Deliberately Losing Control of C−H Activation Processes in the Design of Small-Molecule-Fragment Arrays Targeting Peroxisomal Metabolism

Combined photochemical arylation, “nuisance effect” (S_NAr) reaction sequences have been employed in the design of small arrays for immediate deployment in medium-throughput X-ray protein–ligand structure determination. Reactions were deliberately allowed to run “out of control” in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono- and bisarylations combined with S_NAr processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified.     

Solutions to a combined problem of excessive hydrogen sulfide in biogas and struvite scaling.

The Woodman Point Wastewater Treatment Plant (WWTP) in Western Australia has experienced two separate problems causing avoidable maintenance costs: the build-up of massive struvite (MgNH4PO4. 6H2O) scaling downstream of the anaerobic digester and the formation of hydrogen sulfide (H2S) levels in the digester gas to levels that compromised gas engine operation and caused high operating costs on the gas scrubber. As both problems hang together with a chemical imbalance in the anaerobic digester, we decided to investigate whether both problems could be (feasibly and economically) addressed by a common solution (such as dosing of iron solutions to precipitate both sulfide and phosphate), or by using separate approaches. Laboratory results showed that, the hydrogen sulfide emission in digesters could be effectively and economically controlled by the addition of iron dosing. Slightly higher than the theoretical value of 1.5 mol of FeCl3 was required to precipitate 1 mol of dissolved sulfide inside the digester. Due to the high concentration of PO4(3-) in the digested sludge liquor, significantly higher iron is required for struvite precipitation. Iron dosing did not appear an economic solution for struvite control via iron phosphate formation. By taking advantage of the natural tendency of struvite formation in the digester liquid, it is possible to reduce the risk of struvite precipitation in and around the sludge-dewatering centrifuge by increasing the pH to precipitate struvite out before passing through the centrifuge. However, as the Mg2+/PO4(3-) molar ratio in digested sludge was low, by increasing the pH alone (using NaOH) the precipitation of PO4(3-) was limited by the amount of cations (Ca2+ and Mg2+) available in the sludge. Although this would reduce struvite precipitation in the centrifuge, it could not significantly reduce PO4(3-) recycling back to the plant. For long-term operation, maximum PO4(3-) reduction should be the ultimate aim to minimise PO4(3-) accumulation in the plant. Magnesium hydroxide liquid (MHL) was found to be the most cost-effective chemical to achieve this goal. It enhanced struvite precipitation from both, digested sludge and centrate to the point where more than 95% PO4(3-) reduction in the digested sludge was achieved.     

Juvenile mood disorders and office psychopharmacology

Mood disorders afflict pediatric patients, cause significant impairment, and interfere with normal development. Increasingly, pediatricians are called on to assess and collaborate with mental health practitioners in medicating children and adolescents with mood disorders. Approaching the juvenile with a primary emphasis on clarifying the diagnoses, determining environmental antecedents and sequelae, and investigating suicide risk enables the pediatrician to institute appropriate treatment. Despite limited data from controlled studies, psychotherapy often is used for mild to moderate depression. Pharmacotherapy is indicated in cases unresponsive to psychotherapy and in severe or suicidal cases. First-line pharmacotherapy for depressed adolescents is usually an SRI followed by the atypical or TCA antidepressants. Bipolar disorder typically requires an aggressive medication regimen, including anticonvulsants, lithium, or a combination, as well as environmental modifications. With severe, difficult, or refractory cases, mental health consultation is recommended to clarify diagnoses and to provide psychotherapy and medication input.     

