Miracle-dz/UniFAR-FTUs huggingface dataset:
MDR1 causes resistance to the antitumour drug miltefosine

Miltefosine (hexadecylphosphocholine) is used for topical treatment of breast cancers. It has been shown previously that a high percentage of breast carcinomas express MDR1 or MRP. We investigated the sensitivity of MDR1-expressing cells to treatment with miltefosine. We show that cells overexpressing MDR1 (NCI/ADR-RES, KB-8-5, KB-C1, CCRF/VCR1000, CCRF/ADR5000) were less sensitive to miltefosine treatment when compared to the sensitive parental cell lines. HeLa cells transfected with MDR1 exhibited resistance to the compound, indicating that expression of this gene is sufficient to reduce the sensitivity to miltefosine. The resistance of MDR1-expressing cells to miltefosine was less pronounced than that to adriamycin or vinblastine. Expression of MDR2 did not correlate with the resistance to miltefosine. As shown by a fluorescence quenching assay using MIANS-labelled P-glycoprotein (PGP), miltefosine bound to PGP with a Kd of approximately 7 μM and inhibited PGP-ATPase activity with an IC50 of approximately 35 μM. Verapamil was not able to reverse the resistance to miltefosine. Concentrations of miltefosine up to approximately 60 μM stimulated, whereas higher concentrations inhibited the transport of [3H]-colchicine with an IC50 of approximately 297 μM. Binding studies indicated that miltefosine seems to interact with the transmembrane domain and not the cytosolic nucleotide-binding domain of PGP. These data indicate that expression of MDR1 may reduce the response to miltefosine in patients and that this compound interacts with PGP in a manner different from a number of other substrates. © 2001 Cancer Research Campaign
Neighborhood repulsed metric learning for kinship verification

Kinship verification from facial images is a challenging problem in computer vision, and there is a very few attempts on tackling this problem in the literature. In this paper, we propose a new neighborhood repulsed metric learning (NRML) method for kinship verification. Motivated by the fact that interclass samples (without kinship relations) with higher similarity usually lie in a neighborhood and are more easily misclassified than those with lower similarity, we aim to learn a distance metric under which the intraclass samples (with kinship relations) are pushed as close as possible and interclass samples lying in a neighborhood are repulsed and pulled as far as possible, simultaneously, such that more discriminative information can be exploited for verification. Moreover, we propose a multiview NRM-L (MNRML) method to seek a common distance metric to make better use of multiple feature descriptors to further improve the verification performance. Experimental results are presented to demonstrate the efficacy of the proposed methods.
A year's review of bacterial pneumonia at the central hospital of Lucerne, Switzerland.

Community acquired pneumonia (CAP) remains an important cause of substantial morbidity and mortality in inhospital patients. We conducted a retrospective study of all patients hospitalised at our hospital with the diagnosis of bacterial pneumonia according to ICD-10 within one year. Of 360 identified charts, 335 met the requirements and were reviewed regarding risk factors, diagnosis, treatment, and overall mortality. The typical patient hospitalised with pneumonia was elderly (mean 68 years), male (60%), and suffered from comorbidities or predisposing factors (96.4%). A total of 72.8% of pneumonias were localized in the inferior lobes, and 21.1% had bilateral infiltrates. Etiologic agents were searched for in 297/335 patients (87.5%) and were found positive in 33.4%: of 169 blood cultures 9.5% were positive, of 150 sputum cultures taken 46.6% were positive, of 17 serologies taken 58.8% were positive, and of 9 pleural effusions analysed 22.2% were positive. Encapsulated bacteria were the most common found bacterial etiologies, namely Streptococcus pneumoniae (S. pneumoniae) in 30.9% of patients with known bacterial etiology, Haemophilus in 24.7%, and Klebsiella in 12.4%. Methicillin-resistant S. aureus was not found. The three most commonly used antibiotics were amoxicillin/clavulanic acid used in 77.3% of patients, clarithromycin (41.2%), and ceftriaxone (16.6%). Mean duration of treatment was 12.1 days. 245/335 (73.1%) patients had a favourable outcome, 16.7% (56/335) of patients had a protracted illness with delayed resolution (i.e. prolonged hospital stay, need for intensive care, intubation or several of these complications). Overall mortality in our unit was 8.6%.
Electronic health records and malpractice claims in office practice.

