Unknown Route Research Articles

Using wrist vibrations to guide hand movement and whole body navigation

Summary In the absence of vision, mobility and orientation are challenging. Audio and tactile feedback can be used to guide visually impaired people. In this paper, we present two complementary studies on the use of vibrational cues for hand guidance during the exploration of itineraries on a map, and whole body-guidance in a virtual environment. Concretely, we designed wearable Arduino bracelets integrating a vibratory motor producing multiple patterns of pulses. In a first study, this bracelet was used for guiding the hand along unknown routes on an interactive tactile map. A wizard-of-Oz study with six blindfolded participants showed that tactons, vibrational patterns, may be more efficient than audio cues for indicating directions. In a second study, this bracelet was used by blindfolded participants to navigate in a virtual environment. The results presented here show that it is possible to significantly decrease travel distance with vibrational cues. To sum up, these preliminary but complementary studies suggest the interest of vibrational feedback in assistive technology for mobility and orientation for blind people.

Dynamic Scheduling of Shuttle Robots in the Warehouse of a Polymer Plant Based on Dynamically Configured Timed Automata Models

The increasing demand for customized products and the pressure to produce them on time with low-cost upon customers’ demands not only call for efficient and economical production processes but also require high-performance logistic planning to make the best possible use of the available resources. The elements to be planned besides the production itself include preproduction material handling, such as raw material deliveries and storage, and the postproduction material handling, such as storage and distribution of products. Specialty products are usually stored in warehousing systems where the speed of the removal and the distribution of products can strongly affect the efficiency of the complete system. Hence, optimal scheduling of the distribution operations is required to meet throughput targets and lead to improved efficiency and financial gains. In this contribution, we deal with a bottleneck subsystem of an industrial polymer processing plant, the pallet removal system of a high-rise warehouse. A dynamic scheduling approach that uses optimization to solve the problem on a moving window is proposed. The shuttle management problem is modeled using timed automata and is solved by cost-optimal reachability analysis. The most challenging aspect of the problem is introduced by the a priori unknown arrival times of the pallets and their unknown routes. The proposed dynamic solution approach is compared to an enhanced version of the currently used first-come, first-served dispatching rule. The comparative study shows that the proposed approach leads to makespan reductions of about 30%.

NBOMe Designer Drug Exposures Reported to Texas Poison Centers

Use of 2-methoxybenzyl analogues of 2C-X phenethylamines (NBOMe) is increasing in the United States. Twenty-five NBOMe exposures reported to Texas poison centers during 2012–2013 were identified; 76% involved 25I-NBOMe, 12% involved 25C-NBOMe, and 12% involved an unknown NBOMe. Eighty-eight percent of the patients were men; mean age was 17 years (range, 14–25 years). The exposure route was 72% from ingestion alone, 12% from inhalation alone, 4% from ingestion and inhalation, and 12% from an unknown route. The most common clinical effects were tachycardia (52%), agitation (48%), hallucinations (32%), hypertension (32%), confusion (24%), and mydriasis (20%). Two patients died.

110例丙型肝炎患者流行病学特征和疾病谱分析

Objective To investigate the epidemiological features and disease spectrum of inpatients with hepatitis C in recent years and to provide reference for the control of hepatitis C. Methods A retrospective study of demography, epidemiology, and laboratory examination was performed in 110 hospitalized patients with hepatitis C. Results Of the 110 patients, 60 were male and 50 were female, with a male-to- female ratio of 1. 2: 1. The main transmission routes included blood product transfusion ( 33. 6%) , surgery ( 30. 0%) , intravenous drug use ( 14. 5%) , and sexual transmission ( 4. 5%) . The other 19 cases ( 17. 4%) were of unknown transmission route. The annual numbers of cases from 2008 to 2011 were 16, 18, 32, and 44, respectively. The genotype proportions in patients were as follows: 1b, 60. 7% ( 17 /28) ; 2a, 28. 6% ( 8 /28) ; 1b /2a mixed type, 7. 1% ( 2 /28) ; 3b, 3. 6% ( 1 /28) . Of all patients, 13. 6% ( 15 /110) were found with acute hepatitis C, 67. 3% ( 74 /110) with chronic hepatitis C, 19. 1% ( 21 /110) with liver cirrhosis, and 10. 9% ( 12 /110) with decompensated cirrhosis. Conclusion The incidence of HCV infection has been increasing year by year. The major HCV genotypes are 1b and2a. Hepatitis C is apt to develop into liver cirrhosis. It is necessary to reinforce monitoring and to carry out specific epidemiological study among the target population.

