Report on Reforming Suspended Sentences in Hong Kong

This report is from a study of the suspended sentence power in Hong Kong undertaken by the Centre for Comparative and Public Law at the request of the Law Society of Hong Kong (LSHK). Members of the LSHK’s Criminal Law and Procedure Committee have been concerned about the list of exceptions to the suspended sentence power. The purpose of this report is to inform members of that Committee of the background and law on the suspended sentence power and to aid their ongoing discussion of the topic with the Law Reform Commission of Hong Kong. The study focuses specifically on the exceptions to the power of the courts of Hong Kong to impose suspended sentences under the Criminal Procedure Ordinance (Cap 221) (CPO). The study will consider arguments for maintaining, abolishing or reforming the list of excepted offences for which offenders cannot receive a suspended sentence of imprisonment regardless of circumstances. In doing so, the project will examine the nature of judicial power to order suspended sentences or their equivalent in the following jurisdictions: Australia (Victoria), New Zealand, Canada, Singapore, and the United Kingdom (UK). It will also provide the historical context in which Hong Kong introduced the suspended sentence of imprisonment, and the rationale for excepting the offences listed in Schedule 3 of the CPO.postprin

Changes in Enzyme Structural Dynamics Studied by Hydrogen Exchange-Mass Spectrometry: Ligand Binding Effects or Catalytically Relevant Motions?

It is believed that enzyme catalysis is facilitated by conformational dynamics of the protein scaffold that surrounds the active site, yet the exact nature of catalytically relevant protein motions remains largely unknown. Hydrogen/deuterium exchange (HDX) mass spectrometry (MS) reports on backbone H-bond fluctuations. HDX/MS thus represents a promising avenue for probing the relationship between enzyme dynamics and catalysis. A seemingly straightforward strategy for such studies involves comparative measurements during substrate turnover and in the resting state. We examined the feasibility of this approach using rabbit muscle pyruvate kinase (rM1-PK) which catalyzes the conversion of phosphoenolpyruvate and Mg-ADP to pyruvate and Mg-ATP. HDX/MS revealed that catalytically active rM1-PK undergoes significant rigidification in the active site. This finding is counterintuitive, considering the purported correlation between dynamics and catalysis. Interestingly, virtually the same rigidification was seen upon exposing rM1-PK to substrates or products in the absence of turnover. These data imply that the active site dynamics during turnover are dominated by protein-ligand binding interactions. These interactions stabilize H-bonds in the vicinity of the active site, thereby masking subtle dynamic features that might be uniquely associated with catalysis. Our data uncover an inherent problem with side-by-side turnover/resting state measurements, i.e., the difficulty to design a suitable reference state against which the working enzyme can be compared. Comparative HDX/MS experiments on enzyme dynamics should therefore be interpreted with caution

Active cooling control of the CLEO detector using a hydrocarbon coolant farm

We describe a novel approach to particle-detector cooling in which a modular farm of active coolant-control platforms provides independent and regulated heat removal from four recently upgraded subsystems of the CLEO detector: the ring-imaging Cherenkov detector, the drift chamber, the silicon vertex detector, and the beryllium beam pipe. We report on several aspects of the system: the suitability of using the aliphatic-hydrocarbon solvent PF(TM)-200IG as a heat-transfer fluid, the sensor elements and the mechanical design of the farm platforms, a control system that is founded upon a commercial programmable logic controller employed in industrial process-control applications, and a diagnostic system based on virtual instrumentation. We summarize the system's performance and point out the potential application of the design to future high-energy physics apparatus.Comment: 21 pages, LaTeX, 5 PostScript figures; version accepted for publication in Nuclear Instruments and Methods in Physics Research

Investigations into the Role of Conformational Dynamics in Protein Function: Insights From Hydrogen/Deuterium Exchange-Mass Spectrometry

