cssi/SciSciGPT-SciSciNet huggingface dataset:
Bioinformatic and Reactivity-Based Discovery of Linaridins

Abstract Linaridins are members of the ribosomally synthesized and post-translationally modified peptide (RiPP) family of natural products. Five linaridins have been reported, which are defined by the presence of dehydrobutyrine, a dehydrated threonine residue. This work describes the development of a linaridin specific scoring module for Rapid ORF Description and Evaluation Online (RODEO), a genome-mining tool tailored towards RiPP discovery. Upon mining publicly accessible genomes available in the NCBI database, RODEO identified 561 (382 non-redundant) linaridin biosynthetic gene clusters (BGCs). Linaridin BGCs with unique gene architectures and precursor sequences markedly different from previous predictions were uncovered during these efforts. To aid in dataset validation, two new linaridins, pegvadin A and B, were detected through reactivity-based screening (RBS) and isolated from Streptomyces noursei and Streptomyces auratus, respectively. RBS involves the use of a reactive chemical probe that chemoselectively modifies a functional group present in the natural product. The dehydrated amino acids present in linaridins as α/β-unsaturated carbonyls were appropriate electrophiles for nucleophilic 1,4 addition using a thiol-functionalized probe. The data presented within significantly expands the number of predicted linaridin BGCs and serves as a road map for future work in the area. The combination of bioinformatics and RBS is a powerful approach to accelerate natural product discovery.
Self-care perspective taking and empathy in a student-faculty book club in the United States

PURPOSE We aimed to study the impact of a combined faculty-student book club on education and medical practice as a part of the informal curriculum at the University of Florida College of Medicine in the United States. METHODS Sixteen medical students and 7 faculties who participated in the book club were interviewed through phone and recorded. The interview was then transcribed and entered into the qualitative data analysis program QSR NVivo (QSR International, Burlington, MA, USA). The transcripts were reviewed, and thematic codes were developed inductively through collaborative iteration. Based on these preliminary codes, a coding dictionary was developed and applied to all interviews within QSR Nvivo to identify themes. RESULTS Four main themes were identified from interviews: The first theme, the importance of literature to the development and maintenance of empathy and perspective-taking, and the second theme, the importance of the book club in promoting mentorship, personal relationships and professional development, were important to both student and faculty participants. The third and fourth themes, the need for the book club as a tool for self-care and the book club serving as a reminder about the world outside of school were discussed by student book club members. CONCLUSION Our study demonstrated that an informal book club has a significant positive impact on self-care, perspective-taking, empathy, and developing a “world outside of school” for medical school students and faculty in the United States. It also helps to foster meaningful relationships between students and faculty.
Highly Optimized Montgomery Multiplier for SIKE Primes on FPGA

New primes were proposed for Supersingular Isogeny Key Encapsulation (SIKE) in NIST standardization process of Round 2 after further cryptanalysis research showed that the security levels of the initial primes chosen were over-estimated [1], [2]. In this paper, we develop a highly optimized $\mathbb{F}_p$ Montgomery multiplication algorithm and architecture that further utilizes the special form of SIKE prime compared to previous implementations available in the literature. We then implement SIKE for all Round 2 NIST security levels (SIKEp434 for NIST security level 1, SIKEp503 for NIST security level 2, SIKEp610 for NIST security level 3, and SIKEp751 for NIST security level 5) on Xilinx Virtex 7 using the proposed multiplier. Our best implementation (NIST security level 1) runs 29% faster and occupies 30% less hardware resources in comparison to the leading counterpart available in the literature [3] and implementations for other security levels achieved similar improvement.
Calcium metaborate induced thin walled carbon nanotube syntheses from CO2 by molten carbonate electrolysis.

An electrosynthesis is presented to transform the greenhouse gas CO2 into an unusually thin walled, smaller diameter morphology of Carbon Nanotubes (CNTs). The transformation occurs at high yield and coulombic efficiency of the 4-electron CO2 reduction in a molten carbonate electrolyte. The electrosynthesis is driven by an unexpected synergy between calcium and metaborate. In a pure molten lithium carbonate electrolyte, thicker walled CNTs (100-160 nm diameter) are synthesized during a 4 h CO2 electrolysis at 0.1 A cm-2. At this low current density, CO2 without pre-concentration is directly absorbed by the air (direct air capture) to renew and sustain the carbonate electrolyte. The addition of 2 wt% Li2O to the electrolyte produces thinner, highly uniform (50-80 nm diameter) walled CNTs, consisting of ~ 75 concentric, cylindrical graphene walls. The product is produced at high yield (the cathode product consists of > 98% CNTs). It had previously been demonstrated that the addition of 5-10 wt% lithium metaborate to the lithium carbonate electrolyte boron dopes the CNTs increasing their electrical conductivity tenfold, and that the addition of calcium carbonate to a molten lithium carbonate supports the electrosynthesis of thinner walled CNTs, but at low yield (only ~ 15% of the product are CNTs). Here it is shown that the same electrolysis conditions, but with the addition of 7.7 wt% calcium metaborate to lithium carbonate, produces unusually thin walled CNTs uniform (22-42 nm diameter) CNTs consisting of ~ 25 concentric, cylindrical graphene walls at a high yield of > 90% CNTs.
Kinetics of 2-methylfuran acylation with fatty acid anhydrides for biorenewable surfactants

