Increases in temperature damage plant cells, and plants react to heat stress by inducing of a number of protective mechanisms. In this study, it has been shown that heat damages cells both directly while the plants are being heated, and indirectly through heat induced oxidative stress during recovery from heating. Different stress response pathways are induced in each case. Evidence implicates salicylic acid, abscisic acid, ACC (a precursor of ethylene), calcium ions and active oxygen species in pathways resulting in thermotolerance (i.e. increased survival at high temperature). Addition of these potential second messengers results in increased survival and decreased oxidative damage after heating (as measured using the TBARS assay), while silencing the pathways through use of mutants, inhibitors or transgenes results in decreased thermotolerance. In vivo calcium measurements show cytosolic calcium transients only at initiation of cooling after heat stress. Calcium chloride also induces thermotolerance when added after heating, as does ACC. These substances can induce early increases in ascorbate peroxidase activity after heating, and induce expression of antioxidant genes. Thus they may play a role in heat induced oxidative stress response pathways in recovery. Two different pathways induced during heating appear to result in the expression of genes for heat shock proteins. The predominant pathway induced at 30oC involves ABA, while that at 35-40oC involves an oxidative burst generated through the NADPH oxidase, atrbohB. Addition of SA can induce HSP (heat shock protein) expression, but there is little evidence that this occurs endogenously in plant cells, although nahG plants unable to signal via SA are thermosensitive. Results in this study indicate that there are several signalling pathways associated with heat shock. The pathway induced during recovery from heating involves calcium ions and ethylene, and results in increased antioxidant capacity. During heating two pathways induce expression of HSPs: one involving abscisic acid and possibly salicylic acid and one involving an oxidative burst. At least one further pathway is believed to exist, which involves protein kinases and phosphatases as heat shock causes up-regulation of expression of certain genes for these signalling components.

Compartment syndrome is a rare but a well-documented complication in patients with trauma-induced group A streptococcus infection. Here, we present a case of a male who developed compartment syndrome on the left lower extremity after an injury inoculated by group A streptococcus on the right lower extremity. The patient was resuscitated with antibiotics, urgent fasciotomy, and immunoglobulin. The patient was eventually transferred to a burn center for further care.

Molecular chaperones, commonly known as heat shock proteins (HSPs), are essential for mammalian cells to maintain homeostasis, and HSPs function by inducing an ATPase-coupled structural change, followed by interactions with diverse co-chaperones and over 200 client proteins implicated in many critical signaling networks. These highly expressed HSPs participate in the onset and progression of several human diseases including cancer, and their connection with tumorigenesis has facilitated research and clinical trials related to targeting HSPs as a novel anti-tumor therapy. The predominant mechanism of chaperone inhibition is through either disruption of the HSP association with client protein or an altered binding state that ultimately leads to proteasome-mediated degradation. Importantly, chaperone inhibition results in the degradation of several client proteins that play critical roles in many of the pathways known as the Hallmarks of Cancer, such as proliferation, angiogenesis, invasion, metastasis, and drug resistance. Here, we discuss: (1) the current knowledge of HSPs, particularly studies related to Hsp90-targeted cancer therapy, (2) the targeting of Hsp90-mediated signaling interactions to prevent emergence of core Hallmarks of Cancer, (3) the recent progression of Hsp90 inhibitors in clinical trials. Finally, we propose combinatorial therapy, additional inhibitor discovery, and location-specific inhibition of HSPs as necessary next steps in chaperone-targeted research relevant to cancer therapy.

Further understanding of the cellular and molecular mechanisms involved in traumatic injury, and how they are modulated during drug interaction, can facilitate novel treatment strategies for future trauma patients. We hypothesize that the pharmacological agent, Androstenetriol (AET), up regulates host immune response by modulating the continued expression of mediators, including cytokines. In a double-blinded experiment, rats were hemorrhaged, driven by volume or pressure conditions, then resuscitated with fluids and packed red blood cells following a subcutaneous injection of either vehicle or drug. Blood was collected at various time points and cytokine levels were determined by analyses with both multiplex and conventional ELISA assays. Both MCP-1 and GRO/KC increase in surviving animals; trauma increases IL-lα levels in rat plasma, whereas hemorrhage decreases IL-lα over time; IL-6 plasma levels measured 6 hours after hemorrhage may correlate with mortality; AET may act by mechanisms to modify specific TH1 cytokines (INF-y) to promote survival.

