cssi/SciSciGPT-SciSciNet huggingface dataset:
On the reaction of C2H3Cl+ with C2H3Cl

Abstract A re-investigation of the C 2 H 3 Cl + , C 2 H 3 Cl reaction has been made using a Dempster-ICR tandem mass spectrometer. This study verifies the previous ICR results, for both the low energy branching ratio and the energy dependence of the total rate constant for condensation products. It is shown that the branching ratio is also very energy dependent and quantitative results are presented. The data demonstrate that the tandem configuration employed in this research produces quasi-thermal reactant ions equivalent to those generated in conventional ICR. It is argued that the difference between the ICR results and other mass spectrometric results reflects the participation of significantly higher internal energy reactant ions in the other experiments.
The transcription factor c-Myb primes CD4+CD8+ immature thymocytes for selection into the iNKT lineage

Type I invariant NKT cells (iNKT cells) are a subset of alphabeta T cells characterized by the expression of an invariant alpha-chain variable region 14-alpha-chain joining region 18 (V(alpha)14J(alpha)18) T cell antigen receptor (TCR) alpha-chain. The iNKT cells derive from CD4(+)CD8(+) double-positive (DP) thymocytes, and their generation requires a long half-life of DP thymocytes to allow V(alpha)14-J(alpha)18 rearrangements, expression of glycolipid-loaded CD1d on DP thymocytes, and signaling through the signaling-activation molecule SLAM-adaptor SAP pathway. Here we show that the transcription factor c-Myb has a central role in priming DP thymocytes to enter the iNKT lineage by simultaneously regulating CD1d expression, the half-life of DP cells and expression of SLAMF1, SLAMF6 and SAP.
A systematic review of off-label uses of memantine for psychiatric disorders

Recent data points to glutamatergic dysfunction in mood disorders, anxiety disorders, obsessive-compulsive disorder, and schizophrenia. Memantine, a drug approved by the FDA for the treatment of moderate to severe Alzheimer's disease that acts at the N-methyl-d-aspartate receptor, has been used off-label for various psychiatric disorders. Although promising, the available data for the use of memantine in these disorders is limited. Given this data, the routine use of memantine for depression, schizophrenia, obsessive-compulsive disorder, substance abuse, pervasive developmental disorders, bipolar disorder, and binge eating disorder cannot be recommended at this time.
Second-look laparotomy in advanced ovarian cancer: a critical assessment of morbidity and impact on survival.

Background: The routine inclusion of second-look laparotomy in the management of patients with epithelial ovarian cancer is controversial. At issue is the justification of morbidity incumbent upon surgery and the possible survival benefit of secondary cytoreduction.
Intraoperative radiation therapy in resected pancreatic carcinoma: long-term analysis.

Purpose The combination of external radiotherapy (RT) plus intraoperative radiotherapy (IORT) in patients with pancreatic cancer is still debated. This study presents long-term results (minimum follow-up, 102 months) for 26 patients undergoing integrated adjuvant RT (external RT + IORT). Methods and Materials From 1990 to 1995, a total of 17 patients with pancreatic cancer underwent IORT (10 Gy) and postoperative external RT (50.4 Gy). Preoperative “flash” RT was included for the last 9 patients. The liver and pancreatic head received 5 Gy (two 2.5-Gy fractions) the day before surgery. In the subsequent period (1996–1998), 9 patients underwent preoperative concomitant chemoradiation (39.6 Gy) with 5-fluorouracil, IORT (10 Gy), and adjuvant chemotherapy. Results Preoperative chemoradiation was completed in all patients, whereas postoperative therapy was completed in 13 of 17 patients. All 26 patients underwent pancreatectomy (25 R0 and one R1 resections). One patient died of postoperative complications (3.8%) not related to IORT. The 9 patients undergoing concomitant chemoradiation were candidates for adjuvant chemotherapy; however, only 4 of 9 underwent adjuvant chemotherapy. At last follow-up, 4 patients (15.4%) were alive and disease free. Disease recurrence was documented in 20 patients (76.9%). Sixteen patients (61.5%) showed distant metastasis, and 5 patients (19.2%) showed local recurrence. The incidence of local recurrence in R0 patients was 4 of 25 (16.0%). The overall 5-year survival rate was 15.4%. There was significant correlation with overall survival of tumor diameter ( p = 0.019). Conclusions The incidence of local recurrence in this long follow-up series (19.2%) was definitely less than that reported in other studies of adjuvant RT (∼50%), suggesting a positive impact on local control of integrated adjuvant RT (IORT + external RT).
The importance of structure in early education programs for disadvan‐taged and handicapped children†

An analysis of the amount and type of structure of early intervention programs was conducted as part of a review of literature on the efficacy of early intervention with disadvan‐taged, at‐risk, and handicapped preschoolers. Results indicated that programs with preplanned goals and structured curriculum produced significantly more gains for disadvantaged preschoolers, but the results are less clear cut for handicapped preschoolers. It is not clear just what type of structure for handicapped preschoolers is needed in curriculum and staff model and if this degree in structure is advantageous to children who are not experiencing difficulties. Suggestions for further study of goal setting and evaluation for infants and children and the training and supervison of staff necessary to implement structured programs is given. †The work reported in this article was carried out in part with funds from the U.S. Department of Education (Contract #300‐82‐0367) to the Early Intervention Research Institute at Utah State U...
A case study approach to support needs following the death of a loved one

