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Organohalides are recalcitrant, toxic environmental pollutants. Reductive dehalogenase enzymes (RDases) found in organohalide respiring bacteria (OHRB) utilise organohalides as electron acceptors for cellular energy and growth, producing lesser-halogenated compounds. Consequently, microbial reductive dehalogenation via organohalide respiration represents a promising solution for clean-up of organohalide pollutants. Dehalobacter sp. UNSWDHB is an OHRB capable of respiring highly toxic chloroform (CF) and converting it to dichloromethane (DCM). TmrA has been identified as an RDase responsible for this conversion and different strategies for generation of functional recombinant TmrA is the focus of this article. In this study, TmrA was recovered from inclusion bodies expressed in E. coli and refolded in the presence of FeCl 3 , Na 2 S and cobalamin to yield functional enzyme. TmrA has been previously expressed in a soluble and functional form in the corrinoid-producing Bacillus megaterium. Using a fractional experimental design for cultivation and induction combined with purification under anaerobic conditions resulted in substantially higher activity of recombinant and native TmrA than previously reported. TmrA was then expressed in a soluble and active form in Shimwellia blattae. Co-expression with two different putative chaperone proteins from the original host did not increase the level of soluble expression in S. blattae , however activity assays showed that removing the TAT signal from TmrA increases the dechlorination activity compared to when the TAT signal is present. Finally, TmrA was successfully expressed in a soluble and active form in the H 2 -oxidizing C. necator H16, a novel host for the expression of RDases. • Active recombinant reductive dehalogenase (TmrA) in four different microbial hosts • Improved activity was achieved in Bacillus megaterium by process optimisation • Removal of the Tat signal improved activity when expressed in Shimwella blattae • Functional RDase expression in Cupravidius necator for the first time [ABSTRACT FROM AUTHOR]

Protein self-assembly is a process that often occurs via liquid–liquid phase separation (LLPS), a sequence-specific and environmentally influenced phenomenon. Heuristic analysis of these self-assembling proteins has highlighted the conservation and importance of tyrosine residues and their ability to initiate LLPS and subsequent liquid–solid phase transitions. Generating tyrosine-templated constructs such as those found in nature serves as a promising method to generate responsive, self-assembling systems for a diverse range of applications. We discuss the importance of tyrosine in mediating the self-assembly of proteins, the interactions that enable this, and how it can be exploited for beneficial purposes. Protein self-assembly, guided by the interplay of sequence- and environment-dependent liquid–liquid phase separation (LLPS), constitutes a fundamental process in the assembly of numerous intrinsically disordered proteins. Heuristic examination of these proteins has underscored the role of tyrosine residues, evident in their conservation and pivotal involvement in initiating LLPS and subsequent liquid–solid phase transitions (LSPT). The development of tyrosine-templated constructs, designed to mimic their natural counterparts, emerges as a promising strategy for creating adaptive, self-assembling systems with diverse applications. This review explores the central role of tyrosine in orchestrating protein self-assembly, delving into key interactions and examining its potential in innovative applications, including responsive biomaterials and bioengineering. [ABSTRACT FROM AUTHOR]

We report the antimicrobial activity of bare and surface functionalized indium tin oxide (ITO) conjugated with T4 bacteriophage towards E. coli . A ∼ 10 3 -fold reduction (99.9%) in the bacterial concentration was achieved within 2 h exposure of E. coli to the bare as well as the amine, carboxylic and methyl functionalized ITO/T4 surfaces. Despite the known differences in bacteriophage loading of these ITO/T4 systems, the almost identical extent of antimicrobial activity of all of the ITO/T4 systems resulted from the release of a comparable amount of infective T4 from the systems. As anticipated, a single dose of immobilized bacteriophage was sufficient to eliminate further surge of bacterial population. Upon the 2 h eradication of the ‘1st batch’ of E. coli population, all of the ITO/T4 systems, each system with 10 2 -fold more suspended bacteriophage (due to propagation of the phage at the expense of the ‘1st batch’ E. coli death), reduced the ‘2nd batch’ of E. coli concentration by ∼10 4 -fold in just 30 min, suggesting the potential of immobilized bacteriophage systems as solution to the issues of antimicrobial agent depletion. All of the ITO/T4 systems maintained their antimicrobial activity in the presence of model food components. The antimicrobial activity was however, affected by pH; at pH 5 whereby the bacteria’s growth was physiologically inhibited, generally no reduction in E. coli concentration was detected. The present work provides an understanding of the mode of antimicrobial activity exhibited by an immobilized bacteriophage based substrate and demonstrates efficacy in the presence of food components. [ABSTRACT FROM AUTHOR]

