Miracle-dz/UniFAR-FTUs huggingface dataset:
Contributions of mRNA abundance, ribosome loading, and post- or peri-translational effects to temporal repression of C. elegans heterochronic miRNA targets

miRNAs are post-transcriptional regulators of gene activity that reduce protein accumulation from target mRNAs. Elucidating precise molecular effects that animal miRNAs have on target transcripts has proven complex, with varied evidence indicating that miRNA regulation may produce different molecular outcomes in different species, systems, and/or physiological conditions. Here we use high-throughput ribosome profiling to analyze detailed translational parameters for five well-studied targets of miRNAs that regulate C. elegans developmental timing. For two targets of the miRNA lin-4 (lin-14 and lin-28), functional down-regulation was associated with decreases in both overall mRNA abundance and ribosome loading; however, these changes were of substantially smaller magnitude than corresponding changes observed in protein abundance. For three functional targets of the let-7 miRNA family for which down-regulation is critical in temporal progression of the animal (daf-12, hbl-1, and lin-41), we observed only modest changes in mRNA abundance and ribosome loading. lin-41 provides a striking example in that populations of ribosome-protected fragments from this gene remained essentially unchanged during the L3–L4 time interval when lin-41 activity is substantially down-regulated by let-7. Spectra of ribosomal positions were also examined for the five lin-4 and let-7 target mRNAs as a function of developmental time, with no indication of miRNA-induced ribosomal drop-off or significant pauses in translation. These data are consistent with models in which physiological regulation by this set of C. elegans miRNAs derives from combinatorial effects including suppressed recruitment/activation of translational machinery, compromised stability of target messages, and post- or peri-translational effects on lifetimes of polypeptide products.
Integrating Adaptive Beam-forming and Auditory Features for Robust Large Vocabulary Speech Recognition

We demonstrate a system to integrate adaptive beam-forming and auditory features in order to improve speech recognition accuracy in noisy environments. Adaptive beam-forming based on a microphone array can utilize spatial information to improve the sound recording signal-to-noise ratio (SNR) on a focused speaker for robust speech recognition. Auditory features based on modeling the signal processing functions in the hearing system have shown to largely improve speech recognition accuracy under noisy conditions. According to our experiments, when both adaptive beam-forming and the auditory features are integrated, an absolute gain of more than 50% over a baseline on speech recognition accuracy is achieved when 5dB white noise is added.
Gender and Strain Influence on Neurogenesis in Dentate Gyrus of Young Rats

To investigate whether rat hippocampal neurogenesis varies with strain and gender, the authors examined proliferating progenitor cells and their progeny in young male and female Sprague-Dawley (SD) and spontaneously hypertensive rats (SHR) using the thymidine analog bromodeoxyuridine (BrdU) combined with immunohistochemistry for the neuronal marker Calbindin D28k and glial fibrillary acidic protein. Rats were given 7 consecutive daily BrdU injections and were killed 1 day or 4 weeks later to allow for discrimination between proliferation and cell survival. Stereologic analysis of the numbers of BrdU-immunoreactive cells in the dentate gyrus revealed both a strain difference with significantly higher cell proliferation and net neurogenesis in SHR than in SD and a gender difference with males from both strains producing significantly more cells than their female counterparts. Whereas the number of progenitors four weeks after BrdU injections was still significantly greater in male than in female SHRs, resulting in a greater net neurogenesis in the male, the number of BrdU-immunoreactive cells did not differ between male and female SD rats, suggesting a greater survival of newly generated cells in the dentate gyrus in female than in male SD rats. No sex or strain difference was observed in the relative ratio of neurogenesis and gliogenesis.
Multi-delay, phase-coherent pulse pair generation for precision Ramsey-comb spectroscopy

The realization of optical frequency combs has revolutionized the field of precision metrology [1]. However, these combs typically operate in the near-infrared, while many interesting atomic transitions require wavelengths shorter than 100 nm. Hence high peak power (frequency comb) pulses are required for efficient nonlinear up-conversion of comb lasers. Our approach to realize this goal is based on selective amplification of two frequency comb pulses in a parametric amplifier, and we demonstrated MHz-level extreme ultra-violet frequency comb spectroscopy [2]. The fixed delay of the amplified pulse pairs (maximum ~10 ns) used in [2] limited the achievable accuracy and restricted the method to single-transition recording, as in traditional Ramsey spectroscopy [3]. In addition, the phase-shift introduced by the parametric amplifier had to be monitored carefully to correct the Ramsey-like signals.
Temperature elevation in the eye of anatomically based human head models for plane-wave exposures

