bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Cryptosporidium parvum Active Chemical Series by Repurposing the Open Access Malaria Box
Authors: Bessoff Kovi , Spangenberg Thomas , Foderaro Jenna E. , Jumani Rajiv S. , Ward Gary E. , Huston Christopher D.
Published: February 2014

The apicomplexan parasites
Cryptosporidium parvum
and
Cryptosporidium hominis
are major etiologic agents of human cryptosporidiosis. The infection is typically self-limited in immunocompetent adults, but it can cause chronic fulminant diarrhea in immunocompromised patients and malnutrition and stunting in children. Nitazoxanide, the current standard of care for cryptosporidiosis, is only partially efficacious for children and is no more effective than a placebo for AIDS patients. Unfortunately, financial obstacles to drug discovery for diseases that disproportionately affect low-income countries and technical limitations associated with studies of
Cryptosporidium
biology impede the development of better drugs for treating cryptosporidiosis. Using a cell-based high-throughput screen, we queried the Medicines for Malaria Venture (MMV) Open Access Malaria Box for activity against
C. parvum
. We identified 3 novel chemical series derived from the quinolin-8-ol, allopurinol-based, and 2,4-diamino-quinazoline chemical scaffolds that exhibited submicromolar potency against
C. parvum
. Potency was conserved in a subset of compounds from each scaffold with varied physicochemical properties, and two of the scaffolds identified exhibit more rapid inhibition of
C. parvum
growth than nitazoxanide, making them excellent candidates for further development. The 2,4-diamino-quinazoline and allopurinol-based compounds were also potent growth inhibitors of the related apicomplexan parasite
Toxoplasma gondii
, and a good correlation was observed in the relative activities of the compounds in the allopurinol-based series against
T. gondii
and
C. parvum
. Taken together, these data illustrate the utility of the Open Access Malaria Box as a source of both potential leads for drug development and chemical probes to elucidate basic biological processes in
C. parvum
and other apicomplexan parasites.
NBTI 5463 Is a Novel Bacterial Type II Topoisomerase Inhibitor with Activity against Gram-Negative Bacteria and
In Vivo
Efficacy
Authors: Dougherty Thomas J. , Nayar Asha , Newman Joseph V. , Hopkins Sussie , Stone Gregory G. , Johnstone Michele , Shapiro Adam B. , Cronin Mark , Reck Folkert , Ehmann David E.
Published: February 2014

The need for new antibiotics that address serious Gram-negative infections is well recognized. Our efforts with a series of novel bacterial type II topoisomerase inhibitors (NBTIs) led to the discovery of NBTI 5463, an agent with improved activity over other NBTIs against Gram-negative bacteria, in particular against
Pseudomonas aeruginosa
(F. Reck, D. E. Ehmann, T. J. Dougherty, J. V. Newman, S. Hopkins, G. Stone, N. Agrawal, P. Ciaccio, J. McNulty, H. Barthlow, J. O'Donnell, K. Goteti, J. Breen, J. Comita-Prevoir, M. Cornebise, M. Cronin, C. J. Eyermann, B. Geng, G. R. Carr, L. Pandarinathan, X. Tang, A. Cottone, L. Zhao, N. Bezdenejnih-Snyder, submitted for publication). In the present work, NBTI 5463 demonstrated promising activity against a broad range of Gram-negative pathogens. In contrast to fluoroquinolones, the compound did not form a double-strand DNA cleavable complex with
Escherichia coli
DNA gyrase and DNA, but it was a potent inhibitor of both DNA gyrase and
E. coli
topoisomerase IV catalytic activities. In studies with
P. aeruginosa
, NBTI 5463 was bactericidal. Resistant mutants arose at a low rate, and the mutations were found exclusively in the
nfxB
gene, a regulator of the MexCD-OprJ efflux system. Levofloxacin-selected resistance mutations in GyrA did not result in decreased susceptibility to NBTI 5463. Animal infection studies demonstrated that NBTI 5463 was efficacious in mouse models of lung, thigh, and ascending urinary tract infections.
Protection of Human Podocytes from Shiga Toxin 2-Induced Phosphorylation of Mitogen-Activated Protein Kinases and Apoptosis by Human Serum Amyloid P Component
Authors: Dettmar Anne K. , Binder Elisabeth , Greiner Friederike R. , Liebau Max C. , Kurschat Christine E. , Jungraithmayr Therese C. , Saleem Moin A. , Schmitt Claus-Peter , Feifel Elisabeth , Orth-Höller Dorothea , Kemper Markus J. , Pepys Mark , Würzner Reinhard , Oh Jun
Published: February 2014

Hemolytic uremic syndrome (HUS) is mainly induced by Shiga toxin 2 (Stx2)-producing
Escherichia coli
. Proteinuria can occur in the early phase of the disease, and its persistence determines the renal prognosis. Stx2 may injure podocytes and induce proteinuria. Human serum amyloid P component (SAP), a member of the pentraxin family, has been shown to protect against Stx2-induced lethality in mice
in vivo
, presumably by specific binding to the toxin. We therefore tested the hypothesis that SAP can protect against Stx2-induced injury of human podocytes. To elucidate the mechanisms underlying podocyte injury in HUS-associated proteinuria, we assessed Stx2-induced activation of mitogen-activated protein kinases (MAPKs) and apoptosis in immortalized human podocytes and evaluated the impact of SAP on Stx2-induced damage. Human podocytes express Stx2-binding globotriaosylceramide 3. Stx2 applied to cultured podocytes was internalized and then activated p38α MAPK and c-Jun N-terminal kinase (JNK), important signaling steps in cell differentiation and apoptosis. Stx2 also activated caspase 3, resulting in an increased level of apoptosis. Coincubation of podocytes with SAP and Stx2 mitigated the effects of Stx2 and induced upregulation of antiapoptotic Bcl2. These data suggest that podocytes are a target of Stx2 and that SAP protects podocytes against Stx2-induced injury. SAP may therefore be a useful therapeutic option.
Supraventricular tachycardia precipitated by a peripherally inserted central catheter in an infant with gastroschisis
Authors: Thyoka Mandela , Haq Iram , Hosie Gareth
Published: February 2014

