Miracle-dz/UniFAR-FTUs huggingface dataset:
Stability of mRNA influences osteoporotic bone mass via CNOT3

Significance Osteoporosis is a highly prevalent disease affecting nearly 20 million people in the United States and is life-threatening in elderly patients. However, underlying pathophysiology regarding the posttranscriptional control of bone resorption is incompletely understood. CNOT3 is a molecule involved in mRNA stability in yeast to mammalian cells, but its role in bone regulation is not known. We discovered that Cnot3 deficiency specifically enhances receptor activator of NF-κB (RANK) mRNA stability and leads to osteopenia in healthy young adult animals. Moreover, Cnot3 levels are reduced in ageing-induced osteoporosis, and Cnot3 deficiency further exacerbates such osteoporosis significantly. As a mechanism, Cnot3 binds to RANK mRNA and its 3′-UTR renders Cnot3-dependent instability to the reporter gene. Our results reveal Cnot3 regulation in aging-induced osteoporosis. Osteoclastogenesis is under the control of posttranscriptional and transcriptional events. However, posttranscriptional regulation of osteoclastogenesis is incompletely understood. CNOT3 is a component of the CCR4 family that regulates mRNA stability, but its function in bone is not known. Here, we show that Cnot3 deficiency by deletion of a single allele induces osteoporosis. Cnot3 deficiency causes an enhancement in bone resorption in association with an elevation in bone formation, resulting in high-turnover type bone loss. At the cellular level, Cnot3 deficiency enhances receptor activator of NF-κB ligand (RANKL) effects on osteoclastogenesis in a cell-autonomous manner. Conversely, Cnot3 deficiency does not affect osteoblasts directly. Cnot3 deficiency does not alter RANKL expression but enhances receptor activator of NF-κB (RANK) mRNA expression in bone in vivo. Cnot3 deficiency promotes RANK mRNA stability about twofold in bone marrow cells of mice. Cnot3 knockdown also increases RANK mRNA expression in the precursor cell line for osteoclasts. Anti-CNOT3 antibody immunoprecipitates RANK mRNA. Cnot3 deficiency stabilizes luciferase reporter expression linked to the 3′-UTR fragment of RANK mRNA. In contrast, Cnot3 overexpression destabilizes the luciferase reporter linked to RANK 3′-UTR. In aged mice that exhibit severe osteoporosis, Cnot3 expression levels in bone are reduced about threefold in vivo. Surprisingly, Cnot3 deficiency in these aged mice further exacerbates osteoporosis, which also occurs via enhancement of osteoclastic activity. Our results reveal that CNOT3 is a critical regulator of bone mass acting on bone resorption through posttranscriptional down-regulation of RANK mRNA stability, at least in part, even in aging-induced osteoporosis.
A 2-D Discrete-Time Model of Physical Impairments in Wavelength-Division Multiplexing Systems

Dense wavelength-division multiplexing (DWDM) is a promising approach to design ultrahigh-capacity fiber-optic communication systems ( >; &nbsp;&nbsp;50 Tb/s). However, DWDM gives rise to severe physical impairments that adversely affect system performance. To mitigate various physical impairments in DWDM systems and exploit their system capacity, there is a need to develop a 2-D (time and wavelength) discrete-time input-output model of physical impairments that can become the foundation of signal processing for optical communications. This paper develops such a model based on the Volterra series transfer function (VSTF) method. We overcome the well-known triple integral problem associated with the VSTF method and reduce it to a simple integral. This model takes into account multiple channel effects, fiber losses, frequency chirp, optical filtering, and photo detection, which are ignored in the current literature. The model is in excellent agreement with results obtained by split-step Fourier simulation. Furthermore, with this model, we define coefficients that capture intersymbol interference, interchannel interference, self-phase modulation, intrachannel cross-phase modulation (XPM), intrachannel four-wave mixing (FWM), XPM, and FWM to characterize the impact of these effects individually on the system performance. We also apply this model to analyze the effects of varying system parameters and pulse shapes on the individual physical impairments.
Identification of the epidural space-loss of resistance to saline: An inexpensive modification

