Miracle-dz/UniFAR-FTUs huggingface dataset:
Mitochondrial p53 phosphorylation induces Bak-mediated and caspase-independent cell death

Chemoresistance in cancer has previously been attributed to gene mutations or deficiency. Caspase mutations or Bax deficiency can lead to resistance to cancer drugs. We recently demonstrated that Bak initiates a caspase/Bax-independent cell death pathway. We show that Plumbagin (PL) (5-hydroxy-2-methyl-1,4-napthoquinone), a medicinal plant-derived naphthoquinone that is known to have anti-tumor activity in a variety of models, induces caspase-independent cell death in HCT116 Bax knockout (KO) or MCF-7 Bax knockdown (KD) cells that express wild-type (WT) Bak. The re-expression of Bax in HCT116 Bax KO cells fails to enhance the PL-induced cell death. Additionally, Bak knockdown by shRNA efficiently attenuates PL-induced cell death. These results suggest that PL-induced cell death depends primarily on Bak, not Bax, in these cells. Further experimentation demonstrated that p53 Ser15 phosphorylation and mitochondrial translocation mediated Bak activation and subsequent cell death. Knockdown of p53 or a p53 Ser15 mutant significantly inhibited p53 mitochondrial translocation and cell death. Furthermore, we found that Akt mediated p53 phosphorylation and the subsequent mitochondrial accumulation. Taken together, our data elaborate the role of Bak in caspase/Bax-independent cell death and suggest that PL may be an effective agent for overcoming chemoresistance in cancer cells with dysfunctional caspases.
Inhibition of Dopamine Release Via Presynaptic D2 Receptors: Time Course and Functional Characteristics In Vivo

Most neurotransmitters inhibit their own release through autoreceptors. However, the physiological functions of these presynaptic inhibitions are still poorly understood, in part because their time course and functional characteristics have not been described in vivo. Dopamine inhibits its own release through D2 autoreceptors. Here, the part played by autoinhibition in the relationship between impulse flow and dopamine release was studiedin vivo in real time. Dopamine release was evoked in the striatum of anesthetized mice by electrical stimulation of the medial forebrain bundle and was continuously monitored by amperometry using carbon fiber electrodes. Control experiments performed in mice lacking D2 receptors showed no autoinhibition of dopamine release. In wild-type mice, stimulation at 100 Hz with two to six pulses linearly inhibited further release, whereas single pulses were inefficient. Dopaminergic neurons exhibit two discharge patterns: single spikes forming a tonic activity below 4 Hz and bursts of two to six action potentials at 15 Hz. Stimulation mimicking one burst (four pulses at 15 Hz) promoted extracellular dopamine accumulation and thus inhibited further dopamine release. This autoinhibition was maximal between 150 and 300 msec after stimulation and disappeared within 600 msec. This delayed and prolonged time course is not reflected in extracellular DA availability and thus probably attributable to mechanisms downstream from autoreceptor stimulation. Thus, in physiological conditions, autoinhibition has two important roles. First, it contributes to the attenuation of extracellular dopamine during bursts. Second, autoinhibition elicited by one burst transiently attenuates further dopamine release elicited by tonic activity.
The Presumed-Either Two-Phase Commit Protocol

This paper describes the presumed-either two-phase commit protocol. Presumed-either exploits log piggybacking to reduce the cost of committing transactions. If timely piggybacking occurs, presumed-either combines the performance advantages of presumed-abort and presumed-commit. Otherwise, presumed-either behaves much like the widely-used presumed-abort protocol.
Local Hoare reasoning about DOM

The W3C Document Object Model (DOM) specifies an XML update library. DOM is written in English, and is therefore not compositional and not complete. We provide a first step towards a compositional specification of DOM. Unlike DOM, we are able to work with a minimal set of commands and obtain a complete reasoning for straight-line code. Our work transfers O'Hearn, Reynolds and Yang's local Hoare reasoning for analysing heaps to XML, viewing XML as an in-place memory store as does DOM. In particular, we apply recent work by Calcagno, Gardner and Zarfaty on local Hoare reasoning about simple tree update to this real-world DOM application. Our reasoning not only formally specifies a significant subset of DOM Core Level 1, but can also be used to verify, for example, invariant properties of simple Javascript programs.
Design and implementation of sparse global analyses for C-like languages