Friedel-Crafts acylation using long-chain fatty acid derivatives and biomass-derived furans is the key reaction to produce "alkyl furan ketones", an important precursor for biorenewable oleo-furan surfactants. In this work, the steady-state acylation kinetics and reaction mechanism were investigated using a model system of 2-methylfuran and n-octanoic anhydride in a fixed-bed tubular reactor using Al-MCM-41, a mesoporous aluminosilicate. An apparent activation energy (15.5 +or- 1.4 kcal mol- 1) was obtained for the formation of the acylated product, 2-octanoyl-5-methylfuran (2O5MF), for a temperature range of 348-408 K. The apparent reaction rate orders were ~0.6 and ~0.5 in the 2-methylfuran and anhydride concentrations, respectively, while near-zero apparent rate orders were measured in the product concentrations, indicating negligible product inhibition. An Eley-Rideal catalytic acylation mechanism was proposed to explain the experimentally observed apparent rate orders.
Freeway Network Travel Time Reliability Analysis Methodology and Software Tool Development

Applications in the field often require analysis of freeway travel time reliability (TTR) at the network level. While micro-simulation is suitable for performing network-level analysis, the computa...
Membrane Glycoproteins of Enveloped Viruses.

Publisher Summary This chapter focuses on the recent information of the glycoprotein components of enveloped viruses and points out specific findings on viral envelopes. Although enveloped viruses of different major groups vary in size and shape, as well as in the molecular weight of their structural polypeptides, there are general similarities in the types of polypeptide components present in virions. The types of structural components found in viral membranes are summarized briefly in the chapter. All the enveloped viruses studied to date possess one or more glycoprotein species and lipid as a major structural component. The presence of carbohydrate covalently linked to proteins is demonstrated by the incorporation of a radioactive precursor, such as glucosamine or fucose, into viral polypeptides, which is resolved by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis. Enveloped viruses share many common features in the organization of their structural components, as indicated by several approaches, including electron microscopy, surface-labeling, and proteolytic digestion experiments, and the isolation of subviral components. The chapter summarizes the detailed structure of the glycoproteins of four virus groups: (1) influenza virus glycoproteins, (2) rhabdovirus G protein, (3) togavirus glycoprotein, and (4) paramyxovirus glycoproteins The information obtained includes the size and shape of viral glycoproteins, the number of polypeptide chains in the complete glycoprotein structure, and compositional data on the polypeptide and oligosaccharide portions of the molecules.
An Optimal Control Formulation of Large-Scale Multiclass Machine Scheduling Problems

We consider a broad class of machine scheduling problems that arise in a spatial setting. Machines, which might be drivers and crews, or equipment such as trucks, locomotives or aircraft, need to be assigned to a sequence of jobs over time and space. In practice, the data is often changing in real-time, and schedulers need a rapid, on-line scheduling system to assign machines to jobs. Since there is often local data available to the scheduler that may not be known to the machine, it is often more important to present a set of ranked options to the scheduler than it is to develop the “optimal” solution. In this paper, we use a linearization approximation to develop a control strategy that provides on-line control information, drawing on a concept from work in fleet management called a istics queueing network
Bruton’s Tyrosine Kinase Is Required for TLR-Induced IL-10 Production

Bruton's tyrosine kinase (Btk) is a critical signaling mediator downstream of the B cell Ag receptor. X-linked agammaglobulinemia is caused by mutations in Btk resulting in multiple defects in B cell development and function, and recurrent bacterial infections. Recent evidence has also supported a role for Btk in TLR signaling. We demonstrate that Btk is activated by TLR4 in primary macrophages and is required for normal TLR-induced IL-10 production in multiple macrophage populations. Btk-deficient bone marrow-derived macrophages secrete decreased levels of IL-10 in response to multiple TLR ligands, compared with wild-type (WT) cells. Similarly, Btk-deficient peritoneal and splenic macrophages secrete decreased IL-10 levels compared with WT cultures. This phenotype correlates with Btk-dependent induction of NF-kappaB and AP-1 DNA binding activity, and altered commensal bacteria populations. Decreased IL-10 production may be responsible for increased IL-6 because blocking IL-10 in WT cultures increased IL-6 production, and supplementation of IL-10 to Btk-deficient cultures decreased IL-6 production. Similarly, injection of IL-10 in vivo with LPS decreases the elevated IL-6 serum levels during endotoxemia in Btk-deficient mice. These data further support a role for Btk in regulating TLR-induced cytokine production from APCs and provide downstream targets for analysis of Btk function.
Load balancing and almost symmetries for RAMBO quorum hosting

