Miracle-dz/UniFAR-FTUs huggingface dataset:
Wnt10b and Dkk-1 gene therapy differentially influenced trabecular bone architecture, soft tissue integrity, and osteophytosis in a skeletally mature rat model of osteoarthritis

ABSTRACT Aims: Our goals in the current experiments were to determine if (a) upregulation of Wnt signaling would induce osteoarthritis changes in stable stifle joints and (b) if downregulation of Wnt signaling in destabilized joints would influence the progression of OA. Methods: At 37 weeks of age, rats were injected in the stifle joint with a recombinant adeno-associated viral vector containing the Wnt-inhibitor Dkk-1 or a Wnt10b transgene. At 40 weeks of age, rats underwent surgical destabilization of the joint. At 50 weeks of age, stifle joints were submitted for micro-computed tomography and histopathological analysis. Results: Injection of either Wnt10b or Dkk-1 transgenes in stable joints improved bone architectural parameters, but worsened soft tissue integrity. Osteophytosis was decreased by Dkk-1, but unchanged by Wnt10b. Destabilization negatively influenced bone architecture, increased osteophytosis, and decreased soft tissue integrity. Dkk-1 exacerbated the negative effects of destabilization, whereas Wnt10b had little effect on these parameters. Osteophytosis was improved, whereas soft tissue integrity was worsened by both transgenes in destabilized joints. Conclusions: The Wnt-inhibitor Dkk-1 does not appear to completely inhibit the effects of Wnt signaling on bone remodeling. In vivo upregulation of Wnt10b and its inhibitor, Dkk-1, can produce both parallel or contrasting phenotypic responses depending on the specific parameter measured and the fidelity of the examined joint. These observations elucidate different roles for Wnt signaling in stable versus destabilized joints and may help to explain the conflicting results previously reported for the role of Dkk-1 in joint disease.
Mutations in PITX2 may contribute to cases of omphalocele and VATER‐like syndromes

Omphalocele is a congenital anomaly with substantial morbidity. Rieger syndrome, an autosomal dominant disorder, is characterized by craniofacial abnormalities and abdominal wall defects. PITX2 mutations are etiologic in >40% of cases of Rieger syndrome. We demonstrate that the birth prevalence of omphalocele is significantly higher in Rieger syndrome than in the general population, with omphaloceles found in 0.03% in the Iowa newborn population and 4.3% of patients with Rieger syndrome. Our objective was to screen coding and conserved non‐coding regions of PITX2 for mutations in 209 patients with omphalocele. We identified remarkable evolutionarily conserved regions by comparing the 3′UTR of Pitx2 in 13 vertebrate and 3 invertebrate species. No mutations changing the amino acid sequence were found within the omphalocele population. In one case of omphalocele with VATER‐like additional anomalies, a three nucleotide deletion was found in the 3′UTR. This deletion was not seen in 1,186 controls. Also in the 3′UTR, we identified a single nucleotide polymorphism at a highly conserved residue. Our findings suggest additional studies of PITX2 conserved regions will be valuable. We also screened the omphalocele cases for mutations in exon 5 of the gene FLNA. Mutations in FLNA have been shown to cause a broad range of congenital malformations, including otopalatodigital syndrome type 2 in which a missense mutation occurring in exon 5 of FLNA results in omphalocele as part of the phenotype. We did not find any mutations in exon 5 of FLNA in 179 omphalocele cases studied. © 2004 Wiley‐Liss, Inc.
Sperm cystic fibrosis transmembrane conductance regulator expression level is relevant to fecundity of healthy couples

Cystic fibrosis transmembrane conductance regulator (CFTR) is relevant to sperm quality, sperm capacitation and male fertility. However, it is still unknown whether CFTR can be a potential parameter for fecundity prediction in healthy couples. In this study, 135 healthy couples were divided into groups according to their fertility. We demonstrated that the sperm CFTR expression level of healthy males who never impregnated their partners (49 cases, 38.68 ± 2.71%) was significantly lower than that of fertile men (86 cases, 46.35 ± 2.32%). Sperm CFTR expression level accurately corresponded with fertility through the logistic regression model. Receiver operating characteristic (ROC) curve analysis showed that the cut‐off value of sperm CFTR expression level for fecundity prediction was 43.75%. Furthermore, cumulative pregnancy rates (CPRs) of CFTR > 43.75% group and CFTR ≤ 43.75% group during the follow‐up periods were 80.6% and 49.3% respectively. Meanwhile, the mean time to pregnancy (TTP) of CFTR ≤ 43.75% group (26.79 ± 2.35) was significantly longer than that of CFTR > 43.75% group (16.46 ± 2.42). Therefore, sperm CFTR expression level is relevant to fecundity of healthy couples and shows potential predictive capacity of fecundity.
Influence of metallic substrate surface engineering on peel resistance of adhesively bonded polymer film

