Miracle-dz/UniFAR-FTUs huggingface dataset:
The Circadian Clock Component BMAL1 Is a Critical Regulator of p21WAF1/CIP1 Expression and Hepatocyte Proliferation*

Most living organisms show circadian (∼24 h) rhythms in physiology and behavior. These oscillations are generated by endogenous circadian clocks, present in virtually all cells where they control key biological processes. Although circadian gating of mitosis has been reported for many years in some peripheral tissues, the underlying molecular mechanisms have remained poorly understood. Here we show that the cell cycle inhibitor p21WAF1/CIP1 is rhythmically expressed in mouse peripheral organs. This rhythmic pattern of mRNA and protein expression was recapitulated in vitro in serum-shocked differentiated skeletal muscle cells. p21WAF1/CIP1 circadian expression is dramatically increased and no longer rhythmic in clock-deficient Bmal1–/– knock-out mice. Biochemical and genetic data show that oscillation of p21WAF1/CIP1 gene transcription is regulated by the antagonistic activities of the orphan nuclear receptors REV-ERBα/β and RORα4/γ, which are core clock regulators. Importantly, p21WAF1/CIP1 overexpressing Bmal1–/– primary hepatocytes exhibit a decreased proliferation rate. This phenotype could be reversed using small interfering RNA-mediated knockdown of p21WAF1/CIP1. These data establish a novel molecular link between clock and cell cycle genes and suggest that the G1 progression phase is a target of the circadian clock during liver cell proliferation.
Protective effects of melatonin and ghrelin on spermatogenesis: A narrative review of the literature

Spermatocytogenesis starts from lumens of seminiferous cords and after migration to the basal membrane ends to the lumens again. We attempt to review the protective effects of melatonin and ghrelin on Spermatocytogenesis and in particular on spermatogonial stem cells, as two rather newly-discovered hormones. Testicular freezing prior to chemotherapy and radiotherapy is one of the ways of preserving fertility in children with cancer. The freezing has two methods of slow-freezing (cryopreservation) and rapid-freezing (vitrification). Administration of melatonin can maintain the quality of the germ cells underwent such processes, as well as ghrelin, can protect germ cells from the toxicities secondary to ischemic injuries, and pathologic apoptosis. This review indicates that in vitro or in vivo administration of melatonin or ghrelin, could be effective to preserve fertilization and also they can be used in assisted reproductive technologies to improve the quality of sperms. Future original studies should be propelled toward human studies, of course with observing the ethics.
The Semiconserved Head Structure of Plasmodium falciparum Erythrocyte Membrane Protein 1 Mediates Binding to Multiple Independent Host Receptors

Erythrocytes infected with mature forms of Plasmodium falciparum do not circulate but are withdrawn from the peripheral circulation; they are bound to the endothelial lining and to uninfected erythrocytes in the microvasculature. Blockage of the blood flow, hampered oxygen delivery, and severe malaria may follow if binding is excessive. The NH2-terminal head structure (Duffy binding–like domain 1 [DBL1α]–cysteine-rich interdomain region [CIDR1α]) of a single species of P. falciparum erythrocyte membrane protein 1 (PfEMP1) is here shown to mediate adherence to multiple host receptors including platelet-endothelial cell adhesion molecule 1 (PECAM-1)/CD31, the blood group A antigen, normal nonimmune immunoglobulin M, three virulence-associated receptor proteins, a heparan sulfate–like glucosaminoglycan, and CD36. DBL2δ was found to mediate additional binding to PECAM-1/CD31. The exceptional binding activity of the PfEMP1 head structure and its relatively conserved nature argues that it holds an important role in erythrocyte sequestration and therefore in the virulence of the malaria parasite.
In Vitro Generated Hepatocyte-Like Cells: A Novel Tool in Regenerative Medicine and Drug Discovery

