Showing papers by "University of Virginia published in 1997"

Africa's Growth Tragedy: Policies and Ethnic Divisions

Abstract: Explaining cross-country differences in growth rates requires not only an understanding of the link between growth and public policies, but also an understanding of why countries choose different public policies. This paper shows that ethnic diversity helps explain cross-country differences in public policies and other economic indicators. In the case of Sub-Saharan Africa, economic growth is associated with low schooling, political instability, underdeveloped financial systems, distorted foreign exchange markets, high government deficits, and insufficient infrastructure. Africa's high ethnic fragmentation explains a significant part of most of these characteristics.

Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence.

Abstract: The homeodomain protein IPF1 (also known as IDX1, STF1 and PDX1; see Methods) is critical for development of the pancreas in mice and is a key factor for the regulation of the insulin gene in the beta-cells of the endocrine pancreas. Targeted disruption of the Ipf1 gene encoding IPF1 in transgenic mice results in a failure of the pancreas to develop (pancreatic agenesis). Here, we report the identification of a single nucleotide deletion within codon 63 of the human IPF1 gene (13q12.1) in a patient with pancreatic agenesis. The patient is homozygous for the point deletion, whereas both parents are heterozygotes for the same mutation. The deletion was not found in 184 chromosomes from normal individuals, indicating that the mutation is unlikely to be a rare polymorphism. The point deletion causes a frame shift at the C-terminal border of the transactivation domain of IPF1 resulting in the translation of 59 novel codons before termination, aminoproximal to the homeodomain essential for DNA binding. Expression of mutant IPF1 in Cos-1 cells confirms the expression of a prematurely terminated truncated protein of 16 kD. Thus, the affected patient should have no functional IPF1 protein. Given the essential role of IPF1 in pancreas development, it is likely that this autosomal recessive mutation is the cause of the pancreatic agenesis phenotype in this patient. Thus, IPF1 appears to be a critical regulator of pancreas development in humans as well as mice.

Percutaneous polymethylmethacrylate vertebroplasty in the treatment of osteoporotic vertebral body compression fractures: Technical aspects

Abstract: PURPOSE: To describe a technique for percutaneous vertebroplasty of osteoporotic vertebral body compression fractures and to report early results of its use. METHODS: The technique was used over a 3-year period in 29 patients with 47 painful vertebral fractures. The technique involves percutaneous puncture of the involved vertebra(e) via a transpedicular approach followed by injection of polymethylmethacrylate (PMMA) into the vertebral body. RESULTS: The procedure was technically successful in all patients, with an average injection amount of 7.1 mL PMMA per vertebral body. Two patients sustained single, nondisplaced rib fractures during the procedure; otherwise, no clinically significant complications were noted. Twenty-six patients (90%) reported significant pain relief immediately after treatment. CONCLUSION: Vertebroplasty is a valuable tool in the treatment of painful osteoporotic vertebral fractures, providing acute pain relief and early mobilization in appropriate patients.

Multidimensional Inventory of Black Identity: A Preliminary Investigation of Reliability and Construct Validity

Abstract: The present study presents preliminary evidence regarding the reliability and validity of the Multidimensional Inventory of Black Identity (MIBI). The MIBI consists of 7 subscales representing 3 stable dimensions of African American racial identity (Centrality, Ideology, and Regard). Responses to the MIBI were collected from 474 African American college students from a predominantly African American university (n = 185) and a predominantly White university (n = 289). As the result of factor analysis, a revised 51 -item scale was developed. Evidence was found for 6 subscales. The Public Regard subscale was dropped because of poor internal consistency. Interscale correlations suggest that the MIBI is internally valid. Relationships among the MIBF subscales and race-related behavior suggest that the instrument has external validity. Descriptive statistics for the revised MIBI are provided for the entire sample as well as by school. Racial identity is one of the most heavily researched aspects of African Americans' psychological lives. Racial identity has been associated with a number of phenomena including selfesteem (Hughes & Demo, 1989; Parham & Helms, 1985; Row

