Miracle-dz/UniFAR-FTUs huggingface dataset:
Regime-switching factor models for high-dimensional time series

We consider a factor model for high-dimensional time series with regimeswitching dynamics. The switching is assumed to be driven by an unobserved Markov chain; the mean, factor loading matrix, and covariance matrix of the noise process are different among the regimes. The model is an extension of the traditional factor models for time series and provides flexibility in dealing with applications in which underlying states may be changing over time. We propose an iterative approach to estimating the loading space of each regime and clustering the data points, combining eigenanalysis and the Viterbi algorithm. The theoretical properties of the procedure are investigated. Simulation results and the analysis of a data example are presented.
Hierarchical Document Clustering using Frequent Itemsets

A major challenge in document clustering is the extremely high dimensionality. For example, the vocabulary for a document set can easily be thousands of words. On the other hand, each document often contains a small fraction of words in the vocabulary. These features require special handlings. Another requirement is hierarchical clustering where clustered documents can be browsed according to the increasing specificity of topics. In this paper, we propose to use the notion of frequent itemsets, which comes from association rule mining, for document clustering. The intuition of our clustering criterion is that each cluster is identified by some common words, called frequent itemsets, for the documents in the cluster. Frequent itemsets are also used to produce a hierarchical topic tree for clusters. By focusing on frequent items, the dimensionality of the document set is drastically reduced. We show that this method outperforms best existing methods in terms of both clustering accuracy and scalability.
Treatment needs and current options for postmenopausal osteoporosis

ABSTRACT Introduction: Osteoporosis is a chronic, skeletal disorder characterized by compromised bone strength and increased risk of fractures, affecting up to 50% of postmenopausal women worldwide. Over the past 2 decades there have been consistent developments in the pharmacotherapy of osteoporosis with the availability of potent inhibitors of bone resorption (bisphosphonates, and denosumab) or stimulators of bone formation (PTH analogs) with substantial improvements over calcitonin or estrogen replacement. Areas covered: In this review we summarize the effects of existing treatment options for postmenopausal osteoporosis along with the unmet clinical needs and we discuss about the potential benefits of new compounds under development. Expert opinion: Despite the recent progresses, there are still limitations and unmeet needs with all the available drugs, mainly concerning treatment adherence, efficacy on the prevention of nonvertebral fractures and the long-term adverse events of antiresorptive regimens. Moreover, PTH analogs are the only available compounds able to stimulate bone formation, but with a restricted anabolic window of no more than 2 years. Of interest, the more recent advances in bone biology identified new targets for the development of drugs with a more potent and selective activity on either osteoclasts or osteoblasts, thus making possible to uncouple bone formation from bone resorption.
Hierarchical image probability (HIP) models

We formulate a model for probability distributions on image spaces. We show that any distribution of images can be factored exactly into conditional distributions of feature vectors at one resolution (pyramid level) conditioned on the image information at lower resolutions. We would like to factor this over positions in the pyramid levels to make it tractable, but such factoring may miss long-range dependencies. To capture long-range dependencies, we introduce hidden class labels at each pixel in the pyramid. The result is a hierarchical mixture of conditional probabilities, similar to a hidden Markov model on a tree. The model parameters can be found with maximum likelihood estimation using the EM algorithm. We have obtained encouraging preliminary results on the problems of detecting various objects in SAR images and target recognition in optical aerial images.
Limited Effects of Fasting on Hepatitis B Virus (HBV) Biosynthesis in HBV Transgenic Mice

ABSTRACT Nuclear receptors have a unique role in governing hepatitis B virus (HBV) transcription and replication. Hepatocyte nuclear factor 4α (HNF4α) and retinoid X receptor α (RXRα) plus peroxisome proliferator-activated receptor α (PPARα) have been shown to support viral biosynthesis in nonhepatoma cells in the absence of additional liver-enriched transcription factors. However, the in vivo importance of these nuclear receptors in HBV biosynthesis has been investigated only to a limited extent. Fasting has been shown to activate gluconeogenesis, in part, by activating PPARγ coactivator 1 α, which in turn leads to activation of HNF4α- and RXRα/PPARα-mediated transcription. As HBV pregenomic RNA synthesis is primarily believed to be regulated by HNF4α under normal physiological conditions, it was of interest to determine the effect of fasting on the levels of HBV RNA and DNA synthesis. Fasting was shown to rather modestly increase the levels of viral proteins, transcripts, and replication intermediates in the HBV transgenic mouse model of chronic viral infection, suggesting that caloric restriction may modulate viremia to some extent during natural infection.
A study of monoclonal antibody‐producing CHO cell lines: What makes a stable high producer?