In this article we present a general method for achieving global static analyzers that are precise, sound, yet also scalable. Our method generalizes the sparse analysis techniques on top of the abstract interpretation framework to support relational as well as non-relational semantics properties for C-like languages. We first use the abstract interpretation framework to have a global static analyzer whose scalability is unattended. Upon this underlying sound static analyzer, we add our generalized sparse analysis techniques to improve its scalability while preserving the precision of the underlying analysis. Our framework determines what to prove to guarantee that the resulting sparse version should preserve the precision of the underlying analyzer. We formally present our framework; we present that existing sparse analyses are all restricted instances of our framework; we show more semantically elaborate design examples of sparse non-relational and relational static analyses; we present their implemen- tation results that scale to analyze up to one million lines of C programs. We also show a set of implementation techniques that turn out to be critical to economically support the sparse analysis process.
THE SURVEY OF AN EFFICIENT SEARCH SCHEME OVER ENCRYPTED DATA ON MOBILE CLOUD TEES

Cloud storage provides a convenient and more storage at low cost, but data security is a main concept that prevents users from storing documents on the cloud. One of the methods for improving security from the data owner point of view is to encrypt the document before outsourcing them onto the cloud and decrypt the documents after downloading them. In this paper there is some limitation as follows,(1)data encryption is a heavy overhead for the mobile devices, and(2) data recovery process incurs a difficult communication between the data user and cloud. (3)Typically with limited bandwidth capacity and limited battery life, these issues, established heavy overhead to computing and communication with mobile device users in which makes very difficult for encrypted search over mobile cloud. Now, we have proposed TEES (Traffic and Energy saving Encrypted Search), in which with more bandwidth and better energy efficient encrypted search architecture over mobile cloud.
Gendered Occupational Outcomes : the Case of Professional Training and Work in Turkey

This chapter examines gendered occupational outcomes in the field of professional training and work in Turkey. The results of three empirical studies (the case of engineering students, the case of professorial workers and the case of banking sector employees) inform the discussion in this chapter. In line with our critical realist perspective, we utilise historical and institutional data sources in order to supplement the data from the three studies to present a multi-layered and relational account of the gendered outcomes of professional employment and education situating the phenomenon at macro socio-historical, meso organisational and micro individual levels. We conclude that Turkey presents a complex and paradoxical example for the study of gender and occupations with high levels of female representation in professional work, in contrast to persistent gendered prejudices upholding a male-centred organisation of work-life.
The evaluation of potentiostats: electrochemical detection devices

This study evaluated the performance of three types of potentiostats; EmStat, CheapStat and UTMStat. EmStat is the smallest potentiostat available in the market. CheapStat is an open-source potentiostat suitable for educational applications. In addition, UTMStat is the extension of CheapStat, which was designed to overcome few weaknesses of CheapStat such as the input controller/ switch and data storage handling of the cyclic voltammogram. The cyclic voltammetry and amperometry measurements of ions ferrocyanide ([Fe(CN)6]4−) and chloride (Cl-) were carried out for each potentiostat. EmStat potentiostat is not only able to detect but also to measure ferrocyanide and chloride ions. However, CheapStat and UTMStat are only able to detect and measure ferrocyanide ions. The experiment is unable to be conducted due to limitation of waveform selection on both devices. Nevertheless, CheapStat and UTMStat could provide a reliable measurement to realize miniaturized lab-on-chip applications as shown in this study.
Content determination of the flavonoids in the different parts and different species of Abelmoschus esculentus L. by reversed phase-high performance liquid chromatograph and colorimetric method