Gastroschisis is a common congenital abdominal wall defect requiring surgical correction in early neonatal life. The time to full enteral feeds among infants with gastroschisis is variable. Gastroschisis remains a common surgical cause of intestinal failure in neonates. Peripherally inserted central catheters (PICC) are commonly used to provide long-term venous access for parenteral nutrition during the time enteral feeds are being slowly established. The PICC is placed under fluoroscopic guidance with the distal end of the catheter usually placed at the junction of the superior vena cava with the right atrium. In rare circumstances, the catheter tip may advance into intracardiac chambers, precipitating supraventricular re-entrant tachycardia. We report a case of an infant who was antenatally diagnosed with uncomplicated gastroschisis in whom a supraventricular tachycardia was precipitated by the PICC in the right atrium.
Diagnostic values of soluble mesothelin-related peptides for malignant pleural mesothelioma: updated meta-analysis
Authors: Cui Ai , Jin Xiao-Guang , Zhai Kan , Tong Zhao-Hui , Shi Huan-Zhong
Published: February 2014

Objective

Although the values of soluble mesothelin-related peptides (SMRPs), including mesothelin and megakaryocyte potentiating factor, in serum and/or pleural fluid for diagnosing malignant pleural mesothelioma (MPM) have been extensively studied, the exact diagnostic accuracy of these SMRPs remains controversial. The purpose of the present meta-analysis is to update the overall diagnostic accuracy of SMRPs in serum and, furthermore, to establish diagnostic accuracy of SMRPs in pleural fluid for MPM.

Design

Systematic review and meta-analysis.

Methods

A total of 30 articles of diagnostic studies were included in the current meta-analysis. Sensitivity, specificity and other measures of accuracy of SMRPs in serum and pleural fluid for the diagnosis of MPM were pooled using random effects models. Summary receiver operating characteristic curves were used to summarise overall test performance.

Results

The summary estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic OR were 0.61, 0.87, 5.71, 0.43 and 14.43, respectively, for serum and 0.79, 0.85, 4.78, 0.30 and 19.50, respectively, for pleural fluid. It was also found that megakaryocyte potentiating factor in serum had a superior diagnostic accuracy compared with mesothelin for MPM.

Conclusions

SMRPs in both serum and pleural fluid are helpful markers for diagnosing MPM with similar diagnostic accuracy. The negative results of SMRP determinations are not sufficient to exclude non-MPM, and the positive test results indicate that further invasive diagnostic steps might be necessary for the diagnosis of MPM.
Depression and resilience in women with HIV and early life stress: does trauma play a mediating role? A cross-sectional study
Authors: Spies Georgina , Seedat Soraya
Published: February 2014

Objectives

The present study sought to assess the relationship between depressive symptomatology and resilience among women infected with HIV and to investigate whether trauma exposure (childhood trauma, other discrete lifetime traumatic events) or the presence of post-traumatic stress symptomatology mediated this relationship.

Design

Cross-sectional study.

Setting

Western Cape, South Africa.

Participants

A convenience sample of 95 women infected with HIV in peri-urban communities in the Western Cape, South Africa. All women had exposure to moderate-to-severe childhood trauma as determined by the Childhood Trauma Questionnaire.

Primary and secondary outcome measures

We examined the relationship between depressive symptomatology and resilience (the Connor-Davidson Resilience Scale) and investigated whether trauma exposure or the presence of post-traumatic stress symptomatology mediated this relationship through the Sobel test for mediation and PLS path analysis.

Results

There was a significant negative correlation between depressive symptomatology and resilience (p=<0.01). PLS path analysis revealed a significant direct effect between depression and resilience. On the Sobel test for mediation, distal (childhood trauma) and proximal traumatic events did not significantly mediate this association (p=> 0.05). However, post-traumatic stress symptomatology significantly mediated the relationship between depression and resilience in trauma-exposed women living with HIV.

Conclusions

In the present study, higher levels of resilience were associated with lower levels of self-reported depression. Although causal inferences are not possible, this suggests that in this sample, resilience may act as protective factor against the development of clinical depression. The results also indicate that post-traumatic stress symptoms (PTSS), which are highly prevalent in HIV-infected and trauma exposed individuals and often comorbid with depression, may further explain and account for this relationship. Further investigation is required to determine whether early identification and treatment of PTSS in this population may ameliorate the onset and persistence of major depression.
Sociodemographic factors predicting mother's cervical screening and daughter's HPV vaccination uptake
Authors: Spencer Angela M , Roberts Stephen A , Brabin Loretta , Patnick Julietta , Verma Arpana
Published: February 2014

Background

Achieving high human papillomavirus (HPV) vaccine coverage may reduce inequalities in cervical cancer prevention by mitigating the inequalities seen in the cervical screening programme. This paper assesses whether the same sociodemographic factors are associated with both cervical screening and HPV vaccination.

