cssi/SciSciGPT-SciSciNet huggingface dataset:
The mechanism of somatic hypermutation studied with transgenic and transfected target genes.

Abstract Somatic hypermutation of Ig genes is beginning to be understood in molecular terms. Ig transgenes have served as model test genes and been shown to mutate, just as endogenous genes, with a peak of mutation over the VJ region and a sparing of the C region. The levels of somatic mutation appear to be related to the expression of the transgenes. DNA hypermethylation of modified Ig transgenes interferes with both expression and somatic hypermutation. Test substrates consisting of bacterial lacZα or supF tRNA inserted within κ transgenes were shown to be rescuable as expressible bacterial plasmids, but did not seem to be targeted. A synthetic sequence consisting of alternating restriction enzyme sites, that cannot be subject to methylation, was found to be a reliable transgenic substrate for easy assay of somatic mutation. The generation of a transgenic mouse with a κ transgene in which the transcriptional promoter has been duplicated upstream of the C region has given new clues to the mutation mechanism. In this transgene, transcripts initiate from both the C region and the V region promoters, and both regions, but not the sequences between them, are hypermutated. These results suggest that somatic hypermutation is linked to the initiation of transcription. A model is proposed in which somatic mutation is dependent on transcription coupled DNA repair.
The Intel labs Haskell research compiler

The Glasgow Haskell Compiler (GHC) is a well supported optimizing compiler for the Haskell programming language, along with its own extensions to the language and libraries. Haskell's lazy semantics imposes a runtime model which is in general difficult to implement efficiently. GHC achieves good performance across a wide variety of programs via aggressive optimization taking advantage of the lack of side effects, and by targeting a carefully tuned virtual machine. The Intel Labs Haskell Research Compiler uses GHC as a frontend, but provides a new whole-program optimizing backend by compiling the GHC intermediate representation to a relatively generic functional language compilation platform. We found that GHC's external Core language was relatively easy to use, but reusing GHC's libraries and achieving full compatibility were harder. For certain classes of programs, our platform provides substantial performance benefits over GHC alone, performing 2x faster than GHC with the LLVM backend on selected modern performance-oriented benchmarks; for other classes of programs, the benefits of GHC's tuned virtual machine continue to outweigh the benefits of more aggressive whole program optimization. Overall we achieve parity with GHC with the LLVM backend. In this paper, we describe our Haskell compiler stack, its implementation and optimization approach, and present benchmark results comparing it to GHC.
Phase-contrast enhancements to a speckle-based fiber optic sensor

Speckle based fiber optic sensors have been developed and used in laboratory and field settings for a number of years. In the case of speckle-based fiber optic vibration sensor, optical signal processing of the field emerging form a multimode fiber has been performed through the use of intensity modulating masks. In such cases, portions of the speckle pattern are not allowed to illuminate a photodetector thereby performing forms of statistical selection of modal patterns. While this technique is robust, it does inherently reduce the sensor's operational dynamic range, and signal-to-noise ratio, due to the simple fact that a portion of the light field is not used. By contrast, it is possible to use phase-contrast enhancing techniques found in microscopy to phase-modulate the fiber's speckle pattern. The performance of a multimode fiber optic sensor using these techniques is compared with the more traditional intensity-modulating fiber optic sensor.
Effects of cocaine prior to and during bupropion maintenance in cocaine-abusing volunteers

The effects of cocaine were examined prior to and during bupropion maintenance in nonopioid-dependent cocaine abusers. Prior to bupropion maintenance, subjects underwent an experimental session during which repeated cocaine doses (0, 50, 100 mg/70 kg) were administered intranasally. Then subjects were maintained on bupropion (150 and 300 mg per day) and underwent experimental sessions as before. Cocaine, regardless of bupropion, produced dose-related increases in several stimulant-like self-reports, performance and cardiovascular measures. Bupropion decreased POMS ratings of friendliness and vigor, regardless of cocaine dose. Bupropion enhanced and attenuated cocaine-induced increases in ratings on the LSD and BG subscales of the ARCI, respectively. These results suggest that bupropion does not alter the acute subjective or cardiovascular effects of cocaine in a robust manner.
Canonical ensemble simulation of biopolymers using a coarse-grained articulated generalized divide-and-conquer scheme

Abstract In this paper, a scheme for the canonical ensemble simulation of the coarse-grained articulated polymers is discussed. In this coarse-graining strategy, different subdomains of the system are considered as rigid and/or flexible bodies connected to each other via kinematic joints instead of stiff, but elastic bonds. Herein, the temperature of the simulation is controlled by a Nose–Hoover thermostat. The dynamics of this feedback control system in the context of multibody dynamics may be represented and solved using traditional methods with computational complexity of O ( n 3 ) where n denotes the number of degrees of freedom of the system. In this paper, we extend the divide-and-conquer algorithm (DCA), and apply it to constant temperature molecular simulations. The DCA in its original form uses spatial forces to formulate the equations of motion. The Generalized-DCA applied here properly accommodates the thermostat generalized forces (from the thermostat), which control the temperature of the simulation, in the equations of motion. This algorithm can be implemented in serial and parallel with computational complexity of O ( n ) and O ( log n ) , respectively.
The burdens of age-related and occupational noise-induced hearing loss in the United States.

