Letteratura scientifica selezionata sul tema "813/.3"

Abstract Foetal/neonatal alloimmune thrombocytopenia (FNAIT) is caused by the destruction of fetal platelets by maternal platelet alloantibodies which crossed through the placenta during pregnancy. Alloantibodies (aabs) against Human Platelet Antigen-1a (HPA-1a) residing on the b-subunit of the fibrinogen receptor (alphaIIbbeta3 integrin) on platelets are responsible for intracranial hemorrhage (ICH) in severe FNAIT cases. Recently, we could demonstrate that the deglycosylated mouse mab SZ21 against HPA-1a is able to cross through placenta, and prevents the destruction of platelets in mouse model (Bakchoul et al, Blood 2013). Meanwhile, this mab is humanized as chimeric antibody (mab 813). It is known that the beta3-subunit is abundantly expressed as vitronectin receptor (alphavbeta3 integrin) on endothelial surface. In this study, we sought to investigate the effect of deglycosylated mab 813 (deg-813) towards endothelial function. Deg-813 was prepared and characterized as previously described (Bakchoul et al, Blood 2013). Flow cytometry analysis showed similar binding activity of intact 813 and deg-813 with platelets and endothelial cells. This result could be confirmed by surface plasmon resonance technology; native and deg-813 interacted equally with purified alphavbeta3 immobilized on the sensor chip (Kd 7.43x10-11 and 6.67x10-11, respectively). To study the influence of mab 813 on endothelial function, apoptosis experiment with HUVEC was performed using Tunel and Caspase-3/7 assays. In both assays, endothelial apoptosis was not observed with intact 813 and deg-813. In contrast, inhibitory mabs against alphavbeta3 receptor (clones 23C6, LM609) as well as cyclic Arg-Gly-Asp peptide caused significant apoptosis of these cells. Similar results were obtained with brain endothelial cells (hCMEC/D3). Accordingly, deg-813 did not inhibit the adhesion of HUVEC on vitronectin matrix when compared to alphavbeta3 specific mabs. Furthermore, we asked the question whether maternal anti-HPA-1a aabs may induce endothelial apoptosis. Anti-HPA-1a aabs derived from FNAIT mothers giving birth of babies with ICH (n = 3) were purified by absorption/elution method using HUVEC. Analysis of the eluted material by antigen capture assay showed specific binding to alphavbeta3, but not to alphaIIbbeta3. This result could be confirmed by immunoprecipitation analysis. When alphavbeta3-reactive anti-HPA-1a antibodies were tested with endothelial cells, significant apoptosis was observed. In the control experiment, anti-alphaIIbbeta3 complex specific antibodies did not cause endothelial apoptosis. Finally, incubation of HUVEC with deg-813 prevented cell death mediated by anti-HPA-1a antibodies. Taking together, our observation indicates that deg-813 can protect not only anti-HPA-1a aabs mediated platelet destruction but also endothelial disturbance without altering endothelial function. These results suggest that deg-813 may represent a novel drug to prevent ICH in severe FNAIT during pregnancy. Disclosures No relevant conflicts of interest to declare.

Tujuan penelitian ini adalah untuk mendeskripsikan fase-fase pembentuk stigma pada tokoh utama yang terdapat dalam Novel 813 karya Maurice Leblanc. Pendekatan yang digunakan adalah pendekatan kualitatif struktural karya sastra dengan metode analisis isi. Data berupa kata, frasa, kalimat atau dialog tentang fase-fase pembentuk stigma. Sedangkan sumber data adalah Novel 813 karya Maurice Leblanc. Teori yang digunakan dalam penelitian ini mengacu pada teori stigma menurut Jean-Yves Giordana berupa tiga fase-fase pembentukan stigma yaitu (1) fase pelabelan (Étiquetage) (2) prasangka (Préjudice), dan (3) diskriminasi (Discrimination). Analisis data menggunakan studi dokumen dan mengacu pada teknik analisis data untuk sumber data yaitu Novel 813 karya Maurice Leblanc dengan menganalisis pada setiap unsur intrinsik pada novel mulai dari alur, tokoh dan latar, kemudian mengacu pada teknik analisis data yang digunakan oleh Miles dan Huberman yaitu, reduksi data, penyajian data dan penarikan kesimpulan. Hasil penelitian ini menunjukkan bahwa ada dua puluh dua (22) kutipan yang menunjukkan sebuah fase-fase pembentuk stigma yang dirasakan tokoh utama dalam novel 813 karya Maurice Leblanc. Di antaranya yang pertama fase prasangka berjumlah sebelas (11) kutipan, fase pelabelan berjumlah tujuh (7) kutipan dan fase diskriminasi berjumlah empat (4) kutipan. Berdasarkan penelitian yang telah selesai dilakukan dapat disimpulkan fase prasangka menjadi fase yang paling banyak dirasakan oleh tokoh utama dalam novel 813 karya Maurice Leblanc, kemudian disusul oleh fase kedua adalah fase pelabelan dan yang terakhir adalah fase diskriminasi.

