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The educational environment has been shown to have a great influence on teaching and learning in undergraduate education. The operating theatre can seem an intimidating and frightening environment for medical students. This study used the Surgical Theatre Educational Environmental Measure (STEEM) questionnaire to measure the operating theatre learning environment for 83 final-year medical students at the University of Birmingham. There was a 100% response rate. Data were analysed overall and with regard to gender. The results showed that overall there was an acceptable educational climate within the operating theatre for medical students. Male students viewed the atmosphere in the operating theatre in a less positive light than female students and also perceived more discrimination because of their race than their female counterparts. The STEEM has been shown to be a reliable and practical tool for measuring the operating theatre educational environment in medical students with an overall alpha reliability of 0.86.

Ultrasound imaging of the pelvic floor carries diagnostically important information about the dynamic response of the pelvic floor muscles (PFM) to potentially incontinence-producing stress, which cannot be readily captured and assimilated by the observer during the scanning process. We presented an approach based on motion tracking quantitatively to analyze the dynamic parameters of PFM on the ano-rectal angle (ARA). Perineal ultrasonography was performed on 22 asymptomatic females and nine stress urinary incontinent (SUI) patients with a broad age distribution and parity. The ventral-dorsal and cephalad-caudad movements of the ARA were resolved and kinematic parameters, in terms of displacement, trajectory, velocity and acceleration, were analyzed. The results revealed the possible mechanisms of PFM responses to prevent the urine from incontinence in fast and stress events such as coughs. The statistical analyses showed that the PFM responses of the healthy subjects and the SUI patients are significantly different in both the supine and standing experiments.

This article is based on a white paper commissioned by the Directors of Health Promotion and Education, a national organization representing state health agency directors and practitioners in health promotion and education initiatives. The work reflects an assessment of current understanding of how state-level policy makers receive and use information related to health promotion and chronic disease prevention. Although health education practitioners are routinely encouraged to use policy and environmental change strategies, a systematic approach to communication with policy leaders is not readily available. This work describes the current knowledge of the relationship and offers recommendations for research and practice.

A fundamental challenge to helping underserved women and their families cope with breast cancer is providing them with easily accessible, reliable health care information and support. This is especially true for low-income families living in rural areas where resources are few and frequently distant as well as low-income families in urban areas where access to information and support can be complex and overwhelming. The Internet is one mechanism that has tremendous potential to help these families cope with breast cancer. This article describes a feasibility test of the potential for the National Cancer Institute's (NCI's) Cancer Information Service (CIS) to provide access to an Internet-based system that has been shown to improve quality of life for underserved breast cancer patients. The test was conducted in rural Wisconsin (low socioeconomic status [SES] Caucasian women) and in Detroit, Michigan (low SES African American women), and compares the effectiveness of several different dissemination strategies. Using these results we propose a model for how CIS telephone and partnership program services could efficiently disseminate such information and support systems. In doing so we believe that important steps can be taken to close the digital divide that separates low-income families from the resources they need to effectively face cancer. This is the first of two articles coming from this study. A companion article reports on an evaluation of the use and impact of this system on the women who were given access to it.

This article is the second of a two-part series reporting on a population-based study intended to use an eHealth system to examine the feasibility of reaching underserved women with breast cancer (Gustafson, McTavish et al., Reducing the digital divide for low-income women with breast cancer, 2004; Madison Center for Health Systems Research and Analysis, University of Wisconsin; Comprehensive Health Enhancement Support System [CHESS]) and determine how they use the system and what impact it had on them. Participants included women recently diagnosed with breast cancer whose income was at or below 250% of poverty level and were living in rural Wisconsin (n = 144; all Caucasian) or Detroit (n = 85; all African American). Because this was a population-based study all 229 participants received CHESS. A comparison group of patients (n = 51) with similar demographics was drawn from a separate recently completed randomized clinical trial. Use rates (e.g., frequency and length of use as well as type of use) as well as impact on several dimensions of quality of life and participation in health care are reported. Low-income subjects in this study logged on and spent more time on CHESS than more affluent women in a previous study. Urban African Americans used information and analysis services more and communication services less than rural Caucasians. When all low-income women from this study are combined and compared with a low-income control group from another study, the CHESS group was superior to that control group in 4 of 8 outcome variables at both statistically and practically significant levels (social support, negative emotions, participation in health care, and information competence). When African Americans and Caucasians are separated the control group's sample size becomes 30 and 21 thus reducing power. Statistical significance is retained, however, in all four outcomes for Caucasians and in two of four for African Americans. Practical significance is retained for all four outcomes. We conclude that an eHealth system like CHESS will be used extensively and have a positive impact on low-income women with breast cancer.

