ANALISIS PENGENDALIAN KUALITAS SIX SIGMA DENGAN METODE DEFINE, MEASURE, ANALYZE, IMPROVE, CONTROL (DMAIC) TERHADAP LINI Z PROSES PRODUKSI MOBIL KIJANG PADA PT. TOYOTA MOTOR MANUFACTURING INDONESIA

PT. Toyota Motor Manufacturing Indonesia (TMMI) sebagai salah satu perusahaan otomotif terkemuka di Indonesia dengan salah satu produk unggulannya yaitu mobil kijang berusaha meningkatkan kualitas produk yang dihasilkannya. Salah satu program peningkatan kualitas yang dapat menjadi pilihan dan telah terbukti keefektifannya adalah “Six-Sigma”, yaitu pada GE Company dan Motorola. Program peningkatan kualitas yang diusulkan pada penulisan skripsi ini berfokus pada departemen produksi khususnya pada QE ( Quality Engineering) dengen harapan hasil dari penerapan penelitian dengan metode ini akan memberikan usulan yang berguna bagi perbaikan kualitas proses produksi. Data-data masukan yang digunakan diperoleh selama berada di PT. TMMI sejak bulan Agustus-September 2003, baik secara tertulis maupun secara lisan. Sesuai dengan prinsip Six Sigma yang berfokus pada pelanggan dan berorientasi pada proses maka akan berpengaruh pada hasil akhir yang diharapkan. Metode yang digunakan dalam proses pengolahan data adalah DMAIC (Define, Measure, Analyze, Improve, Control). Proses pengolahan data dimulai dari pendefinisian masalah yang akan dipecahkan, melakukan pengukuran terhadap data, menganalisis hasil pengukuran data, memperbaiki kesalahan produk yang didapatkan, dan kemudian mengendalikan usaha perbaikan yang telah dilakukan. Berdasarkan hasil penelitian, pada tahap define diketahui bahwa jenis cacat terbesar pada lini produksi Z adalah bari. Pada tahap measure diketahui data berdistribusi normal dengan CTQ sebanyak 21 buah dan kinerja berada pada tingkat 4,7 sigma dengan nilai DPMO sebesar 732. Pada tahap analyze diketahui indeks kapabilitas proses sebesar 0,984631, sumber penyebab permasalahan terdapat pada faktor mesin, manusia, dan lingkungan. Pada tahap improve ditetapkan suatu rencana tindakan terhadap sumber-sumber dan akar penyebab dari masalah kualitas yang telah teridentifikasi pada tahap-tahap sebelumnya. Pada tahap terakhir yaitu control, usulan peningkatan kualitas didokumentasikan dan distandarisasikan agar dapat disebarluaskan dengan menggunakan metode 5W -2H

Structure-stiffness relation of live mouse brain tissue determined by depth-controlled indentation mapping

The mechanical properties of brain tissue play a pivotal role in neurodevelopment and neurological disorders. Yet, at present, there is no consensus on how the different structural parts of the tissue contribute to its stiffness variations. Here, we have gathered depth-controlled indentation viscoelasticity maps of the hippocampus of isolated horizontal live mouse brain sections. Our results confirm the highly viscoelestic nature of the material and clearly show that the mechanical properties correlate with the different morphological layers of the samples investigated. Interestingly, the relative cell nuclei area seems to negatively correlate with the stiffness observed