RAMBO is the Reconfigurable Atomic Memory for Basic Objects, a formally specified algorithm that implements atomic read/write shared memory in dynamic networks, where the participating hosts may join, leave, or fail. To maintain availability and consistency in such dynamic settings, RAMBO replicates objects and uses quorum systems that can be reconfigured in response to perturbations in the environment. This is accomplished by installing new quorum configurations and removing obsolete configurations, while preserving data consistency. Given the dynamic nature of the atomic memory service, it is vitally important to reconfigure the system online, while making well-reasoned selections of new quorum configurations. This paper reexamines the quorum hosting problem, concentrating on better load balancing models and a novel use of almost symmetries for breaking similarities among hosts in the target network. The resultant performance improvements allow more reasonably-sized systems to be reconfigured online in a way that optimizes hosting of quorums with respect to relevant performance criteria.
Physiological effects of focused ultrasound pulses on mammalian CNS tissue in an in-vitro preparation

We have investigated the effects of pulsed and highly focused ultrasound on the physiology of 500 micron thick hippocampal slices obtained from 50 male, 120 gram Sprague-Dawley rats. During the study the slices were kept alive in a special in-vitro preparation. We compared the magnitude and latency of the control evoked responses to those of the responses recorded during ultrasound irradiation. Comparisons were made for both the orthodromic and antidromic population responses. For all studies, a highly focused pulsed ultrasonic beam was used with a center frequency of 5 MHz and an intensity (SPTA) of 52 W/cm 2. Significant changes in both the magnitude and the stimulus-response delay were observed. Full recovery was observed when the ultrasound was removed. In addition, temperature effects could be rejected as the sole mechanism producing such changes
Photopolymerizable degradable polyanhydrides with osteocompatibility

We have developed a new family of photopolymerizable, methacrylated anhydride monomers and oligomers that combine high strength, controlled degradation, and photoprocessibility in a singular system. Networks with degradation times ranging from 1 week to nearly 1 year and that retain up to 90% of their tensile modulus at 40% mass loss are attainable. In vivo studies in rats have shown that these networks possess excellent osteocompatibility. These combined properties could offer many advantages in medical applications ranging from dentistry to orthopedics.
Deontological And Teleological Influences On Marketing Research Ethics

Using factorially designed marketing research scenarios this study investigates the influence of deontological and two teleological factors on marketing professionals' (1) ethics judgment and (2) decision to either reward or punish an ethical/unethical research behavior. The results indicate that marketing professionals make research ethics judgment based on deontological considerations (the inherent rightness or wrongness of a researcher's behavior). However, their decisions to either reward or discipline ethical/unethical research behaviors are guided primarily by ethical judgment and only marginally by teleological considerations (the consequences of behaviors on the organization). Implications of results for marketing research ethics and some directions for future research are discussed.
Comparison of Monkeypox Virus Clade Kinetics and Pathology within the Prairie Dog Animal Model Using a Serial Sacrifice Study Design

Monkeypox virus (MPXV) infection of the prairie dog is valuable to studying systemic orthopoxvirus disease. To further characterize differences in MPXV clade pathogenesis, groups of prairie dogs were intranasally infected (8 × 10(3) p.f.u.) with Congo Basin (CB) or West African (WA) MPXV, and 28 tissues were harvested on days 2, 4, 6, 9, 12, 17, and 24 postinfection. Samples were evaluated for the presence of virus and gross and microscopic lesions. Virus was recovered from nasal mucosa, oropharyngeal lymph nodes, and spleen earlier in CB challenged animals (day 4) than WA challenged animals (day 6). For both groups, primary viremia (indicated by viral DNA) was seen on days 6-9 through day 17. CB MPXV spread more rapidly, accumulated to greater levels, and caused greater morbidity in animals compared to WA MPXV. Histopathology and immunohistochemistry (IHC) findings, however, were similar. Two animals that succumbed to disease demonstrated abundant viral antigen in all organs tested, except for brain. Dual-IHC staining of select liver and spleen sections showed that apoptotic cells (identified by TUNEL) tended to colocalize with poxvirus antigen. Interestingly splenocytes were labelled positive for apoptosis more often than hepatocytes in both MPXV groups. These findings allow for further characterization of differences between MPXV clade pathogenesis, including identifying sites that are important during early viral replication and cellular response to viral infection.
SILK: Higher Level Rules with Defaults and Semantic Scalability

We overview the technical approach and motivations of the SILK system for semantic rules and ontologies, that radically extends the knowledge representation (KR) power of currently commercially important business rule systems, including not only Prologs but also production rules and event-condition-action rules, database systems, and semantic web.
Synthesis and release of hyaluronic acid by Swiss 3T3 fibroblasts

