Miracle-dz/UniFAR-FTUs huggingface dataset:
MicroRNA-30c-2* Expressed in Ovarian Cancer Cells Suppresses Growth Factor–Induced Cellular Proliferation and Downregulates the Oncogene BCL9

MicroRNAs (miRNAs) are small noncoding RNAs that function as master regulators of posttranscriptional gene expression with each miRNA negatively regulating hundreds of genes. Lysophosphatidic acid (LPA) is a mitogenic lipid present within the ovarian tumor microenvironment and induces LPA receptor activation and intracellular signaling cascades like ERK/MAPK, leading to enhanced cellular proliferation. Here, we show that in SKOV-3 and OVCAR-3 cells, LPA stimulation at concentrations ranging from 1 nmol/L to 20 μmol/L for 30 to 60 minutes increases miR-30c-2*, and this effect is mediated through a combination of receptors because knock down of multiple LPA receptors is required for inhibition. The epidermal growth factor and platelet-derived growth factor also increase miR-30c-2* transcript expression, suggesting a broader responsive role for miR-30c-2*. Thus, we investigated the functional role of miR-30c-2* through ectopic expression of synthetic miRNA precursors of mature miRNA or antagomir transfection and observed that microRNA-30c-2* reduces, and the antagomir enhances, cell proliferation and viability in OVCAR-3, cisplatin-insensitive SKOV-3 and chemoresistant HeyA8-MDR cells. Ectopic expression of miR-30c-2* reduces BCL9 mRNA transcript abundance and BCL9 protein. Consistent with this observation, miR-30c-2* ectopic expression also reduced BCL9 luciferase reporter gene expression. In comparison with IOSE cells, all cancer cells examined showed increased BCL9 expression, which is consistent with its role in tumor progression. Taken together, this suggest that growth factor induced proliferation mediates a neutralizing response by significantly increasing miR-30c-2* which reduces BCL9 expression and cell proliferation in SKOV-3 and OVCAR-3 cells, likely as a mechanism to regulate signal transduction downstream. Mol Cancer Res; 9(12); 1732–45. ©2011 AACR.
14.8 A 0.009mm2 2.06mW 32-to-2000MHz 2nd-order ΔΣ analogous bang-bang digital PLL with feed-forward delay-locked and phase-locked operations in 14nm FinFET technology

The race to deep sub-micron CMOS technology has resulted in a change in device architectures, from a planar structure to a FinFET to achieve decreased leakage, further downscaling, and better sub-threshold slope, even under a lower power supply. Downscaling trends have forced the analog semiconductor industry to move to the digital domain to maintain functionality in light of increasing short-channel effects and device mismatch. Furthermore, the main goal of the new technology is to achieve faster speed and lower cost. In leading-edge processes and design environments, conventional analog PLLs in systems-on-chip (SoCs) are being replaced by digitally operated PLLs to meet clock requirements for optimal overall system performance. While a widely used time-to-digital converter (TDC)-based digital PLL (TDC-DPLL) has a linear loop characteristic, which is simple and analogous to well-known analog PLLs, it has to overcome noise issues from TDC quantization error and phase noise from the digitally-controlled oscillator (DCO). The in-band noise floor of a TDC-DPLL is determined by the TDC resolution. Thanks to noise shaping techniques with oversampling and a pipelined architecture, noise performance can be improved. However, significant area and power must be spent to meet noise requirements. A bang-bang-based digital PLL (BB-DPLL), as the alternative type of DPLL has advantages in terms of area and power over a TDC-DPLL. However, its non-linear operation implies a longer lock time, limit-cycle noise, and high sensitivity to DCO noise. In addition, the in-band noise floor of a BB-DPLL is dominated by the input-tracking jitter, which mainly arises from the DCO noise. This paper presents a BB-DPLL in 14nm FinFET technology, combining a feed-forward delay-locked part (FFDLP) and phase-locked part (PLP) to mitigate aforementioned weaknesses.
Adherence of Clostridium thermocellum to cellulose