Impaired Social Behavior in 5-HT3A Receptor Knockout Mice

The 5-HT3 receptor is a ligand-gated ion channel expressed on interneurons throughout the brain. So far, analysis of the 5-HT3A knockout mouse revealed changes in nociceptive processing and a reduction in anxiety related behavior. Recently, it was shown that the 5-HT3 receptor is also expressed on Cajal-Retzius cells which play a key role in cortical development and that knockout mice lacking this receptor showed aberrant growth of the dendritic tree of cortical layer II/III pyramidal neurons. Other mouse models in which serotonergic signaling was disrupted during development showed similar morphological changes in the cortex, and in addition, also deficits in social behavior. Here, we subjected male and female 5-HT3A knockout mice and their non-transgenic littermates to several tests of social behavior. We found that 5-HT3A knockout mice display impaired social communication in the social transmission of food preference task. Interestingly, we showed that in the social interaction test only female 5-HT3A knockout mice spent less time in reciprocal social interaction starting after 5 min of testing. Moreover, we observed differences in preference for social novelty for male and female 5-HT3A knockout mice during the social approach test. However, no changes in olfaction, exploratory activity and anxiety were detected. These results indicate that the 5-HT3A knockout mouse displays impaired social behavior with specific changes in males and females, reminiscent to other mouse models in which serotonergic signaling is disturbed in the developing brain

Alterations in Apical Dendrite Bundling in the Somatosensory Cortex of 5-HT3A Receptor Knockout Mice

In various species and areas of the cerebral cortex, apical dendrites of pyramidal neurons form clusters which extend through several layers of the cortex also known as dendritic bundles. Previously, it has been shown that 5-HT3A receptor knockout mice show hypercomplex apical dendrites of cortical layer 2/3 pyramidal neurons, together with a reduction in reelin levels, a glycoprotein involved in cortical development. Other studies showed that in the mouse presubicular cortex, reelin is involved in the formation of modular structures. Here, we compare apical dendrite bundling in the somatosensory cortex of wildtype and 5-HT3A receptor knockout mice. Using a microtubule associated protein-2 immunostaining to visualize apical dendrites of pyramidal neurons, we compared dendritic bundle properties of wildtype and 5-HT3A receptor knockout mice in tangential sections of the somatosensory cortex. A Voronoi tessellation was performed on immunostained tangential sections to determine the spatial organization of dendrites and to define dendritic bundles. In 5-HT3A receptor knockout mice, dendritic bundle surface was larger compared to wildtype mice, while the number and distribution of reelin-secreting Cajal–Retzius cells was similar for both groups. Together with previously observed differences in dendritic complexity of cortical layer 2/3 pyramidal neurons and cortical reelin levels, these results suggest an important role for the 5-HT3 receptor in determining the spatial organization of cortical connectivity in the mouse somatosensory cortex

A feasibility study to investigate chemogenetic modulation of the locus coeruleus by means of single unit activity

Aim: Selective chemogenetic modulation of locus coeruleus (LC) neurons would allow dedicated investigation of the role of the LC-NA pathway in brain excitability and disorders such as epilepsy. This study investigated the feasibility of an experimental set-up where chemogenetic modification of the brainstem locus coeruleus NA neurons is aimed at and followed by LC unit activity recording in response to clozapine. Methods: The LC of male Sprague-Dawley rats was injected with 10 nl of adeno-associated viral vector AAV2/7-PRSx8-hM3Dq-mCherry (n = 19, DREADD group) or AAV2/7-PRSx8-eGFP (n = 13, Controls). Three weeks later, LC unit recordings were performed in anesthetized rats. We investigated whether clozapine, a drug known to bind to modified neurons expressing hM3Dq receptors, was able to increase the LC firing rate. Baseline unit activity was recorded followed by subsequent administration of 0.01 and 0.1 mg/kg of clozapine in all rats. hM3Dq-mcherry expression levels were investigated using immunofluorescence staining of brainstem slices at the end of the experiment. Results: Unit recordings could be performed in 12 rats and in a total of 12 neurons (DREADDs: n = 7, controls: n = 5). Clozapine 0.01 mg/kg did not affect the mean firing rate of recorded LC-neurons; 0.1 mg/kg induced an increased firing rate, irrespective whether neurons were recorded from DREADD or control rats (p = 0.006). Co-labeling of LC neurons and mCherry-tag showed that 20.6 +/- 2.3% LC neurons expressed the hM3Dq receptor. Aspecific expression of hM3Dq-mCherry was also observed in non-LC neurons (26.0 +/- 4.1%). Conclusion: LC unit recording is feasible in an experimental set-up following manipulations for DREADD induction. A relatively low transduction efficiency of the used AAV was found. In view of this finding, the effect of injected clozapine on LC-NA could not be investigated as a reliable outcome parameter for activation of chemogenetically modified LC neurons. The use of AAV2/7, a vector previously applied successfully to target dopaminergic neurons in the substantia nigra, leads to insufficient chemogenetic modification of the LC compared to transduction with AAV2/9