Objectives:Aging and noise are generally considered the most common causes of adult hearing loss in developed countries. This study estimates the contributions of aging and occupational noise in the United States.Design:A model of hearing loss burden in American adults was constructed using data fro
Self-tender offers: The effects of free cash flow, cash flow signalling, and the measurement of Tobin's q

Abstract In their analysis of self-tender offers. Howe et al. (1992) reject the free cash flow hypothesis. We expand their analysis in two ways, exploring implications of using long-run measures of Tobin's q as opposed to current q's and incorporating cash flow signalling. We find that acceptance or rejection of the free cash flow hypothesis is sensitive to the measure of q, raising concern over the reliability of results based on different q measures. Thus, the free cash flow hypothesis should not yet be dismissed. We also find strong evidence supporting cash flow signalling.
Separation of interlocking and regulatory control in programmable electronic systems

Abstract In recent years, the separation of safety interlocks from regulatory control systems has emerged as an important safety issue within the process industries. Most modern control systems are large and complex and may be composed of many different types of programmable electronic system (PES) elements. The degree to which elements of the interlock system are shared with the regulatory control system and the resultant security and reliability risks and consequences are often over-looked in safety analyses of the design. The criteria for utilizing a programmable electronic PES in safety interlock applications, based on the degree of hazard and the potential severity of injury and damage, have been described in a previous paper. That paper presented an Interlock Guideline Matrix, which classified the levels of interlock protection required (based on these criteria) and defined the PES interlock system design to satisfy the safety requirements for each classification. This paper addresses the degree of separation required between interlock functions and regulatory control functions in the PES. These requirements are based primarily on the classification of the risk involved, the potential for injury, and environmental and/or property damage. The Interlock Guideline Matrix has been updated to include the requirements for this separation in the interlock system design criteria.
Correction of adolescent hyperkyphosis with posterior-only threaded rod compression instrumentation: is anterior spinal fusion still necessary?

Study design Retrospective clinical and radiographic review. Objective To assess the need for anterior apical release and fusion before posterior threaded rod compression instrumentation and closing-wedge lamina resection for the treatment of adolescent hyperkyphosis. Summary of background data Traditional treatment of adolescent hyperkyphosis has included a preliminary anterior release and fusion of apical disc segments to achieve and maintain better correction. Methods A total of 27 patients undergoing correction of adolescent hyperkyphosis with posterior threaded rod Texas Scottish Rite Hospital instrumentation was reviewed. Of the 27 patients, 19 had strict Sorensen criteria for Scheuermann kyphosis. There were 20 patients (group 1) who underwent posterior surgery only, while 7 (group 2) underwent same day preliminary open or endoscopic anterior release and fusion of 5-7 apical segments. A closing-wedge laminar resection was used to facilitate shortening of the posterior column. All but 2 patients were braced for up to 3 months after surgery. Preoperative, immediate postoperative, and final follow-up radiographs at 24-56 months postoperatively were analyzed for the amount and loss of correction of measured kyphosis, T2-T12 kyphosis, T10-L2 kyphosis, T12-S1 lordosis, C7 plumbline sagittal balance, and correction of Voutsinas index. Results There was no difference in the amount of correction achieved at final follow-up between the 2 groups (group 1 = 53%, group 2 = 46%, P = 0.47). There was also no difference (P = 0.84) in the amount of correction immediately after surgery compared to final follow-up. No patient lost more than 8 degrees correction after surgery. One asymptomatic rod fracture occurred, with no loss of correction, implying no pseudarthroses. Similarly, there were no differences in any of the other sagittal plane measurements between the 2 groups, except for Voutsinas index (VI) in which group 1 patients had better normalization (VI = 0.11) compared to group 2 (VI = 0.15, P =0.05). Conclusions Traditional anterior/posterior fusion technique provides no additional improvement in radiographic outcome compared to posterior-only surgery for adolescent hyperkyphosis. Preliminary anterior release and fusion is no longer performed when correcting this deformity with a posterior column shortening procedure and threaded rod compression instrumentation.
Colloid Oncotic Pressure and the Clinical Use of Colloidal Solutions

