Internal Library Research Articles

Composition and Antibacterial Activity of the Essential Oil of Phlomidoschema parviflorum from Iran

The monotypic genus Phlomidoschema Vved. belongs to the family Lamiaceae, subfamily Lamioideae and tribe Stachydeae [1]. Phlomidoschema parviflorum (Benth.) Vved. grows in restricted parts of Iran (Khorasan Province) as well as Afghanistan, west of Pakistan, Pamir Mountains, and Punjab of India. Morphologically, the species is characterized by perennial, multi-stemmed and subshrub habit and white subfloccose and canescent hairs on the leaves and stem [2]. The species is considered vulnerable and rare according to IUCN categories [3]. The infusion of the aerial flowering part of the plant is used locally for the treatment of gastrointestinal disorders, colic and stomachache. From the phylogenetic point of view, the genus is closely allied with the genus Stachys. The most relative and closest species of the genus Stachys to the genus Phlomidoschema was found to be S. lavandulifolia Vahl. [1]. As far as our literature survey could ascertain, there is no report on the oil composition and biological activity of P. parviflorum. So, in continuation of our research on the composition and biological activity of Iranian aromatic and essential oil-bearing plants of the mint family [4–10], we have investigated the composition and antibacterial activity of the essential oil of P. parviflorum. The aerial full flowering parts of Phlomidoschema parviflorum were collected from Khorasan-e Razavi Province, Ghayen towards Gonabad, Zirkuh region with an altitude of 1300–1350 m. A voucher specimen was identified and deposited (MPH-1220) in the Medicinal Plants and Drugs Research Institute Herbarium (MPH), Shahid Beheshti University of Tehran, Iran. Air-dried aerial parts (200 g) were subjected to hydrodistillation for 3 h using a Clevenger-type apparatus. The oil was dried over anhydrous sodium sulfate and stored in sealed vials at 4C until analysis and tested. GC analysis was carried out on a Thermoquest-Finnigan Trace GC instrument equipped with a capillary DB-5 fused silica column (60 m 0.25 mm i.d., film thickness 0.25 m). The oven temperature was raised from 60C to 250C at a rate of 5C/min, then held at 250C for 10 min. Nitrogen was used as the carrier gas at a flow rate of 1.1 mL/min; the split ratio was adjusted to 1:50. The injector and detector (FID) temperatures were kept at 250C and 280C, respectively. GC-MS analysis was carried out on a Thermoquest-Finnigan Trace GC-MS instrument equipped with a DB-5 fused silica capillary column. Helium was used as the carrier gas at a flow rate of 1.1 mL/min with a split ratio of 1:50. The quadrupole mass spectrometer was scanned over 45–465 amu with an ionizing voltage of 70 eV. Gas chromatographic conditions were the same as given above for GC. The constituents of the oil were identified by calculation of their retention indices under temperature-programmed conditions for n-alkanes (C 6 –C 24 ), and the essential oil on a DB-5 column. Identification of individual compounds was made by comparison of their mass spectra with those of the internal reference mass spectra library or with authentic compounds and confirmed by comparison of their retention indices with those reported in the literature [11]. In vitro antibacterial activity of the essential oil was assessed against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 as models of Gram positive and Gram negative bacteria, respectively. The broth microdilution susceptibility method using 96 well trays was used to determine the minimum concentration of essential oil required for inhibition of visible growth (MIC) or killing (MBC) of the test strains. For this purpose, the standard protocol of CLSI (Clinical Laboratory and Standards Institute) was used with some modifications [12]. The inoculants of the bacterial strains were prepared from freshly cultured strains using sterile normal saline, which were adjusted to 0.5 McFarland standard turbidity and then further diluted (1:1000 for bacteria) by sterile Mueller-Hinton broth (MHB) just before adding to the wells containing a desired range of diluted essential oil.

Designing Libraries for Research Collaboration in the Network World: An Exploratory Study

Advances in technology and changes in higher education and research are forcing libraries to rethink the services they offer to researchers and how they are presented. Librarians are moving into “higher end support” and adopting new service models based on “deep collaboration” with academic partners. The internal arrangements that form the design of an organization can determine whether it achieves its mission under particular conditions. The present study explores how libraries in 24 leading UK research universities are organizing resources and services to support the research enterprise. Qualitative data were collected from institutional websites and other public domain sources and were analysed using matrix techniques. The results show a trend away from integrated library and computing service organizations; variety in institutional reporting lines, but predominantly in large professional service groups; consistency in internal library groupings, but variation in portfolio and job titles; expansion of specialist positions, with new functional roles complementing traditional subject liaisons; and dedicated spaces, working groups, and integrated websites promoting boundary-spanning activities. The findings confirm and extend prior work and are being used to design a large scale international survey.