Epidural anaesthesia, based on successful localization of epidural space, is an integral part of the practice of anaesthesia. This technique has undergone major modifications as a result of improvement in the syringe, needle, catheter and technique following the first demonstration by Dogliotti in 1933. [1,2,3] Superiority of saline versus air in detecting the loss of resistance has always been a question of debate[4]. Syringes such as the Episure® Autodetect and the Epimatic® syringe are designed for identification of the epidural space using saline or air, using ‘’a both hands on needle technique’’ for superior control. We describe a similar technique herein using the routinely available material for epidural insertion similar to the expensive syringes available in the market. A video presentation of the technique is also provided.
Universal Multiparty Data Exchange and Secret Key Agreement

Multiple parties observing correlated data seek to recover each other’s data and attain omniscience. To that end, they communicate interactively over a noiseless broadcast channel - each bit transmitted over this channel is received by all the parties. We give a universal interactive communication protocol, termed the <italic>recursive data exchange protocol</italic> (RDE), which attains omniscience for any sequence of data observed by the parties and provide an individual sequence guarantee of performance. As a by-product, for observations of length <inline-formula> <tex-math notation="LaTeX">$n$ </tex-math></inline-formula>, we show the universal rate optimality of RDE up to an <inline-formula> <tex-math notation="LaTeX">$ {\mathcal O}(n^{-1/2}\sqrt {\log n})$ </tex-math></inline-formula> term in a generative setting where the data sequence is independent and identically distributed (in time). Furthermore, drawing on the duality between omniscience and secret key agreement due to Csiszár and Narayan, we obtain a universal protocol for generating a multiparty secret key of rate at most <inline-formula> <tex-math notation="LaTeX">$ {\mathcal O}(n^{-1/2}\sqrt {\log n })$ </tex-math></inline-formula> less than the maximum rate possible. A key feature of RDE is its <italic>recursive structure</italic> whereby when a subset <inline-formula> <tex-math notation="LaTeX">$A$ </tex-math></inline-formula> of parties recover each-other’s data, the rates appear as if the parties have been executing the protocol in an alternative model where the parties in <inline-formula> <tex-math notation="LaTeX">$A$ </tex-math></inline-formula> are collocated.
Randomised, double-blind controlled trial by dose reduction of implanted intrathecal morphine delivery in chronic non-cancer pain

Objective This study aimed to investigate the efficacy of intrathecal morphine in the long term by hypothesising that a reduction of the intrathecal opioid dose following long-term administration would increase the level of pain intensity. Design Randomised, double-blind, controlled, parallel group trial. Setting Department of Pain Management, Russells Hall Hospital, Dudley, UK. Participants 24 patients with non-cancer pain implanted with morphine reservoirs were assessed for eligibility. Interventions Participants were randomly allocated to one of two parallel groups in which one of the groups had no change in morphine dose and the other group had a small reduction (20%) in dosage every week during a 10-week follow-up. Outcome Primary outcomes were visual analogue scale (VAS) pain score change and withdrawal from the study due to lack of efficacy. Results 9 of the patients assessed for eligibility declined to participate in the study. 15 patients were randomised to control (n=5) or intervention (n=10) and included in an intention-to-treat analysis. Owing to worsening of pain, seven patients withdrew from the study prematurely. None knew prior to withdrawal which arm of the study they were in, but all turned out to be in the dose-reduction arm. The calculation of dropout rates between groups indicated a significant statistical difference (p=0.026) and recruitment was ceased. The VAS change between baseline and the last observation was smaller in the control group (median, Mdn=11) than in the intervention group (Mdn=30.5), although not statistically significant, Z=−1.839, p=0.070; r=−0.47. Within groups, VAS was significantly lower at baseline (Mdn=49.5) than at the last observation (Mdn=77.5) for the reduction group, Z=−2.805, p=0.002; r=−0.627 but not for the control group (p=0.188). Conclusions This double-blind randomised controlled trial of chronic intrathecal morphine administration suggests the effectiveness of this therapy for the management of chronic non-cancer pain. However, owing to the small number of patients completing the study (n=8), further studies are warranted. Trial registration International Standard Randomised Controlled Trials Centre (ISRCTN 33733462).
Effects of normobaric oxygen and melatonin on reperfusion injury: role of cerebral microcirculation

