Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of tumorigenesis by a cytosine-DNA, methyltransferase, antisense oligodeoxynucleotide.

This paper tests the hypothesis that cytosine DNA methyltransferase (DNA MeTase) is a candidate target for anticancer therapy. Several observations have suggested recently that hyperactivation of DNA MeTase plays a critical role in initiation and progression of cancer and that its up-regulation is a component of the Ras oncogenic signaling pathway. We show that a phosphorothioate-modified, antisense oligodeoxynucleotide directed against the DNA MeTase mRNA reduces the level of DNA MeTase mRNA, inhibits DNA MeTase activity, and inhibits anchorage independent growth of Y1 adrenocortical carcinoma cells ex vivo in a dose-dependent manner. Injection of DNA MeTase antisense oligodeoxynucleotides i.p. inhibits the growth of Y1 tumors in syngeneic LAF1 mice, reduces the level of DNA MeTase, and induces demethylation of the adrenocortical-specific gene C21 and its expression in tumors in vivo. These results support the hypothesis that an increase in DNA MeTase activity is critical for tumorigenesis and is reversible by pharmacological inhibition of DNA MeTase.
Stimulation of L‐type Ca2+ channel in growth cones activates two independent signaling pathways

Although growth cones respond to various modulators of neurite outgrowth, such as neurotrophins, neurotransmitters, and cell adhesion molecules, the signal‐transducing mechanisms for these modulators in growth cones are unclear. Since recent studies have suggested that the signals of these modulators are mediated by Ca2+ influx through L‐type voltage‐sensitive Ca2+ channels (VSCCs) in the growth cone, we examined L‐type VSCC‐dependent signaling pathways, using isolated growth cones (IGCs) from developing rat forebrains. Binding assays revealed that L‐type VSCC is enriched in growth cone membrane and gradually decreased in amount developmentally, while N‐type VSCC has the opposite tendency. In intact IGCs, Bay K 8644 (BK, an L‐type agonist) induced much more rapid elevation of [Ca2+]i than that in adult synaptosomes. Ca2+‐dependent phosphorylation of GAP‐43 and MARCKS protein by protein kinase C (PKC) was enhanced in the IGC by BK, resulting in the release of these proteins from the membrane, which is consistent with our recent report. In addition, the Ca2+‐dependent degradation of brain spectrin (fodrin) by calpain was also enhanced by BK or GABA, consequently inducing the release of α‐actinin from the membrane skeleton of the growth cones. The activities of PKC and calpain were not inhibited by inhibitors of the other, indicating that these reactions occur independently. Our results suggest that Ca2+ influx through L‐type VSCCs activates two distinct signaling branches, probably in the different domains of the growth cone, i.e., Ca2+‐dependent phosphorylation of GAP‐43 and MARCKS protein, and Ca2+‐dependent degradation of brain spectrin and the release of α‐actinin by calpain. J. Neurosci. Res. 51:682–696, 1998. © 1998 Wiley‐Liss, Inc.
Stock returns, velocity dynamics and inflation volatility

ABSTRACT Our model relates the variability of stock returns to the variability of consumption velocity and shows that real stock returns tend to co-vary negatively with expected inflation in a period (or regime) of low and stable inflation and to co-vary positively with expected inflation in a period (or regime) of high and volatile inflation. Long-run real stock returns are shown to be positively related to expected inflation. Our empirical results for 20 countries provide consistent support for our propositions, indicating that the standard deviation of the annual inflation rate roughly equal to 10% is the dividing line between negative and positive return-inflation relations.
Retention of the Human Rad9 Checkpoint Complex in Extraction-resistant Nuclear Complexes after DNA Damage*