Novel approach for analysis of bronchoalveolar lavage fluid (BALF) using HPLC-QTOF-MS-based lipidomics: lipid levels in asthmatics and corticosteroid-treated asthmatic patients.

To better understand the respiratory lipid phenotypes of asthma, we developed a novel method for lipid profiling of bronchoalveolar lavage fluid (BALF) using HPLC-QTOF-MS with an internal spectral library and high-throughput lipid-identifying software. The method was applied to BALF from 38 asthmatic patients (18 patients with nonsteroid treated bronchial asthma [NSBA] and 20 patients with steroid treated bronchial asthma [SBA]) and 13 healthy subjects (NC). We identified 69 lipids, which were categorized into one of six lipid classes: lysophosphatidylcholine (LPC), phosphatidylcholine (PC), phosphatidylglycerol (PG), phosphatidylserine (PS), sphingomyelin (SM) and triglyceride (TG). Compared with the NC group, the individual quantity levels of the six classes of lipids were significantly higher in the NSBA subjects. In the SBA subjects, the PC, PG, PS, SM, and TG levels were similar to the levels observed in the NC group. Using differentially expressed lipid species (p value < 0.05, FDR < 0.1 and VIP score of PLS-DA > 1), 34 lipid biomarker candidates with high prediction performance between asthmatics and controls were identified (AUROC > 0.9). These novel findings revealed specific characteristics of lipid phenotypes in asthmatic patients and suggested the importance of future research on the relationship between lipid levels and asthma.

CXCR4 Antagonists: A Screening Strategy for Identification of Functionally Selective Ligands

The CXC chemokine receptor 4 (CXCR4) is a widely expressed G protein–coupled receptor implicated in several diseases. In cancer, an increased number of surface CXCR4 receptors, in parallel with aberrant signaling, have been reported to influence several aspects of malignancy progression. CXCR4 activation by the specific ligand C-X-C motif chemokine 12 (CXCL12) induces several intracellular signaling pathways that have been selectively related to malignancy depending on the tissue or cell type. We developed a panel of CXCR4 screening assays investigating Gαi-mediated cyclic adenosine monophosphate modulation, β-arrestin recruitment, and receptor internalization. All of the assays were set up in recombinant cells and were used to test four reported CXCR4 antagonists. Consequently, a set of hit compounds, deriving from a screening campaign of a 30,000-small-molecule internal library, was profiled with the different assays. We identified several compounds showing a pathway-selective activity: antagonists on a Gαi-dependent pathway; antagonists on both the β-arrestin and Gαi-dependent pathways, some of which induce receptor internalization; and compounds with an antagonist behavior in all of the readouts. The identified biased antagonists induce different functional states on CXCR4 and preferentially affect specific downstream responses from the activated receptor, thus providing an improved therapeutic profile for correction of CXCR4 abnormal signaling.

Antioxidant properties and quantitative UPLC-MS/MS analysis of phenolic compounds in dandelion (Taraxacum officinale) root extracts

Introduction: There is an increasing effort worldwide to investigate the antioxidant efficacy of traditional medicinal plants, which may be used to alleviate oxidative stress synonymous with the pathophysiology of many metabolic disorders as well as prevent oxidative deterioration of food products. In this study the antioxidant potential of dandelion (Taraxacum officinale) root was evaluated. Methods: The radical scavenging and antioxidant activities of solid-liquid extracts from freeze dried dandelion root was measuring in vitro using the modified DPPH and FRAP colorimetric assay. The phenolic content was also evaluated in vitro using the Folin-Ciocaltteu colorimetric assay. Subsequent identification and quantification of phenolic in active extracts was carried out using UPLC-MS/MS. Results: The ethyl acetate crude extract (E3) demonstrated the highest antioxidant activity for both the DPPH (227.728 ± 11.849 mg TE/g) and FRAP (463.066 ± 3.942 mg TE/g) assays. This extract also contained the highest phenolic content (228.723 ± 2.392 mg GAE/g). UPLC-MS/MS was used to identify and quantify phenolic compounds from E3 extract using an internal library of 36 phenolic standards. In total 18 phenolic compounds were quantified with chlorogenic acid, caffeic acid, syringic and vanillic being the most abundant compounds. The flavonoids apigenin-7-O-glycoside, luteolin-7-O-glycoside and naringenin-7-O-glycoside were detected for the first time in dandelion root. Conclusion: The results of this study suggest that dandelion root is a good source of natural antioxidants and could be used in foods with the potential to delay the onset of diseases linked to metabolic derived reactive oxygen species (ROS).

