Miracle-dz/UniFAR-FTUs huggingface dataset:
Uncoupling stress granule assembly and translation initiation inhibition.

Cytoplasmic stress granules (SGs) are specialized regulatory sites of mRNA translation that form under different stress conditions known to inhibit translation initiation. The formation of SG occurs via two pathways; the eukaryotic initiation factor (eIF) 2alpha phosphorylation-dependent pathway mediated by stress and the eIF2alpha phosphorylation-independent pathway mediated by inactivation of the translation initiation factors eIF4A and eIF4G. In this study, we investigated the effects of targeting different translation initiation factors and steps in SG formation in HeLa cells. By depleting eIF2alpha, we demonstrate that reduced levels of the eIF2.GTP. Met-tRNAi(Met) ternary translation initiation complexes is sufficient to induce SGs. Likewise, reduced levels of eIF4B, eIF4H, or polyA-binding protein, also trigger SG formation. In contrast, depletion of the cap-binding protein eIF4E or preventing its assembly into eIF4F results in modest SG formation. Intriguingly, interfering with the last step of translation initiation by blocking the recruitment of 60S ribosome either with 2-(4-methyl-2,6-dinitroanilino)-N-methylpropionamideis or through depletion of the large ribosomal subunits protein L28 does not induce SG assembly. Our study identifies translation initiation steps and factors involved in SG formation as well as those that can be targeted without induction of SGs.
ERYTHROPOIETIN‐INDEPENDENT REGENERATION OF ERYTHROID PROGENITOR CELLS FOLLOWING MULTIPLE INJECTIONS OF HYDROXYUREA

It was shown previously that colony formation in vitro by early erythroid progenitor cells (BFUe) requires sequential stimulation with a specific glycoprotein termed BFA and erythropoietin (EP). The action exerted by BFA was characterized as induction of proliferation in BFUe resulting after several cell divisions in EP‐responsive progeny. The present study is directed at detection of EP‐independent regulation of erythroid progenitor cells in vivo.
Bilateral subthalamic stimulation in patients with Parkinson disease: long-term follow up.

OBJECT Bilateral subthalamic nucleus (STN) stimulation is increasingly used in patients with advanced Parkinson disease (PD). This study was performed to evaluate the long-term efficacy and safety of bilateral STN stimulation in cases of PD. METHODS The authors performed a prospective, open-label study in patients with PD who underwent bilateral STN stimulation. The authors compared motor scores and activities of daily living (ADL) scores based on the Unified PD Rating Scale (UPDRS) obtained before surgery while patients were in the medication-off state with scores obtained at follow-up evaluations of these patients while in the medication-off/stimulator-on state. Data contained in patient diaries were also compared. Thirty-three patients with PD were evaluated 12 months postoperatively and 19 were evaluated at a mean follow-up time of 28 months. A comparison between UPDRS scores obtained in patients in the medication-off/stimulator-on state and those obtained when patients were in the baseline medication-off state showed a 27% improvement in ADL scores and a 28% improvement in motor scores after surgery. There was a 57% reduction in the use of levodopa-equivalent medication doses. The percentage of the waking day that patients were in the medication-on state increased from 38 to 72%. Surgical complications included seizures (three patients), confusion (five patients), hemiballismus (one patient), and visual disturbance (one patient). Stimulation-related adverse effects were mild. Device-related events included nine lead replacements, seven lead revisions, six extension replacements, and 12 implantable pulse generator (IPG) replacements; one IPG was cleaned and one IPG was placed in a pocket because of the presence of a shunt. CONCLUSIONS Bilateral STN simulation is associated with a significant improvement in the motor features of PD. Device-related events were common in the first 20 patients who underwent surgery, often requiring repeated surgeries.
Radiation From a Dielectric-Filled Waveguide Terminated by a Finite Metallic Flange of Arbitrary Shape

A diagnostic and design tool, based on the method of moments (MoM) technique, is presented for analysing the radiation from an aperture incorporating dielectric material and mounted on a metallic flange of finite size and arbitrary shape. The method can handle aperture problems with a wide variety of geometry and is therefor a very powerful design tool, which can be used to improve the antenna design. Using the equivalence principle, an equivalent problem is derived and when the appropriate boundary conditions are imposed a set of integral equations is obtained with surface currents on the waveguide as the unknowns. These integral equations are solved by the MoM to yield the surface currents, from which the radiation pattern is calculated. The software is validated by a comparison of simulated and measured antenna performances (patterns and SWR).
Bispectral analysis as a tool to investigate dynamics of cardiorespiratory physiology.

