Miracle-dz/UniFAR-FTUs huggingface dataset:
Mathematical models characterising the kinetics and dynamics of topotecan to account for drug resistance mechanisms

This thesis describes the use of mathematical modelling in studying the kinetics and dynamics of the anti-cancer agent topotecan (TPT), a semi-synthetic derivative of the natural extract camptothecin (CPT), which has been found to act as an inhibitor of the DNA enzyme topoisomerase I in a specific and reversible fashion. The drug undergoes reversible hydrolysis from the pharmacologically active parent lactone form (TPTL) to an inactive hydroxy acid form (TPTH). In the cytoplasm the irreversible inactivation of TPTL is catalysed by the enzyme aldehyde dehydrogenase (ALDH). Over-expression of the human breast cancer resistance protein (BCRP/ABCG2) has been linked to high levels of resistance to the anti-cancer agent TPT by promoting an active efflux pump mechanism. The expressions of both ALDH and BCRP have been experimentally identified in a large number of solid tumours and thus play an important role in clinical drug resistance of cancers. To investigate the catalytic reaction and efflux pump mechanism, a state-space model for the in vitro uptake kinetics of TPT has been extended to better describe the drug activity and delivery of TPTL to the DNA target as well as the catalysis by ALDH and the elimination of drug from the cytoplasm via the efflux pump. All unknown model parameters were uniquely estimated to a high level of confidence. Model simulations have been compared with live human breast cancer cells data and found to give good qualitative agreement. In addition, a cell cycle model has been extended to include the inhibition effect of the protein p21CIP1/WAF1 on the cell cycle traverse and the kinetic model has then been linked to the cell cycle model, which facilitates analysis of the response of the growth of single cells in the presence and absence of TPT. All unknown model parameters were uniquely determined by the output structure corresponding to the experiment. Parameter estimation was performed using green fluorescent protein tagged Cyclin B1 data for the osteosarcoma cell line U-2 OS. The novel coupling of both models allows the study of drug perturbation to the cell cycle as well as in silico estimation and prediction of the relationship between the target binding and the dose, also permitting the effects of different levels of expression of the drug resistance protein and the ALDH enzyme. Such a coupled kinetic/dynamic model, once fully validated, has the potential for enhancing the design of optimal dosing regimens.
Antilipase antibodies prevent infection of tomato leaves byBotrytis cinerea

Abstract The role of an inducible lipase (EC 3.1.1.3) during the early stages of host infection byBotrytis cinereawas studied. During growth in a liquid medium with apple cutin as the sole carbon source,B. cinereaproduced a cutinase (18 kDa) and a lipase (60 kDa). The cutinolytic activity of the purified lipase was assayed. Using [3H]cutin as substrate, the lipase showed strong cutinolytic activity at low concentrations of protein. Polyclonal antibodies raised against the lipase were purified and their immunological specificity demonstrated by immunoblotting. Lipase activity was inhibitedin vitroby antilipase antibodies, and their addition with spore suspensions ofB. cinereato tomato leaves suppressed lesion formation. AlthoughB. cinereaconidia germinated on the leaves in the presence of the antilipase antibodies, the germ tubes did not penetrate the cuticle. No immunological cross-reactivity was detected between the antilipase antibodies and any other cutinases produced byB. cinerea. These results suggest that lipase activity is required for the early stages of host infection.
The Deep Determinants of the Middle-Income Trap

The fundamental, underlying factors of development are often neglected when analyzing the question why countries experience a growth slowdown at the middle-income range. Although these so-called ‘deep determinants’ such as geography and institutions have been found to be decisive for the break out of stagnation and for explaining cross-country income differences by many empirical studies, so far, very little has been done to examine to which extent they are also crucial at more subtle stages of economic development. Our paper aims to contribute to close this gap by focusing on the phenomenon of the middle-income trap (MIT) which has reached increasing attention in the last 15 years. In particular, we are interested in whether the deep determinants have positive or negative impacts on the possibility of a country to experience a prolonged stay within the middle-income range. We focus especially on exogenous variables to avoid endogeneity/reverse causality problems. By using simple statistical hypothesis testing, we show that not all findings of the deep determinants literature can be easily transferred to the MIT phenomenon, especially regarding institutional variables. This may raise the question whether we need new deep determinants of growth for the MIT or at least a modified version taking into account the specific circumstances and characteristics of middle-income countries.
Effect of living mulches on white head cabbage (Brassica oleracea var. capitata subvar. alba L.) yielding.