Hepatocyte-like cells (HLCs) are generated from either various human pluripotent stem cells (hPSCs) including induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), or direct cell conversion, mesenchymal stem cells as well as other stem cells like gestational tissues. They provide potential cell sources for biomedical applications. Liver transplantation is the gold standard treatment for the patients with end stage liver disease, but there are many obstacles limiting this process, like insufficient number of donated healthy livers. Meanwhile, the number of patients receiving a liver organ transplant for a better life is increasing. In this regard, HLCs may provide an adequate cell source to overcome these shortages. New molecular engineering approaches such as CRISPR/ Cas system applying in iPSCs technology provide the basic principles of gene correction for monogenic inherited metabolic liver diseases, as another application of HLCs. It has been shown that HLCs could replace primary human hepatocytes in drug discovery and hepatotoxicity tests. However, generation of fully functional HLCs is still a big challenge; several research groups have been trying to improve current differentiation protocols to achieve better HLCs according to morphology and function of cells. Large-scale generation of functional HLCs in bioreactors could make a new opportunity in producing enough hepatocytes for treating end-stage liver patients as well as other biomedical applications such as drug studies. In this review, regarding the biomedical value of HLCs, we focus on the current and efficient approaches for generating hepatocyte-like cells in vitro and discuss about their applications in regenerative medicine and drug discovery.
Splitting the Least-Mean-Square Algorithm

The least-mean-square (LMS) algorithm is an adaptation scheme widely used in practice due to its simplicity. In some applications the involved signals are continuous-time. Then, usually either a fully analog implementation of the LMS algorithm is applied or the input data are sampled by analog-to-digital (AD) converters to be processed digitally. A purely digital realization is most often the preferred choice, however, it becomes costly for high-frequency input signals since fast AD converters are needed. In this paper we propose a hybrid analog/digital approach allowing the AD conversion rate to be as low as the update-rate of the LMS algorithm. We demonstrate the advantage of this approach applying it to an interference cancellation problem occurring in wireline communications: the sampling rate of the AD converters is reduced by a factor of 250. (Less)
A role for descending auditory cortical projections in songbird vocal learning

Many learned motor behaviors are acquired by comparing ongoing behavior with an internal representation of correct performance, rather than using an explicit external reward. For example, juvenile songbirds learn to sing by comparing their song with the memory of a tutor song. At present, the brain regions subserving song evaluation are not known. In this study, we report several findings suggesting that song evaluation involves an avian 'cortical' area previously shown to project to the dopaminergic midbrain and other downstream targets. We find that this ventral portion of the intermediate arcopallium (AIV) receives inputs from auditory cortical areas, and that lesions of AIV result in significant deficits in vocal learning. Additionally, AIV neurons exhibit fast responses to disruptive auditory feedback presented during singing, but not during nonsinging periods. Our findings suggest that auditory cortical areas may guide learning by transmitting song evaluation signals to the dopaminergic midbrain and/or other subcortical targets. DOI: http://dx.doi. org/10.7554/eLife.02152. 001
Theory of Mind and Emotional Awareness Deficits in Patients With Somatoform Disorders

Objective: To explore whether deficits are present in the mental representation of emotion signals and whether these are related to more general deficits in Theory of Mind (ToM) functioning test. To test this hypothesis in patients suffering from somatoform disorders, we used the Frith-Happé-Animations Task (AT)—an established ToM measure. We previously demonstrated that somatization in psychiatric patients is associated with decreased emotional awareness as measured by the Levels of Emotional Awareness Scale (LEAS). These findings suggest that individuals with decreased emotional awareness often fail to experience affective arousal as feelings and instead experience emotional distress somatically. Methods: We administered the AT and the LEAS to 30 hospitalized patients with somatoform disorders and 30 healthy controls matched for sex, age, and educational level. Emotional awareness on the LEAS, the emotional content of AT narratives, and ToM content on the AT were assessed. Results: Patients with somatoform disorders scored significantly lower on the LEAS than healthy controls. Patients also demonstrated both reduced emotional content and reduced ToM functioning on the AT compared with control subjects. Deficits in ToM functioning in patients overlapped with but were not fully explained by deficits in the emotional content of animation narratives. The combination of ToM functioning and LEAS scores permitted a correct classification of 80% of patients and 73% of controls. Conclusions: Patients with somatoform disorders requiring inpatient treatment manifest deficits in both emotional awareness and ToM functioning. These deficits may underlie the phenomenon of somatization. ToM = Theory of Mind; GD = goal-directedness; LEAS = Levels of Emotional Awareness Scale; AT = Frith-Happé Animations Task.
Visuo-motor coordination ability predicts performance with brain-computer interfaces controlled by modulation of sensorimotor rhythms (SMR)