The classic neurotrophin hypothesis is based on the idea that innervating neurons derive 'mature' neurotrophin provided by the target for their survival. Yet large precursor forms of the neurotrophin nerve growth factor (NGF) have been reported in both central and peripheral tissues. In the present study, immunoblotting was used to survey peripheral tissues containing NGF-responsive neurons and to characterize various NGF species. These results demonstrate that 'mature' forms of NGF, i.e., the 13 and 16kDa species, are rare in sympathetic and sensory ganglia and in their peripheral targets, and that large molecular weight NGF precursors are abundant. In addition, certain NGF forms predominate in a given tissue, with each tissue exhibiting a characteristic NGF expression pattern. These findings suggest that NGF processing in peripheral tissues and in NGF-responsive ganglia may involve a variety of NGF species.

Faculty stress is a factor in the current shortage of nursing faculty. New faculty members in schools of nursing are subject to stress from many sources. This article reports on an innovative strategy that decreases stress for new faculty while facilitating faculty tenure success.

The secreted autotransporter toxin (Sat) of uropathogenic Escherichia coli exhibits cytopathic activity upon incubation with HEp-2 cells. We further investigated the effects of Sat on cell lines more relevant to the urinary tract, namely, those derived from bladder and kidney epithelium. Sat elicited elongation of cells and apparent loosening of cellular junctions upon incubation with Vero kidney cells. Additionally, incubation with Sat triggered significant vacuolation within the cytoplasm of both human bladder (CRL-1749) and kidney (CRL-1573) cell lines. This activity has been associated with only a few other known toxins. Following transurethral infection of CBA mice with a sat mutant, no reduction of CFU in urine, bladder, or kidney tissue was seen compared to that in mice infected with wild-type E. coli CFT073. However, significant histological changes were observed within the kidneys of mice infected with wild-type E. coli CFT073, including dissolution of the glomerular membrane and vacuolation of proximal tubule cells. Such damage was not observed in kidney sections of mice infected with a Sat-deficient mutant. These results indicate that Sat, a vacuolating cytotoxin expressed by uropathogenic E. coli CFT073, elicits defined damage to kidney epithelium during upper urinary tract infection and thus contributes to pathogenesis of urinary tract infection.

Childhood asthma has reached near-epidemic levels in the US cities. Innovative strategies to identify children with asthma and prevent asthma morbidity are needed. This study measured asthma outcomes after initiation of an inner-city elementary school health center with a schoolwide focus on asthma detection and treatment. The site was an inner-city elementary school in Minneapolis, Minn. The study design incorporated a pre and post comparison with a longitudinal cohort of children (n = 67) and a cross-sectional cohort of children before (n = 156) and after (n = 114) the intervention. Hospitalization rates for asthma decreased 75% to 80% over the study period. Outpatient visits for care in the absence of asthma symptoms doubled (p < .01), and the percentage of students seeing a specialist for asthma increased (p < .01). Use of peak flow meters, use of asthma care plans, and use of inhalers also improved (p < .01). While no change occurred in school absenteeism, parents reported that their children had less awakening with asthma and that asthma was less disruptive to family plans. This schoolwide intervention that included identification of children with asthma, education, family support, and clinical care using an elementary school health center was effective in improving asthma outcomes for children.

Policymakers are increasingly looking toward expanding the role of private insurance in the financing of long-term care. One effort to blend public and private insurance is the Partnership for Long-Term Care sponsored by the Robert Wood Johnson Foundation. This article examines the characteristics of individuals who purchased long-term care insurance through the Partnership for Long-Term Care, as well as their motivation for purchase. Partnership purchasers are found to be a healthier, higher educated, and wealthier group than a comparison group of 55- to 75-year-olds. Partnership purchasers are also more active financial planners, have more self-reliant attitudes, and are more knowledgeable about long-term care. Findings also suggest that the Partnership for Long-Term Care attracts a substantial number of beneficiaries who would not have purchased long-term care insurance in the absence of the Partnership program.

Although establishment politicians in Moscow insist that Russia is now on the way to recovery, public support for the central government is weak. In fact the gap between popular sentiment and government policy makers is widening. This development causes anxiety for those in power, who fear that the 1995 and 1996 elections will put them out of office. The crux of the problem, from their point of view, is that their political future rests in riding the coattails of a popular president. One solution being considered is replacing Yeltsin. This desperate search for a strong leader explains the instant political prominence of General Lebed, whose defiance of both Yeltsin and Defense Minister Grachev led many to view him as a presidential candidate or alternative to Yeltsin in an authoritarian succession. Another solution being considered is retaining Yeltsin as president by postponing presidential elections until 1998 or beyond. Advocates of such a delay are fully aware that the West may view their plans as a setback to democracy, but are attempting to cultivate U.S. support for this strategy by arguing that a hardline win in 1996 would mean a complete reversal of democratization and marketization in Russia. If establishment elites succeed in prolonging their tenure in power through non-democratic means, the long-term outlook for political stability is bleak. Unless the regime modifies policies to minimize the widening gap between establishment goals and popular aspirations, heightened social discontent will necessitate increased reliance on repressive measures to retain order. As in the past, the key to any successful attempt by government insiders to keep their positions illegally is the military. However, the political role of the military under such circumstances remains difficult to predict.

