• Fabrication and characterization of dexibuprofen nanocrystals using microchannel fluidic reactor

      Khan, J.; Bshir, S.; Khan, M.A.; Mohammad, Mohammad A.; Isreb, Mohammad (2018-08)
      Purpose: Dexibuprofen is an enantiomer of ibuprofen with low bioavailability which results from its hydrophobic nature. Nanosuspensions have developed a podium to solve the in vitro dissolution problem that frequently occurs in current research. Materials and methods: The drug and polymer solutions were mixed in a microchannel fluid reactor and the successive embryonic nanosuspension was decanted into a vial having the polymer solution. The impact of different process and formulation parameters including inlet angle, antisolvent and solvent flow rate(s), mixing time, drug concentration, polymer type and concentration was evaluated. Results and discussion: Stable dexibuprofen nanocrystals with a particle size of 45±3.0 nm and polydispersity index of 0.19±0.06 were obtained. Differential scanning calorimetry and powder X-ray diffraction confirmed the crystallinity. The key parameters observed were inlet angle 10°, antisolvent to solvent volume of 2.0/0.5 mL/min, 60 minutes mixing with 5 minutes sonication, Poloxamer-407 with a concentration of 0.5% w/v and drug concentration (5 mg/mm). The 60-day stability studies revealed that the nanocrystals were stable at 4°C and 25°C. The scanning electron microscopy and transmission electron microscopy images showed crystalline morphology with a homogeneous distribution. Conclusion: Stable dexibuprofen nanocrystals with retentive distinctive characteristics and having marked dissolution rate compared to raw and marketed formulations were efficiently fabricated. In future perspectives, these nanocrystals could be converted to solid dosage form and the process can be industrialized by chemical engineering approach
    • Fabrication of 3D hybrid scaffold by combination technique of electrospinning-like and freeze-drying to create mechanotransduction signals and mimic extracellular matrix function of skin

      Aghmiuni, A.I.; Heidari Keshel, S.; Sefat, Farshid; AkbarzadehKhiyavi, A. (2021-01)
      Fabrication of extracellular matrix (ECM)-like scaffolds (in terms of structural-functional) is the main challenge in skin tissue engineering. Herein, inspired by macromolecular components of ECM, a novel hybrid scaffold suggested which includes silk/hyaluronan (SF/HA) bio-complex modified by PCP: [polyethylene glycol/chitosan/poly(ɛ-caprolactone)] copolymer containing collagen to differentiate human-adipose-derived stem cells into keratinocytes. In followed by, different weight ratios (wt%) of SF/HA (S1:100/0, S2:80/20, S3:50/50) were applied to study the role of SF/HA in the improvement of physicochemical and biological functions of scaffolds. Notably, the combination of electrospinning-like and freeze-drying methods was also utilized as a new method to create a coherent 3D-network. The results indicated this novel technique was led to ~8% improvement of the scaffold's ductility and ~17% decrease in mean pore diameter, compared to the freeze-drying method. Moreover, the increase of HA (>20wt%) increased porosity to 99%, however, higher tensile strength, modulus, and water absorption% were related to S2 (38.1, 0.32 MPa, 75.3%). More expression of keratinocytes along with growth pattern similar to skin was also observed on S2. This study showed control of HA content creates a microporous-environment with proper modulus and swelling%, although, the role of collagen/PCP as base biocomposite and fabrication technique was undeniable on the inductive signaling of cells. Such a scaffold can mimic skin properties and act as the growth factor through inducing keratinocytes differentiation.
    • Fabrication of crystals from single metal atoms