Epidemiologic patterns in HIV infection in Mureş county

Despite the important scientific progress regarding HIV pandemics registered during the last decade, more and more cases of HIV infection are diagnosed every year, as HIV testing practices vary across Europe. Purpose: to identify epidemiologic trends in newly diagnosed patients with HIV infection in the center of Romania. We performed a retrospective, cross-sectional study, over a 5-year period (January 2009 – December 2013), upon all new cases of HIV infection, diagnosed in Mures county. We analyzed demographic data, transmission patterns, level of CD4 T-lymphocytes and patients’ outcome. Over a 5 years-period, we have diagnosed 58 new cases of HIV infection, 63.79% male / 36.21% female. Average age was 27 years, median – 23 years, with extremes between 2 and 55 years. Most cases came from urban areas (65.38%). Transmission patterns included risk groups: men who have sex with men (MSM) – 4 patients, unknown multiple partners – 3 patients, HIV-infected sexual partner – 15 patients, screening at delivery – 4 patients, 1 case of mother-to-child transmission. The dominant pattern was heterosexual transmission – 27 patients. CD4 T-cells count registered an average level of 369 cells/μL, median 335 cells/μL, ranging from 2 to 1304 cells/μL. 23 (39.65%) patients were late presenters. We registered 3 deaths (5.17%). While previous epidemiologic data from our region suggested an unknown route of transmission in children born around the 1990’s, during the last years, the dominant epidemiologic pattern in HIV infection in Mures county was heterosexual transmission. An important category of newly diagnosed patients was represented by late presenters, with potential unfavorable evolution. We registered a concerning trend of sexual transmission of HIV infection in serodiscordant couples, despite medical education.

Toll‐like receptors hit calcium

Mitochondrial Ca(2+) uptake is a multifarious signal that controls both the activity of matrix dehydrogenases and the sensitivity to apoptotic and necrotic challenges. Recent evidence indicates that mitochondria also play a role in triggering inflammation, as mitochondrial DNA, when released by the cell, is an important damage-associated molecular pattern (DAMP). Now, Toll-like receptors (TLRs) are shown to close the loop, by affecting in turn mitochondrial activity. Two studies by Shintani and colleagues, one in this issue of EMBO reports, identify a new TLR transduction mechanism that impinges directly on mitochondrial function. Upon binding of CpG oligodeoxynucleotides, TLR9--which in non-immune cells is retained in the ER--inhibits SERCA2, thus reducing Ca(2+) transfer to the mitochondria and aerobic metabolism.

Molecular Cloning of a Novel Glucuronokinase/Putative Pyrophosphorylase from Zebrafish Acting in an UDP-Glucuronic Acid Salvage Pathway

In animals, the main precursor for glycosaminoglycan and furthermore proteoglycan biosynthesis, like hyaluronic acid, is UDP-glucuronic acid, which is synthesized via the nucleotide sugar oxidation pathway. Mutations in this pathway cause severe developmental defects (deficiency in the initiation of heart valve formation). In plants, UDP-glucuronic acid is synthesized via two independent pathways. Beside the nucleotide sugar oxidation pathway, a second minor route to UDP-glucuronic acid exist termed the myo-inositol oxygenation pathway. Within this myo-inositol is ring cleaved into glucuronic acid, which is subsequently converted to UDP-glucuronic acid by glucuronokinase and UDP-sugar pyrophosphorylase. Here we report on a similar, but bifunctional enzyme from zebrafish (Danio rerio) which has glucuronokinase/putative pyrophosphorylase activity. The enzyme can convert glucuronic acid into UDP-glucuronic acid, required for completion of the alternative pathway to UDP-glucuronic acid via myo-inositol and thus establishes a so far unknown second route to UDP-glucuronic acid in animals. Glucuronokinase from zebrafish is a member of the GHMP-kinase superfamily having unique substrate specificity for glucuronic acid with a Km of 31±8 µM and accepting ATP as the only phosphate donor (Km: 59±9 µM). UDP-glucuronic acid pyrophosphorylase from zebrafish has homology to bacterial nucleotidyltransferases and requires UTP as nucleosid diphosphate donor. Genes for bifunctional glucuronokinase and putative UDP-glucuronic acid pyrophosphorylase are conserved among some groups of lower animals, including fishes, frogs, tunicates, and polychaeta, but are absent from mammals. The existence of a second pathway for UDP-glucuronic acid biosynthesis in zebrafish likely explains some previous contradictory finding in jekyll/ugdh zebrafish developmental mutants, which showed residual glycosaminoglycans and proteoglycans in knockout mutants of UDP-glucose dehydrogenase.