Generating stable, high‐producing cell lines for recombinant protein production requires an understanding of the potential limitations in the cellular machinery for protein expression. In order to increase our understanding of what makes a stable high producer, we have generated a panel of 17 recombinant monoclonal antibody expressing Chinese hamster ovary subclones (CHO‐mAb) with specific productivities ranging between 3 and 75 pg cell−1 day−1 using the dihydrofolate reductase (dhfr) expression system and compared the molecular features of these high‐ and low‐producer clones. The relative heavy chain (HC) and light chain (LC) transgene copy numbers and mRNA levels were determined using real‐time quantitative PCR (RT qPCR). We observed that not only higher transgene copy numbers and mRNA levels of both HC and LC were characteristic for the high‐producer clones as compared to the low‐producer clones but also a more favorable HC to LC transgene copy numbers ratio. By studying the long‐term stability of the CHO‐mAb subclones in the absence of methotrexate (MTX) selective pressure over 36 passages we observed a 35–92% decrease in volumetric productivity, primarily caused by a significant decrease in HC and LC mRNA levels with little change in the transgene copy numbers. Using Southern blot hybridization we analyzed the HC and LC transgene integration patterns in the host chromosome and their changes in course of gene amplification and long‐term culturing. We observed that MTX‐induced gene amplification caused chromosomal rearrangements resulting in clonal variability in regards to growth, productivity, and stability. No further obvious DNA rearrangements occurred during long‐term culturing in the absence of MTX, indicating that other mechanisms were responsible for the decreased transcription efficiency. Our results implicate that the amplified transgene sequences were arranged in tandem repeats potentially triggering repeat‐induced gene silencing. We hypothesize that the decline in transgene mRNA levels upon long‐term culturing without MTX was mainly caused by transgene silencing consequently leading to a loss in mAb productivity. The exact molecular mechanisms causing production instability are not yet fully understood. The herein described extensive characterization studies could help understand the limitations to high‐level, stable recombinant protein production and find ways to improving and accelerating the process for high‐producer cell line generation and selection. Biotechnol. Bioeng. 2009;102: 1182–1196. © 2008 Wiley Periodicals, Inc.
P=BPP unless E has sub-exponential circuits: Derandomizing the XOR Lemma

Yao showed that the XOR of independent random instances of a somewhat hard Boolean problem becomes almost completely unpredictable. In this paper we show that, in non-uniform settings, total independence is not necessary for this result to hold. We give a pseudo-random generator which produces n instances of a problem for which the analog of the XOR lemma holds. Combining this generator with the results of [25, 6] gives substantially improved results for hardness vs randomness trade-offs. In particular, we show that if any problem in E = DTIME(2) has circuit complexity 2, then P = BPP . Our generator is a combination of two known ones the random walks on expander graphs of [1, 10, 19] and the nearly disjoint subsets generator of [23, 25]. The quality of the generator is proved via a new proof of the XOR lemma which may be useful for other direct product results. ∗Research supported by NSF YI Award CCR-92570979, Sloan Research Fellowship BR-3311, grant #93025 of the joint US-Czechoslovak Science and Technology Program, and USA-Israel BSF Grant 92-00043 †Work partly done while visiting the Institute for Advanced Study, Princeton, N. J. 08540 and Princeton University. Research supported the Sloan Foundation, American-Israeli BSF grant 92-00106, and the Wolfson Research Awards, administered by the Israel Academy of Sciences.
Conditional Image Synthesis with Auxiliary Classifier GANs

