Miracle-dz/UniFAR-FTUs huggingface dataset:
SIRT1-FOXO3a Regulate Cocaine Actions in the Nucleus Accumbens

Previous studies have shown that chronic cocaine administration induces SIRT1, a Class III histone deacetylase, in the nucleus accumbens (NAc), a key brain reward region, and that such induction influences the gene regulation and place conditioning effects of cocaine. To determine the mechanisms by which SIRT1 mediates cocaine-induced plasticity in NAc, we used chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-seq), 1 d after 7 daily cocaine (20 mg/kg) or saline injections, to map SIRT1 binding genome-wide in mouse NAc. Our unbiased results revealed two modes of SIRT1 action. First, despite its induction in NAc, chronic cocaine causes depletion of SIRT1 from most affected gene promoters in concert with enrichment of H4K16ac (itself a deacetylation target of SIRT1), which is associated with increased expression of these genes. Second, we deduced the forkhead transcription factor (FOXO) family to be a downstream mechanism through which SIRT1 regulates cocaine action. We proceeded to demonstrate that SIRT1 induction causes the deacetylation and activation of FOXO3a in NAc, which leads to the induction of several known FOXO3a gene targets in other systems. Finally, we directly establish a role for FOXO3a in promoting cocaine-elicited behavioral responses by use of viral-mediated gene transfer: we show that overexpressing FOXO3a in NAc enhances cocaine place conditioning. The discovery of these two actions of SIRT1 in NAc in the context of behavioral adaptations to cocaine represents an important step forward in advancing our understanding of the molecular adaptations underlying cocaine action.
Adjuvant therapies and patient and tumor characteristics associated with survival of adult patients with adrenocortical carcinoma.

CONTEXT Adrenocortical carcinoma is a rare malignant endocrine neoplasia. Studies regarding outcome and prognostic factors rely on fairly small studies. Here we summarize the experience with patients with a diagnosis of adrenocortical carcinoma from a large tertiary referral center. OBJECTIVE The objective of the study was to identify prognostic factors in patients with adrenocortical carcinoma and evaluate adjuvant treatment strategies. DESIGN Patient data were collected in a retrospective single-center study. Epidemiological, patient, and tumor characteristics were analyzed for prognostic factors regarding overall and recurrence-free survival in Cox regression models (multivariable and univariable). RESULTS Three hundred ninety-one adult patients with the diagnosis of adrenocortical carcinoma were identified. Median overall survival was 35.2 months. Cortisol production [hazard ratio (HR) 1.4, HR 1.5], tumor stage (HR stage 3 of 2.1 and 2.1, HR stage 4 of 4.8), and tumor grade (HR 2.4 and 2.0) were identified as negative prognostic factors (HR for death, HR for recurrence). Mitotane therapy increases recurrence-free survival, an effect that was significantly further improved by adjuvant radiation therapy but did not impact overall survival. Patients with open adrenalectomy had improved overall survival. CONCLUSIONS This study increases the evidence for adverse risk factors (cortisol production, high tumor stage, and high tumor grade) and suggests the following therapy approach: adrenocortical carcinoma patients should be treated with open adrenalectomy. Adjuvant therapy, particularly mitotane therapy in conjunction with radiation, should be considered to delay tumor recurrence.
Heme, a Plastid-Derived Regulator of Nuclear Gene Expression in Chlamydomonas[W]

To gain insight into the chloroplast-to-nucleus signaling role of tetrapyrroles, Chlamydomonas reinhardtii mutants in the Mg-chelatase that catalyzes the insertion of magnesium into protoporphyrin IX were isolated and characterized. The four mutants lack chlorophyll and show reduced levels of Mg-tetrapyrroles but increased levels of soluble heme. In the mutants, light induction of HSP70A was preserved, although Mg-protoporphyrin IX has been implicated in this induction. In wild-type cells, a shift from dark to light resulted in a transient reduction in heme levels, while the levels of Mg-protoporphyrin IX, its methyl ester, and protoporphyrin IX increased. Hemin feeding to cultures in the dark activated HSP70A. This induction was mediated by the same plastid response element (PRE) in the HSP70A promoter that has been shown to mediate induction by Mg-protoporphyrin IX and light. Other nuclear genes that harbor a PRE in their promoters also were inducible by hemin feeding. Extended incubation with hemin abrogated the competence to induce HSP70A by light or Mg-protoporphyrin IX, indicating that these signals converge on the same pathway. We propose that Mg-protoporphyrin IX and heme may serve as plastid signals that regulate the expression of nuclear genes.
Vaccination in inflammatory bowel disease patients: attitudes, knowledge, and uptake.

