Miracle-dz/UniFAR-FTUs huggingface dataset:
PAI-1 Leads to G1-Phase Cell-Cycle Progression through Cyclin D3/cdk4/6 Upregulation

The canonical function of plasminogen activator inhibitor-1 (PAI-1/SERPINE1) is as an inhibitor of urokinase-type plasminogen activator for blood clot maintenance, but it is now also considered a pleiotropic factor that can exert diverse cellular and tumorigenic effects. However, the mechanism controlling its pleiotropic effects is far from being understood. To elucidate the tumorigenic role of PAI-1, we tested the effects of PAI-1 after manipulation of its expression or through the use of a small-molecule inhibitor, tiplaxtinin. Downregulation of PAI-1 significantly reduced cellular proliferation through an inability to progress from the G0–G1 phase of the cell cycle. Accordingly, overexpression of PAI-1 augmented proliferation by encouraging S-phase entry. Biochemically, cell-cycle arrest was associated with the depletion of the G1-phase transition complexes, cyclin D3/cdk4/6 and cyclin E/cdk2, in parallel with the upregulation of the cell-cycle inhibitors p53, p21Cip1/Waf1, and p27Kip1. PAI-1 depletion significantly decreased the tumor size of urothelial T24 and UM-UC-14 xenografts, and overexpression of PAI-1 substantially increased the tumor size of HeLa xenografts. Finally, immunohistochemical analysis of human bladder and cervical tumor tissue microarrays revealed increased expression of PAI-1 in cancerous tissue, specifically in aggressive tumors, supporting the relevance of this molecule in human tumor biology. Implications: Targeting PAI-1 has beneficial antitumoral effects and should be further investigated clinically. Mol Cancer Res; 12(3); 322–34. ©2014 AACR.
Control of Ribosome Synthesis in Escherichia coli: Analysis of an Energy Source Shift-Down

The rate of ribosome synthesis and accumulation in Escherichia coli during the transition after an energy source shift-down was analyzed. The shift was imposed on cultures of stringent and relaxed strains growing in glucose minimal medium by the addition of the glucose analogue α-methylglucoside. In the stringent strain, ribosome synthesis was almost instantaneously reduced after the shift, whereas the relaxed strain exhibited a more gradual response. The rate of messenger ribonucleic acid (mRNA) synthesis was affected similarly, though to a smaller extent. A comparison of the rates of synthesis and accumulation of ribosomal RNA (rRNA) and ribosomal proteins showed that far more ribosomal components were synthesized after the shift than were accumulated, indicating that a substantial part of the rRNA made after the shift was unstable. A new method was used to measure relative rates of rRNA synthesis and to estimate the transcription time for the rRNA operon under different conditions. In steady states of growth with growth rates ranging from 0.75 to 2.3 doublings/h, as well as during the transition after a shift-down, the transcription time of the rRNA operon was constant. The rate of synthesis of rRNA correlated during this transition – in contrast to the rate of accumulation (M. T. Hansen et al., J. Bacteriol. 122: 585-591, 1975) – with the ppGpp pool in the same way as has been observed during partial amino acid starvation.
Use of Intrathecal Neostigmine as an Adjunct to Other Spinal Medications in Perioperative and Peripartum Analgesia: A Meta-analysis

Intrathecal neostigmine has been used as an adjunct to intrathecal local anaesthetic or opioid to prolong regional analgesia and improve haemodynamic stability, with variable results. This meta-analysis aims to evaluate the effectiveness and side-effects of intrathecal neostigmine in the perioperative and peripartum settings. The literature search was based on Cochrane Controlled Trials Register, EMBASE and MEDLINE (from 1966 to 14 November 2003) databases. Volunteer and animal studies were excluded. We identified 26 studies and 19 were considered suitable for detailed data extraction. Intrathecal neostigmine increased the incidence of nausea and vomiting (OR 5.0, 95% CI: 3.4 to 7.3; P<0.00001), bradycardia requiring intravenous atropine (OR 2.7, 95% CI: 1.4 to 5.4; P=0.005), and anxiety, agitation, or restlessness (OR 10.3, 95% CI: 3.7 to 28.9; P=0.00001). It improved the overall 24 hour VAS score (–1.4 VAS pain score, 95% CI: -1.7 to -1.2, P<0.00001), delayed the time of first request for rescue analgesia (168 min, 95% CI: 125 to 211; P<0.00001), and reduced the total number of rescue injections of nonsteroidal anti-inflammatory drug within the first 24 hours (-0.8, 95% CI: -1.1 to -0.4; P=0.00001). It did not affect the duration of motor blockade (3.5 min, 95% CI: -1.5 to 8.6; P=0.17) or the total amount of ephedrine required (-0.4 mg, 95% CI: -1.5 to 0.7; P=0.5). Adding intrathecal neostigmine to other spinal medications improves perioperative and peripartum analgesia marginally when compared with placebo. It is associated with significant side-effects and the disadvantages outweigh the minor improvement in analgesia achieved.
Unbalanced-magnetic-pull induced by the EM structure of PM spindle motor

