HIV variánsok genotipus meghatározása: gyógyszer-rezisztens HIV mutánsok kimutatása nem kezelt HIV fertőzöttekben = HIV genotyping: drug resistant HIV mutants in therapy naive patients

A HIV-1 pol gén antiretrovirális szerekkel szembeni gyógyszer-rezisztenciához (GYR) vezető mutációit vizsgáltuk kezelésben még nem részesülő primer HIV fertőzöttekben. A genotipizálást a HIV-1 RT és PR génjeiben in situ DNS hybridizációval, direkt DNS szekvenálással és a Trugene Genotipizáló Rendszerrel végeztük. A pol gén GYR-hez vezető mutációit a vizsgáltak 14%-ában tudtuk kimutatni. A PR inhibítorokkal szembeni rezisztencia 12% volt, az NRTI-kkel 8% és az NNRTI-kkel 5%. A legmagasabb rezisztencia (25%) a homoszexuális átadódású vírusok tartalmazták a NNRTI-kkel szemben. Többszörös, 2-3 gyógyszer családdal szembeni rezisztencia az esetek 3.5%-ában volt kimutatható. Nem-B altipusú vírusokat (HIV-1 C és F1), ill. rekombináns formákat (CRF) is detektáltunk,jelezve Afrikai rekombináns törzsek magyarországi penetrációját. Jelen munkánk az első felmérés volt hazánkban a GYR HIV-1 variánsok kimutatására és elterjedtségére vonatkozóan. Az eredményeink a GYR kialakulásának időbeli evolúcióját jelzik, amely korrelál a hazai kombinációs kezelés bevezetésével, megerősítik a GYR HIV variánsok transzmisszióját terápia-naiv egyénekben komoly klinikai és járványügyi következményeket felvetve. A GYR olyan vírusok megjelenésével jár, amelyek kikerülik a kombinációs kezeléseket és az AIDS progressziójához vezetnek. Munkánk alapján a rezisztencia tesztek (HIV genotipizálás) a klinikai gyakorlat részévé vált, és megalapozta egy rendszeres, országos HIV-1 GYR monitorozás bevezetését | Mutations in the HIV-1 pol gene associated with resistance to anti-retroviral drugs in therapy-naive Hungarian individuals transmitted as primary infection had been analyzed. Drug resistance genotyping of HIV RT and PR genes were done by in situ DNA hybridization, direct DNS sequencing and Truegene HIV-1 Genotyping System. Resistance mutations in the pol gene were detected in 14% of the subjects. The highest rate of resistance to a single class of inhibitors was detected towards PR inhibitors (12%), followed by NRTI (8%) and NNRTI (5%). 25 % of viruses transmitted by homosexual activity had mutations led to resistance to NNRTI. Multiple drug resistant viruses (2-3 drug classes) were present in 3.5%. Non-B subtypes and CRFs were also detected, indicating penetration of non-B subtypes and recombinant African variants into Hungary. Our study was the first survey for detection prevalence of transmission of drug-resistant HIV-1 strains in our country. Findings indicate the evolution of drug resistance showing a correlation with the time of introduction of combination therapy in our country, confirm drug-resistant HIV in therapy-naive patients and raises serious clinical and public health consequences as this viruses escape the control of drug combination therapy and cause AIDS progression. Based upon our work, resistance testing at the time of diagnosis became a standard of clinical care, and a systematic nationwide monitoring of HIV-1 drug resistance has been initiated

The MTA SZTAKI Smart Factory: Platform for Research and Project-oriented Skill Development in Higher Education

Nowadays, the potential of learning factories as test beds and research plants is gaining recognition, and several facilities are extended or built up already with these complementing purposes in mind---among them the Smart Factory at the Fraunhofer Project Center at MTA SZTAKI currently completing a major stage of development. The paper presents the structure and key design principles of the plant, and explains how the composition and functionalities of the equipment implement focal principles of the Industry 4.0 and Cyber-Physical Systems concepts. Furthermore, it is shown how the Smart Factory provides students with challenges and resources for project-oriented development of their skills, and where these opportunities fit into technical higher education by hosting both individual student projects and courses with a specific structure of progress

Magyar Tanítóképző 48 (1935) 10

Magyar Tanítóképző A Tanítóképző-intézeti Tanárok Országos Egyesületének folyóirata 48. évfolyam, 10. szám Budapest, 1935. decembe

Differential vulnerability of different forms of skill learning in Parkinson’s disease

