Miracle-dz/UniFAR-FTUs huggingface dataset:
The Open University ’ s repository of research publications and other research outputs Deconstruction and excision in philosophical posthumanism

I distinguish the ethics of transhumanism from a related metaphysical position which I refer to as “speculative posthumanism. ” Speculative posthumanism holds that posthumans might be radically non-human and thus unintelligible in human terms. I claim that this transcendence can be viewed as analogous to that of the thing-in-itself in Kantian and post-Kantian European philosophy. This schema implies an impasse for transhumanism because, while the radically non-human or posthuman would elude evaluation according to transhumanist principles such as personal autonomy or liberal freedom, it is morally unacceptable for transhumanists to discount the possible outcomes of their favoured policies. I then consider whether the insights of critical posthumanists, who employ a cyborg perspective on human-technology couplings, can dissolve this impasse by “deconstructing” the opposition between the human and its prospective posthuman successors. By exhibiting its logical basis in the postructuralist philosophies of Derrida and Deleuze, I show that the cyborg perspective is consistent with both cyborg humanism and a modified speculative posthumanism. This modified account treats the alterity of the posthuman as a historically emergent feature of human and posthuman multiplicities that must be understood through their technical or imaginative synthesis, not in relation to a transcendental conception of the human. Contemporary transhumanists argue that human nature can and should be altered through technological means where such enhancements are likely to lead to the majority of individuals leading better lives. This ethic is premised on prospective developments in Nanotechnology, Biotechnology, Information Technology, and Cognitive Science – the so-called “NBIC” suite. One of the areas of particular concern for transhumanists is the use of such technologies to enhance human cognitive functions such as learning, memory, and attention. For example, such pharmacological agents as Modafinil are currently used to enhance learning and working memory. Transcranial Magnetic Stimulation of areas of neural tissue may, one day, be routinely employed to increase the neural plasticity associated with learning and memorization (Bostrom and Sandberg 2006). More speculatively, micro-electric neuroprostheses might interface the brain directly with non-biological cognitive or robotic systems (Kurzweil 2005, 317). Such developments could bring the day when all humans will be more intellectually capable, whether because of enhancements of their native biological machinery or through interfacing with artificial information processing systems.
Performance comparison of cache invalidation techniques in mobile computing environment

Advancement in evolution of Internet technologies like 3G, 4G, and 5G, there is a need of good quality of service (QoS) for such wireless networks. Faster responses are required for various queries raised by mobile terminals (MTs) from any mobile computing environment. There has been many research works proposed in the past to address the QoS issue by using an Invalidation Report (IR)-based cache management schemes. In all such cases, IRs become unmanageable due to the poor utilization of available bandwidth and larger size of IRs. Broadcast times are fixed and longer due to which IR looses its effectiveness and hit ratio degrades, So, to address these issues, in this paper, we have simulated cache invalidation techniques scenario on NS2.35, peer cache invalidation techniques like Time Stamping and Update Invalidation Report based techniques are simulated and tested to show performance on basis of various parameters like Hit Ratio, Query Delay by varying cache update interval and cache size. At the end we have also suggested the future directions for such techniques.
Mobile gene cassettes and integrons: capture and spread of genes by site‐specific recombination

