Legal aspects of financing a limited liability company conducting business in the field of modern technologies

Legal aspects of financing a limited liability company conducting business in the field of modern technologies Abstract This thesis deals with the issue of financing limited liability companies that operate in the field of modern technologies, otherwise known as startups. This type of companies is characterized by several specific features that usually make them unable to be financed by banks or similar financial institutions. Startups are therefore financed by specific joint stock companies set up for this purpose in one of two ways. Either through the direct purchase of equity in the company or through a convertible loan. The former approach is referred to as equity financing, while the latter is referred to as debt financing. The description and comparison of these two approaches with respect to their benefits and shortcomings is the main focus of this thesis. In the first chapter, the term startup itself is examined in detail. By synthesizing the definitions of various authors, the basic elements that a company should have in order to be called a startup are presented. Next, it is discussed why startups in the Czech Republic exist in the form of limited liability companies. The second chapter is devoted to the entities that provide startups with support, whether financial or otherwise. Further chapters...Právní aspekty financování společnosti s ručením omezeným podnikající v oblasti moderních technologií Abstrakt Tato diplomová práce se zabývá problematikou financování společností s ručením omezeným, které podnikají v oblasti moderních technologií, jinak také nazývaných jako startupy. Tento typ společností se vyznačuje několika specifiky, kvůli kterým zpravidla nemohou být financovány bankami či obdobnými finančními institucemi. Do startupů proto investují specifické akciové společnosti, které k tomu jsou zřízené, a to jedním ze dvou způsobů. Buďto skrze přímý nákup podílu ve společnosti nebo pomocí konvertibilního úvěru. První jmenovaný přístup je označován jako podílové financování, zatímco druhý jako financování dluhové. Popis a komparace těchto dvou postupů s ohledem na jejich přínosy a nedostatky je hlavní náplní této diplomové práce. V první kapitole je podrobně zkoumán samotný pojem startup. Syntézou definic různých autorů jsou představeny základní prvky, které by měla společnost mít, aby ji takto šlo nazvat. Dále je rozebráno, proč startupy v České republice existují ve formě společností s ručením omezeným. Druhá kapitola je věnována subjektům, které poskytují startupům podporu, ať už finanční, či jinou. Další části práce se věnují výše zmíněným metodám financování. V rámci podílového financování...Department of Business LawKatedra obchodního právaFaculty of LawPrávnická fakult

The \u3ci\u3ePrevotella copri\u3c/i\u3e Complex Comprises Four Distinct Clades Underrepresented in Westernized Populations

Prevotella copri is a common human gut microbe that has been both positively and negatively associated with host health. In a cross-continent metaanalysis exploiting \u3e6,500 metagenomes, we obtained \u3e1,000 genomes and explored the genetic and population structure of P. copri. P. copri encompasses four distinct clades (\u3e10% inter-clade genetic divergence) that we propose constitute the P. copri complex, and all clades were confirmed by isolate sequencing. These clades are nearly ubiquitous and co-present in non-Westernized populations. Genomic analysis showed substantial functional diversity in the complex with notable differences in carbohydrate metabolism, suggesting that multi-generational dietary modifications may be driving reduced prevalence in Westernized populations. Analysis of ancient metagenomes highlighted patterns of P. copri presence consistent with modern non-Westernized populations and a clade delineation time pre-dating human migratory waves out of Africa. These findings reveal that P. copri exhibits a high diversity that is underrepresented in Western-lifestyle populations

A Genome-wide Drosophila Screen for Heat Nociception Identifies α2δ3 as an Evolutionarily Conserved Pain Gene

Worldwide, acute and chronic pain affects 20% of the adult population and represents an enormous financial and emotional burden. Using genome-wide neuronal-specific RNAi knock-down in Drosophila, we report a global screen for an innate behavior and identify hundreds of novel genes implicated in heat nociception, including the α2δ-family calcium channel subunit straightjacket (stj). Mice mutant for the stj ortholog CACNA2D3 (α2δ3) also exhibit impaired behavioral heat pain sensitivity. In addition, in humans, α2δ3 SNP variants associate with reduced sensitivity to acute noxious heat and chronic back pain. Functional imaging in α2δ3 mutant mice revealed impaired transmission of thermal pain evoked signals from the thalamus to higher order pain centers. Intriguingly, in α2δ3 mutant mice thermal pain and tactile stimulation triggered strong cross-activation or synesthesia of brain regions involved in vision, olfaction, and hearing

Large meta-analysis of genome-wide association studies identifies five loci for lean body mass

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 x 10(-8)) or suggestively genome wide (p < 2.3 x 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/ near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/ near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass

Legal aspects of financing a limited liability company conducting business in the field of modern technologies

Legal aspects of financing a limited liability company conducting business in the field of modern technologies Abstract This thesis deals with the issue of financing limited liability companies that operate in the field of modern technologies, otherwise known as startups. This type of companies is characterized by several specific features that usually make them unable to be financed by banks or similar financial institutions. Startups are therefore financed by specific joint stock companies set up for this purpose in one of two ways. Either through the direct purchase of equity in the company or through a convertible loan. The former approach is referred to as equity financing, while the latter is referred to as debt financing. The description and comparison of these two approaches with respect to their benefits and shortcomings is the main focus of this thesis. In the first chapter, the term startup itself is examined in detail. By synthesizing the definitions of various authors, the basic elements that a company should have in order to be called a startup are presented. Next, it is discussed why startups in the Czech Republic exist in the form of limited liability companies. The second chapter is devoted to the entities that provide startups with support, whether financial or otherwise. Further chapters..