Hyaluronic acid (HA) and its synthesis were studied in intact Swiss 3T3 mouse fibroblasts and isolated membranes. HA chains in culture medium, attached to cells and in isolated membranes, were determined to possess average M(r) values of 5.2 x 10(6), 1.8 x 10(6) and 0.14 x 10(6) respectively. Log cells were determined to possess 680,000 HA molecules/cell, and to release 120,000 HA chains/h. The time required for intact cells to synthesize and release a complete HA chain was approximately 4 h, with elongation proceeding at a rate of 57 dimers/min. The amount of cell-associated HA of various cell populations correlated strongly with their rate of HA release into culture media and with the HA synthetase activity determined for their membranes. Prevention of protein synthesis with cycloheximide decreased the rate of HA synthesis of log cells and HA synthetase activity of isolated membranes by 50% within 2-3 h. Because of the similarity between the biological lifetime of HA synthetase and the time required to synthesize a HA chain, we propose a model where each synthetase makes only one HA chain; after synthesis of a complete HA chain, HA synthetase activity is terminated as its HA chain is released from the cell.
A role for postsynaptic neurons in determining presynaptic release properties in the cricket CNS: evidence for retrograde control of facilitation

Intracellular recording sin the cricket cercal system show that the synaptic terminals of a single sensory neuron can facilitate at one target, the medial giant interneuron (MGI), and simultaneously depress at another target, interneuron 10–3. A quantal analysis of transmission at these synapses demonstrates that facilitation and depression are properties of the presynaptic cell. For facilitating synapses contacting MGI, the mean quantal content (m), determined from the probability of the failures, increases for the second EPSP, while the quantal size (q) remains constant. Similarly, an analysis of depression for those synapses contacting 10–3 supports a presynaptic mechanism for depression. Since facilitation and depression are presynaptic and their expression at the synapses of a single, identified sensory neuron are correlated with the target interneuron, we conclude that these properties are regulated locally, at the synapse, possibly by an interaction with the postsynaptic cell.
Linux administration: K-12 special session

Linux is an incredibly popular and powerful operating system, originally developed by Linus Torvalds, in 1991, as an alternative to UNIX. Linux is particularly noted for its a) stability and robustness (some of the largest companies in the world rely on it) b) openness (its complete source code is freely available) c) performance, including its ability to run well on low-end computer hardware d) cost: Linux, and many if not most of its applications, can be downloaded and installed for free, under the GNU General Public License.
Coping with Degeneracies in Delaunay Triangulation

Degeneracy is a serious issue in geometry. In their original form, many geometric algorithms simply assume that there is no degeneracy. As a result, when these methods arc used on data that is degenerate or nearly degenerate, they either fail to complete or else give nonsensical results.
Comparative Studies of Microtubule Mechanics with Two Competing Models Suggest Functional Roles of Alternative Tubulin Lateral Interactions

The dynamic assembly and disassembly of microtubules and the mechanical properties of these polymers are essential for many key cellular processes. Mathematical and computational modeling, especially coupled mechanochemical modeling, has contributed significantly to our understanding of microtubule dynamics. However, critical discrepancies exist between experimental observations and modeling results that need to be resolved before further progress toward a complete model can be made. Open sheet structures ranging in length from several hundred nanometers to one micron have often been observed at the growing ends of microtubules in in vitro studies. Existing modeling studies predict these sheet structures to be short and rare intermediates of microtubule disassembly rather than important components of the assembly process. Atomic force microscopy (AFM) studies also reveal interesting step-like gaps of the force-indentation curve that cannot yet be explained by existing theoretical models. We have carried out computational studies to compare the mechanical properties of two alternative models: a more conventional model where tubulin dimers are added directly into a microtubule lattice, and one that considers an additional type of tubulin lateral interaction proposed to exist in intermediate sheet structures during the microtubule assembly process. The first model involves a single type of lateral interactions between tubulin subunits, whereas the latter considers a second type that can convert to the canonical lateral contact during microtubule closure into a cylinder. Our analysis shows that only the second model can reproduce the AFM results over a broad parameter range. We propose additional studies using different sizes of AFM tips that would allow to unambiguously distinguish the relative validity of the two models.
Isolation and characterization of pyruvate carboxylase from Azotobacter vinelandii OP

Abstract Pyruvate carboxylase has been detected in, and partially purified from, cell-free extracts of Azotobacter vinelandii OP. The best preparations obtained have specific activities in the range of 4 units/mg and appear approximately 15% pure when analyzed by polyacrylamide gel electrophoresis. The partially purified enzyme is activated by both univalent and divalent cations, contains one or more functional biotinyl residues, and exhibits apparent Michaelis constants for the substrates (pyruvate, Mg-ATP2−, and HCO3−) which are in the same range as those observed for other pyruvate carboxylases. However, A. vinelandii pyruvate carboxylase is fully active in the absence of added acetyl-coenzyme A and is insensitive to inhibition by dicarboxylic acids such as l -aspartate, l -glutamate, and α-ketoglutarate. The molecular weight of the catalytically active species is obtained as 296,000. The level of pyruvate carboxylase is highest in extracts of A. vinelandii grown on pyruvate or l -lactate as sole carbon source and this level is further enhanced on addition of succinate to the medium. The enzyme is absent from cells grown on succinate and is present at intermediate levels in cells grown on sucrose, glucose, glycerol, or acetate. In contrast, the level of phosphoenolypyruvate carboxylase in these extracts is essentially independent of the carbon source. These data suggest that pyruvate carboxylase in A. vinelandii is induced by pyruvate or some closely related metabolite.
Molecular evolution of the Saccharomyces cerevisiae histone gene loci.