Building a Library Subculture to Sustain Information Literacy Practice with Second Order Change

This article addresses development for information literacy (IL) practice through building internal library organizational culture. Using an analysis of relevant literature and reflection on lived experience, the authors explore issues and concepts for instruction librarians and leaders to consider as they advance and sustain IL initiatives. Through a lens of second order change the article proposes change agency theory and organizational development as theoretical approaches; calling on librarians to adopt roles and techniques that honor personal learning and continuing education while simultaneously focusing on student learning. It additionally suggests a flexible roadmap for managed change processes including organizational assessment techniques, inspiration for conversations and inclusive dialogues, reasons for and ways to address resistance, and steps to implement action plans. The authors conclude IL initiatives will be more effective if supported by an internal library culture that is embraced and implemented by knowledgeable instruction librarians and their leaders.

Bayesian models for screening and TB Mobile for target inference with Mycobacterium tuberculosis

The search for compounds active against Mycobacterium tuberculosis is reliant upon high-throughput screening (HTS) in whole cells. We have used Bayesian machine learning models which can predict anti-tubercular activity to filter an internal library of over 150,000 compounds prior to invitro testing. We used this to select and test 48 compounds invitro; 11 were active with MIC values ranging from 0.4μM to 10.2μM, giving a high hit rate of 22.9%. Among the hits, we identified several compounds belonging to the same series including five quinolones (including ciprofloxacin), three molecules with long aliphatic linkers and three singletons. This approach represents a rapid method to prioritize compounds for testing that can be used alongside medicinal chemistry insight and other filters to identify active molecules. Such models can significantly increase the hit rate of HTS, above the usual 1% or lower rates seen. In addition, the potential targets for the 11 molecules were predicted using TB Mobile and clustering alongside a set of over 740 molecules with known M.tuberculosis target annotations. These predictions may serve as a mechanism for prioritizing compounds for further optimization.

Feature Analysis and Modeling of 670 nm Laser Optical Endpoint Traces in Tungsten CMP

The measurement of the light reflected by the surface of the wafer during process is one of the most widely used endpoint detection methods for the chemical mechanical polishing of metals. In spite of the many advantages in the process, the endpoint traces are seen just as a drop in reflectivity that marks the end of the process. In this paper, we analyze the optical endpoint traces commonly obtained during tungsten CMP and we focus our attention on different features that characterize the curve shape. Using both measurements and theoretical simulations of reflectivity of the film stack involved, we describe such characteristics and connect them to the layers being polished and to the lifetime of CMP pad installed on the equipment. In particular, we focus on a secondary peak of intensity that can be seen when the thickness of titanium nitride under tungsten increases, and on the darkening of pad window as the lifetime increases. Finally, we simulate the endpoint traces by using internal library values of optical properties of materials involved, achieving a good match between real and simulated curve.

Libraries Today, Libraries Tomorrow: Contemporary Library Practices and the Role of Library Space in the L

ABSTRACTPurpose: The article uses sociological concepts in order to rethink the changes in library practices. Contemporary trends are discussed with regard to the changing nature of working habits, referring mostly to the new technology, and the (emergence of ) the third space phenomenon. The author does not regard libraries only as concrete public service institutions, but rather as complex cultural forms, taking in consideration wider social context with a stress on users’ practices in relation to space.Methodology/approach: The article is based on the (self-) observation of the public library use, and on the (discourse) analysis of internal library documents (i.e. annual reports and plans) and secondary sociological literature. As such, the cultural form approach represents a classic method of sociology of culture.Results: The study of relevant material in combination with direct personal experiences reveals socio-structural causes for the change of users’ needs and habits, and points at the difficulty of spatial redefinition of libraries as well as at the power of the discourse.Research limitations: The article is limited to an observation of users’ practices in some of the public libraries in Ljubljana and examines only a small number of annual reports – the discoveries are then further debated from the sociological perspective.Originality/practical implications: The article offers sociological insight in the current issues of the library science and tries to suggest a wider explanation that could answer some of the challenges of the contemporary librarianship.