Methods

Girls’ HPV vaccination records were linked by address to cervical screening records for their mothers in the North West of England. Index of Multiple Deprivation scores (2010) and census ethnicity data (2001) were used to investigate the association between deprivation and ethnic composition of area of residence with HPV vaccination and cervical screening uptake, along with potential differences between Primary Care Trusts (PCTs), which were responsible for vaccine delivery.

Results

Deprivation was not associated with routine (12–13-year-olds) vaccination initiation, but girls living in the most deprived quintile were significantly less likely to complete the three vaccine doses (OR 0.75; 95% CI 0.63 to 0.88). Mother–daughter pairs failing to engage in either screening or vaccination were also more likely to live in deprived areas (routine vaccination OR for most deprived quintile: 2.35; 95% CI 2.00 to 2.77). There were differences between PCTs after controlling for demographic effects (OR 1.35; 95% CI 1.23 to 1.52).

Conclusions

Ensuring completion of the vaccine schedule is critical for organisations responsible for vaccine delivery in order to reduce cancer risk among girls living in deprived areas. There remains a small minority of mothers and daughters from disadvantaged backgrounds who do not participate in either cervical screening or HPV vaccination.
Hidradenitis suppurativa: a common and burdensome, yet under-recognised, inflammatory skin disease
Authors: Dufour Deirdre Nathalie , Emtestam Lennart , Jemec Gregor B
Published: February 2014

Hidradenitis suppurativa (HS) is a chronic, relapsing, inflammatory skin condition that typically occurs after puberty. The primary clinical presentation is painful inflamed nodules or boils in the apocrine gland-bearing regions (armpits, genital area, groin, breasts and buttocks/anus) that progress to abscesses, sinus tracts and scarring. Severity is typically described according to three Hurley categories, with most patients having mild or moderate disease. Estimated prevalence is 1–4% worldwide and HS is three times more common in women than men. Patients’ disease burden includes intense pain, work disability and overall poor quality of life. Although the clinical signs of the disease can often be hidden by clothing, active HS is associated with a malodorous discharge that contributes to the disabling social stigma. Risk factors include smoking and obesity. Comorbidities include inflammatory bowel disease and spondyloarthropathies. The presentation of the disease is distinct, yet HS is not well-recognised except in dermatology clinics.
Novel amino propyl substituted organo tin compounds
Authors: Pichler Johann , Torvisco Ana , Bottke Patrick , Wilkening Martin , Uhlig Frank
Published: February 2014

In this work, a new synthetic pathway yielding unprotected amino propyl tin compounds is described. For this purpose, mono stannanes with different substitution patterns are used. In a first step, tin hydrides are deprotonated using lithium diisopropyl amide and mixed with an electrophile containing a protected amine in the ω-position. After deprotection via acidic hydrolysis, the desired amino propyl tin compounds are obtained in high yield and purity. The thermal reaction behavior of the amino propyl tin hydrohalide intermediates containing one aromatic residue at the central tin atom is also investigated. For this purpose, amino propyl tin hydrohalides are heated under vacuum until the aromatic hydrocarbon is liberated. This thermal treatment leads to so far unknown tin halides containing an amino propyl side chain. For all of these substances detailed liquid 1H, 13C, and 119Sn-nuclear magnetic resonance (NMR) data were obtained, and in one case solid state NMR is also conducted. Regarding solids, single crystal X-ray analysis is performed. Some derivatization reactions with these new substances are demonstrated, especially the synthesis of an amino propyl tin carboxylate, which might be very interesting for biological, pharmaceutical, or technical processes.
Solid-contact polyvinyl chloride membrane electrode based on the bis[(2-(hydroxyethylimino)phenolato]copper(II) complex for trace level determination of copper ions in wastewater
Authors: Andac Muberra , Coldur Fatih , Bilir Seda , Birinci Aysenur , Demir Serkan , Uzun Harun
Published: February 2014

A miniaturized solid-contact polyvinyl chloride membrane electrode based on the bis[(2-(hydroxyethylimino)phenolato]copper(II) complex has been prepared for the determination of Cu(II) ion in real samples. The influence of coating membrane composition, pH, and possible interfering cations on the response of the ion-selective electrode was investigated. A number of membranes at different compositions were prepared and their Cu2+ sensing capabilities were investigated. The best results for Cu2+ sensing was obtained for the electrode membrane containing ionophore − 2-nitrophenyloctyl ether – polyvinyl chloride and potassium tetrakis(p-chlorophenyl)borate in a ratio of 4:65:30:1 (w/w, mg), respectively. The prepared electrode exhibited a near-Nernstian response (28.3 mV/decade) to Cu2+ in the concentration range from 1.0 × 10−6 to 1.0 × 10−1 mol/L with a limit of detection of 8.3 × 10−7 mol/L. The potentiometric response of the electrode was independent from the pH of the test solution in the pH range of 3.0–6.0. The electrode has a very short response time, about 15 s, and it can be used over a period of 3 months without any divergence in potential. The electrode has been successfully applied as an indicator electrode in potentiometric titration of Cu(II) ions with ethylenediaminetetraacetic acid and in the determination of Cu(II) in wastewater of the copper processing industry.
Photoswitchable organoplatinum complexes containing an azobenzene derivative of 3,6-di(2-pyridyl)pyridazine
Authors: Moustafa Mohamed E. , Boyle Paul D. , Puddephatt Richard J.
Published: February 2014

