Miracle-dz/UniFAR-FTUs huggingface dataset:
Cell-autonomous activation of Hedgehog signaling inhibits brown adipose tissue development

Significance The function of brown adipose tissue (BAT), which converts chemical energy into heat, has been widely characterized, but how BAT forms and what signaling molecules regulate its formation are largely unknown. In this paper, we report that Hedgehog (Hh) signaling inhibits the formation of BAT during development. Activation of Hh signaling, specifically in the BAT of mice during development, resulted in the loss of interscapular BAT due to the impairment of brown-preadipocyte differentiation. Remarkably, the majority of the BAT cells in the neck were replaced by skeletal muscle-like cells in embryos with elevated Hh activity. These findings indicate that Hh is an essential regulator of BAT development and that developing BAT depots respond differentially to Hh signaling. Although recent studies have shown that brown adipose tissue (BAT) arises from progenitor cells that also give rise to skeletal muscle, the developmental signals that control the formation of BAT remain largely unknown. Here, we show that brown preadipocytes possess primary cilia and can respond to Hedgehog (Hh) signaling. Furthermore, cell-autonomous activation of Hh signaling blocks early brown-preadipocyte differentiation, inhibits BAT formation in vivo, and results in replacement of neck BAT with poorly differentiated skeletal muscle. Finally, we show that Hh signaling inhibits BAT formation partially through up-regulation of chicken ovalbumin upstream promoter transcription factor II (COUP-TFII). Taken together, our studies uncover a previously unidentified role for Hh as an inhibitor of BAT development.
Dentate Gyrus and CA1 Ensemble Activity during Spatial Reference Frame Shifts in the Presence and Absence of Visual Input

In rats shuttling between a variably placed landmark of origin and a fixed goal, place fields of hippocampal CA1 cells encode location in two spatial reference frames. On the initial part of the outbound journey, place fields encode location with respect to the origin while on the final segment, place fields are aligned with the goal (Gothard et al., 1996b). An abrupt switch of reference frame can be induced experimentally by shortening the distance between the origin and the goal. Two linked hypotheses concerning this effect were addressed: (1) that the persistent, landmark-referenced firing results from some internal dynamic process (e.g., path integration or “momentum”) and is not a result of maintained sensory input from the landmark of origin; and (2) that this hypothetical process is generated by connections either within CA3 or between CA3 and CA1, in which case the effect might be absent from the dentate gyrus. Neuronal ensemble recordings were made simultaneously from CA1 and the dentate gyrus as rats shuttled on a linear track between a variably located box and a goal, under light or dark conditions. The box-referenced firing persisted significantly longer in the dark in both hippocampal subfields, suggesting a competitive interaction between an internal dynamic process and external sensory cues. The similarity between reference frame transitions in the dentate gyrus and the CA1 region suggests that this process probably occurs before CA3, possibly in the entorhinal cortex or subiculum.
A Reliable Acoustic EMISSION Based Technique for the Detection of a Small Leak in a Pipeline System

This paper proposes a reliable leak detection method for water pipelines under different operating conditions. This approach segments acoustic emission (AE) signals into short frames based on the Hanning window, with an overlap of 50%. After segmentation from each frame, an intermediate quantity, which contains the symptoms of a leak and keeps its characteristic adequately stable even when the environmental conditions change, is calculated. Finally, a k-nearest neighbor (KNN) classifier is trained using features extracted from the transformed signals to identify leaks in the pipeline. Experiments are conducted under different conditions to confirm the effectiveness of the proposed method. The results of the study indicate that this method offers better quality and more reliability than using features extracted directly from the AE signals to train the KNN classifier. Moreover, the proposed method requires less training data than existing techniques. The transformation method is highly accurate and works well even when only a small amount of data is used to train the classifier, whereas the direct AE-based method returns misclassifications in some cases. In addition, robustness is also tested by adding Gaussian noise to the AE signals. The proposed method is more resistant to noise than the direct AE-based method.
Acute hepatic failure in India: A perspective from the East