The adherence of Clostridium thermocellum, a cellulolytic, thermophilic anaerobe, to its insoluble substrate (cellulose) was studied. The adherence phenomenon was determined to be selective for cellulose. The observed adherence was not significantly affected by various parameters, including salts, pH, temperature, detergents, or soluble sugars. A spontaneous adherence-defective mutant strain (AD2) was isolated from the wild-type strain YS. Antibodies were prepared against the bacterial cell surface and rendered specific to the cellulose-binding factor (CBF) by adsorption to mutant AD2 cells. By using these CBF-specific antibodies, crossed immunoelectrophoresis of cell extracts revealed a single discrete precipitation peak in the parent strain which was absent in the mutant. This difference was accompanied by an alteration in the polypeptide profile whereby sonicates of strain YS contained a 210,000-molecular-weight band which was missing in strain AD2. The CBF antigen could be removed from cell extracts by adsorption to cellulose. A combined gel-overlay--immunoelectrophoretic technique demonstrated that the cellulose-binding properties of the CBF were accompanied by carboxymethylcellulase activity. During the exponential phase of growth, a large part of the CBF antigen and related carboxymethylcellulase activity was associated with the cells of wild-type strain YS. However, the amounts decreased in stationary-phase cells. Cellobiose-grown mutant AD2 cells lacked the cell-associated CBF, but the latter was detected in the extracellular fluid. Increased levels of CBF were observed when cells were grown on cellulose. In addition, mutant AD2 regained cell-associated CBF together with the property of cellulose adherence. The presence of the CBF antigen and related adherence characteristics appeared to be a phenomenon common to other naturally occurring strains of this species.
A Self-Regulatory System of Interlinked Signaling Feedback Loops Controls Mouse Limb Patterning

Embryogenesis depends on self-regulatory interactions between spatially separated signaling centers, but few of these are well understood. Limb development is regulated by epithelial-mesenchymal (e-m) feedback loops between sonic hedgehog (SHH) and fibroblast growth factor (FGF) signaling involving the bone morphogenetic protein (BMP) antagonist Gremlin1 (GREM1). By combining mouse molecular genetics with mathematical modeling, we showed that BMP4 first initiates and SHH then propagates e-m feedback signaling through differential transcriptional regulation of Grem1 to control digit specification. This switch occurs by linking a fast BMP4/GREM1 module to the slower SHH/GREM1/FGF e-m feedback loop. This self-regulatory signaling network results in robust regulation of distal limb development that is able to compensate for variations by interconnectivity among the three signaling pathways.
T regulatory cells in cancer: recent advances and therapeutic potential

Importance of the field: The active suppression of immune responses against tumor is a major barrier to the likely success of cancer immunotherapy. There is now compelling evidence implicating T regulatory cells (Tregs) as being key players driving immune suppression. Elevated frequencies of Tregs within the peripheral circulation and tumor microenvironment of cancer patients correlate with poor prognosis and reduced survival. Understanding the mechanism of Treg elevation is critical for the development of new approaches aiming to modulate the frequency and function of Tregs to enhance the efficacy of cancer immune-based therapies. Areas covered in this review: This review focuses on current knowledge concerning Tregs in cancer and discusses putative mechanisms which underlie the expansion of Tregs in cancer patients. Additionally, we review current strategies to deplete/suppress Treg activity, the limitations of these strategies and future perspective for improving their efficacy. What the reader will gain: An insight of the current aspects concerning Treg subsets in cancer and an overview of recent advances in the identification of Treg-specific markers, in addition to the potential strategies to target Tregs for enhancing antitumor immunity. Take home message: Mechanisms by which Treg functions modulate the immune response to tumors are becoming further understood. However, specific markers to tumor-specific/induced Tregs are yet to be clearly identified, which is a major limitation in optimizing strategies to specifically target Tregs in cancer. Despite this, strategies aimed at modulating Tregs in patients are providing some early encouraging results supporting the overall concept and indicating that further studies are clearly warranted.
Synthesis, storage and release of [14C]acetylcholine in isolated rat diaphragm muscles

1. Segments of rat diaphragms were kept in choline‐free media for 4 hr and were then exposed to a physiological concentration of [14C]‐choline (30 μ M) at 37° C. The synthesis, storage and subsequent release of [14C]acetylcholine by the muscles was assessed by isotopic‐ and bio‐assays after isolation of the transmitter by paper electrophoresis.
Neuro-Fuzzy Inference System based controller in 6 DoF in PUMA 560