In this paper we introduce new methods for the improved training of generative adversarial networks (GANs) for image synthesis. We construct a variant of GANs employing label conditioning that results in 128 x 128 resolution image samples exhibiting global coherence. We expand on previous work for image quality assessment to provide two new analyses for assessing the discriminability and diversity of samples from class-conditional image synthesis models. These analyses demonstrate that high resolution samples provide class information not present in low resolution samples. Across 1000 ImageNet classes, 128 x 128 samples are more than twice as discriminable as artificially resized 32 x 32 samples. In addition, 84.7% of the classes have samples exhibiting diversity comparable to real ImageNet data.
Processing speed training increases the efficiency of attentional resource allocation in young adults

Cognitive training has been shown to improve performance on a range of tasks. However, the mechanisms underlying these improvements are still unclear. Given the wide range of transfer effects, it is likely that these effects are due to a factor common to a wide range of tasks. One such factor is a participant's efficiency in allocating limited cognitive resources. The impact of a cognitive training program, Processing Speed Training (PST), on the allocation of resources to a set of visual tasks was measured using pupillometry in 10 young adults as compared to a control group of a 10 young adults (n = 20). PST is a well-studied computerized training program that involves identifying simultaneously presented central and peripheral stimuli. As training progresses, the task becomes increasingly more difficult, by including peripheral distracting stimuli and decreasing the duration of stimulus presentation. Analysis of baseline data confirmed that pupil diameter reflected cognitive effort. After training, participants randomized to PST used fewer attentional resources to perform complex visual tasks as compared to the control group. These pupil diameter data indicated that PST appears to increase the efficiency of attentional resource allocation. Increases in cognitive efficiency have been hypothesized to underlie improvements following experience with action video games, and improved cognitive efficiency has been hypothesized to underlie the benefits of PST in older adults. These data reveal that these training schemes may share a common underlying mechanism of increasing cognitive efficiency in younger adults.
From cell senescence to age-related diseases: differential mechanisms of action of senescence-associated secretory phenotypes

Cellular senescence is a process by which cells enter a state of permanent cell cycle arrest. It is commonly believed to underlie organismal aging and age-associated diseases. However, the mechanism by which cellular senescence contributes to aging and age-associated pathologies remains unclear. Recent studies showed that senescent cells exert detrimental effects on the tissue microenvironment, generating pathological facilitators or aggravators. The most significant environmental effector resulting from senescent cells is the senescence-associated secretory phenotype (SASP), which is constituted by a strikingly increased expression and secretion of diverse pro-inflammatory cytokines. Careful investigation into the components of SASPs and their mechanism of action, may improve our understanding of the pathological backgrounds of age-associated diseases. In this review, we focus on the differential expression of SASP-related genes, in addition to SASP components, during the progress of senescence. We also provide a perspective on the possible action mechanisms of SASP components, and potential contributions of SASP-expressing senescent cells, to age-associated pathologies. [BMB Reports 2015; 48(10): 549-558]
Implication of Left Ventricular Diastolic Dysfunction in Cryptogenic Ischemic Stroke

Background and Purpose— Left ventricular diastolic dysfunction (LVDD) is a predictor for atrial fibrillation (AF). This study was aimed to investigate whether LVDD in cryptogenic ischemic stroke (CS) could be a clue to stroke mechanism. Methods— The clinical and echocardiographic findings of 1589 consecutive patients with acute ischemic stroke or transient ischemic attack between 2004 and 2013 were reviewed. LVDDs among stroke subtypes were graded by transthoracic echocardiography into 4 groups by severity: normal, abnormal relaxation (grade I), pseudonormal (grade II), and restrictive diastolic filling (grade III), whereas severe LVDD was defined as grade III. We classified the lesion pattern of CS into cardioembolism-mimic or non–cardioembolism-mimic and determined whether cardioembolism-mimic lesions were associated with severe LVDD. Results— The fraction of severe LVDD in CS was not different from that of stroke with AF (27.3% versus 37.1%; P=0.173) but was significantly higher than that of stroke without AF (27.3% versus 13.4%; P=0.008). Cardioembolism-mimic CS had more severe LVDD than non–cardioembolism-mimic CS (41.4% versus 11.5%; P=0.013). LVDD of grade II (odds ratio, 4.37; 95% confidence interval, 2.99–6.41) and grade III (odds ratio, 5.60; 95% confidence interval, 3.42–9.17) were independently related to stroke with AF after adjusting covariates. Conclusions— The severe LVDD could be a predictor of stroke with AF, and its frequency was similar between CS and stroke with AF. Cardioembolism-mimic CS had significantly more severe LVDD than non–cardioembolism-mimic CS. LVDD could be helpful to discriminate the stroke mechanism in the patients with acute CS.
Class 1 KNOX genes are not involved in shoot development in the moss Physcomitrella patens but do function in sporophyte development

