling of the cell envelope as oxygen availability increased. The transcriptional responses were consistent with changes in the abundance of cytochrome bd and bo′ and the outer membrane protein OmpW. The observed transcript and protein profiles result from changes in the activities of regulators that respond to oxygen itself or to metabolic and environmental signals that are sensitive to oxygen availability (aerobiosis). A probabilistic model (TFInfer) was used to predict the activity of the indirect oxygen-sensing two-component system ArcBA across the aerobiosis range. The model implied that the activity of the regulator ArcA correlated with aerobiosis but not with the redox state of the ubiquinone pool, challenging the idea that ArcA activity is inhibited by oxidized ubiquinone. The amount of phosphorylated ArcA correlated with the predicted ArcA activities and with aerobiosis, suggesting that fermentation product-mediated inhibition of ArcB phosphatase activity is the dominant mechanism for regulating ArcA activity under the conditions used here.