Back-pressure traffic signal control with unknown routing rates

The control of a network of signalized intersections is considered. Previous works proposed a feedback control belonging to the family of the so-called back-pressure controls that ensures provably maximum stability given pre-specified routing probabilities. However, this optimal back-pressure controller (BP*) requires routing rates and a measure of the number of vehicles queuing at a node for each possible routing decision. It is an idealistic assumption for our application since vehicles (going straight, turning left/right) are all gathered in the same lane apart from the proximity of the intersection and cameras can only give estimations of the aggregated queue length. In this paper, we present a back-pressure traffic signal controller (BP) that does not require routing rates, it requires only aggregated queue lengths estimation (without direction information) and loop detectors at the stop line for each possible direction. A theoretical result on the Lyapunov drift in heavy load conditions under BP control is provided and tends to indicate that BP should have good stability properties. Simulations confirm this and show that BP stabilizes the queuing network in a significant part of the capacity region.

Acquisition of HIV by African-Born Residents of Victoria, Australia: Insights from Molecular Epidemiology

African-born Australians are a recognised “priority population” in Australia's Sixth National HIV/AIDS Strategy. We compared exposure location and route for African-born people living with HIV (PLHIV) in Victoria, Australia, with HIV-1 pol subtype from drug resistance assays and geographical origin suggested by phylogenetic analysis of env gene. Twenty adult HIV positive African-born Victorian residents were recruited via treating doctors. HIV exposure details were obtained from interviews and case notes. Viral RNA was extracted from participant stored plasma or whole blood. The env V3 region was sequenced and compared to globally representative reference HIV-1 sequences in the Los Alamos National Library HIV Database. Twelve participants reported exposure via heterosexual sex and two via iatrogenic blood exposures; four were men having sex with men (MSM); two were exposed via unknown routes. Eight participants reported exposure in their countries of birth, seven in Australia, three in other countries and two in unknown locations. Genotype results (pol) were available for ten participants. HIV env amplification was successful in eighteen cases. HIV-1 subtype was identified in all participants: eight both pol and env; ten env alone and two pol alone. Twelve were subtype C, four subtype B, three subtype A and one subtype CRF02_AG. Reported exposure location was consistent with the phylogenetic clustering of env sequences. African Australians are members of multiple transnational social and sexual networks influencing their exposure to HIV. Phylogenetic analysis may complement traditional surveillance to discern patterns of HIV exposure, providing focus for HIV prevention programs in mobile populations.

Infeção tardia por streptococcus agalactiae – um caso de artrite séptica neonatal

Introduction: The incidence of early -onset group B streptococcus (GBS) disease has decreased substantially due to universal antenatal culture screening of pregnant women for GBS colonization at 35 -37 weeks of gestation and the widespread use of intrapartum antibiotic prophylaxis. However, the incidence of late-onset GBS disease has remained constant in the past decade and it is unaffected by maternal intrapartum chemoprophylaxis. Late-onset GBS infection affects infants who had an unremarkable maternal obstetric and early neonatal history. Other sources rather than vertical route, like horizontal transmission from hospital or community, albeit less frequently proved, can justifies late onset GBS disease.Case report: This case report illustrates a late-onset GBS disease, presenting as neonatal septic arthritis on a caucasian term infant, with unknown route of transmission and highlights the morbidity associated.Discussion: Additional research pertaining to the transmis- sion of late-onset GBS infections is required to develop effective preventive methods.

Neonatal blood transfusion as transmission route in chronic hepatitis C.

The aim of this study was to investigate if neonatal transfusions could underlie chronic hepatitis C in adults for whom the disease transmission route was previously unknown. Questionnaires were sent to 255 patients with chronic hepatitis C born in Sweden in 1960 to 1975. The medical records of 230 of the patients, of whom 98 (43%) had unknown transmission route, were studied regarding the occurrence of neonatal blood transfusions. The clinical, virologic, and histopathologic characteristics of those found to have received transfusions as neonates were also studied. Four of 230 (1.7%; 95% confidence interval, 0.5%-4.4%) patients with hepatitis C had received blood products as neonates. Three of them had reported unknown transmission route. One had cirrhosis, while two had mild histopathologic findings on liver biopsy. Three out of four patients in the transfused group, including the patient with liver cirrhosis, had undergone treatment for hepatitis C, all of them with a sustained viral response. Previously unidentified neonatal blood transfusions explain only a small fraction of chronic hepatitis C cases with unknown transmission route. Individual patients infected early in life can develop progressive liver damage as young adults and may benefit from antiviral treatment. The finding suggests that efforts are needed to actively trace and test adults who have been subjected to neonatal blood product transfusion before 1992.

