Miracle-dz/UniFAR-FTUs huggingface dataset:
Flip-flop is slow and rate limiting for the movement of long chain anthroyloxy fatty acids across lipid vesicles.

An issue that is central to understanding cellular fatty acid (FA) metabolism is whether physiologic transport of FA across cell membranes requires protein mediation or can be satisfied by the rate of spontaneous movement through the lipid phase. For this reason, considerable effort has been devoted to determining the rate-limiting steps for transport of FA across pure lipid bilayer membranes. Previously, we found that transbilayer flip-flop was the rate-limiting step for transport of long chain anthroyloxy FA (AOFA) across lipid bilayers and that the times for long chain AOFA flip-flop were > or = 100 s, yielding rate constants for flip-flop (k(ff)) that were < or = 0.01 s(-1) [Storch, J., & Kleinfeld, A. M. (1986) Biochemistry 25, 1717-1726; Kleinfeld, A. M. , & Storch, J. (1993) Biochemistry 32, 2053-2061]. In those studies, k(ff) values were inferred from the time course of AOFA transfer between lipid vesicles. Recently, Kamp et al. [Kamp, F. , Zakim, D. , Zhang, F. , Noy, N. , & Hamilton, J. A. (1995) Biochemistry 34, 11928-11937], using pyranine trapped within lipid vesicles to detect flip-flop more directly, have reported that flip-flop rates of long chain AOFA are extremely rapid (k(ff) > 10 s(-1)) and are not rate limiting for transbilayer transport. Because no defect was apparent in our previous measurements, we have extended, for AOFA, the pyranine method of Kamp et al. (1995) by using stopped-flow fluorometry to resolve flip-flop rates of both short and long chain AOFA in vesicles. In addition, we have monitored the time course of transbilayer AOFA flip-flop using carboxyfluorescein (CF) trapped within the lipid vesicles as a resonance energy transfer (RET) acceptor of AO fluorescence. The differential quenching of AOFA fluorescence in the outer and inner leaflets of the bilayer allows flip-flop to be separated from the time course of AOFA binding to the vesicles. Results obtained from both the pyranine and CF methods indicate, in agreement with our previous results, that flip-flop of the long chain AOFA is slow relative to either the binding or the rate of dissociation from the vesicle. In particular, we find that the time constant (tau) for pyranine quenching by 2-AO-palmitate (2-AOPA) was > 40 s and that k(ff) obtained from RET in CF vesicles was about 0.003 s(-1). Also, in contrast to Kamp et al. (1995) who reported that k(ff) values were independent of FA chain length or structure for the C-12 to C-18 native and the C-18 AOFA within a factor of 2, we find that the rate of pyranine quenching for the shorter chain 11-AO-undecanoic acid is more than 50-fold faster than for the longer chain AOFA. We conclude, therefore, that transbilayer transport of the AOFA is limited by the rate of flip-flop and that this rate is a sensitive function of the AOFA structure.
Multicapteurs de gaz pour la conception d'un nez électronique de surveillance de la pollution atmosphérique : application à la detection de NO2 et H2S dans une atmosphère humide chargée de CO2

Les systemes multicapteurs de gaz intelligents connaissent actuellement un developpement accru pour de nombreux domaines d'application. Inscrite dans le large domaine de la lutte contre la pollution atmospherique, notre etude a pour but principal la detection de deux gaz polluants antagonistes le sulfure d'hydrogene H2S, reducteur, et le dioxyde d'azote, NO2, oxydant. Apres avoir situe ce sujet dans le cadre de la pollution atmospherique, puis presente le principe des nez electroniques, nous justifions notre choix d'une matrice de capteurs a base d'oxyde metallique, et mettons en evidence les avantages et inconvenients de ces capteurs. L'inconvenient majeur est leur sensibilite croisee, qui peut devenir un avantage par l'utilisation de methodes de reconnaissance de formes. Les deux gaz sont etudies seuls ou en melange, successivement dans trois atmospheres, de plus en plus complexes. Les concentrations etudiees correspondent a une pollution industrielle pres d'une source emissive. De chaque reponse des capteurs obtenue lors de la procedure systematique de caracterisation, nous avons extrait trois variables representatives communes a toutes les mesures et une quatrieme correspondant a un "pic" negatif specifique de la reponse de tous les capteurs a H2S, non utilise dans l'analyse de donnees, car il n'apparait pas toujours dans les melanges. Nous avons construit une base de donnees d'apprentissage de notre systeme (environ 1000 mesures) etudiee a l'aide de l'analyse factorielle discriminante, methode multidimensionnelle supervisee. Nous obtenons identification et quantification des atmospheres gazeuses, en procedant par etapes qui tiennent compte notamment des atmospheres de references. Une identification rapide est obtenue avec deux variables representatives, valable pour la detection d'un seuil. Grâce aux regles de decision fiables obtenues, nous proposons une methode d'identification d'atmospheres inconnues directement exploitable par des utilisateurs
An energy efficient approach for corona based wireless sensor network