INTRODUCTION Recent studies show that cardiorespiratory variables are nonlinearly coupled. In the present study, we tested the feasibility of using bispectral analysis to estimate changes in nonlinear phase coupling. METHODS We stimulated chemo- and baro-reflexes by switching inspired gas between air and air with 5% CO2 added during supine and 70 degrees head-up tilt. Bispectra were estimated using Fourier transform of the triple cumulant and were integrated between 0.04 and 0.3 Hz. Variables analyzed included cardiac RR intervals, systolic BP (SBP), tidal volume (VT), end tidal pressure of CO2 (PETCO2) and mean cerebral blood flow velocity (CBFM). Data were collected in 30 healthy adults who were then grouped according to whether they become presyncopal (PS) during tilt or remained normal with no signs or symptoms of presyncope (NPS). RESULTS Six subjects (20%) developed presyncope. During tilt with room air breathing, phase coupling in RR, SBP, and between RR-SBP and RR-VT was lower in PS than in NPS, while phase coupling between CBFM-SBP was higher. In contrast, during tilt with 5% inhaled CO2, phase coupling between CBFM-PETCO2 was lower for PS than for NPS. DISCUSSION Perturbations to baro- and chemo-reflexes led to changes in nonlinear phase coupling that were altered in presyncope. Although physiological interpretation of changes in phase coupling are less than clear at this time, our results show that such nonlinear indexes may provide a helpful perspective in understanding the complex phenomenon of orthostatically mediated syncope.
The symphonic structure of childhood stress reactivity: Patterns of sympathetic, parasympathetic, and adrenocortical responses to psychological challenge

Abstract Despite widespread recognition that the physiological systems underlying stress reactivity are well coordinated at a neurobiological level, surprisingly little empirical attention has been given to delineating precisely how the systems actually interact with one another when confronted with stress. We examined cross-system response proclivities in anticipation of and following standardized laboratory challenges in 664 4- to 14-year-olds from four independent studies. In each study, measures of stress reactivity within both the locus coeruleus-norepinephrine system (i.e., the sympathetic and parasympathetic branches of the autonomic nervous system) and the corticotrophin releasing hormone system (i.e., the hypothalamic–pituitary–adrenal axis) were collected. Latent profile analyses revealed six distinctive patterns that recurred across the samples: moderate reactivity (average cross-system activation; 52%–80% of children across samples), parasympathetic-specific reactivity (2%–36%), anticipatory arousal (4%–9%), multisystem reactivity (7%–14%), hypothalamic–pituitary–adrenal axis specific reactivity (6%–7%), and underarousal (0%–2%). Groups meaningfully differed in socioeconomic status, family adversity, and age. Results highlight the sample-level reliability of children's neuroendocrine responses to stress and suggest important cross-system regularities that are linked to development and prior experiences and may have implications for subsequent physical and mental morbidity.
Multiple spliced and unspliced transcripts from human cytomegalovirus immediate-early region 2 and evidence for a common initiation site within immediate-early region 1

Human cytomegalovirus immediate-early (IE) region 2 (0.732 to 0.740 map unit) begins 35 nucleotides downstream of IE region 1 (Stenberg et al., J. Virol. 49:190-199, 1984). A series of mRNAs that have different splicing patterns are transcribed from region 2. There is an unspliced 1,589-nucleotide exon present in minor amounts and two spliced exons (836 and 289 nucleotides) present in larger amounts. The IE region 2 exons were found to be spliced onto the first three exons of region 1. Therefore, under IE conditions the region 1 promoter-regulatory region can promote transcription of region 2. Promoter sequences (i.e., CAAT and TATA boxes) are found upstream of the 5' end of IE region 2 but presumably function poorly at IE times after infection. The transcriptional regulation of these IE genes and the possible functional roles of the proteins are discussed. We postulate that a series of unique but related proteins are made from the region 2 transcripts. Some of these proteins should contain the same 169 amino-terminal residues as the major IE 72-kilodalton protein encoded by IE region 1 (Stenberg et al., J. Virol. 49:190-199, 1984). Variations in the amino acid sequences of the region 2 proteins could occur at either the amino terminus, the carboxy terminus, or both termini.
Identiﬁcation and Characterization of a Nucleolar Phosphoprotein, Nopp140, as a Transcription Factor