This study investigated the temperature elevation in the eye of anatomically based human head models for plane-wave exposures. The finite-difference time-domain method is used for analyzing electromagnetic absorption and temperature elevation. The eyes in the anatomic models have average dimensions and weight. Computational results show that the ratio of maximum temperature in the lens to the eye-average SAR (named ‘heating factor for the lens’) is almost uniform (0.112–0.147 °C kg W−1) in the frequency region below 3 GHz. Above 3 GHz, this ratio increases gradually with an increase of frequency, which is attributed to the penetration depth of an electromagnetic wave. Particular attention is paid to the difference in the heating factor for the lens between this study and earlier works. Considering causes clarified in this study, compensated heating factors in all these studies are found to be in good agreement.
Frequent occurrence of deletions in primary mediastinal B‐cell lymphoma

Primary mediastinal B‐cell lymphoma (PMBCL) is a distinct subtype of diffuse large B‐cell lymphoma. PMBCL has been previously studied with a variety of genomic techniques resulting in frequent detection of chromosomal gains; however, chromosomal losses have been rarely reported. This finding contrasts many other types of lymphoma, in which deletions are common. We hypothesize that segmental losses do exist but may have escaped detection by methods used in the previous studies. Using array comparative genomic hybridization to a tiling‐resolution microarray encompassing the entire human genome, PMBCL samples were analyzed for genomic copy number alterations. An almost equal number of gains and losses of chromosomal material were detected throughout the genome (216 vs. 193, respectively). A selection of these DNA copy number alterations were confirmed by quantitative real‐time PCR. Recurrent gains were detected at all previously reported regions of gain, including 9p seen in ∼70% of cases. Recurrent chromosomal losses were observed at 1p, 3p, 4q, 6q, 7p, and 17p, with a novel event at 1p13.1–p13.2 representing the most frequent at 42% of cases analyzed. We conclude that consistent losses are present in the PMBCL genome. Given the similar frequency of losses to that of segmental gains of DNA, they are likely to play an important role in the pathogenesis of PMBCL. © 2007 Wiley‐Liss, Inc.
Hyperglycemia Enhances the Production of Amyloid β1-42 in the Lenses of Otsuka Long-Evans Tokushima Fatty Rats, a Model of Human Type 2 Diabetes.

PURPOSE It has been reported that the accumulation of amyloid β1-42 (Aβ1-42) in human lenses can cause some forms of lens opacification. However, the factors leading to changes in the accumulation of Aβ in the lens remain obscure. In this study, we investigate the effect of hyperglycemia on Aβ1-42 accumulation in lenses. METHODS Otsuka Long-Evans Tokushima Fatty (OLETF) rats and the human lens epithelial cell line SRA 01/04 (HLE cells) were used. The expression of mRNA was determined using a quantitative real-time RT-PCR method; Aβ1-42 levels were analyzed by an ELISA method. RESULTS Otsuka Long-Evans Tokushima Fatty rats at more than 20 weeks of age develop diabetes mellitus with hyperglycemia. Additionally, the levels of the mRNAs for Aβ1-42, amyloid precursor proteins (APP), β-(BACE1), and·γ-secretase (PS) rise in the lenses of OLETF rats with age; high Aβ1-42 levels are observed in the lens capsule-epithelium and cortex. The enhanced expression of the genes for APP, BACE1, and PS in the lenses of OLETF rats is prevented by food restriction (25 g/d/rat). When the effect of glucose levels on the production of Aβ1-42 was investigated in the human lens epithelial cell line SRA 01/04 (HLE cells), the mRNA levels for APP, BACE1, and PS, as well as Aβ1-42 protein levels, were significantly higher under high glucose conditions (20 mM) than under normal glucose conditions (5.6 mM). CONCLUSIONS High glucose leads to the increased expression of genes related to Aβ production, resulting in the accumulation of Aβ in the lens.
Directed Curvature Histograms for Robotic Grasping