Electroconvulsive therapy for major depression within the Veterans Health Administration

Objectives: Electroconvulsive therapy (ECT) is the most effective treatment for severe or treatment resistant depression; however, the lack of widely accepted methods for determining when ECT is indicated may contribute to disparities and variation in use. We examined receipt of ECT among depressed patients in the largest coordinated health system in the US, the Veterans Health Administration. Methods: Using administrative data, we conducted a multivariable logistic regression to identify individual clinical and sociodemographic predictors of receiving ECT, including variables of geographic accessibility to ECT, among patients diagnosed with major depressive disorder between 1999 and 2004. Results: 307 (0.16%) of 187,811 patients diagnosed with major depression received ECT during the study period. Black patients were less likely to receive ECT than whites (odds ratio 0.33; 95% confidence interval: 0.20, 0.55), and patients living in the South (OR: 0.71; 95% CI: 0.53, 0.95) or West (OR: 0.59; 95% CI: 0.42, 0.82) were less likely to receive ECT than patients living in the central US. Patients whose closest VA facility provided ECT had a higher likelihood of receiving ECT (OR: 3.02; 95% CI: 2.22, 4.10). Depressed patients with no major medical comorbidities were also more likely to receive ECT (OR: 2.42; 95% CI: 1.65, 3.55). Limitations: Findings are not adjusted for depression severity. Conclusions: ECT use for major depression was relatively uncommon. Race, US region, geographic accessibility, and general medical health were all associated with whether or not patients received ECT. Clinicians and health systems should work to provide equitable access and more consistent use of this safe and effective treatment

Visceral Adipose Tissue E2F1-miRNA206/210 Pathway Associates with Type 2 Diabetes in Humans with Extreme Obesity

Objective: Up-regulated expression of transcription-factor E2F1 in human visceral adipose tissue (VAT) characterizes a dysmetabolic obesity sub-phenotype. An E2F1-miRNA network has been described in multiple cancers. Here we investigated whether elevated VAT-E2F1 in obesity is associated with VAT-miRNA alterations similar to, or distinct from, those described in cancer. Furthermore, we assessed if E2F1-associated miRNA changes may contribute to the link between high- VAT-E2F1 and a dysmetabolic obesity phenotype. Methods: We assembled a cohort of patients with obesity and high-VAT-E2F1, matched by age, sex, ±BMI to patients with low-VAT-E2F1, with and without obesity (8 patients/groupX3 groups). We performed Nanostring -based miRNA profiling of VAT samples from all 24 patients. Candidate E2F1-related miRNAs were validated by qPCR in an independent cohort of patients with extreme obesity, with or without type-2-diabetes (T2DM) (n = 20). Bioinformatic tools and manipulation of E2F1 expression in cells were used to establish the plausibility of the functional VAT-E2F1-miRNA network in obesity. Results: Among n = 798 identified miRNAs, 17 were differentially expressed in relation to E2F1 and not to obesity itself. No evidence for the cancer-related E2F1-miRNA network was identified in human VAT in obesity. In HEK293-cells, overexpression/downregulation of E2F1 correspondingly altered the expression of miRNA-206 and miRNA-210-5p, two miRNAs with reported metabolic functions consistent with those of E2F1. In VAT from both cohorts, the expression of both miRNA-206 and 210-5p intercorrelated, and correlated with the expression of E2F1. In cohort 1 we did not detect significant associations with biochemical parameters. In cohort 2 of patients with extreme obesity, all those with high VAT-E2F1 showed a diabetes-complicated obesity phenotype and higher expression of miRNA-206 and miRNA-210-5p, which also correlated with fasting glucose levels (both miRNAs) and fasting insulin (miRNA-210-5p). Conclusions: Whilst the previously described cancer-related E2F1-miRNA network does not appear to operate in VAT in obesity, miRNAs-206 and 210-5p may link high-E2F1 expression in VAT with diabetes-complicated extreme obesity phenotype

Visceral Adipose Tissue E2F1-miRNA206/210 Pathway Associates with Type 2 Diabetes in Humans with Extreme Obesity