The purpose of this study was to investigate the prevalence and etiology of hearing loss in primary and middle school students in the Hubei province of China. During a 2-year period, 504,348 students were examined by a speech audiometry test, and 813 deaf students were detected. Among the 813 deaf students, 232 cases were diagnosed with congenital deafness and 560 cases had acquired deafness, among which 276 cases had aminoglycoside-antibiotic-induced deafness. The severity of deafness could be further ascertained in 804 other students, with 402 profound, 363 severe, 21 moderate and 18 mild deafness cases. The age at deafness onset of most students was under 3 years. The prevalence of congenital and acquired deafness was 0.046% (232/504,348) and 0.111% (560/504,348), respectively, much lower than previously reported in other regions of China. Furthermore, the genetic factor was identified as one of the principal causes of deafness by pedigree analysis. Published courtesy of: Audiol Neurootol. 2010; 15(6): 394-398

Waves and Rays in Seismology: Answers to Unasked Questions, second edition, by Michael Slawinski, ISBN 978-9-813-23987-6, 2018, World Scientific, 576 p. Archaeogeophysics: State of the Art and Case Studies, by Gad El-Qady and Mohamed Metwaly, ISBN 978-3-319-78860-9, 2019, Springer International Publishing, 276 p. Earthquake Analysis and Design of Industrial Structures and Infra-structures, by Indrajit Chowdhury and Shambhu Dasgupta, ISBN 978-3-319-90831-1, 2019, Springer International Publishing, 1050 p.

To investigate the functional significance of individual consensus phosphorylation sites within the R domain of cystic fibrosis transmembrane conductance regulator (CFTR), serines were eliminated by substituting them with alanine. Included in this analysis were serine-660, -670, -686, -700, -712, -737, -768, -795, and -813, which lie within protein kinase A consensus sequences, and serine-641, which does not. Elimination of single potential phosphorylation sites altered the sensitivity of CFTR (expressed in Xenopus oocytes) to activating conditions in a manner that was highly site dependent. Substitution at serine-660, -670, -700, -795, or -813 significantly increased the half-maximal activation constant (KA) for activation by 3-isobutyl-1-methylxanthine, which is consistent with the hypothesis that phosphorylation at any of these sites promotes CFTR activation. The effect of substitution at serine-813 was significantly greater than at the other sites. In contrast, alanine substitution at serine-737 or -768 actually decreased the KA for activation, suggesting that phosphorylation at either of these sites is inhibitory. Substitution at serine-641, -686, and -712 had no significant effect on activation sensitivity. The effects of multiple serine to alanine substitutions were consistent with the notion that phosphorylation at individual sites produced roughly additive effects, suggesting that the effect produced by phosphorylation of any one serine was not dependent on the phosphorylation state of other serines. These results are consistent with the notion that, although none of the phosphorylation sites studied here are absolutely necessary for activation of CFTR, individual sites contribute differently to the gating of the channel.

Background Acute myocarditis is an inflammatory disease of the heart mostly diagnosed in young people, which can present as sudden death. The etiology includes infectious agents (mostly viruses), systemic diseases and toxins. We aim to characterize infants and children with myocarditis at post-mortem presenting as sudden deaths. Methods Retrospective evaluation of 813 post-mortems in infants and children dying suddenly and unexpectedly between 2009–2019. Data retrieved included histological features, microbiology and clinical history. Results 23 of 813 post-mortems reviewed corresponded to acute myocarditis and 1 to dilated cardiomyopathy related to remote Parvovirus infection. PCR identified enterovirus (7), parvovirus (7 cases, 2 also with HHV6 and 1 case with EVB), Influenza A (1), Parainfluenza type 3 (1). Two cases corresponded to hypersensitivity myocarditis, 1 was Group A Streptococcus and 5 idiopathic myocarditis. Enterovirus was frequent in infants (7/10), and in newborns was associated with meningoencephalitis or congenital myocarditis. More than 50% were less than 2 years of age and all remained clinically unsuspected. Conclusion Myocarditis represents almost 3% of all sudden pediatric deaths. Enterovirus and parvovirus were the most common viruses. This retrospective analysis showed that patients experienced viral symptoms but remained unsuspected, highlighting the need for more clinical awareness of myocarditis.