The new, unsymmetrical azobenzene-tagged ligand 4-(4-azobenzene)-3,6-di(2-pyridyl)pyridazine, adpp, forms complexes with platinum(II) and platinum(IV), which exist as a mixture of geometrical isomers. The complexes are characterized primarily by their NMR spectra, while the structures of the ligand and its complexes [PtMe2(adpp)], [PtBrMe2(CH2C6H4-4-t-Bu)(adpp)], and [PtBrMe2(CH2C6H3-3,5-t-Bu2)(adpp)] have been structurally characterized. In solution, the compounds undergo easy photochemical trans−cis switching of the azobenzene group, with subsequent slow thermal isomerization back to the more stable trans-azobenzene isomer.
Effect of hydroelectric dam operations on the freshwater productivity of a Columbia River fall Chinook salmon population
Authors: Harnish Ryan A. , Sharma Rishi , McMichael Geoffrey A. , Langshaw Russell B. , Pearsons Todd N.
Published: February 2014

Altering the timing and magnitude of discharge fluctuations can minimize the adverse effects of operating hydroelectric dams on the productivity of downstream salmon populations. Hydroelectric operations at Priest Rapids Dam during the mid-1970s resulted in dewatering of fall Chinook salmon (Oncorhynchus tshawytscha) redds, causing mortality of intragravel life stages. Since then, a series of operational constraints have been implemented at Priest Rapids Dam to reduce the effects of discharge fluctuations on the population of fall Chinook salmon that spawns and rears downstream from the dam. Initial protections that focused on preventing redd dewatering were subsequently increased to include postemergence life stages. We used stock–recruit analyses to identify changes to the population’s freshwater productivity that occurred over a 30-year period and coincided with changes to dam operations. We observed a 217% increase in productivity that corresponded with constraints enacted to prevent redd dewatering and an additional 130% increase that coincided with enactment of constraints to limit stranding and entrapment of juveniles. The information gained from this study may be used to guide efforts elsewhere to mitigate the effects of hydroelectric dam operations on downstream fish populations.
A method to evaluate explosive crystallization velocity of amorphous silicon films during flash lamp annealing
Authors: Ohdaira Keisuke
Published: February 2014

Flash lamp annealing (FLA) of micrometre-order thick amorphous silicon (a-Si) films can induce explosive crystallization (EC), high-speed lateral crystallization driven by the release of latent heat. We develop multipulse FLA system, which emits a quasi-millisecond pulse consisting of a number of subpulses. The emission frequency of the subpulses can be systematically controlled, and the emission of subpulses leads to the periodic modulation of the temperature of a Si film and the resulting formation of macroscopic stripe patterns. The relationship between a subpulse emission frequency and the width of the macroscopic stripe patterns yields EC velocity. Two kinds of EC modes can be observed, depending on the methods of precursor a-Si deposition and (or) a-Si film thickness.
A generalization of gauge symmetry, fourth-order gauge field equations and accelerated cosmic expansion
Authors: Hsu Jong-Ping
Published: February 2014

A generalization of the usual gauge symmetry leads to fourth-order gauge field equations, which imply a new constant force independent of distances. The force associated with the new U 1 gauge symmetry is repulsive among baryons. Such a constant force based on baryon charge conservation gives a field-theoretic understanding of the accelerated cosmic expansion in the observable portion of the universe dominated by baryon galaxies. In consistent with all conservation laws and known forces, a simple rotating "dumbbell model" of the universe is briefly discussed.
DE SITTER TRANSITIVITY, CONFORMAL TRANSFORMATIONS AND CONSERVATION LAWS
Authors: PEREIRA J. G. , SAMPSON A. C. , SAVI L. L.
Published: February 2014

Minkowski spacetime is transitive under ordinary translations, a transformation that do not have matrix representations. The de Sitter spacetime, on the other hand, is transitive under a combination of translations and proper conformal transformations, which do have a matrix representation. Such matrix, however, is not by itself a de Sitter generator: it gives rise to a conformal re-scaling of the metric, a transformation not belonging to the de Sitter group, and in general not associated with diffeomorphisms in spacetime. When dealing with variational principles and Noether's theorem in de Sitter spacetime, it is necessary to regularize the transformations in order to eliminate the conformal re-scaling of the metric.
Study of p-4Hetotal reaction cross-section using Glauber and Coulomb-modified Glauber models
Authors: Tag El-Din Ibrahim M. A. , Taha M. M. , Hassan Samia S. A.
Published: February 2014

The total nuclear reaction cross-section σRfor p-4He in the energy range from 25 MeV to 1000 MeV is calculated within Glauber and Coulomb-modified Glauber models. The Coulomb-modified Glauber model (CMGM) is introduced via modification of the Coulomb trajectory of the projectile from a straight line, and calculation of the effective radius of interaction. The effects of in-medium nucleon–nucleon (NN) total cross-section, phase variation, high order momentum transfer component of nucleon–nucleon elastic scattering amplitude and Pauli blocking are studied. It is pointed out that the phase variation of the nucleon–nucleon amplitude plays a significant role in describing σRwith γ = -1.6 fm2at in-medium nuclear density ϱ = 0 and γ = -2 fm2at ϱ = 0.17 fm-3in the whole energy range. A remarkable fit to the available experimental data is obtained by invoking Pauli blocking and high order momentum transfer of nucleon–nucleon (NN) elastic scattering amplitude for Ep< 100 MeV.
Realizing a fault-tolerant embedded controller on distributed real-time systems
Authors: Kim Junsung , Puranik Praful , Rajkumar Ragunathan (Raj)
Published: February 2014