This work demonstrates the use of bacteriophage conjugated magnetic particles (Fe 3 O 4 ) for the rapid capturing and isolation of Escherichia coli . The investigation of T4 bacteriophage adsorption to silane functionalised Fe 3 O 4 with amine ( NH 2 ), carboxylic ( COOH) and methyl ( CH 3 ) surface functional groups reveals the domination of net electrostatic and hydrophobic interactions in governing bacteriophage adsorption. The bare Fe 3 O 4 and Fe 3 O 4 -NH 2 with high T4 loading captured 3-fold more E. coli (∼70% capturing efficiency) compared to the low loading T4 on Fe 3 O 4 -COOH, suggesting the significance of T4 loading in E. coli capturing efficiency. Importantly, it is further revealed that E. coli capture is highly dependent on the incubation temperature and the presence of tryptone in the media. Effective E. coli capturing only occurs at 37 °C in tryptone-containing media with the absence of either conditions resulted in poor bacteria capture. The incubation temperature dictates the capturing ability of Fe 3 O 4 /T4, whereby T4 and E. coli need to establish an irreversible binding that occurred at 37 °C. The presence of tryptophan-rich tryptone in the suspending media was also critical, as shown by a 3-fold increase in E. coli capture efficiency of Fe 3 O 4 /T4 in tryptone-containing media compared to that in tryptone-free media. This highlights for the first time that successful bacteria capturing requires not only an optimum tailoring of the particle’s surface physicochemical properties for favourable bacteriophage loading, but also an in-depth understanding of how factors, such as temperature and solution chemistry influence the subsequent bacteriophage-bacteria interactions. [ABSTRACT FROM AUTHOR]

In 2012 the Department of Education received a complaint claiming that the Massachusetts Interscholastic Athletic Association's ("MIAA") policy of allowing boys to try out for girls' field hockey constituted a violation of Title IX. This federal statute prohibits discrimination in educational institutions on the basis of sex. This Note looks at the common roots of Title IX and the decision of the Massachusetts Supreme Judicial Court that allowed boys' participation in field hockey. It then examines Title IX as it applies to the MIAA field hockey policy and determines that the Massachusetts Policy does not, in and of itself, create a violation. This Note further suggests that even if the policy did violate Title IX, policy implications suggest that using Title IX to invalidate another provision designed to promote gender equality is unwise. Finally, this Note identifies a number of gender-neutral alternatives to deal with the legitimate problems posed by the participation of boys in what are traditionally girls' sports. [ABSTRACT FROM AUTHOR]

On March 22, 2012, in Cuff ex rel. B.C. v. Valley Central School District, the U.S. Court of Appeals for the Second Circuit held that suspending a student for writing a wish to blow up the school did not violate the student's First Amendment right of expression. The court concluded that the suspension satisfied the substantial disruption test outlined by the Supreme Court in Tinker v. Des Moines Independent Community School District. The Second Circuit, however, could have reached the same result without undermining student speech protections by applying the Supreme Court's narrower standard presented in Bethel School District Number 403 v. Fraser, which allows restrictions on certain types of speech based on the school's role in teaching students societal values. Applying the Fraser standard in this case would have given school officials the tools necessary to protect students from violence, while preserving the students' free speech rights. [ABSTRACT FROM AUTHOR]

A number of studies have shown that, as a result of the ambiguity of US legal mandates, organizations have considerable latitude in how they comply with regulations. In this paper, we address how the different agendas of the federal and state governments increase ambiguities in state-firm relations and how states are interested actors in creating opportunities for firms to navigate the federal legislation. We analyze the institutional forces behind bank acquisitions within and across state lines in order to illuminate the ways that US states take advantage of federal ambiguity and are able to shape corporate practices to their benefit. We specifically examine how patterns of bank acquisitions are shaped by the crucial relationship between the federal Community Reinvestment Act (CRA) and a little-understood provision in the federal tax code that is implemented at the state level, the Low-Income Housing Tax Credit (LIHTC). The relationship is complex because, while the federal government uses the CRA to control bank acquisition activity, states promote use of the LIHTC, through which banks can address federal CRA concerns, and thereby promote bank acquisitions in their jurisdictions. Thus, our findings suggest that the implementation of social legislation at one level in a federal regulatory system undermines the mechanisms of social legislation at another level. We use archival research and in-depth interviews to examine the interaction between these institutional processes and formulate hypotheses that predict the ways in which bank acquisitions are constrained by banks’ CRA ratings and the way states in turn help banks overcome their CRA constraints. Quantitative analyses of all bank acquisitions in the United States from 1990–2000 largely support these hypotheses. [Copyright &y& Elsevier]