Summary The synthetic colloids, dextran and hydroxyethyl starch, have only recently enjoyed widespread use in critically ill veterinary patients. Plasma proteins normally provide colloid oncotic pressure and, thereby, are the primary force responsible for retaining fluid within the vasculature. Abnormally low plasma protein concentrations, common in the critically ill patient, are associated with excessive fluid loss from capillaries and development of peripheral or pulmonary edema. Infusion of colloid solutions decreases the potential for and severity of edema in hypooncotic states. Dextran and hydroxyethyl starch solutions also provide other positive hemodynamic benefits and are a preferable alternative to crystalloid usage in the resuscitation of selected patients from hypotensive and hypovolemic states. Potential side effects of synthetic colloid infusion include anaphylactoid reactions, increased risk of bleeding, interference with cross matching, and acute renal failure. Knowledge of the mechanisms responsible for these adverse effects minimizes their occurrence.
Hans Albert Einstein: Innovation and Compromise in Formulating Sediment Transport by Rivers

This paper is written to mark the hundredth anniversary of the birth of Hans Albert Einstein (1904–1973). It casts his career as that of the archetypal researcher protagonist determined to master intellectually the way water flows and conveys alluvial sediment in rivers. In that effort, Einstein personified the mix of success and frustration experienced by many researchers who have attempted to formulate the complicated behavior of alluvial rivers in terms of mechanically based equations. His formulation of the relationship between rates of bed-sediment transport (especially bedload transport) and water flow comprised an innovative departure from the largely empirical approach that prevailed at the time. He introduced into that relationship the emerging fluid-mechanic concepts of turbulence and boundary layers, and concepts of probability theory. Inevitably the numerous complexities attending sediment transport mire formulation and prompt his use of several approximating compromises in order to make estim...
Present dangers to science and society

AbstractAlthough science has been controversial since its beginnings in classical Greece, the present dangers to it go beyond the financial threats of reduced funding. A few particularly sensitive individuals feel that science has done much to harm the human spirit. The author argues here that science is the new American frontier and that a continuous pursuit of knowledge is essential if further advance is to be achieved. Difficulties and dangers are discussed, such as the loss of interest by most private foundations in the progress of science. It is concluded that an extension of regulations through bureaucracy must be avoided and that common sense and wise leadership are needed.
Characterization of revertants of the CHO EM9 mutant arising during DNA transfection

We have studied reversion in DNA repair deficient EM9 cells, by selection for ethylmethanesulfonate (EMS) resistance. EM9 is a mutant CHO cell line that is hypersensitive to killing by EMS and X-rays and deficient in DNA single-strand break (SSB) repair. EM9 cells were transfected with DNA from a cosmid library, and transfectants resistant to EMS were isolated. Four revertant lines were obtained, which varied in their sensitivity to killing by EMS, ionizing radiation and other genotoxic agents. When the cell lines were analyzed for resistance to killing by chlorodeoxyuridine (CldUrd) or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a different relative ranking among the cell lines was observed. The recently cloned human XRCC1 gene is capable of correcting the deficiencies of the EM9 cell line. Using the human XRCC1 cDNA (pXR1-30) as a probe, we determined that the resistant-transfectant cell lines contained only the endogenous hamster XRCC1 gene, implying that a hamster XRCC1 gene was altered during the transfection/selection procedure and was responsible for the EMS resistance. In these cells the levels of XRCC1 mRNA corresponded roughly to the degrees of resistance of the reverted cell lines to killing by EMS or X-rays. The degree of increased resistance to killing by EMS or X-rays also roughly correlated with increased SSB repair. These results suggest that increased cellular levels of the endogenous XRCC1 gene mRNA may largely, though not completely, explain the phenotypes of revertant, EMS-resistant EM9 cell lines.
Almost Periodic Solutions of Nonlinear Second Order Differential Equations

We provide existence results for almost periodic solutions of nonlinear second order ordinary differential equations. The results extend existence results for periodic solutions of periodic equations, where the existence of periodic sub and supersolutions implied the existence of periodic solutions.
Retinopathy of prematurity: approaches to surgical therapy.