Background: This research will establish the ultraviolet colorimetric method to determine the total flavonoid content in different species and different parts of Abelmoschus esculentus L. Materials and Methods: We establish the reversed-phase high-performance liquid chromatograph (RP-HPLC) method to determine the content of the three flavonoid glycosides in different species and different parts of the A. esculentus. Adopt the NaNO2-Al (NO3)3-NaOH colorimetric method to determine the total flavonoid content; at the same time, adopt the RP-HPLC method to determine the contents of the three flavonoid glycosides. Using the methods of ultraviolet colorimetry and RP-HPLC, we determined and analyzed the total flavonoid content and the content of the three flavonoid glycosides in different species and different parts of A. esculentus. Results: There are great distribution differences of the total flavonoids and the three flavonoid glycosides in different species and parts of A. esculentus. Among them, the content of the effective constituents in the flower is relatively high, next is in the fruit. In the different species of A. esculentus, the content of the flavonoids of finger relatively high. The HPLC method established in this research is simple and convenient and its results are accurate and reliable. In addition, it has a very good repeatability. Conclusion: The results provided the reference data for the medicinal use of A. esculentus and it can be used in quality analyzing of its effective constituents.
Crystal structures of a template‐independent DNA polymerase: murine terminal deoxynucleotidyltransferase

The crystal structure of the catalytic core of murine terminal deoxynucleotidyltransferase (TdT) at 2.35 Å resolution reveals a typical DNA polymerase β‐like fold locked in a closed form. In addition, the structures of two different binary complexes, one with an oligonucleotide primer and the other with an incoming ddATP‐Co2+ complex, show that the substrates and the two divalent ions in the catalytic site are positioned in TdT in a manner similar to that described for the human DNA polymerase β ternary complex, suggesting a common two metal ions mechanism of nucleotidyl transfer in these two proteins. The inability of TdT to accommodate a template strand can be explained by steric hindrance at the catalytic site caused by a long lariat‐like loop, which is absent in DNA polymerase β. However, displacement of this discriminating loop would be sufficient to unmask a number of evolutionarily conserved residues, which could then interact with a template DNA strand. The present structure can be used to model the recently discovered human polymerase μ, with which it shares 43% sequence identity.
Analysis of image stitching error based on scale invariant feature transform and random sample consensus

This article introduced the process of image stitching based on SIFT and RANSAC. It was pointed out that the reliability calculation of the RANSAC algorithm is based on an idealized assumption which does not hold. The false assumption will lead to the instability of image stitching results, especially in multi-map or panorama situations. To solve the problem, this paper presents a strategy to limit the range of randomly points selecting. Experiments show that the strategy can effectively reduce the effect caused by random errors, and obtain more stable image stitching result.
Interventions for acute non-arteritic central retinal artery occlusion.

BACKGROUND Acute central retinal artery occlusion (CRAO) occurs as a sudden interruption of the blood supply to the retina and results in an almost complete loss of vision in the affected eye. There is no generally agreed treatment regimen although a number of therapeutic interventions have been proposed. OBJECTIVES The objective of this review was to examine the effects of treatments used for acute non-arteritic CRAO. SEARCH STRATEGY We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library, Issue 3, 2008), MEDLINE (January 1966 to September 2008), EMBASE (January 1980 to September 2008) and the reference lists of relevant papers. SELECTION CRITERIA We included randomised controlled trials (RCTs) only in which one treatment aimed to re-establish blood supply to the retina in people with acute CRAO was compared to another treatment. DATA COLLECTION AND ANALYSIS Two authors independently assessed the search results for relevant trials. Discrepancies were resolved by discussion. MAIN RESULTS We found two RCTs that met our inclusion criteria. AUTHORS' CONCLUSIONS The included studies in this review were small and from single centres. Neither study was completely clear about it's method of treatment allocation. One study described the use of pentoxifylline tablets (three 600 mg tablets daily) and the other the use of enhanced external counterpulsation (EECP) combined with haemodilution. Both studies indicated improved retinal perfusion in the non-control group but neither showed an improvement in vision. Large, well-designed RCTs are still required to establish the most effective treatment for acute CRAO. These studies should be looking at factors important to the patient i.e. improved vision with acceptable risk/side-effects.
Melatonin blunts the mitochondrial/NLRP3 connection and protects against radiation‐induced oral mucositis