Antiapoptotic signalling by the insulin-like growth factor i receptor, phosphatidylinositol 3-kinase, and akt

Abstract: We have found that insulin-like growth factor I (IGF-I) can protect fibroblasts from apoptosis induced by UV-B light. Antiapoptotic signalling by the IGF-I receptor depended on receptor kinase activity, as cells overexpressing kinase-defective receptor mutants could not be protected by IGF-I. Overexpression of a kinase-defective receptor which contained a mutation in the ATP binding loop functioned as a dominant negative and sensitized cells to apoptosis. The antiapoptotic capacity of the IGF-I receptor was not shared by other growth factors tested, including epidermal growth factor (EGF) and thrombin, although the cells expressed functional receptors for all the agonists. However, EGF was antiapoptotic for cells overexpressing the EGF receptor, and expression of activated pp60v-src also was protective. There was no correlation between protection from apoptosis and activation of mitogen-activated protein kinase, p38/HOG1, or p70S6 kinase. On the other hand, protection by any of the tyrosine kinases against UV-induced apoptosis was blocked by wortmannin, implying a role for phosphatidylinositol 3-kinase (PI3 kinase). To test this, we transiently expressed constitutively active or kinase-dead PI3 kinase and found that overexpression of activated phosphatidylinositol 3-kinase (PI3 kinase) was sufficient to provide protection against apoptosis. Because Akt/PKB is believed to be a downstream effector for PI3 kinase, we also examined the role of this serine/threonine protein kinase in antiapoptotic signalling. We found that membrane-targeted Akt was sufficient to protect against apoptosis but that kinase-dead Akt was not. We conclude that the endogenous IGF-I receptor has a specific antiapoptotic signalling capacity, that overexpression of other tyrosine kinases can allow them also to be antiapoptotic, and that activation of PI3 kinase and Akt is sufficient for antiapoptotic signalling.

Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin

Abstract: The immunosuppressant rapamycin interferes with G1-phase progression in lymphoid and other cell types by inhibiting the function of the mammalian target of rapamycin (mTOR). mTOR was determined to be a terminal kinase in a signaling pathway that couples mitogenic stimulation to the phosphorylation of the eukaryotic initiation factor (eIF)-4E-binding protein, PHAS-I. The rapamycin-sensitive protein kinase activity of mTOR was required for phosphorylation of PHAS-I in insulin-stimulated human embryonic kidney cells. mTOR phosphorylated PHAS-I on serine and threonine residues in vitro, and these modifications inhibited the binding of PHAS-I to eIF-4E. These studies define a role for mTOR in translational control and offer further insights into the mechanism whereby rapamycin inhibits G1-phase progression in mammalian cells.

Customer contributions and roles in service delivery

Abstract: Focuses on the roles of customers in creating quality and productivity in service experiences. Presents two conceptual frameworks to aid managerial understanding and focus research efforts on customer participation. The first framework captures levels of customer participation across different types of services. The second discusses three major roles of customers in the service delivery process. Two examples of the concepts are presented ‐ one in a weight loss context and the other in a mammography screening setting. Both are based on empirical research and illustrate specific applications of customers’ roles in creating the service experience.

Exchange Rate Exposure, Hedging, and the Use of Foreign Currency Derivatives

Abstract: We examine whether firms use foreign currency derivatives for hedging or for speculative purposes. Using the sample of all SP the use of derivatives significantly reduces the exchange-rate risk firms face. We also find that the decision to use derivatives depends on exposure factors (i.e. foreign sales and foreign trade) and on variables largely associated with theories of optimal hedging (i.e., size and R&D expenditures), and that the level of derivatives used depends only on a firm's exposure through foreign sales and trade.