Rietveld neutron powder profile analysis of the compound Na0.5Bi0.5TiO3 (NBT) is reported over the temperature range 5–873 K. The sequence of phase transitions from the high-temperature prototypic cubic structure (above 813 K), to one of tetragonal (673–773 K) and then rhombohedral structures (5–528 K) has been established. Coexisting tetragonal/cubic (773–813 K) and rhombohedral/tetragonal (with an upper temperature limit of 145 K between 528 and 673 K) phases have also been observed. Refinements have revealed that the rhombohedral phase, space group R3c, with a H = 5.4887 (2), c H = 13.5048 (8) Å, V = 352.33 (3) Å3, Z = 6 and D x = 5.99 Mg m−3, exhibits an antiphase, a − a − a − oxygen tilt system, ω = 8.24 (4)°, with parallel cation displacements at room temperature. The tetragonal phase, space group P4bm, with a T = 5.5179 (2), c T = 3.9073 (2) Å, V = 118.96 (1) Å3, Z = 2 and D x = 5.91 Mg m−3, possesses an unusual combination of in-phase, a 0 a 0 c + oxygen octahedra tilts, ω = 3.06 (2)°, and antiparallel cation displacements along the polar axis. General trends of cation displacements and the various deviations of the octahedral network from the prototypic cubic perovskite structure have been established and their systematic behaviour with temperature is reported. An investigation of phase transition behaviour using second harmonic generation (SHG) to establish the centrosymmetric or non-centrosymmetric nature of the various phases is also reported.

