Miracle-dz/UniFAR-FTUs huggingface dataset:
Importance of tacit knowledge in incremental innovation

The purpose of this paper is to examine the role of tacit knowledge in incremental innovation, which has hitherto been neglected. ,Qualitative case analysis was used to focus on two large Japanese pharmaceutical companies’ development of new antihypertensive drugs. The study uses interview data and documentary research materials to explore the knowledge bases of the companies’ research teams as they refined an existing drug to produce new products – a process of incremental innovation. ,Explicit knowledge (chemical structure of preceding drug) was used in both successful and failed cases of drug discovery. In the two successful cases, the tacit knowledge of key researchers, based on their long-term experience of related research, provided insight into developing compounds with good in vivo efficacy, which led to successful clinical development. ,The findings suggest that tacit knowledge may play an important role in incremental innovation processes, and that its influence on product development should be considered in such ways as team and organization structure. ,This study addresses a gap in the literature regarding the impact of tacit knowledge on incremental innovation processes. It is often assumed that incremental innovation is based on existing technology. This study suggests that tacit knowledge may play a hitherto largely unrecognized role in incremental product development.
Dynamics of local governance in natural resource conservation in the Okavango Delta, Botswana

There has been a shift in natural resource management worldwide. This paper describes how modern institutions and policies influence management and shape access to and utilization of resources by rural communities in the Okavango Delta, Botswana. It is rooted in the framework of adaptive co-governance within social-ecological systems, and employs a critical literature review to analyse access to and use of natural resources in rural Botswana. Prior to the establishment of community-based natural resource management (CBNRM) in Botswana in 1989, resource governance was dominated by strong traditional institutions that were responsible for natural resource management and decision-making. Contemporary natural resource governance is characterized by a bureaucratic system that invariably undermines the role of traditional institutions in natural resource governance. Findings indicate that policies and regulatory instruments deny rural communities adequate access to and utilization of resources available within their immediate environment. In spite of an orientation towards an anthropocentric approach to natural resource management (as in the case of CBNRM), the current governance system continues to undermine the inclusion of local resource users as legitimate stakeholders in the decision-making process.
Optimal poly (3-hydroxybutyrate/3-hydroxyvalerate) biosynthesis by fermentation liquid from primary and waste activated sludge

In this paper the production of poly (3-hydroxybutyrate/3-hydroxyvalerate) (PHBV) with activated sludge was investigated by using the fermentation liquid from primary sludge (PS) and waste activated sludge (WAS) as carbon source. First, the suitable concentration and ratio of acetic to propionic (acetic/propionic) for PHBV synthesis with desired hydroxyvalerate (HV) fraction was determined. Then, the conditions for producing fermentation liquid with the required acetic/propionic from the PS/WAS mixture were optimized. Finally, this optimized fermentation liquid was used as the carbon source for PHBV synthesis by the aerobic feeding and discharge process. The PHBV content in the sludge reached 65.5%, with 47.8% (mol-C based) of HV unit content, and the corresponding polyhydroxyalkanoates yield per litre of acclimated sludge was 1.44 g/L. This was the first optimal PHBV biosynthesis reported by using activated sludge as the microbe and sludge fermentation liquid as the carbon source. Polymerase chain reaction-based 454 pyrosequencing analysis revealed that Thauera strains were the predominant species in the PHBV biosynthesis system.
Growth and metastasis of surgical specimens of human breast carcinomas in SCID mice.

PURPOSE We have studied the growth and metastatic potential of surgical specimens of breast carcinomas engrafted into the large abdominal (gonadal) fat pad of severe combined immunodeficient (SCID) mice. We present results of this study, details of the implantation protocol and histologic characterization of several of the tumor xenografts. MATERIALS AND METHODS We evaluated the growth within SCID mice of 48 breast carcinoma specimens derived from 46 patients (45 primary breast cancers or local recurrences and 3 regional metastatic lymph nodes) obtained from resected tissues at this Institute over a 3-year period. The growth of each transplant was assessed by histologic examination of the xenografts at various times after implantation or upon passage into additional mice. RESULTS We observed that placement of human breast tumors within the gonadal fat pad could result in tumors that grew either rapidly, slowly, or not at all. Of 48 tumors studied, 12 (25%), including one of the three lymph node-derived tumors, grew rapidly enough within some or all of the implanted mice (i.e., the tumors reached a diameter of 2-3 cm within 2-6 months) to allow repeated passage. Metastatic spread to the SCID mouse lung, liver, and/or diaphragm and other sites was observed with the xenografts derived from 8 of these 12 rapidly growing tumors. Tumors in a second category often took from 6 months to over 1 year to only double or triple in size. This slow-growth group consisted of 25 patients' tumors (53%), including the remaining two metastatic lymph node-derived tumors. These xenografts would usually maintain a slow growth rate even upon later passage into new animals. A third category consisted ofpatients' tumors (23%) that failed to grow at all (i.e., no evidence of tumor growth in any of the mice implanted), as discerned by histologic evaluation at various times after implantation. Histologic examination of tumor xenografts and metastatic tumors revealed considerable variation in histopathology among the different patients' tumors. DISCUSSION Further examination of the heterogeneous properties of primary human breast carcinomas within SCID mice may provide a simple yet valuable new approach for the long-term study of human breast cancer biology. Importantly, use of the protocol described here can often permit the isolation of substantial quantities of human breast cancer cells for biochemical and molecular analyses. The ability to passage patients' breast tumors into large numbers of mice will permit the preclinical testing of new therapies for the treatment and prevention of this disease.
Associations between carotid atherosclerosis and high factor VIII activity, dyslipidemia, and hypertension.