Anyone who can read must, by now, be well aware that the publishing industry is currently in the throes of those fabled, and cursed, “interesting times.” As an early adaptor of e-readers, I am all in favor of the opportunities that digital publication offers us, as both consumers and creators of content, but it is undeniable that, in publishing, things will never be the same. One might be justified in asking whether things ever were the same in the first place. When did academic publishers produce, at leisure, lengthy tomes on topics of interest to a few dozen scholars, without thought of production cost, but simply for the advancement of knowledge? Probably some time before the invention of the printing press. Doom has been foretold for publishing in general and academic publishing in particular for so long that we are in danger of crisis fatigue. But what is happening now is different from the corporatization of commercial publishing that took place in the 1980s, the explosion in journal subscription costs of the ‘90s, the prophesied death of print publishing that seemed to threaten the early 2000s. The outlines of publishing’s future are finally developing a certain degree of coherence. What the printing press had torn asunder, the Internet threatens to re-join. It is interesting how many publishers do see this as a threat. In April I attended a seminar on “setting new coordinates for scholarly publishing” sponsored by Allen Press. Although the participants were primarily from scientific and medical journals, there were certain conclusions to be drawn that are applicable across the board. First of all, digital-only publication of journals is inevitable—this is hardly news—but its onset may well be sooner than expected. The iPad, Kindle Fire, and other tablets make reading a digital publication not only easy and convenient, but in some ways, for an imageheavy journal like African Arts, it could be argued that tablet reading is superior to print. Virtually all of the images we receive for publication in the journal are not just digital in their transmission to us; they are natively digital. Print publication of these images is in fact adding a layer between the source and the consumer. Digital publication takes the image from the photographer’s camera directly to the eye of the reader. On the other hand, the (potential) ease and speed of digital publication and the “everbody’s a critic” nature of the Internet means that very unrealistic expectations of digital publication are rife. Take peer review. The “visionaries” of digital publishing foresee a future in which peer review is, essentially, crowd-sourced. Everyone who is interesting in Topic X will gladly jump into the fray and comment—at length and with considered sagacity—on a paper that will evolve in multiple, trackable versions into the concentrated essence of scholarly goodness! The more practical, and well-funded, endeavors admit that they get fast turn-around in peer review by paying their reviewers—perhaps possible in fields like medical research, somewhat less realistic in the humanities. In the real world, digital peer review can speed up the process by which critique is created and distributed, but if the goal is the publication of a paper (rather than the sparking of a conversation), then a limited amount of targeted critique from someone who understands the topic is not only all a writer needs, it is all that most writers can cope with. Furthermore, while scholarship in the sciences is a laborintensive enterprise, requiring the input of many people to simply create and record the raw data, as well as run the tests to analyze it, scholarship in the humanities is still primarily a solitary pursuit, for all the discussion, formal and informal, that may lay the groundwork for its production. So, aside from speed, and the savings in the cost of printing, warehousing, transporting, and mailing physical journals to an international audience (a significant component of the production cost of a journal like African Arts, but not the majority of it), what does digital publishing do better than print? Obviously, the portability of digital publications is a major factor in their favor. There is something well-nigh miraculous about a rectangle of glass, metal, rubber, and silicon that fits neatly into the palm of your hand and yet contains a library larger than that of a small rural town in Vermont and can be read more or less anywhere in the world. Sometimes there is nothing that can replace traveling to a distant library or archive to research in the stacks, but in practical terms, digital publications make it possible for scholars in the far corners of the world to access material that they would never see otherwise. Searchability is another important factor; a well-constructed index can be a research tool in and of itself, but still, an index by definition guides the reader to what the indexer thinks is important about a work, not to what the reader may be searching for. Journal archives like JSTOR allow us to search for content in publications we never even knew existed, making cross-disciplinary research more accessible than ever. But these are merely examples of ways that digital publication can make the old ways of doing research more efficient. As I have been thinking about how African Arts might change once the inevitable transition to digital-only publication arrives, I find myself thinking not in terms of books and journals but in terms of museum exhibitions and exhibition books. The current model is for the locationbound exhibition of physical objects, accompanied by text panels and, increasingly, video, audio, interactive media, supplemental lectures, and then a print book including expert analysis and discussion of both the objects and the themes of the exhibition. The exhibition books, naturally, last much longer than the exhibition, which travels on to the next venue and is ultimately disassembled. Seeing an object in person is irreplaceable. Like the relationship between a book and its index, being in the presence of the object allows an individual to ask his or her own questions about it, rather than being guided by the choices of a photographer or writer. But at the same time, photography can bring out aspects of an object that are not visible to the unassisted eye. A digital publication can provide orders of magnitude more images, from different angles and scalable magnification, than print, not to mention the potential for 360° video (or even 3-D imagery). Rather than having multimedia at the museum and text in the exhibition book, both can be simultaneously available to a global audience. And rather than competing for space in a finite number of museums, digital publication could open up an arena for smaller—or larger— scale projects, and collaborations between artists and curators where the production of the art and its contextualization and analysis occur virtually simultaneously. Rather than running an exhibition preview, we would run a version of the exhibition itself. This is just one thought about where digital publication might take African Arts. The lack of page-limit constraints might open us up to both much shorter and much longer pieces; we might publish individual pieces as they are completed rather than waiting for enough content to fill an “issue”; rather than limiting ourselves to text analysis of art, we might offer documentaries, interviews, performances themselves. And we would continue to print—or pixillate—words. Some forms of scholarship work just fine and don’t need changing. The future is upon us. The editors of African Arts are interested in what our readership would like to see in the journal as publishing goes digital, and even more so in what new types of scholarship our authors might envision publishing in these pages. We’re open to your ideas.

