Miracle-dz/UniFAR-FTUs huggingface dataset:
Antibody expression kinetics in glycoengineered Pichia pastoris

Growth of the antibody market has fueled the development of alternative expression systems such as glycoengineered yeast. Although intact antibody expression levels in excess of 1 g L−1 have been demonstrated in glycoengineered yeast, this is still significantly below the titers reported for antibody fragments in fungal expression systems. This study presents a simplified approach to estimate antibody secretion kinetics and oxygen uptake rate requirements as a function of growth‐rate controlled by a limiting methanol feed rate in glycoengineered Pichia pastoris. The yield of biomass from methanol and the specific oxygen requirements predicted in this study compare well with values reported in the literature for wild‐type P. pastoris, indicating the intrinsic nature of these yields independent of glycoengineering or the heterologous protein expressed. Specific productivity was found to be a non‐linear function of specific growth rate. Based on comparison with relationships between specific growth rate and specific productivity reported in the literature this correlation seems empirical in nature and cannot be established a priori. These correlations were then used in a simple mass balance based model to predict the cultivation performance of carbon limited cultivations under oxygen transfer limited conditions to indicate the usefulness of this approach to predict large scale performance and aid in process development. Biotechnol. Bioeng. 2010;106: 918–927. © 2010 Wiley Periodicals, Inc.
Dynamics of the sealing zone in cultured osteoclasts

Bone resorption by osteoclasts (OCs) depends on the formation and stability of the sealing zone (SZ), a peripheral belt of actin and integrin‐based podosomes. Recent studies demonstrated that the SZ is a highly dynamic structure, undergoing cycles of assembly and disassembly. In this study, we explored the mechanisms underlying the regulation of SZ stability and reorganization in OCs cultured on glass slides, and forming an SZ‐like podosome belt (SZL). By monitoring this belt in cultured RAW264.7 cells expressing GFP‐tagged actin, we show here that SZL stability is usually locally regulated, and its dissociation, occurring mostly in concave segments, is manifested in the loss of both podosome coherence, and actin belt continuity. Double labeling of cells for actin and tubulin indicated that microtubules (MTs) are mostly confined by the inner aspect of the stable SZL‐associated actin belt. However, in unstable regions of the SZL, MTs tend to extend radially, across the SZL, toward the cell edge. Disruption of MTs by nocodazole induces SZ disassembly, without affecting individual podosome stability. Inspection of the MT network indicates that it is enriched along stable SZL regions, while bypassing disorganized regions. These results suggest that the SZL is stabilized by MTs flanking its inner aspect, while disruption or misalignment of MTs leads to SZL destabilization. We further demonstrate that the MT‐associated protein dynamin2 is involved in the regulation of SZL stability, and dynamin2 knockdown or inactivation cause SZL destabilization.
Role of Extracellular Superoxide Dismutase in Hypertension

We previously found that angiotensin II–induced hypertension increases vascular extracellular superoxide dismutase (ecSOD), and proposed that this is a compensatory mechanism that blunts the hypertensive response and preserves endothelium-dependent vasodilatation. To test this hypothesis, we studied ecSOD-deficient mice. ecSOD−/− and C57Blk/6 mice had similar blood pressure at baseline; however, the hypertension caused by angiotensin II was greater in ecSOD−/− compared with wild-type mice (168 versus 147 mm Hg, respectively; P<0.01). In keeping with this, angiotensin II increased superoxide and reduced endothelium-dependent vasodilatation in small mesenteric arterioles to a greater extent in ecSOD−/− than in wild-type mice. In contrast to these findings in resistance vessels, angiotensin II paradoxically improved endothelium-dependent vasodilatation, reduced intracellular and extracellular superoxide, and increased NO production in aortas of ecSOD−/− mice. Whereas aortic expression of endothelial NO synthase, Cu/ZnSOD, and MnSOD were not altered in ecSOD−/− mice, the activity of Cu/ZnSOD was increased by 80% after angiotensin II infusion. This was associated with a concomitant increase in expression of the copper chaperone for Cu/ZnSOD in the aorta but not in the mesenteric arteries. Moreover, the angiotensin II–induced increase in aortic reduced nicotinamide-adenine dinucleotide phosphate oxidase activity was diminished in ecSOD−/− mice as compared with controls. Thus, during angiotensin II infusion, ecSOD reduces hypertension, minimizes vascular superoxide production, and preserves endothelial function in resistance arterioles. We also identified novel compensatory mechanisms involving upregulation of copper chaperone for Cu/ZnSOD, increased Cu/ZnSOD activity, and decreased reduced nicotinamide-adenine dinucleotide phosphate oxidase activity in larger vessels. These compensatory mechanisms preserve large vessel function when ecSOD is absent in hypertension.
Finding Parallelism for Future EPIC Machines