Long-term effect of chemogenetic suppression of excitatory hippocampal neurons on spontaneous seizures in a rat model for temporal lobe epilepsy

Objective. One third of epilepsy patients cannot be helped using conventional medication. Selective hippocampal suppression using Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) have potential to address this unmet need. We evaluated whether DREADD-mediated seizure suppression could be obtained in the intraperitoneal kainic acid (IPKA) rat model for temporal lobe epilepsy. Methods. The inhibitory DREADD hM4Di was selectively expressed in excitatory neurons in one hippocampus of IPKA rats. Naïve IPKA rats were included as control group. The effect of clozapine-mediated DREADD activation on dentate gyrus evoked potentials (DGEPs) was evaluated. Next, the effect of DREADD activation on spontaneous seizures was examined using continuous video-electroencephalography. Animals were systemically treated with single (0.1 mg/kg/24h) and repeated (0.1 mg/kg/6h) clozapine injections. Finally, long-term continuous release of clozapine and olanzapine (both 2.8 mg/kg/7d) using implantable osmotic minipumps was evaluated. Results. In the DREADD group, inhibition of DGEPs was observed after clozapine treatment, whereas no effect was observed in control animals. Only in DREADD-expressing animals, a single dose of clozapine reduced seizure frequency during the first six hours post injection. When clozapine was administered every six hours, seizures were suppressed the entire day. Long term treatment resulted in a significant seizure-suppressing effect during the first four days, after which tolerance developed. Significance. This study shows that unilateral inhibition of hippocampus using chemogenetics results in potent seizure suppressing effects in the IPKA rat model, even months after vector injection. It indicates that chemogenetic neuromodulation could contribute to a more optimal treatment for temporal lobe epilepsy

No persistent effects of intracerebral curcumin administration on seizure progression and neuropathology in the kindling rat model for temporal lobe epilepsy

PURPOSE: Curcumin is known for its neuroprotective, anti-inflammatory and anti-oxidant properties and has been investigated as a potential therapeutic drug for Temporal Lobe Epilepsy (TLE). We previously found anti-epileptogenic properties of curcumin in an in vitro brain slice model for epileptogenesis, and inhibitory effects on the MAPK-pathway in vivo after intracerebrally applying curcumin in post-status epilepticus rats. Here, we investigated whether the intracerebral application of curcumin could be anti-epileptogenic in the rapid kindling rat model for TLE. METHODS: Curcumin or vehicle was injected directly into the brain through an intracerebral ventricular cannula at 5 consecutive days during the kindling process. Kindling consisted of repeated electrical stimulations of the angular bundle (12 times a day with a 30 min interval) every other day, until rats were fully kindled or until 36 stimulations were administered. One week after kindling acquisition, additional kindling stimulations were applied in a re-test in the absence of curcumin- or vehicle treatment. RESULTS: Curcumin-treated rats required more stimulations compared to vehicle-treated rats to reach Racine stage IV seizures, indicating that curcumin delayed seizure development. However, it did not prevent the fully kindled state as shown in the re-test. Increasing the dose of curcumin did not produce a delay in seizure development. Immunohistochemistry showed that kindling produced cell loss, astrogliosis, mossy fiber sprouting and neurogenesis in the dentate gyrus, which were not different between vehicle- and curcumin-treated groups. CONCLUSION: Although curcumin's effects on neuropathology were not detected and the delay of kindling development was transient, the data warrant further exploration of its anti-epileptogenic potential using formulations that further increase its bioavailability