Beszállítófejlesztés és lean beszállítófejlesztés = Supplier development and lean supplier development

A tanulmány általános áttekintést ad a beszállítófejlesztésről. A szakmában elterjedt fogalmak, a meghatározó koncepcionális keretek, az ajánlott szervezeti megoldások és az eredményes megvalósítást támogató és gátló tényezők számba vétele arra szolgál, hogy tág kontextusban értelmezhessük a lean beszállítófejlesztést. A lean beszállítófejlesztés intézményesített szervezeti rutinok halmazát jelenti – a japán autóipari nagyvállalatok gyakorlata alapján. Egyszerre van jelen az ad hoc problémamegoldás és a folyamatorientált, tág és stratégiai beszállítófejlesztés. A kulcsbeszállítók állnak a középpontban. A beszállítókkal való együttműködésben a bilaterális kapcsolatok (beszerző-beszállító) és a multilaterális kapcsolatok (beszerző és beszállítók csoportja) is fontos szereppel bírnak. A tevékenységek megvalósításában több tucat alkalmazott főállásban vesz részt. Ezek az alkalmazottak a beszerző vállalat termelési rendszerének, működési filozófiájának is szakértői. A globális nagyvállalatoknál – adott régióban is – több osztály, esetenként egymástól függetlenül is foglalkozik a beszállítók fejlesztésével. A sikeres megvalósítást és részvételt, elköteleződést támogatja, hogy az ösztönzési rutinok is formalizáltak és intézményesítettek (pl. hatalmi kérdések, elért haszon megosztása, partnerek felelőssége). _____ Our study reviews supplier development (SD) and lean supplier development literature. The first part gives an overview about general SD and related definitions, conceptual frameworks, organisational settings and supporting/impeding factors influencing the success of SD efforts. The second part of the study positions lean supplier development in this general SD context. Lean SD is built on sets of institutionalized organisational routines – based on daily practice of Japanese automotive companies. Lean SD contains of different SD approaches. It is pervaded by both ad hoc problem solving activities and process-focused, wide and strategic approaches at the same time. The efforts are focused on key suppliers. The SD is organised through bilateral (purchaser firm and supplier firm) and multilateral (purchaser firm and supplier firms) relations. At global automotive companies more dozens full time employees work on SD. These employees are expert of the production system and operating philosophy of the purchaser company. Global firms – even in a particular geographical area – have usually more departments responsible for SD. Eventually these departments work independently from each other. To achieve the expected performance improvement and real involvement and commitment it is critical to formalize and institutionalize routines influencing motivation as well (eg., power, gain sharing, responsibilities).

The social values of wireless technology in the institutional context

Despite growing attention, social values, compared to economic aspects, of information technology (IT) capture substantially less attention in the mainstream IT literature. In the context of mobile technology, social values might be as critical to help justify technology investment as the predominant economics perspective in the existing IT literature. As wireless networks and relevant mobile technologies continue to penetrate the global society and business world, an emerging social phenomenon rapidly reshapes how organizations interact with the technology and reposition themselves in their specific institutional context where organizations often develop networked alliance to compete against one another. This study thus seeks to shed light on how organizations make sense of the social aspects of wireless network implementation. Preliminary understanding derived from two higher education organizations' experiences is summarized. Implications for future research endeavor are suggested.