      Barry, Nicolas P.E.; Pitto-Barry, Anaïs; Sanchez, A.M.; Dove, A.P.; Procter, R.J.; Soldevila-Barreda, Joan J.; Kirby, N.; Hands-Portman, I.; Smith, C.J.; O'Reilly, R.K.; et al. (2014)
      Metal nanocrystals offer new concepts for the design of nanodevices with a range of potential applications. Currently the formation of metal nanocrystals cannot be controlled at the level of individual atoms. Here we describe a new general method for the fabrication of multi-heteroatom-doped graphitic matrices decorated with very small, ångström-sized, three-dimensional (3D)-metal crystals of defined size. We irradiate boron-rich precious-metal-encapsulated self-spreading polymer micelles with electrons and produce, in real time, a doped graphitic support on which individual osmium atoms hop and migrate to form 3D-nanocrystals, as small as 15 Å in diameter, within 1 h. Crystal growth can be observed, quantified and controlled in real time. We also synthesize the first examples of mixed ruthenium–osmium 3D-nanocrystals. This technology not only allows the production of ångström-sized homo- and hetero-crystals, but also provides new experimental insight into the dynamics of nanocrystals and pathways for their assembly from single atoms.
    • Facet-specific adsorption of tripeptides at aqueous au interfaces: open questions in reconciling experiment and simulation

      Hughes, Zak E.; Kochandra, R.; Walsh, T.R. (2017-04-18)
      The adsorption of three homo-tripeptides, HHH, YYY, and SSS, at the aqueous Au interface is investigated, using molecular dynamics simulations. We find that consideration of surface facet effects, relevant to experimental conditions, opens up new questions regarding interpretations of current experimental findings. Our well-tempered metadynamics simulations predict the rank ordering of the tripeptide binding affinities at aqueous Au(111) to be YYY > HHH > SSS. This ranking differs with that obtained from existing experimental data which used surface-immobilized Au nanoparticles as the target substrate. The influence of Au facet on these experimental findings is then considered, via our binding strength predictions of the relevant amino acids at aqueous Au(111) and Au(100)(1 × 1). The Au(111) interface supports an amino acid ranking of Tyr > HisA ≃ HisH > Ser, matching that of the tripeptides on Au(111), while the ranking on Au(100) is HisA > Ser ≃ Tyr ≃ HisH, with only HisA showing non-negligible binding. The substantial reduction in Tyr amino acid affinity for Au(100) vs Au(111) offers one possible explanation for the experimentally observed weaker adsorption of YYY on the nanoparticle-immobilized substrate compared with HHH. In a separate set of simulations, we predict the structures of the adsorbed tripeptides at the two aqueous Au facets, revealing facet-dependent differences in the adsorbed conformations. Our findings suggest that Au facet effects, where relevant, may influence the adsorption structures and energetics of biomolecules, highlighting the possible influence of the structural model used to interpret experimental binding data.
    • A facile preparation of trehalose analogues: 1,1-thiodisaccharides

      Ribeiro Morais, Goreti; Humphrey, Andrew J.; Falconer, Robert A. (21/03/2009)
      The synthesis of 1,1-thiodisaccharide trehalose analogues in good to excellent yields by a Lewis acid (BF(3).Et(2)O)-catalysed coupling of sugar per-O-acetate with thiosugar is described. The reactivity of different sugar per-O-acetates and thiosugars is explored.
    • Factors affecting patients' use of electronic personal health records in England: cross-sectional study