Defining RNA motif–aminoglycoside interactions via two-dimensional combinatorial screening and structure–activity relationships through sequencing

RNA is an extremely important target for the development of chemical probes of function or small molecule therapeutics. Aminoglycosides are the most well studied class of small molecules to target RNA. However, the RNA motifs outside of the bacterial rRNA A-site that are likely to be bound by these compounds in biological systems is largely unknown. If such information were known, it could allow for aminoglycosides to be exploited to target other RNAs and, in addition, could provide invaluable insights into potential bystander targets of these clinically used drugs. We utilized two-dimensional combinatorial screening (2DCS), a library-versus-library screening approach, to select the motifs displayed in a 3×3 nucleotide internal loop library and in a 6-nucleotide hairpin library that bind with high affinity and selectivity to six aminoglycoside derivatives. The selected RNA motifs were then analyzed using structure–activity relationships through sequencing (StARTS), a statistical approach that defines the privileged RNA motif space that binds a small molecule. StARTS allowed for the facile annotation of the selected RNA motif–aminoglycoside interactions in terms of affinity and selectivity. The interactions selected by 2DCS generally have nanomolar affinities, which is higher affinity than the binding of aminoglycosides to a mimic of their therapeutic target, the bacterial rRNA A-site.

Abstract 5563: Targeting the PH domain of TIAM1 to inhibit prostate cancer metastasis.

Abstract TIAM1 (T-lymphoma invasion and metastasis-inducing protein-1) is a highly conserved guanine nucleotide exchange factor and contains an Dbl Homology (DH)/C-terminal Pleckstrin Homology (PH) domain. The crystal structure of DH-PH of TIAM1 in complex with Rac-1 has been reported. TIAM1 has been found to be over-expressed cancers such as breast, colon and prostate cancers. An increase in TIAM1 expression has been shown to be associated with increased metastatic potential of breast cancer cell lines and is also correlated with poor prognosis of patients with prostate cancer. TIAM1 is thus a novel PH domain-containing drug target directly related to cancer progression, metastasis and patient survival. We have identified and characterized novel small molecule inhibitors targeting the phosphoinositide lipid binding PH domain of TIAM1 in order to selectively inhibit cell migration, invasion and survival. An In Silico screen of our internal and Maybridge library using the crystal structure of TIAM1 has identified 11 compounds that bind to the PH domain. In vitro assays revealed that compounds TPH-3 and TPH-15 significantly reduced the amount of active Rac1 in PC-3 prostate cancer cells (EC50 of 2.73±0.13 and 2.38±0.98 μM) by binding to PH-TIAM1 with high affinity (KD in the micromolar range) using surface plasmon resonance (SPR) spectrometry. Both compounds displaced PtdIns-3,4,5-P3 in a SPR competitive binding assay. TPH-3 and TPH-15 inhibited cell proliferation with EC50 of 19.8±3.2 and 28.7±1.7 μM in prostate cancer cells LnCaP and EC50 of 18.6±1.8 and 33.3±6.7 μM in PC-3. Wound healing assays and lamellipodia formation were both inhibited by the compounds. TPH-15 inhibited ≈70% of PC-3 invasion using a matrigel invasion assay. Finally, TPH-15 exhibits anti-tumor properties in a PC-3 mouse xenograft study (%T/C≈38.8) with good pharmacokinetic properties (T1/2≈5 hours). Cardio-injection of prostate PC-3 cells in SCID mice was used to test the effects of TPH-15 in the prevention of bone metastasis. Mice were treated with 50mg/kg ip of TPH-15 once a day for 5 days. TPH-15-treated mice developed significantly less pelvic bone lesions than the untreated group and TPH-15 treated mice lived longer, on average, than the untreated group. Overall, we have identified novel compounds which exhibit the ability to reduce prostate cancer bone metastasis by binding to the PH domain of TIAM1, an important GEF in the process of metastasis. Citation Format: Emmanuelle J. Meuillet, Sylvestor A. Moses, Jana Jandova, Eugene A. Mash, Shuxing Zhang. Targeting the PH domain of TIAM1 to inhibit prostate cancer metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5563. doi:10.1158/1538-7445.AM2013-5563

Owning Faculty Status: A Manifesto

Since the first moment librarians were granted tenured faculty status in the academic arena, questions have been raised by university and library administration, faculty members in other departments, and non-academics as to why they were given the opportunity to achieve such a prestigious rank. Not only did the majority of tenured/tenure track faculty librarians not have the standard doctorate degree possessed by most other tenured/tenure track faculty, but there were also questions surrounding the librarians’ purported lack of teaching and their ability to perform original research as required for those tenure and promotion standards set by the academic institution. Sadly, this perception is due not only to incorrect external opinions about what academic librarians do and how they serve their profession but also to various internal library misunderstandings of what it means to be a tenured/tenure track faculty member. As a result of this misunderstanding, some librarians are unable to communicate what it means to be a librarian with tenured faculty status and thus the importance of academic freedom for their profession as a whole. This paper describes some key challenges tenured/tenure track faculty librarians face within their academic institutions as they attempt to grapple with what it means to be a librarian with tenured/tenure track status.