In order to protect the brain before an irreversible injury occurs, penumbral oxygenation is the primary goal of current acute ischemic stroke treatment. However, hyperoxia treatment remains controversial due to the risk of free radical generation and vasoconstriction. Melatonin is a highly potent free radical scavenger that protects against ischemic stroke. Considering its anti-oxidant activity, we hypothesized that melatonin may augment the survival-promoting action of normobaric oxygen (NBO) and prevent brain infarction. Herein, we exposed mice to 30 or 90 min of intraluminal middle cerebral artery occlusion (MCAo) and evaluated the effects of NBO (70% or 100% over 90 min), administered either alone or in combination with melatonin (4 mg/kg, i.p.), on disseminate neuronal injury, neurological deficits, infarct volume, blood-brain barrier (BBB) permeability, cerebral blood flow (CBF) and cell signaling. Both NBO and particularly melatonin alone reduced neuronal injury, neurological deficits, infarct volume and BBB permeability, and increased post-ischemic CBF, evaluated by laser speckle imaging (LSI). They also improved CBF significantly in the ischemic- core and penumbra, which was associated with reduced IgG extravasation, DNA fragmentation, infarct volume, brain swelling and neurological scores. Levels of phosphorylated Akt, anti-apoptotic Bcl-xL, pro-apoptotic Bax and endothelial nitric oxide synthase (NOS) were re-regulated after combined oxygen and melatonin delivery, whereas neuronal and inducible NOS, which were increased by oxygen treatment, were not influenced by melatonin. Our present data suggest that melatonin and NBO are promising approaches for the treatment of acute-ischemic stroke, which encourage proof-of-concept studies in human stroke patients.
Dimension estimation based detector for multiple-antenna cognitive radio networks

In this paper, a spectrum sensing approach for multiple-antenna cognitive radio networks will be proposed. Specifically, we will apply dimension estimation based spectrum sensing technique using minimum description length (MDL) criteria to sense the presence of primary users signals. Therefore, we consider a cognitive radio network with cognitive user equipped with M received antennas and K (M >; K) primary users and we try to estimate the number of primary users present in this network using MDL criteria. We detect then presence of primary signals for a fixed false alarm probability derived analytically using the distribution of Tracy-Widom of order two. Performance study of the proposed detector using different properties DVB-T systems will be presented. Simulation results show high performances detection even with a very small number of antennas.
Cellular Ti6Al4V with carbon nanotube-like structures fabricated by selective electron beam melting

Purpose – The purpose of this paper is to fabricate cellular Ti6Al4V with carbon nanotube (CNT)-like structures by selective electron beam melting and study the resultant mechanical properties based on each respective geometry to provide fundamental information for optimizing molecular architectures and predicting the mechanical properties of cellular solids. Design/methodology/approach – Cellular Ti6Al4V with CNT-like zigzag and armchair structures are fabricated by selected electron beam melting. The microstructures and mechanical properties of these samples are evaluated utilizing scanning electron microscopy, synchrotron radiation X-ray and compressive tests. Findings – The mechanical properties of the cellular solids depend on the geometry of strut architectures. The armchair-structured Ti6Al4V samples exhibit Young’s modulus from 501.10 to 707.60 MPa and compressive strength from 8.73 to 13.45 MPa. The zigzag structured samples demonstrate Young’s modulus from 548.19 to 829.58 MPa and compressive st.
Effects of the condition of the tubular electrode on hole size and shape in micro deep hole electrical discharge machining

An attempt has been made to find out the effects of the electrode condition on the micro drilled deep holes with electrical discharge machining process. With optimised machining parameters for copper electrode–brass work material combination, experiments were carried out with different electrode conditions viz. straight, tilted and bent electrodes. The objective was to find out the signatures of these electrode conditions on the size and shape of the hole obtained from the experimental results. Based on the results a geometrical model is constructed and presented.
Lineage Commitment in the Thymus Pathway Discriminates CD4 Versus CD8 Kinase/Mitogen-Activated Protein Kinase Activation of the Extracellular Signal-Related