Acute hepatic failure (AHF) in India almost always presents with encephalopathy within 4 weeks of the onset of acute hepatitis. Further subclassification of AHF into hyperacute, acute and subacute forms may not be necessary in this geographical area, where the rapidity of onset of encephalopathy does not seem to influence survival. Viral hepatitis is the cause in approximately 95–100% of patients, who therefore constitute a more homogeneous population than AHF patients in the West. In India, hepatitis E (HEV) and hepatitis B (HBV) viruses are the most important causes of AHF; approximately 60% of cases are caused by to these viruses. Hepatitis B virus core mutants are very important agents in cases where hepatitis B results in AHF in this country. Half of the patients with AHF admitted to our centre are female, one‐quarter of whom are pregnant. Therefore, pregnant females who contract viral hepatitis constitute a high‐risk group for the development of AHF. However, the outcome of AHF in this group is similar to that in non‐pregnant women and men. No association with any particular virus has been identified among sporadic cases of AHF. In our centre, approximately one‐third of AHF patients survive with aggressive conservative therapy, whereas two‐thirds of deaths occur within 72 h of hospitalization. Cerebral oedema and sepsis are the major fatal complications. Both fungal and Gram‐negative bacteria are major causes of sepsis. Among patients with AHF, despite the presence of sepsis, its overt clinical features (i.e. fever, leucocytosis) may be absent and objective documentation of the presence of sepsis in such patients is achieved by repeated culture of various body fluids. It should be possible to develop simple, clinical prognostic markers for AHF in this geographical region, in order to identify patients suitable for liver transplantation.
Uniformly reweighted belief propagation: A factor graph approach

Tree-reweighted belief propagation is a message passing method that has certain advantages compared to traditional belief propagation (BP). However, it fails to outperform BP in a consistent manner, does not lend itself well to distributed implementation, and has not been applied to distributions with higher-order interactions. We propose a method called uniformly-reweighted belief propagation that mitigates these drawbacks. After having shown in previous works that this method can sub-stantially outperform BP in distributed inference with pairwise interaction models, in this paper we extend it to higher-order interactions and apply it to LDPC decoding, leading performance gains over BP.
Nematic to smectic-A transition in the asymptotic limit of very long hard spherocylinders.

We study a system of hard spherocylinders with rotational freedom in which the length-to-diameter ratio of the spherocylinder L/D is large. The asymptotic expressions for the one-particle distribution function and the free-energy functional in the limit L/D\ensuremath{\rightarrow}\ensuremath{\infty} are found. The virial expansion of the free energy is used to study the nematic to smectic-A transition by means of a bifurcation analysis and the third-order term of the expansion is taken into account. Then the bifurcation analysis is extended to the next order to determine the order of the transition. We also compare our results with computer simulations and other density-functional theories.
Chlamydial and gonococcal reinfection among men: a systematic review of data to evaluate the need for retesting

This study aimed to systematically review and describe the evidence on chlamydia and gonorrhoea reinfection among men, and to evaluate the need for retesting recommendations in men. PubMed and STI conference abstract books from January 1995 to October 2006 were searched to identify studies on chlamydia and gonorrhoea reinfection among men using chlamydia and gonorrhoea nucleic acid amplification tests or gonorrhoea culture. Studies were categorised as using either active or passive follow-up methods. The proportions of chlamydial and gonococcal reinfection among men were calculated for each study and summary medians were reported. Repeat chlamydia infection among men had a median reinfection probability of 11.3%. Repeat gonorrhoea infection among men had a median reinfection probability of 7.0%. Studies with active follow-up had moderate rates of chlamydia and gonorrhoea reinfection among men, with respective medians of 10.9% and 7.0%. Studies with passive follow-up had higher proportions of both chlamydia and gonorrhoea reinfections among men, with respective medians of 17.4% and 8.5%. Proportions of chlamydia and gonorrhoea reinfection among men were comparable with those among women. Reinfection among men was strongly associated with previous history of sexually transmitted diseases and younger age, and inconsistently associated with risky sexual behaviour. Substantial repeat chlamydia and gonorrhoea infection rates were found in men comparable with those in women. Retesting recommendations in men are appropriate, given the high rate of reinfection. To optimise retesting guidelines, further research to determine effective retesting methods and establish factors associated with reinfection among men is suggested.
T regulatory cells: aid or hindrance in the clearance of disease?

• Introduction • Characteristics – The forkhead/winged‐helix protein transcription factor (FoxP3) – Cytotoxic T lymphocyte–associated antigen 4 (CTLA‐4) – Glucocorticoid‐induced TNFR Related Protein (GITR) – L‐Selectin (CD62L) – Chemokine (C‐C motif) Receptor 7 (CCR7) – Alpha E integrin (CD103) – Other cell markers with potential • Manipulation of CD4+ CD25+ Tregs – Induction and regulation of CD4+ CD25+ Tregs – Interleukin‐2 (IL‐2) – Interferon gamma (IFN‐γ) – Transforming growth factor β1 (TGF‐β1) – FoxP3 – Cytokines and drugs with potential • Depletion of CD4+ CD25+ Tregs • Role of CD4+ CD25+ FoxP3+ Tregs in disease – Bacterial and fungal – Parasitic infections – Viral infections – Autoimmunity and cancer • Conclusions
Do private clinics or expedited fees reduce disability duration for injured workers following knee surgery?