Soundscape Ecology of Hawaiian Spinner Dolphin Resting Bays

Sound is a key sensory modality for Hawaiian spinner dolphins. Like many other marine animals, these dolphins rely on sound and their acoustic environment for many aspects of their daily lives, making it is essential to understand soundscape in areas that are critical to their survival. Hawaiian spinner dolphins rest during the day in shallow coastal areas and forage offshore at night. In my dissertation I focus on the soundscape of the bays where Hawaiian spinner dolphins rest taking a soundscape ecology approach. I primarily relied on passive acoustic monitoring using four DSG-Ocean acoustic loggers in four Hawaiian spinner dolphin resting bays on the Kona Coast of Hawai‛i Island. 30-second recordings were made every four minutes in each of the bays for 20 to 27 months between January 8, 2011 and March 30, 2013. I also utilized concomitant vessel-based visual surveys in the four bays to provide context for these recordings. In my first chapter I used the contributions of the dolphins to the soundscape to monitor presence in the bays and found the degree of presence varied greatly from less than 40% to nearly 90% of days monitored with dolphins present. Having established these bays as important to the animals, in my second chapter I explored the many components of their resting bay soundscape and evaluated the influence of natural and human events on the soundscape. I characterized the overall soundscape in each of the four bays, used the tsunami event of March 2011 to approximate a natural soundscape and identified all loud daytime outliers. Overall, sound levels were consistently louder at night and quieter during the daytime due to the sounds from snapping shrimp. In fact, peak Hawaiian spinner dolphin resting time co-occurs with the quietest part of the day. However, I also found that humans drastically alter this daytime soundscape with sound from offshore aquaculture, vessel sound and military mid-frequency active sonar. During one recorded mid-frequency active sonar event in August 2011, sound pressure levels in the 3.15 kHz 1/3rd-octave band were as high as 45.8 dB above median ambient noise levels. Human activity both inside (vessels) and outside (sonar and aquaculture) the bays significantly altered the resting bay soundscape. Inside the bays there are high levels of human activity including vessel-based tourism directly targeting the dolphins. The interactions between humans and dolphins in their resting bays are of concern; therefore, my third chapter aimed to assess the acoustic response of the dolphins to human activity. Using days where acoustic recordings overlapped with visual surveys I found the greatest response in a bay with dolphin-centric activities, not in the bay with the most vessel activity, indicating that it is not the magnitude that elicits a response but the focus of the activity. In my fourth chapter I summarize the key results from my first three chapters to illustrate the power of multiple site design to prioritize action to protect Hawaiian spinner dolphins in their resting bays, a chapter I hope will be useful for managers should they take further action to protect the dolphins.

Insights into Nonpilus Adhesin Functionality and the Molecular Determinants of Nontypeable Haemophilus influenzae Colonization

Bacterial colonization of the upper respiratory tract is the first step in the pathogenesis of nontypeable Haemophilus influenzae (NTHi) disease. Examination of the determinants of NTHi colonization process has been hampered by the lack of an appropriate animal model. To address this, we have developed a model of NTHi colonization in adult rhesus macaques that involves intranasal inoculation of 1x105 CFU and results in persistent colonization of the upper respiratory tract for at least three weeks with no signs of disease, mimicking asymptomatic colonization of humans. Using this model, we assessed the contributions to colonization of the HMW1 and HMW2 adhesive proteins. In competition experiments, the parent strain expressing both HMW1 and HMW2 was able to efficiently out-compete an isogenic mutant strain expressing neither HMW1 nor HMW2. In experiments involving inoculation of single isogenic derivatives of NTHi strain 12, the strains expressing HMW1 or HMW2 or both were able to colonize efficiently, while the strain expressing neither HMW1 nor HMW2 colonized inefficiently. Furthermore, colonization resulted in antibody production against HMW1 and HMW2 in one-third of the animals, demonstrating that colonization can be an immunizing event. In conclusion, we have established that NTHi is capable of colonizing the upper respiratory tract of rhesus macaques, in some cases associated with stimulation of an immune response. The HMW1 and HMW2 adhesive proteins play a major role in the process of colonization.