The peel resistance of adhesively bonded polymer films to a stainless steel sheet substrate (SSSS) with different engineered surface characteristics was examined in two different loading directions and for two different peel speeds. The SSSS was laminated with two thin polymeric adherends using two different pressure-sensitive adhesives. The SSSS surface was altered by grinding and knurling techniques before lamination and the effects of surface alterations on peel resistance were compared with peel resistance of the adherend from as-received SSSS with a bright annealed surface condition. For ground surface, an increase in adherend peel resistance was observed and the increase was attributed to increase in contact area between the adhesive and SSSS surface. For knurled surfaces which involved deeper and less frequent grooves, however, a decrease in peel resistance was observed. This was attributed to a more complex stress state at the peel front in the SSSS groove region during peeling. An increase in peel speed enhanced the peel resistance from both ground and knurled surfaces.
Root Mean Square Error of Neural Spike Train Sequence Matching with Optogenetics

Optogenetics is an emerging field of neuroscience where neurons are genetically modified to express light-sensitive receptors that enable external control over when the neurons fire. Given the prominence of neuronal signaling within the brain and throughout the body, optogenetics has significant potential to improve the understanding of the nervous system and to develop treatments for neurological diseases. This paper uses a simple optogenetic model to compare the timing distortion between a randomly-generated target spike sequence and an externally-stimulated neuron spike sequence. The distortion is measured by filtering each sequence and finding the root mean square error between the two filter outputs. The expected distortion is derived in closed form when the target sequence generation rate is sufficiently low. Derivations are verified via simulations.
Sampling and reconstructing manifolds using alpha-shapes

There is a growing interest for the problem of reconslructing thc shape of an object from multiple range images. Several methods, based on heuristics, have been described in the literature. We propose the use of alpha-shapes, which allow us to give a formal characterization of the reconstruction problem and to prove that, when certain sampling requirements are satisfied, the reconstructed alpha-shape is homeomorphic to the original object and approximate it within a fixed error bound. In a companion paper, we describe practical methods to automatically select an optimal alpha value, to deal with less-than-ideal scans, and to fit smooth piecewise algebraic surface to the data points.
Azoospermia Factor C Subregion of the Y Chromosome

The azoospermia factor (AZF) region on the Y chromosome consists of genes required for spermatogenesis. Among the three subregions, the AZFc subregion located at the distal portion of AZF is the driver for genetic variation in Y chromosome. The candidate gene of AZFc is known as deleted in azoospermia gene, which is studied with interest because it is involved in germ cell development and most frequently deleted genes leading to oligozoospermia and azoospermia. Recently, two partial deletions in AZFc gr/gr and b2/b3 are characterized at the molecular level which showed homologous recombination between amplicons, affecting spermatogenesis process. There are novel methods and commercially available kits for accurate screening and characterization of microdeletions. It is important to detect the AZFc microdeletions through genetic screening and counseling those infertile men who planned to avail assisted reproduction techniques such as undergoing intracytoplasmic sperm injection or in vitro fertilization.
High-Resolution PET Imaging with Therapeutic Antibody-based PD-1/PD-L1 Checkpoint Tracers