Objective: Up-regulated expression of transcription-factor E2F1 in human visceral adipose tissue (VAT) characterizes a dysmetabolic obesity sub-phenotype. An E2F1-miRNA network has been described in multiple cancers. Here we investigated whether elevated VAT-E2F1 in obesity is associated with VAT-miRNA alterations similar to, or distinct from, those described in cancer. Furthermore, we assessed if E2F1-associated miRNA changes may contribute to the link between high- VAT-E2F1 and a dysmetabolic obesity phenotype. Methods: We assembled a cohort of patients with obesity and high-VAT-E2F1, matched by age, sex, ±BMI to patients with low-VAT-E2F1, with and without obesity (8 patients/groupX3 groups). We performed Nanostring -based miRNA profiling of VAT samples from all 24 patients. Candidate E2F1-related miRNAs were validated by qPCR in an independent cohort of patients with extreme obesity, with or without type-2-diabetes (T2DM) (n = 20). Bioinformatic tools and manipulation of E2F1 expression in cells were used to establish the plausibility of the functional VAT-E2F1-miRNA network in obesity. Results: Among n = 798 identified miRNAs, 17 were differentially expressed in relation to E2F1 and not to obesity itself. No evidence for the cancer-related E2F1-miRNA network was identified in human VAT in obesity. In HEK293-cells, overexpression/downregulation of E2F1 correspondingly altered the expression of miRNA-206 and miRNA-210-5p, two miRNAs with reported metabolic functions consistent with those of E2F1. In VAT from both cohorts, the expression of both miRNA-206 and 210-5p intercorrelated, and correlated with the expression of E2F1. In cohort 1 we did not detect significant associations with biochemical parameters. In cohort 2 of patients with extreme obesity, all those with high VAT-E2F1 showed a diabetes-complicated obesity phenotype and higher expression of miRNA-206 and miRNA-210-5p, which also correlated with fasting glucose levels (both miRNAs) and fasting insulin (miRNA-210-5p). Conclusions: Whilst the previously described cancer-related E2F1-miRNA network does not appear to operate in VAT in obesity, miRNAs-206 and 210-5p may link high-E2F1 expression in VAT with diabetes-complicated extreme obesity phenotype

Visceral Adipose Tissue E2F1-miRNA206/210 Pathway Associates with Type 2 Diabetes in Humans with Extreme Obesity

Objective: Up-regulated expression of transcription-factor E2F1 in human visceral adipose tissue (VAT) characterizes a dysmetabolic obesity sub-phenotype. An E2F1-miRNA network has been described in multiple cancers. Here we investigated whether elevated VAT-E2F1 in obesity is associated with VAT-miRNA alterations similar to, or distinct from, those described in cancer. Furthermore, we assessed if E2F1-associated miRNA changes may contribute to the link between high- VAT-E2F1 and a dysmetabolic obesity phenotype. Methods: We assembled a cohort of patients with obesity and high-VAT-E2F1, matched by age, sex, ±BMI to patients with low-VAT-E2F1, with and without obesity (8 patients/groupX3 groups). We performed Nanostring -based miRNA profiling of VAT samples from all 24 patients. Candidate E2F1-related miRNAs were validated by qPCR in an independent cohort of patients with extreme obesity, with or without type-2-diabetes (T2DM) (n = 20). Bioinformatic tools and manipulation of E2F1 expression in cells were used to establish the plausibility of the functional VAT-E2F1-miRNA network in obesity. Results: Among n = 798 identified miRNAs, 17 were differentially expressed in relation to E2F1 and not to obesity itself. No evidence for the cancer-related E2F1-miRNA network was identified in human VAT in obesity. In HEK293-cells, overexpression/downregulation of E2F1 correspondingly altered the expression of miRNA-206 and miRNA-210-5p, two miRNAs with reported metabolic functions consistent with those of E2F1. In VAT from both cohorts, the expression of both miRNA-206 and 210-5p intercorrelated, and correlated with the expression of E2F1. In cohort 1 we did not detect significant associations with biochemical parameters. In cohort 2 of patients with extreme obesity, all those with high VAT-E2F1 showed a diabetes-complicated obesity phenotype and higher expression of miRNA-206 and miRNA-210-5p, which also correlated with fasting glucose levels (both miRNAs) and fasting insulin (miRNA-210-5p). Conclusions: Whilst the previously described cancer-related E2F1-miRNA network does not appear to operate in VAT in obesity, miRNAs-206 and 210-5p may link high-E2F1 expression in VAT with diabetes-complicated extreme obesity phenotype

The \u3ci\u3ePrevotella copri\u3c/i\u3e Complex Comprises Four Distinct Clades Underrepresented in Westernized Populations

Prevotella copri is a common human gut microbe that has been both positively and negatively associated with host health. In a cross-continent metaanalysis exploiting \u3e6,500 metagenomes, we obtained \u3e1,000 genomes and explored the genetic and population structure of P. copri. P. copri encompasses four distinct clades (\u3e10% inter-clade genetic divergence) that we propose constitute the P. copri complex, and all clades were confirmed by isolate sequencing. These clades are nearly ubiquitous and co-present in non-Westernized populations. Genomic analysis showed substantial functional diversity in the complex with notable differences in carbohydrate metabolism, suggesting that multi-generational dietary modifications may be driving reduced prevalence in Westernized populations. Analysis of ancient metagenomes highlighted patterns of P. copri presence consistent with modern non-Westernized populations and a clade delineation time pre-dating human migratory waves out of Africa. These findings reveal that P. copri exhibits a high diversity that is underrepresented in Western-lifestyle populations