Chronic inflammation has been linked to cancer. Prostaglandin E2 (PGE2) is the most pro-inflammatory lipid and one of the downstream products of 2 isoforms of cyclooxygenase (COX) enzymes: COX-1 and COX-2. Although both COX isoforms have similar structure and function, they are encoded by different genes and show distinct expression patterns. COX-1 is expressed in most cells and tissues and remains constant under most physiologic conditions to play a housekeeping role whereas the COX-2 form is inducible and usually only expressed in response to various inflammatory stimuli. COX enzymes may be involved in both tumor establishment and maintenance of existing tumors. PGE2 exerts its effects on target cells by coupling to four subtypes of receptors which have been classified as EP1-4. Ovarian cancer is the most lethal gynecological malignancy and mainly occurs in older women. Prevention may be the best approach to reduce ovarian cancer. Ovarian cancer is the fifth leading cause of cancer death among women and the most lethal gynecological malignancy. There are at least 3 well established risk factors for ovarian cancer: age, family history and environmental factors. Ovarian cancer is mainly seen in older women when their ovaries are not reproductively functional. Close to half of the women with ovarian cancer (48%) are in the age group of 65 or older. Epidemiological and preclinical studies indicate that increased dietary intake of omega-3 fatty acids (OM-3FAs) reduces the incidence and growth of various cancers. Thus, increasing the consumption of OM-3FAs may be a nontoxic way to prevent or suppress ovarian cancer. Flaxseed is the richest vegetable source of omega-3 fatty acids which may be effective in the prevention of ovarian cancer. Fish oil is a source of OM-3FAs which may be effective in prevention of ovarian cancer. The main OM-6FA, Linoleic Acid (LA), is a direct precursor of the Arachidonic Acid (AA). Alpha-linolenic acid (ALA) is the main OM-3FA found in flax oil, whereas eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the OM-3FAs in fish oil. ALA is elongated to form EPA and DHA in the intestine. Celecoxib is a non-steroidal anti-inflammatory (NSAID) drug that selectively inhibits COX-2. There are evidences showing that Celecoxib has some anti-cancer properties. Progress in the treatment and prevention of ovarian cancer has been hampered due to the lack of an appropriate animal model and absence of effective chemo-prevention strategies. The domestic hens spontaneously develop ovarian adenocarcinomas that share similar histological appearance and symptoms such as ascites and metastasis with humans. Our first objective was to investigate the effect of flaxseed supplementation for one year on ovarian cancer and correlate its effects to expression of COX enzymes and concentrations of prostaglandins. White Leghorn hens were fed 10% flaxseed-enriched or standard diet for one year. The severity of ovarian cancer was determined by gross pathology and histology. COX-1 and COX-2 localization and protein and mRNA expression and PGE2 and PGE3 concentrations in ovaries were measured by Immunohistochemistry, western blot, quantitative real-time PCR and LC-MS-MS, respectively. The results demonstrated a significant reduction in late stage ovarian tumors in the flaxseed-fed hens compared with the control diet-fed hens. In correlation with decreased ovarian cancer severity, concentrations of PGE2 and expression of COX-2 were diminished in ovaries of flaxseed-fed hens. PGE3 concentrations were below the level of detection. The results demonstrated that in normal ovaries, COX-1 was localized to the granulosa cell layer surrounding the follicles and ovarian surface epithelium (OSE) whereas COX-2 protein was localized to the granulosa cell layer in the follicle. Extensive COX-1 and COX-2 protein expression was found throughout the ovarian carcinoma. Our findings suggest that the flaxseed-mediated reduction in the severity of ovarian cancer in hens is correlated to the reduction in PGE2 in the ovaries of flaxseed-fed hens. Since no effect on ovarian cancer incidence was detected after feeding the 2. 5 year old hens with 10% flaxseed for 1 year, we designed a long-term study using 6 month old hens. Our objectives were: 1) to examine the expression of COX enzymes and PGE2 levels in ovaries and correlate them to ovarian cancer and aging 2) to determine if long-term consumption of a flaxseed enriched diet decreases ovarian cancer severity and incidence in the laying hen and to investigate its potential correlation with the expression of COX enzymes and PGE2 concentration. White Leghorn hens were fed 10% flaxseed-enriched or standard diet for 4 years. The severity and incidence of ovarian cancer were determined by gross pathology and histology. COX-1 and COX-2 protein and mRNA expression and PGE2 concentrations in ovaries were measured by western blot, quantitative real-time PCR and ELISA, respectively. Our results indicated an increase in ovarian cancer incidence and expression of both COX enzymes in ovaries of older hens. In correlation with ovarian cancer incidence and COX enzymes expression, PGE2 concentrations were elevated with age. Ovaries with tumor had elevated COX-1 expression and PGE2 concentration compared to normal ovaries. Our findings suggest that the up-regulation of COX enzymes with age is the main contributing factor in the age associated increase in PGE2. Furthermore, elevated PGE2 in ovaries of hens concomitant with age suggests its important role in early stages of ovarian carcinogenesis. The results demonstrated that there was a reduction in ovarian cancer severity and incidence in hens fed flaxseed diet. In correlation with decreased ovarian cancer severity and incidence, concentration of PGE2 and expression of COX-2 were diminished in ovaries of hens fed flaxseed. Our findings suggest that the lower levels of COX-2 and PGE2 are the main contributing factors in the chemo-suppressive role of long-term flaxseed consumption in ovarian cancer in laying hens. These findings may provide the basis for clinical trials of dietary intervention targeting prostaglandin biosynthesis for the prevention and treatment of ovarian cancer. Based on our previous findings, targeting COX expression and prostaglandin biosynthesis by dietary intervention using OM-3FAs and selective COX inhibitor can be an effective approach to prevent or suppress ovarian cancer. Thus, we conducted a series of studies to assess effect of fish oil, flax oil, Celecoxib, fish oil and Celecoxib combined or flax oil and Celecoxib combined on COX-1 and COX-2 expression, PGE2 concentrations, proliferation and apoptosis in normal and cancerous ovaries of laying hens. This study had not been performed in hens before, thus the first step was to find the optimum doses. In order to do so, we utilized one year old hens, divided them to groups of 6 hens, and fed them different doses of fish oil (50, 100, 175, 375 and 700 mg/kg), flax oil (100, 250, 500, 1000 and 1500 mg/kg) or Celecoxib (35, 65 and 100 mg/kg) for three weeks. The OM3-FAs andomega-6 fatty acids contents of egg yolks were determined by gas chromatography. Proliferation, apoptosis,COX-1, COX-2 and prostaglandin receptor subtype 4 (EP4) protein and mRNA expression and PGE2 concentration in ovaries were measured by PCNA, TUNEL, western blot, quantitative real-time qPCR and ELISA, respectively. The results indicated that 100 mg/kg fish oil was the most effective dose in reducing COX enzymes and PGE2, and increased apoptosis and reduced proliferation in ovaries. The lower doses of fish oil incorporated more OM-3FAs into yolks, reduced OM-6FAs and increased the egg laying frequency but did not affect EP4 expression. Unlike fish oil, the highest dose of flax oil (1500 mg/kg) caused the most significant reduction in COX expression and PGE2 concentration. Celecoxib was not perfectly selective in targeting COX-2, however, treating the hens with 65 mg/kg Celecoxib resulted in the most significant amelioration of PGE2 levels in ovaries. Using the optimum doses of fish oil, flax oil and Celecoxib, we aimed to investigate if these components can alter ovarian cancer end-points in normal and cancerous hen ovaries. There is an adverse relation between ovulation and health of ovaries. Thus, 3-4 year old hens were monitored for egg laying frequency and the hens with the least ovulation rate were selected for health assessment. The hens presenting poor health were scanned using ultrasound and if tumor mass and/or ascites were detected, they were chosen for this study. The hens with normal and cancerous ovaries were divided to groups and were fed fish oil, flax oil, Celecoxib, fish oil and Celecoxib combined, or flax oil and Celecoxib combined for 42 days. The results showed that fish oil and flax oil increased the incorporation of OM-3FAs into egg yolks in both normal and cancerous ovaries of hens. Fish oil reduced COX-1 and COX-2 in normal and cancerous ovaries. Fish oil, flax oil and Celecoxib reduced the COX-2 expression in ovaries. Combination of fish oil and Celecoxib and flax oil and Celecoxib decreased COX and PGE2 more than each of these treatments alone. The cancerous ovaries of hens treated with fish oil, flax oil, Celecoxib, and flax oil and Celecoxib combined increased the percentage of apoptotic cells compared to cancerous ovaries of control hens. The cancerous ovaries of hens treated with fish oil and Celecoxib had the highest number of apoptotic cells indicating that the combination of fish oil and Celecoxib is more effective than fish oil or Celecoxib alone. To our knowledge the present study provides the first insight into the efficacy of fish oil, flax oil, Celecoxib, alone or combined on the reduction of COX enzyme expression, PGE2 concentration and apoptosis in the normal and cancerous ovaries and further demonstrates the utility of the hen model for ovarian cancer. Our studies provided new insight into the potential mechanism of action of flaxseed, fish oil, flax oil and Celecoxib in the reduction of ovarian cancer and will establish the foundation for clinical trials to test the efficacy of dietary intervention for the prevention and suppression of ovarian cancer in women.