BACKGROUND Electronic health records (EHRs) may improve patient safety and health care quality, but the relationship between EHR adoption and settled malpractice claims is unknown. METHODS Between June 1, 2005, and November 30, 2005, we surveyed a random sample of 1884 physicians in Massachusetts to assess availability and use of EHR functions, predictors of use, and perceptions of medical practice. Information on paid malpractice claims was accessed on the Massachusetts Board of Registration in Medicine (BRM) Web site in April 2007. We used logistic regression to assess the relationship between the adoption and use of EHRs and paid malpractice claims. RESULTS The survey response rate was 71.4% (1345 of 1884). Among 1140 respondents with data on the presence of EHR and available BRM records, 379 (33.2%) had EHRs. A total of 6.1% of physicians with an EHR had a history of a paid malpractice claim compared with 10.8% of physicians without EHRs (unadjusted odds ratio, 0.54; 95% confidence interval, 0.33-0.86; P = .01). In logistic regression analysis controlling for sex, race, year of medical school graduation, specialty, and practice size, the relationship between EHR adoption and paid malpractice settlements was of smaller magnitude and no longer statistically significant (adjusted odds ratio, 0.69; 95% confidence interval, 0.40-1.20; P = .18). Among EHR adopters, 5.7% of physicians identified as "high users" of EHR had paid malpractice claims compared with 12.1% of "low users" (P = .14). CONCLUSIONS Although the results of this study are inconclusive, physicians with EHRs appear less likely to have paid malpractice claims. Confirmatory studies are needed before these results can have policy implications.
Ca2+ Signaling in Mouse Cortical Neurons Studied by Two-Photon Imaging and Photoreleased Inositol Triphosphate

IP3-mediated Ca2+ release is a crucial neuronal signaling mechanism that has not been extensively characterized in the mammalian cerebral cortex. We used two-photon, video-rate microscopy to image Ca2+ signals evoked by photoreleased IP3 in pyramidal neurons of mouse prefrontal cortex. Ca2+ responses to photoreleased IP3 varied greatly between different neurons; however, within IP3-responsive neurons, the soma invariably showed highest sensitivity, with signals increasing nonlinearly with [IP3]. Responses to paired photorelease displayed inhibition, whereas IP3-evoked Ca2+liberation was potentiated by Ca2+ entry during action potentials and vice versa. IP3-mediated Ca2+ signals strongly inhibited spike firing through activation of K+ membrane conductance. Metabotropic signaling via the phosphoinositide pathway thus serves as a powerful and sustained modulator of excitability in cortical neurons and displays complex reciprocal interactions between electrical and chemical signals.
Single-source/sink network error correction is as hard as multiple-unicast

We study the problem of communicating over a single-source single-terminal network in the presence of an adversary that may jam a single link of the network. If any one of the edges can be jammed, the capacity of such networks is well understood and follows directly from the connection between the minimum cut and maximum flow in single-source single-terminal networks. In this work we consider networks in which some edges cannot be jammed, and show that determining the network communication capacity is at least as hard as solving the multiple-unicast network coding problem for the error-free case. The latter problem is a long standing open problem.
A novel tunable gain equalizer based on a long-period fiber grating written by high-frequency CO2 laser pulses

A novel tunable gain equalizer based on the long-period fiber grating (LPFG) induced by high-frequency CO/sub 2/ laser pulses is demonstrated, for the first time, to our knowledge. Both the resonant wavelength and the resonant peak amplitude of the novel LPFG have a good linearity with temperature and transverse load, respectively. The wavelength and the peak amplitude of the gain equalizer can be tuned by the means of adjusting temperature and transverse load independently, showing that this tunable equalizer is a practical approach to realizing dynamic gain equalization in erbium-doped fiber amplifier systems.
Differential Regulation of the Overlapping Kaposi's Sarcoma-Associated Herpesvirus vGCR (orf74) and LANA (orf73) Promoters