OBJECTIVE To investigate the effect of workers' compensation policies related to expedited surgical fees and private clinic surgical setting on disability duration among injured workers. METHODS The study included 1,380 injured workers with knee meniscectomy between 2001 and 2005 in British Columbia. Using linked workers' compensation claim and surgery/clinical records, wait time for surgery (time from last surgical consult to surgery) and time from surgery to return to work were computed and compared for workers who received care in public versus private facilities, and according to whether their surgeons received fees intended to expedite care. RESULTS The public expedited group had the shortest disability duration from surgical consult to return to work; the expedited fee reduced the surgery wait time (~2 work weeks), and surgeries performed in public hospitals had a shorter return-to-work time (~1 work week). DISCUSSION An overall difference of approximately three work weeks in disability duration may have meaningful clinical and quality-of-life implications for injured workers. However, minimal differences in expedited surgical wait times by private clinics versus public hospitals, and small differences in return-to-work outcomes favouring the public hospital group, suggest that a future economic evaluation of workers' compensation policies related to surgical setting is warranted.
The MONARCA self-assessment system: Persuasive personal monitoring for bipolar patients

An increasing number of persuasive personal healthcare monitoring systems are being researched, designed and tested, many of them being based on Smartphone technology. These systems could help patients and clinicians monitor and manage mental illness. Mental illness is complex, difficult to treat, and carries social stigma. We describe our setup to support the treatment of bipolar patients using a persuasive mobile phone monitoring system and a web portal.
Changes in hippocampal excitatory synaptic transmission during cholinergically induced theta and slow oscillation states

Neural processing in the hippocampus (HPC) during sleep is important for declarative memory storage. Previously, we have shown that alternations of sleep‐like REM and non‐REM brain states that involve changing patterns of synchronized oscillatory network activity in the HPC [i.e., theta and the slow oscillation (SO), respectively] robustly and differentially influence excitatory synaptic transmission in a variety of hippocampal pathways. Given that state in the HPC is dependent on variations in cholinergic tone in both sleep and under urethane anesthesia, in the present study we induced theta and SO states via systemic cholinergic manipulations in urethane‐anesthetized rats to confirm similar changes in synaptic responsiveness. This was conducted using linear multiprobe recordings and current source density analysis of electrically evoked potentials in commissural and temporal ammonic inputs to CA1 and medial and lateral perforant path inputs to dentate gyrus (DG). Cholinergic agonism and antagonism induced theta and the SO, respectively, and similarly to the case with spontaneous states, also diminished and promoted, respectively, excitatory synaptic currents in all pathways (except for the medial perforant path input to DG which showed the opposite modulation). These results suggest that both state and cholinergic tone bias the hippocampal network during natural sleep across REM and non‐REM episodes and that this modulation may play an important role in the consolidation of declarative memories. © 2009 Wiley‐Liss, Inc.
High resolution MRI study of circumlental space in the aging eye.

he controversy and confusion regarding the mechanism of presbyopia results in large part from an inability to directly measure the anatomical structures in question. In this study, magnetic resonance imaging (MRI) has been used to directly detect age related changes in circumlental space of 47 emmetropes and mild myopes. MRI offers unparalleled soft tissue contrast, providing differentiation between muscle and other soft tissue, thus allowing the ciliary muscle to be visualized. Moreover, MRI produces undistorted images of the entire lens surface. As previously presented 1 , both the ciliary muscle ring diameter and the circumlental space decrease with age, the decrease in circumlental space is primarily the result of an age dependent decrease in the ciliary muscle ring diameter since the length of the lens equator is not significantly correlated with age. Recently, investigators 2 found evidence that the lens is not symmetrically positioned in the ciliary ring of the rhesus monkey. Specifically, Croft and colleagues 2 reported that during resting accommodation, the temporal ciliary processes are 0.21 mm closer to the lens equator than to the nasal ciliary processes. Here,we present MRI based on data that demonstrate this asymmetry also occurs in the position of the human lens. METHODS A 1.5 Tesla MR imager (1.5T-Signa, General Electric Medical Systems, Waukesha, WI) was used to obtain images from 47 subjects, ages 21 through 83. The soft tissue image contrast available with MRI is superior to that obtained with any other imaging modality. Moreover, by varying MR pulse sequences and timing parameters, desired contrast differences can be maximized. We used a T1 weighted spin-echo pulse sequence to differentiate between muscle and other soft tissue, while clearly delineating lens shape. A series of contiguous axial slices through the lens were acquired simultaneously, requiring 5 minutes. These images were collected with a 4 cm field-of-view and 256 x 256 pixel matrix, resulting in 0.156 mm in-plane resolution. The contiguous 3 mm thick axial slices ensured that the entire lens was captured and allowed the desired “center” slice as well as its flanking slices to be evaluated in order to determine the lens dimensions, as previously described. 3 A custom eye coil consisting of a three-turn solenoid with a 2.5 cm diameter, posi
Cycle-consistent Adversarial Networks for Non-parallel Vocal Effort Based Speaking Style Conversion