Increasing use of titanium dioxide (TiO) nanoparticles in many commercial applications has led to emerging concerns regarding the safety and environmental impact of these materials. In this study, we have investigated the biological impact of nano-TiO (with particle primary size of 20 nm Aeroxide P25) on human lung cell lines in vitro and also the effect of particle size distribution on the particle uptake and apparent toxicity. The biological impact of nano-TiO is shown to be influenced by the concentration and particle size distribution of the TiO and the impact was shown to differ between the two cell lines (A549 and H1299) investigated herein. A549 cell line was shown to be relatively resistant to the total amount of TiO particles uptaken, as measured by cell viability and metabolic assays, while H1299 had a much higher capacity to ingest TiO particles and aggregates, with consequent evidence of impact at concentrations as low as 30-150 μg/mL TiO. Evidence gathered from this study suggests that both viability and metabolic assays (measuring metabolic and mitochondrial activities and also cellular ATP level) should be carried out collectively to gain a true assessment of the impact of exposure to TiO particles. [ABSTRACT FROM AUTHOR]

• An integrated system consisting of two membrane-less microfiltration techniques. • Miniaturized hydrocyclone developed using additive manufacturing and soft lithography. • Recapturing of cells using the multiplexed spiral microchannels. • More than 90% efficiency at the estimated cell density of 80 million cells/mL. Large-scale cell culture processes are required to produce biopharmaceuticals, cells for tissue engineering, and vaccine production while being effective in toxicity testing, gene therapy vector production for cancer research, and drug development. A growing trend in these industries, particularly for suspension cells, involves implementation of continuous cell perfusion processes, which require an aseptic, efficient, cost-effective, and reliable cell separation and retention scheme. Many cell separation techniques (membrane-based systems, lateral displacement devices, and acoustophoresis) have proven to be highly efficient, but suffer from issue of clogging and high cost, limiting their reliability, and thus, their overall feasibility. Some cell retention devices—those based on inertial microfluidics—offer high reliability (i.e., clog-free), but their efficiency reduces at higher cell concentrations. To overcome this apparent trade-off, we report the development of an integrated system consisting of two different membrane-less microfiltration techniques for cell separation from spent cell media. Although it could be adapted to numerous cell culture applications, this system was optimized and tested for suspension-adapted Chinese Hamster Ovary (CHO) cells. As the first step of the cell retention system, a miniaturised hydrocyclone was developed that could separate the cells with macroscopic volume processing rates (~200 mL/min). At this stage, up to 75% of the cells were isolated with minimal (<5%) change in the viability. The remaining cells passed through the overflow of the device and entered to a multiplexed spiral microchannel system, where more than 90% of the remaining cells were recovered, yielding an overall efficiency of up to 95%. The proposed integrated system is thus ideal for continuous and high throughput cell retention even at high cell concentrations (~80 million cells/mL), which is in range of current need in the bioprocessing industry. [ABSTRACT FROM AUTHOR]