The effect of meadow fescue, common vetch, and whit e clover, used as living mulches, on white cabbage yielding, soil aggregates water resistance, and weed infestation was investigated in Garlica Murowana ne r Kraków in 1998 and 2000. After the living mulches were broad-seeded, transpl ants of white cabbage ‘Lennox F1’ were planted (at the beginning of May) into mulch , with spacing of 70 × 50 cm. During the two years all the used mulch es decreased the total and marketable yield of cabbage in comparison with the control. The beneficial effect of living mulches on aggregates water resistance wa s found. The number of aggregates of 2.50-1.00 mm in diameter increased in mulched soils in both years, whereas the number of the smallest ones (0.25 mm) decreased. The pronounced effect of living mulches on the reduction of weed i nfestation was found in the two years of the investigation. ElŜbieta Jędrszczyk, Małgorzata Poniedziałek, Agnieszka S ękara 30
Transforming growth factor‐β responsiveness in DPC4/SMAD4‐null cancer cells

DPC4/SMAD4 is a candidate tumor suppressor gene with a strikingly high frequency of gene alterations in pancreatic cancer that suggests a discrete role for DPC4 in these tumors. DPC4 tumor‐suppressive function has been implicated to mediate the transforming growth factor‐β (TGFβ)–suppressive pathway; however, in a DPC4‐null pancreatic cancer cell line, TGFβ growth‐inhibitory and transcriptional responses were found to be DPC4‐independent. This was observed within native cells having a natural homozygous deletion and in clones engineered for stable expression of wild‐type DPC4 integrated into the genome. This observation contrasted with the absolute DPC4 dependence of TGFβ responses in a breast cancer cell line studied in parallel. This growth‐inhibitory response to TGFβ in DPC4‐null cells relied on an intact ras effector pathway. These data further suggest a major categorization of TGFβ responses into DPC4‐dependent and ‐independent signaling pathways and specifically suggest that disruption of the TGFβ‐independent signal might be a basis of selection for the emergence of DPC4 alterations during tumorigenesis in the pancreas and other sites. Mol. Carcinog. 26:37–43, 1999. © 1999 Wiley‐Liss, Inc.
Tractor-drawn broad bed furrow seed drill machine to overcome moisture stress for soybean (Glycine max) in Vertisols

A tractor-drawn broad bed furrow (BBF) seed drill machine for soybean [Glycine max (L.) Merrill] was conceived, fabricated and farm validated. It effectively operates in Vertisols and associated soils and is attachable to the tractor for facilitating formation of broad bed along with furrows on both the sides of the beds of desired width and depths and subsequent sowing in one go. Plant population mortality in soybean with tractor-drawn BBF seed drill for Vertisols was reduced in the range of 14–19% as compared to flat bed under the vagaries of monsoon which subsequently resulted in yield enhancement to the extent of 18.65%. Study also indicated that tractor-operated BBF seed drill specifically fabricated for individual tractor performed better in Vertisols and under prevailing field draft conditions.
Growth and Physiological Responses of Tomato Landrace "Rohaba"(Lycopersicon Esculentum Mill.) to in Vitro Induced Water Deficit

Influence of in vitro induced water deficit upon vegetative growth and physiology of tomato landrace “Rohaba” (Lycopersicon esculentum Mill.), was investigated using 0.1, 0.2, 0.3 and 0.4 M sucrose, or 0, 0.1, 0.2 and 0.3 M sorbitol or mannitol as osmotic agents. Shoot height and shoot fresh weight were significantly reduced as sucrose was increased to 0.4 M. While a significant increase in shoot dry weight was obtained when sucrose levels were increased, rooting percentage and root number decreased. Root length was significantly increased at 0.3 M and reduced at 0.4 M sucrose. In the case of sorbitol, shoot height was significantly reduced at 0.3 M, shoot fresh and dry weight were significantly reduced as sorbitol levels were increased in the media. Rooting percentage, root number and root length were not affected at all by the sorbitol levels. When using mannitol, shoot height was significantly increased at 0.1 M and then significantly reduced at 0.2 M and 0.3 M. Shoot dry weight and fresh weight were reduced as mannitol levels were increased. Rooting percentage and root number were enhanced at 0.1 M. Root length was increased in response to different mannitol levels. The osmotic potential of tomato microshoots was significantly reduced (became more negative) as sucrose, sorbitol, or mannitol levels were increased. Tomato microshoots contents of N, K, Mg, Na and ash percentage were reduced significantly in response to increased levels of sucrose, sorbitol, or mannitol. Ca and P contents were not affected by elevated concentrations of osmoticums. Fiber content of tomato microshoots was not significantly affected at all by the sucrose levels, but a significant reduction in fiber content was obtained as sorbitol and mannitol levels were increased. Reducing sugar percentage, carbohydrate percentage and proline accumulation were increased and the protein (crude and soluble) and fat contents were reduced as the levels of sucrose, sorbitol and mannitol were increased.
Estructura, composición y diversidad de la selva baja caducifolia del Cerro Verde, Nizanda (Oaxaca), México