Retinopathy of prematurity (ROP) is a vaso-proliferative disease with infiltration of the vitreous gel. Contraction of the infiltrate results in traction detachment with typical peripheral trough formation. Cryotherapy inhibits proliferation in the active stages of the disease (Stage 3, ‘plus’). With development of traction detachment involving the macula (Stage 48) encircling buckling procedures should first be tried. Closed vitrectomy is considered when high retinal detachment and opacification by vitreous strands occur. The surgical technique is described. Anatomical (64%) and functional (43%) successes are reasonably high for Stage 4 cases, but disappointing (anatomical 40%, functional 16%) for Stage 5 ROP. Open funnels of detached retina fare better than closed ones. It is probably best to perform surgery not before the cicatricial stage, i.e. six months after birth.
Measured Turbulence and Its Effect on Thrombus Formation

Turbulence is one of the hydraulic disturbances implicated in thrombus formation, even though absolute proof of its contributory effect is lacking. Because of the importance of a possible effect of turbulence on thrombus formation, the relation was studied in eight dogs. In each dog, two arteriovenous shunts were established, one from each femoral artery to the contralateral femoral vein. Only one shunt contained a turbulence-producing device; otherwise, the shunts were identical in shape, size, and material. The intensity of turbulence distal to the turbulence generator was quantified in vitro by measuring the relative magnitude of the randomly fluctuating velocities. In each of the eight dogs, more thrombi, by weight, accumulated in the turbulent shunt than in the laminar shunt (P < 0.001). Thrombi from the turbulent shunt weighed 180 ± 30 (SE) mg, whereas those from the laminar shunt weighed 0.9 ± 0.6 mg. The weight of thrombi that accumulated within the turbulent system appeared to be related to the i...
An economic evaluation of site-specific herbicide application

The objective of this study was to determine if site-specific application of postemergence herbicide was economically viable with current technologies. This objective was accomplished by: developing an algorithm that determined the economic optimal postemergence herbicide rate; creating models to determine the impact that postemergence herbicide rate has on yield; and determining whether site-specific application of postemergence herbicide has greater net returns than those from a uniform application of postemergence herbicide. Weed species identification and population counts were done on a regular grid in five fields across Kansas. A decision algorithm was developed to determine the economic optimal rate of postemergence herbicide for each grid cell. The site-specific herbicide rate and four standard herbicide rates [0, 0.5, 0.75, and full (1×) label rate] were applied according to a split-plot design. Weed population observations made three weeks after application showed that the site-specific treatment controlled the weeds present in the fields. Production functions developed to determine whether postemergence herbicide rate had an impact on yield showed that it had a positive, yet statistically insignificant, effect on yield. The difference in estimated net returns between applications of site-specific rate and uniform full-label rate covered all of the costs associated with site-specific application of postemergence herbicide. The margin between the estimated net returns for site-specific and uniform application of the economic optimal rate covered only a portion of the costs associated with site-specific application of postemergence herbicide.
Malignant pheochromocytoma. Severe clinical exacerbation and release of stored catecholamines during lymphoma chemotherapy.

The association of malignant pheochromocytoma and poorly differentiated lymphocytic lymphoma has not previously been reported. A case is presented of a 58-year old man with a 20-year history of malignant pheochromocytoma well controlled on Dibenzyline who was found to have poorly differentiated lymphocytic lymphoma. During lymphoma chemotherapy with cyclophosphamide, vincristine and prednisone (VCP) he developed tachycardia and syncope accompanied by severe hypertension. During the next course of chemotherapy one month later, 24-hour urinary VMA, metanephrine and catecholamine values were determined before, during and after the chemotherapy and were found to have increased two- to ten-fold. This suggests that VCP caused tumor lysis with release of catecholamines into the circulation. Cancer 50:1739-1741, 1982.
Three-body recombination of cold helium atoms

We have developed a method for calculating the rates for three-body recombination of cold atoms This method allows us to treat not only zero total angular momentum, J = 0, states but also J>0 states, so that recombinations at nonzero collision energies can be considered. Our method is applied to ground-state helium atoms 4 He, using a realistic interaction potential. In addition we obtain the rates for collision induced dissociation.
Structure and function of the β2 subunit of brain sodium channels, a transmembrane glycoprotein with a CAM motif

Abstract Voltage-gated sodium channels in brain neurons are complexes of a pore-forming a subunit with smaller β1 and β2 subunits. cDNA cloning and sequencing showed that the β2 subunit is a 186 residue glycoprotein with an extracellular NH 2 -terminal domain containing an immunoglobulin-like fold with similarity to the neural cell adhesion molecule (CAM) contactin, a single transmembrane segment, and a small intracellular domain. Coexpression of β2 with α subunits in Xenopus oocytes increases functional expression, modulates gating, and causes up to a 4-fold increase in the capacitance of the oocyte, which results from an increase in the surface area of the plasma membrane microvilli. β2 subunits are unique among the auxiliary subunits of ion channels in combining channel modulation with a CAM motif and the ability to expand the cell membrane surface area. They may be important regulators of sodium channel expression and localization in neurons.
Projection lithography by means of parametric photon pairs