BACKGROUND AND PURPOSE A subsample of 147 Chinese subjects from a population-based study of cardiovascular diseases (Cardiovascular Disease Risk Factor Two-Township Study) participated in an ancillary study on extracranial carotid color duplex ultrasonography that aimed to assess the relations of coagulation factors to stroke and carotid atherosclerosis. METHODS Logistic models were used to study the associations between cardiovascular disease risk factors and stroke/carotid atherosclerosis, controlling for the effects of age and sex. RESULTS Stroke was significantly associated with hypertension and high values of plasma glucose but not with fibrinogen, factor VIIc, or factor VIIIc. Carotid plaques identified in this study were mostly mild and moderate. The presence of these mild and moderate carotid plaques was significantly associated with high values of factor VIII activity, hypercholesterolemia, hypertriglyceridemia, and hypertension. The highest tertile of factor VIIIc (> 1.53) was associated with an odds ratio of 3.35 for carotid atherosclerosis when compared with the lowest tertile (< 1.20). A multiple logistic regression including all significant risk factors showed that the degree of association between factor VIIIc and atherosclerosis was attenuated to an odds ratio of 2.65 (P = .061). CONCLUSIONS In the present study, the roles of hypertension, hypercholesterolemia, and hypertriglyceridemia have been implicated in the pathogenesis of carotid atherosclerosis, and roles for hypertension and hyperglycemia in stroke were indicated. A positive association between factor VIIIc and carotid atherosclerosis in this Chinese population was found. Whether this association is independent of the effect of other cardiovascular risk factors awaits further study.
Shedding light on disulfide bond formation: engineering a redox switch in green fluorescent protein

To visualize the formation of disulfide bonds in living cells, a pair of redox‐active cysteines was introduced into the yellow fluorescent variant of green fluorescent protein. Formation of a disulfide bond between the two cysteines was fully reversible and resulted in a >2‐fold decrease in the intrinsic fluorescence. Inter conversion between the two redox states could thus be followed in vitro as well as in vivo by non‐invasive fluorimetric measurements. The 1.5 Å crystal structure of the oxidized protein revealed a disulfide bond‐induced distortion of the β‐barrel, as well as a structural reorganization of residues in the immediate chromophore environment. By combining this information with spectroscopic data, we propose a detailed mechanism accounting for the observed redox state‐dependent fluorescence. The redox potential of the cysteine couple was found to be within the physiological range for redox‐active cysteines. In the cytoplasm of Escherichia coli, the protein was a sensitive probe for the redox changes that occur upon disruption of the thioredoxin reductive pathway.
Electron transfer dissociation provides higher‐order structural information of native and partially unfolded protein complexes

Top–down sequencing approaches are becoming ever more popular for protein characterization, due to the ability to distinguish and characterize different protein isoforms. Under non‐denaturing conditions, electron transfer dissociation (ETD) can furthermore provide important information on the exposed surface of proteins or complexes, thereby contributing to the characterization of their higher‐order structure. Here, we investigate this approach using top–down ETD of tetrameric hemoglobin, concanavalin A, and alcohol dehydrogenase combined with ion mobility (IM) on a commercially available quadrupole/ion mobility/time‐of‐flight instrument (Waters Synapt G2). By applying supplemental activation in the transfer cell (post‐IM), we release ETD fragments and attain good sequence coverage in the exposed terminal regions of the protein. We investigate the correlation between observed sites of fragmentation with regions of solvent accessibility, as derived from the crystal structure. Ion acceleration prior to ETD is also used to cause collision‐induced unfolding (CIU) of the complexes without monomer ejection, as evidenced by the IM profiles. These partially unfolded tetramers show efficient fragmentation in some regions which are not sequenced under more gentle MS conditions. We show that by increasing CIU in small increments and monitoring the changes in the fragmentation pattern, it is possible to follow the initial steps of gas‐phase protein unfolding. Fragments from partially unfolded protein complexes are released immediately after electron transfer, prior to IM (they do not share the drift time of their precursor), and observed without the need for supplemental activation. This is further evidence that the higher‐order structure in these protein regions has been disrupted.
Neural activation in the “reward circuit” shows a nonlinear response to facial attractiveness