We have investigated the role of the mitogen-activated protein kinase (MAPK) pathway in the differentiation of CD4 1 and CD8 1 T cells by looking speciﬁcally at the effects of inhibitors of MAPK-activating enzyme, MAPK/extracellular signal-related kinase (ERK) kinase (MEK), during the positive selection step from double-positive to single-positive (SP) thymocytes. Using a variety of transgenic/knockout mouse strain combinations that fail to differentiate individual lineages of SP thymocytes together with genetically engineered F(ab * ) 2 reagents that induce maturation preferentially to either the CD4 or CD8 subpopulations, we show that induction of CD4 differentiation cells is highly sensitive to levels of MEK inhibition that have no effect on CD8 maturation. In addition, the presence of MEK inhibitor is able to modify signals that normally induce CD4 differentiation to instead promote CD8 differentiation. Finally, we show that continuous culture in the presence of inhibitor interferes with TCR up-regulation in SP thymocytes, suggesting that MAPK signaling may be involved in ﬁnal maturation steps for both lineages. These data indicate that there is discrimination in the biochemical pathways that are necessary to specify CD4 and CD8 lineage commitment and can reconcile previously conﬂicting reports on the inﬂuence of MAPK activation in commitment and maturation of thymocytes. The Journal of Immunology, 1999, 163: 715–722. CD4 subset (13) or monospeciﬁc CD3 F(ab 9 ) 2 to induce CD8 differentiation (6, 14) in neonatal thymus organ culture (NTOC). Here we examine the contribution of the mitogen-activated protein (MAP) kinase (MAPK) signaling pathway on the induction of CD4 and CD8 thymocyte differentiation. Using the speciﬁc MEK inhibitors, PD98059, (15) and UO126 (16), we show that conditions that fully inhibit differentiation of mature CD4 SP cells, whether induced by endogenous ligands or by BsAbs, do not affect differentiation of functional CD8 cells. This is despite the fact that F(ab 9 ) 2 reagents that preferentially induce commitment to the CD8 lineage do activate ERK kinases. Furthermore, inhibition of ERK activity modiﬁes a CD4
Computational modeling of human coreceptor CCR5 antagonist as a HIV-1 entry inhibitor: using an integrated homology modeling, docking, and membrane molecular dynamics simulation analysis approach

Chemokine receptor 5 (CCR5) is an integral membrane protein that is utilized during human immunodeficiency virus type-1 entry into host cells. CCR5 is a G-protein coupled receptor that contains seven transmembrane (TM) helices. However, the crystal structure of CCR5 has not been reported. A homology model of CCR5 was developed based on the recently reported CXCR4 structure as template. Automated docking of the most potent (14), medium potent (37), and least potent (25) CCR5 antagonists was performed using the CCR5 model. To characterize the mechanism responsible for the interactions between ligands (14, 25, and 37) and CCR5, membrane molecular dynamic (MD) simulations were performed. The position and orientation of ligands (14, 25, and 37) were found to be changed after MD simulations, which demonstrated the ability of this technique to identify binding modes. Furthermore, at the end of simulation, it was found that residues identified by docking were changed and some new residues were introduced in the proximity of ligands. Our results are in line with the majority of previous mutational reports. These results show that hydrophobicity is the determining factor of CCR5 antagonism. In addition, salt bridging and hydrogen bond contacts between ligands (14, 25, and 37) and CCR5 are also crucial for inhibitory activity. The residues newly identified by MD simulation are Ser160, Phe166, Ser180, His181, and Trp190, and so far no site-directed mutagenesis studies have been reported. To determine the contributions made by these residues, additional mutational studies are suggested. We propose a general binding mode for these derivatives based on the MD simulation results of higher (14), medium (37), and lower (25) potent inhibitors. Interestingly, we found some trend for these inhibitors such as, salt bridge interaction between basic nitrogen of ligand and acidic Glu283 seemed necessary for inhibitory activity. Also, two aromatic pockets (pocket I – TM1-3 and pocket II – TM3-6) were linked by the central polar region in TM7, and the simulated inhibitors show important interactions with the Trp86, Tyr89, Tyr108, Phe112, Ile198, Tyr251, Leu255, and Gln280 and Glu283 residues. These results shed light on the usage of MD simulation to identify more stable, optimal binding modes of the inhibitors.
Impact of apolipoprotein A5 variants on statin treatment efficacy.