Pathologic staging of renal clear cell carcinoma (ccRCC) provides useful but limited prognostic information suggesting that there are underlying molecular processes not readily identified through conventional histopathological techniques in the primary tumor. At the molecular level, transcript, metabolomic and protein expression patterns have indicated a striking Warburg Effect profile in ccRCC tissues, with major affects on sugar and lipid metabolism. Our group has been applying MALDI-MS imaging approaches to ccRCC tissues to profile lipids and glycans associated with disease progression. As both lipids and glycans can act as signaling molecules and have been associated with cancer progression, ccRCC tissues were selected by a pathologist to contain substantial tumor, non-tumor and tumor margin regions to characterize the differential localization of lipid and glycan species within the tissue. Lipid profiles from fresh-frozen tissue slides coated in DHB matrix were obtained on a dual source Bruker Solarix 70 FTICR mass spectrometer. Glycans were imaged in a similar fashion with a method developed by our lab using protein N-glycanase F to release protein bound N-glycans. There are clear patterns of specific lipid and glycan species that are only present along the margin of the tumor and non-tumor interface, or those primarily localized in non-tumor or tumor regions. Off-tissue extraction of lipids and glycans from similarly processed tissues and further mass spectrometry analysis was done to confirm structural designations. Linkage of differentially expressed lipid and glycan species with clinical data and other molecular markers of ccRCC is ongoing. This approach has the potential to not only improve prognostic assessment and enhance post-operative surveillance, but also to better define the underlying biology of ccRCC aggressiveness and identify new rational targets for therapeutic intervention. Citation Format: Richard R. Drake, Thomas Powers, Ellen Jones, Raymond S. Lance, Anand S. Mehta, Dean A. Troyer. MALDI mass spectrometry imaging for on-tissue spatial profiling of tumor-specific N-linked glycans and lipids in renal carcinomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1523. doi:10.1158/1538-7445.AM2013-1523

RATIONALE: Surgery, chemotherapy and radiation have not appreciably improved lung cancer patient survival rates over the past 20 years. Preclinical anti-tumor efficacy testing models could be improved by being rapid, reliable and capable of demonstrating tumor responses to dosing (concentration/timing) and drug interactions, while accounting for inter-patient variation. High-throughput, 3D in vitro systems hold promise as such therapeutic models, but linking these models to clinical responses in patients has been a dilemma. METHODS: We developed a lung tissue cryopreservation/banking method that optimizes cell viability and maintains tissue architecture after thawing. This method involves the expansion-perfusion of fresh patient lung tissue samples with non-toxic cryoprotectant solutions, followed by controlled-rate freezing of samples. RESULTS: We used this method to cryopreserve lung tissues from multiple patients. Although inter-patient variability in lung tissue compliance was anticipated, a wide range of expansion volumes can be tolerated without architectural damage. In contrast, tissue integrity was more sensitive to variations in expansion-perfusion rates (as gauged by lymphatic expansion/tearing). Cryosubstitution demonstrated that crystal formation varies with cryoprotectant cocktail and region within the lung, but can be virtually eliminated under certain conditions. From thawed lung tissues, we have 1) isolated and expanded viable lung cell types; 2) isolated decellularized extracellular components; and, 3) reconstituted intact lung tissue with fluorescent-tagged lung tumor cells. We performed patient surgeries/preservations individually, thawing, processing and analysis of lung tissue from multiple patients was performed simultaneously. CONCLUSION: Cancer cell drug responses are being compared in lung tissues ex vivo versus on standard monolayer culture using advanced proteo-/lipidomic mapping techniques (including MALDI MS and DIGE). Comparing multiple patient-specific lung tissues simultaneously should afford patient population stratification based on molecular profiles and achieve more rapid methods for determining personalized clinical treatment regiments. Citation Format: Demetri D. Spyropoulos, Chadrick E. Denlinger, Ellen C. Riemer, Danforth A. Newton, E. Ellen Jones, Richard R. Drake, John E. Baatz. Cryopreserved, viable and architecturally intact lung tissue from patients as a model to study drug therapies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3848. doi:10.1158/1538-7445.AM2013-3848