The electromagnetic structure of the permanent-magnet spindle motor may induce intrinsic unbalanced-magnetic-pull (UMP). In the paper, this kind of UMP is analyzed with a method developed from the magnetic-circuit and magnetic field analysis. The principle of the method is introduced in the paper. The analysis shows that using the even slot can avoid the generation of the intrinsic UMP. Several spindle motors are used as example to explain the application, and the results prove the effectiveness of the proposed method.
Protease-defective, gp120-containing human immunodeficiency virus type 1 particles induce apoptosis more efficiently than does wild-type virus or recombinant gp120 protein in healthy donor-derived peripheral blood T cells

Apoptosis and syncytium formation are two mechanisms by which human immunodeficiency virus type 1 (HIV-1) impairs uninfected CD4+ T-cell function and are mainly involved in the progression of the disease to AIDS. Previously, we showed that gp120-containing, protease-deficient HIV-1 (L-2) particles generated syncytia by particle-mediated fusion with uninfected cultured CD4+ T cells. Here, we present evidence that such L-2 particles can induce apoptosis in 40 to 50% of T cells which were enriched from HIV-1-negative healthy donor-derived peripheral blood mononuclear cells (PBMC-Ts). Activation of PBMC-Ts with phytohemagglutinin, concanavalin A, or ionomycin after incubation with L-2 particles resulted in the loss of proliferative capacity and gradual induction of apoptosis over 3 days. Wild-type strain LAI particles or recombinant gp120 were markedly less efficient (< or = 15%) at inducing such apoptosis. Western blot (immunoblot) analysis revealed that L-2 particles contained a larger amount of Env gp120 than LAI particles. Either preincubation of PBMC-Ts with a Fas antagonist or preincubation of L-2 particles with soluble CD4 blocked most of the apoptosis. This suggests that L-2-like particles can play a major role in HIV-1-induced apoptosis of uninfected bystander cells.
Parathyroid hormone signaling in bone and kidney

Purpose of reviewParathyroid hormone (PTH) maintains a physiological balance of calcium and phosphate concentrations by binding to its receptor on the plasma membrane of cells in bone and kidney. It signals through multiple pathways, including protein kinase A and protein kinase C, although a preference for certain pathways is apparent in each organ and function. Here, we will review the recent advancements regarding PTH signaling in bone and kidney. Recent findingsWnt proteins have been reported as important regulators of bone metabolism in both PTH-dependent and independent pathways. Recent studies emphasize its role as a mediator of PTH signaling, as PTH treatment increased the expression of wnt4 and sfrp4 and decreased the expression of Wnt inhibitors such as Sost and sclerostin, leading to an increase in Wnt signaling. In kidney, sodium–hydrogen exchanger regulatory factor 1, originally known for its role in the retention of NaPi-IIa at the apical membrane, was shown to have multiple roles in PTH signaling, both as a mediator and regulator. SummaryPTH activates a number of different signaling pathways by binding to a single receptor in bone and kidney. Recent studies demonstrate the involvement of novel factors as well as additional roles for previously identified downstream factors of PTH.
Theories of emotion causation: A review

I present an overview of emotion theories, organised around the question of emotion causation. I argue that theories of emotion causation should ideally address the problems of elicitation, intensity, and differentiation. Each of these problems can be divided into a subquestion that asks about the relation between stimuli and emotions (i.e., the functional level of process description, cf. Marr, 1982) and a subquestion that asks about the mechanism and representations that intervene (i.e., the algorithmic level of process description). The overview reveals that theories of emotion causation sometimes differ with regard to the kind of process that they hold responsible for emotion causation. More precisely, they hold different assumptions regarding the conditions under which the process is supposed to operate (optimal versus suboptimal), the format of the representations involved (propositional versus perceptual), and the object or input of the central process (stimulus versus responses/experience). Further, the overview reveals that theories of emotion causation sometimes differ with regard to the level of process description that they focus on. Finally, the overview brings to light several similarities among the theories discussed.
Improving k‐t SENSE by adaptive regularization