One of the problems in robotics field is, to find the orientation and framing of arm's end to desired location there for the new method must be find the solution of forward and inverse Kinematics (IK) problem. Traditional methods such as iterative, geometric and algebraic are used to solve (IK) inadequate if the joint structure of the robot is more complex. As the complexity of manipulator increases, solution of IK is difficult and computationally expensive. In this paper the use of the ability of Adaptive Neuro-Fuzzy Inference System (ANFIS) to learn from training data is implemented. Then the creation of ANFIS with limited mathematical representation of the system is performed. In the proposed method, forward kinematics relations of robot arm are used to obtain the data for training and testing of ANFIS. Simulation using MATLAB and microcontroller is used to show the effectiveness of the approach. Also the practical results which are carried out on PUMA 560 with 6DoF robot arm are used to show the effectiveness of the approach and proved that this method has good performance.
Control of RNA Polymerase II Elongation Potential by a Novel Carboxyl-terminal Domain Kinase*

The entry of RNA polymerase II into a productive mode of elongation is controlled, in part, by the postinitiation activity of positive transcription elongation factor b (P-TEFb) (Marshall, N. F., and Price, D. H. (1995) J. Biol. Chem. 270, 12335-12338). We report here that removal of the carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase II abolishes productive elongation. Correspondingly, we found that P-TEFb can phosphorylate the CTD of pure RNA polymerase II. Furthermore, P-TEFb can phosphorylate the CTD of RNA polymerase II when the polymerase is in an early elongation complex. Both the function and kinase activity of P-TEFb are blocked by the drugs 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) and H-8. P-TEFb is distinct from transcription factor IIH (TFIIH) because the two factors have no subunits in common, P-TEFb is more sensitive to DRB than is TFIIH, and most importantly, TFIIH cannot substitute functionally for P-TEFb. We propose that phosphorylation of the CTD by P-TEFb controls the transition from abortive into productive elongation mode.
Reducing distress for children during invasive procedures: randomized clinical trial of effectiveness of the PediSedate®

Background: Procedural pain control remains problematic for young children, especially during anxiety‐causing procedures for which children should not be deeply sedated. The PediSedate® was designed to address this problem by delivering nitrous oxide in oxygen through a simple nosepiece, combined with an interactive video component, so that children can use attention and distraction with drug delivery.
Routine two-step skin testing for tuberculosis in the staff of a geriatric hospital in Israel: booster and conversion rates.

The objective of this study was to determine the prevalence of positive skin tests amongst the staff of a 200 bed geriatric hospital in Haifa, Israel. By comparing the findings with those of a study performed five years previously, we hoped to ascertain the number of conversions which had occurred in the period studied. This was undertaken in order to assess a new policy from the Israel Ministry of Health regarding skin testing for health care workers. We also hoped to decide upon the frequency of skin testing required and to compare data from recent immigrants from countries with a high prevalence of TB. In 1997, we performed two-step skin testing (TSST) on 318 health care workers. We ascertained the number of positive reactions on the first and second testing and calculated the number of subjects who showed significant boosting. We also compared the results to those obtained in a study in 1992 and calculated the rate of conversion. We used multivariate analysis to examine the effects of age, gender, country of origin, years in Israel, previous BCG vaccination, previous exposure to contagious TB, work site and area of residence in the city, on the response to TSST. Between 1990 and 1996, 655 000 immigrants from the former USSR arrived; 'recent immigration' was defined from that date onward. The final number of positive reactions out of 282 subjects, who were either positive or negative on step 1 and presented for step 2, was 171 (60%). Booster effect was not significantly associated with any of the variables examined. The size of reaction in TSST was related to country of origin and recent immigration. The 83 recent immigrants from the former USSR had more frequent (61%) and larger reactions (mean (sd): 9.0 (6.46) mm) than the 114 native-born Israelis with 39% positive reactions (6.2 (5.89) P= 0.009). Comparison with 1992 revealed 26 (31%) of previous negatives as positive. Conversion was associated with age. All conversions save one were in individuals younger than 50 years (P= 0.07). In conclusion, TSST, performed to enable detection of recent infection after exposure to contagious TB, was relevant for 40% of health care workers (HCWs). Second step testing contributed an additional 23% positive reactions. New immigrants had larger initial reactions. Conversion occurred mostly in younger workers and could be either due to unrecognized TB in the hospital or to exposure in the community.
Dictyostelium Tom1 Participates to an Ancestral ESCRT‐0 Complex