Advances in real-time, embedded and distributed systems along with control and communication theory have catalyzed the rapid emergence of cyber-physical systems such as a self-driving car. The importance of fault-tolerance support on a cyber-physical system (CPS) has been greatly emphasized by recent research due to the nature of CPS that senses its surroundings, processes sensor data, and reacts using its actuators. In order to tackle this challenge, we proposed SAFER (System-level Architecture for Failure Evasion in Real-time Applications) in our previous work. SAFER is able to tolerate fail-stop processor and/or task failures for distributed embedded real-time systems. One of its limitations, however, is that SAFER is not capable of tolerating a failure of a processor with a dedicated connection to an actuator. This paper provides a method that relaxes this limitation by (1) deploying a small piece of hardware to avoid a dedicated connection between a processor and an actuator, (2) adding a software module that monitors and controls the hardware, and (3) enhancing the failure detection and recovery mechanisms of SAFER to support these changes. The detailed implementation and evaluation of the SAFER extension is on-going work.
Transition-aware task scheduling and configuration selection in reconfigurable embedded systems
Authors: Kooti Hessam , Bozorgzadeh Eli
Published: February 2014

This paper presents a novel graph representation that captures the transition overhead due to runtime configuration of underlying hardware in reconfigurable embedded systems resulting from various configuration schemes such as FPGA-like reconfiguration or dynamic voltage/frequency scaling (DVFS). We propose an intuitive heuristic to solve combined configuration selection and task scheduling problem on this graph. In addition, when applied to DVFS, our algorithm provides simultaneous task ordering and configuration selection of the system which outperforms the state-of-the-art DVFS methods applied after task ordering.
Adaptive EDF
Authors: Tanaka Kiyofumi
Published: February 2014

Along with the growing diversity and complexity of real-time embedded systems, significance of real-time scheduling is increasing. Rate monotonic (RM) and earliest deadline first (EDF) are representative scheduling algorithms for periodic tasks. RM has a merit that tasks with high-priority (short-period) have small jitters and short response times. However, it is impossible that processor utilization reaches 100% while maintaining schedulability or that tasks are given importance independent of their periods. On the other hand, EDF can utilize processors by 100% with schedulability, while it cannot give tasks fixed priorities or importance, therefore, it is difficult to keep jitters or response times of particular tasks short. This paper, in EDF algorithm, proposes a method of shortening response times of a task that is important for the system by introducing predictive execution times and dividing execution of the important task into two instances based on the predictive execution times. The use of predictive execution times has an effect of making deadline of the first instance earlier and therefore the first instance would be executed earlier by EDF. In the evaluation by simulation, the proposed method reduced average response times of the most important task by up to 14.2%.
The 2014 SIGCSE computer science education awards
Authors: Tymann Paul
Published: February 2014

Every year SIGCSE recognizes two individuals for outstanding contributions to computer science education. The SIGCSE Award for Outstanding Contribution to Computer Science Education honors an individual or group in recognition of a significant contribution to computer science education. The SIGCSE Award for Lifetime Service to the Computer Science Education Community honors an individual who has a long history of volunteer service to the computer science education community. For interviews with this year's award winners, see the Member Spotlight column on the next page.
NSF computing education funding
Authors: Tymann Paul
Published: February 2014

With many changes to the NSF education funding model, we thought this might be a good opportunity to highlight two programs that are of direct interest to the computing community.
November 2013 special projects grant awards
Authors: Barnes Tiffany , Fitzgerald Sue
Published: February 2014

SIGCSE is pleased to announce a Special Projects Grant award from the November 2013 funding cycle: Elissa Redmiles (University of Maryland, College Park) and Jandelyn Plane (University of Maryland, College Park) received a grant for a project entitled "Computer Science Connect 'Curriculum-In-A-Box'."
AnSIRSModel for Assessing Impact of Media Coverage
Authors: Cui Jing’an , Wu Zhanmin
Published: February 2014

AnSIRSmodel incorporating a general nonlinear contact function is formulated and analyzed. When the basic reproduction numberℛ0<1, the disease-free equilibrium is locally asymptotically stable. There is a unique endemic equilibrium that is locally asymptotically stable ifℛ0>1. Under some conditions, the endemic equilibrium is globally asymptotically stable. At last, we conduct numerical simulations to illustrate some results which shed light on the media report that may be the very effective method for infectious disease control.
Effect of Acute Gamma Irradiation onCurcuma alismatifoliaVarieties and Detection of DNA Polymorphism through SSR Marker
Authors: Taheri Sima , Abdullah Thohirah Lee , Ahmad Zaiton , Abdullah Nur Ashikin Psyquay
Published: February 2014