ABSTRACT Similar to that of other herpesviruses, Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) lytic replication destroys the host cell, while the virus can persist in a latent state in synchrony with the host. During latency only a few genes are transcribed, and the question becomes one of what determines latent versus lytic gene expression. Here we undertake a detailed analysis of the latency-associated nuclear antigen (LANA [orf73]) promoter (LANAp). We characterized a minimal region that is necessary and sufficient to maintain high-level transcription in all tissues tested, including primary endothelial cells and B cells, which are the suspected natural host for KSHV. We show that in transient-transfection assays LANAp mimics the expression pattern observed for the authentic promoter in the context of the KSHV episome. Unlike other KSHV promoters tested thus far, LANAp is not affected by tetradecanoyl phorbol acetate or viral lytic cycle functions. It is, however, subject to control by LANA itself and cellular regulatory factors, such as p53. This is in contrast to the K14/vGCR (orf74) promoter, which overlaps LANAp and directs transcription on the opposite strand. We isolated a minimal cis-regulatory region sufficient for K14/vGCR promoter activity and show that it, too, mimics the regulation observed for the authentic viral promoter. In particular, we demonstrate that its activity is absolutely dependent on the immediate-early transactivator orf50, the KSHV homolog of the Epstein-Barr virus Rta transactivator.
Attention and performance.

Recent progress in the study of attention and performance is discussed, focusing on the nature of attentional control and the effects of practice. Generally speaking, the effects of mental set are proving more pervasive than was previously suspected, whereas automaticity is proving less robust. Stimulus attributes (e.g. onsets, transients) thought to have a "wired-in" ability to capture attention automatically have been shown to capture attention only as a consequence of voluntarily adopted task sets. Recent research suggests that practice does not have as dramatic effects as is commonly believed. While it may turn out that some mental operations are automatized in the strongest sense, this may be uncommon. Recent work on task switching is also described; optimal engagement in a task set is proving to be intimately tied to learning operations triggered by the actual performance of a new task, not merely the anticipation of such performance.
Ecosystem-Service Tradeoffs Associated with Switching from Annual to Perennial Energy Crops in Riparian Zones of the US Midwest

Integration of energy crops into agricultural landscapes could promote sustainability if they are placed in ways that foster multiple ecosystem services and mitigate ecosystem disservices from existing crops. We conducted a modeling study to investigate how replacing annual energy crops with perennial energy crops along Wisconsin waterways could affect a variety of provisioning and regulating ecosystem services. We found that a switch from continuous corn production to perennial-grass production decreased annual income provisioning by 75%, although it increased annual energy provisioning by 33%, decreased annual phosphorous loading to surface water by 29%, increased below-ground carbon sequestration by 30%, decreased annual nitrous oxide emissions by 84%, increased an index of pollinator abundance by an average of 11%, and increased an index of biocontrol potential by an average of 6%. We expressed the tradeoffs between income provisioning and other ecosystem services as benefit-cost ratios. Benefit-cost ratios averaged 12.06 GJ of additional net energy, 0.84 kg of avoided phosphorus pollution, 18.97 Mg of sequestered carbon, and 1.99 kg of avoided nitrous oxide emissions for every $1,000 reduction in income. These ratios varied spatially, from 2- to 70-fold depending on the ecosystem service. Benefit-cost ratios for different ecosystem services were generally correlated within watersheds, suggesting the presence of hotspots – watersheds where increases in multiple ecosystem services would come at lower-than-average opportunity costs. When assessing the monetary value of ecosystem services relative to existing conservation programs and environmental markets, the overall value of enhanced services associated with adoption of perennial energy crops was far lower than the opportunity cost. However, when we monitized services using estimates for the social costs of pollution, the value of enhanced services far exceeded the opportunity cost. This disparity between recoverable costs and social value represents a fundamental challenge to expansion of perennial energy crops and sustainable agricultural landscapes.
Social amoebae mating types do not invest unequally in sexual offspring