After establishing that the HMW1 and HMW2 proteins are colonization factors we further investigated the determinants of HMW1 function. HMW1 is encoded in the same genetic locus as two other proteins, HMW1B and HMW1C, with which HMW1 must interact in order to be functional. Interaction with HMW1C in the cytoplasm results in the glycosylation of HMW1. By employing homologues of HMW1C that glycosylate HMW1 in slightly different patterns we show that the pattern of modification is critical to HMW1 function. Structural analysis showed a change in protein structure when the pattern of HMW1 modification differed. We also identified two specific sites which must be glycosylated for HMW1 to function properly. These point mutations did not have a significant effect on protein structure, suggesting that glycosylation at those specific sites is instead necessary for interaction of HMW1 with its receptor. HMW1B is an outer membrane pore through which HMW1 is transported to reach the bacterial cell surface. We observed that HMW1 isolated from the cytoplasm has a different structure than HMW1 isolated from the bacterial cell surface. By forcing HMW1 to be secreted in a non-HMW1B dependent manner, we show that secretion alone is not sufficient for HMW1 to obtain a functional structure. This leads us to hypothesize that there is something specific in the interaction between HMW1 and HMW1B that aids in proper HMW1 folding.

The NTHi HMW1C glycosyltransferase mediates unconventional N-linked glycosylation of HMW1. In this system, HMW1 is modified in the cytoplasm by sequential transfer of hexose residues. To determine if this mechanism of N-linked glycosylation is employed by species other than NTHi, we examined Kingella kingae and Aggregatibacter aphrophilus homologues of HMW1C. We found both homologues to be functional glycosyltransferases and identified their substrates as the K. kingae Knh and the A. aphrophilus EmaA trimeric autotransporter proteins. LC-MS/MS analysis revealed multiple sites of N-linked glycosylation on Knh and EmaA. Without glycosylation, Knh and EmaA failed to facilitate wild type levels of bacterial autoaggregation or adherence to human epithelial cells, establishing that glycosylation is essential for proper protein function.

Transcriptome and Functional Analysis of Carotid Body Glomus Cells

The carotid body (CB) is a major arterial chemoreceptor containing glomus cells that are activated by changes in arterial blood contents including oxygen. Despite significant advancement in the characterization of their physiological properties, our understanding on the underlying molecular machinery and signaling pathway in CB glomus cells is still limited.

To overcome these limitations, in chapter 1, I demonstrated the first transcriptome profile of CB glomus cells using single cell sequencing technology, which allowed us to uncover a set of abundantly expressed genes, including novel glomus cell-specific transcripts. These results revealed involvement of G protein-coupled receptor (GPCR) signaling pathway, various types of ion channels, as well as atypical mitochondrial subunits in CB function. I also identified ligands for the mostly highly expressed GPCR (Olfr78) in CB glomus cells and examined this receptor’s role in CB mediated hypoxic ventilatory response.

Current knowledge of CB suggest glomus cells rely on unusual mitochondria for their sensitivity to hypoxia. I previously identified the atypical mitochondrial subunit Ndufa4l2 as a highly over-represented gene in CB glomus cells. In chapter 2, to investigate the functional significance of Ndufa4l2 in CB function, I phenotyped both Ndufa4l2 knockout mice and mice with conditional Ndufa4l2 deletion in CB glomus cells. I found that Ndufa4l2 is essential to the establishment of regular breathing after birth. Ablating Ndufa4l2 in postnatal CB glomus cells resulted in defective CB sensitivity to hypoxia as well as CB mediated hypoxic ventilatory response. Together, our data showed that Ndufa4l2 is critical to respiratory control and the oxygen sensitivity of CB glomus cells.

Mechanisms of Cdc42 Polarization in Yeast

Polarization is important for the function and morphology of many different cell types. The keys regulators of polarity in eukaryotes are the Rho-family GTPases. In the budding yeast Saccharomyces cerevisiae, which must polarize in order to bud and to mate, the master regulator is the highly conserved Rho GTPase, Cdc42. During polarity establishment, active Cdc42 accumulates at a site on the plasma membrane characterizing the “front” of the cell where the bud will emerge. The orientation of polarization is guided by upstream cues that dictate the site of Cdc42 clustering. However, in the absence of upstream cues, yeast can still polarize in a random direction during symmetry breaking. Symmetry breaking suggests cells possess an autocatalytic polarization mechanism that can amplify stochastic fluctuations of polarity proteins through a positive feedback mechanism.