Sorting of ubiquitinated proteins to multivesicular bodies (MVBs) in mammalian cells relies on proteins with a Vps27/Hrs/STAM (VHS) domain. Here, we show that the amoeba Dictyostelium presents only one protein with a VHS domain: DdTom1. We demonstrate that the VHS domain of DdTom1 is followed by a Golgi‐localized, γ‐ear‐containing, ADP‐ribosylation‐factor‐binding and Tom1 (GAT) domain that binds ubiquitin, and by a non‐conserved C‐terminal domain that can recruit clathrin, EGFr pathway substrate 15 and tumor susceptibility gene 101, a component of the MVB biogenesis machinery [endosomal complexes required for transport (ESCRT) complexes]. Both VHS and GAT domains interact with phospholipids and therefore could ensure the recruitment of DdTom1 to endosomal membranes. We propose that DdTom1 participates in an ancestral ESCRT‐0 complex implicated in the sorting of ubiquitinated proteins into MVBs.
Studying multiple protein profiles over time to assess biomarker validity

Protein profile analysis is increasingly used for identification of disease biomarkers. The approaches vary from surface-enhanced laser desorption/ionization to protein arrays. Newer platforms are constantly being developed. Almost all are based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and are often coupled with sophisticated software tools. Protein profiling has been applied to a variety of samples including plasma, urine, cerebrospinal fluid, saliva and solid tissue. This article focuses on those instances where it is possible to obtain sequential samples from the same individual. In the authors use of a profile method, many protein changes with highly significant correlations to disease have been found. The main challenge lies in the validation of the marker to demonstrate its adequacy for use in the clinical setting. The latter requires a methodology that is robust and amenable to high-throughput. One problem is that interindividual variability among the healthy population can mask major changes that occur on an intraindividual basis. Often, a large change for an individual may remain within the range of healthy individuals. Thus, one strategy to optimize biomarker discovery is to examine serial samples from a given individual, where a disease biomarker is established by comparison with the individual’s own baseline sample. The focus of this review is to illustrate the principle and value of serial protein profiling using a rapid protein extraction method.
Clinical and instrumented measurements of hip laxity and their associations with knee laxity and general joint laxity.

CONTEXT Hip-joint laxity may be a relevant anterior cruciate ligament injury risk factor. With no devices currently available to measure hip laxity, it is important to determine if clinical measurements sufficiently capture passive displacement of the hip. OBJECTIVE To examine agreement between hip internal-external-rotation range of motion measured clinically (HIER(ROM)) versus internal-external-rotation laxity measured at a fixed load (HIER(LAX)) and to determine their relationships with knee laxity (anterior-posterior [KAP(LAX)], varus-valgus [KVV(LAX)], and internal-external rotation [KIER(LAX)]) and general joint laxity (GJL). Design : Cross-sectional study. SETTING Controlled research laboratory. PATIENTS OR OTHER PARTICIPANTS Thirty-two healthy adults (16 women, 16 men; age = 25.56 ± 4.08 years, height = 170.94 ± 10.62 cm, weight = 68.86 ± 14.89 kg). MAIN OUTCOME MEASURE(S) Participants were measured for HIER(ROM), HIER(LAX) at 0° and 30° hip flexion (-10 Nm, 7 Nm), KAP(LAX) (-90 N to 133 N), KVV(LAX) (±10 Nm), KIER(LAX) (±5 Nm), and GJL. We calculated Pearson correlations and 95% limits of agreement between HIER(ROM) and HIER(LAX)_0° and HIER(LAX)_30°. Correlation analyses examined the strength of associations between hip laxity, knee laxity, and GJL. RESULTS The HIER(ROM) and HIER(LAX) had similar measurement precision and were strongly correlated (r > 0.78). However, HIER(ROM) was systematically smaller in magnitude than HIER(LAX) at 0° (95% limits of agreement = 29.0° ± 22.3°) and 30° (21.4° ± 19.3°). The HIER(ROM) (r = 0.51-0.66), HIER(LAX)_0° (r = 0.52-0.69) and HIER(LAX)_30° (r = 0.53-0.76) were similarly correlated with knee laxity measures and GJL. The combinations of KVV(LAX) and either HIER(ROM), HIER(LAX)_0°, or HIER(LAX)_30° (R2 range, 0.42-0.44) were the strongest predictors of GJL. CONCLUSIONS Although HIER(ROM) and HIER(LAX) differed in magnitude, they were measured with similar consistency and precision and were similarly correlated with knee laxity and GJL measures. Individuals with greater GJL also had greater hip laxity. These findings are relevant to clinicians and investigators conducting prospective risk factor studies, given the need for accessible, efficient, and low-cost alternatives for characterizing an individual's laxity profile.
Pre-employment Background Checks on Social Networking Sites - May Your Boss Be Watching?