Conclusions * Politicians advocating restoration of Russia as a great power strengthened their position in the December 1995 Duma elections. Although communist and nationalist gains fell short of the two-third majority needed to override a presidential veto, these groups (who are united in their suspicion of Western intentions) now enjoy a solid majority in the new lower house. * By contrast, parties advocating integration with Western security systems suffered significant losses, even though they had muted the pro-Western components of their programs. * The dominant role of great power restorationists in the new Duma will increase pressure on the Yeltsin regime to assume a more assertive stance vis-a-vis the West. * The most important consequence of the parliamentary election is its impact on the election that really counts: the presidential race. The main beneficiary of the strong conservative showing is Communist Party leader Gennadiy Zyuganov, who emerged as the strongest challenger to both President Boris Yeltsin and the still-disunited reformists. Great Power Restorationist Victory at the Polls The new Duma which began its session on January 16th is considerably more nationalist in its orientation than the one it replaced. Communist and nationalist parties--deeply divided on some domestic issues but united in the idea that Russia must be restored as a great international power--significantly strengthened their position, from 39% in the old Duma to 62% in the new one. These great power restorationist deputies share many common national security goals, such as reintegration of some of the other Soviet successor states and strengthening the armed forces. They also share a strong suspicion of Western, particularly U.S., intentions toward Russia. The strong showing of the mainstream Communist Party (which advocates restoration of the USSR and won 157 of the 450 Duma seats) is symptomatic of the shift in political alignments in the new Duma. At the same time, parties advocating Russia's integration with Western security systems were soundly defeated. Such groups controlled a quarter of the seats in the old Duma; in the new one, they represent only 15%. For instance, in 1993, the pro-Western Russia's Choice party came in second in the party list race and did well in the single seat races, winning 76 seats in all. In the most recent election, Choice won less than 4% on the party list vote (failing to break the 5% barrier), garnering only nine seats in the new Duma--not enough to form their own faction. Centrist parties also fared poorly, mirroring their modest results in the 1993 election. Most significantly, Prime Minister Viktor Chernomyrdin's "Russia is Our Home" party received only 10% of the vote, despite its advantages as the incumbent party in control of major electronic media and patronage and at least some tinkering with voting results (i.e., in Chechnya). Yeltsin staffers and party spokesmen tried to buffer the negative public relations consequences of the vote by pre-election statements stressing their modest expectations. Nevertheless, 90% of the electorate voted for groups running in explicit opposition to the Government's policies--an undeniable rejection of the President's and Prime Minister's policies. Reform-minded commentators and officials have also tried to portray the election not as a victory for conservative forces, but a defeat for "democrats," who bungled their chances of victory by refusing to unite. Nine percent of the party list vote went to parties that support integration with Western security systems but failed to gain the 5% minimum needed to acquire a share of the party list seats. In fact, however, candidates on the opposite end of the foreign policy spectrum--great power restorationists--suffered even more from the failure of conservative forces to unite: 21% of the party list vote went to communist or nationalist parties that failed to make the 5% cutoff. …

Publisher Summary The importance of maintaining balanced pyrimidine nucleotide metabolism is evident because it has been shown that many biosynthetic pathways are dependent on pyrimidines. Pyrimidine nucleotides are also important for the continued biosynthesis of various macromolecules, such as phospholipids and polysaccharides, for which specific nucleotides are required as cofactors in activating appropriate precursors, as exemplified by CMP-choline and UDP-glucose. Even the conversion of uracil to β-alanine is a biosynthetic pathway, although historically this has been referred to as catabolism. A biosynthetic designation for this pathway comes from the importance of β-alanine, which functions as a neurotransmitter, as well as a building block for various dipeptides. These peptides include the ubiquitous pantothenate, the precursor for the acyl-carrier protein in fatty acid synthase and for coenzyme A. The inability of humans to synthesize pantothenate makes it a vitamin. The biochemical roles of carnosine and other dipeptides containing β-alanine are discussed in the chapter. Nucleotides presumably exist at very low concentrations in the extracellular environment, though no values have been published for their concentration in blood. DNA sequencing suggests that many mammalian or human proteins may be coded by two or more genes, and that such gene duplication may provide a simple safety factor in the event of a mutation in one gene, or provide a more sophisticated regulatory strategy if the genes lead to slightly altered isozymes to be expressed in unique tissues.

Human UMP synthase is a bifunctional protein containing two separate catalytic domains, orotate phosphoribosyltransferase (EC 2.4.2.10) and orotidine-5′-phosphate decarboxylase (EC 4.1.1.23). These studies address the question of why the last two reactions in pyrimidine nucleotide synthesis are catalyzed by a bifunctional enzyme in mammalian cells, but by two separate enzymes in microorganisms. From existing data on subunit associations of the respective enzymes and calculations showing the molar concentration of enzyme to be far lower in mammalian cells than in microorganisms, we hypothesize that the covalent union in UMP synthase stabilizes the domains containing the respective catalytic centers. Evidence supporting this hypothesis comes from studies of stability of enzyme activity in vitro, at physiological concentrations, of UMP synthase, the two isolated catalytic domains prepared by site-directed mutagenesis of UMP synthase, and the yeast ODCase. The two engineered domains have activities very similar to the native UMP synthase, but unlike the bifunctional protein, the domains are quite unstable under conditions promoting the dissociated monomer.