Selective Hepatitis B Virus Vaccination Has Reduced Hepatitis B Virus Transmission in The Netherlands

Background & AimsIn the Netherlands, a selective hepatitis B virus (HBV) vaccination programme started in 2002 for men having sex with men, drug users, commercial sex workers and heterosexuals with frequent partner changes. We assessed the programme's effectiveness to guide policy on HBV prevention.MethodsWe analysed reports of acute HBV infection in the Netherlands between 2004 and 2010 requesting serum from patients for HBV-genome S- and C-region sequencing. We used coalescence analyses to assess genetic diversity of nonimported genotype-A cases over time.Results1687 patients with acute HBV infection were reported between 2004 and 2010. The incidence of reported acute HBV infection decreased from 1.8 to 1.2 per 100,000 inhabitants, mostly due to a reduction in the number of cases in men who have sex with men. Men were overrepresented among cases with an unknown route of transmission, especially among genotype A2 cases mainly associated with transmission through male homosexual contact. The genetic diversity of nonimported genotype-A strains obtained from men who have sex with men decreased from 2006 onwards, suggesting HBV incidence in this group decreased.ConclusionsThe selective HBV-vaccination programme for behavioural high-risk groups very likely reduced the incidence of HBV infection in the Netherlands mainly by preventing HBV infections in men who have sex with men. A considerable proportion of cases in men who did not report risk behaviour was probably acquired through homosexual contact. Our findings support continuation of the programme, and adopting similar approaches in other countries where HBV transmission is focused in high-risk adults.

Epidemiological distribution and genotype characterization of hepatitis C virus and HIV co-infection in Wuhan, China, where the prevalence of HIV is low

Little is known about the epidemiological characteristics of HIV/hepatitis C virus (HCV) co-infection in cities in China with low HIV prevalence. This study evaluated the level of exposure to different risk factors associated with HCV transmission and characterized the distribution of HCV genotypes in 356 HIV-1-positive patients in Wuhan, central China. HIV transmission routes were distributed as follows: heterosexual contact, male-to-male sexual contact, intravenous drug use, blood transfusion, and unknown route. HCV antibodies were detected by a third-generation enzyme-linked immunosorbent assay. HCV-positive plasmas were subjected to RNA extraction, RT-PCR amplification, and sequencing. Phylogenetic analysis characterized HCV subtypes and the evolutionary origin of circulating HCV strains. Ninety-two of 356 (25.8%) patients infected with HIV were anti-HCV-positive. Among co-infected patients, the predominant risk for HCV transmission was intravenous drug use (87.3%). Six HCV subtypes (1a, 1b, 2a, 3a, 3b, and 6a) were detected. HCV genotype 6a was most prevalent, occurring in 39.3% of all patients, followed by genotypes 1b (24.7%), 3b (18.0%), and 3a (9.8%). The least frequent genotypes were 1a (4.9%) and 2a (3.3%). Intravenous drug use was strongly associated with genotype 6a, and infection by blood or blood product transfusion was strongly associated with genotype 1b. Genotype 2a was detected only among those infected by male-to-male sexual contact. The distribution of HCV subtypes suggests that the city plays a crucial role as a hub of HCV transmission in China. Exposure to multiple risk factors associated with HCV transmission was common among patients co-infected with HIV and HCV.