Three-dimensional descriptors are a common tool nowadays, used in a wide range of tasks. Most of the descriptors that have been proposed in the literature focus on tasks such as object recognition and identiﬁcation. This paper proposes a novel three-dimensional local descriptor, structured as a set of histograms of the curvature observed on the surface of the object in different directions. This descriptor is designed with a focus on the resolution of the robotic grasping problem, especially on the determination of the orientation required to grasp an object. We validate our proposal following a data-driven approach using grasping information and examples generated using the Gazebo simulator and a simulated PR2 robot. Experimental results show that the proposed descriptor is well suited for the grasping problem, exceeding the performance observed with recent descriptors.
Differential involvement of the basolateral amygdala and orbitofrontal cortex in the formation of sensory‐specific associations in conditioned flavor preference and magazine approach paradigms

Four experiments examined the roles of the basolateral amygdala and orbitofrontal cortex in the formation of sensory‐specific associations in conditioned flavor preference and conditioned magazine approach paradigms using unconditioned stimulus (US) devaluation and selective Pavlovian‐instrumental transfer procedures in Long Evans rats. Experiment 1 found that pre‐training amygdala and orbitofrontal cortex lesions had no detectable effect on the formation or flexible use of sensory‐specific flavor–nutrient associations in a US devaluation task, where flavor cues were paired either simultaneously or sequentially with nutrient rewards in water‐deprived subjects. In Experiment 2, pre‐training amygdala and orbitofrontal cortex lesions both attenuated outcome‐specific Pavlovian‐instrumental transfer. Experiment 3 indicated that amygdala lesions have no effect on the formation of sensory‐specific flavor–nutrient associations in a US devaluation task in food‐deprived subjects. Finally, Experiment 4 demonstrated that the outcomes used in Experiment 3 were sufficiently motivationally significant to support conditioned flavor preference. These findings suggest that, although both orbitofrontal cortex and amygdala lesions attenuate the acquisition of sensory‐specific associations in magazine approach conditioning, neither lesion reduces the ability to appropriately respond to a flavor cue that was paired with a devalued outcome.
Spectral Domain Anterior Segment Optical Coherence Tomography in Microbial Keratitis

Purpose: To investigate the spectral domain anterior segment optical coherence tomography (SDAS-OCT) parameters in microbial keratitis. Design: Prospective, cross-sectional, observational study. Methods: Thirty eyes of 30 patients with proven microbial keratitis (fungal, bacterial and viral), at different stages of the disease, underwent SDAS-OCT imaging. Results 12 eyes were diagnosed with proven fungal keratitis, 10 eyes with proven bacterial keratitis and 8 eyes with proven of viral keratitis. Different types of SDAS- OCT presentations of microbial keratitis were found in this study. Conclusion: SDAS-OCT imaging provided a range of characteristic patterns that could be used as an additional tool in management and assessing the response to treatment of microbial keratitis.
Ethanol treatment increases triacylglycerol and cholesteryl ester content of cultured hepatoma cells.

Well-differentiated Reuber H35 rat hepatoma cells in culture maintain a variety of biochemical functions characteristic of hepatocytes [Deschatrette, J., and M. C. Weiss. 1974. Biochimie. 56: 1603-1611]. To demonstrate the suitability of this system as a model for exploring mechanisms of ethanol hepatotoxicity, the following were investigated: 1) ethanol metabolism in whole cells and cell extracts and 2) effects of ethanol exposure on cellular lipid content. Cultures of H35 cells exposed to 10 mm ethanol metabolized the ethanol at rates similar to those reported in rat liver. Under these conditions, soluble alcohol dehydrogenase activity accounted for greater than 87% of total ethanol metabolism. H35 cells exposed to 240 mm ethanol for 3 days contained four times more triacylglycerol and cholesteryl ester than control cells. Total phospholipid and unesterified cholesterol levels were unaffected by ethanol. Neutral lipid content of Chinese hamster ovary cells was unchanged after ethanol exposure. The increased triacylglycerol content of ethanol-treated H35 cells appeared to result from an accelerated rate of conversion of long chain fatty acids into triacylglycerol. Several lines of evidence indicated that alcohol dehydrogenase-mediated ethanol oxidation was critical in promoting increased triacylglycerol content of cultured cells. Since 240 mm ethanol blocked cellular proliferation, long term effects of ethanol were studied at a level of 10 mm, which allowed a nearly normal growth rate. After 7 weeks of continuous exposure, 10 mm ethanol-treated H35 cells contained five times more triacylglycerol than paired controls. The well-differentiated H35 cell appears to be an excellent in vitro model system for studying both short-term and long-term effects of ethanol on liver cells. -Polokoff, M. A. , M. Iwahashi, and F. R. Simon. Ethanol treatment increases triacylglycerol and cholesteryl ester content of cultured hepatoma cells.
High-Throughput Cytotoxicity Testing System of Acetaminophen Using a Microfluidic Device (MFD) in HepG2 Cells