Modulation of sensorimotor rhythms (SMR) was suggested as a control signal for brain-computer interfaces (BCI). Yet, there is a population of users estimated between 10 to 50% not able to achieve reliable control and only about 20% of users achieve high (80–100%) performance. Predicting performance prior to BCI use would facilitate selection of the most feasible system for an individual, thus constitute a practical benefit for the user, and increase our knowledge about the correlates of BCI control. In a recent study, we predicted SMR-BCI performance from psychological variables that were assessed prior to the BCI sessions and BCI control was supported with machine-learning techniques. We described two significant psychological predictors, namely the visuo-motor coordination ability and the ability to concentrate on the task. The purpose of the current study was to replicate these results thereby validating these predictors within a neurofeedback based SMR-BCI that involved no machine learning.Thirty-three healthy BCI novices participated in a calibration session and three further neurofeedback training sessions. Two variables were related with mean SMR-BCI performance: (1) a measure for the accuracy of fine motor skills, i.e., a trade for a person’s visuo-motor control ability; and (2) subject’s “attentional impulsivity”. In a linear regression they accounted for almost 20% in variance of SMR-BCI performance, but predictor (1) failed significance. Nevertheless, on the basis of our prior regression model for sensorimotor control ability we could predict current SMR-BCI performance with an average prediction error of M = 12.07%. In more than 50% of the participants, the prediction error was smaller than 10%. Hence, psychological variables played a moderate role in predicting SMR-BCI performance in a neurofeedback approach that involved no machine learning. Future studies are needed to further consolidate (or reject) the present predictors.
A nationwide prospective cohort study on return to gainful occupation after stroke in Denmark 1996–2006

Background Return to work is an important outcome factor for working-age patients poststroke. Previous epidemiological studies on this topic have been small (on average 125 patients per study). Their estimated effects are therefore associated with a tremendous statistical uncertainty. The present study estimates the effect of various predictors on the odds of returning to work after stroke in the total population of 20–57-year-old previously employed hospital treated patients with stroke in Denmark 1996–2006 (N=19 985). Methods and results The patients were followed through national registers; 62% were gainfully occupied 2 years after stroke. The odds of returning to work were higher among people with intracerebral infarction, OR 1.0 (the reference group), than they were among people with subarachnoid haemorrhage, OR 0.79 (95% CI 0.71 to 0.88), and intracerebral haemorrhage, OR 0.39 (0.35 to 0.43). The odds of returning to work were lower among workers in elementary occupations OR 1.0 (reference group) than they were among workers in occupations that require skills at a basic level, OR 1.50 (1.38 to 1.64), technicians and associate professionals, OR 2.33 (2.05 to 2.65) and professionals, OR 3.04 (2.70 to 3.43). Patients in municipalities with a brain-injury rehabilitation centre did not have a better prognosis than patients in other municipalities, OR 0.91 (0.78 to 1.06). Being a woman, OR 0.79 (0.74 to 0.84), self-employed, OR 0.87 (0.78 to 0.96), or ≥50 years, OR 0.61 (0.57 to 0.65), was associated with an adverse prognosis. Conclusion Further research is needed to explain the gender inequality, which suggests either a potential to improve return-to-work rates among the females or a tendency among the males to return too early.
Behavior Based User Interests Extraction Algorithm