An integron is a genetic unit that includes the determinants of the components of a site‐specific recombination system capable of capturing and mobilizing genes that are contained in mobile elements called gene cassettes. An integron also provides a promoter for expression of the cassette genes, and integrons thus act both as natural cloning systems and as expression vectors. The essential components of an integron are an int gene encoding a site‐specific recombinase belonging to the integrase family, an adjacent site, attl, that is recognized by the integrase and is the receptor site for the cassettes, and a promoter suitably oriented for expression of the cassette‐encoded genes. The cassettes are mobile elements that include a gene (most commonly an antibiotic‐resistance gene) and an integrase‐specific recombination site that is a member of a family of sites known as 59‐base elements. Cassettes can exist either free in a circularized form or integrated at the attl site, and only when integrated is a cassette formally part of an integron. A single site‐specific recombination event involving the integron‐associated attl site and a cassette‐associated 59‐base element leads to insertion of a free circular cassette into a recipient integron. Multiple cassette insertions can occur, and integrons containing several cassettes have been found in the wild. The integrase also catalyses excisive recombination events that can lead to loss of cassettes from an integron and generate free circular cassettes. Due to their ability to acquire new genes, integrons have a clear role in the evolution of the genomes of the plasmids and transposons that contain them. However, a more general role in evolution is also likely. Events involving recombination between a specific 59‐base‐element site and a nonspecific secondary site have recently been shown to occur. Such events should lead either to the insertion of cassettes at non‐specific sites or to the formation of stable cointegrates between different plasmid molecules, and a cassette situated outside the integron context has recently been identified.
Public Opinion and Political Vulnerability: Why Has the National Endowment for the Arts Been Such an Attractive Target?

Federal government arts programs appear to deviate from the rule that legislative behavior closely follows public preferences. Between the mid-1970s and the late 1980s, despite stability in public opinion, the NEA evolved from Congress's bipartisan darling to its controversial scapegoat. We inspect 55 items from public opinion surveys and re-analyze data from 2 state and 8 national surveys undertaken between 1975 and 1996 to resolve this puzzle. Our conclusions: (1) Arts support is not a salient issue to most voters, leaving legislators relatively unconstrained. (2) Positive responses to general questions about arts funding often mask complex, ambivalent views. (3) The core constituency for federal arts support - college graduates - is difficult to mobilize because their interest in the arts is balanced by skepticism about federal government programs. (4) Opponents of arts spending successfully built on ties to Christian conservative and Republican loyalists to mobilize the stable minorities opposed to the NEA. As a result, arts politics in the U.S. has consisted of a standoff between a committed minority of 15 to 20 percent of the public that strongly opposes federal support for the arts and a weakly committed majority of about 60 percent that favors the federal role.
Effects of study precision and risk of bias in networks of interventions: a network meta-epidemiological study.

BACKGROUND Empirical research has illustrated an association between study size and relative treatment effects, but conclusions have been inconsistent about the association of study size with the risk of bias items. Small studies give generally imprecisely estimated treatment effects, and study variance can serve as a surrogate for study size. METHODS We conducted a network meta-epidemiological study analyzing 32 networks including 613 randomized controlled trials, and used Bayesian network meta-analysis and meta-regression models to evaluate the impact of trial characteristics and study variance on the results of network meta-analysis. We examined changes in relative effects and between-studies variation in network meta-regression models as a function of the variance of the observed effect size and indicators for the adequacy of each risk of bias item. Adjustment was performed both within and across networks, allowing for between-networks variability. RESULTS Imprecise studies with large variances tended to exaggerate the effects of the active or new intervention in the majority of networks, with a ratio of odds ratios of 1.83 (95% CI: 1.09,3.32). Inappropriate or unclear conduct of random sequence generation and allocation concealment, as well as lack of blinding of patients and outcome assessors, did not materially impact on the summary results. Imprecise studies also appeared to be more prone to inadequate conduct. CONCLUSIONS Compared to more precise studies, studies with large variance may give substantially different answers that alter the results of network meta-analyses for dichotomous outcomes.
Glomerular Ultrafiltration Coefficient after Ischemic Renal Injury in Dogs