Parallelism has been the primary architectural mechanism to increase computer system performance. To continue pushing the performance envelope, identifying new sources of parallelism for future architectures is critical. Current hardware exploits local instruction level parallelism (ILP) as hardware resources and information communicated by the instruction-set architecture (ISA) permit. From this perspective, the Explicitly Parallel Instruction Computing (EPIC) ISA is an interesting model for future machines as its primary design allows software to expose analysis information to the underlying processor for it to exploit parallelism. In this effort, EPIC processors have been more or less successful, however the question of how to identify (or create) additional parallelism remains. This paper analyzes the potential of future relationships of compilers, ISAs, and hardware resources to collectively exploit new levels of parallelism. By experimentally studying the ILP of applications under ideal execution conditions (e.g., perfect memory disambiguation, infinite instruction-issue window, and infinite machine resources), the impact of aggressive compiler optimization and the underlying processor ISA on parallelism can be explored. Experimental comparisons involving an Itanium-based EPIC model and an Intel x86-based CISC (Complex Instruction Set Computing) model indicate that the compiler and certain ISA details directly affect local and distant instruction-level parallelism. The experimental results also suggest promising research directions for extracting the distant ILP.
Kinetic dissection of the catalytic mechanism of taurine:alpha-ketoglutarate dioxygenase (TauD) from Escherichia coli.

Recent studies on taurine:alpha-ketoglutarate dioxygenase (TauD) from Escherichia coli have provided evidence for a three-step, minimal kinetic mechanism involving the quaternary TauD.Fe(II). alpha-ketoglutarate.taurine complex, the taurine-hydroxylating Fe(IV)-oxo intermediate (J) that forms upon reaction of the quaternary complex with O(2), and a poorly defined, Fe(II)-containing intermediate state that converts in the rate-limiting step back to the quaternary complex [Price, J. C. , Barr, E. W. , Tirupati, B. , Bollinger, J. M. , Jr., and Krebs, C. (2003) Biochemistry 42, 7497-7508]. The mapping of this kinetic mechanism onto the consensus chemical mechanism for the Fe(II)- and alpha-ketoglutarate-dependent engendered several predictions and additional questions that have been experimentally addressed in the present study. The results demonstrate (1) that postulated intermediates between the quaternary complex and J accumulate very little or not at all; (2) that decarboxylation of alpha-ketoglutarate occurs prior to or concomitantly with formation of J; (3) that the second intermediate state comprises one or more product complex with Mossbauer features that are partially resolved from those of the binary TauD.Fe(II), ternary TauD.Fe(II). alpha-ketoglutarate, and quaternary TauD.Fe(II). alpha-ketoglutarate.taurine complexes; and (4) that the rate-determining step in the catalytic cycle is release of product(s) prior to the rapid, ordered binding of alpha-ketoglutarate and then taurine to regenerate the O(2)-reactive quaternary complex. The results thus integrate the previously proposed kinetic and chemical mechanisms and indicate which of the postulated intermediates in the latter will be detectable only upon perturbation of the kinetics by changes in reaction conditions (e.g., temperature), protein mutagenesis, the use of substrate analogues, or some combination of these.
Learning-Specific Changes in Long-Term Depression in Adult Perirhinal Cortex

Learning is widely believed to involve synaptic plasticity, using mechanisms such as those used in long-term potentiation (LTP). We assess whether the mechanisms used in alternative forms of plasticity, long-term depression (LTD) and depotentiation, play a role in learning. We have exploited the involvement of the perirhinal cortex in two different forms of learning to compare simultaneously, within the same brain region, their effects on LTD and depotentiation. Multiple-exposure learning but not single-exposure learning in vivo prevented, in a muscarinic receptor-dependent manner, subsequent induction of LTD and depotentiation, but not LTP, in perirhinal cortex in vitro. The contrast in the effects of the two types of learning under these particular experimental conditions indicate that the in vitro change is unlikely to be attributable to synapse-specific plastic changes registering the precise details of the individual learned associations. Instead, it is concluded that the lack of LTD and depotentiation arises from, and establishes the importance of, a learning-related generalized change in plasticity gain. The existence of this additional mechanism has important implications for interpretations of how plasticity relates to learning.
Novel, secondary sensory cell organ in ascidians: In search of the ancestor of the vertebrate lateral line

