True to oneself? Broad and narrow ideas on authenticity in the enhancement debate

Our knowledge of the human brain and the influence of pharmacological substances on human mental functioning is expanding. This creates new possibilities to enhance personality and character traits. Psychopharmacological enhancers, as well as other enhancement technologies, raise moral questions concerning the boundary between clinical therapy and enhancement, risks and safety, coercion and justice. Other moral questions include the meaning and value of identity and authenticity, the role of happiness for a good life, or the perceived threats to humanity. Identity and authenticity are central in the debate on psychopharmacological enhancers. In this paper, I first describe the concerns at issue here as extensively propounded by Carl Elliott. Next, I address David DeGrazia’s theory, which holds that there are no fundamental identity-related and authenticity-related arguments against enhancement technologies. I argue, however, that DeGrazia’s line of reasoning does not succeed in settling these concerns. His conception of identity does not seem able to account for the importance we attach to personal identity in␣cases where personal identity is changed through enhancement technology. Moreover, his conception of authenticity does not explain the reason why we find inauthentic values objectionable. A broader approach to authenticity can make sense of concerns about changes in personal identity by means of enhancement technologies

Remodeling and control of homologous recombination by DNA helicases and translocases that target recombinases and synapsis

Recombinase enzymes catalyse invasion of single-stranded DNA (ssDNA) into homologous duplex DNA forming "Displacement loops" (D-loops), a process called synapsis. This triggers homologous recombination (HR), which can follow several possible paths to underpin DNA repair and restart of blocked and collapsed DNA replication forks. Therefore, synapsis can be a checkpoint for controlling whether or not, how far, and by which pathway, HR proceeds to overcome an obstacle or break in a replication fork. Synapsis can be antagonized by limiting access of a recombinase to ssDNA and by dissociation of D-loops or heteroduplex formed by synapsis. Antagonists include DNA helicases and translocases that are identifiable in eukaryotes, bacteria and archaea, and which target synaptic and pre-synaptic DNA structures thereby controlling HR at early stages. Here we survey these events with emphasis on enabling DNA replication to be resumed from sites of blockage or collapse. We also note how knowledge of anti-recombination activities could be useful to improve efficiency of CRISPR-based genome editing

High Speed Photometry of SDSS J013701.06-091234.9

We present high speed photometry of the Sloan Digital Sky Survey cataclysmic variable SDSS J013701.06-091234.9 in quiescence and during its 2003 December superoutburst. The orbital modulation at 79.71\pm0.01 min is double humped; the superhump period is 81.702\pm0.007 min. Towards the end of the outburst late superhumps with a period of 81.29\pm0.01 min were observed. We argue that this is a system of very low mass transfer rate, and that it probably has a long outburst interval.Comment: 5 pages, 8 figures. Accepted for publication in MNRA

The development of the Meaning in Life Index (MILI) and its relationship with personality and religious behaviours and beliefs among UK undergraduate students

The scales available for assessing meaning in life appear to be confounded with several related constructs, including purpose in life, satisfaction with life, and goal-directed behaviour. The Meaning in Life Index (MILI), a new instrument devised as a specific measure of meaning in life, was developed from responses to a pool of 22 items rated by a sample of 501 undergraduate students in Wales. The nine-item scale demonstrated sufficient face validity, internal consistency, and scale reliability to commend the instrument for future use. With respect to personality, the MILI scores were most strongly predicted by neuroticism (negatively), and less strongly by extraversion (positively) and psychoticism (negatively). With respect to several religious behavioural variables, those who attended church at least weekly returned significantly higher MILI scores than those who attended church less frequently. Intrinsic religiosity was the only orientation to be significantly associated with the MILI scale scores, although the magnitude of the association was smaller than anticipated. These results suggest that meaning in life is associated more strongly with individual differences in personality than with specific religious behaviours and attitudes. The implications of these results are discussed in terms of individual's personal values and attitudes that might underlie their experience of a meaning in life

Cathepsin-D in primary breast cancer: prognostic evaluation involving 2810 patients