SUMMARY Although the number and form of metazoan organs are determined in the embryo, plants continuously form organs via pluripotent stem cells contained within the meristem. Flowering plants have an indeterminate meristem in their diploid generation, whereas the common ancestor of land plants is inferred to have formed an indeterminate meristem in its haploid generation, as observed in the extant basal land plants, bryophytes, including mosses. It is hypothesized that the underlying gene networks for the diploid meristem were initially present in the haploid generation of the basal land plants and were eventually co‐opted for expression in the diploid generation. In flowering plants, the class 1 KNOTTED1‐LIKE HOMEOBOX (KNOX) transcription factors are essential for the function of the indeterminate apical meristem. Here, we show that the class 1 KNOX orthologs function in the diploid organ, with determinate growth in the moss Physcomitrella patens, but do not function in the haploid indeterminate meristem. We propose that the genetic networks governing the indeterminate meristem in land plants are variable, and the networks governing the diploid indeterminate meristem with the class 1 KNOX genes likely evolved de novo in the flowering plant lineage.
Short-Lived, Transitory Cell-Cell Interactions Foster Migration-Dependent Aggregation

During embryonic development, motile cells aggregate into cohesive groups, which give rise to tissues and organs. The role of cell migration in regulating aggregation is unclear. The current paradigm for aggregation is based on an equilibrium model of differential cell adhesivity to neighboring cells versus the underlying substratum. In many biological contexts, however, dynamics is critical. Here, we provide evidence that multicellular aggregation dynamics involves both local adhesive interactions and transport by cell migration. Using time-lapse video microscopy, we quantified the duration of cell-cell contacts among migrating cells that collided and adhered to another cell. This lifetime of cell-cell interactions exhibited a monotonic decreasing dependence on substratum adhesivity. Parallel quantitative measurements of cell migration speed revealed that across the tested range of adhesive substrata, the mean time needed for cells to migrate and encounter another cell was greater than the mean adhesion lifetime, suggesting that aggregation dynamics may depend on cell motility instead of the local differential adhesivity of cells. Consistent with this hypothesis, aggregate size exhibited a biphasic dependence on substratum adhesivity, matching the trend we observed for cell migration speed. Our findings suggest a new role for cell motility, alongside differential adhesion, in regulating developmental aggregation events and motivate new design principles for tuning aggregation dynamics in tissue engineering applications.
DISTRIBUTION AND BIOACCUMULATION OF HEAVY METALS Pb AND Cd ON BIVALVES Anadara nodifera, Meretrix lyrata, AND Solen lamarckii IN COASTAL WATERS OF THE WEST MADURA STRAIT

Madura strait receives waste disposal from various activites in the mainland, making it vulnerable to contamination of harmful pollutants. Some of the harmful pollutants are heavy metal Pb and Cd. The high concentration Cd and Pb give negative impacts to the biota including bivalves. This study was conducted to assess the distribution of heavy metals Pb and Cd in the waters and their accumulation in bivalves Anadara nodifera , Meretrix lyrata , and Solen lamarckii in coastal waters of the West Madura Strait. Heavy metal analysis refer to APHA 2012 using AAS. The results showed that concentration of Cd and Pb in water were below the quality standards, while in sediment were above the standard (Cd of 7.20 mg/kg and Pb of 62.06 mg/kg). The concentration of Cd in bivalve were different among the species tested A. nodifera of 6.10 mg/kg, M. lyrata of 3.65 mg/kg, and S. lamarckii of 2.74 mg/kg, as well as Pb concentration A. nodifera of 60.10 mg/kg, M . lyrata of 51.48 mg/kg, and S. lamarckii of 45.29 mg/kg). These results indicate d that the three shells have exceeded the maximum limit of heavy metal contamination in food (Cd of 1.0 mg/kg and Pb of 1.5 mg/kg). Keywords: bivalve, heavy metal, Madura Strait
Age- and Sex-Specific Impact of Health Literacy on Healthy Lifestyle Characteristics among Japanese Residents in a Rural Community