AIMS Despite the fact that statin treatment efficacy is very high, there are substantial differences in treatment effectiveness among individuals. It is supposed that genetic predisposition plays an important role in these differences, but the contribution of individual polymorphisms is poorly understood. So far, more than 30 genes have been examined with ambiguous results. Apolipoprotein A5 is an important determinant of plasma lipid concentrations and its genetic variation could account for some of the observed differences in the response to statin therapy. However, this has not been analyzed before. MATERIALS AND METHODS We examined the putative association between APOA5 SNPs (c.-1131T>C, c.56C>G and c.457G>A) and efficacy during 3 months of statin treatment in 187 adult Caucasians. Patients were treated with low-dose (10 or 20 mg per day) simvastatin (46.3%), atorvastatin (40.5%) and lovastatin (13.2%). RESULTS The decrease in cholesterol was not significantly associated with the type or dose of statin. Carriers of the APOA5 genotype TT-1131 (n = 154) benefited more from statin treatment when compared with the C-1131 allele carriers (n = 33) (Delta low-density lipoprotein cholesterol: -36.3 +/- 15.1% vs Delta low-density lipoprotein cholesterol: -29.9 +/- 12.5%; p < 0.005, Mann-Whitney test). This result was independent of sex, age, BMI and APOE polymorphism. CONCLUSION Our results suggest that the APOA5 gene variants may play an important role in the pharmacogenetics of statin treatment.
Joint Estimation of Inverse Covariance Matrices Lying in an Unknown Subspace

We consider the problem of joint estimation of inverse covariance matrices lying in an unknown subspace of the linear space of symmetric matrices. We perform the estimation using groups of measurements with different covariances. Assuming the inverse covariances span a low-dimensional subspace, our aim is to determine this subspace and to exploit this knowledge in order to improve the estimation. We develop a novel optimization algorithm discovering and exploiting the underlying low-dimensional subspace. We provide a computationally efficient algorithm and derive a tight upper performance bound. Numerical simulations on synthetic and real world data are presented to illustrate the performance benefits of the algorithm.
Site preparation affects survival, growth of koa on degraded montane forest land

Banana poka vines (Possifloro mollisrimo) and k i i y u pass (Pennirerurn clondestinum) can limitkoa(Acociokoo)rreforertation in Hawaii. Performanceofplanted koaseedlings was studied in relation to type of site preparation: broadcast spraying of Roundup herbicide at threerates (2.M.4.05, and 6.07 kg active ingredient per hectare) andhand scalping vegetation fmm each planting spot. One year after planting, survival and growth of koa seedlings were significantly greaterinplotsspraycd with a he~vydoseofRoundup thanincon~Ip1ots. Ten-year survival and height were significantly greater for the heavydose treatment than for the scalp ueament, but none of the Utes in thc control treatment were alive. Site preparation must control competing vegetation over the entire planting area, to give koa a competitive edge during establishment. in cwwration with lhe Division of Faresw and Wildlife. Hawaii Depanment of Land and ~ a t u r k Resources. We lhmk Gerald Waltcrs and Howard Sakai for help in study design and establishment; lamer Baldwin for statistical guidance: Restoring native, mixed-species forests on degraded montane lands of Hawaii has become a desirable goal forFederal, State, and private land owners. For some owners the main objective is to restore habitat for recovery of threatened and endangered forest species. For others the main objective is to grow commercial size koa and other high-quality native hardwoods. And for still others the objective is to reestablish the flow of multiple, forest-derived benefits. Regardless of the objective forrestoring native forests, owners share a common concern-what can be done to establish and speed development of such forests? The question is difficult to answer partly because many aggressive introduced plants and animals have become naturalized ; they compete intensely with native forest species. Cattle grazing is incompatible with maintenance and restoration of nativeforests. Koa(Acacia koa), oneof the two main overstory trees inHawaiian forests and a key species in reforestationplans, is particularly vulnerable to damage by cattle. Banana poka (Passflora mollissima) and kikuyu grass (Pennisetum clandestinum) are two introduced plant species that can limit reforestation success in Hawaii. This paper reports the results of alternative types of site preparation on survival and growth of planted koa seedlings in an area heavily infested with banana poka and k i u y u grass. A randomized complete blockdesign was used to study theeffects of (a) broadcast spraying of Roundup herbicide at three rates (2.02,4.05, and 6.07 kg active ingredient per hectare) and (b) handscalping ofvegetationfroma0.3 square-meter areaaround each planting spot. The heavy-dose herbicide treatment …