The recently proposed method known as k‐t sensitivity encoding (SENSE) has emerged as an effective means of improving imaging speed for several dynamic imaging applications. However, k‐t SENSE uses temporally averaged data as a regularization term for image reconstruction. This may not only compromise temporal resolution, it may also make some of the temporal frequency components irrecoverable. To address that issue, we present a new method called spatiotemporal domain‐based unaliasing employing sensitivity encoding and adaptive regularization (SPEAR). Specifically, SPEAR provides an improvement over k‐t SENSE by generating adaptive regularization images. It also uses a variable‐density (VD), sequentially interleaved k‐t space sampling pattern with reference frames for data acquisition. Simulations based on experimental data were performed to compare SPEAR, k‐t SENSE, and several other related methods, and the results showed that SPEAR can provide higher temporal resolution with significantly reduced image artifacts. Ungated 3D cardiac imaging experiments were also carried out to test the effectiveness of SPEAR, and real‐time 3D short‐axis images of the human heart were produced at 5.5 frames/s temporal resolution and 2.4 × 1.2 × 8 mm3 spatial resolution with eight slices. Magn Reson Med 57:918–930, 2007. © 2007 Wiley‐Liss, Inc.
A Mission-Driven Organization Case Study: The Joshua Collingsworth Memorial Foundation

5 Acronyms & Definitions . 6 Introduction . 7 Research Statement . 8 Primary Research Question . 8 Sub-questions . 8 Literature Review. 9 Organizational Mission Statements. 9 Aligning Strategy to the Mission . 10 Dangers of Not Focusing on Mission. 12 Bolman and Deal Four Frame Approach. 13 Methodology . 14 Design. 14 Procedure. 15 Participants. 15 Limitations. 16 Results and Findings. 16 Organizational Background. 17 Presentation of Data. 19 Importance of Organizational Mission Statements. 20 Resources Needed to Remain Mission-Focused Organizationally. 22 Strengths Discovered in Mission-Focused Environment. 24 Challenges Discovered in Mission-Focused Environment. 25 Board Responsibilities in a Mission-Driven Organization. 26 Organizational Analysis. 28 The Structural Frame . 28 The Human Resource Frame . 30 The Political Frame . 32 The Symbolic Frame . 34 Summary of Findings . 37 Recommendations and Conclusions. 40 Recommendations . 41 Focus on Strategic Planning: External and Internal Analysis. 41 Succession Planning. 42 Develop Concrete Open Door Policy. 43 Build a Strong Fundraising & Development Plan. 43 Additional Hiring of Staff: Marketing & Public Relations. 45 Conclusion . 46 Limitations. 46 Research Contribution to Existing Knowledge. 46 Future Research Considerations. 47 Bibliography . 48 Appendix . 51 JCMF Strategic Plan . 51 Data Gathering: Interview Questions for JCMF Leadership. 54 Informed Consent Letter. 55 JCMF Financial Reports 2009-2011. 57
Covalent immobilization of xylanase produced from Bacillus pumilus SV‐85S on electrospun polymethyl methacrylate nanofiber membrane

Polymethyl methacrylate (PMMA) nanofiber membrane (NFM) was synthesized by an electrospinning technique. These membranes were utilized as a support for immobilization of xylanase enzyme to study its pH stability, thermal stability, and reusability. The morphology of aligned NFM was studied by optical microscopy and scanning electron microscopy. The PMMA NFM was functionalized with phenylenediamine and activated with glutaraldehyde to yield an aldehyde group on its surface for covalent immobilization of xylanase. The Fourier transform infrared analysis of the covalently immobilized xylanase confirmed that the enzyme was immobilized on PMMA NFM via amide linkages. The immobilization efficiency of covalently bound xylanase was found experimentally to be 90%. A forward shift in pH optima from 6.0–7.0 (soluble enzyme) to 7.0–9.0 (immobilized enzyme) was observed after xylanase immobilization. The pH and temperature stability of xylanase were enhanced upon its covalent immobilization. The immobilized enzyme was active on repeated use and retained ∼80% of its initial activity after 11 reaction cycles. The improved thermal and operational stability of the covalently immobilized enzyme on PMMA NFM might be advantageous for industrial applications.
Autoregulation allows Escherichia coli RNase E to adjust continuously its synthesis to that of its substrates