Deciphering protein structure and dynamics is a key prerequisite for understanding biological function. The current work aims to apply HDX-MS to improve the understanding of protein structure and dynamics for systems that remain challenging for other techniques. Following a general overview of the field (Chapter 1), Chapter 2 investigates the relationship between enzyme dynamics and catalysis. By conducting comparative HDX-MS measurements on rM1-PK during substrate turnover and in the resting state, catalytically active rM1-PK undergoes significant rigidification of the active site. However, virtually the same rigidification was seen upon exposing rM1-PK to substrate or product in the absence of turnover. These findings demonstrate that comparative experiments on enzyme dynamics by HDX-MS (and other bioanalytical techniques) should be interpreted with caution. In Chapter 3, HDX-MS is used to probe the intrinsically disordered protein Nrf2. HDX-MS is used to investigate the structure and dynamics of the full-length Nrf2 and its interaction with the Kelch domain. The data obtained demonstrate the highly-disordered nature of Nrf2. Its interaction with Kelch causes protection of the binding sites on Nrf2, while the rest of the protein becomes slightly more dynamic. This works highlights the limitations of using truncated protein constructs when investigating their structure and dynamic properties using biophysical techniques

Developing a pilot study of evidence-based PTSD treatment in Port-au-Prince, Haiti

Post-Traumatic Stress Disorder (PTSD) is a significant public health problem in Haiti, with prevalence as high as 36.8% in Port-au-Prince. Untreated PTSD is known to result in high rates of depression, anxiety, substance use, suicide, premature mortality, medical complications, homelessness, unemployment, sexual-risk-taking behaviors, domestic violence, and second-generation mental and physical health problems. The clinical science of PTSD has advanced quickly, producing gold-standard therapies with strong evidentiary support and effectiveness rates of approximately 85%. While prevalence of PTSD in Port-au-Prince is five times that seen in the United States, there are no published studies testing these therapies’ effectiveness and no treatment programs offering these gold-standard approaches in Haiti. Bringing effective PTSD therapy to Haiti requires a careful analysis of the historical, political, cultural, and religious context. Haiti’s experience of public health interventions has been shaped by a complex history of colonialism, foreign intervention, missionary medicine, conflict between belief systems, second-class or non-existent services for the poor majority, and persistent power imbalances between provider institutions and the patients they serve. Such troubling dynamics have been particularly acute in mental health. For a mental health intervention to be effective and accepted in this context, practitioners must be aware of these undercurrents, define services as a concrete benefit to participants, not compromise international gold-standards of care, position services as compliments to existing healing strategies, establish local oversight, transparently share findings, and partner with local organizations to scale up. The proposed pilot program aims to fill these gaps in the literature and services by testing whether individual Prolonged Exposure (PE) Therapy, an intensive 12-week talk therapy protocol, is effective at reducing symptom severity among adults with PTSD in the Cité Soleil neighborhood of Port-au-Prince. This thesis develops the pilot program implementation plan, evaluation plan, and supporting literature reviews. If the pilot is able to show effectiveness on this small scale, the proposed project will make a significant contribution to public health by advancing the literature of evidence-based PTSD treatment in Haiti, and laying the foundation for expanding effective PTSD care to the hundreds of thousands of Haitians suffering from this debilitating, but highly treatable condition

Canine distemper virus neutralization activity is low in human serum and it is sensitive to an amino acid substitution in the hemagglutinin protein

© 2015 Elsevier Inc.Serum was analyzed from 146 healthy adult volunteers in eastern Africa to evaluate measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb) prevalence and potency. MV plaque reduction neutralization test (PRNT) results indicated that all sera were positive for MV nAbs. Furthermore, the 50% neutralizing dose (ND50) for the majority of sera corresponded to antibody titers induced by MV vaccination. CDV nAbs titers were low and generally were detected in sera with high MV nAb titers. A mutant CDV was generated that was less sensitive to neutralization by human serum. The mutant virus genome had 10 nucleotide substitutions, which coded for single amino acid substitutions in the fusion (F) and hemagglutinin (H) glycoproteins and two substitutions in the large polymerase (L) protein. The H substitution occurred in a conserved region involved in receptor interactions among morbilliviruses, implying that this region is a target for cross-reactive neutralizing antibodies