Studies in yeasts and mammals have identified many genes important for DNA damage-induced checkpoint activation, including Rad9, Hus1, and Rad1; however, the functions of these gene products are unknown. In this study we show by immunolocalization that human Rad9 (hRad9) is localized exclusively in the nucleus. However, hRad9 was readily released from the nucleus into the soluble extract upon biochemical fractionation of un-irradiated cells. In contrast, DNA damage promptly converted hRad9 to an extraction-resistant form that was retained at discrete sites within the nucleus. Conversion of hRad9 to the extraction-resistant nuclear form occurred in response to diverse DNA-damaging agents and the replication inhibitor hydroxyurea but not other cytotoxic stimuli. Additionally, extraction-resistant hRad9 interacted with its binding partners, hHus1 and an inducibly phosphorylated form of hRad1. Thus, these studies demonstrate that hRad9 is a nuclear protein that becomes more firmly anchored to nuclear components after DNA damage, consistent with a proximal function in DNA damage-activated checkpoint signaling pathways.
A case-matching study of the analgesic properties of electroconvulsive therapy.

OBJECTIVE Chronic pain improves with electroconvulsive therapy (ECT), yet few case reports account for treatment of comorbid major depression, a significant confounder of the analgesia of ECT. This study reports on the analgesia of ECT, controlling for treatment of depression. METHODS This is a case-matching study comparing outcomes of inpatients with chronic pain and major depression in a multidisciplinary pain treatment unit treated with ECT and medications (cases) with those of inpatients treated with medications only (controls). Both groups received the same behavioral and pharmacological treatments for depression and chronic pain. Outcome measures included 0-10 pain rating scales and the Montgomery-Asberg Depression Inventory. Patients were matched on sex, age within 5 years, admission date within 6 months, psychiatric diagnoses, and, as much as possible, on race and pain syndrome diagnosis. Percentage changes in depression scores and pain scores were calculated from the beginning to the end of admission. RESULTS There were nonsignificant differences in demographics, except in the proportion married. Twenty-five of 28 ECT patients were matched. Depression improvements were similar between cases and controls (55.9% vs 40.5%). Despite higher initial pain (8.1 vs 6.9 on a 10-point scale), the ECT group had less final pain (3.4 vs 5.5). The ECT group had a 59.8% drop in pain versus a 15.8% drop in the control group, P > 0.01. CONCLUSIONS ECT has analgesic properties independent of its improvement of depression in patients with chronic pain and major depression. Improvements in depression were similar, while there was a significantly greater improvement in pain with ECT. The lower post-ECT treatment pain scores suggest a specific analgesic effect of ECT.
Adaptive reconfigurable voting for enhanced reliability in medium-grained fault tolerant architectures

The impact of SRAM-based FPGAs is constantly growing in aerospace industry despite the fact that their volatile configuration memory is highly susceptible to radiation effects. Therefore, strong fault-handling mechanisms have to be developed in order to protect the design and make it capable of fighting against both soft and permanent errors. In this paper, a fully reconfigurable medium-grained triple modular redundancy (TMR) architecture which forms part of a runtime adaptive on-board processor (OBP) is presented. Fault mitigation is extended to the voting mechanism by applying our reconfiguration methodology not only to domain replicas but also to the voter itself. The proposed approach takes advantage of adaptive configuration placement and modular property of the OBP, thus allowing on-line creation of different medium-grained TMRs and selection of their granularity level. Consequently, we are able to narrow down the fault-affected area thus making the error recovery process faster and less power consuming. The conventional hardware based voting is supported by the ICAP-based one in order to additionally strengthen the reconfigurable intermediate voting. In addition, the implementation methodology ensures using only one memory footprint for all voters and their voting adaptations thus saving storing resources in expensive rad-hard memories.
Word Spotting in Historical Document Collections with Online-Handwritten Queries