The Legion vision of a worldwide virtual computer

Abstract: of a Worldwide Virtual Computer Long a vision of science fiction writers and distributed systems researchers, the notion of a worldwide computer, now taking shape through the Legion project, distributes computation like the World-Wide Web distributes multimedia, creating the illusion for users of a very, very powerful desktop computer. T ODAY’S DRAMATIC INCREASE IN AVAILABLE NETWORK BANDWIDTH WILL qualitatively change how the world computes, communicates, and collaborates. The rapid expansion of the World-Wide Web and the changes it has wrought are just the beginning. As high-bandwidth connections become available, they shrink distances and change our modes of computation, storage, and interaction. Inevitably, users will operate in a wide-area environment transparently consisting of workstations, PCs, graphics-rendering engines, supercomputers, and nontraditional computing devices, such as televisions. The relative physical locations of users and their resources is increasingly irrelevant. Realization of such an environment, sometimes called a “metasystem,” is not without problems. Today’s experimental high-speed networks, such as the Very

Severe reduction in leukocyte adhesion and monocyte extravasation in mice deficient in CC chemokine receptor 2

Abstract: CC chemokine receptor 2 (CCR2) is a prominent receptor for the monocyte chemoattractant protein (MCP) group of CC chemokines. Mice generated by gene targeting to lack CCR2 exhibit normal leukocyte rolling but have a pronounced defect in MCP-1-induced leukocyte firm adhesion to microvascular endothelium and reduced leukocyte extravasation. Constitutive macrophage trafficking into the peritoneal cavity was not significantly different between CCR2-deficient and wild-type mice. However, after intraperitoneal thioglycollate injection, the number of peritoneal macrophages in CCR2-deficient mice did not rise above basal levels, whereas in wild-type mice the number of macrophages at 36 h was ≈3.5 times the basal level. The CCR2-deficient mice showed enhanced early accumulation and delayed clearance of neutrophils and eosinophils. However, by 5 days neutrophils and eosinophils in both CCR2-deficient and wild-type mice had returned to near basal levels, indicating that resolution of this inflammatory response can occur in the absence of macrophage influx and CCR2-mediated activation of the resident peritoneal macrophages. After intravenous injection with yeast β-glucan, wild-type mice formed numerous large, well-defined granulomas throughout the liver parenchyma, whereas CCR2-deficient mice had much fewer and smaller granulomas. These results demonstrate that CCR2 is a major regulator of induced macrophage trafficking in vivo.

A Cross-National Comparative Study of New Product Development Processes: Japan and the United States:

Abstract: Drawing on the marketing and management literatures, the authors identify strategic, tactical, and environmental factors that influence the commercial success of new products. They test the resulti...

Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenzavirus infections

Abstract: Background: The sialic acid analogue zanamivir (GG167) is a selective inhibitor of influenza A and B virus neuraminidases. These viral enzymes are essential for the release of virus from infected cells, and they may also reduce the inactivation of virus by respiratory secretions. When administered experimentally directly to the respiratory tract, zanamivir has potent antiviral effects. We assessed the therapeutic activity of zanamivir in adults with acute influenza. Methods: We conducted separate randomized, double-blind studies in 38 centers in North America and 32 centers in Europe during the influenza season of 1994-1995. A total of 417 adults with influenza-like illness of 448 hours duration were randomly assigned to one of three treatments: 6.4 mg of zanamivir by intranasal spray plus 10 mg by inhalation, 10 mg of zanamivir by inhalation plus placebo spray, or placebo by both routes. Treatments were self-administered twice daily for five days. Results: Of 262 patients with confirmed influenza-virus infection (63 percent of all patients), the median length of time to the alleviation of all major symptoms was one day shorter (four days vs. five days) in the 88 patients given inhaled and intranasal zanamivir (P=0.02) and the 85 patients given inhaled zanamivir alone (P=0.05) than in the 89 patients given placebo. Among the infected patients who were febrile at enrollment and among those who began treatment within 30 hours after the onset of symptoms, the median time to the alleviation of major symptoms was four days in both zanamivir groups and seven days in the placebo group (P≤0.01). Viral titers of nasal washings in the group given inhaled and intranasal zanamivir were significantly lower than those in the placebo group. The topically administered zanamivir was well tolerated. Conclusions: In adults with influenza A or B virus infections, direct administration of a selective neuraminidase inhibitor, zanamivir, to the respiratory tract is safe and reduces symptoms if begun early.