The effects of eight different doses (0, 10, 20, 25, 35, 40, 60, and 100 Gy) of acute gamma irradiation on 44 (three varieties ofCurcuma alismatifolia: Chiang Mai Red, Sweet Pink, Kimono Pink, and oneCurcumahybrid (Doi Tung 554) individual plants were investigated. Radiation sensitivity tests revealed that the LD50values of the varieties were achieved at 21 Gy for Chiang Mai Red, 23 Gy for Sweet Pink, 25 Gy for Kimono Pink, and 28 Gy for Doi Tung 554. From the analysis of variance (ANOVA), significant variations were observed for vegetative traits, flowering development, and rhizome characteristics among the four varieties ofCurcuma alismatifoliaand dose levels as well as the dose × variety interaction. In irradiated plants, the leaf length, leaf width, inflorescence length, the number of true flowers, the number of pink bracts, number of shoots, plant height, rhizome size, number of storage roots, and number of new rhizomes decreased significantly (P<0.05) as the radiation dose increased. The cophenetic correlation coefficient (CCC) between genetic dissimilarity matrix estimated from the morphological characters and the UPGMA clustering method wasr=0.93, showing a proof fit. In terms of genetic variation among the acutely irradiated samples, the number of presumed alleles revealed by simple sequence repeats ranged from two to seven alleles with a mean value of 3.1, 4.5, and 5.3 alleles per locus for radiation doses of 0, 10, and 20 Gy, respectively. The average values of the effective number of alleles, Nei’s gene diversity, and Shannon’s information index were 2.5–3.2, 0.51–0.66, and 0.9–1.3, respectively. The constructed dendrogram grouped the entities into seven clusters. Principal component analysis (PCA) supported the clustering results. Consequently, it was concluded that irradiation with optimum doses of gamma rays efficiently induces mutations inCurcuma alismatifoliavarieties.
The Multifunctional Growth Factor Midkine Promotes Proliferation and Migration in Pancreatic Cancer
Authors: Rawnaq Tamina , Dietrich Luisa , Wolters-Eisfeld Gerrit , Uzunoglu Faik G. , Vashist Yogesh K. , Bachmann Kai , Simon Ronald , Izbicki Jakob R. , Bockhorn Maximilian , Güngör Cenap
Published: February 2014

Pancreatic ductal adenocarcinoma (PDAC) has a devastating prognosis among solid tumors and despite increased knowledge of the molecular mechanisms contributing to progression and metastasis, minimal progress has been done in establishing new targeted therapies for this deadly disease. The expression of the multifunctional growth/differentiation factor midkine (MK) promotes a variety of cellular functions leading to increased angiogenesis, proliferation, migration, and survival. Moreover, MK is intensively discussed as a potential new-therapy target and as biomarker for cancer progression and chemotherapeutic resistance in multiple cancers. Therefore, the present study investigated the molecular role of MK in pancreatic cancer. It was found that MK is elevated in PDAC and differentially expressed in other histologic subtypes of pancreatic cancer, whereas normal pancreatic cells did not express MK, thus making it an attractive candidate for targeted therapies. As a secreted growth/differentiation factor, MK was investigated as a biomarker in clinical serum specimens using ELISA. In addition, knockdown studies of MK revealed a link to proliferation and migration status in vitro. Finally, upstream signaling pathways were analyzed, with TNF-α and EGF being the main inductors of MK expression in PDAC.

Implications: This study presents novel MK functions and new upstream signaling effectors that induce its expression to promote PDAC and therefore defines an attractive new therapeutic target in pancreatic cancer. Mol Cancer Res; 12(5); 670–80. ©2014 AACR.
Analysis of Relative Expression Level of VEGF (Vascular Endothelial Growth Factor), HIF-1α (Hypoxia Inducible Factor 1α) and CTGF (Connective Tissue Growth Factor) Genes in Chronic Glomerulonephritis (CGN) Patients
Authors: Donderski Rafał , Szczepanek Joanna , Domagalski Krzysztof , Tretyn Andrzej , Korenkiewicz Jadwiga , Marszałek Andrzej , Szymański Andrzej , Wolski Zbigniew , Odrowąż-Sypniewska Grażyna , Manitius Jacek
Published: February 2014

Background/Aims: Analysis of gene expression in renal tissue is considered to be a diagnostic tool predicting the clinical course of glomerulonephritis. The present study quantified the relative transcript levels of VEGF, CTGF and HIF-1α in renal tissue to establish their relationship with some clinical variables in patients suffering from chronic glomerulonephritis (CGN). Methods: 28 patients (6F and 22M, mean age 51.2±15.0) with CGN were enrolled. Type of CNG recognized by kidney biopsy (histopatological evaluation) was as follows: minimal change disease (MCD)-3pts, IgA nephropathy-5pts, FSGS-3pts, membranous nephropathy-4pts, mesangio-proliferative glomerulonephritis-3pts; MPGN-1pts, lupus nephritis-6pts, granulomatosis with polyangitis-2 pts; hypertensive nephropathy- 3pts. Renal tissue from 3 individuals with normal eGFR and histology was taken as control. Mean clinical follow-up of patients was 12 months after biopsy eGFR and daily urinary protein excretion (DPE) was assessed at the time of biopsy and then in 6 months intervals. Real-time PCR was used to determine relative gene expression. The housekeeping gene GAPDH was used as normalization control. Results: At the time of the biopsy relative expression of 3 analyzed genes was diminished in comparison to control. There were statistically significant differences in VEGF gene relative expression level in patients which varied according to eGFR and tendency in patients which varied according to DPE. HIF-alfa and CTGF gene showed only a tendency. Conclusions: Overexpression of the VEGF gene in subjects with DPE>3,5g may point to insufficient oxygen supply in renal tissue which may result in tubulointerstitial fibrosis with further functional renal impairment and decline of eGFR.
Limited Significance of Activated Akt-Mammalian Target of Rapamycin Signaling Pathway in Prostate Cancer Progression
Authors: Ko Young Hwii , Miyake Hideaki , Behnsawy Hosny M. , Cheon Jun , Fujisawa Masato
Published: February 2014