Abstract The loss of a close relational partner, whether a family member, friend, spouse, or romantic partner, is one of the most difficult, and at the same time predictable, situations that individuals can experience. Although the grieving process is very individual, one's support network can either facilitate or hinder the coping process. This article utilizes a case study approach to consider the ways that one's social network provides emotional and instrumental support following the death of a close relational partner. A 21-year-old female whose fiance was killed in a traffic accident participated in three separate interviews at 4, 9, and 16 months after the accident. Interpretive analyses support the assertion that, as individuals progress through the various phases of bereavement, their needs for specific forms of social support change, as do their perceptions of what is helpful and unhelpful.
Color characterization for inkjet copiers

Copier color mapping is the color modeling and mapping from the scanner RGB color space to the printer device color space. It may be aimed for exact/closest color matching or for preference color matching from the source hardcopy to the reproduced hardcopy. It is not simply the linking of a scanner color characterization and a printer color characterization. Unlike other cross-color reproduction systems in which both the source color space and the destination color space are well-defined, copy source types are not controllable in general. Since the source color space (e.g. the black and white points, color gamut, and the scanner response to the source) cannot be well-defined, no exact color characterization can be made for general copy. A trade-off for the balance of overall copy reproduction is important for copy color characterization. In this paper, we present a method for scanner characterization preserving the neutral balance, a method to characterize scanners with controllable extrapolation, how to select a gamut mapping method to optimize system color reproduction, and overall characterization methods for different source types and different print modes for the trade-off for overall copy color reproduction.
Indirect and direct acoustic aggression in cicadas: first observations in the Palaearctic genus Tibicina Amyot (Hemiptera: Cicadomorpha: Cicadidae)

Tibicina Amyot is a cicada genus of the Palaearctic biogeographical region with seven taxa (species and subspecies) distributed in France. As in other cicadas, the sound production by tymbal vibration is restricted to males. In Tibicina, males are attracted by conspecific calling songs and tend to form groups of several individuals which maintain a minimal distance between each other. Observations based upon male–male interactions in such aggregations and on some preliminary experiments conducted with males kept in captivity revealed for the first time both indirect and direct aggression. Spacing and chorusing are interpreted as a by-product of indirect aggression mediated through the calling song. Direct aggression occurred when spacing is not respected. It is achieved through a ritualistic sequence that involves mainly the production of the rivalry song, an acoustic signal previously reported in the literature for two cicada species only. In addition, satellite males and male–male courting are reported....
Molecular indicators (biomarkers) of past life.

Biomarkers in geological samples on Earth are products derived from biochemical precursors (i.e., natural products) by reductive and oxidative alteration processes (e.g., cholestanes from cholesterol). Generally, lipids, pigments, and some biomembranes are preserved best over longer geological times, and labile compounds such as amino acids, sugars, etc. are useful biomarkers for recent times. Thus, the detailed characterization of biomarker composition permits the assessment of the major contributing species of extinct and/or extant life. Nonbiomarkers and abiogenic organic compounds are also discussed. In the case of the early Earth, work has progressed to elucidate biomarker structures and carbon isotopic signals preserved in ancient sedimentary rocks. In addition, the combination of bacterial biochemistry with the organic geochemistry of contemporary and ancient hydrothermal ecosystems permits the modeling of the nature, behavior, and preservation potential of primitive microbial communities. This approach entails combined molecular and isotopic analyses to characterize lipids and biopolymers produced by cultured bacteria (representative of ancient strains) and to test a variety of culture conditions that affect their biosynthesis processes. In regards to Mars, the biomarkers from lipids and biopolymers would be expected to be preserved best if life flourished there during its early history (3.5-4 x 10(9) years ago). Both oxidized and reduced products would be expected. This is based on the inference that hydrothermal activity occurred during that time, with the concomitant preservation of biochemically-derived carbonaceous matter. Known biomarkers (i.e., as elucidated for early terrestrial samples and for primitive terrestrial microbiota) as well as novel, potentially unknown compounds, should be characterized.
Relational influences on career paths: Siblings in context.

This investigation examined participants' perceptions of sibling relational influence on career exploration and decision making. Career path influence on sibling relationships and times when these relationships were most important also were explored. Individual interviews were conducted with urban commuter college students, and narrative data were analyzed using consensual qualitative research methods as described by C. E. Hill, B. J. Thompson, and E. N. Williams (1997). Consistent with attachment theory (J. Bowlby, 1982) and literature on social support (C. E. Cutrona, 1996), one of the most prominent factors associated with relational influence was multidimensional social support. Predictable differences were found in relational influence between participants' most important siblings and other siblings.
Child Sexual Abuse and the Superfluous Association with Negative Parenting Outcomes: The Role of Symptoms as Predictors