Mucositis is a common and distressing side effect of chemotherapy or radiotherapy that has potentially severe consequences, and no treatment is available. The purpose of this study was to analyze the molecular pathways involved in the development of oral mucositis and to evaluate whether melatonin can prevent this pathology. The tongue of male Wistar rats was subjected to irradiation (X‐ray YXLON Y.Tu 320‐D03 irradiator; the animals received a dose of 7.5 Gy/day for 5 days). Rats were treated with 45 mg/day melatonin or vehicle for 21 days postirradiation, either by local application into their mouths (melatonin gel) or by subcutaneous injection. A connection between reactive oxygen species, generating mitochondria and the NLRP3 (NLR‐related protein 3 nucleotide‐binding domain leucine‐rich repeat containing receptor‐related protein 3) inflammasome, has been reported in mucositis. Here, we show that mitochondrial oxidative stress, bioenergetic impairment and subsequent NLRP3 inflammasome activation are involved in the development of oral mucositis after irradiation and that melatonin synthesized in the rat tongue is depleted after irradiation. The application of melatonin gel restores physiological melatonin levels in the tongue and prevents mucosal disruption and ulcer formation. Melatonin gel protects the mitochondria from radiation damage and blunts the NF‐κB/NLRP3 inflammasome signaling activation in the tongue. Our results suggest new molecular pathways involved in radiotherapy‐induced mucositis that are inhibited by topical melatonin application, suggesting a potential preventive therapy for mucositis in patients with cancer.
The use of AFLP to find an informative SNP: genetic differences across a migratory divide in willow warblers

We used the amplified fragment length polymorphism (AFLP) method to obtain genetic markers distinguishing two subspecies of willow warblers Phylloscopus trochilus that have different migratory behaviours but are not differentiated in mitochondrial DNA or at several microsatellite loci. With the inverse‐polymerase chain reaction (PCR) approach we converted a dominant AFLP‐marker to a codominant single nucleotide polymorphism (SNP). Across Scandinavia we typed 621 birds at the SNP locus AFLP‐WW1 and we found a sigmoid change in allele frequencies centred around 62 degrees latitude. North of the latitudinal cline was a west‐east cline. Both clines are narrower than one would expect from dispersal distances in willow warblers, which suggests that these are maintained by selection. The latitudinal cline at the locus AFLP‐WW1 is paralleled by changes in several other traits, all of which might be maintained by a single selective force. The most plausible selection factor that we have identified is selection against hybrids because of inferior migratory behaviour. The selective force maintaining the east–west cline is less obvious. We discuss alternatives to the selection scenario, involving colonization history and asymmetric gene flow.
Yarrowia lipolytica Lipase 2 Is Stable and Highly Active in Test Meals and Increases Fat Absorption in an Animal Model of Pancreatic Exocrine Insufficiency.

BACKGROUND & AIMS Pancreatic exocrine insufficiency (PEI) reduces pancreatic secretion of digestive enzymes, including lipases. Oral pancreatic enzyme replacement therapy (PERT) with pancreatin produces unsatisfactory results. The lipase 2 produced by the yeast Yarrowia lipolytica (YLLIP2; GenBank: AJ012632) might be used in PERT. We investigated its ability to digest triglycerides in a test meal and its efficacy in reducing fecal fat in an animal model of PEI. METHODS YLLIP2 was produced by genetically engineered Y lipolytica and purified from culture media. YLLIP2 or other gastric (LIPF) and pancreatic (PNLIPD) lipases were added to a meal paste containing dietary triglycerides, at a range of pH values (pH 2-7), with and without pepsin or human bile and incubated at 37°C. We collected samples at various time points and measured lipase activities and stabilities. To create an animal model of PEI, steatorrhea was induced by embolization of the exocrine pancreas gland and pancreatic duct ligation in minipigs. The animals were given YLLIP2 (1, 4, 8, 40, or 80 mg/d) or pancreatin (100,000 US Pharmacopeia lipase units/d, controls) for 9 days. We then collected stool samples, measured fat levels, and calculated coefficient of fat absorption (CFA) values. RESULTS YLLIP2 was highly stable and poorly degraded by pepsin, and had the highest activity of all lipases tested on meal triglyceride at pH 4-7 (pH 6 with bile: 94 ± 34 U/mg; pH 4 without bile: 43 ± 13 U/mg). Only gastric lipase was active and stable at pH 3, whereas YLLIP2 was sensitive to pepsin hydrolysis after pH inactivation. From in vitro test meal experiments, the lipase activity of YLLIP2 (10 mg) was estimated to be equivalent to that of pancreatin (1200 mg; 100,000 US Pharmacopeia units) at pH 6. In PEI minipigs, CFA values increased from 60.1% ± 9.3% before surgery to 90.5% ± 3.2% after administration of 1200 mg pancreatin (P < .05); CFA values increased to a range of 84.6% ± 3.0% to 90.0% ± 3.8% after administration of 4-80 mg YLLIP2 (P < .05). CONCLUSIONS The yeast lipase YLLIP2 is stable and has high levels of activity against test meal triglycerides in a large pH range, with and without bile. Oral administration of milligram amounts of YLLIP2 significantly increased CFA values, similar to that of 1.2 g pancreatin, in a minipig model of PEI.
Global Profiling of Proteolysis during Rupture of Plasmodium falciparum from the Host Erythrocyte*