Unequal investment by different sexes in their progeny is common and includes differential investment in the zygote and differential care of the young. The social amoeba Dictyostelium discoideum has a sexual stage in which isogamous cells of any two of the three mating types fuse to form a zygote which then attracts hundreds of other cells to the macrocyst. The latter cells are cannibalized and so make no genetic contribution to reproduction. Previous literature suggests that this sacrifice may be induced in cells of one mating type by cells of another, resulting in a higher than expected production of macrocysts when the inducing type is rare and giving a reproductive advantage to this social cheat. We tested this hypothesis in eight trios of field‐collected clones of each of the three D. discoideum mating types by measuring macrocyst production at different pairwise frequencies. We found evidence that supported differential contribution in only two of the 24 clone pairs, so this pattern is rare and clone‐specific. In general, we did not reject the hypothesis that the mating types contribute cells relative to their proportion in the population. We also found a significant quadratic relationship between partner frequency and macrocyst production, suggesting that when one clone is rare, macrocyst production is limited by partner availability. We were also unable to replicate previous findings that macrocyst production could be induced in the absence of a compatible mating partner. Overall, mating type‐specific differential investment during sex is unlikely in microbial eukaryotes like D. discoideum.
Helicenes—A New Class of Organic Spin Filter

Chiral helicene, a fully conjugated system without stereogenic carbon, can filter spins effectively at room temperature, a consequence of the chiral-induced spin-selectivity effect. The chirality dictates the spin of the electrons transferred through helicene, and magnetoresistance devices based on these molecules show antisymmetric magnetoresistance versus H plots.
Designing a Brief Alzheimer Screen (BAS).

CONTEXT With advances in the treatment of Alzheimer's disease (AD), clinical focus has shifted to early patient identification. Memory recall tests and category fluency distinguish normal individuals from early AD patients. OBJECTIVE Develop a brief test for general practitioners to screen for AD. Design. Examination of items from the MMSE and category fluency. SETTING AND PARTICIPANTS A Brief Alzheimer Screen (BAS) was developed from cognitive assessments on 406 normal subjects and 342 mild AD patients in the CERAD (Consortium to Establish a Registry for AD) dataset. The derived measure was then applied to a second validation sample. MAIN OUTCOME MEASURE Logistic regression was used to derive a predictive equation, which was then applied to two validation samples to estimate sensitivity and specificity. RESULTS The resulting logistic model for discriminating between mild AD and controls included: recall of 3 words, number of animals named in 30 seconds, date, and spelling of WORLD backwards, (p < 0.001 for each) accounting for 77% of the variance. When applied to the validation samples, sensitivity and specificity were over 99% and 87%, respectively. CONCLUSIONS These data support the use of the BAS as a potential screen of patients over 60 years of age.
Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of natural killer T cells and IL-17

Exposure to ozone, which is a major component of air pollution, induces a form of asthma that occurs in the absence of adaptive immunity. Although ozone-induced asthma is characterized by airway neutrophilia, and not eosinophilia, it is nevertheless associated with airway hyperreactivity (AHR), which is a cardinal feature of asthma. Because AHR induced by allergens requires the presence of natural killer T (NKT) cells, we asked whether ozone-induced AHR had similar requirements. We found that repeated exposure of wild-type (WT) mice to ozone induced severe AHR associated with an increase in airway NKT cells, neutrophils, and macrophages. Surprisingly, NKT cell–deficient (CD1d−/− and Jα18−/−) mice failed to develop ozone-induced AHR. Further, treatment of WT mice with an anti-CD1d mAb blocked NKT cell activation and prevented ozone-induced AHR. Moreover, ozone-induced, but not allergen-induced, AHR was associated with NKT cells producing interleukin (IL)-17, and failed to occur in IL-17−/− mice nor in WT mice treated with anti–IL-17 mAb. Thus, ozone exposure induces AHR that requires the presence of NKT cells and IL-17 production. Because NKT cells are required for the development of two very disparate forms of AHR (ozone- and allergen-induced), our results strongly suggest that NKT cells mediate a unifying pathogenic mechanism for several distinct forms of asthma, and represent a unique target for effective asthma therapy.
Angiogenin Enhances Cell Migration by Regulating Stress Fiber Assembly and Focal Adhesion Dynamics