Positive behavioral responses to attractive faces have led neuroscientists to investigate underlying neural mechanisms in a “reward circuit” that includes brain regions innervated by dopamine pathways. Using male faces ranging from attractive to extremely unattractive, disfigured ones, this study is the first to demonstrate heightened responses to both rewarding and aversive faces in numerous areas of this putative reward circuit. Parametric analyses employing orthogonal linear and nonlinear regressors revealed positive nonlinear effects in anterior cingulate cortex, lateral orbital frontal cortex (LOFC), striatum (nucleus accumbens, caudate, putamen), and ventral tegmental area, in addition to replicating previously documented linear effects in medial orbital frontal cortex (MOFC) and LOFC and nonlinear effects in amygdala and MOFC. The widespread nonlinear responses are consistent with single cell recordings in animals showing responses to both rewarding and aversive stimuli, and with some human fMRI investigations of non-face stimuli. They indicate that the reward circuit does not process face valence with any simple dissociation of function across structures. Perceiver gender modulated some responses to our male faces: Women showed stronger linear effects, and men showed stronger nonlinear effects, which may have functional implications. Our discovery of nonlinear responses to attractiveness throughout the reward circuit echoes the history of amygdala research: Early work indicated a linear response to threatening stimuli, including faces; later work also revealed a nonlinear response with heightened activation to affectively salient stimuli regardless of valence. The challenge remains to determine how such dual coding influences feelings, such as pleasure and pain, and guides goal-related behavioral responses, such as approach and avoidance.
The effect of perfluorocarbon vapour on the measurement of respiratory tidal volume during partial liquid ventilation

During partial liquid ventilation perfluorocarbon vapour is present in the exhaled gases. The volumes of these gases are measured by pneumotachometers. Error in measuring tidal volumes will give erroneous measurement of lung compliance during partial liquid ventilation. We aim to compare measured tidal volumes with and without perfluorocarbon vapour using tidal volumes suitable for use in neonates. Tidal volumes were produced with a 100 ml calibration syringe from 20 to 100 ml and with a calibrated Harvard rodent ventilator from 2.5 to 20 ml. Control tidal volumes were drawn from a humidifier chamber containing water vapour and the PFC tidal volumes were drawn from a humidifier chamber containing water and perfluorocarbon (FC-77) vapour. Tidal volumes were measured by a fixed orifice, target, differential pressure flowmeter (VenTrak) or a hot-wire anenometer (Bear Cub) placed between the calibration syringe or ventilator and the humidifier chamber. All tidal volumes measured with perfluorocarbon vapour were increased compared with control (ANOVA p < 0.001 and post t-test p < 0.0001). Measured tidal volume increased from 7 to 16% with the fixed orifice type flow-meter, and from 35 to 41% with the hot-wire type. In conclusion, perfluorocarbon vapour flowing through pneumotachometers gives falsely high tidal volume measurements. Calculation of lung compliance must take into account the effect of perfluorocarbon vapour on the measurement of tidal volume.
Thoughts on a Fiscal Union in EMU

Abstract Using an estimated large-scale New Keynesian model, we assess the consequences of introducing a fiscal union within EMU. We differentiate between three different scenarios: public revenue equalisation, tax harmonisation and a centralised fiscal authority. Our results indicate that no country would significantly benefit from introducing any form of fiscal union. Comparing long-term, that is, steady state, effects we have winners and losers depending on the scenario. Differences in terms of business cycle statistics as well as in terms of risk sharing of asymmetric shocks are minor. This also explains why welfare differences are small across the fiscal union scenarios. A counterfactual exercise indicates that with a fiscal union regime already installed at the start of EMU, key macroeconomic variables would have reacted very similarly while debt dynamics would have changed notably.
The effects of a competitive rugby union game on tuck jump assessment performance in female rugby players

To include: collation of information and ideas and evaluation of those ideas relative to the extant literature/concept/theory and research question/problem; adoption of a personal position on the study by linking and combining different elements of the data reported; discussion of the real-life impact of your research findings for coaches and/or practitioners (i.e. practical implications); discussion of the limitations and a critical reflection of the approach/process adopted; and indication of potential improvements and future developments building on the study; and a conclusion which summarises the relationship between the research question and the major findings.
Synapsin knockdown is associated with decreased neurite outgrowth, functional synaptogenesis impairment, and fast high‐frequency neurotransmitter release