Checkpoint-blocking antibodies like those targeting the PD-1/PD-L1 pathway have revolutionized oncology. We developed radiotracers based on therapeutic checkpoint-blocking antibodies permitting sensitive and high-resolution PET imaging of both PD-1 and PD-L1 in immunocompetent mice. ImmunoPET of naive mice revealed similar overall expression patterns for PD-1 and PD-L1 in secondary lymphoid organs (spleen and lymph nodes). Interestingly, PD-L1 was also detected in brown adipose tissue (BAT), confirming the notion that BAT is immunologically relevant. Under pathophysiological conditions, strong expression of the receptor/ligand pair was also found in non-lymphoid tissues. Both were specifically detected in malignant tumors. PD-1 was readily detected after combined immunoradiotherapy causing massive tumor infiltration by PD-1+ lymphocytes. PD-L1 tracer uptake was reduced in PD-L1 knockout tumors. Moreover, monitoring the expression changes of PD-L1 in response to its main inducer, the effector T cell cytokine IFN-γ, revealed robust upregulation in the lung. This suggests that T cell responses in the lung, a vital organ continuously exposed to a variety of antigens, are strongly restrained by the PD-1 checkpoint. In turn, this could explain the association of PD-1 checkpoint inhibition with potentially fatal immune-mediated pneumonitis and partially also its efficacy in lung cancer.
Assessment of Cochlear Function during Cochlear Implantation by Extra- and Intracochlear Electrocochleography

Objective: The aims of this study were: (1) To investigate the correlation between electrophysiological changes during cochlear implantation and postoperative hearing loss, and (2) to detect the time points that electrophysiological changes occur during cochlear implantation. Material and Methods: Extra- and intracochlear electrocochleography (ECoG) were used to detect electrophysiological changes during cochlear implantation. Extracochlear ECoG recordings were conducted through a needle electrode placed on the promontory; for intracochlear ECoG recordings, the most apical contact of the cochlear implant (CI) electrode itself was used as the recording electrode. Tone bursts at 250, 500, 750, and 1000 Hz were used as low-frequency acoustic stimuli and clicks as high-frequency acoustic stimuli. Changes of extracochlear ECoG recordings after full insertion of the CI electrode were correlated with pure-tone audiometric findings 4 weeks after surgery. Results: Changes in extracochlear ECoG recordings correlated with postoperative hearing change (r = −0.44, p = 0.055, n = 20). Mean hearing loss in subjects without decrease or loss of extracochlear ECoG signals was 12 dB, compared to a mean hearing loss of 22 dB in subjects with a detectable decrease or a loss of ECoG signals (p = 0.0058, n = 51). In extracochlear ECoG recordings, a mean increase of the ECoG signal of 4.4 dB occurred after opening the cochlea. If a decrease of ECoG signals occurred during insertion of the CI electrode, the decrease was detectable during the second half of the insertion. Conclusion: ECoG recordings allow detection of electrophysiological changes in the cochlea during cochlear implantation. Decrease of extracochlear ECoG recordings during surgery has a significant correlation with hearing loss 4 weeks after surgery. Trauma to cochlear structures seems to occur during the final phase of the CI electrode insertion. Baseline recordings for extracochlear ECoG recordings should be conducted after opening the cochlea. ECoG responses can be recorded from an intracochlear site using the CI electrode as recording electrode. This technique may prove useful for monitoring cochlear trauma intraoperatively in the future.
Tumor suppressor identity can contribute to heterogeneity of phenotype in hair follicle stem cell‐induced squamous cell carcinoma

DSG3 or IgG failed to elicit this effect. This observation is in line with earlier observations on the significance of DSG1 in HaCaT cells (8) and may also imply a specific role for DSG1 in ER stress. Cell survival assays showed that both anti-DSG1 and anti-DSG3 – albeit at a lesser extent – were inhibitory in HaCaT cells. However, ablation of CHOP expression partially restored cell survival only for anti-DSG1. In view of the role of CHOP in mediating the proapoptotic effects of ER stress, this observation suggests that anti-DSG1-related, but not anti-DSG3-related growth inhibition is associated with UPR induction. The fact that restoration of cell viability by siRNA for CHOP was only partial may reflect the canonical UPR-associated effects and the more wide effects of anti-DSGs in cell viability. Of those, only the former are linked to anti-DSG1 and depend on CHOP, while the latter are inflicted by both anti-DSG1 and anti-DSG3 and appear to be CHOP independent. To that end, a specific association between DSG1 and ER stress induction should be considered. It is noted that while anti-DSG1 antibodies are not causative for the PV development of mucosal lesions as opposed to the anti-DSG3 antibodies that are present in all cases of PV exhibiting mucosal lesions, their presence, which is detected in about 60% of the cases, has been associated with increased aggressiveness of the disease (9). A limitation of the current study is that the anti-DSG antibodies used do not simulate all aspects of IgGs from patients with PV. However, they provide hints on the potential association between ER stress and pemphigus. The fact that interference with ER stress induction abrogated, even partially, anti-DSG1-induced growth arrest suggests that modulation of the UPR may provide means for the management of PV. Acknowledgements CM, NK, EP and EF performed the research; AS, HK and IC designed the research study; HK and IC analysed the data; CM and IC wrote the manuscript. This study was supported by a grant from Empeirikion Foundation (to IC). Disclosure statement The authors have nothing to declare. Supporting Information
Quality Assessment of the French OpenStreetMap Dataset