Micropuncture studies of acute renal failure after ischemic renal injury suggest that glomerular ultrafiltration coefficient may remain normal in the period immediately after ischemia and decline significantly during the following 18–24 hours. The present series of in vitro experiments was designed to evaluate glomerular ultrafiltration coefficient and glomerular onco- metric and rheological properties in ischemic acute renal failure in dogs. To obtain glomeruli prior to ischemia, a right nephrectomy was performed and glomeruli were isolated for studies of filtration and cell and extracellular spaces. The left renal pedicle then was occluded for 90 minutes; glomeruli isolated from biopsies of this kidney were studied at intervals up to 48 hours after ischemia. Glomeruli were isolated by sieving renal cortical fragments, and filtration was induced by an oncouc gradient. The glomerular ultrafiltration coefficient remained near control levels for the first hour after ischemia, but declined significantly at 24 and 48 hours. Specifically, glomerular ultrafiltration coefficient of glomeruli isolated from normal kidneys was 16.5 ± 0.9 nl/min per mm Hg(n = 15). Immediately following ischemia, glomerular ultrafiltration coefficient remained essentially unchanged (15.9 ±1. 1 nl/min per mm Hg, n = 4). At 1 hour, there was a small decrease in glomerular ultrafiltration coefficient (14.4 ± 1.3 nl/min per mm Hg, n = 4). At 24 hours, glomerular ultrafiltration coefficient was significantly decreased (9.8 ± 0.5 nl/min per mm Hg, n = 9, P < 0.01) and remained at that level at 48 hours (9.5 ± 0.5 nl/min per mm Hg, n = 8, P < 0.001). In experimental glomeruli, the oncometric response was diminished and erythrocyte movement along glomerular capillaries was impaired. Total water and inulin spaces were measured in glomeruli from control and 48-hour postischemic periods, and glomerular morphology was studied by transmission and scanning electron microscopy at the same time. Intracellular water comprised a significantly larger portion of total glomerular water 48 hours after ischemia than during the control period. Concurrent morphological changes included a decrease in the diameter of endothelial fenestrae and widening of epithelial foot processes. These results are consistent with the view that one or more nonglomerular factors are responsible for profound oliguria during the early phase of acute renal failure after ischemia. However, reduction of glomerular ultrafiltration coefficient, probably secondary to altered glomerular cellular characteristics, may be an important determinant to decreased glomerular filtration rate in established acute renal failure.
Towards reliable partial anaphora resolution

This paper assumes that currently, anaphora resolution at a desired level of reliability has to remain partial. It presents the thesis that multiple small ("expert") procedures of known reliability that are conceived for partial analysis have to be developed and combined in order to increase coverage. These resolution experts will be specific to style, domain, task, etc. The paper describes corpus analysis that suggests such experts and their potential ordering. A quick and partial implementation of the ideas is evaluated on Wall Street Journal articles.
Recent Developments in Drug Discovery for Leishmaniasis and Human African Trypanosomiasis

Leishmaniasis is a parasitic disease that presents four main clinical syndromes: cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), visceral leishmaniasis/kala azar (VL), and post kala azar dermal leishmaniasis (PKDL). Causative Leishmania are protozoan parasites that are transmitted among mammalian hosts by phlebotomine sandflies. In mammalian hosts, parasite cells proliferate inside the host phagocytic cells as round amastigotes. Infection of sandflies with Leishmania occurs during insect feeding on infected mammalian hosts. After introduction into the insect gut together with the blood meal, Leishmania amastigotes transform into elongated flagellated promastigotes that propagate in the insect gut. A new round of infection is initiated after the infected sandfly takes a blood meal from a naive mammalian host and introduces Leishmania parasites into the bite wound in the host dermis (Scheme 1). More than 20 different Leishmania species have been found to cause human leishmaniasis (Table 1). Leishmaniasis is endemic in 98 countries and is closely associated with poverty. More than a million new cases are reported per year and 350 million people are at risk of contracting the infection. For the most severe form of leishmaniasis, VL, ∼300 000 new cases are estimated to occur annually resulting in ∼40 000 deaths. Approximately 90% of all VL cases occur in 3 endemic foci: 1. India, Bangladesh, and Nepal; 2. East Africa; and 3. Brazil. In spite of the high prevalence, currently available treatments for leishmaniasis are inadequate. Pentavalent antimonials, the standard treatment for leishmaniasis for many decades, are not efficacious in Bihar (∼60% of VL cases worldwide) any longer due to widespread resistance to the drug in this region. Several new VL treatments have emerged during the past 10–15 years, but each has serious shortcomings (summarized in Table 2). These include paromomycin (injectable, long treatment, region-dependent efficacy), miltefosine (cost, teratogenicity, long treatment), and liposomal amphotericin B (cost, hospitalization, region-dependent efficacy). An additional challenge is represented by patients with HIV/VL coinfections who are more difficult to cure (lower initial and final cure rates), have greater susceptibility to drug toxicity, and have higher rates of death and relapse. Due to the limitations of the existing treatments, better drugs are urgently needed. Ideally, new VL drugs would be efficacious across all endemic regions, would affect cure in ≤10 days, and would cost <$10 per course (for a complete target product profile for new VL drugs, which was formulated by DNDi, see Table 4). 1 Here we describe the disease history and parasite biology followed by a summary of the currently available treatments and, finally, review reports of novel small molecules with antileishmanial activity.
Estrogen-dependent signaling in a molecularly distinct subclass of aggressive prostate cancer.