It is well known that entangled-photon pairs generated by spontaneous parametric down-conversion exhibit a property that is analogous to that of ordinary incoherent lights. We formulate an image-forming optical theory of quantum lithography that comprehends the both conceptions of partial coherence and partial entanglement by extending a classical image-forming optical theory. Our optical system consists of an image-forming system, an illumination system with a second-order nonlinear medium, and two-photon absorbing materials. We evaluate the resolution of the quantum lithography system by using the optical transfer function and show a special case to be a super-resolving system.
Optimization of a Light-Weight Composite Blast Containment Vessel Structural Response

This paper proposes an optimization technique for increasing the structural integrity of a light-weight composite blast containment vessel. The vessel is cylindrical with two hemispherical ends. It has a steel liner that is internally reinforced with throttles and gusset plates and wrapped with a basalt-plastic composite. A finite element model of the blast containment vessel was proposed and verified in an earlier work. The parameters of the vessel are incorporated within an iterative optimization procedure to decrease the peak strains within the vessel, which are caused by internal blast loading due to an explosive charge placed at the center of the vessel. The procedure is validated for different initial guesses of the design variables.Copyright © 2007 by ASME
Surgical acquired aganglionosis: myth or reality?

A number of patients operated on for Hirschsprung disease continue to have constipation and abdominal distension for years after surgery. Some authors have proposed that ischemia during surgery may induce secondary aganglionosis. The aim of the present study was to study the effects of ischemia on the enteric nervous system of sigmoid colon in an animal model. A surgical model of colonic ischemia was created. 34 adult Sprague–Dawley rats underwent a laparotomy where the marginal arterioles of the sigmoid colon were ligated. After that, a section in the middle segment of the sigmoid colon was performed followed by an anastomosis. The presence of ischemia was assessed by measurement of visible light spectroscopy tissue oximetry and histological examination. Colonic function was assessed by evaluation of stool weight. Rats were killed at 1, 8 and 12 weeks after the operation. 12 rats were sham-operated. Enteric nervous system was evaluated by means of immunohistochemistry with NGFR p75. Quantitative analysis of the number of ganglia and ganglion cells in the myenteric plexus was performed. The surgical model of colonic ischemia significantly decreased tissue oxygenation (pre-surgical = 54.69 ± 7.32 %; post-surgical = 27.37 ± 9.2 %; p < 0.001). There was no disturbance in body-weight gaining in experimental groups and daily stool output did not vary after surgery (pre-surgical = 4.24 ± 0.94 g; post-surgical = 3.82 ± 1 g; p = 0.09). All experimental groups showed persistent ganglia. However, there was a significant decrease in the number of ganglia in all the experimental groups compared to control (1w: 45.91 ± 7.66; 8w: 44.17 ± 10.56; 12w: 36.17 ± 15.06 vs control: 56.88 ± 8.66; p < 0.01). The number of total ganglion cells was significantly reduced only in the experimental group killed at week 12 compared to control (1w: 539 ± 167.58; 8w: 488.58 ± 154.41; 12w: 343.94 ± 161.91 vs control: 513.96 ± 126.97; p < 0.01). The rate of ganglion cells per ganglia was significantly higher in the groups killed at week 1 and 8 versus control group (1w: 11.63 ± 2.53; 8w: 11.11 ± 2.56; 12w: 9.34 ± 1.16 vs control: 9.02 ± 1.81; p < 0.05). Long-term follow-up after surgically induced colonic ischemia in the rat showed a decreased number of ganglion cells and ganglia. Nevertheless, it did not produce aganglionosis.
NEAR-MINIMUM-TIME CONTROL OF DISTRIBUTED PARAMETER-SYSTEMS - ANALYTICAL AND EXPERIMENTAL RESULTS

We present a method for generating globally stable feedback control laws for maneuvers of distributed parameter structural systems. The method can accommodate system nonlinearity, and our proof of Lyapunov stability does not rely upon spatially discretizing distributed parameter systems. The approach applies directly to controllable distributed parameter systems that are open-loop conservative or dissipative. The most fundamental version of the formulation leads to controls that drive the system to a fixed point in the state space, but more generally, we develop tracking-type control laws to null the departure of the system state from a smooth target trajectory. Both analytical developments and experimental results are presented. The analytical results provide a theoretical foundation for the approach, whereas the experimental results provide conclusive evidence that the approach can be efficiently realized in actual hardware.
The Sources of Wilt‐resistance in the World Cotton Collection