The practice of using social networking sites (SNS) for pre-employment screening has become increasingly popular. Although using SNS as a hiring tool may prove to be a potentially promising source of applicants’ information, it is also fraught with potential risks that uncover both legal and ethical challenges. The latter is also the reason why there are conflicting views about the practice both among the employers and employees as well as legal systems. In this paper I first aim to compare the privacy approaches in the US and Europe to investigate whether a job applicant actually has a right to expect privacy on SNS, and then I will examine the practices in a set of European countries (Estonia, United Kingdom, Germany, Finland) to analyze under what conditions employers are allowed to carry out background checks on SNS and weather the employer may base their hiring decision on the information found from these public domains. My analysis suggests that pre-employment background checks are generally considered to be acceptable in the US and also in Estonia; employers in the UK, Germany and Finland however, are not always allowed to investigate applicant’s background on SNS and should thus not be able to base one’s hiring decisions on the information found from SNS. My analysis reveals that the countries and employers need to work towards clarifying privacy standards and policies that would take into account the context created by the new technologies.
The effects of a novel anti-inflammatory compound (AHI-805) on cyclooxygenase enzymes and the recovery of ischaemia injured equine jejunum ex vivo.

REASONS FOR PERFORMING STUDY Flunixin meglumine is used for treatment of equine colic despite evidence of inhibited recovery of mucosal barrier function following small intestinal ischaemic injury. This study aimed to characterise an alternative treatment (AHI-805) for abdominal pain in the horse. OBJECTIVE To determine the effect of AHI-805, an aza-thia-benzoazulene derivative, on the cyclooxygenase enzymes and the recovery of mucosal barrier function following ischaemic injury. METHODS Effect of AHI-805 on in vitro COX-1 and COX-2 activity was determined by measuring coagulation-induced thromboxane B(2) (TXB(2)) and lipopolysaccharide-stimulated prostaglandin E(2) concentrations in equine whole blood. Horses (n = 6) were anaesthetised and jejunum subjected to ischaemia for 2 h. Control and ischaemia injured mucosa was placed in Ussing chambers and treated with Ringer's solution containing control treatment (DMSO), flunixin meglumine (27 µmol/l), or AHI-805 (27 µmol/l). Transepithelial electrical resistance (TER), mucosal-to-serosal flux of (3) H-mannitol, and bathing solution TXB(2) and prostaglandin E metabolites (PGEM) were measured over a 4 h recovery period. RESULTS Treatment with AHI-805 had no significant effect on TXB(2) production but significantly inhibited production of PGE(2) at a concentration of 1 µmol/l or greater. TER of flunixin or AHI-805 treated ischaemia-injured jejunum was significantly lower than control treated injured tissue over the recovery period. Mannitol flux and grade of histological damage were significantly increased by ischaemic injury only. There was a significant increase in PGEM and TXB(2) in control tissues over the 240 min recovery period, but not in flunixin or AHI-805 treated tissues. CONCLUSIONS Flunixin meglumine and AHI-805 inhibit recovery of barrier function in ischaemic-injured equine jejunum in vitro through inhibition of the COX enzymes. POTENTIAL RELEVANCE The novel compound AHI-805 may not be suitable for the treatment of equine colic associated with ischaemic injury.