Expression of the alpha-1 acid glycoprotein (AGP) gene ( agp ) is activated by a key transcription factor, AGP/enhancer-binding protein (AGP/EBP, commonly called C/EBP (cid:98) ), in the liver during the acute-phase response. In addition to this positive regulation, agp is negatively regulated by nucleolin (T. H. Yang et al., Mol. Cell. Biol. 14:6068–6074, 1994). Other factors involve in positive regulation of the agp gene are poorly characterized. In a systematic search for factors that may interact with AGP/EBP, we have identiﬁed Nopp140, a phosphoprotein of 140 kDa, by immunoafﬁnity chromatography. Nopp140 not only functions as a transcriptional activator per se but also interacts with AGP/EBP to synergistically activate the agp gene in an AGP/ EBP-binding motif-dependent manner. In addition to interacting with AGP/EBP, Nopp140 interacts speciﬁ- cally with TFIIB. Distinct regions of Nopp140 that interact with AGP/EBP and TFIIB have been characterized. The sequence of Nopp140 contains
Dual-source CT in step-and-shoot mode: noninvasive coronary angiography with low radiation dose.

PURPOSE To prospectively investigate computed tomographic (CT) image quality parameters by using different protocols and to calculate radiation dose estimates for noninvasive coronary angiography performed with dual-source CT in the step-and-shoot (SAS) mode. MATERIALS AND METHODS This study was local ethics board approved; written informed consent was obtained from all patients. In the preliminary portion of the study, 40 patients underwent CT coronary angiography in the SAS mode: at 100 kV (protocol A) in 22 patients with a body mass index (BMI) of less than 25 kg/m(2) and at 120 kV (protocol B) in 18 patients with a BMI of 25-30 kg/m(2). Both protocols involved use of an attenuation-based tube current and 1 mL of contrast material per kilogram of body weight. The final portion of the study involved 50 additional patients: 21 patients with a BMI of 25-30 kg/cm(2) assigned to protocol B and 29 patients with a BMI of less than 25 kg/cm(2) assigned to protocol C, which was performed with 100 kV, an attenuation-based tube current, and a reduced contrast material dose of 0.8 mL/kg. Image quality was independently assessed. Attenuation in the aorta and coronary arteries and image noise were measured. Radiation dose was estimated. RESULTS Mean image noise was similar with protocols A and B. Mean attenuation in the aorta and coronary arteries with protocol A (444 HU) was significantly (P < .001) higher than that with protocol B (358 HU). The reduced contrast material dose in protocol C yielded attenuation similar to that with protocol B. Diagnostic image quality was achieved with all protocols in 1237 (97.9%) of 1264 coronary segments. No significant differences in image quality between the 100- and 120-kV protocols were found. Mean heart rate had a significant effect on motion artifacts (area under receiver operating characteristic curve [AUC] = 0.818; 95% confidence interval [CI]: 0.723, 0.892; P < .001), whereas heart rate variability had a significant effect on stair-step artifacts (AUC = 0.79; 95% CI: 0.687, 0.865; P < .001). The mean estimated effective dose was 1.2 mSv +/- 0.2 for protocols A and C and 2.6 mSv +/- 0.5 for protocol B. CONCLUSION Dual-source SAS-mode CT coronary angiography yielded diagnostic image quality for 97.9% of coronary segments at a low radiation dose.
E. coli‐expressed recombinant norovirus capsid proteins maintain authentic antigenicity and receptor binding capability

The baculovirus expression system has been widely used to produce the capsid proteins of Norovirus (NV) and the proteins form virus‐like particles (VLPs) that are useful in many studies, such as immunology, diagnosis, and host‐receptor interaction. We report here the application of the E. coli expression system in the production of recombinant NV capsid proteins. In a direct comparison of a previous well‐characterized NV strain (VA387), we have demonstrated that the E. coli‐expressed capsid proteins maintain the same antigenicity and receptor binding specificity as that of the baculovirus‐expressed capsid, although the E. coli‐expressed VA387 proteins did not form VLPs. Using the E. coli‐expression system, we characterized the receptor‐binding patterns of three additional NV strains (OIF1998, Parris Island and VA115), in which OIF1998 binds to HBGA of nonsecretors but did not bind or binds weakly to the HBGA of secretors, as seen in strain VA207. Parris Island binds to HBGA of types A and B but not type O secretors and nonsecretors. VA115 did not show specific binding to any A, B, O secretor nor nonsecretor, which is also observed when the capsid protein of this strain was expressed in baculovirus. Our data indicate that VLP formation is not required for receptor binding, and that the bacteria expression system offers a simple alternative for large production of NV capsid protein for various research purposes, particularly for strains generating low yields in the insect cells. J. Med. Virol. 74:641–649, 2004. © 2004 Wiley‐Liss, Inc.
The Right Ventricular Outflow Tract as an Alternative Permanent Pacing Site: Long‐Term Follow‐Up