The Escherichia coli endonuclease RNase E plays a key role in rRNA maturation and mRNA decay. In particular, it controls the decay of its own mRNA by cleaving it within the 5′‐untranslated region (UTR), thereby autoregulating its synthesis. Here, we report that, when the synthesis of an RNase E substrate is artificially induced to high levels in vivo, both the rne mRNA concentration and RNase E synthesis increase abruptly and then decrease to a steady‐state level that remains higher than in the absence of induction. Using rne–lacZ fusions that retain or lack the rne 5′UTR, we show that these variations reflect a transient mRNA stabilization mediated by the rne 5′UTR. Finally, by putting RNase E synthesis under the control of an IPTG‐controlled promoter, we show that a similar, rne 5′UTR‐mediated mRNA stabilization can result from a shortage of RNase E. We conclude that the burst in substrate synthesis has titrated RNase E, stabilizing the rne mRNA by protecting its 5′UTR. However, this stabilization is self‐correcting, because it allows the RNase E pool to expand until its mRNA is destabilized again. Thus, autoregulation allows RNase E to adjust its synthesis to that of its substrates, a behaviour that may be common among autoregulated proteins. Incidentally, this adjustment cannot occur when translation is blocked, and we argue that the global mRNA stabilization observed under these conditions originates in part from this defect.
IDENTIFICATION OF TRANSCRIPTS GENERATED DURING THE RESPONSE OF RESISTANT BIOMPHALARIA GLABRATA TO SCHISTOSOMA MANSONI INFECTION USING SUPPRESSION SUBTRACTIVE HYBRIDIZATION

Suppression subtractive hybridization (SSH) was used to construct a complementary DNA library enriched for transcripts more abundantly expressed in the resistant BS90 strain of Biomphalaria glabrata at 12 hr postinfection with Schistosoma mansoni as compared with the susceptible M-line strain under the same circumstances. One hundred and twelve clones of the library were sequenced, yielding 88 unique SSH–expressed sequence tags (ESTs). Differential expression screening indicated that 22 of the 88 unique transcripts were strong candidates for differential expression in the BS90 strain relative to the M-line strain. Analysis of a subset of 4 transcripts using quantitative reverse transcriptase–polymerase chain reaction (qPCR) substantially supports the patterns obtained using the differential expression screen. Furthermore, the qPCR results revealed that gene upregulation in resistant snails, downregulation in susceptible snails, and differences in constitutive gene expression can all account for differential expression during the defense responses of resistant and susceptible snails. The majority (71.6%) of the SSH-ESTs recovered consisted of novel sequences not identified by sequence similarity to known genes. This work complements previous efforts to elucidate the genetic components underlying a successful response to S. mansoni by B. glabrata and identifies a series of transcripts deserving additional study in comparing susceptible and resistant snails.
Shaping a new Ca2+ conductance to suppress early afterdepolarizations in cardiac myocytes

Non‐technical summary Diseases, genetic defects, or ionic imbalances can alter the normal electrical activity of cardiac myocytes causing an anomalous heart rhythm, which can degenerate to ventricular fibrillation (VF) and sudden cardiac death. Well‐recognized triggers for VF are aberrations of the cardiac action potential, known as early afterdepolarizations (EADs). In this study, combining mathematical modelling and experimental electrophysiology in real‐time (dynamic clamp), we investigated the dependence of EADs on the biophysical properties of the L‐type Ca2+ current (ICa,L) and identified modifications of ICa,L properties which effectively suppress EAD. We found that minimal changes in the voltage dependence of activation or inactivation of ICa,L can dramatically reduce the occurrence of EADs in cardiac myocytes exposed to different EAD‐inducing conditions. This work assigns a critical role to the L‐type Ca2+ channel biophysical properties for EADs formation and identifies the L‐type Ca2+ channel as a promising therapeutic target to suppress EADs and their arrhythmogenic effects.
Hypochlorous acid-promoted loss of metabolic energy in Escherichia coli