      Abd-Alrazaq, A.; Bewick, B.M.; Farragher, T.; Gardner, Peter H. (2019-07)
      Background: Electronic personal health records (ePHRs) are secure Web-based tools that enable individuals to access, manage, and share their medical records. England recently introduced a nationwide ePHR called Patient Online. As with ePHRs in other countries, adoption rates of Patient Online remain low. Understanding factors affecting patients’ ePHR use is important to increase adoption rates and improve the implementation success of ePHRs. Objective: This study aimed to examine factors associated with patients’ use of ePHRs in England. Methods: The unified theory of acceptance and use of technology was adapted to the use of ePHRs. To empirically examine the adapted model, a cross-sectional survey of a convenience sample was carried out in 4 general practices in West Yorkshire, England. Factors associated with the use of ePHRs were explored using structural equation modeling. Results: Of 800 eligible patients invited to take part in the survey, 624 (78.0%) returned a valid questionnaire. Behavioral intention (BI) was significantly influenced by performance expectancy (PE; beta=.57, P<.001), effort expectancy (EE; beta=.16, P<.001), and perceived privacy and security (PPS; beta=.24, P<.001). The path from social influence to BI was not significant (beta=.03, P=.18). Facilitating conditions (FC) and BI significantly influenced use behavior (UB; beta=.25, P<.001 and beta=.53, P<.001, respectively). PE significantly mediated the effect of EE and PPS on BI (beta=.19, P<.001 and beta=.28, P=.001, respectively). Age significantly moderated 3 paths: PE→BI, EE→BI, and FC→UB. Sex significantly moderated only the relationship between PE and BI. A total of 2 paths were significantly moderated by education and internet access: EE→BI and FC→UB. Income moderated the relationship between FC and UB. The adapted model accounted for 51% of the variance in PE, 76% of the variance in BI, and 48% of the variance in UB. Conclusions: This study identified the main factors that affect patients’ use of ePHRs in England, which should be taken into account for the successful implementation of these systems. For example, developers of ePHRs should involve patients in the process of designing the system to consider functions and features that fit patients’ preferences and skills to ensure systems are useful and easy to use. The proposed model accounted for 48% of the variance in UB, indicating the existence of other, as yet unidentified, factors that influence the adoption of ePHRs. Future studies should confirm the effect of the factors included in this model and identify additional factors.
    • Factors influencing accuracy of referral and the likelihood of false positive referral by optometrists in Bradford, United Kingdom

      Davey, Christopher J.; Scally, Andy J.; Green, Clare; Mitchell, E.S.; Elliott, David B. (2016-07)
      Aims: Levels of false positive referral to ophthalmology departments can be high. This study aimed to evaluate commonality between false positive referrals in order to find the factors which may influence referral accuracy. Methods: In 2007/08, a sample of 431 new Ophthalmology referrals from the catchment area of Bradford Royal Infirmary were retrospectively analysed. Results: The proportion of false positive referrals generated by optometrists decreases with experience at a rate of 6.2% per year since registration (p < 0.0001). Community services which involved further investigation done by the optometrist before directly referring to the hospital were 2.7 times less likely to refer false positively than other referral formats (p = 0.007). Male optometrists were about half as likely to generate a false positive referral than females (OR = 0.51, p = 0.008) and as multiple/corporate practices in the Bradford area employ less experienced and more female staff, independent practices generate about half the number of false positive referrals (OR = 0.52, p = 0.005). Conclusions: Clinician experience has the greatest effect on referral accuracy although there is also a significant effect of gender with women tending to refer more false positives. This may be due to a different approach to patient care and possibly a greater sensitivity to litigation. The improved accuracy of community services (which often refer directly after further investigation) supports further growth of these schemes.
    • Factors supporting and constraining the implementation of robot-assisted surgery: a realist interview study

      Randell, Rebecca; Honey, S.; Alvarado, Natasha; Greenhalgh, J.; Hindmarsh, J.; Pearman, A.; Jayne, D.; Gardner, Peter H.; Gill, A.; Kotze, A.; et al. (2019-06-14)
      To capture stakeholders’ theories concerning how and in what contexts robot-assisted surgery becomes integrated into routine practice. A literature review provided tentative theories that were revised through a realist interview study. Literature-based theories were presented to the interviewees, who were asked to describe to what extent and in what ways those theories reflected their experience. Analysis focused on identifying mechanisms through which robot-assisted surgery becomes integrated into practice and contexts in which those mechanisms are triggered. Nine hospitals in England where robot-assisted surgery is used for colorectal operations. Forty-four theatre staff with experience of robot-assisted colorectal surgery, including surgeons, surgical trainees, theatre nurses, operating department practitioners and anaesthetists. Interviewees emphasised the importance of support from hospital management, team leaders and surgical colleagues. Training together as a team was seen as beneficial, increasing trust in each other’s knowledge and supporting team bonding, in turn leading to improved teamwork. When first introducing robot-assisted surgery, it is beneficial to have a handpicked dedicated robotic team who are able to quickly gain experience and confidence. A suitably sized operating theatre can reduce operation duration and the risk of de-sterilisation. Motivation among team members to persist with robot-assisted surgery can be achieved without involvement in the initial decision to purchase a robot, but training that enables team members to feel confident as they take on the new tasks is essential. We captured accounts of how robot-assisted surgery has been introduced into a range of hospitals. Using a realist approach, we were also able to capture perceptions of the factors that support and constrain the integration of robot-assisted surgery into routine practice. We have translated these into recommendations that can inform future implementations of robot-assisted surgery.
    • Falls in older people: effects of age and blurring vision on the dynamics of stepping