Conclusions * Russia's legislative elections, scheduled for 17 December, have only limited legal significance, because most power is concentrated in the presidency. However, the elections will be viewed in Moscow as an indicator of the popular mood and will serve as a surrogate presidential primary. * All indications are that the parliamentary election will not represent a fair sounding of the electorate. Virtually all participants in the election process will use the levers they control to manipulate the outcome: from buying signatures, to obstructing competitors' access to the media, to tampering with the vote count after the election. * Government attempts to influence the outcome of the parliamentary elections probably will temper, but not neutralize, the anti-Government and anti-Yeltsin sentiment of the electorate. However, it is still too early to assess the likelihood of the Communist/nationalist sweep predicted by reformists like Yegor Gaydar. * If hardliners do particularly well in the December elections and use their enhanced position in the new Duma to publicly challenge Boris Yeltsin, this could set the stage for another legislative/executive crisis. Significance of the Legislative Elections The two-year terms of both the lower houses (State Duma) and upper house (Federation Council) are due to expire in December. However, the only election currently scheduled is for the State Duma. The chances are remote that elections to a new Federation Council will be on the ballot this December, primarily because Yeltsin fiercely opposes an upper house directly elected by the people and has vetoed legislation mandating upper house elections. The Duma elections have limited significance from a legal standpoint. The bicameral legislature--thanks to the Constitution drafted by the executive branch and adopted through a referendum in 1993--has little legal authority. In fact, over the past two years, the executive branch has ruled with very little direct interference from parliament. When the legislature adopts measures distasteful to the executive, Yeltsin generally vetoes the legislation and issues a presidential decree on the issue. Regardless of the outcome of the election, the legislature can do little to effect direct changes in policy. The December elections, however, have symbolic significance that goes well beyond the parliament's ability to directly affect policy. * First, Duma elections--in particular the party list vote, which will determine the makeup of half of the Duma's 450 deputies--will be seen by the Moscow political elite as a rough measure of which political forces enjoy the most popular support. In that sense, the Duma elections are a test of the legitimacy of the Yeltsin regime. The pattern of populist support revealed through the elections will also play a role in the formation of future political alliances. * Second, because several of the parties vying in the legislative election are associated with presidential contenders, the elections will function as a kind of presidential primary, shaping perceptions within the Moscow political elite and Kremlin insiders as to the probable outcome of the June presidential elections. * Third, if one group or coalition manages to sweep the elections and gain an overwhelming majority, it would be in a position to override a presidential veto or initiate impeachment proceedings--moves that could pave the way for a replay of the executive-legislative conflict that ended in Yeltsin's attack on the old parliament in the fall of 1993. Weakness of Democracy Although the mere holding of elections is a positive step towards the development of democratic practices, the election process itself has highlighted the fragility of democracy in Russia. It has also demonstrated how deeply ingrained are the habits of bureaucratic politics and authoritarian thinking inherited from the Soviet era. …

Human uridine monophosphate (UMP) synthase, a bifunctional protein containing orotate phsophoribosyltransferase (OPRTase, EC 2.4.2.10) and orotidine 5'-monophosphate decarboxylase (ODCase, EC 4.1.1.23) activities, has been overproduced by construction and use of a recombinant baculovirus containing the cDNA for this protein. Expression of the virus in cabbage looper larvae produces a crude larval homogenate having UMP synthase enriched about 180-fold over human placental homogenates and allows larger quantities of this human protein as well as analog proteins to be prepared for structure/function studies. A vastly improved purification procedure using a monoclonal immunoaffinity column was developed. Human UMP synthase purified from larval extracts yielded a product which comigrates in SDS gel electrophoresis with UMP synthase purified from human placenta; pure proteins prepared from these two tissue sources have the same specific activities. We found that OPRTase requires Pi ions in the assay buffers for optimal OPRTase activity; BSA in the assay vessel increases to a lesser degree both OPRTase and ODCase activities. These changes in the assay are essential to observe a parallel enrichment of the two enzyme activities. The baculovirus system was used to express human UMP synthase because it usually yields a product with posttranslational modifications that reflect those of the organism that provided the cDNA. We report data to show that human UMP synthase derived from either human placenta or larval extracts both have a sequence in which the N-terminal methionine has been removed and the formerly penultimate alanine has been acetylated.

Secure object-oriented database models discuss features necessary to ensure access control to object-oriented data. Discretionary and mandatory access control models have recently been proposed for object-oriented systems. One of the primary discretionary methods proposed is based on the role of a user within the system and is called user role based security. In this paper we discuss the addition of new roles at run time to facilitate interoperation between secure databases which use user role based security. We discuss a promising approach to dynamic addition of roles, and propose future research to develop a role calculus for describing and merging role lattices.