The core histone genes ofSaccharomyces cerevisiae are arranged as duplicate nonallelic sets of specifically paired genes. The identity of structural organization between the duplicated gene pairs would have its simplest evolutionary origin in the duplication of a complete locus in a single event. In such a case, the time since the duplication of one of the genes should be identical to that since duplication of the gene adjacent to it on the chromosome. A calculation of the evolutionary distances between the coding DNA sequences of the histone genes leads to a duplication paradox: The extents of sequence divergence in the silent component of third-base positions for adjacent pairs of genes are not identical. Estimates of the evolutionary distance between the two H3-H4 noncoding intergene DNA sequences are large; the divergence between the two separate sequences is indistinguishable from the divergence between either of the regions and a randomly generated permutation of itself. These results suggest that the duplication event may have occurred much earlier than previously estimated. The potential age of the duplication, and the attractive simplicity of the duplication of both the H3-H4 and the H2A-H2B gene pairs having taken place in a single event, leads to the hypothesis that modern haploidS. cerevisiae may have evolved by diploidization or fusion of two ancient fungi.
Prototyping a distributed information retrieval system that uses statistical ranking

Abstract Centralized systems continue to dominate the information retrieval market, with increased competition from CD-ROM based systems. As more large organizations begin to implement office automation systems, however, many will find that neither of these types of retrieval systems will satisfy their requirements, especially those requirements involving easy integration into other systems and heavy usage by casual end users. A prototype distributed information retrieval system was designed and built using a distributed architecture and using statistical ranking techniques to help provide better service for the end user. The distributed architecture was shown to be a feasible alternative to centralized or CD-ROM information retrieval, and user testing of the ranking methodology showed both widespread user enthusiasm for this retrieval technique and very fast response times (on the order of one second for 300 megabytes of data).
ISOLATING A ROLE FOR NATURAL SELECTION IN SPECIATION: HOST ADAPTATION AND SEXUAL ISOLATION IN NEOCHLAMISUS BEBBIANAE LEAF BEETLES

Muller (1942) and Mayr (1963) hypothesized that natural selection indirectly causes the evolution of reproductive barriers between allopatric populations by causing adaptive genetic divergence that pleiotropically pro- motes prezygotic or postzygotic incompatibility. Under this mechanism, herbivorous insect populations should be more prone to speciate if they are adapting to different host plants, because the evolution of reproductive isolation will be accelerated above the rate promoted by genetic drift and host-independent sources of selection alone. Although the Muller-Mayr hypothesis is widely accepted, little direct evidence has been collected in support of selection's role in allopatric speciation. This paper offers a method for isolating and evaluating the contribution of host plant-related natural selection pressures to the reproductive isolation between allopatric herbivore populations. The host-related selection hypothesis (HRSH) predicts that herbivore populations using different host plants should be more reproductively isolated than those using the same host, other things being equal. Here, I test this hypothesis using Neochlamisus bebbianae, an oligophagous leaf beetle with a geographically variable host range. In each of two sets of experiments (contrast I, contrast II), I compared two beetle populations (Georgia and New York) that use the same host (Acer) in nature and a third population that natively uses a different host (Betula in Oklahoma (CI), Salix in Ontario (CII)). Experiments showed that "different-host" populations were more strongly differentiated in host- use traits (oviposition, host fidelity, feeding response, larval performance) than were "same-host" populations and that each population most readily uses foliage from its native host. As predicted by the HRSH, sexual isolation was also greater between the adaptively divergent different-host populations (from Betula vs. Acer, from Salix vs. Acer) than between the same-host populations (from Acer), which were undifferentiated in host-use traits. Interpreting these results in a historical context provided by mtDNA sequences from test populations indicated: (1) that Acer- and Betula-associated N. bebbianae represent separate sibling species whose causal origins have been lost to history, and whose incomplete sexual isolation is fortified by host-associated ecological and "physiological" isolation; and (2) that incipiently speciating Acer- and Salix-associated populations are more closely related to each other than are the two Acer-associated populations, which is consistent with the HRSH. This study thus illustrates the consequences of host-related selection for both the origin and maintenance of reproductive isolation. More important, it provides evidence that the pleiotropic effects of natural selection promote allopatric speciation.
Nonoperative management of blunt abdominal trauma: The role of sequential diagnostic peritoneal lavage, computed tomography, and angiography