      Heasley, Karen; Buckley, John G.; Scally, Andy J.; Twigg, Peter C.; Elliott, David B. (2005)
      PURPOSE: The risk of falling increases dramatically with age, and visual impairment is known to be an important risk factor. Therefore, it is highly pertinent to assess the effects of age and vision on the performance of everyday tasks linked to falling, such as stepping from one level to another. METHODS: Nine young (age, 26 +/- 4 years) and ten elderly (age, 72 +/- 5 years) subjects performed a stepping-up task of three different heights. Their stepping strategies with blurred and optimally corrected vision were compared. Center of mass (CM), center of pressure (CP) dynamics (in the mediolateral and anteroposterior directions), and foot clearance parameters were determined, and statistical regression modeling was applied. RESULTS: Elderly subjects spent 20% more time (P = 0.03) than young subjects during double support and they had reduced anteroposterior CM-CP divergence (P < 0.001) during double support and slower anteroposterior (P < 0.001) and mediolateral (P = 0.002) CM velocities during initiation of movement and single limb support. Blur caused similar adaptations, such as increased toe clearance, across both age groups, though mediolateral (ML) CM-CP divergence in elderly subjects was significantly more reduced than in young subjects (P < 0.001). CONCLUSIONS: Findings indicate, in general, that older subjects used a more cautious and controlled stepping strategy. However, the lack of significant age differences in toe clearance suggests this strategy was mainly aimed at reducing ML instability rather than increasing margins of safety regarding toe clearance.
    • Fas signaling is involved in the control of hair follicle response to chemotherapy.

      Sharov, A.A.; Siebenhaar, F.; Sharova, T.Y.; Botchkareva, Natalia V.; Gilchrest, B.A.; Botchkarev, Vladimir A. (2004)
      Chemotherapeutic agents induce p53-dependent apoptosis in the hair follicle (HF) resulting in hair loss, a common side effect of cancer therapy. Here, we show that Fas as a p53 target plays important role in the HF response to cyclophosphamide. Specifically, we demonstrate that Fas is up-regulated in HF keratinocytes after cyclophosphamide treatment, Fas ligand-neutralizing antibody partially inhibits HF response to cyclophosphamide in wild-type mice, and Fas knockout mice show significant retardation of cyclophosphamide-induced HF involution associated with reduced Fas-associated death domain and caspase-8 expression. These data raise a possibility to explore blockade of Fas signaling as a part of complex local therapy for inhibiting keratinocyte apoptosis and hair loss induced by chemotherapy.
    • Fast versus gradual adaptation of soft monthly contact lenses in neophyte wearers

      Wolffsohn, J.S.; Ghorbani Mojarrad, Neema; Vianya-Estopa, M.; Nagra, M.; Huntjens, B.; Terry, L.; Sweeney, L.E.; Dutta, D.; Joshi, M.R.; Wright, D.; et al. (2022-08-01)
      To determine if a gradual adaptation period is necessary for neophytes when fitted with modern hydrogel or silicone hydrogel reusable disposable contact lenses. Across four sites, 74 neophytes (18-28 years) were randomly assigned to a reusable lens cleaned nightly with Opti-Free® Puremoist® multi-purpose contact lens solution: Proclear® (hydrogel) or Biofinity® (silicone hydrogel) and an adaptation schedule: fast (10 h wear from the first day) or gradual (4 h on the first day, increasing their wear time by 2 h on each subsequent day until they had reached 10 h). Masked investigators graded ocular surface physiology and non-invasive tear breakup time (NIBUT) and a range of comfort, vision and lens handling subjective ratings (0-100 visual analogue scales) were recorded at the baseline visit and after 10 h of lens wear, 4-6 days and 12-14 days after lens fitting. Subjective scores were also repeated after 7 days. There was no difference (p > 0.05) in ocular surface physiology or NIBUT between fast and gradual adaptation groups at any time point in either lens type with the exception of increased corneal staining (p = 0.019) in the silicone hydrogel fast adaptation group after 4-6 days, but was similar by 12-14 days. Subjective scores were also similar across the visits and lens types with the exception of 'lens awareness' (p = 0.019) which was less in the gradual versus the fast adaptation silicone hydrogel lens group at 12-14 days. There seems to be no clinical benefit for recommending a gradual adaptation period in new wearers fitted with modern soft reusable disposable contact lenses. The findings of this work add to a growing body of evidence suggesting that such advice is unnecessary in regular soft contact lens wear, which has important ramifications for the initial clinical management of these patients.
    • Fast, facile and solvent‐free dry melt synthesis of oxovanadium(IV) complexes: Simple design with high potency towards cancerous cells