Infrared spectroscopy of proteins and peptides in lipid bilayers

Abstract: Infrared spectroscopy is a useful technique for the determination of conformation and orientation of membrane-associated proteins and lipids. The technique is especially powerful for detecting conformational changes by recording spectral differences before and after perturbations in physiological solution. Polarized infrared measurements on oriented membrane samples have revealed valuable information on the orientation of chemical groupings and substructures within membrane molecules which is difficult to obtain by other methods. The application of infrared spectroscopy to the static and dynamic structure of proteins and peptides in lipid bilayers is reviewed with some emphasis on the importance of sample preparation. Limitations of the technique with regard to the absolute determination of secondary structure and orientation and new strategies for structural assignments are also discussed.

Traffic flow forecasting: comparison of modeling approaches

Abstract: The capability to forecast traffic volume in an operational setting has been identified as a critical need for intelligent transportation systems (ITS). In particular, traffic volume forecasts will support proactive, dynamic traffic control. However, previous attempts to develop traffic volume forecasting models have met with limited success. This research effort focused on developing traffic volume forecasting models for two sites on Northern Virginia's Capital Beltway. Four models were developed and tested for the freeway traffic flow forecasting problem, which is defined as estimating traffic flow 15 minutes into the future. They were the historical average, time-series, neural network, and nonparametric regression models. The nonparametric regression model significantly outperformed the other models. A Wilcoxon signed-rank test revealed that the nonparametric regression model was easy to implement, and proved to be portable, performing well at two distinct sties. Based on its success, research is ongoing to refine the nonparametric regression model and to extend it to produce multiple interval forecasts.

The Esophagogastric Junction

Abstract: The lower esophageal sphincter regulates the flow of food between the esophagus and the stomach. It is now clear that both the intrinsic smooth muscle of the distal esophagus and the skeletal muscle of the crural diaphragm constitute the sphincter mechanism at the lower end of the esophagus.1 Furthermore, in normal subjects and patients with reflux esophagitis, transient relaxation of both sphincters rather than diminished lower esophageal sphincter pressure is the major mechanism of gastroesophageal reflux.2 In this article we review the current understanding of the physiology of the sphincter mechanism at the esophagogastric junction and its relation to esophageal . . .

The Determinants of Japanese New Product Successes

Abstract: The authors report the results from a three-year study of new product development practices in Japanese firms. They develop a causal model of factors correlated with new product success. They test ...

Genetic determinants of susceptibility to excitotoxic cell death: implications for gene targeting approaches.

Abstract: Recent studies have sought to identify the genes involved in excitotoxic neurodegeneration. Here we report that certain strains of mice, including strains that are used for gene targeting studies, do not exhibit excitotoxic cell death after kainic acid seizures. Kainic acid produced excitotoxic cell death in the CA3 and CA1 subfields of the hippocampus in 129/SvEMS and FVB/N mice, in the same pattern as described in rats. C57BL/6 and BALB/c mice exhibited excitotoxic cell death only at very high doses of kainate, and then only in a very restricted area, although they exhibited comparable seizures. Hybrids of 129/SvEMS × C57BL/6 mice created using embryonic stem cells from 129/SvEMS mice also did not exhibit excitotoxic cell death. These results demonstrate that C57BL/6 and BALB/c strains carry gene(s) that convey protection from glutamate-induced excitotoxicity. This differential susceptibility to excitotoxicity represents a potential complication for gene targeting studies.