BACKGROUND Immunomodulators and biological agents, used to treat inflammatory bowel disease [IBD], are associated with an increased risk of infection, including vaccine-preventable infections. We assessed patient attitudes towards vaccination, knowledge of vaccine recommendations, and uptake of recommended vaccines. METHODS Patients attending IBD clinics completed a self-administered, structured, paper-based questionnaire. We collected demographic data, medical and immunisation history, self-reported patient uptake, knowledge, and perceptions of childhood and adult vaccinations. RESULTS The prevalence of treatment with biologicals, steroids, thiopurines, and methotrexate among the 300 respondents were 37.3%, 16.0%, 16.0%, and 5.7%, respectively. Self-reported vaccine completion was reported by 45.3% of patients. Vaccination uptake rates were 61.3% for influenza, 10.3% for pneumococcus, 61.0% for hepatitis B, 52.0% for hepatitis A, 26.0% for varicella, 20.7% for meningococcus, 5.3% for herpes zoster, and 11.0% for herpes papilloma virus [females only]. Significant predictors of vaccine completion were annual vaccination review by family physician (odds ratio [OR] = 1.82) or gastroenterologist [OR = 1.72], current steroid use [OR = 1.28], and current or prior treatment with biologicals [OR = 1.42]. The majority of patients reported that the primary responsibility to ensure vaccine completion lies with the patient [41.7%] and the family physician [32.3%]. Uncertainty about indications, fears of side effects, and concerns regarding vaccine safety were the most commonly reported reasons for non-uptake [22.0%, 20.7%, and 5.3%, respectively]. CONCLUSIONS Uptake of recommended vaccines among IBD patients is suboptimal. Annual vaccination reviews by both family physician and gastroenterologist may improve vaccine uptake. Interventions targeted at improving vaccination uptake in IBD patients are needed.
A Temporally Situated Self-Agency Theory of Information Technology Reinvention

Our knowledge of how users reinvent information technologies (IT) in ways that depart from their intended purposes to achieve new goals is relatively limited. Drawing on a human agency theory that situates actors in the flow of time, this paper develops a theory of IT reinvention. It identifies the key subprocesses of IT reinvention, describes two patterns of reinvention (performance-oriented and mastery-oriented), and explains how the present and the past influence the ambiguities, demands, and dilemmas inherent to each pattern. The outcomes associated with each pattern of IT reinvention are also discussed. The paper provides the theoretical foundations to understand how users reinvent IT as well as new insights into a broader range of post-adoption behaviors.
Milk yield and mammary function in goats during and after once-daily milking

Summary Starting in week 5 of lactation, goats were milked unilaterally once daily for 4 ½ weeks, then twice daily for 12 weeks and finally thrice daily for 2 weeks. The control gland was milked twice daily throughout. During less frequent milking, yield fell by 26%. There was a rapid and essentially complete recovery of milk yield on resumption of twice-daily milking, and five of the six goats subsequently responded to thrice-daily milking with a small increase in milk yield. Mammary function was assessed during each phase by determining enzyme activities and in vitro synthesis rates of lactose and casein in mammary biopsies. There was a trend towards reduced differentiation of secretory cells during infrequent milking, with very little recovery during twice-daily milking but complete recovery during thrice-daily milking. The differentiative state of the control gland remained unchanged throughout.
Cytogenetic effects of low-energy X-rays