The once-pampered Russian officer corps, angry and resentful over the loss of status and decline in living standards, feels abandoned by virtually all political institutions. Most officers are pessimistic about the future of both Russia and the army. The officer corps is polarized between those attracted to moderate reformers and those who favor hardliners. The gap between the "haves" and "have-nots" is increasing. The latter are particularly susceptible to ultratraditionalists. Officers are highly critical of President Yeltsin and many blame him for the military's precarious position. Most would oppose using the military to defend the President. The officer corps, even more than the civilian population, is dismayed at the breakdown in law and order. Although officers support democracy in principle, they condemn Western-style democracy and support authoritarian rule as a way to restore stability. As with the populace at large, a majority of officers express nostalgia for the old Soviet Union and advocate restoration of some sort of union, particularly a Slavic union. Most feel that the three Slavic republics will be reunited by the end of the century. Most military officers see the West as a threat. As a result, most officers strongly advocate maintaining a balance in strategic weapons. They see the top priority for Russian foreign policy as that of restoring Russia to the status of a superpower.

The presence of a proton-donating catalytic amino acid side chain in orotidylate decarboxylase (ODCase) was sought by site-directed mutagenesis. Replacement of yeast ODCase Lys93 with a cysteine resulted in a mutant protein (K93C) with no measurable activity, representing a decrease in activity by a factor of, at most, 2 x 10(-8) times the activity of the wild-type enzyme. Treatment of this mutant protein with 2-bromoethylamine, designed to append Cys93 to yield S-(2-aminoethyl)cysteine, restored activity by a factor of at least 5 x 10(5) over the untreated mutant protein. Activity could not be restored by treatment with other brominated reagents designed to replace the epsilon-amino of S-(2-aminoethyl)Cys93 with a different functional group. The overall architecture of the K93C protein was not significantly changed, as judged by the similar dimerization properties (in the absence of ligands) of the mutant enzyme compared to the wild-type enzyme. The binding affinity of the substrate orotidylate was not measurably changed by the mutation, indicating that Lys93 has an essential role in catalysis which is mechanistically distinguishable from substrate binding. Apparently the mutation removes an integral portion of the active site and does not drastically affect the structural or substrate binding properties. However, the affinities of the mutant protein for the competitive inhibitors 6-azauridylate (6-azaUMP) and UMP are significantly altered from the pattern seen with the wild-type enzyme. The K93C protein has an affinity for the neutral ligand UMP which is greater than that for the anionic 6-azaUMP, in clear contrast to the preference for 6-azaUMP displayed by the wild-type enzyme. Lys93 is apparently critical for catalysis of the substrate to product and for the binding of anionic inhibitors; the data are discussed in terms of previously existing models for transition-state analogue inhibitor binding and catalysis.

The purpose of this study was to determine what education and training pediatric nurse practitioners receive about injury prevention and control and what kinds of clinical activities PNPs perform with regard to injury prevention and control. Sixty-four members of the Greater New York Chapter of the National Association of Pediatric Nurse Associates and Practitioners were questioned. Data on demographic, professional, and practice characteristics and on education and training and clinical activities in injury prevention and control were collected. Results indicated that advice about child car restraints and automobile seat belts was routinely given by less than 30% of practitioners, information about smoke detectors was given by about 15%, and advice about firearms in the home was given by 7% or less. Implications for counseling to prevent injuries are discussed.

Publisher Summary This chapter discusses orotidylate decarboxylase of yeast and man. Uridylic acid (UMP) biosynthesis is essential for most living organisms, providing the precursor of the three pyrimidine trinucleotides as well as for the synthesis of di- and polysaccharides that utilize UTP and for the synthesis of lipids which require CTP. The amounts of the UDP sugars in mammalian liver can equal the amount of UTP. In man and other animals, the last two enzyme reactions of the de novo pathway are catalyzed by a single protein, UMP synthase. This bifunctional protein has both orotate phosphoribosyltransferase and orotidylate decarboxylase activities. In bacteria, six genes code for the monofunctional proteins that catalyze the six required enzyme reactions. In fungi, such as yeast, there are only five genes for the first two enzymes packaged into a large bifunctional polypeptide, whereas the remaining four enzymes are monofunctional. The mechanism for ODCase appears to involve the formation of a zwitterion of OMP and a ylid on decarboxylation. Thiamin pyrophosphate catalyzes various decarboxylation and transfer reactions involving ketone groups because the thiazolium ring with its positively charged N atom can, on the loss of a proton from the adjacent C-2, generate a ylid that adds to carbonyl groups to produce a substrate ylid.

I will present the recently established mechanism (1,2) for the reaction catalyzed by orotidylate decarboxylases (ODCases) and detail the characteristics of one altered ODCase that we have prepared using biotechnology. The modified protein shows the dramatic loss of activity one would expect to see when a site-specific mutation is made to change an amino acid residue that is essential for catalysis.