The long‐term characteristics of the right ventricular outflow tract have been assessed as an alternative permanent pacing site to the right ventricular apex. Thirty‐three consecutive patients requiring ventricular pacing were randomized to be paced from one of the two sites. Pacing was performed using a screw‐in lead, and a programmable pacemaker was used to facilitate threshold testing. There was no significant difference in the lead positioning time or any acute implant measurement (e.g., threshold at 0.5 msec 0.4 ± 0.2 V for both sites, P = 0.99). Chronic measurements were also comparable during follow‐up (mean 73 months) with a mean threshold at most recent follow‐up of 0.15 ± 0.2 msec (apex) and 0.13 ± 0.21 msec (outflow tract) at 5 V, P = 0,81, There was only one pacing related complication, a lead dislodgment (outflow tract) in a pacemaker twiddler. Overall, both sites were highly satisfactory.
Uncoupling of Promitogenic and Antiapoptotic Functions of IL-2 by Smad-Dependent TGF-β Signaling1

TGF-β opposes proliferative signaling by IL-2 through mechanisms that remain incompletely defined. In a well-characterized CD8+ T cell model using wild-type and mutated IL-2 receptors, we examined the effects of TGF-β on distinct IL-2 signaling events in CD8+ T cells. IL-2 induces c-myc, cyclin D2, and cyclin E in a redundant manner through the Shc and STAT5 pathways. TGF-β inhibited the ability of either the Shc or STAT5 pathway to induce these genes, as well as T cell proliferation. The inhibitory effects of TGF-β were reversed by expression of a dominant-negative form of Smad3. TGF-β did not impair proximal signaling by Shc or STAT5, and induction of some downstream genes, including cytokine-inducible Src homology-2-containing protein (CIS), bcl-xL, and bcl-2, was spared. Experiments with c-fos, cyclin D2, and CIS reporter genes revealed that promoter-proximal regulatory elements dictate the sensitivity of IL-2 target genes to inhibition by TGF-β. By leaving the Shc and STAT5 pathways functional while inhibiting their target genes selectively, TGF-β was found to uncouple the proliferative and antiapoptotic functions of IL-2. Thus, TGF-β is not a simple antagonist of IL-2, but rather serves to qualitatively modify the IL-2 signal to create a unique pattern of gene expression that neither cytokine can induce independently.
INDUCTION OF ANTIGEN‐SPECIFIC UNRESPONSIVENESS TO PANCREATIC ISLET ALLOGRAFTS BY ANTILYMPHOCYTE SERUM

The mechanism (or mechanisms) underlying the indefinite survival of DBA/2 islet allografts in strongly histoincompatible (C57BL/6·A)F1 (B6AF1) mice, induced either by the combined use of Ficoll-prepared crude islets and treatment of recipients with antilymphocyte serum (ALS), or by the use of handpicked, purified islets in nonimmunosuppressed recipients, was examined. B6AF1 mice bearing DBA/2 crude islet allografts for more than 100 days following ALS treatment accepted secondary DBA/2 crude islet allografts, but acutely rejected third-party A.SW crude islet allografts. This antigen-specific unresponsiveness to islet allografts can be successfully transferred into syngeneic BGAF1 mice by spleen cells. However, the state of unresponsiveness to donor antigen observed in these animals appears to be relatively weak, since transplantation of DBA/2 skin allografts or injection of DBA/2 spleen cells (5×107) caused acute rejection of long-term-accepted islet allografts. In contrast, B6AF1 mice bearing DBA/2 purified islet allografts over 100 days without immunosuppression rejected the secondary DBA/2 crude islet allografts acutely. Transfer of spleen cells obtained from these animals to syngeneic B6AF1 mice failed to induce prolongation of DBA/2 crude islet allografts. Thus, the mechanism (or mechanisms) involved in the long-term acceptance of islet allografts induced
Cost-effectiveness of a primary care based physical activity intervention in 45-74 year old men and women: a randomised controlled trial.