Study objective: To determine the usefulness of sequential nonoperative diagnostic studies in the evaluation and treatment of stable patients after blunt abdominal trauma. Design and setting: Retrospective review of a prospective treatment plan in a large urban Level I trauma center. Participants: Fifty-two patients deemed stable after initial evaluation following blunt abdominal trauma. Interventions: Patients with a positive diagnostic peritoneal lavage for red blood cells underwent abdominal computed tomography (CT) scanning. If CT demonstrates a visceral injury, it was followed by diagnostic angiography. Attempts were made to treat on-going bleeding by transcatheter embolization. Results: Fifteen patients had negative CT scans and were successfully observed. In the other 37 patients, CT identified 17 liver, 16 splenic, and eight kidney injuries; eight extraperitoneal bleeds; and one mesenteric hematoma. Six of these patients were observed. Thirty underwent diagnostic angiograms. Twelve had no active bleeding, and all were observed successfully. Seventeen underwent successful embolization of the bleeding site(s). One had injuries not controllable by embolization and required exploration. Six patients required laparotomy later in their course, but none had intraabdominal bleeding or a missed intestinal injury. Despite being performed after diagnostic peritoneal lavage, CT missed only two injuries. There was one main complication, delayed recognition of a diaphragmatic injury. Three patients died, two from multiple organ failure and one from a pulmonary embolus; none was believed to be related to this technique. With our algorithm, 45 patients (86%) were spared laparotomy. Conclusion: Diagnostic peritoneal lavage and CT are complementary when evaluating blunt abdominal trauma. Diagnostic peritoneal lavage is an effective screening tool. CT may be reserved for stable patients with a positive diagnostic peritoneal lavage to specify the organs injured. Bleeding often may be treated by embolization, limiting the rate of surgery.
Uplift of the Sierra Nevada of California

Gravity and most seismic interpretations agree that the Sierra Nevada is at present isostatically compensated by a crustal root. The most reasonable timing for emplacement of the root was during Mesozoic batholithic intrusions. This is difficult to reconcile with the evidence that major uplift of the mountains occurred in the past 10 m.y. A simple quantitative model for flexural isostasy of an elastic plate before and after breaking resolves this problem and explains the tilt of the Sierra Nevada block and variations in topography along the range. We postulate that cooling and elastic strengthening of the Mesozoic magmatic arc prevented its reaching local isostatic equilibrium during erosion in the Cenozoic. Thus, an overcompensated residual mountain range was held down elastically until Basin and Range extension broke the elastic plate along the Owens Valley and allowed rapid uplift. The Moho density contrast that best models the amplitude of both late Cenozoic uplift and prior topography is slightly larger than seismic and gravity models suggest; this implies that up to 20% of the uplift may be driven by density contrasts in the upper mantle. The idea of overcompensated erosional remnants and their release upon lithospheric faulting has a more general application to “anorogenic” uplift of mountain blocks.
A Formulation of Quantum Theory Based on Two Physical Principles

We demonstrate two points: 1) the formalism of quantum mechanics can be understood simply as a structure for the expression of the physical notion that not all observables can have values simultaneously; 2) the specific uncertainty relations can be derived (rigorously) by combination of the invariance principle with a general uncertainty relation based only on the existence of unspecified pairs of conjugate observables. For this purpose, we present a formulation of quantum mechanics based strictly on the invariance principle and a “weak” statement of the uncertainty principle that asserts only the existence of incompatible (conjugate) observables without specifying which observables are incompatible. We go on to show that the invariance principle can be used to develop the equations of motion of the theory, including the Klein-Gordon and Schrodinger equations.
A model of microvascular oxygen transport in sickle cell disease

Abstract The model of local control of oxygen delivery in the microvasculature developed by H. J. Granger and A. P. Shepherd (1973, Microvasc. Res. 5, 49–72) was extended to describe microcirculatory blood flow in sickle cell disease. Two major characteristics of sickle cell blood were incorporated into the model: (1) an abnormal blood viscosity which is dependent on the degree of hemoglobin oxygen saturation and hematocrit, and (2) a reduced affinity of hemoglobin (Hb) for oxygen. Sickle cell blood viscosity as a function of oxygen saturation and hematocrit was modeled empirically based upon existing data. Alterations in HbO 2 affinity were studied in the model by introducing P 50 as an independent variable. The altered oxygen supply/demand relationship in sickle cell disease was simulated following an increase in tissue metabolic demand and a decrease in arteriolar blood flow. The results were analyzed to evaluate the roles of the various rheological characteristics of sickle cell blood in affecting microcirculatory dynamics and tissue oxygen delivery. It was demonstrated that, within the hematocrit range of 20 to 45%, the elevation of P 50 from 27 to 38 mm Hg in sickle cell blood is adequate to compensate for the diminished O 2 content, despite an elevated blood viscosity, and maintain near normal tissue p O 2 .
ACTH peptides stimulate motor nerve sprouting in development

Abstract Maturational changes at the neuromuscular junction (nmj) of rat neonates were studied using scanning electron microscopy and light microscopy that permitted quantification of muscle fiber diameter, length of nerve terminal branching, end-plate area, and perimeter. Administration of ACTH 4–10 (10 μg/kg s.c. daily from day of birth) stimulated nerve terminal branching, an effect most evident in 14-day-old pups. The trisubstituted derivative of ACTH 4–9 (Org 2766) when administered at 0.01 μg/kg/daily, had a more potent effect, increasing end-plate perimeter and nerve terminal branching at the first postnatal week and markedly increasing only nerve terminal branching at 14 days of age. This is a dose-responsive action since 10 μg/kg/daily severely inhibits nerve sprouting. By 21 days, there were no differences between peptide- and saline-treated neonates. Peptide-induced sprouting was elicited only in the first 2 weeks of postnatal life. This time course corresponds with the critical period for nmj maturation and ceases when polyneuronal innervation of muscle fibers also terminates. It is suggested that ACTH peptides may exert a physiological role on nerve sprouting during development.
Modeling of metamagnetism in metallic-based materials with first-order transitions