Angiogenin (ANG) acts on both vascular endothelial cells and cancer cells, but the underlying mechanism remains elusive. In this study, we carried out a co-immunoprecipitation assay in HeLa cells and identified 14 potential ANG-interacting proteins. Among these proteins, β-actin, α-actinin 4, and non-muscle myosin heavy chain 9 are stress fiber components and involved in cytoskeleton organization and movement, which prompted us to investigate the mechanism of action of ANG in cell migration. Upon confirmation of the interactions between ANG and the three proteins, further studies revealed that ANG co-localized with β-actin and α-actinin 4 at the leading edge of migrating cells. Down-regulation of ANG resulted in fewer but thicker stress fibers with less dynamics, which was associated with the enlargements of focal adhesions. The focal adhesion kinase activity and cell migration capacity were significantly decreased in ANG-deficient cells. Taken together, our data demonstrated that the existence of ANG in the cytoplasm optimizes stress fiber assembly and focal adhesion formation to accommodate cell migration. The finding that ANG promoted cancer cell migration might provide new clues for tumor metastasis research.
Brain-specific Angiogenesis Inhibitor-1 Signaling, Regulation, and Enrichment in the Postsynaptic Density*

Background: BAI1 is an adhesion receptor; little is known about its signaling or localization. Results: BAI1 activates Rho in a G protein-dependent manner, binds to synaptic scaffold proteins, and is highly enriched in the postsynaptic density. Conclusion: BAI1 is a synaptic receptor that signals through G proteins. Significance: BAI1 may play a previously unappreciated role as a regulator of synaptic function. Brain-specific angiogenesis inhibitor-1 (BAI1) is an adhesion G protein-coupled receptor that has been studied primarily for its anti-angiogenic and anti-tumorigenic properties. We found that overexpression of BAI1 results in activation of the Rho pathway via a Gα12/13-dependent mechanism, with truncation of the BAI1 N terminus resulting in a dramatic enhancement in receptor signaling. This constitutive activity of the truncated BAI1 mutant also resulted in enhanced downstream phosphorylation of ERK as well as increased receptor association with β-arrestin2 and increased ubiquitination of the receptor. To gain insights into the regulation of BAI1 signaling, we screened the C terminus of BAI1 against a proteomic array of PDZ domains to identify novel interacting partners. These screens revealed that the BAI1 C terminus interacts with a variety of PDZ domains from synaptic proteins, including MAGI-3. Removal of the BAI1 PDZ-binding motif resulted in attenuation of receptor signaling to Rho but had no effect on ERK activation. Conversely, co-expression with MAGI-3 was found to potentiate signaling to ERK by constitutively active BAI1 in a manner that was dependent on the PDZ-binding motif of the receptor. Biochemical fractionation studies revealed that BAI1 is highly enriched in post-synaptic density fractions, a finding consistent with our observations that BAI1 can interact with PDZ proteins known to be concentrated in the post-synaptic density. These findings demonstrate that BAI1 is a synaptic receptor that can activate both the Rho and ERK pathways, with the N-terminal and C-terminal regions of the receptor playing key roles in the regulation of BAI1 signaling activity.
Automating knowledge capture in the aerospace domain

We present an approach to automating knowledge extraction in the aerospace engineering domain which has had a fundamental impact on the way engineers manage their collective knowledge built with years of experience. Even though obtaining labelled data in this domain is hard due to the high cost of domain experts' time, the application of the machine learning-based technology was successful, yielding results comparable to the state-of-the-art. Moreover, we present a comparison between several machine learning approaches in extracting knowledge from reports about jet engines. We show that the application of a semi-supervised approach does not provide a significant increase in accuracy so as to justify its adoption due to its much higher computational cost, but that the application of a large-scale approach considerably reduces both training and testing time while keeping accuracy comparable to the standard supervised approach, making it a good choice for this class of application scenarios.