      Zegke, Markus; Spencer, H.L.M.; Lord, Rianne M. (2019-09)
      A range of oxobis(phenyl‐1,3‐butanedione) vanadium(IV) complexes have been successfully synthesized from cheap starting materials and a simple and solvent‐free one‐pot dry‐melt reaction. This direct, straightforward, fast and alternative approach to inorganic synthesis has the potential for a wide range of applications. Analytical studies confirm their successful synthesis, purity and solid‐state coordination, and we report the complexes’ uses as potential drug candidates for the treatment of cancer. After a 24‐hour incubation of A549 lung carcinoma cells with the compounds, they reveal cytotoxicity values 11‐fold greater than cisplatin, and remain non‐toxic towards normal cell types. Additionally, the complexes are stable over a range of physiological pH values and show the potential for interactions with BSA.
    • Faster visual reaction times in elite athletes are not linked to better gaze stability

      Barrett, Brendan T.; Cruickshank, Alice G.; Flavell, J.C.; Bennett, S.J.; Buckley, John G.; Harris, J.M.; Scally, Andy J. (2020-08)
      The issue of whether visually-mediated, simple reaction time (VRT) is faster in elite athletes is contentious. Here, we examined if and how VRT is afected by gaze stability in groups of international cricketers (16 females, 28 males), professional rugby-league players (21 males), and non-sporting controls (20 females, 30 males). VRT was recorded via a button-press response to the sudden appearance of a stimulus (circular target—diameter 0.8°), that was presented centrally, or 7.5° to the left or right of fxation. The incidence and timing of saccades and blinks occurring from 450 ms before stimulus onset to 225 ms after onset were measured to quantify gaze stability. Our results show that (1) cricketers have faster VRT than controls; (2) blinks and, in particular, saccades are associated with slower VRT regardless of the level of sporting ability; (3) elite female cricketers had steadier gaze (fewer saccades and blinks) compared to female controls; (4) when we accounted for the presence of blinks and saccades, our group comparisons of VRT were virtually unchanged. The stability of gaze is not a factor that explains the difference between elite and control groups in VRT. Thus we conclude that better gaze stability cannot explain faster VRT in elite sports players.
    • Female sterility associated with increased clonal propagation suggests a unique combination of androdioecy and asexual reproduction in populations of Cardamine amara (Brassicaceae)

      Tedder, Andrew; Helling, M.; Pannell, J.R.; Shimizu-Inatsugi, R.; Kawagoe, T.; van Campen, J.; Sese, J.; Shimizu, K.K. (2015-04)
      The coexistence of hermaphrodites and female-sterile individuals, or androdioecy, has been documented in only a handful of plants and animals. This study reports its existence in the plant species Cardamine amara (Brassicaceae), in which female-sterile individuals have shorter pistils than seed-producing hermaphrodites. Morphological analysis, in situ manual pollination, microsatellite genotyping and differential gene expression analysis using Arabidopsis microarrays were used to delimit variation between female-sterile individuals and hermaphrodites. Female sterility in C. amara appears to be caused by disrupted ovule development. It was associated with a 2.4- to 2.9-fold increase in clonal propagation. This made the pollen number of female-sterile genets more than double that of hermaphrodite genets, which fulfils a condition of co-existence predicted by simple androdioecy theories. When female-sterile individuals were observed in wild androdioecious populations, their ramet frequencies ranged from 5 to 54 %; however, their genet frequencies ranged from 11 to 29 %, which is consistent with the theoretically predicted upper limit of 50 %. The results suggest that a combination of sexual reproduction and increased asexual proliferation by female-sterile individuals probably explains the invasion and maintenance of female sterility in otherwise hermaphroditic populations. To our knowledge, this is the first report of the coexistence of female sterility and hermaphrodites in the Brassicaceae.
    • Feminist Pedagogy: implications and practice