Mammography, using 26-30 kV X-rays, is a method routinely used to screen early stages of breast cancer, but some discussion about radiation-related risk associated with this methodology exists. For radioprotection purposes, it has been assigned a quality factor of 1 for all photon energies. However, the relative biological effectiveness (RBE) could increase as photon energy decreases. Analysing different biological parameters, for 30 kV X-rays RBE values from 1 to 8 has been estimated. In the present study a cytogenetic evaluation of the effect of X-rays of 30, 80 and 120 kV using three fluorescence in situ hybridisation (FISH) techniques is presented. The yields of apparently simple translocations (AST) and dicentrics (dic), by using whole chromosome probes for chromosomes 1, 4 and 11 together with a pancentromeric probe, have been analyzed to estimate the RBEM. The ratio between complete and incomplete chromosome aberrations was evaluated using a pan-centromeric and a pan-telomeric probes; and the percentage of complex chromosome aberrations was evaluated using mFISH. Using as reference the curves obtained for 120 kV, the estimated RBEM for dicentrics were 1.08±0.43 and 1.73±0.59 for 80 and 30 kV X-rays respectively, and for AST were 1.26±0.40 and 1.51±0.47. The ratio between incomplete and complete aberrations for 80 and 120 kV were 0.37 and 0.38, lower than the 0.59 observed for 30 kV. The percentage of complex aberrations increased as X-ray energy decreased (0.08, 0.09 and 0.16 at 120, 80 and 30 kV respectively). The results obtained in the present study, indicate that X-rays used in screening mammography (30 kV) are 1.5 times more efficient in inducing dicentrics, translocations and incomplete chromosome aberrations, and two times more efficient in inducing complex aberrations than X-rays of higher energies (120 kV).
Septo-optic dysplasia plus: A spectrum of malformations of cortical development

Article abstract The authors describe three children with septo-optic dysplasia (SOD)-plus: SOD and an associated malformation of cortical development. All three children had developmental delay, and two of the children had significant associated motor deficits. The associated cortical malformations with SOD include a spectrum of disorders of neuronal organization, not limited, as previously described, to schizencephaly. SOD-plus should be suspected in children with SOD and developmental delay.
Biochemical maturation of Spam1 (PH‐20) during epididymal transit of mouse sperm involves modifications of N‐linked oligosaccharides

Indirect immunofluorescence of mouse caput and caudal sperm shows distinctly different distributions of Spam1 protein, which is associated with structural and functional differences of the molecule. Spam1 is uniformly distributed over the surface of the head of caput sperm while in caudal sperm, light and confocal microscopy demonstrate that it is localized to the anterior and posterior regions. The hyaluronidase activity of Spam1 in acrosome‐intact caput sperm was significantly lower (4.3‐fold; P < 0.0001) than that of caudal sperm. The increase in enzymatic activity in caudal sperm is accompanied by a reduction in the molecular weight (MW): in extracts from caput sperm there was a major band at ∼74 kDa and a minor band at ∼67 kDa; while for the cauda there was a major band at ∼67 kDa and minor bands at ∼70 and ∼56 kDa. Additionally, the bands from caput sperm were 4.9 to 7.7‐fold less intense than those from caudal sperm. This decreased affinity for the polyclonal anti‐Spam1 suggests the presence of different surface characteristics of the molecule from the two epididymal regions. Computer analysis of the protein structure from Spam1 cDNA sequence reveals four putative N‐linked glycosylation sites, and enzymatic deglycosylation suggests that all sites are functional. After endoglycosidase activity of extracts from caput and caudal sperm, both show a major band with a MW of ∼56 kDa, the size of the membrane‐anchored polypeptide backbone. Based on the difference in size and intensity of the Spam1 bands and hyaluronidase activities from caput and caudal sperm, the data suggest that the activation of Spam1 during epididymal maturation is regulated by deglycosylation. Mol. Reprod. Dev. 52:196–206, 1999. © 1999 Wiley‐Liss, Inc.
Phylloid Pigmentary Pattern with Mosaic Trisomy 13

Abstract: In most patients with hypomelanosis of Ito, the hypopigmentation is characterized by narrow bands following the lines of Blaschko. We report a 13‐year‐old severely retarded girl with leaf‐shaped patches of hypopigmentation on the back together with short stature, scoliosis, facial dysmorphism, and asymmetrical leg length. The cytogenetic examination of both lymphocytes and fibroblasts demonstrated a mosaicism of 46,XX/47,XX,+13. This result was confirmed by in situ hybridization using a chromosome 13‐specific library in interphase cells. The pigmentary disturbance of our patient was similar to the phylloid pattern (type 3) of the classification of pigmentary patterns postulated by Happle. This type has been described in four patients so far, along with additional anomalies and a chromosomal mosaisicm in two patients.
Identification of RNA targets for the nuclear multidomain cyclophilin atCyp59 and their effect on PPIase activity