A wireless sensor network (WSN) is formed by self-governing sensor nodes to keep an eye on deployment surroundings and freely exchange their data to a base station. The WSNs operates under various constraints like energy, accuracy, coverage and connectivity etc. The objective of this paper is to propose an approach which efficiently utilizes the energy in coronas based WSN. The proposed approach is combination of three different phases and these are termed as node distribution, coalition and network data reconstruction. The node distribution phase deploys the sensor nodes non-uniformly across the network to avoid the formation of energy holes. In next phase, a voting process is proposed to elect a coalition representative (CR) within individual coronas. The vote function which is used to cast a vote is derived from residual energy and spatial correlation factor among the nodes. Further, each CR forms a coalition and the CR transmits their self sensed data to the sink on behalf of a coalition. The CR communicates its data to the sink using a multi-hop routing. Coalitions are used in this work to reduce the number of transmissions in the network which prolongs the network operation. Finally, a matrix completion based strategy is used at the sink to reconstruct the data of the entire network. The simulation results for the proposed approach confirms that energy efficient WSN is achieved when compared with existing approaches.
Mouse strain‐specific patterns of mammary epithelial ductal side branching are elicited by stromal factors

Variations in mammary ductal side branching patterns are known to occur between different strains of mice and this is related to the rate of spontaneous mammary cancers, which are increased in those strains which show highly side‐branched mammary architecture. The cause of the variation in ductal side branching between mouse strains is unknown, but epithelial, stromal, and endocrine factors have been implicated. To define the mammary elements responsible for controlling strain‐specific ductal side branching patterns, we formed recombined mammary glands from epithelial and stroma elements taken from highly side‐branched 129 and poorly side‐branched C57BL/6J mammary glands and transplanted them to Rag1‐/‐ hosts on the inbred C57BL/6J background. When 129 epithelium was recombined with C57BL/6J stroma the poorly side‐branched C57BL/6J pattern was observed. C57BL/6J epithelium recombined with 129 stroma resulted in development of the highly side‐ branched pattern, as did 129 epithelium recombined with 129 stroma. All transplants used the same C57BL/6J endocrine background, demonstrating that strain differences in the mammary stroma are responsible for the strain‐specific ductal side branching patterns and that strain differences in epithelium or endocrine background play no part. Genes currently known to influence side branching by means of the stroma include activin/inhibin, epidermal growth factor receptor (EGFR), Wnt‐2, Wnt‐5a, and Wnt‐6. Of these, Wnt‐5a mRNA expression was decreased in 129 mammary glands compared with C57BL/6J mammary glands, but in F2 129:C57BL/6J animals Wnt‐5a mRNA expression level did not correlate with the highly variable side branching patterns observed. These experiments exclude variation in the expression level of known candidate genes as the mechanism responsible. Regardless of underlying mechanism, transplantation without regard to the genetic background of the stromal donor, whether inbred or mixed, will compromise experiments with side branching and associated gene expression endpoints. © 2002 Wiley‐Liss, Inc.
Minocycline Attenuates Ototoxicity and Enhances Antitumor Activity of Cisplatin Treatment In Vitro