Decompressive bifrontal craniectomy in the treatment of severe refractory posttraumatic cerebral edema.

Abstract: Objective The management of malignant posttraumatic cerebral edema remains a frustrating endeavor for the neurosurgeon and the intensivist. Mortality and morbidity rates remain high despite refinements in medical and pharmacological means of controlling elevated intracranial pressure; therefore, a comparison of medical management versus decompressive craniectomy in the management of malignant posttraumatic cerebral edema was undertaken. Methods At the University of Virginia Health Sciences Center, 35 bifrontal decompressive craniectomies were performed on patients suffering from malignant posttraumatic cerebral edema. A control population was formed of patients whose data was accrued in the Traumatic Coma Data Bank. Patients who had undergone surgery were matched with one to four control patients based on sex, age, preoperative Glasgow Coma Scale scores, and maximum preoperative intracranial pressure (ICP). Results The overall rate of good recovery and moderate disability for the patients who underwent craniectomies was 37% (13 of 35 patients), whereas the mortality rate was 23% (8 of 35 patients). Pediatric patients had a higher rate of favorable outcome (44%, 8 of 18 patients) than did adult patients. Postoperative ICP was lower than preoperative ICP in patients who underwent decompression (P = 0.0003). Postoperative ICP was lower in patients who underwent surgery than late measurements of ICP in the matched control population. A statistically significant increased rate of favorable outcomes was seen in the patients who underwent surgery compared to the matched control patients (15.4%) (P = 0.014). All patients who exhibited sustained ICP values above 40 torr and those who underwent surgery more than 48 hours after the time of injury did poorly. Evaluation of the 20 patients who did not fit into either of those categories revealed a 60% rate of favorable outcome and a statistical advantage over control patients (P = 0.0001). Conclusion Decompressive bifrontal craniectomy provides a statistical advantage over medical treatment of intractable posttraumatic cerebral hypertension and should be considered in the management of malignant posttraumatic cerebral swelling. If the operation can be accomplished before the ICP value exceeds 40 torr for a sustained period and within 48 hours of the time of injury, the potential to influence outcome is greatest.

The subtype 2 (AT2) angiotensin receptor mediates renal production of nitric oxide in conscious rats.

Abstract: The angiotensin AT2 receptor modulates renal production of cyclic guanosine 3',5'-monophosphate (cGMP; J. Clin. Invest. 1996. 97:1978-1982). In the present study, we hypothesized that angiotensin II (Ang II) acts at the AT2 receptor to stimulate renal production of nitric oxide leading to the previously observed increase in cGMP. Using a microdialysis technique, we monitored changes in renal interstitial fluid (RIF) cGMP in response to intravenous infusion of the AT2 receptor antagonist PD 123319 (PD), the AT1 receptor antagonist Losartan, the nitric oxide synthase (NOS) inhibitor nitro--arginine-methyl-ester (-NAME), the specific neural NOS inhibitor 7-nitroindazole (7-NI), or Ang II individually or combined in conscious rats during low or normal sodium balance. Sodium depletion significantly increased RIF cGMP. During sodium depletion, both PD and -NAME caused a similar decrease in RIF cGMP. Combined administration of PD and -NAME decreased RIF cGMP to levels observed with PD or -NAME alone or during normal sodium intake. During normal sodium intake, Ang II caused a twofold increase in RIF cGMP. Neither PD nor -NAME, individually or combined, changed RIF cGMP. Combined administration of Ang II and either PD or -NAME produced a significant decrease in RIF cGMP compared with that induced by Ang II alone. Combined administration of Ang II, PD, and -NAME blocked the increase in RIF cGMP produced by Ang II alone. During sodium depletion, 7-NI decreased RIF cGMP, but the reduction of cGMP in response to PD alone or PD combined with 7-NI was greater than with 7-NI alone. During normal sodium intake, 7-NI blocked the Ang II-induced increase in RIF cGMP. PD alone or combined with 7-NI produced a greater inhibition of cGMP than did 7-NI alone. During sodium depletion, 7-NI (partially) and -NAME (completely) inhibited RIF cGMP responses to -arginine. These data demonstrate that activation of the renin- angiotensin system during sodium depletion increases renal nitric oxide production through stimulation by Ang II at the angiotensin AT2 receptor. This response is partially mediated by neural NOS, but other NOS isoforms also contribute to nitric oxide production by this pathway.