The purpose of this study was to investigate the relationship between child sexual abuse and high-risk maternal parenting indicators and the extent to which maternal depression and self-perceived parenting competence influence that relationship. Using path analysis, results indicate maternal depression and parenting sense of competence mediate the relationship between child sexual abuse and outcome variables. Post hoc analyses indicated that child sexual abuse was significantly associated with decreased parenting sense of competence, controlling for depression. These results highlight that the pathways for increased risk in parenting outcomes for child sexual abuse survivors may be indirect and associated with beliefs of their own sense of competence and depression as opposed to a direct association with sexual abuse itself. Implications are discussed.
Disruption of cytochrome P4501A2 in mice leads to increased susceptibility to hyperoxic lung injury

Hyperoxia contributes to acute lung injury in diseases such as acute respiratory distress syndrome. Cytochrome P450 (CYP) 1A enzymes have been implicated in hyperoxic lung injury, but the mechanistic role of CYP1A2 in pulmonary injury is not known. We hypothesized that mice lacking the gene Cyp1a2 (which is predominantly expressed in the liver) will be more sensitive to lung injury and inflammation mediated by hyperoxia and that CYP1A2 will play a protective role by attenuating lipid peroxidation and oxidative stress in the lung. Eight- to ten-week-old WT (C57BL/6) or Cyp1a2(-/-) mice were exposed to hyperoxia (>95% O2) or maintained in room air for 24-72 h. Lung injury was assessed by determining the ratio of lung weight/body weight (LW/BW) and by histology. Extent of inflammation was determined by measuring the number of neutrophils in the lung as well as cytokine expression. The Cyp1a2(-/-) mice under hyperoxic conditions showed increased LW/BW ratios, lung injury, neutrophil infiltration, and IL-6 and TNF-α levels and augmented lipid peroxidation, as evidenced by increased formation of malondialdehyde- and 4-hydroxynonenal-protein adducts and pulmonary isofurans compared to WT mice. In vitro experiments showed that the F2-isoprostane PGF2-α is metabolized by CYP1A2 to a dinor metabolite, providing evidence for a catalytic role for CYP1A2 in the metabolism of F2-isoprostanes. In summary, our results support the hypothesis that hepatic CYP1A2 plays a critical role in the attenuation of hyperoxic lung injury by decreasing lipid peroxidation and oxidative stress in vivo.
Controlling Measurement Errors in Models of Advertising Competition

Abstract Commercial market research firms provide information on advertising variables of interest, such as brand awareness or gross rating points, that are likely to contain measurement errors. This unreliability of measured variables induces bias in the estimated parameters of dynamic models of advertising. Consequently, advertisers either under- or overspend on advertising to maintain a desired level of brand awareness. Monte Carlo studies show that the magnitude of bias can be serious when conventional estimation methods, such as ordinary least squares and errors in variables, are employed to obtain parameter estimates. Therefore, the authors have developed two new approaches that either reduce or eliminate parameter bias. Using these methods, advertisers can determine an unbiased optimal advertising budget, even if advertising variables are measured with error. The application of these methods to estimate the extent of measurement noise in empirical advertising data is illustrated.
Theoretical determination of the electron affinity of O2 molecule from the binding energy of O−2☆

From the simple Hess cycle EA(O2) = D0(O−2) − D0(O2) + EA(O), since the dissociation energy for O2 and the electron affinity (EA) for O are well known, it is possible to determine the electron affinity of O2 if the dissociation energy for O−2 is known accurately. The method of optimized valence configurations is used to determine the binding energy of the ground state of the O−2 molecule-ion. All important correlation contributions within and between valence shells are obtained using the multiconfiguration self-consistent field (MC SCF) process. The calculations yield an O−2 dissociation energy value of 4.14 eV which results in EA(O2) = 0.42 eV. This theoretical value is in good agreement with the generally accepted experimental value of 0.43 ± 0.003 eV.
A hairpin conformation for the 3' overhang of Oxytricha nova telomeric DNA.

Abstract The solution secondary structure of the Oxytricha nova telomeric 3′ overhang, d(T 4 G 4 ) 2 , has been investigated by Raman spectroscopy, hydrogen-deuterium exchange kinetics and gel electrophoresis. The electrophoretic mobility of d(T 4 G 4 ) 2 in non-denaturing gels indicates a highly compact conformation, consistent with a hairpin secondary structure. Raman markers show that the d(T 4 G 4 ) 2 hairpin contains equal numbers of C2′- endo/syn and C2′- endo/anti deoxyguanosine conformers, as well as G·G base-pairs of the Hoogsteen type. The hydrogen-deuterium exchange kinetics of d(T 4 G 4 ) 2 , monitored by time-resolved Raman spectroscopy, reveal two kinetically distinct classes of guanine imino (N1H) protons. The more slowly exchanging fraction ( k N1H (1) = 4.6 × 10 −3 min −1 ), which represents 50% of N1H groups, is attributed to Hoogsteen-paired residues. The more rapidly exchanging fraction ( k N1H (2) ⩾ 0.3 min −1 ) is attributable to solvent-exposed residues. Raman dynamic probe of the kinetics of guanine C8H → C8 2 H exchange in d(T 4 G 4 ) 2 reveals modest retardation vis-a-vis dGMP, which rules out quadruplex formation by the telomeric repeat and confirms an ordered secondary structure consistent with a Hoogsteen-paired hairpin. Similar Raman, hydrogen-isotope exchange and electrophoretic mobility experiments on the related telomeric model, dT 6 (T 4 G 4 ) 2 , also reveal a hairpin stabilized by Hoogsteen G·G pairs. Presence of the 5′ thymidine tail preceding the Oxytricha telomeric repeat has no apparent effect on the hairpin secondary structure. We propose a molecular model for the hairpin conformation of the Oxytricha nova telomeric repeat and consider its possible roles in mechanisms of telomeric DNA interaction in vitro and telomere function in vivo .
The Dynamics in the Enculturation and the Work in the Assistant Principalship