The most important issue in personalized services is how to build a proper user model for individual user. Extracting user interests is an essential question, which attracts many researchers' investigation. But most of them don't consider enough the history of user behaviors. This paper proposes a method to extract user interests from user behavior history and document information, so called Behavior based User Interests extraction (BUIE) algorithm. By analyzing document information of English scientific literatures with domain ontology, the interest items of the documents can be extracted. Then combining with the user behavior history, the user interest items' weights can be refined. Experimental results show that, BUIE algorithm could get better performance on user interests extraction than those that don't consider user behaviors. The user interests calculated by this method are quite consistent with user's real interests. The different kinds of behaviors' contribution degrees to user interests are analyzed, and it's found that the behaviors of copying, saving, printing are important factors in extracting user interests. The contribution degree of printing is higher than that of saving and copying. But the stability of these three behaviors is less than that of relative browsing time.
Process-Variation Statistical Modeling for VLSI Timing Analysis

SSTA requires accurate statistical distribution models of non-Gaussian random variables of process parameters and timing variables. Traditional quadratic Gaussian model has been shown to have some serious limitations. In particular, it limits the range of skewness that can be modeled and it can not model the kurtosis. In this paper, we presented complex-coefficient quadratic Gaussian polynomial model and higher order Gaussian polynomial model to resolve these difficulties. Experimental results show how our methods and new algorithms expose some enhancements in both accuracy and versatility.
Changes in the Daily Rhythm of Lipid Metabolism in the Diabetic Retina

Disruption of circadian regulation was recently shown to cause diabetes and metabolic disease. We have previously demonstrated that retinal lipid metabolism contributed to the development of diabetic retinopathy. The goal of this study was to determine the effect of diabetes on circadian regulation of clock genes and lipid metabolism genes in the retina and retinal endothelial cells (REC). Diabetes had a pronounced inhibitory effect on the negative clock arm with lower amplitude of the period (per) 1 in the retina; lower amplitude and a phase shift of per2 in the liver; and a loss of cryptochrome (cry) 2 rhythmic pattern in suprachiasmatic nucleus (SCN). The positive clock arm was increased by diabetes with higher amplitude of circadian locomotor output cycles kaput (CLOCK) and brain and muscle aryl-hydrocarbon receptor nuclear translocator-like 1 (bmal1) and phase shift in bmal1 rhythmic oscillations in the retina; and higher bmal1 amplitude in the SCN. Peroxisome proliferator-activated receptor (PPAR) α exhibited rhythmic oscillation in retina and liver; PPARγ had lower amplitude in diabetic liver; sterol regulatory element-binding protein (srebp) 1c had higher amplitude in the retina but lower in the liver in STZ- induced diabetic animals. Both of Elongase (Elovl) 2 and Elovl4 had a rhythmic oscillation pattern in the control retina. Diabetic retinas lost Elovl4 rhythmic oscillation and had lower amplitude of Elovl2 oscillations. In line with the in vivo data, circadian expression levels of CLOCK, bmal1 and srebp1c had higher amplitude in rat REC (rREC) isolated from diabetic rats compared with control rats, while PPARγ and Elovl2 had lower amplitude in diabetic rREC. In conclusion, diabetes causes dysregulation of circadian expression of clock genes and the genes controlling lipid metabolism in the retina with potential implications for the development of diabetic retinopathy.
Line watermark embedding method for affine transformed images

This paper describes a new content-based affine-invariant digital watermarking technique. With the proposed embedding and detecting scheme, the watermark patterns are located along the lines constructed from pairs of imagepsilas salient points. By using a pair of feature points, the method can perform a search for a watermark faster than other schemes that require at least three correspondence points. The problem of limited embedding capacity, which results in weak robustness, is addressed. A solution to increase the method robustness using multiple line averaging is described. In addition, by utilizing a certain constraint on cropping pattern, the method can be used to provide an estimation of a cropping boundary.
Depleted plural marking in two Afro-Hispanic dialects: Separating inheritance from innovation