Over the last 20 years, much work has focused on computer-aided clinical decision support systems due to a rapid increase in the need for management and processing of medical knowledge. Among all fields of medicine, trauma care has the highest need for proper information management due to the high prevalence of complex, life-threatening injuries. In particular, hemorrhage, which is encountered in most traumatic injuries, is a dominant factor in determining survival in both civilian and military settings. This complication can be better managed using a more in-depth analysis of patient information. Trauma physicians must make precise and rapid decisions, while considering a large number of patient variables and dealing with stressful environments. The ability of a computer-aided decision making system to rapidly analyze a patient’s condition can enable physicians to make more accurate decisions and thereby significantly improve the quality of care provided to patients. The first part of this study is focused on classification of highly complex databases using a hierarchical method which combines two complementary techniques: logistic regression and machine learning. This method, hereafter referred to as Classification Using Significant Features (CUSF), includes a statistical process to select the most significant variables from the correlated database. Then a machine learning algorithm is used to identify the data into classes using only the significant variables. As the main application addressed by CUSF, a set of computer-assisted rule-based trauma decision making system are designed. Computer aided decision-making system not only provides vital assistance for physicians in making fast and accurate decisions, proposed decisions are supported by transparent reasoning, but also can confirm a physicians’ current knowledge, enabling them to detect complex patterns and information which may reveal new knowledge not easily visible to the human eyes. The second part of this study proposes an algorithm based on a set of novel wavelet features to analyze physiological signals, such as Electrocardiograms (ECGs) that can provide invaluable information typically invisible to human eyes. These wavelet-based method, hereafter referred to as Signal Analysis Based on Wavelet-Extracted Features (SABWEF), extracts information that can be used to detect and analyze complex patterns that other methods such as Fourier cannot deal with. For instance, SABWEF can evaluate the severity of hemorrhagic shock (HS) from ECG, while the traditional technique of applying power spectrum density (PSD) and fractal dimension (FD) cannot distinguish between the ECG patterns of patients with HS (i.e. blood loss), and those of subjects undergoing physical activity. In this study, as the main application of SABWEF, ECG is analyzed to distinguish between HS and physical activity, and show that SABWEF can be used in both civilian and military settings to detect HS and its extent. This is the first reported use of an ECG analysis method to classify blood volume loss. SABWEF has the capability to rapidly determine the degree of volume loss from hemorrhage, providing the chance for more rapid remote triage and decision making.

The thesis is focused on the specifics of care for women with postpartum bleeding in intensive care. Part of this work are two segments, theoretical and empirical. The first segment focuses on the theoretical part, which lists the existing knowledge from literature approaching the issue of bleeding complications accompanying childbirth, especially postpartum period, when the lack of timely solution can endanger the woman's life. This section defines the terms postpartum bleeding, hemorrhagic shock, DIC, intensive care and severe postpartum bleeding complications. The work also focuses on nursing care for women with postpartum bleeding. The theoretical part is concluded postoperative nursing care. The second segment of the work is of empirical character. The main objective of this thesis was to investigate how the care provided to the ARO / ICU for women with problems postpartum bleeding. This part of the non-standardized using an anonymous questionnaire identifies issues of bleeding complications in postpartum period. The work deals with the level of care provided in intensive care for women with severe postpartum bleeding complications, knowledge of the healthcare paramedical personnel in the care of patients with postpartum bleeding and acquiring new information on nursing care in case postpartum...

The cells are capable of very quick and specific reactions on stress conditions. Influence of translation, specifically initiation of translation by inhibition factors, is one of the main regulatory process. Two of eIF4E-binding proteins (4E-BP), Eap1p and Caf20p, are known as cap-dependent translation repressors in yeast Saccharomyces cerevisiae. We used in vivo fluorescent microscopy analysis to show different reaction of Caf20p and Eap1p to heat stress. Protein Caf20p does not react on heat shock and stays difused in cytoplasm. Contrary to Caf20p reaction, protein Eap1p accumulates in cytoplasm close to stress granules (SGs). This work shows that Eap1p is involved in stress granules assembly. In the absence of Eap1p, yeast cells react to the heat stress with small and less focused SGs. Dele- tion of CAF20 does not affect SG assembly. This points to specific function of SG in distribution of factors connected with stress reaction. Polysomal analysis shows that deletion of one of initiation translation repressors does not affect heat induced global repression of translation. In permisive condition deletion of EAP1 may cause defect in addition of 60S ribosomal subunits. Absence of protein Eap1p causes morphological defect. That point to a different reactions of Eap1p and Caf20p on heat stress and possible...