      Croucher, Karina T.; Cobb, H.; Casella, E. (2014-02)
      Rosemary Joyce’s research in gender archaeology and archaeologies of the body and identity have not only impacted on our interpretations of the body and identity in the past, but have contributed vastly to our understandings of epistemologies of academic practice, particularly with relation to addressing the androcentric and hetero-normative frameworks in which the disciplines of archaeology and anthropology have traditionally operated. Furthermore, through reassessing ways of viewing, researching, and interpreting the past, Joyce and her contemporaries have changed the face of archaeological theory, method and practice, pre-empting current theoretical concepts (for instance, Ingold’s ‘meshworks’ and Hodder’s ‘entanglement’ theories as lenses for interpreting the past (and the present)) by over twenty years. This paper explores Joyce’s contribution in redressing our epistemologies, which influence our understanding of the past, and impact on archaeological research and practice. For instance, recognition of multiple narratives and the democratization of the archaeological voice have created new understandings and interpretations of our archaeological record. Taking a case study of an archaeological field school and research excavation, the Ardnamurchan Transitions Project, this paper explores how an approach grounded in feminist ways of seeing the world, and a democratization of communication, impact on student learning, both in the field and the classroom, and ultimately, in our archaeological interpretations and understanding. Crucially, this paper also highlights that our discipline has some way to go in realizing the foundations laid by Joyce and her contemporaries.
    • A FFLUX water model: flexible, polarizable and with a multipolar description of electrostatics

      Hughes, Zak E.; Ren, E.; Thacker, J.C.R.; Symons, B.C.B.; Silva, A.F.; Popelier, P.L.A. (2020-03)
      Key to progress in molecular simulation is the development of advanced models that go beyond the limitations of traditional force fields that employ a fixed, point charge‐based description of electrostatics. Taking water as an example system, the FFLUX framework is shown capable of producing models that are flexible, polarizable and have a multipolar description of the electrostatics. The kriging machine‐learning methods used in FFLUX are able to reproduce the intramolecular potential energy surface and multipole moments of a single water molecule with chemical accuracy using as few as 50 training configurations. Molecular dynamics simulations of water clusters (25–216 molecules) using the new FFLUX model reveal that incorporating charge‐quadrupole, dipole–dipole, and quadrupole–charge interactions into the description of the electrostatics results in significant changes to the intermolecular structuring of the water molecules.
    • Fibroblast cell-based therapy prevents induction of alopecia areata in an experimental model

      Jalili, R.B.; Kilani, R.T.; Li, Y.; Khosravi-maharlooie, M.; Nabai, L.; Wang, E.H.C.; McElwee, Kevin J.; Ghahary, A. (2018-06)
      Alopecia areata (AA) is an autoimmune hair loss disease with infiltration of proinflammatory cells into hair follicles. Current therapeutic regimens are unsatisfactory mainly because of the potential for side effects and/or limited efficacy. Here we report that cultured, transduced fibroblasts, which express the immunomodulatory molecule indoleamine 2,3-dioxygenase (IDO), can be applied to prevent hair loss in an experimental AA model. A single intraperitoneal (IP) injection of IDO-expressing primary dermal fibroblasts was given to C3H/HeJ mice at the time of AA induction. While 60–70% of mice that received either control fibroblasts or vehicle injections developed extensive AA, none of the IDO-expressing fibroblast-treated mice showed new hair loss up to 20 weeks post injection. IDO cell therapy significantly reduced infiltration of CD4+ and CD8+ T cells into hair follicles and resulted in decreased expression of TNF-α, IFN-γ and IL-17 in the skin. Skin draining lymph nodes of IDO fibroblast-treated mice were significantly smaller, with more CD4+ CD25+ FoxP3+ regulatory T cells and fewer Th17 cells than those of control fibroblast and vehicle-injected mice. These findings indicate that IP injected IDO-expressing dermal fibroblasts can control inflammation and thereby prevent AA hair loss.
    • Fibroblast growth factor receptor 1 promotes proliferation and survival via activation of the mitogen-activated protein kinase pathway in bladder cancer

