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Please help with the following questions: 1a) “It was hypothesized that the solitary presence, and not the amount of blood, could be responsible for the severe expansion of the secondary damage.”  In...

Please help with the following questions:

1a) “It was hypothesized that the solitary presence, and not the amount of blood, could be responsible for the severe expansion of the secondary damage.”  In terms of the solitary presence, is this a null hypothesis or an alternate/alternative hypothesis? How do you know?

1b) “It was hypothesized that the solitary presence, and not the amount of blood, could be responsible for the severe expansion of the secondary damage.”  In terms of the amount of blood, is this a null hypothesis or an alternate/alternative hypothesis? How do you know?

1c) “We hypothesize that the acute release of thrombin from the subdural hematoma could be one of the harmful blood constituents, which trigger long-term lesion enlargement through early activation of PARI.”  Is this hypothesis a null hypothesis or an alternate/alternative hypothesis? How do you know?

1d) “PARI blockage resulted in the following lesion volumes: Animals treated with vehicle had an average tissue loss of 6.5 ±2.0 mm3with one µg SCH-79797 lesion volume was 4.3 ±0.7 mm3and with five µg SCH-7979 the average damage was 3.8 ±1.1 mm3 (all p: n.s., Fig. 2b).”  Based on this quote, why was there tissue loss?

1e) “Thrombin influences signal transduction in the brain predominantly via PARI.”  What is the role of PARI in signal transduction?

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Answer #1

Ans- 1a- The actual test begins by considering two hypotheses. They are called the null hypothesis and the alternative hypothesis. These hypotheses contain opposing viewpoints.

H0: The null hypothesis: It is a statement about the population that either is believed to be true or is used to put forth an argument unless it can be shown to be incorrect beyond a reasonable doubt.

Ha: The alternative hypothesis: It is a claim about the population that is contradictory to H0 and what we conclude when we reject H0.

Since the null and alternative hypotheses are contradictory, you must examine evidence to decide if you have enough evidence to reject the null hypothesis or not. The evidence is in the form of sample data.

After you have determined which hypothesis the sample supports, you make adecision. There are two options for a decision. They are “reject H0” if the sample information favors the alternative hypothesis or “do not reject H0” or “decline to reject H0” if the sample information is insufficient to reject the null hypothesis.

H0 Ha

equal (=) . not equal (≠)

or greater than (>) or less than (<)

greater than or equal to (≥) less than (<)

less than or equal to (≤) more than (>)

H0 always has a symbol with an equal in it. Ha never has a symbol with an equal in it. The choice of symbol depends on the wording of the hypothesis test. However, be aware that many researchers (including one of the co-authors in research work) use = in the null hypothesis, even with > or < as the symbol in the alternative hypothesis. This practice is acceptable because we only make the decision to reject or not reject the null hypothesis.

Ans-1b-

A hypothesis is an approximate explanation that relates to the set of facts that can be tested by certain further investigations. There are basically two types, namely, null hypothesis and alternative hypothesis. A research generally starts with a problem. Next, these hypotheses provide the researcher with some specific restatements and clarifications of the research problem.

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The criteria of the research problem in the form of null hypothesis and alternative hypothesis should be expressed as a relationship between two or more variables. The criteria is that the statements should be the one that expresses the relationship between the two or more measurable variables. The null hypothesis and alternative hypothesis should carry clear implications for testing and stating relations.

The major differences between the null hypothesis and alternative hypothesis and the research problems are that the research problems are simple questions that cannot be tested. These two hypotheses can be tested, though.

The null hypothesis and alternative hypothesis are required to be fragmented properly before the data collection and interpretation phase in the research. Well fragmented hypotheses indicate that the researcher has adequate knowledge in that particular area and is thus able to take the investigation further because they can use a much more systematic system. It gives direction to the researcher on his/her collection and interpretation of data.

The null hypothesis and alternative hypothesis are useful only if they state the expected relationship between the variables or if they are consistent with the existing body of knowledge. They should be expressed as simply and concisely as possible. They are useful if they have explanatory power.