Objective: The objective of this study was to investigate the significance of the activated Akt-mammalian target of rapamycin (Akt-mTOR) signaling pathway in the progression of prostate cancer. Materials and Methods: The expression levels of Akt, phosphorylated Akt (p-Akt), mTOR and phosphorylated mTOR (p-mTOR) in 175 prostate specimens, including 61 normal prostate tissues as a control, 24 high-grade prostatic intraepithelial neoplasias (HGPINs) and 90 clinically localized prostate cancers, were evaluated by immunohistochemical staining. p-Akt and p-mTOR ratios, which were defined as the expression level of p-Akt in relation to that of Akt and the expression level of p-mTOR in relation to that of mTOR, respectively, in these specimens were calculated. Results: Expression levels of all four molecules, including Akt, p-Akt, mTOR and p-mTOR, were significantly greater in the HGPIN group compared with the normal control and prostate cancer groups. Furthermore, the p-Akt ratio in the prostate cancer group was significantly lower than that in the HGPIN group, while there was no significant difference in the p-mTOR ratio between the HGPIN and prostate cancer groups. In the prostate cancer group, no significant relationships were observed between major clinicopathological parameters and the expression levels as well as the ratios of p-Akt or p-mTOR. Conclusions: The Akt-mTOR signaling pathway may play a limited role in the progression of prostate cancer.
Caries Process on Occlusal Surfaces: Evolving Evidence and Understanding
Authors: Carvalho J.C.
Published: February 2014

Management of the caries process on occlusal surfaces of permanent molars has proven a major challenge. The onset of caries on these surfaces takes place soon after their eruption, and the permanent first molars, followed by the second molars, remain the sites in the dentition which show the highest caries prevalence. This paper is structured in the form of questions and answers in which traditional concepts of caries susceptibility of occlusal surfaces are appraised and confronted with the current evidence. Then, research studies examining the role of biological determinants on the development and arrest of occlusal caries in young permanent teeth are discussed. Finally, the contribution of these studies in terms of developing the available scientific evidence and our understanding of the caries process on occlusal surfaces is analyzed. The current evidence does not support the concept that the early onset and high prevalence of occlusal caries in young permanent teeth are due to a particularly low inherent resistance of the occlusal surface or due to the presence of inaccessible fissure-like structures on these surfaces. Evidence is provided to show that the most influential biological determinants of the development and arrest of occlusal caries are thick plaque accumulation on the groove-fossa system and the stage of tooth eruption limiting mechanical oral function. Consequently, active occlusal lesions are significantly more prevalent in erupting than in fully erupted teeth. The major contribution of this review is to provide updated knowledge about the biological principles determining the development and arrest of caries on occlusal surfaces of erupting teeth.
Characteristics and Clinical Evolution of Patients with Acute Myeloblastic Leukemia in Northeast Mexico: An Eight-Year Experience at a University Hospital
Authors: Jaime-Pérez José Carlos , Brito-Ramirez Alma Sirenia , Pinzon-Uresti Monica Andrea , Gutiérrez-Aguirre Homero , Cantú-Rodríguez Olga G. , Herrera-Garza José Luis , Gomez-Almaguer David
Published: February 2014

Background/Objective: Acute myeloid leukemia (AML) is the most common acute leukemia in adults. We documented the characteristics and results of treatment of patients with AML at a single reference center. Methods: Patients diagnosed with AML between June 2003 and July 2011 at a university hospital in northeast Mexico were studied. Overall survival (OS) and event-free survival (EFS) were determined, and risk factors were analyzed with respect to their influence on prognosis. Results: A total of 132 AML patients were included. Median age was 32 years. Complete remission (CR) was achieved by 55% of patients. CR was achieved by 65.1% of patients <60 years (n = 109), compared to 8.7% of those >60 years (n = 23; p < 0.001). In all, 39% of patients >60 years suffered an early death, compared to 14.7% of those <60 years (p < 0.001). OS for patients with AML was 35%, whereas EFS was 32%. On multivariate analysis, patients >60 years had a lower OS and EFS (p < 0.001). A total of 28% of patients received a transplant, and they had higher OS and EFS. Conclusions: Our patients were considerably younger and had remarkably lower survival rates than reported for other populations; those >60 years had a higher early death rate, and fewer of these patients achieved CR.
Multiplicity of Risk Factors in Ischemic Stroke Patients: Relations to Age, Sex, and Subtype - A Study of 2,505 Patients from the Lund Stroke Register
Authors: Starby Heléne , Delavaran Hossein , Andsberg Gunnar , Lövkvist Håkan , Norrving Bo , Lindgren Arne
Published: February 2014