Several specific syndromes within the RASopathies spectrum lead to an increased risk of seizures up to developing refractory epileptic encephalopathy. Management remains symptomatic. Here we report two patients treated with trametinib, a MEK1-2 inhibitor, as a precision strategy for drug-resistant epilepsy. Patient 1 is a six-year-old girl with cardiofaciocutaneous syndrome (BRAF p.F595L, germline mutation), and Patient 2 is a 14-month-old boy with Schimmelpenning syndrome (KRAS p.G12D, postzygotic somatic mutation). Trametinib was initiated at a dosage of 0.025 mg/kg/day. Patient 1 had multiple seizures per day, multifocal motor to bilateral tonic-clonic. Electroencephalography (EEG) showed a dramatic reduction in EEG discharges three months after trametinib onset, while a marked clinical improvement occurred after about five months, at the same dosage, and the girl is currently seizure-free for more than six months. Patient 2 had left cerebral hemiatrophy leading to right focal motor seizures, multiple per week to multiple per day, since the age of three months. On trametinib, he experienced an early benefit, remaining seizure-free for more than three months. However, after six months we observed recurrence of seizures. After 22 months of treatment, trametinib was discontinued because of a suspected drug-induced inflammatory colitis. After discontinuation, we observed a significant clinical and EEG "rebound effect." We provide proof of concept that MEK inhibition is a promising approach for the treatment of patients with refractory epilepsy with selected germline and mosaic RASopathies. Future trials are encouraged to better investigate their potentials and limitations. [ABSTRACT FROM AUTHOR]

A hydrocyclone is a macroscale separation device employed in various industries, with many advantages, including high-throughput and low operational costs. Translating these advantages to microscale has been a challenge due to the microscale fabrication limitations that can be surmounted using 3D printing technology. Additionally, it is difficult to simulate the performance of real 3D-printed micro-hydrocyclones because of turbulent eddies and the deviations from the design due to printing resolution. To address these issues, we propose a new experimental method for the direct observation of particle motion in 3D printed micro-hydrocyclones. To do so, wax 3D printing and soft lithography were used in combination to construct a transparent micro-hydrocyclone in a single block of polydimethylsiloxane. A high-speed camera and fluorescent particles were employed to obtain clear in situ images and to confirm the presence of the vortex core. To showcase the use of this method, we demonstrate that a well-designed device can achieve a 95% separation efficiency for a sample containing a mixture of (desired) stem cells and (undesired) microcarriers. Overall, we hope that the proposed method for the direct visualization of particle trajectories in micro-hydrocyclones will serve as a tool, which can be leveraged to accelerate the development of micro-hydrocyclones for biomedical applications. [ABSTRACT FROM AUTHOR]

Abstract In this study, a cashew allergen, Ana o 3 (2S albumin), was used as a protein marker to develop two sensitive and specific sandwich ELISAs (denoted as CAS-ELISA-2 and Ano3-ELISA-1) with the limits of detection (LOD, determined as a concentration that yield 20% of maximum colour development) at 0.04 and 0.06 mg protein kg−1, respectively. The ELISAs were highly specific to cashew nut with very low cross-reactivity with pistachio, pecan, almond, peanut, and hazelnut. Assay validation on the model cookies observed lower cashew protein recovery of 40.2–44.9% with the CAS–ELISA–2 assay and 25.2–79.8% with the Ano3–ELISA–1 assay. Both assays exhibited a limit of quantitation (LOQ) of 40 mg protein kg−1 cookies. While for the model chocolate, the acceptable protein recoveries were obtained with both CAS–ELISA–2 (74.0–87.7%) and Ano3–ELISA–1 (62.8–136.2%). The LOQ of 4 mg protein kg−1 chocolate were achieved. Highlights • Simple one-step purification of Ana o 3 from cashew nuts. • Very low cross-reactivity with pistachio, pecan, almond, peanut, and hazelnut. • LOQ at 0.4 mg and 40 mg protein kg−1 for chocolate and cookies respectively. [ABSTRACT FROM AUTHOR]

Nanosilver (Ag NPs) is currently one of the most commercialized antimicrobial nanoparticles with as yet, still unresolved cytotoxicity origins. To date, research efforts have mostly described the antimicrobial contribution from the leaching of soluble silver, while the undissolved solid Ag particulates are often considered as being microbiologically inert, serving only as source of the cytotoxic Ag ions. Here, we show the rapid stimulation of lethal cellular oxidative stress in bacteria by the presence of the undissolved Ag particulates. The cytotoxicity characteristics are distinct from those arising from the leached soluble Ag, the latter being locked in organic complexes. The work also highlights the unique oxidative stress-independent bacterial toxicity of silver salt. Taken together, the findings advocate that future enquiries on the antimicrobial potency and also importantly, the environmental and clinical impact of Ag NPs use, should pay attention to the potential bacterial toxicological responses to the undissolved Ag particulates, rather than just to the leaching of soluble silver. The findings also put into question the common use of silver salt as model material for evaluating bacterial toxicity of Ag NPs. [ABSTRACT FROM AUTHOR]