Abstract During the past decade, the magnetic properties of metallic-based materials with first-order transitions have been extensively studied, motivated in part by the observation of large magnetocaloric effect (MCE) peaks displayed by these materials near room temperature. These large peaks are believed to be the result of the materials' magnetic properties at the metamagnetic region, characterized by (i) the thermal-induced transition from the ferromagnetic state (FM) to the paramagnetic state (PM) near the Curie temperature (TC) and (ii) the field-induced transition from PM state to FM state above TC. We developed a phenomenological model that utilizes the materials' mixed-state probability function to model the materials' complex hysteretic and properties at metamagnetic region. The approximate probability functions are obtained from the first and second derivatives of the magnetization curve. The probability functions are used to separate the materials' magnetization into a FM state component and a PM state component. The applicability of the model is demonstrated for a metallic-based metamagnetic material, Gd5Si2Ge2 compound, where the modeled behaviors show remarkable agreement with the experimental data at the metamagnetic region and provide new physical insights in this mixed-state region. Specifically, in the region of metamagnetic transition, the PM state component is non-reversible and is a function of the FM state component.
Molecular conformational transition for sugar nucleotides

Optical rotation changes were for the first time observed with sugar nucleotides in urea solution. This change is interpreted as a dissociation of an ordered conformation of sugar nucleotides into a random conformation in solution.
Differential effects of donor and recipient IL28B and DDX58 SNPs on severity of HCV after liver transplantation

Background & Aims IL28B single nucleotide polymorphisms are strongly associated with spontaneous HCV clearance and treatment response in non-transplant populations. A DDX58 single nucleotide polymorphism is associated with the antiviral response of innate lymphocytes. We aimed at evaluating the associations of donor and recipient IL28B (rs12979860 and rs8099917) and DDX58 (rs10813831) genotypes with severity of HCV recurrence after liver transplantation. Methods In a case-control study of 523 liver transplantation recipients with HCV, we matched severe with mild recurrent HCV based on 2-year clinical and histologic follow-up. A total of 440 liver transplantation recipients (severe, n=235; mild, n=205) with recipient DNA and 225 (severe, n=123; mild, n=102) with both recipient and donor DNA were analyzed. Results IL28B [rs12979860, non-CC ( vs . CC) and rs8099917, non-TT ( vs . TT)] in the recipient-only analysis had higher risk of severe recurrent HCV [OR 1.57 and 1.58, p 0.05]. However, for the 225 with donor and recipient DNA, IL28B rs12979860 CC ( vs . non-CC) and rs8099917 TT ( vs . non-TT) and DDX58 rs10813831 non-GG ( vs . GG) were associated with more (not less) severe recurrent HCV. The greatest risk of severe recurrent HCV was for rs12979860 CC donors in non-CC recipients (OR 7.02, p 0.001, vs . non-CC donor/recipient) and for rs8099917 TT donors in non-TT recipients (OR 5.78, p =0.001, vs. non-TT donor/recipient). These associations persisted after controlling for donor age, donor race, and donor risk index. Conclusions IL28B and DDX58 single nucleotide polymorphisms that are favorable when present in the non-transplant setting or in the recipient are unfavorable when present in a donor liver graft.
Uranium nitride as LWR TRISO fuel: Thermodynamic modeling of U–C–N

Abstract TRISO coated particle fuel is envisioned as a next generation replacement for current urania pellet fuel in LWR applications. To obtain adequate fissile loading the kernel of the TRISO particle will likely need to be UN instead of UO2. In support of the necessary development effort for this new fuel system, an assessment of phase regions of interest in the U–C–N system was undertaken as the fuel will be prepared by the carbothermic reduction of the oxide followed by nitriding, will be in equilibrium with carbon within the TRISO particle, and will react with minor actinides and fission products. The phase equilibria and thermochemistry of the U–C–N system is reviewed, including nitrogen pressure measurements above various phase fields. Measurements were used to confirm an ideal solution model of UN and UC adequately represents the UC1−xNx phase. Agreement with the data was significantly improved by effectively adjusting the Gibbs free energy of UN by +12 kJ/mol. This also required adjustment of the value for the sesquinitride by +17 kJ/mol to obtain agreement with phase equilibria. The resultant model together with reported values for other phases in the system was used to generate isothermal sections of the U–C–N phase diagram. Nitrogen partial pressures were also computed for regions of interest.
Inverse Thinking about Double Mutants of Enzymes