The concept of Volunteered Geographic Information (VGI) has recently emerged from the new Web 2.0 technologies. The OpenStreetMap project is currently the most significant example of a system based on VGI. It aims at producing free vector geographic databases using contributions from Internet users. Spatial data quality becomes a key consideration in this context of freely downloadable geographic databases. This article studies the quality of French OpenStreetMap data. It extends the work of Haklay to France, provides a larger set of spatial data quality element assessments (i.e. geometric, attribute, semantic and temporal accuracy, logical consistency, completeness, lineage, and usage), and uses different methods of quality control. The outcome of the study raises questions such as the heterogeneity of processes, scales of production, and the compliance to standardized and accepted specifications. In order to improve data quality, a balance has to be struck between the contributors' freedom and their respect of specifications. The development of appropriate solutions to provide this balance is an important research issue in the domain of user‐generated content.
Continuous State-Space Models for Optimal Sepsis Treatment: a Deep Reinforcement Learning Approach

Sepsis is a leading cause of mortality in intensive care units (ICUs) and costs hospitals billions annually. Treating a septic patient is highly challenging, because individual patients respond very differently to medical interventions and there is no universally agreed-upon treatment for sepsis. Understanding more about a patient's physiological state at a given time could hold the key to effective treatment policies. In this work, we propose a new approach to deduce optimal treatment policies for septic patients by using continuous state-space models and deep reinforcement learning. Learning treatment policies over continuous spaces is important, because we retain more of the patient's physiological information. Our model is able to learn clinically interpretable treatment policies, similar in important aspects to the treatment policies of physicians. Evaluating our algorithm on past ICU patient data, we find that our model could reduce patient mortality in the hospital by up to 3.6% over observed clinical policies, from a baseline mortality of 13.7%. The learned treatment policies could be used to aid intensive care clinicians in medical decision making and improve the likelihood of patient survival.
Continuous-Time Delta-Sigma Modulators With Time-Interleaved FIR Feedback

The use of a single-bit quantizer in a wideband CT<inline-formula> <tex-math notation="LaTeX">$\Delta \Sigma \text{M}$ </tex-math></inline-formula> is attractive, as the quantizer can be implemented in a power and area-efficient manner. Unfortunately, 1-bit CT<inline-formula> <tex-math notation="LaTeX">$\Delta \Sigma $ </tex-math></inline-formula>Ms are plagued by a host of difficulties. Clock jitter and quantizer metastability are particularly problematic, and the higher loop filter linearity needed to process the full-scale feedback waveform results in increased power dissipation. The use of a finite impulse response (FIR) feedback DAC is a power efficient way of addressing the challenges above. However, even this technique runs into difficulties at multi-GHz clock rates. This paper introduces the idea of time-interleaved (TI) FIR feedback to enhance the performance of a conventional FIR DAC. A single-bit CT<inline-formula> <tex-math notation="LaTeX">$\Delta \Sigma \text{M}$ </tex-math></inline-formula> that uses a <inline-formula> <tex-math notation="LaTeX">$2\times $ </tex-math></inline-formula> TI-FIR DAC achieves 67.6/68.8/76 dB SNDR/SNR/DR in a 60 MHz bandwidth. Designed in a low leakage 65 nm CMOS process, the modulator operates at 6 GHz and occupies only 0.07 mm<sup>2</sup>. Its Walden Figure of Merit is 56.5 fJ/lvl.
Investigation of Lithium Ion Diffusion Behavior in a Li4Ti5O12 Thin Film Electrode by In Situ UV-Visible Measurements