Two different positive feedback mechanisms have been proposed to polarize Cdc42 in budding yeast. One model posits that Cdc42 activation must be localized to a site at the plasma membrane. Another model posits that Cdc42 delivery must be localized to a particular site at the plasma membrane. Although both mechanisms could work in parallel to polarize Cdc42, it is unclear which mechanism is critical to polarity establishment. We directly tested the predictions of the two positive feedback models using genetics and live microscopy. We found that localized Cdc42 activation is necessary for polarity establishment.

While this explains how active Cdc42 localizes to a particular site at the plasma membrane, it does not address how Cdc42 concentrates at that site. Several different mechanisms have been proposed to concentrate Cdc42. The GDI can extract Cdc42 from membranes and selective mobilize GDP-Cdc42 in the cytoplasm. It was proposed that selectively mobilizing GDP-Cdc42 in combination with local activation could locally concentrate total Cdc42 at the polarity site. Although the GDI is important for rapid Cdc42 accumulation at the polarity site, it is not essential to Cdc42 concentration. It was proposed that delivery of Cdc42 by actin-mediated vesicle can act as a backup pathway to concentrate Cdc42. However, we found no evidence for an actin-dependent concentrating pathway. Live microscopy experiments reveal that prenylated proteins are not restricted to membranes, and can enter the cytoplasm. We found that the GDI-independent concentrating pathway still requires Cdc42 to exchange between the plasma membrane and the cytoplasm, which is supported by computational modeling. In the absence of the GDI, we found that Cdc42 GAP became essential for polarization. We propose that the GAP limits GTP-Cdc42 leak into the cytoplasm, which would be prohibitive to Cdc42 polarization.

Stimulus Integration and Parsing in the Primate Auditory Midbrain

Integrating information from multiple sources is a crucial function of the brain. Examples of such integration include multiple stimuli of different modalties, such as visual and auditory, multiple stimuli of the same modality, such as auditory and auditory, and integrating stimuli from the sensory organs (i.e. ears) with stimuli delivered from brain-machine interfaces.

The overall aim of this body of work is to empirically examine stimulus integration in these three domains to inform our broader understanding of how and when the brain combines information from multiple sources.

First, I examine visually-guided auditory, a problem with implications for the general problem in learning of how the brain determines what lesson to learn (and what lessons not to learn). For example, sound localization is a behavior that is partially learned with the aid of vision. This process requires correctly matching a visual location to that of a sound. This is an intrinsically circular problem when sound location is itself uncertain and the visual scene is rife with possible visual matches. Here, we develop a simple paradigm using visual guidance of sound localization to gain insight into how the brain confronts this type of circularity. We tested two competing hypotheses. 1: The brain guides sound location learning based on the synchrony or simultaneity of auditory-visual stimuli, potentially involving a Hebbian associative mechanism. 2: The brain uses a ‘guess and check’ heuristic in which visual feedback that is obtained after an eye movement to a sound alters future performance, perhaps by recruiting the brain’s reward-related circuitry. We assessed the effects of exposure to visual stimuli spatially mismatched from sounds on performance of an interleaved auditory-only saccade task. We found that when humans and monkeys were provided the visual stimulus asynchronously with the sound but as feedback to an auditory-guided saccade, they shifted their subsequent auditory-only performance toward the direction of the visual cue by 1.3-1.7 degrees, or 22-28% of the original 6 degree visual-auditory mismatch. In contrast when the visual stimulus was presented synchronously with the sound but extinguished too quickly to provide this feedback, there was little change in subsequent auditory-only performance. Our results suggest that the outcome of our own actions is vital to localizing sounds correctly. Contrary to previous expectations, visual calibration of auditory space does not appear to require visual-auditory associations based on synchrony/simultaneity.