Features of hepatitis E virus infection in humans and animals in Japan

In Japan, hepatitis E had long been considered to be a rare liver disease which can be accidentally imported from endemic countries in Asia and Africa, where the sanitation conditions are suboptimal. However, since the identification of the first autochthonous hepatitis E case and hepatitis E viremic domestic pigs in Japan in 2001, our understanding of hepatitis E virus (HEV) infection in this country has been changing markedly. This has largely been due to the development of serological and gene-based diagnostic assays, the accumulation of molecular epidemiological findings on HEV infection in humans and animals (as potential reservoirs for HEV in humans) and the recognition of the importance of zoonotic food-borne and other routes of transmission of HEV, including blood-borne transmission. Although it is now evident that autochthonous hepatitis E in Japan is far more common than was previously thought, clinical and subclinical HEV infections indigenous to Japan remain underdiagnosed and their prevalence is still underestimated due to the presence of unknown transmission routes and a low awareness of the infection status by many physicians in Japan. This review focuses on the features of HEV infection in humans and animals, as definitive or potential reservoirs for HEV, in Japan, and updates the current knowledge on the routes of transmission, including zoonotic routes, which are important for the maintenance and spread of HEV in Japan.

Advances in tracking small migratory birds: a technical review of light-level geolocation

Light-level geolocation data loggers, or geologgers, have recently been miniaturized to the extent that they can be deployed on small songbirds, allowing us to determine many previously unknown migration routes, breeding locations, and wintering sites. Use of geologgers on small birds has great potential to help address major research and conservation questions, but the method is not without its shortcomings. Among these shortcomings are the need to recapture birds after they have carried a device throughout a migration cycle and the potential for the devices to affect survival and behavior. We examined return rates of birds with geologgers in published and unpublishedstudiesandfoundnoevidenceofageneralnegativeeffectofgeologgersonsurvival,althoughtherewere a few individual studies where such an effect was evident. From these same studies, we found that most currently used harness materials are equivalent in terms of failure rates, and the most reliable geologgers are those made by the British Antarctic Survey (although these were also the largest geologgers used in the studies we examined). With regard to analysis methods, we believe there is much room for improvement. Use of online archiving of both data and analysis parameters would greatly improve the repeatability and transparency of geologger research. RESUMEN. Avances en el rastreo de peque˜ nas aves migratorias: una revisi´

Arctic TernsSterna paradisaeafrom the Netherlands Migrate Record Distances Across Three Oceans to Wilkes Land, East Antarctica

Arctic Terns Sterna paradisaea have an exceptionally long-distance migration, annually travelling back and forth between the Arctic and the Antarctic. Birds from Greenland, Iceland and the USA were recently found to spend most of the non-breeding period in the Weddell Sea, a small part of the large Antarctic range of Arctic Terns. Based on ring recoveries and sightings of West European Arctic Terns in the Indian Ocean and Australian waters, we expected that terns from The Netherlands (the southern limit of the breeding range) inhabit different Antarctic regions during the non-breeding season to their conspecifics from Greenland. To find out, geolocators were deployed on seven Arctic Terns captured on the nest in 2011 in The Netherlands. All birds were recaptured in 2012 and five devices yielded information on migration routes. The tracked terns spent on average 273 ± 7 days away from The Netherlands, and visited known staging areas in the North Atlantic and the Benguela Current, on both the outward and return journey. Similar tracks were observed in the terns from Greenland. However, hereafter the terns from The Netherlands moved to a previously unknown staging area in the central Indian Ocean, between 20–40°N and 65–100°E, and spent most of the non-breeding season in the Southern Ocean between 35–150°E. One bird migrated as far as New Zealand. Eventually, all five birds spent the austral summer in Wilkes Land, Antarctica, before flying back to the breeding colonies with a small detour to the same North Atlantic staging area they visited on their southward migration. The total travel distance in the course of the non-breeding period was ∼90,000 ± 2000 km, which substantially exceeds previous estimates for this species. Our study revealed new offshore staging areas and a yet unknown route through three different oceans, the longest bird migration described thus far.

Distinct HIV Type 1 Strains in Different Risk Groups and the Absence of New Infections by Drug-Resistant Strains in Lithuania

To analyze HIV-1 genotypes in Lithuania and the transmission of drug-resistant viruses, HIV-1 sequences were obtained from 138 individuals, who were diagnosed as HIV-1 infected in 1990-2008 and represented all major risk groups. Subtype A strains, dominating in the former Soviet Union (90% of cases), were found in 60% of individuals, followed by subtype B (22%) and CRF03_AB (12%) strains. The remaining 7% of the strains included variants belonging to subtype C, CRF01_AE, CRF02_AG, more complex recombinant forms, and strains that could not be reliably genotyped. Analysis of virus genotypes per risk group revealed the circulation of distinct HIV-1 strains in different risk groups: subtype A viruses were present in 82% of injecting drug users (IDUs), but less than a half of heterosexually infected individuals and cases with unknown transmission route, and none of men having sex with men (MSM). We observed no mutations causing drug resistance among 27 newly diagnosed HIV-1 cases.