Li 4Ti5O12 thin film was prepared on an ITO glass substrate by using solgel method. Poly(vinylpyrrolidone) (PVP) was used as additives to suppress a c rack formation and stabilize sol. The film was prepared by heat treatment at 600 °C for 30 min. Both electrochemical and electrochromic properties were evaluated with cyclic voltamme try and UV-Visible measurement, respectively. From these results, it was shown that Li 4Ti5O12 thin film had good electrochemical and electrochromic properties. The electrochromic property of t he ilm was used to investigate a diffusion of lithium ion through a solid matrix of Li 4Ti5O12. The result showed that an extraction process of lithium ion (bleaching process) from Li 4Ti5O12 thin film occurred for a short time (20 s), meaning that a mobility of lithium ions in Li 4Ti5O12 thin film was high.
Pyruvate Kinase-Deficient Escherichia coli Exhibits Increased Plasmid Copy Number and Cyclic AMP Levels

ABSTRACT Previously established consequences of abolishing pyruvate kinase (Pyk) activity in Escherichia coli during aerobic growth on glucose include reduced acetate production, elevated hexose monophosphate (HMP) pathway flux, elevated phosphoenolpyruvate carboxylase (Ppc) flux, and an increased ratio of phosphoenolpyruvate (PEP) to pyruvate. These traits inspired two hypotheses. First, the mutant (PB25) may maintain more plasmid than the wild type (JM101) by combining traits reported to facilitate plasmid DNA synthesis (i.e., decreased Pyk flux and increased HMP pathway and Ppc fluxes). Second, PB25 likely possesses a higher level of cyclic AMP (cAMP) than JM101. This is based on reports that connect elevated PEP/pyruvate ratios to phosphotransferase system signaling and adenylate cyclase activation. To test the first hypothesis, the strains were transformed with a pUC-based, high-copy-number plasmid (pGFPuv), and copy numbers were measured. PB25 exhibited a fourfold-higher copy number than JM101 when grown at 37°C. At 42°C, its plasmid content was ninefold higher than JM101 at 37°C. To test the second hypothesis, cAMP was measured, and the results confirmed it to be higher in PB25 than JM101. This elevation was not enough to elicit a strong regulatory effect, however, as indicated by the comparative expression of the pGFPuv-based reporter gene, gfp uv , under the control of the cAMP-responsive lac promoter. The elevated cAMP in PB25 suggests that Pyk may participate in glucose catabolite repression by serving among all of the factors that tighten gene expression.
An ANMS‐NASPGHAN consensus document on anorectal and colonic manometry in children

Over the last few years, the study of the colon and anorectal function has experienced great technical advances that have facilitated the performance of the tests and have allowed a more detailed characterization of reflexes and motor patterns. As a result, we have achieved a much better understanding of the pathophysiology of children with defecation problems. Anorectal and colonic manometry are now commonly used in all major pediatric referral centers as diagnostic tools and to guide the management of children with intractable constipation and fecal incontinence, particularly when a surgical intervention is being considered.
Radiochemical Evaluation and In Vitro Assessment of the Targeting Ability of a Novel 99mTc-HYNIC-RGD for U87MG Human Brain Cancer Cells.

BACKGROUND Labeled RGD peptide that specifically targets ανβ3 integrin has great potential for the early diagnosis of malignant tumors. αvβ3 integrin receptors appear specifically more on the surface of glioblastoma (malignant glioma) cells rather than normal cells. OBJECTIVE The aim of this study was to identify a novel RGD that can be radiolabeled with99mTc with in vitro assessment of its targeting ability for U87MG human brain cancer cells. METHOD Novel RGD was designed by Amino Acid retro-inversion technique. The peptide HYNIC conjugate was radiolabeled with 99mTc at 95°C for 10 min and radiochemical analysis was performed using ITLC and HPLC methods. The stability of the radiopeptide was checked in the presence of human serum at 37°C up to 24 h. Binding properties and internalization were studied with U87MG cells. RESULTS Novel HYNIC-RGD has shown high radiochemical purity over 98%. Radioconjugate binding and internalization in U87MG cells were high and specific (13.96% and 12.38% at 4 h respectively). The radiolabeled peptide revealed good affinity for glioblastoma cells (Kd =1.46 ±0.26nM). CONCLUSION The in vitro study demonstrated the targeting ability of novel 99mTc-HYNIC-RGD for glioblastoma cells. Therefore, more in vivo studies are required.