Enculturation of assistant principals tends to result in "custodial, nonrisk-taking, noninstructional" orientations of potential educational leaders.
Modifying the dispensing of reinforcers: Some implications for behavior modification with hospitalized patients

This study systematically examined the effects of instructions, verbal prompts, and monetary reinforcement given to psychiatric aides for reinforcing patients within a token economy program. Baseline observations revealed that psychiatric aides dispensed low rates of reinforcement for appropriate patient behavior. Instructing the aides had no effect, verbal prompts produced a slight increase, and a monetary bonus resulted in a substantial increase in aide-dispensed reinforcement. This latter change in aide behavior was accompanied by improved functioning in two of the three patients selected for observation. When the monetary bonus was withdrawn, aide-dispensed reinforcement as well as task-oriented patient behavior declined to a near baseline level. Procedures for maintaining the reiforcing behavior of aides toward patients are briefly discussed.
Quantum tunnelling of muonium reactions in solutions

Muonium spin rotation experiments have been performed in a system of benzene in liquid isopentane solutions in the temperature range between 136 K and 295 K. The observed chemical reaction rate constants show a concave curve in an Arrhenius plot. These results are interpreted in terms of to a significant quantum tunnelling effect for muonium reaction in solutions. The oscillating frequency and the width of barrier for such reactions were found to be 400 cm−1 and 2.1 A respectively by curve-shape analysis. The reaction barrier (6.0 kJ/mol) is found to be less than the activation energy due to viscous flow of the solvent.
A novel design for a radiative fin array system

Abstract This paper analyzes and optimizes a new design four-fin radiating array in which the horizontal fins have a rectangular profile and the vertical fins can have either a rectangular or triangular profile. The optimum dimensions of the fins are obtained and the results are presented in an extremely simple algebraic form which is very convenient for use by thermal designers. Comparisons are made between the conventional two-fin array and the proposed optimum design of the four-fin array. It is found that the latter saves about 30% in material for a typical emissivity of the radiative fins.
Urease oligomerizes in a linear pattern: further hydrodynamic evidence from intrinsic viscosity theories and measurement.

Measurements of the intrinsic viscosity of the urease “monomer” and of a mixture of oligomers are shown to lead to the conclusion that urease oligomerizes in a linear fashion, when viewed in the light of several available theories of intrinsic viscosity of rigid protein macromolecules. This conclusion is also consistent with previously reported work on the sedimentation coefficients of the urease oligomers. The use of a detailed subunit structure for the urease “monomer” and oligomers is explored and found to give quantitatively good results for all hydrodynamic properties of all urease oligomers. The realm of validity of the intrinsic viscosity theories proposed by Garcia de la Torre and Bloomfield, by Tsuda, and by Abdel-Khalik and Bird is explored in this context.
Similarities in the proteins synthesized by Sciara salivary gland cells in response to electromagnetic fields and to heat shock

Abstract We have studied changes in the biosynthetic responses of salivary gland cells from Sciara coprophila to two stresses, electromagnetic (EM) fields and heat shock (HS). To characterize the entire field of proteins synthesized, we converted the data from two-dimensional gels into protein distribution curves (%mass vs. MW, %mass vs. pI). The responses to the two different stimuli, EM and HS, are quite similar to each other and different from those of the control. There are new peaks at MW = 30 kD and pI = 7.1 for both EM and HS. There is also a shift of the peak in pI distribution from 5.8 to 6.3 for both EM and HS. A plot of the changes in the two pI peaks as a function of EM field strength defines a dose-response curve as well as the range of the effect. These changes appear to be characteristic of the cellular response to stress.
La Crosse: An Under-Recognized, Dangerous and Possibly Treatable Central Nervous System Infection of Childhood. • 742