Objective. Some agents have been shown to prevent cisplatin-induced ototoxicity. The objective is to show that the agent minocycline protects the cochlea against cisplatin damage and enhances the cytotoxicity of anticancer therapies. Study Design. In vitro chemotherapeutic assessments of minocycline. Setting. Research laboratory. Subjects and Methods. Hep-2 cells were cultured with and without 100 µM cisplatin, and cell growth inhibition was assessed. Autophagy in the samples was visually evaluated by electron microscopy and by beclin-1 expression using Western blotting. In another experiment, cochlear basilar membranes of 3-day-old rats were isolated and cultured. The cultures were treated with the same concentration of cisplatin or cisplatin combined with minocycline. Immunofluorescence staining was used to identify changes in spiral ganglions. Results. Cell growth was inhibited in a dose-dependent manner following minocycline treatment. Furthermore, the combination of cisplatin and minocycline effectively increased tumor cell death (P < .01). Autophagosomes were also evident in cells treated with minocycline. Beclin-l protein expression was increased after minocycline treatment in Hep-2 cells. In an experiment evaluating cochlear spiral ganglion neuron survival, it was found that the number of surviving cochlear neurons significantly increased in the minocycline pretreatment group compared with the group treated with cisplatin alone (P < .01). Conclusion. This study shows that minocycline alone, or in combination with chemotherapeutic drugs, inhibits the growth of tumor cells and attenuates ototoxicity. It is also shown that minocycline activates cell autophagy via the beclin-1 signaling pathway, which may be an additional underlying cause of Hep-2 cell death.
Compression and expansion of the temporal envelope: evaluation of speech intelligibility and sound quality.

Sensorineural hearing loss is accompanied by loudness recruitment, a steeper-than-normal rise of perceived loudness with presentation level. To compensate for this abnormality, amplitude compression is often applied (e.g., in a hearing aid). Alternatively, since speech intelligibility has been modeled as the perception of fast energy fluctuations, enlarging these (by means of expansion) may improve speech intelligibility. Still, even if these signal-processing techniques prove useful in terms of speech intelligibility, practical application might be hindered by unacceptably low sound quality. Therefore, both speech intelligibility and sound quality were evaluated for syllabic compression and expansion of the temporal envelope. Speech intelligibility was evaluated with an adaptive procedure, based on short everyday sentences either in noise or with a competing speaker. Sound quality was measured by means of a rating-scale procedure, for both speech and music. In a systematic setup, both the ratio of compression or expansion and the number of independent processing bands were varied. Individual hearing thresholds were compensated for by a listener-specific filter and amplification. Both listeners with normal hearing and listeners with sensorineural hearing impairment participated as paid volunteers. The results show that, on average, both compression and expansion fail to show better speech intelligibility or sound quality than linear amplification.
Surveying the serologic proteome in a tissue‐specific kras(G12D) knockin mouse model of pancreatic cancer

We have applied a serologic proteomic workflow involving three complementary MS approaches to a tissue‐specific KrasG12D‐knockin mouse model of pancreatic cancer that consistently forms precancerous lesions by 4 months of age. The three proteomics applications were highly complementary and allowed us to survey the entire range of low to high molecular weight serologic proteins. Combined, we identified 121 (49↓, 72↑) unique and statistically relevant serologic biomarkers with 88% previously reported to be associated with cancer and 38% specifically correlated with pancreatic cancer. Four markers, lysozyme C2, cytokeratin 19, Serpina1A and Pcf11, were further verified by Western blotting. When applying systems analysis, the top‐associated gene ontology functions were tied to wound healing, RXR signaling, growth, differentiation and innate immune activation through the JAK/STAT pathway. Upon further investigation of the apparent immune response using a multiplex cytokine screen, we found that IFN‐γ, VEGF and GM‐CSF were significantly increased in serum from the KrasG12D animals compared to littermate controls. By combining three complementary MS applications, we were able to survey the native intact peptidome and the global proteome in parallel, unveiling pathways that may be biologically relevant to promotion of pancreatic cancer progression and serologic markers of noninvasive early‐stage neoplasia.
Identification of an Inverted CCAAT Box Motif in the Fatty-acid Synthase Gene as an Essential Element for Mediation of Transcriptional Regulation by cAMP (*)