Eight samples which were almost non-susceptible to wilt were isolated from the many forms in the world cotton collection. All of these forms are wild or semi-wild. Complex population varieties, especially those with varieties of Gossypium barbadense as ancestors, are also considered to be a source of wilt-resistance. Diploid wild species may also be used in the creation of wilt-resistant varieties.
Superior segment facet joint violation and cortical violation after minimally invasive pedicle screw placement

Abstract Background context Minimally invasive approaches to the lumbar spine allow for pedicle screw placement through a muscle-splitting paraspinal approach. These techniques are highly dependent on fluoroscopy and do not allow for direct visualization of anatomic landmarks. The effect of this on the accuracy of pedicle screw placement is not well described. The purpose of this study was to evaluate the rate of violation of the superior segment facet joint and rates of cortical violation after minimally invasive pedicle screw placement. Purpose To evaluate the rate of cortical violation and involvement of the superior segment facet after minimally invasive pedicle screw placement. Study design/setting Retrospective chart review. Patient sample Patients who underwent minimally invasive pedicle screw placement by a single surgeon between January 2004 and July 2009. Outcome measures Violation of the superior segment facet joint or cortical violation identified on computed tomography (CT). Methods This study consisted of a consecutive series of adult patients undergoing minimally invasive pedicle screw placement by a single surgeon for degenerative lumbar spinal conditions. Routine postoperative CT was obtained and evaluated for involvement of the superior segment facet joint and for cortical violation. Results Sixty-one consecutive patients (282 pedicle screws) met the study criteria and were included in the study, including 42 single-level fusions and 19 two-level fusions. Seven cortical breaches were identified for a rate of 2.48%. Seven patients had involvement of the superior-level facet for an incidence of 11.48%. One patient required revision for a malpositioned pedicle screw. Conclusions This study revealed a low rate of superior segment facet violation and cortical violation after minimally invasive pedicle screw placement. This rate of superior-level facet involvement is significantly lower than previously reported after open procedures. The rate of cortical violation is similar to previous reports in the literature with a low revision rate.
Induction chemotherapy and radiation therapy for T4 oropharyngeal carcinoma.

Between 1964 and 1996, 123 patients were treated for T4 oropharyngeal carcinoma; 93 were treated with radiation therapy alone; 30 were treated with induction chemotherapy and radiation therapy. Patients who received induction chemotherapy and radiation therapy were treated between 1985 and 1996; during this time 39 patients were treated with radiation therapy alone. Five-year local control rates for patients undergoing chemotherapy and radiation therapy, radiation therapy alone (all patients), and radiation therapy alone (patients treated since September 1985) were 63%, 38%, and 48%, respectively. The five-year rates of freedom from distant metastasis were 87%, 73%, and 76%, respectively. The five-year actuarial cause-specific survival rates were 58%, 27%, and 37%, respectively, while the five-year absolute survival rates were 42%, 17%, and 23%, respectively. Improvements in local control and freedom from distant metastasis in those receiving chemotherapy were not statistically significant, while the improvements in cause-specific survival and absolute survival were significant at the P ≤ 0.05 level. Induction chemotherapy may improve the cure rate for patients with T4 oropharyngeal carcinoma. Although encouraging, these data are nonrandomized and should be interpreted with caution. Radiat. Oncol. Invest. 7:98–105, 1999. © 1999 Wiley-Liss, Inc.
Proceedings: The SEED Grant Program: A Brief Synopsis of the Outcomes and Impact of CIRM’s First Research Initiative

In late 2006, the California Institute for Regenerative Medicine (CIRM) launched its first major research initiative to catalyze the nascent field of human embryonic stem cell (hESC) research at a time when federal funding of such studies was severely restricted. This Scientific Excellence through Exploration and Development (SEED) grant program supported a portfolio of scientific endeavors ranging from the most fundamental studies of hESC biology and behavior to exploring the therapeutic potential and value of these cells as tools of biomedical innovation. The SEED program attracted new investigators from all stages of their career into the field of hESC research, many of whom continue to pursue related studies through CIRM’s ongoing research and development programs or with the support of other funding organizations. The scientific impact of the SEED grant program can be measured in the scientific publications, disclosures of inventions, and measurable progress toward advancing CIRM’s mission and strategic objectives. In addition, CIRM has obtained valuable insights on how grant administration and policy considerations can affect the progress and conduct of scientific programs in a challenging period of both limits and opportunity.
Bimolecular Fluorescence Complementation

