A Healthy and Ecologically Balanced Environment: An Argument for a Third Generation Right

Chymotrypsin-like serine proteases are found in high abundance in mast cell granules. By site-directed mutatgenesis, we have previously shown that basic amino acids in positions 143 and 192 (Arg and Lys respectively) of the human mast cell chymase are responsible for an acidic amino acid residue preference in the P2' position of substrates. In order to study the influence of these two residues in determining the specificity of chymase inhibitors, we have synthesized five different potent inhibitors of the human chymase. The inhibitory effects of these compounds were tested against the wild-type enzyme, against two single mutants Arg143Gln and Lys192Met and against a double mutant, Arg143Gln+Lys192Met. We observed a markedly reduced activity of all five inhibitors with the double mutant, indicating that these two basic residues are involved in conferring the specificity of these inhibitors. The single mutants showed an intermediate phenotype, with the strongest effect on the inhibitor by the mutation in Lys192. The Lys192 and the double mutations also affected the rate of cleavage of angiotensin I but did not seem to affect the specificity in the cleavage of the Tyr(4)-Ile(5) bond. A more detailed knowledge about which amino acids that confer the specificity of an enzyme can prove to be of major importance for development of highly specific inhibitors for the human chymase and other medically important enzymes

Short-Term Visual Deprivation, Tactile Acuity, and Haptic Solid Shape Discrimination

The visual cortex of human observers changes its functionality in response to visual deprivation (Boroojerdi et al., 2000). Behavioral studies have recently documented enhanced tactile abilities following a short period of visual deprivation (Facchini & Aglioti, 2003; Weisser, Stilla, Peltier, Hu, & Sathian, 2005). The current study investigated the effects of visual deprivation on two unique tactile tasks. While Facchini and Aglioti observed significant effects of visual deprivation, neither Wong, Hackeman, Hurd, and Goldreich (2011) nor Merabet et al. (2008) observed these effects. Corroborating these more recent results, no difference in grating orientation discrimination performance was observed between the sighted and visually deprived participants in the first experiment. A significant effect of experience was seen in both groups, however, irrespective of the deprivation period of 90 minutes. The second experiment immediately followed the conclusion of the first experiment. Using the same stimuli and procedures from past experiments (Norman, Clayton, Norman, & Crabtree, 2008), it investigated the participants’ haptic discrimination of 3-dimensional object shape. Again, no significant difference in performance was found between the sighted and visually deprived participants. Together, the current results show that a brief period of visual deprivation (1.5 hours) produces no significant behavioral changes for these tactile and haptic tasks

Truth as Right and Remedy in International Human Rights Experience

This Note seeks to explore the origins, scope, and key possibilities of an evolving right to the truth. It will argue that truth is not only an essential component of the universally recognized right to an effective remedy, but that it also serves as the gateway to a broader reparative framework necessary for victims of gross human rights abuse. The analysis shall span the Inter-American, European, and United Nations systems of human rights protection, and also will treat the burgeoning idea of the truth commission, a very prominent means of extra-judicial inquiry in contemporary transitional societies. At the conclusion, the essay will evaluate the implications of a broader, victim-oriented concept of remedy-in which truth plays a crucial role-for the United States as well

Truth as Right and Remedy in International Human Rights Experience

Early this year, the Inter-American Court of Human Rights in San Jose, Costa Rica, was faced yet again with a seemingly basic question: Does an individual have a legal right to know the truth about the circumstances surrounding the serious human rights violations a loved one has suffered? One might expect to encounter such a privilege in our victim centered system of international human rights protection-especially within the progressive jurisprudence of the Inter-American Court. Yet, it is simply not to be found as a substantive, explicit right. This essay seeks to explore the origins, scope, and key possibilities of an evolving right to the truth. It will argue that truth is not only an essential component of the universally recognized right to an effective remedy, but that it also serves as the gateway to a broader reparative framework necessary for victims of gross human rights abuse. The analysis shall span the Inter-American, European, and United Nations systems of human rights protection, and also will treat the burgeoning idea of the truth commission, a very prominent means of extra-judicial inquiry in contemporary transitional societies. At the conclusion, the essay will evaluate the implications of a broader, victim-oriented concept of remedy-in which truth plays a crucial role-for the United States as well

Deep brain stimulation for Parkinson's disease:Sound asleep or wide awake?

Parkinson's disease (PD) presents a growing global health challenge due to its increasing incidence among an aging population. While medication initially helps manage symptoms, patients often face complications as the disease progresses. Deep brain stimulation (DBS) surgery, targeting the subthalamic nucleus (STN), offers relief, but is not without risks. This thesis aims to optimize STN DBS by refining imaging, enhancing patient comfort, and assessing risks to broaden its accessibility and positive impact (Chapter 1).Chapter 2 shows that the introduction of Intraoperative imaging streamlines the DBS procedure by enhancing efficiency and patient comfort. Chapter 3 introduces the study protocol for the GALAXY trial, comparing STN DBS under general anesthesia with local anesthesia. In Chapter 4 the results of this study are revealed showing no significant differences in cognitive or mood effects post-surgery. Both methods significantly improve motor symptoms and quality of life. Chapter 5 is an in-depth analysis of the neuropsychological and psychiatric outcomes of the Galaxy study, indicating minor differences in memory between anesthesia methods. Chapter 6 proposes a novel targeting strategy for electrode placement based on patient specific MRI landmarks, creating a targeting ‘hotspot’, and thereby reducing variability in therapeutic response.Lastly, Chapter 7 evaluates surgical complications of STN DBS over 25 years, showing a decline in risk with evolving techniques.To conclude, we should continuously evaluate whether we can further improve an already established treatment. For this, we should not only be guided by the treatment effects, but also by the burden of the treatment and the possible risks