The work is divided into two chapters. In the first one the World's and Czech poets (chosen on the basis of Orten's list of reading) are analyzed. Those authors could be understood as impersonators or predecessors of the existential tendencies and it's provable Orten knew their works well (i.a. Rilke, Rimbaud, Akhmatova, Mácha, Weiner, Halas, Holan, Zahradníček, Bonn and Daniel). The second and more voluminous chapter consists of the motives' and topics' analysis of Orten's literary work, focused mainly on the poetry and less on the other literary genres - notes, letters, prose. The most of his poems and notes is based on the factual life experience and their ethos is founded on both existential and Christian moral philosophy. There's also an influence of some other intellectual tendencies and artistic styles like folk literature, romanticism, impressionism, less intensively expressionism, naturalism, psychoanalysis, surrealism and naturism. To get the coherent interpretation of Orten's work it's necessary to reflect (beside the existential motives) the pathos of the intimate traumatic relationship to the father, the girl(friend)s and the unborn child as well as the deeply Christian understanding of reality (connected with the biblical /The Old Testament/ dialogical relation to the God, the...

M.Sc. / Heat shock (HS) proteins and HS transcription factors (HSFs) have been coined as the ‘Achilles Heel’ for cancer therapy, since they have been found to be overexpressed in cancer cells and are required for cell survival during tumour progression and metastasis. Hsp70 and other members of the Hsp family have been shown to inhibit apoptosis at several different stages, contributing to resistance to chemotherapy. NSAIDs, like salicylates and aspirin, are used for the treatment and prevention of cancers such as breast cancer. SA has been shown to enhance HSF-DNA binding and results in the increased expression of heat-induced Hsp70 which is antiapoptotic. We hypothesise that SA treatment can result in the potentiation of Hsp70 in MCF-7 cells further increasing their resistance to apoptosis and thus the aim of this study was to investigate the dose-responsive effects of salicylic acid (SA) in the presence and absence of heat shock on components of the pro and antiapoptotic components of the apoptotic pathway. MCF-7 cells, which naturally overexpress Hsp70, were treated with several doses of SA in the presence and absence of a mild heat shock, followed by analysis of Hsp70 and several pro and antiapoptotic members of intrinsic and extrinsic apoptotic pathways, including Bcl-2, Bax, caspase 6 and 8, JNK, AIF and APAF-1. Induced Hsp70 accumulation by the SA treatments in the presence and absence of heat shock enhanced apoptosis in cells exposed to SA whereas higher concentrations of SA combination with heat shock induced necrosis and a decrease in Hsp70 accumulation in MCF-7 cells. Identification of the effects which specific concentrations of SA in the presence and absence of heat shock had on the apoptotic pathway constituents helped highlight potential pathways by which cell death could occur in MCF-7 cells through the downregulation of Hsp70. It is most likely that MCF-7 cell death is occurring due to the release of reactive oxygen species (ROS) which in turn lead to necrosis or death may be achieved via a cathepsin-B-mediated cell death pathway where both of these possibilities need to be further investigated.

Diploma Thesis Abstract JEL Classification Z13, O12, O13, Z91 Keywords income shock, endogeneity, ethnicity, instrumental variables Title Income Shocks and Ethnic Group Bias Author's e-mail 61618416@fsv.cuni.cz Supervisor's e-mail bauerm@fsv.cuni.cz Abstract The thesis explores how individual income shocks impact ethnic group bias using a survey dataset from Uganda and meteorological data. Previous research has shown that the majority of civil conflicts break down along ethnic lines, and that ethnic tribalism harms economic performance of countries. A better understanding of the causal mechanism behind ethnic bias could help alleviate both of those problems. The author finds that income shocks have no measurable effect on ethnic out-group bias, but they might influence ethnic in-group bias. Since the regression of ethnic bias variables on income proxies likely suffers from endogeneity, the author employs the copula endogeneity correction model, which, however, does not prove to perform well with a binary dependent variable. In addition, the author demonstrates that ethnic group bias is most likely not directly influenced by variations in rainfall and that instrumenting for income with rainfall variation leads to non- robust results with even a small violations of model assumptions.