In this study we describe the structure, floristic composition, and diversity of the tropical dry forest established on the Cerro Verde (Verde Hill), located at Nizanda (Isthmus of Tehuantepec, Oaxaca, Mexico). We censused woody plants with DBH Ɛ 1 cm (upper stratum) present in 30 100-m2 plots, and in five 4-m2 subplots within each of them, those plants with height > 30 cm but < 1 cm DBH (lower stratum). A total of 194 species belonging to 52 families were recorded. Species richness was identical in both strata (145 species), each contributing exclusively with ca. 25% of total recorded richness. Leguminosae was the most speciose family (27), followed by Asteraceae (20) and Euphorbiaceae (18). The most frequent species were Bursera simaruba + B. aff. cinerea (not distinguished in the field), Euphorbia schlechtendalii, Pilosocereus collinsii and Capparis verrucosa. Average richness by plot was 30 species. Mean values of indices based on species richness and abundances (Berger-Parker = 0.20; Simpson = 0.09; Fisher’s[= 9.47; Shannon = 2.78; eveness = 0.82) indicated a high diversity and consequently a low dominance in this forest. Extrapolated values showed a total (upper + lower strata) density of 23,950 ind. ha-1 (830 ind. ha-1 with DBH Ɛ 10 cm), a forest cover of 446.7%, and a basal area of 53 m2 ha-1. Mean height of those individuals accounting for 10% of the highest trees by plot was 9.1 m. Tropical dry forest structure at Cerro Verde is comparable to other Mexican communities within the seasonally dry tropical region and indicates a good conservation status. This feature, together with its particular floristic composition, makes of this area a high priority site which requires inclusion in a formal conservation scheme.
Enhanced Brain Network Activity in Complex Movement Rhythms: A Simultaneous Functional Magnetic Resonance Imaging and Electroencephalography Study

Generating movement rhythms is known to involve a network of distributed brain regions associated with motor planning, control, execution, and perception of timing for the repertoire of motor actions. What brain areas are bound in the network and how the network activity is modulated by rhythmic complexity have not been completely explored. To contribute to answering these questions, we designed a study in which nine healthy participants performed simple to complex rhythmic finger movement tasks while undergoing simultaneous functional magnetic resonance imaging and electroencephalography (fMRI-EEG) recordings of their brain activity during the tasks and rest. From fMRI blood oxygenation-level-dependent (BOLD) measurements, we found that the complexity of rhythms was associated with brain activations in the primary motor cortex (PMC), supplementary motor area (SMA), and cerebellum (Cb), and with network interactions from these cortical regions to the cerebellum. The spectral analysis of single-trial EEG source waveforms at the cortical regions further showed that there were bidirectional interactions between PMC and SMA, and the complexity of rhythms was associated with power spectra and Granger causality spectra in the beta (13-30 Hz) frequency band, not in the alpha (8-12 Hz) and gamma (30-58 Hz) bands. These results provide us new insights into the mechanisms for movement rhythm complexity.
The Role of Stakeholder Involvement in the Governance of Tourist Museums: Evidence of Management Models in the Canary Islands

ABSTRACT The responsible management of cultural heritage requires the formation of a competitive tourism product, which in turn requires a high level of collaboration, the need for diversification and differentiation from other tourism sites. The application of governance mechanisms and their effect on the optimization of visitorship in the heritage tourism industry has been understudied. Although there are four models of management in museums, the needs of heritage sites invite an analysis of them, particularly in the consideration of the role of the stakeholders in shaping the product offered. Four case studies in Gran Canaria (Canary Islands, Spain) examine how the application of local governance mechanisms affects museums and interpretation centers to optimize the goals of the tourism product. For this analysis, a qualitative analysis has been carried out through direct observation and interviews, analyzing the results with CAQDAS. The study found that strategic planning linked to the territory and public-private partnerships could increase effectiveness and efficiency in the allocation of public resources, and that the application of certain governance strategies could increase the impact of stakeholder involvement in the efficacy of the site management. Future study needs are established for other institutions that manage cultural heritage.
Survey of antibiotic resistant bacteria in fish gut collected from selected sites.