The lack of long-term detrimental effects on liver allografts caused by donor-specific anti-HLA antibodies

Recent reports indicate a higher incidence of both acute and chronic liver allograft rejection when, at the time of transplantation, the recipients serum contains donor-specific anti-HLA antibodies. From 9/89 to 5/91, 133 liver allografts were performed at our institution. Thirteen liver recipients had donor-specific IgG anti-HLA antibodies (complement-fixing) at the time of transplantation. In eleven patients, antibodies reacted to donor class I antigens while in 1 patient the donor-specific antibody had class II reactivity. Twelve patients have been followed for a minimum of 12 months (median 18 months, range 28-12 months). No hyperacute rejection was seen in any of the cases and four patients had acute rejections. Thus far only one of the twelve patients has biopsy evidence suggestive of chronic liver injury. The remaining have normal liver enzymes and bilirubin. Three of these twelve patients died (one from a myocardial infarction and the others from sepsis) accounting for a one-year graft survival of 75%. There was no significant statistical difference in the one-year graft survival in those recipients without donor-specific antibodies (i.e., 80.5%). In eight of the twelve patients, pretransplant preformed antibody level (PRA) was > 50%. In six of the thirteen patients donor-specific antibody was present at dilutions greater than 1:64. As previously reported, the donor-specific antibody disappeared from the serum posttransplant within hours and did not reappear. In vitro studies demonstrated no factor in portal or hepatic artery blood that could inhibit rabbit complement mediated lysis of anti-HLA antibodies. We conclude that it is not a contraindication to do liver transplants in the presence of donor-specific anti-HLA antibodies.     

Freestanding Alumina Membrane by Double-Layer Anodization

A novel method has been developed for fabricating full or partial freestanding anodic alumina. In our method a sacrificial metal layer is introduced between an Al film and a Si₃N₄ substrate. A freestanding alumina film at wafer scale is successfully achieved by anodizing the double metal layer, during which the alumina is spontaneously stripped off the Si₃N₄ substrate due to the anodic oxidation of the sacrificial layer. The barrier oxide of the alumina film is effectively removed either by H₃PO₄ dissolution or by CF₄ reactive ion etching. The freestanding alumina film is utilized as a contact mask to transfer its nanoporous pattern to a Si substrate. By patterning the sacrificial metal layer with contact lithography, a partial freestanding alumina film is successfully achieved on the silicon chip, producing a unique micro/nanofluidic channel. Compared with previous techniques, the method reported here is advantageous for its simplicity and flexibility     

A case of intractable epistaxis

The surgical management of intractable epistaxis by external carotid artery ligation may become complicated if there is a high bifurcation of the common carotid artery. Occlusion of the bleeding vessels by catheter embolization is described in a patient in whom exploration of the neck had failed to locate the external carotid artery.     

Continuity and change: past experience as adaptive repertoire in occupational adaptation

Narratives are gaining recognition as important ways occupational therapists and other clinicians can think about the life stories of clients. The purpose of this article is to examine a conceptualization of how changes from one chapter to another occur in life stories, using the metaphor of an adaptive repertoire, and to consider how this notion can be useful in helping clients maintain continuity and a coherent life story in times of change. Three premises based on the concept of adaptation address (a) configurations of occupational forms embedded in particular local worlds, (b) cumulative development of an adaptive repertoire that allows one to perform both competently and appropriately, and (c) adaptive transitions and application of one's repertoire to new circumstances. Implications for research and clinical practice in occupational therapy also are examined.     

Designing a Senior Capstone Course to Satisfy Industrial Customers

It is sometimes forgotten that industry is an important customer of engineering education. Ignoring this relationship has produced graduates that often fail to meet the changing needs of industry in today's competitive environment. On the basis of feedback from our industrial customers, faculty from Mechanical Engineering and Manufacturing Engineering at Brigham Young University have jointly developed a new senior capstone design course entitled “Integrated Product and Process Design.” This new capstone course is centered on industrial design and manufacturing projects. These projects involve both product and process design activities. Multidisciplinary teams of students are taught a structured development approach to produce typical industrial deliverables. These deliverables include a functional specification, product and process design, prototype, and first production sample. This paper identifies changing industrial needs, describes how the course was designed to meet these needs, and presents results from the initial offerings of the course.