The obligate intracellular parasite pathogen Plasmodium falciparum is the causative agent of malaria, a disease that results in nearly one million deaths per year. A key step in disease pathology in the human host is the parasite-mediated rupture of red blood cells, a process that requires extensive proteolysis of a number of host and parasite proteins. However, only a relatively small number of specific proteolytic processing events have been characterized. Here we describe the application of the Protein Topography and Migration Analysis Platform (PROTOMAP) (Dix, M. M., Simon, G. M., and Cravatt, B. F. (2008) Global mapping of the topography and magnitude of proteolytic events in apoptosis. Cell 134, 679–691; Simon, G. M. , Dix, M. M. , and Cravatt, B. F. (2009) Comparative assessment of large-scale proteomic studies of apoptotic proteolysis. ACS Chem. Biol. 4, 401–408) technology to globally profile proteolytic events occurring over the last 6–8 h of the intraerythrocytic cycle of P. falciparum. Using this method, we were able to generate peptographs for a large number of proteins at 6 h prior to rupture as well as at the point of rupture and in purified merozoites after exit from the host cell. These peptographs allowed assessment of proteolytic processing as well as changes in both protein localization and overall stage-specific expression of a large number of parasite proteins. Furthermore, by using a highly selective inhibitor of the cysteine protease dipeptidyl aminopeptidase 3 (DPAP3) that has been shown to be a key regulator of host cell rupture, we were able to identify specific substrates whose processing may be of particular importance to the process of host cell rupture. These results provide the first global map of the proteolytic processing events that take place as the human malarial parasite extracts itself from the host red blood cell. These data also provide insight into the biochemical events that take place during host cell rupture and are likely to be valuable for the study of proteases that could potentially be targeted for therapeutic gain.
Nuclear and Cytoplasmic Expression of ERβ1, ERβ2, and ERβ5 Identifies Distinct Prognostic Outcome for Breast Cancer Patients

Purpose: Previous conflicting results about the prognostic significance of estrogen receptor (ER)-β in breast cancer may be explained by contribution of isoforms, of which five exist. Our aim was to elucidate the prognostic significance of ERβ1, ERβ2, and ERβ5 by immunohistochemistry in a large cohort of breast carcinomas with long-term follow-up. Experimental Design: Tissue microarrays were stained with ERβ1, ERβ2, and ERβ5 antibodies and scored as percentage of positive tumor cells and using the Allred system. Nuclear and cytoplasmic staining was evaluated and correlated with histopathologic characteristics, overall survival (OS), and disease-free survival (DFS). Results: Nuclear ERβ2 and ERβ5, but not ERβ1, significantly correlated with OS (P = 0.006, P = 0.039, and P = 0.099, respectively), and ERβ2 additionally with DFS (P = 0.013). ERβ2 also predicted response to endocrine therapy (P = 0.036); correlated positively with ERα, progesterone receptor, androgen receptor, and BRCA1; and correlated inversely with metastasis and vascular invasion. Tumors coexpressing ERβ2 and ERα had better OS and DFS. Cytoplasmic ERβ2 expression, alone or combined with nuclear staining, predicted significantly worse OS. Notably, patients with only cytoplasmic ERβ2 expression had significantly worse outcome (P = 0.0014). Conclusions: This is the first study elucidating the prognostic role of ERβ1, ERβ2, and ERβ5 in a large breast cancer series. ERβ2 is a powerful prognostic indicator in breast cancer, but nuclear and cytoplasmic expression differentially affect outcome. Measuring these in clinical breast cancer could provide a more comprehensive picture of patient outcome, complementing ERα.