A new mechanoreceptor organ, the “coronal organ,” located in the oral siphon, is described by light and electron microscopy in the colonial ascidians Botryllus schlosseri and Botrylloides violaceus. It is composed of a line of sensory cells (hair cells), accompanied by supporting cells, that runs continuously along the margin of the velum and tentacles of the siphon. These hair cells resemble those of the vertebrate lateral line or, in general, the acoustico‐lateralis system, because they bear a single cilium, located centrally or eccentrically to a hair bundle of numerous stereovilli. In contrast to other sensory cells of ascidians, the coronal hair cells are secondary sensory cells, since they lack axonal processes directed towards the cerebral ganglion. Moreover, at their base they form synapses with nerve fibers, most of which exhibit acetylcholinesterase activity. The absence of axonal extensions was confirmed by experiments with lipophilic dyes. Different kinds of synapses were recognized: usually, each hair cell forms a few afferent synapses with dendrites of neurons located in the ganglion; efferent synapses, both axo‐somatic (between an axon coming from the ganglion and the hair cell) and axo‐dendritic (between an axon coming from the ganglion and an afferent fiber) were occasionally found. The presence of secondary sensory cells in ascidians is discussed in relation to the evolution of sensory cells and placodes in vertebrates. It is proposed that the coronal organ in urochordates is homologous to the vertebrate acoustico‐lateralis system. J. Comp. Neurol. 461:236–249, 2003. © 2003 Wiley‐Liss, Inc.
Yes, Personality Matters: Moving on to More Important Matters

Over the years, personality has had at best a checkered reputation as a predictor of work outcomes. From Guion and Gottier (1965) and Mischel (1968) to Davis-Blake and Pfeffer (1989), personality has been roundly criticized as an ineffective predictor of performance. In recent years, however, researchers have acknowledged and documented the fact that we all have personalities (e.g., Goldberg, 1993), and that personality matters because it predicts and explains behavior at work. This research, based on a construct-oriented approach primarily using the “Big Five” traits, has consistently shown that personality predicts job performance across a wide variety of outcomes that organizations value, in jobs ranging from skilled and semiskilled (e.g., baggage handlers, production employees) to executives. Yet the magnitude of these effects, as reported in the Murphy and Dzieweczynski (this issue) article, can be characterized as modest, at best. If this is true, why should we care about personality? We begin this article with a review of what researchers have learned about the role of personality at work, and conclude with a discussion about personality’s future. Later, we discuss the findings from seven divergent research streams that, when taken together, demonstrate why we should care about personality. The first reason is that managers care about personality. Research has shown that managers weight individual personality characteristics as if they were nearly as important as general mental ability, during the hiring decision (Dunn, Mount, Barrick, & Ones, 1995). In fact, it is hard to find a manager who says they would prefer to hire someone who is careless, irresponsible, lazy, impulsive, and low in achievement striving (low in Conscientiousness). Similarly, not many managers seek to hire individuals who are anxious, hostile, personally insecure, and deHUMAN PERFORMANCE, 18(4), 359–372 Copyright © 2005, Lawrence Erlbaum Associates, Inc.
FORMATION OF RADIATION FIELDS OF LINEAR VIBRATOR ARRAYS BY USING IMPEDANCE SYNTHESIS

A new method of impedance synthesis of antenna array radiation fields based on a single methodological conception is presented. At first, an approximate solution for the current in the thin vibrator with variable impedance was obtained using the partial averaging operation of the integraldifferential equation. The variable impedance of the vibrator was taken into account in the form of an integral coefficient averaged along the vibrator length. The approach turns out to be common for radiators with impedance coatings of different configurations and/or different distributions of lumped impedances. It is established that the shape of the vibrator radiation pattern (RP) does not depend on the form of the impedance distribution function, and it is determined only by the averaged value of the impedance distribution along the vibrator axis. The solution shows that the impedance coating of a symmetrical thin vibrator excited at the center by the voltage δ-generator affects the shape of the radiation pattern in the wave zone, and the effect is directly proportional to the small natural parameter of the problem. The synthesis problem of the radiator impedances for the spatial scanning of the RP was solved for the linear vibrator array. The analytical solution of the problem was obtained for the equidistant array of symmetric vibrators with equal excitation currents. The possibility of changing the RP shape over a wide range by varying the intrinsic complex impedances of the vibrators is demonstrated for an equidistant linear array consisting of 5 half-wave vibrators located at a distance of one eighth wavelength from each other in the free space.
Users' views on supported employment and social inclusion: a qualitative study of 30 people in work1

Summary This paper outlines the findings from interviews exploring the perceptions of people with learning difficulties in relation to work and employment support. We look at what people told us about their experiences in seeking employment, getting a job, being in work and about the support they received. We also make inferences from the data about the nature and extent of social inclusion associated with being in work. The varying experiences of our sample illustrate the scope of the task in hand to achieve the vision of social inclusion expressed in Valuing People.
Homicide Trends in Finland and Estonia in 1880–1940: Consequences of the Demographic, Social and Political Effects of Industrialization