ix INTRODUCTION 1 MATERIALS AND METHODS 4 Field Sampling Sites 4 Field Fish 5 Laboratory Fish 6 Measurement and Dissection 6 Collection of Bacterial Samples 6 Antibiotic Sensitivity Tests 7 Selection of Bacterial Isolates for Further Tests 7 Gel Electrophoresis 8 Restriction Enzyme Digestion 8 Identification of Plasmid Bearing Bacterial Isolates 9 Water Parameters 10 RESULTS 11 Ampicillin Resistant Bacterial Isolates 11 Antibiotic Sensitivity Test 14 Selection of Bacterial Isolates for Presence of Plasmid 20 Restriction Enzyme Digestion 22 Identification of Three Bacterial Isolates 26 DISCUSSION 29 Field Fish and Antibiotic Resistance 29 Hatchery-raised Fish and Antibiotic Resistance 32 Conclusion 35
Studies on the response of integrated nutrient management on growth and yield of ber

Studies were conducted to determine the effect of organic and inorganic sources of NPK and foliar spray of chemicals on plant growth, fruit yield and quality of ber cv. Gola. Different graded levels of FYM (37.5, 75 and 150 kg/plant) and Vermicompost (11, 22 and 45 kg/plant) were supplemented with different doses of inorganic fertilizers and foliar spray of chemicals (control, borax 0.4 per cent and thiourea 0.5 per cent) to balance fertilizer requirement of ber under semi-arid region of northern India. Experimental results revealed that application of 22 kg vermicompost + 0.82 kg urea + 1.15 kg SSP + 0.41 kg MOP per tree (F5) and foliar spray of thiourea @ 0.5 per cent (T2) significantly increased the plant height, plant spread, leaf area, average weight of fruit and fruit yield per tree and reduced the fruit drop. The ascorbic acid and iron content of fruits and NPK uptake by fruits were enhanced alongwith improvement in relative leaf water content (RLWC) and chlorophyll content in leaves under treatment F5 and T2. All these parameters were appeared to be dose and source dependent and best results were achieved with the combined application of 22 kg vermicompost + 0.82 kg urea + 1.15 kg SSP + 0.41 kg MOP per tree + foliar spray of thiourea @ 0.5 per cent under integrated nutrient management systems of ber orchard.
Blue-Green Catastrophe: remote sensing of mass viral lysis of cyanobacteria

remote sensing of mass viral lysis of cyanobacteria Blue-green catastrophe: remote sensing of mass viral lysis of cyanobacteria. In Dutch: Blauwgroene catastrofe: remote sensing van massale virussterfte van cyanobacteriën [ac. proefschrift, Vrije Universiteit Amsterdam] NIOO Thesis 48 1. General introduction 7 Optical changes associated with cyanobacterial bloom termination 2. Optical changes associated with cyanobacterial bloom termination by viral lysis 15 3. Optical signatures of the filamentous cyanobacterium Leptolyngbya boryana during mass viral lysis 37 Remote sensing of cyanobacterial biomass 4. Remote sensing of the cyanobacterial pigment phycocyanin in turbid inland water 61 5. Influence of phytoplankton pigment composition on remote sensing of cyanobacterial biomass 77 MERIS potential for inland water quality monitoring 6. MERIS potential for remote sensing of water quality parameters for turbid inland water 97 7. General discussion 121 References 127 Samenvatting 135 Acknowledgments 141
Zmienność składu chemicznego nasion roślin strączkowych i ich odporności na obciążenia mechaniczne