Background: DNA methylation is a critical molecular mark involved in cellular differentiation and cell-specific processes. Single-cell whole genome DNA methylation profiling methods hold great potential to resolve the DNA methylation profiles of individual cell-types. Here we present a method that couples single-cell combinatorial indexing (sci) with enzymatic conversion (sciEM) of unmethylated cytosines. Results: The sciEM method facilitates DNA methylation profiling of single-cells that is highly correlated with single-cell bisulfite-based workflows (r2 > 0.99) whilst improving sequencing alignment rates, reducing adapter contamination and over-estimation of DNA methylation levels (CpG and non-CpG). As proof-of-concept we perform sciEM analysis of the temporal lobe, motor cortex, hippocampus and cerebellum of the human brain to resolve single-cell DNA methylation of all major cell-types. Conclusion: To our knowledge sciEM represents the first non-bisulfite single-cell DNA methylation sequencing approach with single-base resolution. [ABSTRACT FROM AUTHOR]

The work investigates the influence of surface physicochemical properties of planar indium tin oxide (ITO) as a model substrate on T4 bacteriophage adsorption. A comparative T4 bacteriophage adsorption study shows a significant difference in bacteriophage adsorption observed on chemically modified planar ITO when compared to similarly modified particulate ITO, which infers that trends observed in virus-particle interaction studies are not necessarily transferrable to predict virus-planar surface adsorption behaviour. We also found that ITO surfaces modified with methyl groups, (resulting in increased surface roughness and hydrophobicity) remained capable of adsorbing T4 bacteriophage. The adsorption of T4 onto bare, amine and carboxylic functionalised planar ITO suggests the presence of a unique binding behaviour involving specific functional groups on planar ITO surface beyond the non-specific electrostatic interactions that dominate phage to particle interactions. The paper demonstrates the significance of physicochemical properties of surfaces on bacteriophage-surface interactions. [ABSTRACT FROM AUTHOR]

Abstract: The kinetics of the enzymatic conversion of coconut oil to biodiesel (fatty acid alkyl esters) have been investigated using ethanol and 1% (w/v) lipase at 50°C. Coconut oil is being evaluated for biofuel production and an enzymatic process was selected to minimize side reactions (such as saponification) which can occur with the alkali-catalysed route if free fatty acid (FFA) concentration is significant. Rate data comparison showed that the NaOH-promoted conversion was about 2 orders of magnitude faster than the lipase-catalysed system but resulted in saponification/partial solidification of the reaction mixture. Analysis also revealed that the ratios of the kinetic constants for ester:glycerol (1:1.12) and that for ester:ethanol (1:3.11) during enzymatic transesterification are in agreement with reaction stoichiometry. Additionally, FFA esterification rates were higher (1.5 to 2.5) than triglyceride transesterification rates under similar conditions. Supplementation with ultrasonics at 43kHz also permitted nearly 20-fold improvement in conversion rate. The study also demonstrated that with Saccharomyces cerevisiae, the growth yield on glycerol of 0.77gg−1 is greater than that usually found for growth of yeast on glucose (viz. 0.4–0.45gg−1). Thus, opportunities for process enhancement exist through the use of increased enzyme concentrations, ultrasound techniques and growth of yeast on residual by-product glycerol. [Copyright &y& Elsevier]

Abstract: Background: The study compared three-dimensional (3D) changes in geometry of the first metatarsal following scarf osteotomy performed on standardised Sawbone® models by consultant foot and ankle surgeons. The study considered the inter-surgeon variances in interpretation and performance of the scarf osteotomy with respect to intra-surgeon variances. Methods: The analysis used an accurate digitising system to measure and record points on the Sawbone® models in 3D space. Computer software performed vector analysis to calculate 3D rotations and translations of the first metatarsal head as well as the inter-metatarsal angle. Bone cut lengths and displacements were measured using a digital Vernier caliper. One surgeon performed the osteotomy 10 times to form an intra-surgeon control dataset, while 10 different surgeons each did one scarf osteotomy to form an inter-surgeon test dataset. Results: Both surgical groups produced reductions in the 3D inter-metatarsal angle with non-significant differences between the groups (p >0.05). In contrast, the test group demonstrated highly significant (p =0.000) greater variance compared with the control dataset for all of the variables associated with surgical technique. In addition, there were highly significant (p =0.02 and 0.002) greater variances in the interpretation of the degree to which the metatarsal head should be translated medially (X) and inferiorly (Z). There was also a significant (p =0.001) increase in variances in the rotations about the dorsi/plantar-flexion (X) axis. The only significant differences (all p =0.000) attributable solely to differences in mean values were in proximal–distal (Y) translation, pronation (Y) rotation and medial (Z) rotation. The test group applied greater medial and plantar-flexion rotation of the metatarsal head than the control surgeon and significantly less (p =0.000) shortening of the first metatarsal than the control surgeon. Conclusions: The results of this geometric study demonstrate the versatility of the scarf osteotomy. As a result of the multi-planar nature of the osteotomy, there is a potential risk of producing unintended rotational mal-unions in all three planes. These rotational mal-unions may account for some of the poorer outcomes documented within the literature. [Copyright &y& Elsevier]