La Crosse encephalitis (LE), a mosquito-borne viral disease which can be mistaken for herpes simplex encephalitis, is under-recognized in the US, despite case reports from 28 states and an incidence in endemic areas(20-30/100,000) exceeding that of bacterial meningitis. The following is our 10-year experience (1987-1996) with 128 LE admissions, which is the largest single series reported and the first including experience with intracranial pressure (ICP) monitoring and specific antiviral therapy. Diagnosis was by La Crosse IgM and IgG serum titers. Typical cases occurred in school-age children(mean = 7.81, range 0.5-16 years), presenting between early July and late October. Symptoms usually involved headache and fever (83%) for 3-4 days and vomiting (71%) for 1-2 days, with progression to seizures (46%) and/or disorientation (44%). Only 24.5% had nuchal rigidity. Of those presenting with seizures, 1 in 4 occurred abruptly, and 1 in 4 evolved to status epilepticus(SE). Cerebrospinal fluid yielded: 1) white blood cells (WBC) modestly elevated (mean = 129, range 2-867), with 10% of patients having 210 WBC's; 2) negative viral cultures. Peripheral WBC's were elevated (mean = 15.7K, s.d. = 5.9K) with left shift. One in four children required intubation for seizures and/or coma and more than one-half (57.1%) required intensive care. Notably, 3 patients developed acute uncal herniation within 48 hours of admission and received IV ribavirin per FDA approval for emergency use. Those who had significant in-hospital deterioration (e.g., herniation, SE) tended to have decline in sodium (p <0.025) concurrent with the event. Except for the sentinel case in 1987, all patients have survived. LE should be considered in the the child presenting with meningoencephalitis in summer/early fall, particularly for children living in (or recent travel to) endemic areas in midatlantic and midwestern states. Early diagnosis can be made via IgM and IgG serology using indirect immunoflourescence. We are conducting a randomized clinical trial of IV ribavirin for severe cases.
The association of major, minor and trace inorganic elements with lignites. I. Experimental approach and study of a North Dakota lignite

Abstract Lignites resemble peats, the precursors of coals, in containing many carboxylic acid and other functional groups. Consequently much of the relatively small amount of inorganic matter in lignites is present as cations in carboxylates and in chelated coordination complexes, and not only as distinct mineral phases. Consequently the distribution of inorganic matter in lignites will be influenced by the structure of the organic matter, as well as by microbial processes in peats and the geochemical processes involving erosion of rocks and transport of mineral grains and cations in solution. The objective of this study was to seek information on the distribution of major, minor and trace elements in different forms of combination, and in particular to document organic/inorganic interactions in coal formation. Study of the first of five lignites is reported here. The coal (from the Hagel seam in North Dakota) was separated into five fractions by float/ sink methods, and the fractions were further separated into an ammonium acetate extract, an HCl extract and an insoluble residue. Analysis of the fractions (by atomic absorption, plasma arc emission, emission spectroscopy and neutron activation) was found to give much information on how elements were combined in the coals. Results of the fractionation indicate that Ca, Mg, Na, K, Sr, Ba and Mn were present largely or partly in ion-exchangeable form; appreciable amounts of K (illite), Ba (sulfate, carbonate) and Mn were also present in mineral phases. Some Al appeared to be present in organic association. Ti often occurs in sediments by substitution in clays, but we infer that substantial amounts are present here in both acidsoluble and acid-insoluble organic chelates. The considerable enrichment of a number of elements in the fractions of lowest specific gravity suggests that Be, Sc, Cr, Y, Yb, V, Ni, Cu and Zn are associated primarily or partly with the organic matter. The extent to which these elements are associated with the organic matter in this lignite is much greater than it is with the bituminous coals studied by others.
Immunogenicity of Subcutaneously Administered Therapeutic Proteins—a Mechanistic Perspective

The administration of therapeutic proteins via the subcutaneous route (sc) is desired for compliance and convenience, but could be challenging due to perceived immunogenic potential or unwanted immune responses. There are clinical and preclinical data supporting as well as refuting the generalized notion that sc is more immunogenic. We provide a mechanistic perspective of immunogenicity of therapeutic proteins administered via the sc route and discuss strategies and opportunities for novel therapeutic approaches to mitigate immunogenicity.
A personal history of markers of myocyte injury [myocardial infarction].

Abstract Background The measurement of proteins in blood to reflect damage to the heart is one of the most successful examples of easily measured biomarkers identifying a serious major health problem. The concept of using a blood test to reflect organ or cell injury requires a substance that is very abundant in the target cell, has a means of reaching blood, a reasonable half-life in blood, and ideally a specific form reflective only of the target cell in tissue. The myocyte's major role is contraction so proteins involved in contraction or the energy to support it should be good candidate markers. Conclusions All the various biomarkers that have been used to detect cardiac damage are involved in contraction or energy metabolism, but the markers evolved empirically starting with transaminases in the 1950s leading to troponins in the 1990s. This history is reviewed with reflections on my experiences with developing assays for CK-MB and Troponin I.
Paleocurrent analysis of sedimentary crossbed data with graphic output using three integrated computer programs

Basin analysis for paleocurrent directions commonly makes use of hundreds of cross-bedding dip and strike measurements taken on structurally tilted sedimentary beds which may be parts of plunging folds. For regional interpretations the desired forms of data are vector means and rose diagrams of dip directions after reduction to the assumed horizontal plane of deposition. Three FORTRAN computer programs have been integrated to perform the data reduction from raw field measurements to graphic plotted rose diagrams. Program PLUNGR rotates the raw field data back to the original horizontal plane of deposition. Output from PLUNGR is a deck of punched cards suitable for input into the second and third programs, with provision for various regroupings of data. VECMEN computes vector mean and other statistics on data groups defined by inserted control cards. Program ROSE, with a variety of options, plots a rose diagram of dip direction azimuths on a CalComp plotter.
Mitochondria and cell death: outer membrane permeabilization and beyond