AtCyp59 is a multidomain cyclophilin containing a peptidyl-prolyl cis/trans isomerase (PPIase) domain and an evolutionarily highly conserved RRM domain. Deregulation of this class of cyclophilins has been shown to affect transcription and to influence phosphorylation of the C-terminal repeat domain of the largest subunit of the RNA polymerase II. We used a genomic SELEX method for identifying RNA targets of AtCyp59. Analysis of the selected RNAs revealed an RNA-binding motif (G[U/C]N[G/A]CC[A/G]) and we show that it is evolutionarily conserved. Binding to this motif was verified by gel shift assays in vitro and by RNA immunopreciptation assays of AtCyp59 in vivo. Most importantly, we show that binding also occurs on unprocessed transcripts in vivo and that binding of specific RNAs inhibits the PPIase activity of AtCyp59 in vitro. Surprisingly, genome-wide analysis showed that the RNA motif is present in about 70% of the annotated transcripts preferentially in exons. Taken together, the available data suggest that these cyclophilins might have an important function in transcription regulation.
A Review of Patient Safety Measures Based on Routinely Collected Hospital Data

The literature on patient safety measures derived from routinely collected hospital data was reviewed to inform indicator development. MEDLINE and Embase databases and Web sites were searched. Of 1738 citations, 124 studies describing the application, evaluation, or validation of hospital-based medical error or complication of care measures were reviewed. Studies were frequently conducted in the United States (n = 88) between 2005 and 2009 (n = 77) using Agency for Healthcare Research and Quality patient safety indicators (PSIs; n = 79). The most frequently cited indicators included “postoperative hemorrhage or hematoma” and “accidental puncture and laceration. ” Indicator refinement is supported by international coding algorithm translations but is hampered by data issues, including coding inconsistencies. The validity of PSIs and similar adverse event screens beyond internal measurement and the effects of organizational factors on patient harm remain uncertain. Development of PSIs in ambulatory care settings, including general practice and psychiatric care, needs consideration.
Bioarchaeological Insights into the Process of Domestication of Grapevine (Vitis vinifera L.) during Roman Times in Southern France

Grapevine (Vitis vinifera), one of the most important fruit species in the Classical Mediterranean world, is thought to have been domesticated first in South-Western Asia, during the Neolithic. However, the domestication process remains largely unknown. Crucial unanswered questions concern the duration of the process (rapid or slow? ) and the related geographical area (single or multiple-origins? ). Seeds from domesticated grapevine and from its wild ancestor are reported to differ according to shape. Our work aims, first, to confirm this difference and secondly to identify the extent of domestication in the grapes cultivated by Romans in Southern France during the period 50 BCE–500 CE. We had the opportunity to analyze uncharred waterlogged grape pips from 17 archaeological sites. Based on an extended reference sample of modern wild grapevines and cultivars our work shows that both subspecies can be discriminated using simple measurements. The elongation gradient of the pip’s body and stalk may be regarded as an indicator of the strength of the selection pressures undergone by domesticated grapes. Grapevines cultivated during the Roman period included a mix of morphotypes comprising wild, intermediate and moderately selected domesticated forms. Our data point to a relative shift towards more selected types during the Roman period. Domestication of the grapevine appears to have been a slow process. This could result from the recurrent incorporation into cultivation of plants originating from sexual reproduction, when grape cultivation essentially relies on vegetative propagation.
Learning to Generate Samples from Noise through Infusion Training

In this work, we investigate a novel training procedure to learn a generative model as the transition operator of a Markov chain, such that, when applied repeatedly on an unstructured random noise sample, it will denoise it into a sample that matches the target distribution from the training set. The novel training procedure to learn this progressive denoising operation involves sampling from a slightly different chain than the model chain used for generation in the absence of a denoising target. In the training chain we infuse information from the training target example that we would like the chains to reach with a high probability. The thus learned transition operator is able to produce quality and varied samples in a small number of steps. Experiments show competitive results compared to the samples generated with a basic Generative Adversarial Net
Photoinduced Dedoping of Conducting Polymers: An Approach to Precise Control of the Carrier Concentration and Understanding Transport Properties