Speaking style conversion (SSC) is the technology of converting natural speech signals from one style to another. In this study, we propose the use of cycle-consistent adversarial networks (CycleGANs) for converting styles with varying vocal effort, and focus on conversion between normal and Lombard styles as a case study of this problem. We propose a parametric approach that uses the Pulse Model in Log domain (PML) vocoder to extract speech features. These features are mapped using the CycleGAN from utterances in the source style to the corresponding features of target speech. Finally, the mapped features are converted to a Lombard speech waveform with the PML. The CycleGAN was compared in subjective listening tests with 2 other standard mapping methods used in conversion, and the CycleGAN was found to have the best performance in terms of speech quality and in terms of the magnitude of the perceptual change between the two styles.
Developmental decisions in Aspergillus nidulans are modulated by Ras activity

To better understand how Ras controls development of multicellular organisms, we have chosen Aspergillus nidulans as a model system. When grown on solid medium, this fungus follows a well-defined program of development, sequentially giving rise to several cell types which produce three distinct structures: vegetative hyphae, aerial hyphae, and the conidiophore structure. Here we describe a ras homolog found in this fungus (Aras) and demonstrate that it is an essential gene that regulates the ordered program of development. We created dominant alleles of this gene and expressed them to different levels in order to vary the ratio of GTP-bound (active) to GDP-bound (inactive) A-Ras protein. When the amount of active Ras is large, nuclear division proceeds, but further development is inhibited at the early step of germ tube formation. At an intermediate level of active Ras, aerial hypha formation is inhibited, while at a low level, conidiophore formation is inhibited. Maintenance of an even lower level of the active Ras is essential for initiation and progression of conidiophore formation, the final stage of development. When the level of active Ras is artificially lowered, each stage of development is initiated prematurely except germination, the initial stage of development. Therefore, the progression of the ordered developmental pathway of A. nidulans is dependent upon an initial high level of active Ras followed by its gradual decrease. We propose that several concentration threshold exist, each of which allows development to proceed to a certain point, producing the proper cell type while inhibiting further development.
Critical Regions of secM That Control Its Translation and Secretion and Promote Secretion-Specific secA Regulation

ABSTRACT SecA is an essential ATP-driven motor protein that binds to presecretory or membrane proteins and the translocon and promotes the translocation or membrane integration of these proteins. secA is subject to a protein secretion-specific form of regulation, whereby its translation is elevated during secretion-limiting conditions. A novel mechanism that promotes this regulation involves translational pausing within the gene upstream of secA, secM. The secM translational pause prevents formation of an RNA helix that normally blocks secA translational initiation. The duration of this pause is controlled by the rate of secretion of nascent SecM, which in turn depends on its signal peptide and a functional translocon. We characterized the atypical secM signal peptide and found that mutations within the amino-terminal region specifically affect the secM translational pause and secA regulation, while mutations in the hydrophobic core region affect SecM secretion as well as translational pausing and secA regulation. In addition, mutational analysis of the 3′ end of secM allowed us to identify a conserved region that is required to promote the translational pause that appears to be operative at the peptide level. Together, our results provide direct support for the secM translational pause model of secA regulation, and they pinpoint key sequences within secM that promote this important regulatory system.
A 28-GHz fractional-N frequency synthesizer with reference and frequency doublers for 5G cellular

This paper presents a 27.5-29.6GHz fractional-N frequency synthesizer using reference and frequency doublers to achieve low in-band and out-of-band phase-noise for 5G mobile communications. The push-push amplifier and 28GHz balun help achieving differential signals with low out-of-band phase noise while consuming low power. A charge pump with gated offset as well as reference doubler help reducing noise-folding effect resulting low in-band phase noise while sampling loop filter helps reducing spurs. The proposed synthesizer has been implemented in 65nm CMOS technology achieving an in-band and out-of-band phase noise of -78dBc/Hz and -126dBc/Hz, respectively while consuming only 33mW. The jitter-power figure-of-merit (FoM) is -231dB which is the highest among the state-of-the-art >20GHz fractional-N PLLs. Reference spurs are less than -80 dBc.
Rule Extraction From Dynamic Cell Structure Neural Network Used in a Safety Critical Application

This paper describes an algorithm to extract rules from a dynamic cell structure (DCS) neural network and the rationale for extracting these rules. The DCS is a form of self-organizing map (SOM) neural network that has been used in a real-time adaptive flight control application. The purpose for extracting rules in this instance is to determine whether such rules, along with other techniques, could be used in the verification and validation (V&V) of a neural network being used in a safety-critical role. This paper will explain the intelligent flight control application of the DCS, describe the method used for rule extraction, provide experimental results of the rule extraction techniques applied to several data sets, and examine the relevance of the rules to the V&V process.