While in western Europe and Scandinavia homicide rates reached their all time low during the period of industrialization, in Finland and Estonia they increased considerably. The rapid growth of criminal violence during the late 1800s and first half of the 1900s in these two countries seems to have been the result of interaction of several factors, partly non-simultaneous and unrelated. They do not seem to have been identical either, although the underlying equation was the same: the quick social and economic change following industrialization, and the modernisation of agriculture, the pressures it put especially on the youth in the form of uncertain prospects for the future and a new competition-oriented set of values, connected with the authoritarian political system of Russian Empire, which prevented necessary political reforms and left behind a legacy of social thinking idealizing violence as a political and social instrument. A legacy, which affected large parts of Finnish and Estonian population still for years after the czarist system itself already passed into history. The criminal violence arisen from the equation, however, had quite a different face on the northern coast of the Gulf of Finland from that on the southern one. In Finland the violence was centered in the new forest industrial communities, in Estonia again among the landless population of the countryside.
Joint Sparse Channel Estimation and Decoding: Continuous and Discrete Domain Sparsity

Recent progress in wireless receiver design has been towards iterative processing, where channel estimation and decoding is considered a joint optimization problem. Sparse channel estimation is another recent advancement, which exploits the inherent structure of those wireless channels that are composed of a small number of multipath components. In this work we design iterative receivers which incorporate sparse channel estimation. State-of-the-art sparse channel estimators simplify the estimation problem to be a finite basis selection problem by restricting the multipath delays to the discrete domain (i.e. to a grid). Our main contribution is a receiver without such a restriction; the delays are estimated directly as continuous values. As a result, our receiver does not suffer from the leakage effect which destroys sparsity when the delays are restricted to the discrete domain. We discuss certain connections between continuous and discrete domain sparse estimation methods. Our receivers outperform state-of-the-art sparse channel estimation iterative receivers in terms of bit error rate.
G protein‐coupled receptor for asthma susceptibility associates with respiratory distress syndrome

Background. Respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) have some common features with asthma. Aim. To study whether G protein‐coupled receptor for asthma susceptibility (GPRA) contributes to RDS or BPD. Methods. A haplotype association study was performed in a case‐control setting of 521 Finnish infants (including 176 preterm neonates with RDS and 37 with BPD). Immunoreactivity of GPRA isoforms A and B was determined in pulmonary samples of fetuses, term infants and preterm infants with RDS or BPD. GPRA mRNA expression was determined by quantitative real‐time polymerase chain reaction (PCR) in samples from nasal respiratory epithelium of adults, term infants and preterm infants. Results. In infants with RDS born at 32–35 weeks of gestation, GPRA haplotype H1 was significantly underrepresented in RDS, whereas haplotype H4/H5 was associated with an increased risk. As in asthma, GPRA B isoform was induced in bronchial smooth muscle cells in RDS and BPD. In nasal respiratory epithelium, relative GPRA mRNA expression was strong in adults, weak in preterm and slightly higher in term samples. Conclusions. The results suggest that near‐term RDS and asthma share the same susceptibility and protective GPRA haplotypes. Altered GPRA expression may play a role in the pathogenesis of RDS and BPD in preterm infants.
Measuring the Incentive to Collude: The Vitamin Cartels, 1990-1999

Why do some cartels survive for a decade but others collapse within a few years? We study one of the most prominent cases in recent history, the vitamin cartels, to quantify the member firms' incentives to collude. American court documents and European criminal investigation provide direct evidence on the cartels' organization as well as the leading firms' internal cost data, which we analyze within a standard repeated game framework. Preliminary results suggest the cartel leader's incentive diminished significantly at the time of the Vitamin C cartel's actual collapse in 1995, mainly because of growing supply from fringe competitors in China, whereas the markets for Beta Carotene, Vitamin A, and Vitamin E remained stable. We also find that the BASF-Takeda merger in 2001, if consummated a decade earlier, would have prolonged the Vitamin C cartel.
Decreased SH3BP2 inhibits osteoclast differentiation and function

Germline mutations in SH3BP2 gene have been identified in patients with cherubism, a skeletal disorder characterized by excessive osteoclastic bone resorption that is limited to the mandible and maxilla. We previously demonstrated that SH3BP2 overexpression in Raw264.7 cells increased RANKL‐induced osteoclastogenesis. Here, we examine the effect of decreased SH3BP2 on osteoclastogenesis. shRNA knockdown of SH3BP2 decreased PLCγ2 phosphorylation and NFATc1 expression, and reduced the expression of osteoclast‐specific genes. In BMMs knockdown of SH3BP2 led to reductions in both the number and the surface area of TRAP positive and multinucleated osteoclasts. Bone resorptive activity was also dramatically blocked by shRNA knockdown of SH3BP2. Similarly Sh3bp2(−/−) deficient mice BMMs formed smaller osteoclasts that stained less with TRAP than wild‐type mice. Taken together, this study demonstrates that SH3BP2 knockdown significantly decreases osteoclast differentiation and function. These results suggest that SH3BP2 plays a critical role in osteoclastogenesis and is a potential target for suppression of pathologic bone resorption. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1521–1527, 2011