Using an incomplete factorial experimental design, we have identified conditions for crystallization of yeast orotidine 5'-monophosphate decarboxylase (ODCase) in an unliganded state and complexed separately to two inhibitors: 6-azauridine 5'-monophosphate (aza-UMP) and 1-(5'-phospho-beta-D-ribofuranosyl) barbituric acid (BMP). Crystals of X-ray diffraction quality have been obtained of yeast ODCase complexed with BMP, a putative transition state analog inhibitor (Ki = 8.8 x 10(-12) M). ODCase:BMP complex crystals with a hexagonal rod habit were grown from a solution initially containing 12 mg/ml ODCase (205 microM dimer) plus 450 microM BMP by microdialysis at 4 degrees C against a mother liquor which consisted of 0.1 M Na-PIPES-acetate (pH 6.4), 37.5 microM BMP, 5 mM mercaptoethanol, 1% polyethylene glycol 400, and 2.3 M ammonium sulfate. Crystals were analyzed using precession photography and were assigned to trigonal space group R32 with unit cell dimensions a = b = 115 A, c = 385 A. The crystal density is 1.245 g/cm3 indicating the presence of two ODCase: BMP complex dimers (118 kDa each) per asymmetric unit with a packing density of 2.08 A3/Da and 41% solvent content. The morphological habit of crystals of the ODCase:BMP complex changed when the initial ammonium sulfate concentration was increased in 0.05 M steps from 2.3 to 2.45 M. All of these crystals diffracted to at least 3.0 A resolution over a period of several weeks at room temperature and are isomorphous.

New sensitive and direct spectrophotometric assays for orotate phosphoribosyltransferase and orotidylate-5′-monophosphate (OMP) decarboxylase are described. The assays utilize a thioketone derivative of orotate (4-thio-6-carboxyuracil) which is converted into 4-thio-OMP by the transferase in the presence of phosphoribosyl pyrophosphate. 4-Thio-OMP is subsequently decarboxylated to 4-thio-UMP by OMP decarboxylase. A novel, efficient synthesis of thioorotate is described. Unlike the natural substrates, the interconversion of the thioketone derivatives yields large spectral changes in the near-visible absorption region. Orotate phosphoribosyltransferase is assayed at 333 nm with a molar extinction coefficient of 10,300 m −1 cm−1 for the conversion of thioorotate to either 4-thio-OMP or 4-thio-UMP. Orotidylate decarboxylase is assayed at 365 nm with a molar extinction coefficient of 3350 m −1 cm−1 for the conversion of 4-thio-OMP to 4-thio-UMP. Another advantage of these substrates is that they bind less tightly to orotate phosphoribosyltransferase and OMP decarboxylase than orotate or OMP, respectively. Thus, the initial rates of substrate conversion to product are readily measurable near the Km values for the thioketone substrates. The ability to follow the reactions directly permits the rapid determination of Km values for the thioketone substrates and Ki values for inhibitors of the enzymes.

The enzymatic decarboxylation of orotidine 5'-monophosphate may proceed by an addition-elimination mechanism involving a covalently bound intermediate or by elimination of CO2 to generate a nitrogen ylide. In an attempt to distinguish between these two alternatives, 1-(phosphoribosyl)barbituric acid was synthesized with 13C at the 5-position. Interaction of this potential transition-state analogue inhibitor with yeast orotidine-5'-monophosphate decarboxylase resulted in a small (0.6 ppm) downfield displacement of the C-5 resonance, indicating no rehybridization of the kind that might have been expected to accompany 5,6-addition of an enzyme nucleophile. When the substrate orotidine 5'-monophosphate was synthesized with deuterium at C-5, no significant change in kcat (H/D = 0.99 +/- 0.06) or kcat/KM (H/D = 1.00 +/- 0.06) was found to result, suggesting that C-5 does not undergo significant changes in geometry before or during the step that determines the rate of the catalytic process. These results are consistent with a nitrogen ylide mechanism and offer no support for the intervention of covalently bound intermediates in the catalytic process.

We have studied the ability of the enzyme pyrroline-5-carboxylate dehydrogenase to oxidize aldehydes which are structurally similar to pyrroline-5-carboxylate, the enamine of γ-glutamyl semialdehyde. These studies required the organic synthesis of semialdehydes not commercially available. Accurate quantitation of the concentration of these compounds in solution is necessary because they polymerize upon evaporation to dryness. Reported here is a method for colorimetric measurement of semialdehydes in solution by formation of an oxidized covalent adduct with 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole. This adduct after oxidation produces a product that has an absorption maximum at 302 ± 2 nm. This characteristic absorbance maximum was not found in the spectra of the covalent adducts of simple aliphatic aldehydes with the chromophore. Using glyoxylic acid as standard, the values obtained for the concentration of semialdehydes in solution were independently verified from quantitation of the proton concentration of the oxidized adducts by integration of the area under the peaks of their 1H NMR signals. These latter values were compared to the signal strengths of an internal standard. The values obtained by the colorimetric and NMR techniques were in excellent agreement, thus allowing use of the colorimetric technique as a simple method for routine laboratory analysis of semialdehydes.

(1997). A Lesson in Teaching Art Self-Confidence from Drawing on the Right Side of the Brain. Art Education: Vol. 50, Concerns in Secondary Art Education, pp. 33-38.