The HIV epidemic in Greenland – a slow spreading infection among adult heterosexual Greenlanders

Introduction. We aimed to characterise the HIV epidemic in Greenland and to determine incidence, prevalence, mortality rates (MR) and specific causes of deaths.Study design. The study design used was population-based nationwide cohort study.Methods. We included all patients diagnosed with HIV in Greenland before 2011. Data were obtained from patient files, death certificates and the mandatory reports of HIV cases.Incidence and prevalence were estimated as cases/100,000 adults/year and MR as deaths/1,000 person-years (PYR). MRs were estimated for the pre-HAART (≤1996), early-HAART (1997–2004) and late-HAART (≥2005) periods. Deaths were considered AIDS related, if CD4 count <6 months before death was <200 cells/µL and/or an AIDS-related event occurred <12 months of death.Results. We identified 171 cases of HIV among adult Greenlanders. Of these, 133 (78%) were infected in Greenland, 17 (10%) in Denmark and 21 (12%) in other places. The majority was infected through heterosexual contact [127 (74%)], 30 (18%) through homosexual contact, 3 (2%) through intravenous drug use and 11 (6%) through other or unknown routes of transmission.The median age at HIV diagnosis was 46 years (interquartile range 34–56). The incidence increased from 3.8 before 1989 to 29.7 cases/100,000 adults/year in the late 1990s. The incidence has slowly declined to approximately eight cases/100,000 adults/year. Prevalence increased to a maximum in 2009 (174.9/100,000 inhabitants), and slowly declined since then. A total of 79 have died and 25 have emigrated. MRs were high in the pre- and early-HAART periods, 65.3 [95% confidence intervals (CI) 40.0–106.6] and 87.0 [95% CI 63.5–119.0], and a large fraction of deaths were AIDS related. In the late-HAART period, MR has declined markedly to 53.4 (95% CI 35.8–79.7) with a substantial decline in AIDS-related MR.Conclusion. Heterosexual contact is the main route of HIV infection and the patients are diagnosed at a median age of 46. The incidence of newly diagnosed HIV patients has decreased markedly since year 2000. Mortality is high although declining in recent years.To access the supplementary material to this article please see Supplementary files under Article Tools online

An unknown migration route of the ‘globally threatened’ Aquatic Warbler revealed by geolocators

The globally-threatened Aquatic Warbler (Acrocephalus paludicola) breeds in Europe and spends the northern winter in sub-Saharan West Africa. We attached 30 geolocators to breeding birds in the central Ukraine in 2010. Three geolocators which collected data from the autumn migration were recovered in 2011. They revealed a previously-unknown migration route via southern Europe to stopover sites in south-western France and Spain. In West Africa, one bird spent some time well south of known non-breeding areas. For the conservation of some Aquatic Warbler populations, protection of hitherto unknown stopover sites in southern Europe and Africa may be crucial.

Transfection of a human glioblastoma cell line with liver‐type glutaminase (LGA) down‐regulates the expression of DNA‐repair gene MGMT and sensitizes the cells to alkylating agents

O(6)-methylguanine-DNA methyltransferase (MGMT) is a DNA-repair protein promoting resistance of tumor cells to alkylating chemotherapeutic agents. Glioma cells are particularly resistant to this class of drugs which include temozolomide (TMZ) and carmustine (BCNU). A previous study using the RNA microarray technique showed that decrease of MGMT mRNA stands out among the alterations in gene expression caused by the cell growth-depressing transfection of a T98G glioma cell line with liver-type glutaminase (LGA) [Szeliga et al. (2009) Glia, 57, 1014]. Here, we show that stably LGA-transfected cells (TLGA) exhibit decreased MGMT protein expression and activity as compared with non-transfected or mock transfected cells (controls). However, the decrease of expression occurs in the absence of changes in the methylation of the promoter region, indicating that LGA circumvents, by an as yet unknown route, the most common mechanism of MGMT silencing. TLGA turned out to be significantly more sensitive to treatment with 100-1000 μM of TMZ and BCNU in the acute cell growth inhibition assay (MTT). In the clonogenic survival assay, TLGA cells displayed increased sensitivity even to 10 μM TMZ and BCNU. Our results indicate that enrichment with LGA, in addition to inhibiting glioma growth, may facilitate chemotherapeutic intervention.