The antagonistic effect of cAMP on the insulin-induced expression of fatty acid synthase (FAS) in liver could be mimicked in vitro using H4IIE hepatoma cells, both by measuring the response of the endogenous FAS gene and by assaying expression of transfected reporter genes containing promoter elements of the FAS gene. 5′-Deletion analysis and replacement mutagenesis revealed that an essential element required for cAMP antagonism of the insulin effect is an inverted CCAAT box located between nucleotides −99 and −92. DNase I footprinting and gel shift analysis revealed that this region can bind a protein present in nuclei of liver and spleen, organs that express high and undetectable levels of FAS, respectively. This protein is not a CCAAT/enhancer-binding protein, C/EBP. Thus, the FAS gene appears unusual in that the sequence element required for transcriptional regulation by cAMP is neither a cAMP response element (CRE) nor a binding site for AP-1, AP-2, or C/EBP. These results suggest that essential to the regulation of FAS transcription by cAMP is the interaction of an inverted CCAAT box motif with a constitutively produced trans-acting factor that either itself undergoes modification in response to cAMP or associates with a protein that is produced or modified by cAMP exposure.
Speeding-Up Association Rule Mining With Inverted Index Compression

The growing interest in data storage has made the data size to be exponentially increased, hampering the process of knowledge discovery from these large volumes of high-dimensional and heterogeneous data. In recent years, many efficient algorithms for mining data associations have been proposed, facing up time and main memory requirements. Nevertheless, this mining process could still become hard when the number of items and records is extremely high. In this paper, the goal is not to propose new efficient algorithms but a new data structure that could be used by a variety of existing algorithms without modifying its original schema. Thus, our aim is to speed up the association rule mining process regardless the algorithm used to this end, enabling the performance of efficient implementations to be enhanced. The structure simplifies, reorganizes, and speeds up the data access by sorting data by means of a shuffling strategy based on the hamming distance, which achieve similar values to be closer, and considering both an inverted index mapping and a run length encoding compression. In the experimental study, we explore the bounds of the algorithms' performance by using a wide number of data sets that comprise either thousands or millions of both items and records. The results demonstrate the utility of the proposed data structure in enhancing the algorithms' runtime orders of magnitude, and substantially reducing both the auxiliary and the main memory requirements.
Inhibitory actions of ZENECA ZD7288 on whole‐cell hyperpolarization activated inward current (If) in guinea‐pig dissociated sinoatrial node cells

1 ZENECA ZD7288 (4‐(N‐ethyl‐N‐phenylamino)‐1,2‐dimethyl‐6‐(methylamino) pyrimidinium chloride) is a sinoatrial node (SAN) modulating agent which produces a selective slowing of the heart rate. Its effects have been studied in single, freshly dissociated guinea‐pig SAN cells, by standard patch clamp procedures. 2 Whole‐cell inward currents were evoked by hyperpolarizing voltage clamp steps from a holding potential of −40 mV. ZD7288 inhibited the hyperpolarization activated cationic current (If) in a concentration‐dependent manner. The ‘selective bradycardic agents' alinidine and UL‐FS 49 (zatebradine) both also inhibited If. 3 The activation of If was investigated by measuring tail current amplitudes at +20 mV after hyperpolarizing steps to different potentials to activate the current. The reduction in If resulted from both a shift in the If current activation curve in the negative direction on the voltage axis, and also a reduction in the activation curve amplitude. 4 ZD7288 did not affect the ion selectivity of the If channel, since the tail current reversal potential was unchanged in the presence of the drug. 5 With ZD7288 the inhibition of If was not use‐dependent, whereas UL‐FS 49 displayed use‐dependence in the block of the If current. 6 Whereas ZD7288 had no significant effect on the delayed rectifier current (Ik) in these cells, both alinidine and UL‐FS 49 significantly reduced Ik at the same concentrations which reduced If. 7 The data show that ZD7288 reduces If by affecting the activation characteristics of the If current; this inhibition may account for this agent's selective bradycardic properties.
Shocking HIV out of hiding: where are we with clinical trials of latency reversing agents?