Oxidation of Escherichia coli by hypochlorous acid (HOCl) or chloramine (NH2Cl) gives rise to massive hydrolysis of cytosolic nucleotide phosphoanhydride bonds, although no immediate change occurs in either the nucleotide pool size or the concentrations of extracellular end products of AMP catabolism. Titrimetric curves of the extent of hydrolysis coincide with curves for loss of cell viability, e.g., reduction in the adenylate energy charge from 0.8 to 0.1-0.2 accompanies loss of 99% of the bacterial CFU. The oxidative damage caused by HOCl is irreversible within 100 ms of exposure of the organism, although nucleotide phosphate bond hydrolysis requires several minutes to reach completion. Neither HOCl nor NH2Cl reacts directly with nucleotides to hydrolyze phosphoanhydride bonds. Loss of viability is also accompanied by inhibition of induction of beta-galactosidase. The proton motive force, determined from the distribution of 14C-radiolabeled lipophilic ions, declines with incremental addition of HOCl after loss of respiratory function; severalfold more oxidant is required for the dissipation of the proton motive force than for loss of viability. These observations establish a causal link between loss of metabolic energy and cellular death and indicate that the mechanisms of oxidant-induced nucleotide phosphate bond hydrolysis are indirect and that they probably involve damage to the energy-transducing and transport proteins located in the bacterial plasma membrane.
Application of voltage- and current-controlled voltage source inverters for distributed generation systems

Voltage source inverters (VSI) have been widely used in uninterruptible power supplies, unified power flow controllers or unified power quality conditioners, and distributed generation systems (DGS). VSIs are inherently efficient, compact, and economical devices used to control power flow and provide quality supply. VSIs can be classified as voltage-controlled VSIs (VCVSIs) and current-controlled VSIs (CCVSIs), depending on their control mechanism. In this paper, a detailed comparison of VCVSIs and CCVSIs for DGS applications is presented. This paper examines the advantages and limitations of each control technique in a single-phase DGS, without incorporating additional hardware and/or extra complex control techniques. Discussions on the concepts, hypotheses, and computer simulations of different VSIs in the presence of different loads and conditions are presented. The experimental results confirm the validity of the analysis and simulations outlined. The paper provides design recommendations for the use of VCVSIs and CCVSIs in various applications
An introduction to genetic algorithms

From the Publisher: "This is the best general book on Genetic Algorithms written to date. It covers background, history, and motivation; it selects important, informative examples of applications and discusses the use of Genetic Algorithms in scientific models; and it gives a good account of the status of the theory of Genetic Algorithms. Best of all the book presents its material in clear, straightforward, felicitous prose, accessible to anyone with a college-level scientific background. If you want a broad, solid understanding of Genetic Algorithms -- where they came from, what's being done with them, and where they are going -- this is the book. -- John H. Holland, Professor, Computer Science and Engineering, and Professor of Psychology, The University of Michigan; External Professor, the Santa Fe Institute. Genetic algorithms have been used in science and engineering as adaptive algorithms for solving practical problems and as computational models of natural evolutionary systems. This brief, accessible introduction describes some of the most interesting research in the field and also enables readers to implement and experiment with genetic algorithms on their own. It focuses in depth on a small set of important and interesting topics -- particularly in machine learning, scientific modeling, and artificial life -- and reviews a broad span of research, including the work of Mitchell and her colleagues. The descriptions of applications and modeling projects stretch beyond the strict boundaries of computer science to include dynamical systems theory, game theory, molecular biology, ecology, evolutionary biology, and population genetics, underscoring the exciting "general purpose" nature of genetic algorithms as search methods that can be employed across disciplines. An Introduction to Genetic Algorithms is accessible to students and researchers in any scientific discipline. It includes many thought and computer exercises that build on and reinforce the reader's understanding of the text. The first chapter introduces genetic algorithms and their terminology and describes two provocative applications in detail. The second and third chapters look at the use of genetic algorithms in machine learning (computer programs, data analysis and prediction, neural networks) and in scientific models (interactions among learning, evolution, and culture; sexual selection; ecosystems; evolutionary activity). Several approaches to the theory of genetic algorithms are discussed in depth in the fourth chapter. The fifth chapter takes up implementation, and the last chapter poses some currently unanswered questions and surveys prospects for the future of evolutionary computation.