My next line of research examines how electrical stimulation of the inferior colliculus influences perception of sounds in a nonhuman primate. The central nucleus of the inferior colliculus is the major ascending relay of auditory information before it reaches the forebrain, and thus an ideal target for understanding low-level information processing prior to the forebrain, as almost all auditory signals pass through the central nucleus of the inferior colliculus before reaching the forebrain. Thus, the inferior colliculus is the ideal structure to examine to understand the format of the inputs into the forebrain and, by extension, the processing of auditory scenes that occurs in the brainstem. Therefore, the inferior colliculus was an attractive target for understanding stimulus integration in the ascending auditory pathway.

Moreover, understanding the relationship between the auditory selectivity of neurons and their contribution to perception is critical to the design of effective auditory brain prosthetics. These prosthetics seek to mimic natural activity patterns to achieve desired perceptual outcomes. We measured the contribution of inferior colliculus (IC) sites to perception using combined recording and electrical stimulation. Monkeys performed a frequency-based discrimination task, reporting whether a probe sound was higher or lower in frequency than a reference sound. Stimulation pulses were paired with the probe sound on 50% of trials (0.5-80 µA, 100-300 Hz, n=172 IC locations in 3 rhesus monkeys). Electrical stimulation tended to bias the animals’ judgments in a fashion that was coarsely but significantly correlated with the best frequency of the stimulation site in comparison to the reference frequency employed in the task. Although there was considerable variability in the effects of stimulation (including impairments in performance and shifts in performance away from the direction predicted based on the site’s response properties), the results indicate that stimulation of the IC can evoke percepts correlated with the frequency tuning properties of the IC. Consistent with the implications of recent human studies, the main avenue for improvement for the auditory midbrain implant suggested by our findings is to increase the number and spatial extent of electrodes, to increase the size of the region that can be electrically activated and provide a greater range of evoked percepts.

My next line of research employs a frequency-tagging approach to examine the extent to which multiple sound sources are combined (or segregated) in the nonhuman primate inferior colliculus. In the single-sound case, most inferior colliculus neurons respond and entrain to sounds in a very broad region of space, and many are entirely spatially insensitive, so it is unknown how the neurons will respond to a situation with more than one sound. I use multiple AM stimuli of different frequencies, which the inferior colliculus represents using a spike timing code. This allows me to measure spike timing in the inferior colliculus to determine which sound source is responsible for neural activity in an auditory scene containing multiple sounds. Using this approach, I find that the same neurons that are tuned to broad regions of space in the single sound condition become dramatically more selective in the dual sound condition, preferentially entraining spikes to stimuli from a smaller region of space. I will examine the possibility that there may be a conceptual linkage between this finding and the finding of receptive field shifts in the visual system.

In chapter 5, I will comment on these findings more generally, compare them to existing theoretical models, and discuss what these results tell us about processing in the central nervous system in a multi-stimulus situation. My results suggest that the brain is flexible in its processing and can adapt its integration schema to fit the available cues and the demands of the task.

Polyploidy and Mitotic Cell Death are Two Distinct HIV-1 Vpr-Driven Outcomes in Renal Tubule Epithelial Cells

Given the emerging epidemic of renal disease in HIV+ patients and the fact that HIV DNA and RNA persist in the kidneys of HIV+ patients despite therapy, it is necessary to understand the role of direct HIV-1 infection of the kidney. HIV-associated kidney disease pathogenesis is attributed in large part to viral proteins. Expression of Vpr in renal tubule epithelial cells (RTECs) induces G2 arrest, apoptosis and polyploidy. The ability of a subset of cells to overcome the G2/M block and progress to polyploidy is not well understood. Polyploidy frequently associates with a bypass of cell death and disease pathogenesis. Given the ability of the kidney to serve as a unique compartment for HIV-1 infection, and the observed occurrence of polyploid cells in HIV+ renal cells, it is critical to understand the mechanisms and consequences of Vpr-induced polyploidy.