A lab-on-a-chip (LOC) is a microfluidic device (MFD) that integrates several lab functions into a single chip of only millimeters in size. LOC provides several advantages, such as low fluidic volumes consumption, faster analysis, compactness, and massive parallelization. These properties enable a microfluidic-based high-throughput drug screening (HTDS) system to acquire cell-based abundant cytotoxicity results depending on linear gradient concentration of drug with only few hundreds of microliters of the drug. Therefore, a microfluidic device was developed containing an array of eight separate microchambers for cultivating HepG2 cells to be exposed to eight different concentrations of acetaminophen (APAP) through a diffusive-mixing-based concentration gradient generator. Every chamber array with eight different concentrations (0, 5.7, 11.4, 17.1, 22.8, 28.5, 34.2, or 40 mM) APAP had four replicating cell culture chambers. Consequently, 32 experimental results were acquired with a single microfluidic device experiment. The microfluidic high-throughput cytotoxicity device (μHTCD) and 96-well culture system showed comparable cytotoxicity results with increasing APAP concentration of 0 to 40 mM. The HTDS system yields progressive concentration-dependent cytotoxicity results using minimal reagent and time. Data suggest that the HTDS system may be applicable as alternative method for cytotoxicity screening for new drugs in diverse cell types.
Open source innovation: Towards a generalization of the open source model beyond software

Cet article s’interesse a la question de l’exportation du modele « open source », qui s’est impose avec succes dans le cas du logiciel, a d’autres secteurs. Nous proposons une definition generale de l’innovation « open source » qui repose sur deux piliers : l’ouverture et l’interactivite. Tout d’abord, les connaissances produites doivent etre ouvertes, c’est-a-dire accessibles a tous sans discrimination. En second lieu, les acteurs du processus d’innovation doivent developper une dynamique d’interaction sur le mode « bazar » (Raymond, 1999). L’innovation open source est ainsi differente de l’innovation ouverte theorisee par Chesbrough (2003). Nous discutons egalement de l’importance de la propriete intellectuelle, et des brevets en particulier, pour securiser cette dynamique d’innovation « open source ». Ensuite, nous etudions les contextes propices a l’emergence de l’innovation « open source ». Nous montrons que cette derniere est particulierement interessante lorsqu’elle est envisagee comme permettant de construire un stock de connaissances et de technologies ouvertes, que les entreprises peuvent ensuite utiliser afin de developper des applications innovantes. Nous concluons l’article en presentant deux exemples : le cas de la biologie « open source » (Hope, 2008) et le cas des industries creatives (Bach et al., 2010).
Computer supported collaborative working: lessons from elsewhere

In this paper we review two application areas in the field of IT concerning advanced manufacturing technology and office automation. We argue that new systems in both these areas have been predominantly technology-led in their development and implementation, excluding adequate attention to their human and organizational aspects. We describe two case studies as illustrations of these points and argue that the reasons for this technology-led approach lie in a complex interacting set of social systems that work effectively to marginalize the human and organizational aspects of the new technologies.The applicability of these findings to the domain of Computer Supported Collaborative Working (CSCW) is examined. There are two main sets of lessons that can be learned: those that apply generally to the field of IT, and thereby have relevance also to the special case of CSCW; and those that are particular to the conduct and content of research and development into CSCW. These lessons are outlined in the form of sets of suggestions.
An Improved Secure Cloud Storage Auditing Protocol Based on Distributed String Equality Checking