Problem‐solving strategies that Kenyan academic librarians utilize when presented with copyright queries

PurposeThe purpose of this paper is to examine how Kenyan academic librarians, with varying education levels, solve and handle copyright issues when presented to them by library users.Design/methodology/approachA survey questionnaire was administered to 253 librarians in 14 universities in Nairobi, Kenya. Of those who responded to the survey, a think aloud protocol and critical incident technique interview were administered to a convenience sample of 32 librarians.FindingsLearned helplessness was found to exist among librarians who were Certificate and Diploma holders when faced with copyright queries. Librarians from the different education levels differed in their ranking of problem‐solving strategies they employ when it comes to stopping copyright infringement in libraries.Practical implicationsThis study helps to inform internal library policies regarding copyright and the type of staff member a library can utilize to serve library users whenever they present queries on copyright issues. The study supports the need for thorough copyright education for librarians.Originality/valueThis is the first time that a study has tried to compare how academic librarians in Africa with varying education levels in Library Science respond to copyright queries presented to them and approaches they use to fight copyright infringement.

Library services in the media environment: a students' perspective

PurposeThe paper aims to show which media are accepted by students in higher education and which are not. It explains how library media services and other text and information media are related to each other and what part they play in the whole media and learning environment. It examines which library services are most important to students and on which areas university libraries should focus when developing strategies for the future.Design/methodology/approachTwo student surveys and one teacher survey were carried out at Karlsruhe Institute of Technology in 2009 and 2011. They measured the acceptance of 45 media services by using a fully standardized print questionnaire. Possible influence factors were also evaluated.FindingsThe acceptance of electronic text media amongst students is still growing, while acceptance of print media is decreasing. The use of external text‐related services is growing, while the use of the internal library catalogue is declining. A certain student user type who prefers text media seems of high interest.Practical implicationsThe paper suggests that libraries should focus on the different types of electronic text in their strategy and should refrain from implementing media services with a low rate acceptance, for example wikis, Twitter or weblogs.Originality/valueThe research carried out here draws a comprehensive picture of how students use media in their studies and how they accept the different kinds of media services compared to each other. The survey reveals hidden structures and classifies media and media users into certain types.

A Glimpse at Discovery Tools within the HBCU Library Landscape

Discussions involving discovery tools range from dissatisfaction to celebration. Some contend that discovery tools present IT setbacks, expose internal library cataloging or metadata challenges, inhibit students from developing true information navigation skills, and create sustainability problems amidst realities of shrinking library budgets coupled with increasing electronic resource costs. Conversely, other librarians are optimistic; they claim that discovery tools help bridge the information divide and excite users to navigate, and, thereby, utilize the maze of library resources. Virtually no library literature analyzes discovery tool usage from the Historically Black College or University (HBCU) perspective. The goal here is to assess discovery tool acquisition, library instruction, challenges, and librarian attitudes relating to Web-scale discovery tools.

Canadian Public Libraries Are Aware of Their Role as Information Literacy Training Providers, but Face Several Challenges

Abstract&#x0D; &#x0D; Objective – To explore the current state of information literacy (IL) training in Canadian public libraries, and to identify strategies used for improving IL training skills for staff and patrons.&#x0D; &#x0D; Design – Mixed-methods approach, including document analysis, observations, and focus group interviews.&#x0D; &#x0D; Setting – Two libraries of a large public library system in Canada: the central library and one branch library.&#x0D; &#x0D; Subjects – Six staff members (manager, administrator, training coordinator, instructor, and computer technician) who have been involved in designing and teaching information literacy courses for library patrons and staff.&#x0D; Methods – The researcher analyzed internal and external library documents related to information literacy, including, but not limited to, reports, posters, lesson plans, newsletters, and training scripts. He also observed interactions and behaviours of patrons during IL training sessions. Finally, he conducted a focus group with people involved in IL training, asking questions about facilities and resources, programs, patron reaction, librarian knowledge of IL theory, and impediments and benefits of IL training programs in public libraries.&#x0D; &#x0D; Main Results – Staff were aware of the importance of IL training in the library. Attracting more library patrons (including building partnerships with other organizations), improving staff IL and training skills, employing effective strategies for running training programs, and dealing with financial issues were all concerns about running IL training that were highlighted.&#x0D; &#x0D; Conclusion – Canadian public libraries are well aware of their role as IL training providers, but they still face several challenges in order to improve their effectiveness.