Here I determined effects of HIV-1 Vpr expression in renal cells using highly efficient transduction with VSV.G pseudotyped lentiviral vectors expressing Vpr in the HK2 human tubule epithelial cell line. Using FACS, fluorescence microscopy, and live cell imaging I show that G2 escape immediately precedes a critical junction between two distinct outcomes in Vpr+ RTECs: mitotic cell death and polyploidy. Vpr+ cells that evade aberrant mitosis and become polyploid have a substantially higher survival rate than those that undergo complete mitosis, and this survival correlates with enrichment for polyploidy in cell culture over time. Further, I identify a novel role for ATM kinase in promoting G2 arrest escape and polyploidy in this context. In summary, my work identifies ATM-dependent override of Vpr-mediated G2/M arrest as a critical determinant of cell fate Vpr+ RTECs. Further, our work highlights how a poorly understood HIV mechanism, ploidy increase, may offer insight into key processes of reservoir establishment and disease pathogenesis in HIV+ kidneys.

Ordered magnetic dipoles: controlling anisotropy in nanomodulated continuous ferromagnetic films

In this paper, the research focus is how to entangle magnetic dipoles to control/engineer magnetic properties of different devices at a submicron/nano scale. Here, we report the generation of synthetic arrays of tunable magnetic dipoles in a nanomodulated continuous ferromagnetic film. In-plane magnetic field rotations in modulated Ni 45Fe 55 revealed various rotational symmetries of magnetic anisotropy due to dipolar interaction with a crossover from lower to higher fold as a function of modulation geometry. Additionally, the effect of aspect ratio on symmetry shows a novel phase shift of anisotropy, which could be critical to manipulate the overall magnetic properties of the patterned film. The tendency to form vortex is in fact found to be very small, which highlights that the strong coupling between metastable dipoles is more favorable than vortex formation to minimize energy in this nanomodulated structure. This has further been corroborated by the observation of step hysteresis, magnetic force microscopy images of tunable magnetic dipoles, and quantitative micromagnetic simulations. An analytical expression has been derived to estimate the overall anisotropy accurately for nanomodulated film having low magnetocrystaline anisotropy. Derived mathematical expressions based on magnetic dipolar interaction are found to be in good agreement with our results.

Police is Dead: On the Birth of Economism

Police is Dead is an historiographic analysis whose objective is to change the terms by which contemporary humanist scholarship assesses the phenomenon currently termed neoliberalism. It proceeds by building an archeology of legal thought in the United States that spans the nineteenth and twentieth centuries. My approach assumes that the decline of certain paradigms of political consciousness set historical conditions that enable the emergence of what is to follow. The particular historical form of political consciousness I seek to reintroduce to the present is what I call “police:” a counter-liberal way of understanding social relations that I claim has particular visibility within a legal archive, but that has been largely ignored by humanist theory on account of two tendencies: first, an over-valuation of liberalism as Western history’s master signifier; and second, inconsistent and selective attention to law as a cultural artifact. The first part of my dissertation reconstructs an anatomy of police through close studies of court opinions, legal treatises, and legal scholarship. I focus in particular on juridical descriptions of intimate relationality—which police configured as a public phenomenon—and slave society apologetics, which projected the notion of community as an affective and embodied structure. The second part of this dissertation demonstrates that the dissolution of police was critical to emergence of a paradigm I call economism: an originally progressive economic framework for understanding social relations that I argue developed at the nexus of law and economics at the turn of the twentieth century. Economism is a way of understanding sociality that collapses ontological distinctions between formally distinct political subjects—i.e., the state, the individual, the collective—by reducing them to the perspective of economic force. Insofar as it was taken up and reoriented by neoliberal theory, this paradigm has become a hegemonic form of political consciousness. This project concludes by encouraging a disarticulation of economism—insofar as it is a form of knowledge—from neoliberalism as its contemporary doctrinal manifestation. I suggest that this is one way progressive scholarship can think about moving forward in the development of economic knowledge, rather than desiring to move backwards to a time before the rise of neoliberalism. Disciplinarily, I aim to show that understanding the legal historiography informing our present moment is crucial to this task.