Pen-based systems are becoming more and more important due to the growing availability of touch sensitive devices in various forms and sizes. Their interfaces offer the possibility to directly interact with a system by natural handwriting. In contrast to other input modalities it is not required to switch to special modes, like software-keyboards. In this paper we propose a new method for querying digital archives of historical documents. Word images are retrieved with respect to search terms that users write on a pen-based system by hand. The captured trajectory is used as a query which we call query-by-online-trajectory word spotting. By using attribute embeddings for both online-trajectory and visual features, word images are retrieved based on their distance to the query in a common subspace. The system is therefore robust, as no explicit transcription for queries or word images is required. We evaluate our approach for writer-dependent as well as writer-independent scenarios, where we present highly accurate retrieval results in the former and compelling retrieval results in the latter case. Our performance is very competitive in comparison to related methods from the literature.
Association between the 5q31.1 gene neurogenin1 and schizophrenia

Multiple lines of evidence suggest that schizophrenia results from aberrant neurodevelopment. The neurogenin1 gene (neurog1) consists of a single 1,666 bp exon that encodes a basic helix‐loop‐helix (bHLH) transcription factor that causes neuronal differentiation and induces cortical and glutamatergic differentiation programs. Because of its function and its location in 5q31.1, which has been linked to schizophrenia in multiple samples, we tested it for association with the disorder. We sequenced neurog1 in 25 affected subjects from the Irish Study of High‐Density Schizophrenia Families. We observed a 5′‐UTR SNP at position −60, already present in databases as rs8192558, and tested it along with rs2344485, rs8192559, and rs2344484. Narrow, intermediate, and broad diagnostic definitions were used. The major alleles of rs8192558 and rs2344484 were over‐transmitted to affected subjects using both Pedigree Disequilibrium Test (PDT) (0.01 ≤ P ≤ 0.06) and FBAT (0.02 ≤ P ≤ 0.07). A haplotype consisting of the major alleles of all four SNPs was significantly over‐transmitted in FBAT to the broad definition (P = 0.049), with trend significance to the narrow and intermediate definitions, and with trend significance in PDT. In confirmatory tests using 657 cases and 411 controls, this haplotype was slightly but not significantly over‐represented in cases (81% vs. 77%, P = 0.21). These results, along with a priori evidence for the involvement of neurog1 in neurodevelopment, suggest that variants in neurog1 might have a small effect on susceptibility to schizophrenia. This gene should be tested in additional and larger samples. © 2006 Wiley‐Liss, Inc.
Micro-invasive glaucoma surgery: current perspectives and future directions

Purpose of review There is an increasing interest and availability of micro-invasive glaucoma surgery (MIGS) procedures. It is important that this increase is supported by sound, peer-reviewed evidence. This article will define MIGS, review relevant publications in the period of annual review and discuss future directions. Recent findings The results of the pivotal trial comparing a trabecular micro-bypass stent (iStent, Glaukos Corporation, Laguna Hills, CA, USA) combined with phacoemulsification to phacoemulsification alone showed a significantly higher percentage of patients with unmedicated intraocular pressure (IOP) ⩽ 21 mmHg, and a comparable safety profile. Initial results are published regarding a second-generation micro-bypass stent (iStent inject, Glaukos Corporation, Laguna Hills, CA, USA), a canalicular scaffold (Hydrus, Ivantis Inc., Irvine, CA, USA) and an ab interno suprachoroidal microstent (CyPass, Transcend Medical, Menlo Park, CA, USA), showing a decrease in mean postoperative IOP. Phaco-Trabectome (Ab interno trabeculectomy Trabectome, NeoMedix Inc., Tustin, CA, USA) was compared to phacotrabeculectomy and showed less IOP reduction, less postoperative complications, and a similar success rate. Similar success rates were found with the comparison of excimer laser trabeculostomy (ELT, AIDA, Glautec AG, Nurnberg, Germany) and selective laser trabeculoplasty. A number of publications review the importance of the location of implantable devices, intraoperative gonioscopy, cost–effectiveness and quality-of-life studies, and randomized clinical trials. Summary MIGS procedures offer reduction in IOP, decrease in dependence on glaucoma medications and an excellent safety profile. Their role within our glaucoma treatment algorithm continues to be clarified and differs from the role of more invasive glaucoma surgeries such as trabeculectomy or glaucoma drainage devices.
Automatic measurement based on stereo vision system using a single PTZ camera