The quantitative effect of a second damaging mutation on a mutated enzyme may be additive, partially additive, synergistic, antagonistic, or absent, in the double mutant. Each of these five possible types of interactions has its own mechanistic explanation [Mildvan, A. S., Weber, D. J., and Kuliopulos, A. (1992) Arch. Biochem. Biophys. 294, 327-340]. Additive effects indicate independent functioning of the two residues in the process being studied, such as catalysis (k(cat)) or substrate binding (K(S)). Departures from additivity reflect interaction of the two residues. Thus, partial additivity indicates cooperativity, synergy indicates anticooperativity, and antagonism indicates opposing structural effects of the two mutations. No additional effects represent limiting cases of either partial additivity or antagonism. A significant conceptual simplification is achieved by applying inverse thinking, namely, by using the parameters of the double mutant rather than those of the wild-type enzyme as the reference point. To explain partially additive effects on k(cat), inverse thinking starts with the k(cat) of the double mutant. Restoring only one residue increases k(cat) by the factor A. Restoring only the other residue increases k(cat) by the factor B. Restoring both residues is shown to increase k(cat) by a factor greater than A x B, with the excess directly measuring the cooperativity. Similarly, inverse thinking provides simpler and more intuitive explanations of synergistic and antagonistic effects, as illustrated by specific examples.
Visual search characteristics in mammography: malignant vs. benign breast masses

Mammography screening is the most widely utilized tool to screen for breast cancer. Radiologists read a mammogram using a two-pass strategy where the first pass is guided by salient features of the image (the so-called 'pop-out' elements), and the second pass is a systematic search. It is assumed that most breast masses that are reported by the radiologist are in fact detected during the first pass of this search strategy, and that the second pass is useful for the detection of microcalcification clusters. Furthermore, experiments in other visual domains have shown that observers are attracted faster to incongruous elements in a display than to normal (i.e., more expected) elements. In this sense, it can be argued that benign findings constitute more expected findings, because they encompass a large percentage of all abnormalities found on a mammogram. In this experiment we sought to determine whether the search for malignant masses was indeed faster than the search for benign masses. We also aimed to determine whether the observers' overall visual search behavior was different between benign and malignant cases, not only in terms of how long it took the observers to hit the location of the lesion, but also how long the observers took analyzing the case, how different the distribution of false positive responses were between the two types of cases, etc.
Chronic exposure to a benzodiazepine partial agonist does not alter GABAA receptor function in cultured neurons.

Abstract The benzodiazepine partial agonist Rol6-6028 does not lead to GABA A receptor downregulation in vivo. To assess effects of this compound in vitro, cultured neurons were exposed to Rol6-6028, 1 and 10 μM. GABA-dependent chloride uptake was unaffected at either dose of Rol6-6028 from 2 to 10 days, in contrast to decreased function observed with clonazepam, 1 μM, at 10 days. Ro16-6028 exposure did not alter GABA-independent chloride uptake, total neuronal protein, or cellular protein synthesis.
Mixture diffusion in nanoporous adsorbents: equivalence of Fickian and Maxwell-Stefan approaches.

Nanopore diffusion in multicomponent adsorption is described using different macroscopic theories: Onsager irreversible thermodynamics, Maxwell−Stefan, and Fickian approaches. A new equivalence between Fickian and Maxwell−Stefan formulations is described by [D] = [ns][B]−1[Γ][ns]−1. The elements of D and B are explicitly related to the Fickian and Maxwell−Stefan diffusivities, respectively. Only when the saturation loadings nis for different components are the same can the matrix be reduced to the generally accepted equation [D] = [B]−1[Γ]. On the basis of the relationship between the irreversible thermodynamics and Maxwell−Stefan approaches, an equation is derived for a binary system with the symmetric form (1/Ð1 + θ2/Ð12)(1/Ð2 + θ1/Ð21) = (L11L22)/(L12L21)(θ1θ2)/(Ð12Ð21) The Maxwell−Stefan binary exchange coefficients Ðij are shown to depend not only on the Maxwell−Stefan diffusivities, Ði, but also on the Onsager coefficients. For a strong molecular interaction, that is, Ði ≫ Ðij, the ratio of Onsager ...
Studies of Pure Pancreatic Secretions in Chronic Alcoholic Subjects without Pancreatic Insufficiency

To determine the role alcohol might play in altering pancreatic function, we have examined pure pancreatic juice, obtained by endoscopic cannulation of the pancreatic duct, from a group of 10 chronic alcoholic subjects without history or clinical or laboratory evidence of pancreatic disease and compared the results with those obtained from 15 healthy, non-alcoholic subjects. These findings confirm observations in experimental animals made by others and support the hypothesis that chronic alcohol abuse may damage the pancreas via a sequence of events involving protein hypersecretion. Increase in concentration was not uniform for all proteins measured. Unexpectedly, chronic alcoholics exhibited a highly significant elevation (two- to three-fold over normal) in trypsinogen, in contrast to statistically insignificant increases of other zymogens and trypsin inhibitor. The strikingly increased ratio of trypsinogen to trypsin inhibitor observed in all our alcoholic patients may indicate a weakening of the defens...