Mitochondrial outer membrane permeabilization (MOMP) is often required for activation of the caspase proteases that cause apoptotic cell death. Various intermembrane space (IMS) proteins, such as cytochrome c, promote caspase activation following their mitochondrial release. As a consequence, mitochondrial outer membrane integrity is highly controlled, primarily through interactions between pro- and anti-apoptotic members of the B cell lymphoma 2 (BCL-2) protein family. Following MOMP by pro-apoptotic BCL-2-associated X protein (BAX) or BCL-2 antagonist or killer (BAK), additional regulatory mechanisms govern the mitochondrial release of IMS proteins and caspase activity. MOMP typically leads to cell death irrespective of caspase activity by causing a progressive decline in mitochondrial function, although cells can survive this under certain circumstances, which may have pathophysiological consequences.
Abstract LB-97: Optimizing SELEX with high-throughput sequencing

SELEX (systematic evolution of ligands by exponential enrichment) identifies oligonucleotide “aptamers” that bind their protein targets with high affinity and specificity. Beyond inhibiting all protein function, aptamers can target specific functional regions (e.g., phosphorylation sites and catalytic domains) leaving other function intact. This selective inhibition is a valuable tool for dissection of signal transduction pathways, such as the growing list implicated in cancer by sequencing efforts interrogating tumor genomes. New technological innovations in aptamer discovery aim to keep pace with this need by improving the efficiency of the traditional SELEX enrichment process wherein oligonucleotides are iteratively bound to target, eluted, and amplified to purify an initial random library to a few high-affinity aptamers. Principal among these advances is the adoption of high-throughput sequencing (HTS-SELEX) to detect enrichment of candidate aptamers within the evolving pool. The improved sensitivity of high-throughput sequencing over the traditional use of cloning and sequencing reduces the number of rounds required to reach detectable enrichment. As with traditional SELEX, enrichment and hence number of rounds and overall efficiency are dependent on the free target and oligonucleotide pool concentrations. Though early theoretical approaches have addressed these issues for traditional SELEX, realizing the potential efficiency gains of the new HTS-SELEX approach requires an analysis and resulting protocol tailored to it specifically. Here we provide such an analysis and also re-examine earlier theoretical approaches to traditional SELEX. We show that HTS-SELEX motivates an optimization condition different from that of traditional SELEX and consider the role of stochastic fluctuations in the relatively low multiplicities of the enriched species resulting from the earlier enrichment detection of HTS-SELEX. Unlike previous approaches seeking to maximize some measure of per-round enrichment, this analysis is a global optimization of the entire SELEX process. It results in a specific recommendation for free target concentration, constant across rounds and simply related to the desired affinity, and for corresponding total ligand concentration. Applying the global analysis to an optimization condition appropriate for traditional SELEX again yields recommendations that are provably optimal and that differ from those previously published. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-97. doi:1538-7445.AM2012-LB-97
First glimpse of the crystal structure of YaeT's POTRA domains.

The Omp85/YaeT family of proteins, which are conserved from bacteria to human, catalyzes insertion and assembly of proteins in the outer membrane. The structure consists of a transmembrane β-barrel domain and a soluble polypeptide-transport-associated (POTRA) domain. The POTRA domain is critical for substrate recognition and perhaps substrate folding, while the β-barrel domain assists in membrane insertion. The resolution of the crystal structure of the POTRA domain of the Escherichia coli YaeT protein provides a possible molecular mechanism by which the diverse group of substrates is recognized. Knowledge gained from the crystal structure may also spur the development of a novel class of chemotherapeutic inhibitors.
Using counterconditioning to treat behavioural distress during subcutaneous injections in a paediatric rehabilitation patient

A counterconditioning-based intervention was conducted to supplement topical anaesthesia during repeated parent-administered subcutaneous injections performed on a 7-year-old girl for anticoagulation post-stroke. Preferred activities were paired with in vivo exposure to medical stimuli, first during simulated, then actual injections. Differential positive reinforcement was provided contingent on engagement with preferred activities, button pressing in response to an auditory stimulus, and general compliance with adult instructions. Child distress was measured by direct observations and intervention effects examined using an A-B, single-subject case study design with an interrupted time-series statistical analysis for brief single-subject data. Child distress decreased significantly when behavioural intervention was provided. Parent ratings indicated that treatment effects were maintained after the intervention was turned over to the mother and continued at home. Heart rate data provided physiological evidence of counterconditioning. The results are discussed in relation to the application of conditioning and counterconditioning theory in the paediatric rehabilitation setting.
Organizational Culture and Professional Identities in the Soviet Nuclear Power Industry