Synapsins (Syns) are an evolutionarily conserved family of synaptic vesicle‐associated proteins related to fine tuning of synaptic transmission. Studies with mammals have partially clarified the different roles of Syns; however, the presence of different genes and isoforms and the development of compensatory mechanisms hinder accurate data interpretation. Here, we use a simple in vitro monosynaptic Helix neuron connection, reproducing an in vivo physiological connection as a reliable experimental model to investigate the effects of Syn knockdown. Cells overexpressing an antisense construct against Helix Syn showed a time‐dependent decrease of Syn immunostaining, confirming protein loss. At the morphological level, Syn‐silenced cells showed a reduction in neurite linear outgrowth and branching and in the size and number of synaptic varicosities. Functionally, Syn‐silenced cells presented a reduced ability to form synaptic connections; however, functional chemical synapses showed similar basal excitatory postsynaptic potentials and similar short‐term plasticity paradigms. In addition, Syn‐silenced cells presented faster neurotransmitter release and decreased postsynaptic response toward the end of long tetanic presynaptic stimulations, probably related to an impairment of the synaptic vesicle trafficking resulting from a different vesicle handling, with an increased readily releasable pool and a compromised reserve pool. © 2015 Wiley Periodicals, Inc.
Immunogenicity and Safety of Hepatitis A Vaccine in Children With Chronic Liver Disease

Background Acute hepatitis A superimposed on chronic liver disease has been associated with a more severe course of disease and development of fulminant hepatitis. The aim of this study was to evaluate the immunogenicity and safety of an inactivated hepatitis A virus vaccine in children with chronic liver disease. Patients and Methods This was an open, prospective, and controlled trial with 89 anti-HAV negative children between 1 and 16 years of age studied at a pediatric liver disease and transplantation referral center. Inactivated HAV vaccine (Havrix), from GlaxoSmithKline Biologicals containing 720 Elisa units of alum-adsorbed hepatitis A antigen per 0.5 ml dose was used. Thirty-four pediatric patients with chronic liver disease (mean age: 7.0 ± 4.86 years) and 55 healthy controls (mean age: 4.8 ± 2.7 years) received two doses of Havrix vaccine in months zero and six. Seroconversion and anti-HAV titers expressed as geometric mean titers (GMT) in mIU/ml were measured at months one and seven, by a modified Hepatitis A virus andibodies (HAVAB) assay. Results Seroconversion rates at four weeks after primary immunization were 76% and 94% and the GMT 107.77 and 160.77 mIU/ml in the patient and control groups, respectively. One month after second dose the seroconversion rates were 97% and 100% in the groups with GMT of 812.40 and 2344.90 mIU/ml. Both doses were well tolerated with no significant adverse events observed. Local injection-site symptoms were the most common reactions reported in both groups. Conclusion Although GMTs were significantly lower in children with chronic liver disease compared to healthy controls, the overall seroconversion rates were not different. Hepatitis A virus vaccine was safe, well-tolerated, and immunogenic in children with chronic liver disease.
Effects of Extremely Low-Frequency Electromagnetic Fields on Neurogenesis and Cognitive Behavior in an Experimental Model of Hippocampal Injury

Exposure to extremely low-frequency electromagnetic fields may induce constant modulation in neuronal plasticity. In recent years, tremendous efforts have been made to design a suitable strategy for enhancing adult neurogenesis, which seems to be deterred due to brain senescence and several neurodegenerative diseases. In this study, we evaluated the effects of ELF-EMF on neurogenesis and memory, following treatment with trimethyltin chloride (TMT) as a neurotoxicant. The mice in all groups (n = 56) were injected with BrdU during the experiment for seven consecutive days to label newborn cells. Spatial memory was assessed by the Morris water maze (MWM) test. By the end of the experiment, neurogenesis and neuronal differentiation were assessed in the hippocampus, using immunohistochemistry and Western blot analysis. Based on the findings, exposure to ELF-EMF enhanced spatial learning and memory in the MWM test. ELF-EMF exposure significantly enhanced the number of BrdU+ and NeuN+ cells in the dentate gyrus of adult mice (P < 0.001 and P < 0.05, resp.). Western blot analysis revealed significant upregulation of NeuroD2 in ELF-EMF-exposed mice compared to the TMT-treated group (P < 0.05). These findings suggest that ELF-EMF might have clinical implications for the improvement of neurodegenerative processes and could help develop a novel therapeutic approach in regenerative medicine.
High-Throughput Nanogap Formation Using Single Ramp Feedback Control

We demonstrate a technique for simultaneously fabricating arrays of electromigrated nanogaps using a single-ramp feedback-controlled voltage clamp. The parallel formation is achieved by controlling the applied bias with a voltage clamp directly adjacent to a nanogap array containing low-impedance shunts. Self-balancing of the electromigration permits the two voltage leads to fix the applied voltage across all the forming nanogaps simultaneously. This single-ramp feedback-controlled voltage clamp method is at least a 100 times faster than previous work utilizing computer feedback control of parallel nanojunctions and also circumvents the deleterious thermal runaway that occurs in the conventional single-ramp technique.