ABS T R AC T Spanish is characterized by number concord in determiner phrases (DPs) and predicate nominals; the plural marker /s/ is attached to all relevant elements in a plural DP. Exceptions to this rule usually involve phonetically motivated processes of /s/-weakening in coda position, and do not result in a functionally different system of plural marking. A distinct pattern is found in two isolated dialects of Spanish spoken in ethnically cohesive Afro-descendent communities where Spanish was originally acquired as a second language by speakers of African languages. In both varieties, characterized by the absence of /s/-reducing phenomena, plural /-s/ tends to be marked only on the first element of plural DPs, usually a determiner. In one of the dialects, spoken in Ecuador, these “stripped plurals” alternate with full multiple plural concord, similar to vernacular Brazilian Portuguese. In the other dialect, spoken in Bolivia, stripped plurals appear to be a recent development, emerging from a more restructured traditional variety in which plural /-s/ was not used at all. A variational analysis of both dialects finds little evidence for spontaneous drift away from canonical multiple plural marking, but rather suggests an evolution from earlier contact-induced interlanguages that exhibited even less systematic plural marking. The appearance of Afro-Hispanic stripped plurals is tentatively correlated with the shift from a depleted definite article system to a configuration more closely resembling modern Spanish. A similar set of circumstances may have contributed to the formation of stripped plurals in vernacular Brazilian Portuguese.
The Review of Economics and Statistics

This paper examines the properties of instrumental variables (IV) applied to models with essential heterogeneity, that is, models where responses to interventions are heterogeneous and agents adopt treatments (participate in programs) with at least partial knowledge of their idiosyncratic response. We analyze two-outcome and multiple-outcome models, including ordered and unordered choice models. We allow for transitionspecific and general instruments. We generalize previous analyses by developing weights for treatment effects for general instruments. We develop a simple test for the presence of essential heterogeneity. We note the asymmetry of the model of essential heterogeneity: outcomes of choices are heterogeneous in a general way; choices are not. When both choices and outcomes are permitted to be symmetrically heterogeneous, the method of IV breaks down for estimating treatment parameters.
Early localization of 125-I-labelled human growth hormone in adrenals and other organs of immature hypophysectomized rats.

Human growth hormone (HGH) labeled with 125I was injected intravenously into hypophysectomized, immature rats. One rat was frozen 6 min and another 20 min after injection by immersion in hexane cooled with dry ice. Whole-body sections were made of the frozen rats and autoradiograms were prepared by placing these sections on x-ray film. The autoradiograms revealed that, at both time intervals after injection, there was a high concentration of radioactive material in the kidney, liver and adrenal cortex. The only other tissues found to have a higher radioactive density than that of blood were the submandibular glands, nasal mucosa, gastric mucosa, bone and follicles of vibrissae. The radioactivity in the adrenal cortex was slightly higher in the zona glomerulosa than in the zona fasciculata and it was lowest in the zona reticularis. The concentration in the epiphyseal plates was no higher than that in bone or soft tissues. The radioactivity in the submandibular gland had the electrophoretic mobility of grow.
A polymicrobial perspective of pulmonary infections exposes an enigmatic pathogen in cystic fibrosis patients

Lung disease is the leading cause of morbidity and mortality in cystic fibrosis (CF) patients. A modest number of bacterial pathogens have been correlated with pulmonary function decline; however, microbiological and molecular evidence suggests that CF airway infection is polymicrobial. To obtain a more complete assessment of the microbial community composition and dynamics, we undertook a longitudinal study by using culture-independent and microbiological approaches. In the process, we demonstrated that within complex and dynamic communities, the Streptococcus milleri group (SMG) can establish chronic pulmonary infections and at the onset of 39% of acute pulmonary exacerbations, SMG is the numerically dominant pathogen. We report the comprehensive polymicrobial community dynamics of a CF lung infection in a clinically relevant context. If a given organism, such as Pseudomonas aeruginosa, becomes resistant to antibiotic therapy, an alternative treatment avenue may mediate the desired clinical response by effectively managing the composition of the microbial community.