OPTIMIZATION OF SURFACE ROUGHNESS OF AISI 304 AUSTENITIC STAINLESS STEEL IN DRY TURNING OPERATION USING TAGUCHI DESIGN METHOD

The present work is concentrated with the dry turning of AISI 304 Austenitic Stainless Steel (ASS). This paper presents the influence of cutting parameters like cutting speed, feed rate and depth of cut on the surface roughness of austenitic stainless steel during dry turning. A plan of experiments based on Taguchi’s technique has been used to acquire the data. An orthogonal array, the signal to noise (S/N) ratio and the analysis of variance (ANOVA) are employed to investigate the cutting characteristics of AISI 304 austenitic stainless steel bars using TiC and TiCN coated tungsten carbide cutting tool. Finally the confirmation tests that have been carried out to compare the predicted values with the experimental values confirm its effectiveness in the analysis of surface roughness

Psychology input to an orthognathic clinic: patients' perception of service quality

Aims: The aim of this study was to assess patient satisfaction with a clinical psychology service, integrated within an inter-disciplinary orthognathic planning clinic. Method: A self-report, custom-designed questionnaire was sent to patients who had completed orthognathic treatment within the last three years. Of the 60 patients approached, 49 responded. Results: The great majority of patients agreed that there was a need for a psychological assessment and that its purpose was adequately explained. Most patients were happy with the information given during their appointment and found the experience helpful. A number of patients felt that additional appointments would have been helpful shortly before, and after, surgery. Conclusions: The group of orthognathic patients studied found the pre-treatment psychology assessment, provided for them through the combined clinic, to be very acceptable and beneficial. Some suggested that further appointments, throughout the treatment journey, as well as supportive literature, might also have been helpful

EXPERIMENTAL INVESTIGATIONS OF NITROGEN ALLOYED DUPLEX STAINLESS STEEL IN DRY MILLING PROCESS

Duplex stainless steels are generally more difficult to cut because of their high toughness, low heat conductivity, more strain hardening rate and more built-up edge formation. Milling is an important machining process for manufacturing flat, curved and profiled surfaces. In this work, an attempt has been taken to investigate the machining performance of two different types of cast duplex stainless steels in dry milling operation using coated tungsten carbide tools. A 15 run experiment was designed to investigate the effect of spindle speed and feed rate on the surface roughness and cutting force. The end milling experiments were conducted with five different spindle speeds and three different feed rates with a constant axial depth of cut. The result revealed that the increasing spindle speed decreased the surface roughness and the cutting force values up to 1000 rpm and then increased. The increase of feed rate increased the surface roughness and cutting force values. The presence of higher austenite in 5A grade duplex stainless steel was responsible for higher surface roughness and cutting force values compared with 4A grade duplex stainless steel

Lifetime cancer risk and combined oral contraceptives : the Royal College of General Practitioners’ Oral Contraception Study

Funding: The study has received funding from the Royal College of General Practitioners, Medical Research Council, Imperial Cancer Research Fund, British Heart Foundation, Schering AG, Schering Health Care Ltd, Wyeth Ayerst International, Ortho Cilag and, Searle. None of these funders have contributed to the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review or approval of the manuscript.Peer reviewedPostprin

Investigating the performance of 410, PH13-8Mo and 300M steels in a turning process with a focus on surface finish

This study generated novel behavioural data for three engineering steels undergoing a turning process. The materials were hardened 410, PH13-8Mo and 300M, two stainless steels and one high strength steel respectively. A primary aim was obtaining low machined surface roughness. A surface finish investigation compared tool geometries and tool materials. Multi-response cutting parameter screening was undertaken using a novel trade study and iteration method, where the calculated cut quality was used to identify better feed rates and surface speeds. In addition the sub-surface machined microstructure was examined. Tools with a small nose radius produced the roughest surfaces. A surface roughness below 0.4 μm Ra could be consistently achieved on all three materials using rhombic wiper inserts and a feed rate up to 0.1 mm/rev. PH13-8Mo had the lowest machined surface roughness, as low as 0.11 μm in terms of Ra. In the parameter screening stage a generalised recommendation for good cut quality was a surface speed of at least 120 m/min and a feed rate of 0.088 mm/rev. The microstructure examination showed that for all materials under the conditions tested, there was no evidence of white amorphous layer formation and there was grain deformation for the 410 material only