BACKGROUND The majority of prostate cancers harbor gene fusions of the 5'-untranslated region of the androgen-regulated transmembrane protease serine 2 (TMPRSS2) promoter with erythroblast transformation-specific transcription factor family members. The common fusion between TMPRESS2 and v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) is associated with a more aggressive clinical phenotype, implying the existence of a distinct subclass of prostate cancer defined by this fusion. METHODS We used complementary DNA-mediated annealing, selection, ligation, and extension to determine the expression profiles of 6144 transcriptionally informative genes in archived biopsy samples from 455 prostate cancer patients in the Swedish Watchful Waiting cohort (1987-1999) and the United States-based Physicians(') Health Study cohort (1983-2003). A gene expression signature for prostate cancers with the TMPRSS2-ERG fusion was determined using partitioning and classification models and used in computational functional analysis. Cell proliferation and TMPRSS2-ERG expression in androgen receptor-negative (NCI-H660) prostate cancer cells after treatment with vehicle or estrogenic compounds were assessed by viability assays and quantitative polymerase chain reaction, respectively. All statistical tests were two-sided. RESULTS We identified an 87-gene expression signature that distinguishes TMPRSS2-ERG fusion prostate cancer as a discrete molecular entity (area under the curve = 0.80, 95% confidence interval [CI] = 0.792 to 0.81; P < .001). Computational analysis suggested that this fusion signature was associated with estrogen receptor (ER) signaling. Viability of NCI-H660 cells decreased after treatment with estrogen (viability normalized to day 0, estrogen vs vehicle at day 8, mean = 2.04 vs 3.40, difference = 1.36, 95% CI = 1.12 to 1.62) or ERbeta agonist (ERbeta agonist vs vehicle at day 8, mean = 1.86 vs 3.40, difference = 1.54, 95% CI = 1.39 to 1.69) but increased after ERalpha agonist treatment (ERalpha agonist vs vehicle at day 8, mean = 4.36 vs 3.40, difference = 0.96, 95% CI = 0.68 to 1.23). Similarly, expression of TMPRSS2-ERG decreased after ERbeta agonist treatment (fold change over internal control, ERbeta agonist vs vehicle at 24 hours, NCI-H660, mean = 0.57- vs 1.0-fold, difference = 0.43-fold, 95% CI = 0.29- to 0.57-fold) and increased after ERalpha agonist treatment (ERalpha agonist vs vehicle at 24 hours, mean = 5.63- vs 1.0-fold, difference = 4.63-fold, 95% CI = 4.34- to 4.92-fold). CONCLUSIONS TMPRSS2-ERG fusion prostate cancer is a distinct molecular subclass. TMPRSS2-ERG expression is regulated by a novel ER-dependent mechanism.
A CURRENT-MODE RMS-TO-DC CONVERTER BASED ON TRANSLINEAR PRINCIPLE