OBJECTIVE: To assess the cost-effectiveness of a primary care based intervention aimed at increasing levels of physical activity in inactive people aged 45-74. METHODS: A total of 714 inactive people aged 45-74, taken from two west London general practices, were randomised into two groups. Intervention subjects were invited to a consultation with an exercise development officer, and offered a personalised 10 week programme to increase their level of regular physical activity, combining leisure centre and home based activities. Control subjects were sent information on local leisure centres. All subjects were followed up at eight months. RESULTS: There was a net 10.6% (95% confidence interval 4.5 to 16.9%) reduction in the proportion of people classified as sedentary in the intervention group compared with the control group, eight months after the intervention. The intervention group also reported an increase in the mean number of episodes of physical activity per week, as compared with the control group (an additional 1.52 episodes (95% confidence interval 1.14 to 1.95)). The cost of moving a person out of the sedentary group was shown to be less than 650 Pounds. The cost of moving someone to the now commonly recommended level was estimated at almost 2500 Pounds. CONCLUSIONS: Moderate physical activity can be successfully encouraged in previously sedentary men and women aged 45-74 through a primary care based intervention. The process of recruitment was the most important variable cost. A high uptake rate would maximise cost-effectiveness, and sensitivity analysis suggests that unit costs could be halved with a more effective recruitment strategy.
On the mechanism of horse spleen apoferritin assembly: a sedimentation velocity and circular dichroism study.

The apoferritin shell is known to assemble spontaneously from its subunits obtained at acid pH upon neutralization. The reassembly of apoferritin from horse spleen has been followed by means of sedimentation velocity and circular dichroism experiments as a function of the pH and the nature of the assembly buffer in order to obtain information on the assembly pathway. In all the buffer systems tested the subunits sediment as a single peak of varying sedimentation and diffusion coefficients, and shell assembly starts at pH values around 3.5. In dilute glycine-acetate buffers the subunits are essentially dimeric up to this pH value. Therefore, the dimeric building blocks of the apoferritin shell that are apparent in the X-ray structure represent the first assembly intermediates. When the pH is increased to 4.0-4.3, the weight-average sedimentation velocity of the subunits increases to 3.6-4.7 S, respectively, and the subunit population becomes heterogeneous. Concomitantly, significant changes in the circular dichroism properties of the aromatic residues take place. On the basis of the X-ray structure, where aromatic residues appear to be located at or near the fourfold symmetry axes, these data suggest that assembly proceeds from dimers through tetramers and octamers. In the pH range 4.5-6.5 the reassembly process cannot be followed due to reversible precipitation of the subunits near their isoelectric point; at neutral pH values essentially quantitative reassembly is obtained. (ABSTRACT TRUNCATED AT 250 WORDS)
A homogeneous chemiluminescent assay for telomerase.

I have designed an unamplified assay for human telomerase based on the hybridization protection assay. This assay measures in vitro synthesis of the human telomeric repeat DNA sequence (TTAGGG)N by solution hybridization with a chemiluminescent acridinium ester oligonucleotide probe. The assay is capable of detecting less than 0. 1 fmol of the telomerase repeat DNA sequence, and has a linear range extending to 3.5 fmol/reaction. Using this assay, telomerase activity can be measured in less than 60 min. The hybridization protection assay can be used to determine the amount of telomerase activity in a cell-free extract obtained from as few as 10(5) cells, and is three to four orders of magnitude less sensitive than PCR-based telomerase assays. However, the precision, accuracy, and rapidity of this telomerase assay make it suitable for enzyme isolation, enzyme characterization, and high-throughput screening applications.
A new saw-like self-recovery of interface states in nitride-based memory cell

A new saw-like self-recovery Self-Aligned Nitride (SAN) memory cell is proposed and fabricated in 28nm high-k metal gate (HKMG) CMOS process for high-density logic NVM applications. The cell is operated with Source-Side Injection (SSI) for programming and band-to-band hot holes (BBHH) for erasing. Two effective self-heating recovery mechanisms are proposed and performed to maintain a stable On/Off read window after cycling stresses. Besides, the characteristic and reliability comparison of the SAN cell in other technology nodes, 90nm/45nm/32nm, are characterized to further verify the saw-like self-detrapping and self-recovery operation. The new 28nm HKMG SAN memory cell with the self-detrapping recovery results excellent and superior endurance performance and can provide a very promising solution for logic NVM in advanced technologies.