Dissertação de Mestrado em Psicologia Educacional
Investigações recentes no âmbito do quadro teórico de K. Nelson têm demonstrado que uma das primeiras formas de tratamento da informação utilizadas pelas crianças são baseadas nas experiências de vida e nas representações destes acontecimentos rotineiros. Nelson e colaboradores propõem que estas representações de acontecimentos são como que "sementes" cognitivas, funcionando não só como formatos nas interacções sociais, mas também como organizadores estáveis do conhecimento, permitindo o desenvolvimento de estruturas de conhecimento mais complexas. Este trabalho insere-se nesta problemática. Pretendeu-se estudar como é que as estruturas de acontecimentos familiares podem influenciar o desenvolvimento cognitivo / linguístico das crianças de idade pré-escolar. A partir de relatos de crianças dos 3 aos 6 anos sobre um dia de escola e uma festa de aniversário. Estudámos : 1- estrutura do discurso tipo-script e graus de complexidade; 2- diferentes indicadores linguísticos referentes a estruturas de tempo; 3- a capacidade de resolução de um problema de ordem linguística. Para além de um efeito da idade, os resultados evidenciam a importância dos scripts enquanto organizadores do conhecimento e sua influência na produção / compreensão dos termos linguísticos analisados. Revelam ainda um efeito do estimulo (dia de escola / festa de aniversário) apontando para o facto de que acontecimentos mais familiares e estruturados têm influência nas representações verbalizadas e no domínio dos termos linguísticos das crianças destas idades.

Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2007.
Title from electronic title page (viewed Dec. 18, 2007). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Biology." Discipline: Biology; Department/School: Biology.

PetroChina’s West to East Natural Gas Pipeline Project (WEPP) has been under construction since October of 2001. Upon completion, construction will be completed on the following major facilities: 3,800 km of 1,016 mm mainline; 294 km of 813 mm, 508 mm, and 406 mm lateral lines; Dual fiber optic conduits with the mainline pipeline; 1,100 km of access roads; 23 metering stations; 18 pigging stations; 10 compressor stations; 16 mountain tunnels; 16 aerial crossings; 41 mainline and 18 lateral line HDDs; 1 crossing of the Yangtze River (a 4.4 m concrete lined tunnel); 3 crossings of the Yellow River (pipe jacking, tunnel and aerial methods); gas control center and SCADA system. This paper covers topics including construction management; engineering, procurement, and construction; major construction challenges; and, business in China.

The differential absorption lidar (DIAL) technique was first applied to the remote measurement of atmospheric water vapor profiles from airborne platforms in 1981 [1]. The successful interpretation of the lidar profiles relies strongly on an accurate knowledge of specific water vapor absorption line parameters: line strength, pressure broadening coefficient, pressure-induced shift coefficient and the respective temperature-dependence factors [2]. NASA Langley Research Center has developed and is currently testing an autonomous airborne water vapor lidar system: LASE (Lidar Atmospheric Sensing Experiment). This DIAL system uses a Nd:YAG-pumped Ti:Sapphire laser seeded by a diode laser as a lidar transmitter. The tunable diode has been selected to operate in the 813-818 nm wavelength region. This 5-nm spectral interval offers a large distribution of strengths for temperature-insensitive water vapor absorption lines. In support of the LASE project, a series of spectroscopic measurements were conducted for the 16 absorption lines that have been identified for use in the LASE measurements. Prior to this work, the experimental data for this water vapor absorption band were limited - to our knowledge - to the line strengths and to the line positions [3].

The author offers new possibilities for interpretation of Frankish, domestic and Byzantine sources regarding the Bulgarian political control over territories of Avar Khaganate, destroyed by Charlemagne. The main focus is placed on the certificate of embassy led by Princeрs Avarum and Canizauci in Aachen in November 811. Coordinating it with Bulgarian and Byzantine sources, leads to the following conclusions. 1. It is likely that the diplomatic mission to Charlemagne in 811, involving representatives of the Avar com­munity, led by its Tudun and Slavic tribal princes, was led by the Bulgarian prince – Omurtag, the younger brother of the ruler Krum (802? – 814), in his capacity as prince (princeps) and ombritag. i. e. Avars hegem­on, in the northwestern borders after 803 and „Khan’s beloved younger brother” (khani sev`ingi or khani sev(inč) ingi). In Aachen, he introduced himself as a cani zautzi, that is, with his post of „Khan’s envoy”. 2. The khanas uvigi Omurtag (814–831) missions to Emperor Louis in 824 and 825–826 appear to have also been led by a member of the ruling family in Plisk oba (Pliska), maybe from his second son – Zvinitsa/Zvinichis. They also appear to have had a representative/s of settlers between 813 and 837 in Trans­Danubian Bulgaria (probably in the Lower Tisza region) of Bulgarian captives of Eastern Thrace of Armenian origin. One of their leaders in 837 was named Tzantzès, and his son, Stilian, and his descendants gained fame in Byzantium under the surname Ζαούτζης, Ζαούτζας. It coincides exactly with the pro­Bulgarian official title (position) zautzi (tzautci), (=chaush) and probably derived from it. On this basis, we conclude that Τζάντζην (Öан¤·þ воеводэ) was performing the carrier of messages or emissary functions of the Bulgarian state before 837. 3. The considered evidence, facts and circumstances surrounding the Bulgarian diplomatic missions of 811, 824 and 825/6 provide new testifies for the Bulgarian state’s control over the south-eastern parts of the Avar Khaganate after its collapse in the period 791–803. They have a contribution to clarify important aspects of the Bulgarian state’s relations with the East Frankish Kingdom, as well as with the local population of Avars, Bulgarians and Slavs there.