Purpose of reviewTo provide an overview of the initial experiences with the use of latency-reversing agents (LRAs) in clinical trials in HIV and to discuss and contrast results arising from these studies. Recent findingsAlthough the clinical administration of histone deacetylase inhibitors (HDACis) and disulfiram to HIV-infected individuals on antiretroviral therapy significantly increased cell-associated HIV RNA in CD4+ T cells and in some cases plasma HIV RNA, this did not reduce the frequency of latently infected cells in blood. Potential reasons for this include insufficient potency in latency reversal, lack of virus or immune-mediated cytolysis of virus-expressing cells and/or a high frequency of immune escape mutations in the recently activated virus. Analyses of HIV-specific T-cell responses in vivo did not demonstrate that HDACis impair immune cell effector functions. SummaryMore effective latency-reversing interventions and additional strategies to eliminate virus-expressing cells are needed. Key challenges include testing combinations of LRAs and/or LRAs with immune modulation to optimize potency in the absence of adverse events. A better understanding of the mechanisms of action of LRAs as well as strategies to enhance potency and penetration in tissue are key challenges for future studies.
Validating the Allogeneic Stem Cell Transplantation Disease Risk Index: Sample Size, Follow-up, and Local Data Are Important

Background Reporting allogeneic hematopoietic stem cell transplantation (alloHSCT) outcomes by disease and disease stage can limit statistical power. Recently, the disease risk index (DRI) was developed and validated to stratify clusters of patients with various combinations of disease and stage for overall survival (OS), progression-free survival (PFS), and cumulative incidence of relapse (CIR). However, the DRI has not been tested for smaller cohorts or cohorts with shorter follow-up. Methods Data from recipients of a first alloHSCT between 2000 and 2011 (n=466; median follow-up, 55.2 months) were extracted from our database. Each patient was assigned to one of four risk categories according to the DRI. Results The DRI was validated as being significantly predictive of OS, PFS, and CIR (P<0.001 for all). The OS, PFS, and CIR from a contemporaneous cohort (n=324) from our institution were superior to the original training cohort. Using randomized patient subsets, the DRI stratified a cohort of 100 patients (OS, P=0.010; PFS, P=0.016; CIR, P=0.027), but failed to stratify a cohort of 50 patients (OS, P=0.385; PFS, P=0.167; CIR, P=0.026). When simulating shorter follow-up, the DRI stratified a cohort (n=322) with a median follow-up of 40.6 months for OS and PFS, but failed to stratify a cohort (n=242) with a median follow-up of 33.1 months. Conclusion The DRI is a simple, robust pre-alloHSCT risk stratification tool. However, users should calibrate with local data before using the DRI to estimate absolute OS, PFS, and CIR and understand its limitations when applied to smaller cohorts or cohorts with shorter follow-up.
Estimating effective dose to pediatric patients undergoing interventional radiology procedures using anthropomorphic phantoms and MOSFET dosimeters.

OBJECTIVE The purpose of this study was to estimate the effective doses received by pediatric patients during interventional radiology procedures and to present those doses in "look-up tables" standardized according to minute of fluoroscopy and frame of digital subtraction angiography (DSA). MATERIALS AND METHODS Organ doses were measured with metal oxide semiconductor field effect transistor (MOSFET) dosimeters inserted within three anthropomorphic phantoms, representing children at ages 1, 5, and 10 years, at locations corresponding to radiosensitive organs. The phantoms were exposed to mock interventional radiology procedures of the head, chest, and abdomen using posteroanterior and lateral geometries, varying magnification, and fluoroscopy or DSA exposures. Effective doses were calculated from organ doses recorded by the MOSFET dosimeters and are presented in look-up tables according to the different age groups. RESULTS The largest effective dose burden for fluoroscopy was recorded for posteroanterior and lateral abdominal procedures (0.2-1.1 mSv/min of fluoroscopy), whereas procedures of the head resulted in the lowest effective doses (0.02-0.08 mSv/min of fluoroscopy). DSA exposures of the abdomen imparted higher doses (0.02-0.07 mSv/DSA frame) than did those involving the head and chest. CONCLUSION Patient doses during interventional procedures vary significantly depending on the type of procedure. User-friendly look-up tables may provide a helpful tool for health care providers in estimating effective doses for an individual procedure.