Rational, aims and objectives The objective of the study was to assess prescribers' compliance with guidelines for acute community-acquired pneumonia management in a paediatric university hospital centre before and after its dissemination. Method This quasi-experimental study without a control group was conducted before and after new community-acquired pneumonia management guidelines were disseminated in a tertiary care paediatric hospital. The pre-intervention (baseline) period was from October 2004 to March 2005. The intervention period was divided into two phases: (1) October 2005 to January 14, 2006 (consultation by peer leaders and networking) and (2) January 15, 2006, to March 2006 (dissemination of official guidelines and of a pre-printed prescription sheet, an educational session led by a peer leader for residents and further networking). We used a compliance score to assess prescriptions written by prescribers who practised in the units where the guidelines had to be followed. Results The study included a total of 1151 prescriptions. The prescription compliance with the guidelines increased from 131/652 (20.1%) in the pre-intervention period to 264/499 (52.9%) in the post-intervention intervention period: a difference of 32.8% (CI 95% 27.4–38.0). Similar results were found if analysed according to affiliation (emergency department or wards). An inappropriate choice of antibiotic agent represented 347/521 (66.6%) of the causes of non-compliance in the pre-intervention period and 99/235 (42.1) in the intervention period: a difference of −24.5% (95% CI −31.8, −16.8). Conclusion Guideline dissemination for the management of acute community-acquired pneumonia significantly increased prescriber compliance in the emergency department and on wards. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the management of emergency drugs in a mother-child teaching hospital. Methods: A physical inventory of all the resuscitation carts, emergency carts, and emergency boxes was taken. Fifteen compliance criteria were established to evaluate partial trays of emergency medications. The contents of full and partial emergency medication trays and boxes were revised, and an improved process was implemented based on a review of the literature. The research team included 2 pharmacists, 1 anesthetist, 1 intensivist, 1 emergency doctor, 1 nurse, and 1 research assistant. Results: Before the harmonization process, there were 11 full resuscitation carts with 48 items and 30 partial emergency carts with an average item count of 15.4 ± standard deviation 4.4, as well as 16 pediatric boxes and 3 emergency boxes in pediatrics and obstetrics, respectively. During the evaluation process, 1,911 distribution units were checked, 2.5% of which had expired. Following the process there were 14 identical resuscitation carts with 43 items and 25 emergency carts with 21 items. Conclusion: There are few examples of steps that can be taken to evaluate and update the management of emergency medications in health care facilities. This evaluative study outlines an approach that entailed taking a physical inventory, evaluating the process, and improving the management model within a tertiary care university hospital center. A review of the new process will be performed in 12 months' time. [ABSTRACT FROM AUTHOR]

Economic and organizational sociologists have increasingly demonstrated that the actions of individuals and firms are affected by the social networks within which they are embedded. In recent years scholars have begun to recognize that the effects of these social networks may vary across populations or types of relations. This article examines the extent to which the effects of interfirm networks on the behavior of firms are historically contingent. Focusing on the level of debt financing among approximately 140 large U.S. corporations over a 22-year period, the authors show that the extent to which the firms' use of debt was influenced by those with which they were tied through director interlocks declined over time. The authors argue that this decline in the network effect reflected a shift in the institutional environment within which the firms operated, and that it was driven by three processes: the professionalization of the finance function within the firm, the internalization of financial decision-making, and the increased volatility of the environment. They conclude that corporate financing is socially embedded, but this embeddedness is historically contingent. [ABSTRACT FROM AUTHOR]