Background: The prevalence of risk factors for ischemic stroke may vary between different groups of stroke patients. We examined the distribution of individual well-established risk factors as well as the multiplicity of risk factors in different age groups and among subtypes. Methods: In the Lund Stroke Register, we consecutively enrolled 2,505 patients with first-ever ischemic stroke from 2001 to 2009 and registered hypertension, diabetes mellitus, heart disease, current smoking, hypercholesterolemia as well as stroke subtype. Results: Among young patients (<55 years), at least 50% had ≥2 risk factors and 20-25% had ≥3 risk factors. In patients aged 55 years or older, the proportion with ≥2 risk factors was 70-80% and with ≥3 risk factors 35-45%. Men and women had a similar burden of risk factors. Approximately 50% of the cases classified as cardioembolism (CE) and large artery atherosclerosis (LAA) had ≥3 risk factors, which was significantly more than the other TOAST (Trial of Org 10172 in Acute Stroke Treatment) subtypes (CE p < 0.001, LAA p = 0.001). Conclusions: The prevalence of well-established risk factors is similar among young and old stroke patients with large proportions (50-80%) having ≥2 risk factors. Even though the prevalence of well-established risk factors differs between pathogenetic subtypes, these risk factors as well as the multiplicity of risk factors seem to be of clinical importance in all major subtypes of ischemic stroke.
Use of Selective Serotonin Reuptake Inhibitors in the Treatment of Burning Mouth Syndrome
Authors: Fleuret Camille , Le Toux Guy , Morvan Jehanne , Ferreira Felipe , Chastaing Myriam , Guillet Gérard , Misery Laurent
Published: February 2014

Background: Patients with burning mouth syndrome (BMS) are frequently treated with antidepressants. Selective serotonin reuptake inhibitors (SSRIs) are increasingly used. Nonetheless, few studies have examined the effects of SSRIs in BMS. Objective: We performed a retrospective study to confirm the need for a prospective study on this topic in the future. Patients and Methods: 51 patients suffering from primary BMS were included in this study. Results: The frequency of side effects due to SSRIs was low, with mainly digestive side effects. Treatment with SSRIs was more efficient in patients reporting a psychogenic origin for their symptoms. Antidepressants were more frequently stopped when patients did not declare such an origin. Conclusions: SSRIs appear to be effective and well tolerated. Declaring a psychogenic component may be considered as a potentiating or predictive factor for the efficacy of treatment with SSRIs. These results should be confirmed by a prospective randomised study.
A Case of Gray Platelet Syndrome Masked by Immune Thrombocytopenia at Presentation
Authors: Mizuno Nana , Kanamori Eriko , Saito Hiroko , Murakami Naomi , Tojo Naoko , Tohda Shuji
Published: February 2014

We report a case of gray platelet syndrome (GPS) associated with immune thrombocytopenia (ITP) at presentation. A 22-year-old male patient presenting with petechiae on his limbs was diagnosed with ITP due to a gradual decrease of his platelet count to a minimum of 26 × 109/liter and an elevated platelet-associated IgG (PA-IgG) level in the absence of any other specific cause of thrombocytopenia. Administration of prednisolone increased his platelet count, but this dropped again to approximately 50 × 109/liter as the dose was tapered, and remained at the same level after the treatment was terminated. Thirteen years later, we reassessed the cause of the thrombocytopenia because the PA-IgG level was found to be within the normal range. There were large hypogranular platelets on the blood film and a deficit of α-granules in the platelets on electron microscopy. On this basis, we diagnosed his thrombocytopenia as GPS. To our knowledge, this is the first report of a GPS case associated with ITP at presentation. This case illustrates the importance of carefully reviewing blood film results in the differential diagnosis of thrombocytopenia.
Trends in Pre-Liver Transplant Screening for Cholangiocarcinoma among Patients with Primary Sclerosing Cholangitis
Authors: Trilianos Panagiotis , Selaru Florin , Li Zhiping , Gurakar Ahmet
Published: February 2014

Background: Cholangiocarcinoma (CCA) is the most common hepatobiliary malignancy complicating primary sclerosing cholangitis (PSC). Unfortunately, timely diagnosis of CCA in PSC patients remains challenging. Aim: To investigate the strategies among liver centers regarding pre-transplant screening for CCA in patients with PSC. Methods: An online survey was returned from 46 US transplant centers, inquiring on the frequency of screening, the use of specific tests, or tactical approaches to high-grade dysplasia (HGD) or CCA. Results: Most centers screen their PSC patients for CCA prior to orthotopic liver transplantation (OLT) (89%). Serum carbohydrate antigen 19-9 and magnetic resonance cholangiopancreatography are first-line screening tools (93 and 84% respectively). Endoscopic retrograde cholangiopancreatography with biliary brushings is routinely performed in only 30% of the centers. In the case of HGD, 61% would choose close monitoring. In the event of non-resectable CCA, 37% have an OLT protocol, 33% resort to palliative treatment and the remaining 30% make an outside referral. Finally, half the participating centers perform CCA surveillance among their listed PSC patients every 6 months. Conclusion: Screening for CCA among PSC patients prior to OLT varies greatly among centers. Serum carbohydrate antigen 19-9 and magnetic resonance cholangiopancreatography are widely used. HGD warrants surveillance rather than intervention among most experts. Protocolized chemoradiation followed by OLT has yet to become a widely accepted approach. The very poor survival of PSC patients who develop CCA underlines the importance of an effective and universally accepted screening process that will aid in its earlier detection.
Systematic Review Focusing on the Excretion and Protection Roles of Sweat in the Skin
Authors: Peng Yan , Cui Xiao , Liu Yanhua , Li Yaoyin , Liu Jian , Cheng Biao
Published: February 2014

The skin excretes substances primarily through sweat glands. Several conditions have been demonstrated to be associated with diminished sweating. However, few studies have concentrated on the metabolism and excretion of sweat. This review focuses on the relationship between temperature and the thermoregulatory efficacy of sweat, and then discusses the excretion of sweat, which includes the metabolism of water, minerals, proteins, vitamins as well as toxic substances. The potential role of sweat secretion in hormone homeostasis and the effects on the defense system of the skin are also clarified.