Abstract This essay describes the evolution and interaction of powerful constituencies within the Soviet nuclear energy community since the late 1950s. It elucidates the historical origins of the alleged distinction between nuclear specialists (atomshchiki) and power engineers (energetiki) and explores why there was not more disagreement with and resistance to state authorities. The emerging civilian nuclear industry faced the dual legacy of the atomic bomb project and the state electrification program, a legacy that informed attempts to regulate a complex, dual‐use technology, as well as the values and routines of specialists involved with the design and operation of nuclear power reactors. The essay argues that rather than cynicism, a deep commitment to scientific rationality and an often personal conviction of the necessity of nuclear energy permeated this heterogeneous community of experts. The secrecy imposed on their work only reinforced these experts’ loyalty to a state that embodied their own tech...
Correlation between velocity dependence of friction and strain localization in large displacement experiments on feldspar, muscovite and biotite gouge

Abstract Room temperature rotary shear experiments on rock powders of albite feldspar and muscovite and biotite micas show that the degree of localization of shear strain in these materials correlates with the frictional behavior. In both feldspar and mica experiments, increasing localization correlates with a lower coefficient of friction and a more negative velocity dependence of friction. Feldspar gouges tend to have localized deformation along one or more boundary-parallel shears and a negative velocity dependence. More localized deformation correlates with a lower coefficient of friction and a more negative velocity dependence. In general, micas deform throughout a broader zone than feldspar and have a lower coefficient of friction. Compared to muscovite, biotite is weaker, has a negative rather than a positive velocity dependence, and shows more localized deformation. For materials as diverse as feldspars and micas, localization along boundary-parallel shears correlates with negative velocity dependence. Along compliant natural faults, a negative velocity dependence would result in a greater tendency for unstable sliding. Thus, localized boundary-parallel shears may indicate negative velocity dependence and slip by earthquakes on natural faults.
Radiocarbon distribution and the effect of legacy in lakes of the McMurdo Dry Valleys, Antarctica

The water of the ice-covered lakes of the McMurdo Dry Valleys is derived primarily from glacial melt streams and to a lesser extent permafrost seeps and subglacial outflow. The result is a mixture of radiocarbon ages that reflect both the end-member water source and the biogeochemical processing of waters as they migrate to the lake-water column. Samples were collected from various locations within perennially ice-covered Antarctic lakes and the streams that feed them, and they were analyzed for radiocarbon abundance of organic and inorganic carbon. Stream gradient and length were shown to affect the degree of equilibration of water with the modern atmosphere prior to entering the lakes. Stream microbial mats assimilate inorganic carbon flowing over them. Seasonal ice-free ‘moat’ water dissolved inorganic carbon (DIC) is largely dependent on the amount of meltwater input from streams (modern) vs. that from direct glaciers input (old). Under the ice cover, 14C ages of lake-water DIC and organic matter are dependent on lake history, composition, and quantity of particulate matter fallout. Bottom waters of the west lobe of Lake Bonney have a DIC age of µ 27,000 14C yr before present, which we believe are the most radiocarbon-deficient lake waters on Earth. Comparison of the radiocarbon profiles in the two lobes of Lake Bonney, along with previously published geochemical data, provides a new chronology of the evolution of these two waterbodies and shows that currently deep saline water is being displaced over the sill separating them.
Oxidative metabolism of the GABAA receptor antagonist t-butylbicycloortho[3H]benzoate.

1. The trioxabicyclooctane ring of t-butylbicycloortho[3H]benzoate (TBOB), (CH3)3CC(CH2O)3CC6H5, is cleaved to yield the 3-oxo-benzoate, (CH3)3CC(CHO)(CH2OH)CH2OC(O)C6H 5, on O-methylene hydroxylation by microsomes from mouse liver or houseflies in the presence of NADPH.2. The methyl and phenyl substituents are tentatively identified as additional sites of oxidative metabolism.3. The 3-oxo-benzoate from oxidative cage opening and the bis-(hydroxymethyl)-benzoate, (CH3)3CC(CH2OH)CH2OC(O)C6H 5, from enzymic reduction of the 3-oxobenzoate undergo esteratic hydrolysis to benzoic acid.4. Metabolites of TBOB excreted by rats and houseflies include the bis-(hydroxymethyl)-benzoate and benzoic and hippuric acids.5. Metabolic hydroxylation of TBOB at O-methylene, alkyl and aryl substituents may serve as a model for detoxication reactions of related potent GABAA receptor antagonists and insecticides.
Sodium hydroxide permethylation of heparin disaccharides

Permethylation is a valuable and widely used tool for the mass spectrometry of carbohydrates, improving sensitivity and fragmentation and increasing the amount of information that can be obtained from tandem mass spectrometric experiments. Permethylation of most glycans is easily performed with sodium hydroxide and iodomethane in dimethyl sulfoxide (DMSO). However, permethylation has not been widely used in the mass spectrometry of glycosaminoglycan (GAG) oligosaccharides, partly because it has required the use of the difficult Hakomori method employing the methylsulfinylmethanide ('dimsyl') base, which has to be made in a tedious process. Additionally, the Hakomori method is not as effective as the sodium hydroxide method in making fully methylated derivatives. A further problem in the permethylation of highly sulfated oligosaccharides is their limited solubility in DMSO. This paper describes the use of the triethylammonium counterion to overcome this problem, as well as the application of the sodium hydroxide method to make permethylated heparin disaccharides and their workup to yield fully methylated disaccharides for electrospray ionization mass spectrometry. The ease, speed, and effectiveness of the described methodology should open up permethylation of GAG oligosaccharides to a wider circle of mass spectrometrists and enable them to develop further derivatization schemes in the effort to rapidly elucidate the structure of these important molecules. Permethylation may also provide new ways of separating GAG oligosaccharides in LC/MS, their increased hydrophobicity making them amenable for reversed-phase chromatography without the need for ion pairing reagents.
Parametric analysis of dynamic postural responses