There is controversy regarding the prognostic value of cathepsin-D in primary breast cancer. An increased level of cathepsin-D in tumour extracts has been found to be associated with a poor relapse-free and overall survival. Studies performed with immunohistochemistry or Western blotting have produced diverse results. We have analysed 2810 cytosolic extracts obtained from human primary breast tumours for cathepsin-D expression, and have correlated their levels with prognosis. The median follow-up of the patients still alive was 88 months. Patients with high cathepsin-D levels had a significantly worse relapse-free and overall survival, also in multivariate analysis (P < 0.0001). Adjuvant therapy which was associated with an improved prognosis in node-positive patients in univariate analysis, also significantly added to the multivariate models for relapse-free and overall survival. There were no statistically significant interactions between the levels of cathepsin-D and any of the classical prognostic factors in analysis for relapse-free survival, suggesting that the prognostic value of cathepsin-D is not different in the various subgroups of patients. Indeed, multivariate analyses in subgroups of node-negative and -positive patients, pre- and post-menopausal patients, and their combinations, showed that tumours with high cathepsin-D values had a significantly poor relapse-free survival, with relative hazard rates ranging from 1.3 to 1.5, compared with tumours with low cathepsin-D levels. The results presented here on 2810 patients confirm that high cytosolic cathepsin-D values are associated with poor prognosis in human primary breast cancer. © 1999 Cancer Research Campaig

Pretending to be a Normal Human Being: Peep Show, Sitcom, and the Momentary Invocation of Disability

This interdisciplinary article presents research about the place of disability in the British sitcom Peep Show, whose 54 episodes span more than a decade in their transmission (2003-2015). The methodology of Critical Discourse Analysis is employed to probe the relationship between casual word choice and broader themes such as normalcy, humour, and social attitudes. This analysis is informed by classic and new work in cultural disability studies, as well as by work in literary studies and television studies. The conclusion is that, despite its apparent irrelevance to disability studies, Peep Show reveals much about conversational invocations of disability

Cas1–Cas2 physically and functionally interacts with DnaK to modulate CRISPR Adaptation

Prokaryotic Cas1-Cas2 protein complexes generate adaptive immunity to mobile genetic elements (MGEs), by capture and integration of MGE DNA in to CRISPR sites. De novo immunity relies on naive adaptation-Cas1-Cas2 targeting of MGE DNA without the aid of pre-existing immunity 'interference' complexes-by mechanisms that are not clear. Using E. coli we show that the chaperone DnaK inhibits DNA binding and integration by Cas1-Cas2, and inhibits naive adaptation in cells that results from chro-mosomal self-targeting. Inhibition of naive adaptation was reversed by deleting DnaK from cells, by mutation of the DnaK substrate binding domain, and by expression of an MGE (phage) protein. We also imaged fluorescently labelled Cas1 in living cells, observing that Cas1 foci depend on active DNA replica-tion, and are much increased in frequency in cells lacking DnaK. We discuss a model in which DnaK provides a mechanism for restraining naive adaptation from DNA self-targeting, until DnaK is triggered to release Cas1-Cas2 to target MGE DNA

Assessing the impact of chemotherapy-induced peripheral neurotoxicity on the quality of life of cancer patients: The introduction of a new measure

Item does not contain fulltextPURPOSE: To investigate the impact of chemotherapy-induced neurotoxicity on daily activities and quality of life (QoL) of cancer patients. METHODS: QoL of all patients visiting the oncological outpatient ward of the Maxima Medical Centre in the Netherlands from October 2006 until March 2007 treated with taxanes, vinca-alkaloids and/or platinum compounds (n = 88) was compared with the QoL of patients that did not receive these treatments yet (n = 43). Patient-reported neuropathy symptoms were evaluated with the newly developed Chemotherapy Induced Neurotoxicity Questionnaire (CINQ) and the Functional Assessment of Cancer Therapy/Gynaecologic Oncology Group/Neurotoxicity (FACT/GOG-Ntx) questionnaire. RESULTS: Patients treated with chemotherapy reported significantly more complaints of neuropathy (p < 0.001) and more paresthesias and dysesthesias in the upper (p < 0.001; p < 0.01) and lower extremities (p < 0.001) compared to those not treated with chemotherapy. They additionally experienced problems with fine motor function (e.g., getting (un)dressed, writing, and picking up small objects). Moreover, cold-induced paresthesias were frequently reported. Overall, patients indicated that their neuropathy had a negative effect on QoL. CONCLUSIONS: The newly developed CINQ and the FACT/GOG-Ntx results suggest a considerable negative impact of patient-reported neuropathy symptoms on daily activities and QoL in cancer patients treated with chemotherapy. However, further validation of the CINQ is needed