      Tomlinson, D.C.; Lamont, F.R.; Shnyder, Steven D.; Knowles, M.A. (2009)
      Fibroblast growth factor receptors (FGFR) play key roles in proliferation, differentiation, and tumorigenesis. Many urothelial carcinomas contain activating point mutations or increased expression of FGFR3. However, little is known about the role of other FGFRs. We examined FGFR expression in telomerase-immortalized normal human urothelial cells, urothelial carcinoma cell lines, and tumor samples and showed that FGFR1 expression is increased in a high proportion of cell lines and tumors independent of stage and grade. To determine the role of FGFR1 in low-stage bladder cancer, we overexpressed FGFR1 in telomerase-immortalized normal human urothelial cells and examined changes in proliferation and cell survival in response to FGF2. FGFR1 stimulation increased proliferation and reduced apoptosis. To elucidate the mechanistic basis for these alterations, we examined the signaling cascades activated by FGFR1. FRS2alpha and PLCgamma were activated in response to FGF2, leading to activation of the mitogen-activated protein kinase pathway. The level of mitogen-activated protein kinase activation correlated with the level of cyclin D1, MCL1, and phospho-BAD, which also correlated with FGFR-induced proliferation and survival. Knockdown of FGFR1 in urothelial carcinoma cell lines revealed differential FGFR1 dependence. JMSU1 cells were dependent on FGFR1 expression for survival but three other cell lines were not. Two cell lines (JMSU1 and UMUC3) were dependent on FGFR1 for growth in soft agar. Only one of the cell lines tested (UMUC3) was frankly tumorigenic; here, FGFR1 knockdown inhibited tumor growth. Our results indicate that FGFR1 has significant effects on urothelial cell phenotype and may represent a useful therapeutic target in some cases of urothelial carcinoma.
    • Fieldwork at Chapel Road, Fillingham.

      Buckberry, Jo; Hadley, D.M. (2001)
    • Filtration Suppresses Laser-Induced Nucleation of Glycine in Aqueous Solutions

      Javid, Nadeem; Kendall, T.; Burns, I.S.; Sefcik, J. (2016-08-03)
      We demonstrate that nanofiltration of aqueous glycine solutions has a pronounced effect on laser-induced nucleation. Two nucleation regimes were observed in nonfiltered, irradiated solutions under isothermal conditions: a rapid initial regime associated with laser-induced nucleation and a second much slower spontaneous nucleation regime. Filtration of the solutions prior to irradiation greatly suppressed the rapid regime, while the slow regime was similar regardless of filtration or irradiation, for all supersaturations studied. A clear effect of filtration on crystal polymorphism was also observed. Nonfiltered irradiated solutions at a lower supersaturation almost exclusively yielded the α-polymorph, while at higher supersaturations there was significant presence (∼40%) of the γ-polymorph. On the other hand, filtered solutions almost exclusively yielded the α-polymorph of glycine at all supersaturations studied. These surprising results challenge some established ideas about laser-induced nucleation, showing that previously reported laser-induced nucleation phenomena in glycine aqueous solutions can be effectively suppressed by filtration, so that the underlying mechanism is unlikely to be based on molecular scale interactions involving just the solute and the solvent alone. Instead, laser-induced nucleation in this system appears to be related to either colloidal scale solution clusters or foreign solid or molecular impurities that can be removed by nanofiltration.