The Role of TET Proteins in the Epigenetic Regulation of Neural Gene Expression and Behavior

Understanding how genes affect behavior is critical to develop precise therapies for human behavioral disorders. The ability to investigate the relationship between genes and behavior has been greatly advanced over the last few decades due to progress in gene-targeting technology. Recently, the Tet gene family was discovered and implicated in epigenetic modification of DNA methylation by converting 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). 5hmC and its catalysts, the TET proteins, are highly abundant in the postnatal brain but with unclear functions. To investigate their neural functions, we generated new lines of Tet1 and Tet3 mutant mice using a gene targeting approach. We designed both mutations to cause a frameshift by deleting the largest coding exon of Tet1 (Tet1Δe4) and the catalytic domain of Tet3 (Tet3Δe7-9). As Tet1 is also highly expressed in embryonic stem cells (ESCs), we generated Tet1 homozygous deleted ESCs through sequential targeting to compare the function of Tet1 in the brain to its role in ESCs. To test our hypothesis that TET proteins epigenetically regulate transcription of key neural genes important for normal brain function, we examined transcriptional and epigenetic differences in the Tet1Δe4 mouse brain. The oxytocin receptor (OXTR), a neural gene implicated in social behaviors, is suggested to be epigenetically regulated by an unknown mechanism. Interestingly, several human studies have found associations between OXTR DNA hypermethylation and a wide spectrum of behavioral traits and neuropsychiatric disorders including autism spectrum disorders. Here we report the first evidence for an epigenetic mechanism of Oxtr transcription as expression of Oxtr is reduced in the brains of Tet1Δe4-/- mice. Likewise, the CpG island overlapping the promoter of Oxtr is hypermethylated during early embryonic development and persists into adulthood. We also discovered altered histone modifications at the hypermethylated regions, indicating the loss of TET1 has broad effects on the chromatin structure at Oxtr. Unexpectedly, we discovered an array of novel mRNA isoforms of Oxtr that are selectively reduced in Tet1Δe4-/- mice. Additionally, Tet1Δe4-/- mice display increased agonistic behaviors and impaired maternal care and short-term memory. Our findings support a novel role for TET1 in regulating Oxtr expression by preventing DNA hypermethylation and implicate TET1 in social behaviors, offering novel insight into Oxtr epigenetic regulation and its role in neuropsychiatric disorders.

Pyramid Multi-resolution Scanning for Two-sample Comparison

Testing for two-sample differences is challenging when the differences are local and only involve a small portion of the data. To solve this problem, we apply a multi- resolution scanning framework that performs dependent local tests on subsets of the sample space. We use a nested dyadic partition of the sample space to get a collection of windows and test for sample differences within each window. We put a joint prior on the states of local hypotheses that allows both vertical and horizontal message passing among the partition tree to reflect the spatial dependency features among windows. This information passing framework is critical to detect local sample differences. We use both the loopy belief propagation algorithm and MCMC to get the posterior null probability on each window. These probabilities are then used to report sample differences based on decision procedures. Simulation studies are conducted to illustrate the performance. Multiple testing adjustment and convergence of the algorithms are also discussed.

Preparation of Boron by Pyrolytic Decomposition of Boron Tribromide

The national shortage of helium-3 has made it critical to develop an alternative to helium-3 neutron detectors. Boron-10, if it could be produced in macroscopic alpha-rhombohedral crystalline form, would be a viable alternative to helium-3. This work has determined the critical parameters needed for the preparation of alpha-rhombohedral boron by the pyrolytic decomposition of boron tribromide on tantalum wire. The primary parameters that must be met are wire temperature and feedstock purity. The minimum purity level for boron tribromide was determined to be 99.999% and it has been found that alpha-rhombohedral boron cannot be produced using 99.99% boron tribromide. The decomposition temperature was experimentally tested between 830°C and 1000°C. Alpha-rhombohedral boron was found at temperatures between 950°C and 1000°C using 99.999% pure boron tribromide.