Isotopic evidence for extraterrestrial non- racemic amino acids in the Murchison meteorite

Abstract: Many amino acids contain an asymmetric centre, occurring as laevorotatory, L, or dextrorotatory, D, compounds. It is generally assumed that abiotic synthesis of amino acids on the early Earth resulted in racemic mixtures (L- and D-enantiomers in equal abundance). But the origin of life required, owing to conformational constraints, the almost exclusive selection of either L- or D-enantiomers, and the question of why living systems on the Earth consist of L-enantiomers rather than D-enantiomers is unresolved. A substantial fraction of the organic compounds on the early Earth may have been derived from comet and meteorite impacts. It has been reported previously that amino acids in the Murchison meteorite exhibit an excess of L-enantiomers, raising the possibility that a similar excess was present in the initial inventory of organic compounds on the Earth. The stable carbon isotope compositions of individual amino acids in Murchison support an extraterrestrial origin -- rather than a terrestrial overprint of biological amino acids-although reservations have persisted. Here we show that individual amino-acid enantiomers from Murchison are enriched in 15N relative to their terrestrial counterparts, so confirming an extraterrestrial source for an L-enantiomer excess in the Solar System that may predate the origin of life on the Earth.

Did Unilateral Divorce Raise Divorce Rates? Evidence from Panel Data

Abstract: This paper revisits the evidence on the impact of unilateral divorce laws on divorce rates in the United States. Most states switched from requiring mutual consent to allowing unilateral or no-fault divorce between 1970 and 1985, while the national divorce rate more than doubled after 1965. According to the Coase theorem, however, the legal shift should have had no effect on divorce rates. Recent papers using cross-sectional micro data have disputed the empirical importance of unilateral divorce, disagreeing in particular about controls for state-level heterogeneity in divorce propensities. This paper uses a panel of state-level divorce rates which includes virtually every divorce in the U.S. over the entire period of the law changes. Adding comprehensive controls ? year and state fixed effects and state fixed trends ? for changing unobservable divorce propensities reveals that the divorce rate would have been about 6% lower if states had not switched to unilateral divorce, accounting for 17% of the increase in the divorce rate between 1968 and 1988. Additional results in this paper demonstrate that the type of unilateral divorce law that states adopted matters. Weaker versions of unilateral divorce, which retain elements of mutual divorce, raised the divorce rate significantly, but by less than the strongest versions of unilateral divorce did.

Patient Preferences for Communication with Physicians about End-of-Life Decisions

Abstract: Background: Physicians are frequently unaware of patient preferences for end-of-life care. Identifying and exploring barriers to patient–physician communication about end-of-life issues may help gu...

Image plane interaction techniques in 3D immersive environments

Abstract: This paper presents a set of interaction techniques for use in headtracked immersive virtual environments. With these techniques, the user interacts with the 2D projections that 3D objects in the scene make on his image plane. The desktop analog is the use of a mouse to interact with objects in a 3D scene based on their projections on the monitor screen. Participants in an immersive environment can use the techniques we discuss for object selection, object manipulation, and user navigation in virtual environments. CR Categories and Subject Descriptors: 1.3.6 [Computer Graphics]: Methodology and Techniques - InteractionTechniques; 1.3.7 [Computer Graphics]: Three-Dimensional Graphics and Realism - VirtualReality. Additional Keywords: virtual worlds, virtual environments, navigation, selection, manipulation.