A detailed theoretical understanding of postural control mechanisms must be preceded by careful quantification of both the deterministic and stochastic aspects of postural behavior of normal and abnormal subjects under various dynamic conditions. Toward this end, concise parametric transfer function plus noise models were derived for both shoulder and waist position data obtained by applying a linear anteriorposterior bandlimited pseudorandom disturbance to the base of support of human subjects. Model orders as well as model parameters were determined empirically. One advantage of this modeling procedure is the conciseness of the postural models, permitting easy statistical analysis of the data obtained under different dynamic conditions from many subjects. Model features, including pole and zero locations, from 6 normal subjects each tested on 5 consecutive days under 3 input amplitudes and eyes open and closed conditions are presented. The resulting transfer function models consist of only 1 or 2 poles near the integration position on the Z plane unit circle and 0 to 2 zeros. Locations of the poles indicate that the eyes closed responses are more oscillatory, less damped, and with higher gains than the eyes open responses. These transfer functions are similar to nonparametric ones of other authors. The noise model orders are also small. Their spectra are those of low pass systems. Also, the quantity and frequency range of the postural noise is positively related to the amplitude of platform motion as well as related to the presence or absence of vision.
Temporal interrelationships among circulating levels of estradiol progesterone and LH during the rat estrous cycle: effects of exogenous progesterone.

Serum progesterone (P) levels display a circadian rhythm of varying amplitude during the estrous cycle. This rhythm is characterized by lowest levels of the day around noon and maximal levels at 1600 or 2300 hr. Amplitude was smallest on estrus and progressively greater on diestrus II, diestrus I and proestrus. Serum estradiol (E2) concentrations declined gradually through estrus till 0800 hr of diestrus I. Thereafter, levels increased rapidly to peak at noon, and returned later to near nadir at 2300 hr of diestrus I. During diestrus II and morning of proestrus serum E2 concentrations increased in a biphasic pattern; a moderate increase till 1800 hr of diestrus II was followed by relatively rapid rise to peak levels at 0800 hr of proestrus. A reciprocal relationship between circulating levels of E2 and P during the estrous cycle was also detected. The elevations in serum P levels during estrus, diestrus I and proestrus appeared to coincide with a gradual reduction in serum E2 levels. In addition to the su...
Chitosan Sponges for Local Synergistic Infection Therapy: A Pilot Study

Background Although bacterial antibiotic resistance is increasing, fewer new antibiotics are being developed to compensate. Localized delivery of synergistic antiseptics and antibiotics with a chitosan sponge device may offer an alternative infection treatment.
Acoustic Scattering in the Time Domain Using an Equivalent Source Method

A numerical method to solve acoustic scattering in the time domain is presented in the present paper. Equivalent sources are embedded within a scattering surface and their strengths are determined as a function of time by the pressure-gradient boundary condition on a scattering surface. Once the strengths are determined, the equivalent sources are used to predict the scattered pressure. Linear shape functions are used to discretize the strength of the equivalent sources in time, and singular value decomposition is used to find the least-squares solution and to overcome potential numerical instabilities. The predictions are found to be in excellent agreement with the exact solutions for sound from a point monopole source and band-passed broadband sound. The method works well even at the irregular frequencies at which internal resonance modes occur. Finally, the method is used to predict the scattering of sound from a moving source. It is shown that the method has the capability to capture aperiodic characteristics very well.
Modeling the risks to complex industrial networks due to loss of natural capital

Several recent events in the U.S. have highlighted the criticality and vulnerability of infrastructure systems to sudden shocks such as natural disasters, terrorist attacks, and food shortages. Proper understanding of such disruptive scenarios and their impact using holistic and integrated systems modeling techniques is crucial for effective resource allocation and disaster management. An Input-Output (IO) based framework is presented for studying the effect of sudden shocks and quantifying the associated risks on complex industrial networks. We are specifically using the IO model to understand the impact of changes in the availability of natural resources including natural capital on industrial systems. This includes understanding the potential impact of loss of services such as pollination, water scarcities, and soil fertility. The utility of the framework is highlighted using two case studies involving loss of pollination services provided by managed honeybees and reduction in the availability of crude oil. The approach is suitable for modeling the effect of sudden perturbations such as resource shortage on the complex industrial systems and identifying industrial sectors with greatest sensitivity to a given perturbation. This work is expected to complement the traditional biophysical models and methods by including the behavior of complex industrial networks under sudden shocks, quantifying the associated risks and support a decision-making framework for risk management.