Common Bound: The Small Groups of Methodism

The system of small groups John Wesley established to promote a proper life of discipleship in early Methodist converts was, in many respects, the strength of the Methodist movement. Those who responded to Wesley’s initial invitation to “flee the wrath to come” were organized into large gatherings called “societies,” which were then subdivided into smaller bands, class meetings, select societies, and penitent bands. The smaller groups gave Wesley the opportunity, through a system of appointed leaders, to keep track of the spiritual progress of every member in his movement, which grew to tens of thousands by the time of his death in 1791. As Methodism shifted from renewal movement to institutional church in the nineteenth century, however, growth slowed, and participation in such groups declined rapidly. By the early twentieth century, classes and bands were virtually extinct in every sector of Methodism save the African-American tradition. In recent years, scholars in various sectors of the Wesleyan tradition, particularly David Lowes Watson and Kevin Watson, have called for a recovery of these small groups for purposes of renewal in the church. There is no consensus, however, concerning what exactly contributed to the vitality of these groups during Wesley’s ministry.

Over the last century, sociological studies of group dynamics have revealed three common traits that are crucial to highly functioning groups: interdependence created by the existence of a common goal, interaction among group members that is “promotive” or cooperative in nature, and high levels of feedback associated with personal responsibility and individual accountability. All three of these were prevalent in the early Methodist groups. Interdependence existed around a shared goal, which for Wesley and the Methodists was holiness. That interdependence was cooperative in nature; individuals experienced the empowering grace of God as they each pursued the goal in the company of fellow pilgrims. Finally, the groups existed for purposes of feedback and accountability as individuals took responsibility both for themselves and others as they progressed together toward the goal of holy living. Wesley seemed to instinctively understand the essential nature of each of these characteristics in maintaining the vitality of the movement when he spoke of the importance of preserving the “doctrine, spirit and discipline” of early Methodism. Analysis of some of the present-day attempts to restore Wesley’s groups reveals frequent neglect to one or more of these three components. Perhaps most critical to recovering the vitality of the early Methodist groups will be reclaiming the goal of sanctification and coming to a consensus on what its pursuit means in the present day.

Primary care physician decision making regarding severe obesity treatment and bariatric surgery: a qualitative study.

BACKGROUND: Less than 1% of severely obese US adults undergo bariatric surgery annually. It is critical to understand the factors that contribute to its utilization. OBJECTIVES: To understand how primary care physicians (PCPs) make decisions regarding severe obesity treatment and bariatric surgery referral. SETTING: Focus groups with PCPs practicing in small, medium, and large cities in Wisconsin. METHODS: PCPs were asked to discuss prioritization of treatment for a severely obese patient with multiple co-morbidities and considerations regarding bariatric surgery referral. Focus group sessions were analyzed by using a directed approach to content analysis. A taxonomy of consensus codes was developed. Code summaries were created and representative quotes identified. RESULTS: Sixteen PCPs participated in 3 focus groups. Four treatment prioritization approaches were identified: (1) treat the disease that is easiest to address; (2) treat the disease that is perceived as the most dangerous; (3) let the patient set the agenda; and (4) address obesity first because it is the common denominator underlying other co-morbid conditions. Only the latter approach placed emphasis on obesity treatment. Five factors made PCPs hesitate to refer patients for bariatric surgery: (1) wanting to "do no harm"; (2) questioning the long-term effectiveness of bariatric surgery; (3) limited knowledge about bariatric surgery; (4) not wanting to recommend bariatric surgery too early; and (5) not knowing if insurance would cover bariatric surgery. CONCLUSION: Decision making by PCPs for severely obese patients seems to underprioritize obesity treatment and overestimate bariatric surgery risks. This could be addressed with PCP education and improvements in communication between PCPs and bariatric surgeons.