Classification of Salmonella enterica serotypes from Australian poultry using repetitive sequence-based PCR

To evaluate a semi-automated repetitive extragenic palindromic sequence-based PCR (rep-PCR) system for the classification of Salmonella serotypes from Australian poultry. Using a DNA fingerprint library within the DiversiLab(®) System, four separate databases were constructed (serogroup B, C, E and Other). These databases contained 483 serologically confirmed (reference laboratory) Salmonella isolates. A blinded set of Salmonella cultures (n = 155) were typed by rep-PCR, matched against the internal library and compared with traditional serotyping. The predicted (Kullback-Leibler) serotype of 143 (92·3%) isolates matched traditional typing (P < 0·05). Of the 12 (7·7%) remaining isolates, ten (6·5%) resulted in 'No Match', one (0·65%) was incorrectly matched to the library (Salm. subsp 1 ser 4,12:-:-), and the other (0·65%) was referenced as Salm. ser. Sofia, whereas rep-PCR and in-house serotyping concurred as Salmonella serovar Typhimurium. Financial analysis showed higher material cost (215%) and a lower labour component (47·5%) for rep-PCR compared with serotyping. The DiversiLab(®) System, with serogroup databases, was successfully implemented as an adjunct for reference serotyping of Salmonella enterica. The DiversiLab(®) System platform is a cost-effective and easy-to-use system, which can putatively determine Salmonella enterica serotypes within a few hours.

New benzimidazole derivatives as antiplasmodial agents and plasmepsin inhibitors: Synthesis and analysis of structure–activity relationships

The newly synthesized benzimidazole compounds were suggested to be inhibitors of Plasmodium falciparum plasmepsin II and human cathepsin D by virtual screening of an internal library of synthetic compounds. This was confirmed by enzyme inhibition studies that gave IC(50) values in the low micromolar range (2-48μM). Ligand docking studies with plasmepsin II predicted binding of benzimidazole compounds at the center of the extended substrate-binding cleft. According to the plausible mode of binding, the pyridine ring of benzimidazole compounds interacted with S1' subsite residues whereas the acetophenone moiety was in contact with S1-S3 subsites of plasmepsin II active center. The benzimidazole derivatives were evaluated for capacity to inhibit the growth of intraerythrocytic P. falciparum in culture. Four benzimidazole compounds inhibited parasite growth at ⩽3μM. The most active compound 10, 1-(4-phenylphenyl)-2[2-(pyridinyl-2-yl)-1,3-benzdiazol-1-yl]ethanone showed an IC(50) of 160nM. The substitution of a phenyl group and a chlorine atom at the para position of the acetophenone moiety were shown to be crucial for antiplasmodial activity.

Novel anti-inflammatory peptides as cosmeceutical peptides

Ultraviolet (UV) radiation induced inflammation plays an important role in the aging of human skin. Prostaglandin (PG) E2 is the primary mediator of UVB induced photoinflammation. We screened an internal library for dipeptides that inhibited UVB induced PGE2 synthesis but showed no cytotoxicity toward human keratinocytes. We identified three highly active inhibitory sequences, LE (Leu+Glu), MW (Met+Trp) and MY (Met+Tyr). To evaluate their efficacy in human skin, 24 sites of abdomen skin were irradiated with a 308nm excimer laser (300mJ/cm2), after which 2% LE, MW, MY or a control were applied to the irradiated sites for 24h. The erythema index (EI) was measured before and 24h after treatment. The results showed that LE and MW significantly decreased UVB induced erythema (p=0.041 and p=0.036, respectively), but ME did not. Overall, LE and MW are candidate cosmeceutical peptides that can protect skin from UVB induced photoinflammation.

Synthesis and SAR of new pyrazolo[4,3-h]quinazoline-3-carboxamide derivatives as potent and selective MPS1 kinase inhibitors

The synthesis and SAR of a series of novel pyrazolo-quinazolines as potent and selective MPS1 inhibitors are reported. We describe the optimization of the initial hit, identified by screening the internal library collection, into an orally available, potent and selective MPS1 inhibitor.