The study aimed to examine age- and sex-specific associations between health literacy (HL) and healthy lifestyle characteristics. The cross-sectional study was conducted to examine a total 1348 Japanese participants (613 male and 735 female) who took the health check-up program in April 2013, at Tsumagoi Village, Japan. Information was collected by self-administered questionnaire on three communicative and two critical HL items, and healthy lifestyle characteristics listed in Bres-low’s seven health practices. In multivariate logistic analysis, high HL (≥18) was significantly asso-ciated with healthy lifestyle characteristics in both non-elderly (<65 years old) and elderly (≥65 years old) [Odds ratio (OR) = 1.40, 95% Confidence interval (CI) = 1.13 - 1.75 for non-elderly, OR = 1.34, 95% CI = 1.02 - 1.76 for elderly], as well as female participants (OR = 1.43, 95% CI = 1.06 - 1.94), while the significance was borderline in male participants (OR = 1.34, 95% CI = 0.96 - 1.88). Among 5 HL items, the ability to extract health-related information was significantly associated with healthy lifestyle characteristics (OR = 1.52, 95% CI = 1.11 - 2.07 for non-elderly, OR = 1.55, 95% CI = 1.04 - 2.30 for elderly, OR = 1.95, 95% CI = 1.28 - 2.97 for female participants. HDL-C concentration in the high HL group was significantly higher than that in the low HL group. Among healthy lifestyle characteristics, proportions of smoking behavior (non-smoker), exercise frequency (twice or more per week), and sleep duration (7 - 8 hours) were significantly higher in the high HL group than in the low HL group. The present study revealed a positive association between HL and healthy lifestyle characteristics, which suggests that people are likely to engage in health-promoting behaviours based on access and ability to understand medical information for both age groups and female participants. Significant findings among female participants may be emphasized since it’s important from the entire family's perspective as women are the caretakers of the family. These findings may indicate the importance of comprehensive assessment, including HL, for health promotion in the community.
Clostridial Neurotoxins and Substrate Proteolysis in Intact Neurons

Clostridial neurotoxins are zinc endopeptidases that block neurotransmission and have been shown to cleave, in vitro, specific proteins involved in synaptic vesicle docking and/or fusion. We have used immunohistochemistry and immunoblotting to demonstrate alterations in toxin substrates in intact neurons under conditions of toxin-induced blockade of neurotransmitter release. Vesicle-associated membrane protein, which co-localizes with synaptophysin, is not detectable in tetanus toxin-blocked cultures. Syntaxin, also concentrated in synaptic sites, is cleaved by botulinum neurotoxin C. Similarly, the carboxyl terminus of the synaptosomal-associated protein of 25 kDa (SNAP-25) is not detectable in botulinum neurotoxin A-treated cultures. Unexpectedly, tetanus toxin exposure causes an increase in SNAP-25 immunofluorescence, reflecting increased accessibility of antibodies to antigenic sites rather than increased expression of the protein. Furthermore, botulinum neurotoxin C causes a marked loss of the carboxyl terminus of SNAP-25 when the toxin is added to living cultures, whereas it has no action on SNAP-25 in in vitro preparations. This study is the first to demonstrate in functioning neurons that the physiologic response to these toxins is correlated with the proteolysis of their respective substrates. Furthermore, the data demonstrate that botulinum neurotoxin C, in addition to cleaving syntaxin, exerts a secondary effect on SNAP-25.