HNRNPK alleviates RNA toxicity by counteracting DNA damage in C9orf72 ALS

A 'GGGGCC' repeat expansion in the first intron of the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The exact mechanism resulting in these neurodegenerative diseases remains elusive, but C9 repeat RNA toxicity has been implicated as a gain-of-function mechanism. Our aim was to use a zebrafish model for C9orf72 RNA toxicity to identify modifiers of the ALS-linked phenotype. We discovered that the RNA-binding protein heterogeneous nuclear ribonucleoprotein K (HNRNPK) reverses the toxicity of both sense and antisense repeat RNA, which is dependent on its subcellular localization and RNA recognition, and not on C9orf72 repeat RNA binding. We observed HNRNPK cytoplasmic mislocalization in C9orf72 ALS patient fibroblasts, induced pluripotent stem cell (iPSC)-derived motor neurons and post-mortem motor cortex and spinal cord, in line with a disrupted HNRNPK function in C9orf72 ALS. In C9orf72 ALS/FTD patient tissue, we discovered an increased nuclear translocation, but reduced expression of ribonucleotide reductase regulatory subunit M2 (RRM2), a downstream target of HNRNPK involved in the DNA damage response. Last but not least, we showed that increasing the expression of HNRNPK or RRM2 was sufficient to mitigate DNA damage in our C9orf72 RNA toxicity zebrafish model. Overall, our study strengthens the relevance of RNA toxicity as a pathogenic mechanism in C9orf72 ALS and demonstrates its link with an aberrant DNA damage response, opening novel therapeutic avenues for C9orf72 ALS/FTD.</p

Effect of Citalopram on Emotion Processing in Humans:A Combined 5-HT [C]CUMI-101 PET and Functional MRI Study

A subset of patients started on a selective serotonin reuptake inhibitor (SSRI) initially experience increased anxiety, which can lead to early discontinuation before therapeutic effects are manifest. The neural basis of this early SSRI effect is not known. Presynaptic dorsal raphe neuron (DRN) 5-HT1A receptors are known to play a critical role in affect processing. Thus we investigated the effect of acute citalopram on emotional processing and the relationship between DRN 5-HT1A receptor availability and amygdala reactivity. Thirteen (mean age 48±9 years) healthy male subjects received either a saline or citalopram infusion intravenously (10 mg over 30 min) on separate occasions in a single-blind, random order, cross-over design. On each occasion, participants underwent a block design face-emotion processing task during fMRI known to activate the amygdala. Ten subjects also completed a positron emission tomography (PET) scan to quantify DRN 5-HT1A availability using [(11)C]CUMI-101.Citalopram infusion when compared to saline resulted in a significantly increased bilateral amygdala responses to fearful vs. neutral faces (Left p=0.025; Right p=0.038 FWE-corrected). DRN [(11)C]CUMI-101availability significantly positively correlated with the effect of citalopram on the left amygdala response to fearful faces (Z=2.51, p=0.027) and right amygdala response to happy faces (Z=2.33, p=0.032). Our findings indicate that the initial effect of SSRI treatment is to alter processing of aversive stimuli, and that this is linked to DRN 5-HT1A receptors in line with evidence that 5-HT1A receptors have a role in mediating emotional processing

C9orf72-derived arginine-containing dipeptide repeats associate with axonal transport machinery and impede microtubule-based motility

A hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). How this mutation leads to these neurodegenerative diseases remains unclear. Here, we show using patient stem cell-derived motor neurons that the repeat expansion impairs microtubule-based transport, a process critical for neuronal survival. Cargo transport defects are recapitulated by treating neurons from healthy individuals with proline-arginine and glycine-arginine dipeptide repeats (DPRs) produced from the repeat expansion. Both arginine-rich DPRs similarly inhibit axonal trafficking in adult Drosophila neurons in vivo. Physical interaction studies demonstrate that arginine-rich DPRs associate with motor complexes and the unstructured tubulin tails of microtubules. Single-molecule imaging reveals that microtubule-bound arginine-rich DPRs directly impede translocation of purified dynein and kinesin-1 motor complexes. Collectively, our study implicates inhibitory interactions of arginine-rich DPRs with axonal transport machinery in C9orf72-associated ALS/FTD and thereby points to potential therapeutic strategies.</p

C9orf72-derived arginine-containing dipeptide repeats associate with axonal transport machinery and impede microtubule-based motility

A hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). How this mutation leads to these neurodegenerative diseases remains unclear. Here, we show using patient stem cell-derived motor neurons that the repeat expansion impairs microtubule-based transport, a process critical for neuronal survival. Cargo transport defects are recapitulated by treating neurons from healthy individuals with proline-arginine and glycine-arginine dipeptide repeats (DPRs) produced from the repeat expansion. Both arginine-rich DPRs similarly inhibit axonal trafficking in adult Drosophila neurons in vivo. Physical interaction studies demonstrate that arginine-rich DPRs associate with motor complexes and the unstructured tubulin tails of microtubules. Single-molecule imaging reveals that microtubule-bound arginine-rich DPRs directly impede translocation of purified dynein and kinesin-1 motor complexes. Collectively, our study implicates inhibitory interactions of arginine-rich DPRs with axonal transport machinery in C9orf72-associated ALS/FTD and thereby points to potential therapeutic strategies.</p