The striatal dopaminergic dysfunction in Parkinson’s disease (PD) has been associated with deficits in skill learning in a number of studies, but the results are inconclusive so far. Motor sequence learning (especially sequence-specific learning) is found to be deficient in the majority of studies using the Serial Reaction Time Task (SRTT; Siegert, Taylor, Weatherall, & Abernethy, 2006; Jackson et al., 1995; Ferraro, Balota and Connor, 1993; Pascual-Leone et al., 1993, Muslimovic et al., 2007; Gobel et al., 2013; but see Kwak et al., 2012), although results are contradictory when verbal response is required instead of button presses (Westwater et al. 1998; Smith, Siegert and McDowall 2001). While problems with motor sequences seem to be prevalent, PD patients show intact performance on Artificial Grammar Learning (AGL) tasks, suggesting that the sequencing problem may be response type- or task type-dependent (Smith, Siegert and McDowall 2001; Witt, Nühsman and Deuschl, 2002) Acquisition of nonsequential probabilistic associations also seems to be vulnerable as evidenced by impaired PD performance on a probabilistic category learning task (Knowlton, Mangels et al., 1996; Shohamy, Myers, Onlaor, & Gluck, 2004). Our aim was to explore the nature of the skill learning deficit by testing different types of skill learning (sequential versus nonsequential, motor versus verbal) in the same group of Parkinson’s patients. 14 patients with PD (mean age: 59.77 range: 45.5-74) were compared to age-matched typical adults using 1) a Serial Reaction Time Task (SRTT) testing the learning of motor sequences, 2) an Artificial Grammar Learning (AGL) task testing the extraction of regularities from auditory sequences and 3) a Weather prediction task (PCL-WP), testing probabilistic category learning in a non-sequential task. In motor sequence learning on the SRTT task, the two groups did not differ in accuracy; PD patients were generally slower, and analysis of z-transformed reaction times showed no evidence of sequence learning in PD. A deficit in artificial grammar learning was present only as a tendency in the PD group. The PD group showed evidence of learning on the PCL task, and their learning performance was not statistically different from that of the control group. These results partly support and also extend previous findings suggesting that motor skill learning is vulnerable in PD, while other forms of skill learning are less prone to impairment. Results are also in line with previous assumptions that mechanisms underlying artificial grammar learning and probabilistic categorization do not depend on the striatum (Reber & Squire, 1999; Skosnik et al., 2002)

Differential vulnerability of different forms of skill learning in Parkinson’s disease Different forms of skill learning in Parkinson’s disease

The striatal dopaminergic dysfunction in Parkinson’s disease (PD) has been associated with deficits in skill learning, but results are inconclusive so far. Motor sequence learning (especially sequence-specific learning) is found to be deficient in the majority of studies using the SRT task (Jackson, Jackson, Harrison, Henderson, & Kennard, 1995; Siegert, Taylor, Weatherall, & Abernethy, 2006). While problems with motor sequences seem to be prevalent, PD patients show intact performance on AGL tasks, suggesting that the sequencing problem may be response- or taskdependent (Reber & Squire, 1999). Acquisition of nonsequential probabilistic associations also seems to be vulnerable as evidenced by impaired probabilistic category learning performance in PD (Knowlton, Mangels, & Squire, 1996; Shohamy, Myers, Onlaor, & Gluck, 2004). Our aim was to explore the nature of the skill learning deficit by testing different types of skill learning (sequential versus nonsequential, motor versus verbal) in the same group of Parkinson’s patients. 34 patients with PD (mean age: 62.59.77 years, SD: 7.67) were compared to age-matched typical adults using 1) a Serial Reaction Time Task (SRT) testing the learning of motor sequences, 2) an Artificial Grammar Learning (AGL) task testing the extraction of regularities from auditory sequences and 3) a Weather prediction task (PCL-WP), testing probabilistic category learning in a non-sequential task. In motor sequence learning (SRT task), the two groups did not differ in accuracy; PD patients were generally slower, and analysis of z-transformed reaction times also revealed deficient motor sequence learning in PD compared to the control group. The PD group showed no evidence of sequence learning. The PD group showed the same amount of learning on the PCL task as controls, and we observed higher rates of learning on the AGL task in PD patients than in controls. These results support and also extend previous findings suggesting that motor skill learning is vulnerable in PD, while other forms of skill learning are less prone to impairment. Results are also in line with previous assumptions that mechanisms underlying artificial grammar learning and probabilistic categorization do not depend on the striatum (Reber & Squire, 1999)

Szabályok kiemelése nyelvi és nem nyelvi ingerekből

A bemutatott kísérletben a mesterséges nyelvtan paradigma keretében tanulmányoztuk egy egyszerű szabály hangszekvenciákból való kiemelését nyelvi és nem nyelvi ingerkészlet esetén. A kísérletben részt vevő vizsgálati személyeknek egy egyszerű rövid távú emlékezeti feladat keretében kellett nyelvi, illetve nem nyelvi elemekből álló szabályos és szabálytalan hangszekvenciákat hallgatniuk és visszaadniuk. Az eredmények szerint a szabályosságot tartalmazó szekvenciák esetében az emlékezeti terjedelem nagyobb volt a nyelvi ingerkészlet esetén, mint a nem nyelvi esetben. A szabályosságot nem tartalmazó szekvenciáknál azonban nem volt hatással az emlékezeti terjedelemre, hogy az ingerkészlet a nyelvi vagy a nem nyelvi tartományba tartozott-e. Az eredmények alapján hatékonyabb a szabályok kiemelése nyelvi szekvenciákból a mesterséges nyelvtan feladat esetében. A kísérlet eredményei felvetik a nyelvi ingerekben lévő szabályosságokra kiemelten érzékeny implicit-procedurális alrendszerek lehetőségét