A parallel binocular stereo vision system and its application to dimensional measurement is introduced in this paper. The proposed system is established by controlling a single PTZ (pan-tilt-zoom) camera linear motion on a one dimensional precision displacement platform. To achieve accurate measurement results, an improved matching algorithm called as DC-SURF (Distortion Compensated-Speeded Up Robust Feature) by using adaptative filtering in terms of the image distortion during generating scale space is presented. Furthermore, the classic eight-point algorithm and the designed zoom strategy for PTZ camera are adopted for the measurement. The experimental results show that the proposed matching algorithm has better performance than other two classic matching algorithms over distorted images. Furthermore, the experiments demonstrate that without any reference materials the stereo vision dimensional measurement system proposed in this paper can be successfully applied to human height measurement with high precision. The results indicate a potential possibility of our approach to be used in other computer vision applications.
Use of Cutometer to assess epidermal hydration

Background/aims: The Cutometer equipped with a 2‐mm diameter suction probe is a device suitable for assessment of epidermal mechanics. The objectives of this study were to determine the sensitivity of Cutometer parameters to epidermal hydration, to evaluate the correlation between skin mechanical parameters and skin capacitance, and to study the role of pretension of the skin.
Free and integrated recombinant murine leukemia virus DNAs appear in preleukemic thymuses of AKR/J mice

We studied the appearance and structure of murine leukemia viral genomes in preleukemic AKR/J mice by Southern hybridization. Up to an average of one to two copies per thymocyte of unintegrated murine leukemia virus DNA appears in the thymuses of preleukemic mice beginning at 4 to 5 months of age and disappears in leukemic thymuses. The free viral genomes are absent in the spleens, livers, and brains of preleukemic mice. Using a series of ecotropic and nonecotropic murine leukemia virus hybridization probes, we showed that the unintegrated viral genomes are structurally analogous to those of recombinant mink cell focus-forming viruses that appear as proviruses in leukemic AKR thymocytes, suggesting that these free viral DNAs are the direct precursors to the leukemia-specific proviruses. The mosaic of ecotropic and nonecotropic sequences within these unintegrated viral DNAs varies from one preleukemic thymus to another but often appears structurally homogeneous within individual thymuses, indicating that often each thymus was being infected by a unique mink cell focus-forming virus. Analysis of high-molecular-weight DNA shows that recombinant proviruses reside in the chromosomal DNA of thymocytes within the preleukemic thymus, with the number rising to an average of several copies per thymocyte, but we do not detect any preferred integration sites. These results suggest that, in general, before the development of thymic leukemias in AKR mice there is a massive infection by a unique mink cell focus-forming virus which then integrates into many different sites of individual thymocytes, one of which grows out to become a tumor.
Micro-Raman study of the role of sterilization on carbon nanotubes for biomedical applications.

AIM We investigate the effect of four different types of sterilization procedures on the structural properties and morphological features of single-wall carbon nanotube samples approachable by micro-Raman spectroscopy. Sterilization procedures (treatment in humid heat autoclave or ethylene oxide and irradiation with gamma-rays or UV light) are necessary in view of the use of carbon nanotube sterile samples in in vivo toxicity tests on laboratory rats. Micro-Raman spectroscopy allows us to estimate several details about the morphology of the single-wall carbon nanotube mixture (mainly the presence of disorder and diameter distribution) before and after the sterilization treatment. RESULTS The best of these treatments, in other words, the one that least affected the morphology and structural properties of carbon nanotubes, was found to be UV irradiation and has thus been selected for future in vivo tests on rats.
Tunnel FETs for Ultra-Low Voltage Digital VLSI Circuits: Part II–Evaluation at Circuit Level and Design Perspectives