Przeprowadzone badania miały na celu ocenę wewnątrzgatunkowej zmienności odmian i rodów roślin strączkowych pod względem odporności nasion na obciążenia mechaniczne i ich składu chemicznego. Materiał do badań stanowiły nasiona odmian i rodów reprezentujących cztery gatunki łubinu oraz groch i lędźwian siewny. Do analiz wybierano powietrznie suche nasiona pochodzące z Hodowli Roślin Przebędowo i tego samego roku zbioru. Wzrost i rozwój roślin w tej samej lokalizacji i w podobnych warunkach glebowo-klimatycznych umożliwiał porównanie uzyskanych wyników między odmianami. Oceniano właściwości fizyczne nasion w celu określenia ich reakcji na obciążenia mechaniczne. Na pierwszym etapie określano grubość nasion, a następnie pojedyncze nasiona podawano obciążeniom mechanicznym wyrażając uzyskane wyniki wartościami siły maksymalnej (N), maksymalnego odkształcenia (mm), modułu elastyczności (MPa) i energii (J). Ponadto nasiona z każdej odmiany i rodu posłużyły do oceny zawartości białka, tłuszczu i profilu kwasów tłuszczowych. Wyniki opracowano za pomocą wielocechowej analizy statystycznej. Wiedza o fizycznych parametrach nasion wyrażona stopniem ich odporności na uszkodzenia mechaniczne ma istotne znaczenie dla optymalizacji technologii zbioru, suszenia i przechowywania przyczyniając się do zminimalizowania strat ilościowych i jakościowych oraz uszkodzeń mechanicznych zebranych nasion. Wykazano, że analizowane nasiona odmian i rodów charakteryzowały się zróżnicowaną grubością nasion i szerokim zakresem ich zmienności w reakcji na zastosowane obciążenia mechaniczne. Pozwoliło to na wyodrębnienie gatunków, ale przede wszystkim odmian i rodów o zwiększonej odporności nasion na obciążenia mechaniczne wyrażone między innymi wartością siły maksymalnej, której użycie powoduje zniszczenie ich struktury. Analizowane rody i odmiany charakteryzowały się ponadto szerokim zakresem zmienności składu chemicznego nasion. Pod względem zawartości białka dominowały nasiona łubinu andyjskiego tradycyjnego (44,2%) i epigonalnego (41,3%), a wartościami powyżej 40% charakteryzowały się ponadto nasiona łubinu żółtego reprezentowane przez odmianę Lord oraz rody: R 1017/03 i R 851/03. Najwyższą zawartością tłuszczu wyróżniały się formy łubinu andyjskiego z dominującą pozycją nasion formy samokończącej na poziomie 15,5%, a najniższą nasiona grochu, przy znacznych różnicach odmianowych i gatunkowych w profilu kwasów tłuszczowych.
A modified emergence trap for quantitative adult corn rootworm studies (Coleoptera: Chrysomelidae).

An emergence trap was designed to make use of the negative geotactic behavior of adult corn rootworm, Diabrotica spp. This trap has the following advantages: efficiency, nondis turbance after placement, speed of collection, and easy interpre tation of beetle counts for population dynamics and pest manage ment programs. It was used successfully in establishing patterns of beetle density and emergence for artificially infested and natural populations. Numerous types of traps have been devised for assessing adult popula tions of Diabrotica spp. emerging from the soil. However, most of these traps developed problems with either collection efficiency, speed of collec tion, or interpretation of measurements. For example, with large walk-in type cages (Branson and Ortman, 1967; Hill and Mayo, 1974), much time is spent in collection, and efficiency is lost. Also, these cages have a problem with soil compaction. Chiang et al. (1971) used a 30.5 cm (1 ft) diameter cage over one plant, but the area contained within the cage was not appli cable to usual field situations, and the results may not be indicative of the actual field situation. Pruess et al. (1968) used a 0.279 m2 (3 ft2) cone-shaped cage over cut plants; however, the insects were not easy to retrieve from inside the cages. Musick and Fairchild (1970) described a highly efficient trap that was designed to make use of the negative geotactic behavior of the adult beetle; however, there were difficulties in retaining the beetles in the trap jar, catch closure, and catch collection. The trap described herein is a modification of that of Musick and Fairchild (1970).
Espaçamento e densidade de semeadura para cultivares de sorgo granífero no semiárido

There is little information about sorghum management in semiarid areas. Therefore, three row spacing and three sowing den- sities of sorghum grain cultivars were evaluated during two crop seasons, in the North of Minas Gerais State, Brazil. In each season, two experiments were carried out on contiguous areas, adopting 50 cm, 70 cm and 90 cm as row spacing in the first one and three sowing densities (100000, 140000, 180000 plants ha -1 ) in the second one. In both experiments, four cultivars were evaluated: SHS400, 1G220, BRS310 and 0992045. The experimental design was in random blocks, in 3 x 4 factorial schemes, with three repetitions. Reduction in row spacing promotes increases in grain and panicles productivity of grain sor- ghum. The viability of increasing sowing density depends on cultivar and row spacing and of climatic conditions prevailing in cropping year. The BRS310 and 1G220 cultivars are promising for grain production in the North of Minas Gerais State.