Carrier Concentration and Understanding Transport Properties 産総研 , OPERANDO-OIL, JST-PRESTO 産総研 1 衛 慶碩 ,向田 雅一 ,石田 敬雄 1,2 AIST, OPERANDO-OIL, JST-PRESTO Qingshuo Wei, Masakazu Mukaida, and Takao Ishida E-mail: qingshuo.wei@aist.go. jp Improvement of the performance of organic electronic devices requires the improvement of electrical properties, such as conductivity, of conjugated polymers. To attain this goal, a better understanding of the physical properties of conjugated polymers as a function of doping level is of fundamental importance. In this presentation, we report the use of a solid-state photoinduced charge-transfer reaction to dedope the highly conductive polymer PEDOT/PSS. For photoinduced dedoping, a photobase generator is mixed with a conducing polymer so that dedoping occurs upon optical illumination due to the photodecarboxylation reaction in the photobase generator. Scheme 1 presents the photoinduced dedoping reaction exploited in this study. 2-(9-Oxoxanthen-2-yl)propionic acid 1,5,7-triazabicyclo[4.4. 0]dec-5-ene salt (PBG; see Scheme 1) is a commercially available water-soluble photobase generator used in low-temperature UV-curing systems. When irradiated at 365 nm, the quantum yield of PBG is high for forming 1,5,7triazabicyclo[4.4. 0]dec-5-ene (TBD). TBD is a strong base with high pKa values. Thus, doped PEDOT should accept electrons from TBD to form neutral PEDOT. By varying the UV-irradiation time, the carrier density in these films is precisely controlled over more than three orders of magnitude. The carrier mobility in the film varies from 10 to 8.2 cm Vs depending on the carrier density. We attribute this result to the variation in the screening of Coulomb traps from PSS at different carrier concentrations. In addition, by measuring the Seebeck coefficient of the film as a function of the UV-irradiation time, we find a maximum power factor of ~42 W/mK at a carrier density of ~5 × 10 cm. Thus, the use of photoinduced dedoping not only provides a platform for understanding the physical properties of conducting polymers but also is useful for developing applications requiring patterned, large-area conducting polymers.
Optical and infrared photometry of the Type IIn SN 1998S: days 11–146

We present contemporaneous optical and infrared (IR) photometric observations of the Type IIn SN 1998S covering the period between 11 and 146 d after discovery. The IR data constitute the first ever IR light curves of a Type IIn supernova. We use blackbody and spline fits to the photometry to examine the luminosity evolution. During the first 2–3 months, the luminosity is dominated by the release of shock-deposited energy in the ejecta. After ∼100 d the luminosity is powered mostly by the deposition of radioactive decay energy from 0.15±0.05 M⊙ of 56Ni which was produced in the explosion. We also report the discovery of an astonishingly high IR excess, K−L′=2.5, that was present at day 130. We interpret this as being due to thermal emission from dust grains in the vicinity of the supernova. We argue that to produce such a high IR luminosity so soon after the explosion, the dust must be pre-existing and so is located in the circumstellar medium of the progenitor. The dust could be heated either by the UV/optical flash (IR echo) or by the X-rays from the interaction of the ejecta with the circumstellar material.
A short counterexample property for safety and liveness verification of fault-tolerant distributed algorithms

Distributed algorithms have many mission-critical applications ranging from embedded systems and replicated databases to cloud computing. Due to asynchronous communication, process faults, or network failures, these algorithms are difficult to design and verify. Many algorithms achieve fault tolerance by using threshold guards that, for instance, ensure that a process waits until it has received an acknowledgment from a majority of its peers. Consequently, domain-specific languages for fault-tolerant distributed systems offer language support for threshold guards. We introduce an automated method for model checking of safety and liveness of threshold-guarded distributed algorithms in systems where the number of processes and the fraction of faulty processes are parameters. Our method is based on a short counterexample property: if a distributed algorithm violates a temporal specification (in a fragment of LTL), then there is a counterexample whose length is bounded and independent of the parameters. We prove this property by (i) characterizing executions depending on the structure of the temporal formula, and (ii) using commutativity of transitions to accelerate and shorten executions. We extended the ByMC toolset (Byzantine Model Checker) with our technique, and verified liveness and safety of 10 prominent fault-tolerant distributed algorithms, most of which were out of reach for existing techniques.