In Part II of this paper, the potential of tunnel FETs (TFETs) for ultra-low voltage (ULV)/ultra-low power (ULP) operation at 32-nm node is investigated through Verilog-A simulations of appropriate reference circuits. Critical issues arising at ultra-low voltages are analyzed, including static robustness of TFET logic gates, performance degradation, and sensitivity to process variations. Guidelines to design ultra-low energy standard cell libraries are derived. The minimum energy point is analyzed in a wide range of conditions, and guidelines for microarchitectural optimization for ultra-low energy are introduced. Voltage scalability of static RAM memories is also analyzed as main limitation to aggressive voltage scaling of very large scale integration (VLSI) systems, and improved precharge schemes are introduced to reduce leakage. The impact of variations of the main device parameters on VLSI digital circuits is investigated to identify the most critical variations that need to be controlled at process level. This investigation permits to understand the potential of TFETs and their advantages over traditional devices within a unitary framework that is based on fair design and comparison from device to circuit level, as well as to develop clear design perspectives in the context of ULV/ULP VLSI digital circuits.
Effect of corporate social responsibility on Jordan pharmaceutical industry’s business performance

Purpose The purpose of this study is to investigate the effect of implementing corporate social responsibility (CSR) initiatives (social responsibility, economic responsibility and environmental responsibility) on Jordanian Pharmaceutical Manufacturing (JPM) industry’s business performance. Design/methodology/approach This study follows a quantitative descriptive design. The data were collected from 116 managers working at seven JPM organizations by questionnaire. After confirming validity and reliability of the tool, the statistical analysis means, standard deviations and t-values were used to test implementation and finally multiple regressions were used to test the hypothesis. Findings Results show that there are relationships between CSR variables, and all the three variables are strongly related to business performance. The results also indicate that the three sub-variables together affect JPM industry’s business performance. The environmental responsibility has the highest effect on JPM industry’s business performance, followed by the economic responsibility, and then the social responsibility. Research limitations/implications This study was directed toward pharmaceutical industry in Jordan. Generalizing the results to other industries and countries is questionable. Therefore, further research on other industries and countries will help mitigate the issue of generalizing conclusions. Practical implications CSR should be formulated clearly within JPM corporate strategy. The elements of CSR need to be integrated with the present performance management criteria, leadership development programs and organizational development programs, and a champion for CSR needs to be assigned. Social implications The CSR initiatives should be derived from local culture and match with international initiatives because CSR is the responsibility of every person. Originality/value Still the topic of CSR is not well implemented and does not have priority by Jordanian companies; therefore, this study may be considered as one of the few studies dedicated to study this topic and create awareness about it in Jordan.
Mitochondrial Potassium Channels as Pharmacological Target for Cardioprotective Drugs

Brief periods of ischemia are known to confer to the myocardium an increased resistance to the injury due to a later and more prolonged ischemic episode. This phenomenon, known as ischemic preconditioning (IPreC), is ensured by different biological mechanisms. Although an exhaustive comprehension of them has not been reached yet, it is widely accepted that mitochondria are pivotally involved in controlling cell life and death, and thus in IPreC. Among the several signaling pathways involved, as triggers and/or end effectors, in the mitochondrial mechanisms of cardioprotection, an important role is played by the activation of potassium channels located in the mitochondrial inner membrane (mitoK) of cardiomyocytes. Presently, different types of mitoK channels have been recognized in the heart, such as ATP‐sensitive (mitoKATP) and calcium‐activated (mitoBKCa and mitoSKCa) potassium channels. Consistently, drugs modulating mitoK, on one hand, have been employed as useful experimental tools for early basic studies on IPreC. On the other hand, activators of mitoK are promising and innovative therapeutic agents for limiting the myocardial injury due to ischemic episodes. In this review, we report the experimental evidence supporting the role of mitoK in signaling pathways in the mechanisms of cardioprotection and an overview on the most important molecules acting as modulators of these channels, with their profiles of selectivity. Some innovative pharmaceutical strategies for mitochondriotropic drugs have been also reported. Finally, an appendix describing the main experimental approaches usually employed to study mitoK in isolated mitochondria or in intact cells has been added.