The purpose and importance of the null hypothesis and alternative hypothesis are that they provide an approximate description of the phenomena. The purpose is to provide the researcher or an investigator with a relational statement that is directly tested in a research study. The purpose is to provide the framework for reporting the inferences of the study. The purpose is to behave as a working instrument of the theory. The purpose is to prove whether or not the test is supported, which is separated from the investigator’s own values and decisions. They also provide direction to the research.

The null hypothesis is generally denoted as H0. It states the exact opposite of what an investigator or an experimenter predicts or expects. It basically defines the statement which states that there is no exact or actual relationship between the variables.

The alternative hypothesis is generally denoted as H1. It makes a statement that suggests or advises a potential result or an outcome that an investigator or the researcher may expect. It has been categorized into two categories: directional alternative hypothesis and non directional alternative hypothesis.

The directional hypothesis is a kind that explains the direction of the expected findings. Sometimes this type of alternative hypothesis is developed to examine the relationship among the variables rather than a comparison between the groups.

The non directional hypothesis is a kind that has no definite direction of the expected findings being specified.

Ans-1c- Answer is unable to find. No results is available.

Ans 1d- As the rodent placenta has numerous structures and functions that are comparatively similar to the human placenta, mouse models have been useful in establishing the importance of TGF-β and Smad proteins in placental development. Placental labyrinthine cells are closest to the fetus and are important for the transport of nutrients and wastes between the mother and developing fetus.

SM10 cells are a mouse labyrinthine progenitor cell line, which have been previously shown to differentiate after treatment with TGF-β and can be used as a model for the transport layer of the placenta. The pathway activated by TGF-β to induce SM10 progenitor differentiation, however, has yet to be fully investigated. Our previous studies have shown that TGF-β induced down regulation of the stem cell regulator, Id2, is necessary for SM10 trophoblast progenitor differentiation. In this study, we show that all three TGF-β isoforms have the ability to terminally differentiate SM10 cells, whereas other members of the TGF-β superfamily, i.e. Activin A and Nodal, do not. Additionally, we have identified that TGF-β signaling in SM10 placental labyrinthine cells is primarily induced via Smad2 phosphorylation and transactivation of the Activin response element, in contrast to the more classical activation of 3TP and SBE promoter response elements, to alter gene expression necessary to induce differentiation.

Mouse SM10 cells were maintained in RPMI1640/L-glutamine medium supplemented with 1mM sodium pyruvate, 50 μM 2β-mercaptoethanol, 1% antibiotic-antimycotic, and 10% FBS. SM10 cells were treated with TGF-β1 (5 ng/ml), TGF-β2 (5 ng/ml), TGF-β3 (2 ng/ml), Activin A (5 ng/ml), Nodal (250 μg/ml), or vehicle (4mM HCl, 0.5% mg/ml BSA) for 72 hrs to induce differentiation. COS-7 cells were obtained from ATCC (CRL-1651) and were cultured in DMEM/High glucose, 10% heat inactivated fetal bovine serum, and 1% antibiotic-antimycotic. All cell types were passaged at 80~90% confluence.

Receptor inhibition
Inhibition of Alk receptors in SM10 cells was conducted by plating 3×105 SM10 cells in p60s. Cells were then treated with or without the ALK-5 (TGF-β receptor) specific inhibitor SB431542 (10 μM) for 1 hour, followed by treatment without or with TGF-β2 (5 ng/ml) for 48 hours.

Growth inhibition
SM10 cells were plated at 1×105 cells/ml in 24 well plates for 24 h prior to treatment. Cells were then treated with TGF-β2 or Activin A for 72 hours and subsequently incubated with 1 μCi/ml 3H-Thymidine (ICN) per well for 4 h. The cells were washed twice with 10 per cent tri-chloroacetic acid (TCA) for 10 min and lysed by adding 300 μl of 0.2 N NaOH containing 40 μg/ml of salmon sperm DNA. Cell lysates (100 μl) were counted in Scintiverse scintillation fluid.

Ans 1e- Role of PARI in signal transduction-

The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway."

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