In this paper a low-power current-mode RMS-to-DC converter is proposed. The proposed converter includes absolute value circuit, squarer/divider circuit, low-pass filter and square root circuit which employ CMOS transistors operating in weak inversion region. The RMS-to-DC converter has low power consumption (<1μW), low supply voltage (0.9V), wide input range (from 50 nA to 500 nA), low relative error (<3 %), and low circuit complexity. Comparing the proposed circuit with two other current-mode circuits shows that the former outperforms the latters in terms of power dissipation, supply voltage, and complexity. Simulation results by HSPICE show high performance of the circuit and confirm the validity of the proposed design technique. Keywordscurrent-mode; RMS-to-DC converter; weak inversion; low power; low voltage ;
How to Repair Multi-agent Plans : Experimental Approach

Deterministic domain-independent multi-agent planning is an approach to coordination of cooperative agents with joint goals. Provided that the agents act in an imperfect environment, such plans can fail. The straightforward approach to recover from such situations is to compute a new plan from scratch, that is to replan. Even though, in a worst case, plan repair or plan re-use does not yield an advantage over replanning from scratch, there is a sound evidence from practical use that approaches trying to repair the failed original plan can outperform replanning in selected problems. One of the possible plan repairing techniques is based on preservation of
Chlamydophila pneumoniae Induces ICAM-1 Expression in Human Aortic Endothelial Cells via Protein Kinase C–Dependent Activation of Nuclear Factor-&kgr;B

Abstract— Chlamydophila pneumoniae has an epidemiological link with atherosclerosis and acute cardiovascular events. One mechanism that may explain such a link is the increased expression of intracellular adhesion molecule-1 (ICAM-1) in C pneumoniae–infected endothelial cells. Upregulation of ICAM-1 by C pneumoniae is well recognized and has been extensively studied, but the signaling pathways involved are not yet defined. Because upregulation of ICAM-1 by cytokines and other stimuli has been shown to be mediated by either mitogen-activated protein kinase, protein kinase C (PKC), or nuclear factor-&kgr;B (NF-&kgr;B) pathways, we examined whether these pathways were involved in the ICAM-1 upregulation induced by C pneumoniae. Our data show a time-dependent phosphorylation of p44/p42 and SAPK/JNK pathways in C pneumoniae–infected cells. However, inhibition of the classic mitogen-activated protein kinase pathway using the PD98059 and U0126 inhibitors and inhibition of SAPK/JNK pathway did not suppress C pneumoniae–induced ICAM-1 expression. C pneumoniae also activates the NF-&kgr;B pathway at 30 minutes after infection. Treatment of human aortic endothelial cells (HAECs) with the NF-&kgr;B inhibitors BAY117085 and caffeic acid phenethyl ester led to a concentration-dependent inhibition of C pneumoniae–induced ICAM-1 upregulation. Finally, C pneumoniae–infected HAECs show membrane translocation of total PKC 30 minutes after cell infection. Calphostin C, a general PKC inhibitor, blocked both C pneumoniae–induced ICAM-1 expression and C pneumoniae–induced NF-&kgr;B translocation. In conclusion, we demonstrated that C pneumoniae–induced ICAM-1 expression in HAECs requires NF-&kgr;B and PKC activation and that NF-&kgr;B activation is PKC dependent.
Social and Ecological Impact of PES Program in Arid Region: The case from Zhang-ye in Northwest China

This paper research provides applications of the integrated assessment approach, appraise effects of the payments for environmental services (PES) program in Zhang-ye from social and ecological impact. The results find that, from 2002 to 2004, the score of social impact (voluntary action and satisfaction) in all districts is more than 0.5, but ecological impact in almost countries is below 0.5. It indicates that we gain a better effect on social impact in the implementation of the PES program, but there is not better ecological impact in the implementation of the PES program.