Recently how to audit cloud storage correctly and securely is a very hot research topic for cloud storage. At Infocom 2015, Chen et al. proposed a novel secure cloud storage audit protocol based on distributed string equality checking, which is a very interesting result. In this paper, we give some improvements to their protocol to strengthen its security. In particular, we show that if the data owners reuse pseudorandom function on the same order number of file block when uploading file block’s tag to the cloud, the protocol maybe not secure any more. We also show that there can exist many (mi, ci) pairs which will result in the same inner product sum ∑n i=1mi · ci, while mi denotes the file block, ci denotes the challenge value, and n denotes the number of blocks. We emphasis here that the flaw maybe does not lie in the traditional security model of cloud storage auditing protocol, but we think it is actually a serious drawback for current secure cloud storage audit protocols. We emphasis these two flaws can also exist in some famous cloud auditing protocols such as PDP and POR. Finally, we give an improvement to their protocol, and thus also give a way to strengthen the famous PDP and POR protocols.
The cost-effectiveness of expanding intensive behavioural intervention to all autistic children in Ontario: in the past year, several court cases have been brought against provincial governments to increase funding for Intensive Behavioural Intervention (IBI). This economic evaluation examines the c

Intensive Behavioural Intervention (IBI) describes behavioural therapies provided to autistic children to overcome intellectual and functional disabilities. The high cost of IBI has caused concern regarding access, and recently, several court cases have been brought against provincial governments to increase funding for this intervention. This economic evaluation assessed the costs and consequences of expanding an IBI program from current coverage for one-third of children to all autistic children aged two to five in Ontario, Canada. Data on the hours and costs of IBI, and costs of educational and respite services, were obtained from the government. Data on program efficacy were obtained from the literature. These data were modelled to determine the incremental cost savings and gains in dependency-free life years. Total savings from expansion of the current program were $45,133,011 in 2003 Canadian dollars. Under our model parameters, expansion of IBI to all eligible children represents a cost-saving policy whereby total costs of care for autistic individuals are lower and gains in dependency-free life years are higher. Sensitivity analyses carried out to address uncertainty and lack of good evidence for IBI efficacy and appropriate discount rates yielded mixed results: expansion was not cost saving with discount rates of 5% or higher and with lower IBI efficacy beyond a certain threshold. Further research on the efficacy of IBI is recommended.
Targeted resequencing identifies PTCH1 as a major contributor to ocular developmental anomalies and extends the SOX2 regulatory network

Ocular developmental anomalies (ODA) such as anophthalmia/microphthalmia (AM) or anterior segment dysgenesis (ASD) have an estimated combined prevalence of 3.7 in 10,000 births. Mutations in SOX2 are the most frequent contributors to severe ODA, yet account for a minority of the genetic drivers. To identify novel ODA loci, we conducted targeted high-throughput sequencing of 407 candidate genes in an initial cohort of 22 sporadic ODA patients. Patched 1 (PTCH1), an inhibitor of sonic hedgehog (SHH) signaling, harbored an enrichment of rare heterozygous variants in comparison to either controls, or to the other candidate genes (four missense and one frameshift); targeted resequencing of PTCH1 in a second cohort of 48 ODA patients identified two additional rare nonsynonymous changes. Using multiple transient models and a CRISPR/Cas9-generated mutant, we show physiologically relevant phenotypes altering SHH signaling and eye development upon abrogation of ptch1 in zebrafish for which in vivo complementation assays using these models showed that all six patient missense mutations affect SHH signaling. Finally, through transcriptomic and ChIP analyses, we show that SOX2 binds to an intronic domain of the PTCH1 locus to regulate PTCH1 expression, findings that were validated both in vitro and in vivo. Together, these results demonstrate that PTCH1 mutations contribute to as much as 10% of ODA, identify the SHH signaling pathway as a novel effector of SOX2 activity during human ocular development, and indicate that ODA is likely the result of overactive SHH signaling in humans harboring mutations in either PTCH1 or SOX2.