Defining the subcellular distribution of signaling complexes is imperative to understanding the output from that complex. Conventional methods such as immunoprecipitation do not provide information on the spatial localization of complexes. In contrast, BiFC monitors the interaction and subcellular compartmentalization of protein complexes. In this method, a fluororescent protein is split into amino- and carboxy-terminal non-fluorescent fragments which are then fused to two proteins of interest. Interaction of the proteins results in reconstitution of the fluorophore (Figure 1). A limitation of BiFC is that once the fragmented fluorophore is reconstituted the complex is irreversible. This limitation is advantageous in detecting transient or weak interactions, but precludes a kinetic analysis of complex dynamics. An additional caveat is that the reconstituted flourophore requires 30min to mature and fluoresce, again precluding the observation of real time interactions. BiFC is a specific example of the protein fragment complementation assay (PCA) which employs reporter proteins such as green fluorescent protein variants (BiFC), dihydrofolate reductase, b-lactamase, and luciferase to measure protein:protein interactions. Alternative methods to study protein:protein interactions in cells include fluorescence co-localization and Forster resonance energy transfer (FRET). For co-localization, two proteins are individually tagged either directly with a fluorophore or by indirect immunofluorescence. However, this approach leads to high background of non-interacting proteins making it difficult to interpret co-localization data. In addition, due to the limits of resolution of confocal microscopy, two proteins may appear co-localized without necessarily interacting. With BiFC, fluorescence is only observed when the two proteins of interest interact. FRET is another excellent method for studying protein:protein interactions, but can be technically challenging. FRET experiments require the donor and acceptor to be of similar brightness and stoichiometry in the cell. In addition, one must account for bleed through of the donor into the acceptor channel and vice versa. Unlike FRET, BiFC has little background fluorescence, little post processing of image data, does not require high overexpression, and can detect weak or transient interactions. Bioluminescence resonance energy transfer (BRET) is a method similar to FRET except the donor is an enzyme (e.g. luciferase) that catalyzes a substrate to become bioluminescent thereby exciting an acceptor. BRET lacks the technical problems of bleed through and high background fluorescence but lacks the ability to provide spatial information due to the lack of substrate localization to specific compartments. Overall, BiFC is an excellent method for visualizing subcellular localization of protein complexes to gain insight into compartmentalized signaling.
The hysteresis properties of multidomain magnetite and titanomagnetite/titanomaghemite in mid-ocean ridge basalts

Abstract Hysteresis measurements have been carried out on a suite of ocean-floor basalts with ages ranging from Quaternary to Cretaceous. Approximately linear, yet separate, relationships between coercivity (Bc) and the ratio of saturation remanence/saturation magnetization (Mrs/Ms) are observed for massive doleritic basalts with low-Ti magnetite and for pillow basalts with multi-domain titanomagnetites (with x=0.6). Even when the MORB has undergone low-temperature oxidation resulting in titanomaghemite, the parameters are still distinguishable, although offset from the trend for unoxidized multidomain titanomagnetite. The parameters for these iron oxides with different titanium content reveal contrasting trends that can be explained by the different saturation magnetizations of the mineral types. This plot provides a previously underutilized and non-destructive method to detect the presence of low-titanium magnetite in igneous rocks, notably MORB.
Left bundle branch block: Angiographic segmental wall motion abnormalities

Ventricular wall motion as studied with contrast ventriculography has been judged normal in the few previously reported cases of patients with left bundle branch block who have neither coronary artery disease nor diffuse cardiomyopathy. However, recent echocardiographic studies have demonstrated a high frequency of segmental asynergy of the septal wall in such patients. In this study left ventricular wall motion was analyzed in 15 patients with left bundle branch block and without significant coronary artery disease or diffuse cardiomyopathy. Biplane cineangiograms from these patients were compared with those from 100 consecutive patients with normal intraventricular conduction and without coronary artery disease or cardiomyopathy using two techniques: qualitative visual inspection and a computer-assisted quantitative method. By qualitative review, 6 of 15 patients with left bundle branch block had regional akinesia or dyskinesia as compared with none of 100 patients with normal intraventricular conduction (chi square = 42.3; P < 0.001). By quantitative review, 10 of 12 patients with left bundle branch block had abnormal wall motion along at least one hemiaxis. It is concluded that angiographic regional wall motion abnormalities are common in patients with left bundle branch block, even in the absence of coronary artery disease or diffuse cardiomyopathy. The abnormalities may result from the abnormal sequence of ventricular activation rather than from myocardial fibrosis.
Does Money Whiten? Intergenerational Changes in Racial Classification in Brazil:

The idea that “money whitens” is a classic topic in the sociological literature on race in Brazil. This article estimates the extent to which socioeconomic status translates into racial boundary-crossing (“whitening” and “darkening”) across generations. I do so by highlighting specifically how parents' racial classification of their children varies by status (i.e., parents' own educational levels). Results from a national household survey (PNAD 2005) show that highly educated nonwhite parents are more likely to classify their children as white than are comparable less-educated nonwhite parents. This happens because (1) more-educated nonwhite parents are more likely to marry whites and less likely to marry nonwhites and (2) more-educated interracial couples label their children white more often than do less-educated interracial couples. Comparisons with 1996 data suggest that recent shifts in racial politics have offset the whitening effects of college education for nonwhite men with white wives. The resul...
Overexpression of sarcolipin decreases myocyte contractility and calcium transient

Objective : Sarcolipin (SLN) is a novel 31-amino-acid protein associated with the sarcoplasmic reticulum (SR) whose function in cardiac muscle is poorly defined. In this study, we tested the hypothesis that SLN is a regulator of SR Ca2+ transport function by overexpressing SLN in adult rat ventricular myocytes which express low levels of SLN. Methods : Expression of SLN mRNA in rat tissues was analyzed by Northern blot as well by RT-PCR analysis. To define the role of SLN in cardiac muscle contractility, we overexpressed SLN in adult rat ventricular myocytes using adenoviral gene transfer techniques. Localization of SLN in the adult rat ventricular myocytes was determined using confocal microscopy. Myocyte contractility and calcium transients were measured using edge detection and Fura 2AM. Results : Our results demonstrate that overexpression of SLN decreased the cell shortening significantly when compared to control myocytes, whereas the time to peak contraction was not altered. In addition, SLN overexpression prolonged the time of 50% relaxation. Calcium transient analysis shows that time to 50% decay of [Ca2+]i was markedly prolonged in SLN-overexpressing myocytes (control −245.0 ± 3.78 vs. SLN −199.0 ± 3.25 ms, p <0.001). However, there were no significant differences in peak amplitudes of [Ca2+]i between SLN-overexpressing and control myocytes. We further demonstrate that SLN is localized within the SR membrane similar to PLB and SR Ca2+ ATPase. Co-immunoprecipitation studies indicate that SLN can physically interact with phospholamban. Conclusions : We conclude that SLN may play an important role in regulating the SR calcium ATPase pump, possibly by interacting with phospholamban.
Flame structure in aluminized wide-distribution AP composite propellants

Abstract Flame structure in wide-distribution ammonium-perchlorate (AP), hydroxyl-terminated-polybutadiene (HTPB) binder, aluminum (Al) composite propellants is studied using 2-D laminates with oxygenated binder. Very fine (2-μm) AP (FAP) is used to produce fuel-rich, matrix propellant (oxygenated binder) with a FAP/binder ratio of 75/25. Coarse AP (CAP) is simulated by pressed AP lamina. A flame-structure regime map for the CAP/oxy-fuel matrix interaction flame is generated as a function of oxy-fuel matrix thickness and pressure using high-speed video imaging analysis. The flame structure is found to be similar to that previously described using UV and IR imaging for non-aluminized laminates with split (diffusion) flame structure at high pressures ( P ) and low fuel thicknesses ( L ) and merged (partially premixed) flame structure for low P and L . The CAP/matrix flame regime boundary is shown to be correlated by Peclet number, indicating the relevance of conserved-scalar (Shvab–Zeldovich) theory with simple, global AP/hydrocarbon chemistry to describe the CAP/matrix diffusion-flame stoichiometry. Other findings include a slight stabilizing effect of Al on the 1-D premixed combustion of the marginally stable fuel-rich matrix. Also, when burning in 2-D laminates assisted slightly by the CAP/matrix interaction flame, the 75/25 matrix is found to burn flat (perpendicular to regression direction) even in the split-flame regime, in contrast to lower FAP/binder ratio matrices, which protrude into the gas-phase. Findings such as these are essential for developing a fundamental understanding of and truly predictive simulation capability for combustion of wide-distribution AP propellants, including plateau, mesa and bi-plateau propellants.
Developments in juvenile justice during the decade of the 70s: Juvenile detention facilities

A number of important developments in juvenile justice during the decade of the 70s are identified. Data were obtained from a sample of juvenile detention facilities in the late 1960s and again, from the same sample, in the late 1970s. The data obtained included the perceived purpose of detention, information concerning the detainees and personnel, and procedural and program information. The two sets of data were compared to determine whether the developments in the juvenile justice system were reflected in the detention segment of the system.
Transverse interaction in configuration mixing calculations

Abstract An expression of the general matrix element of the transverse interaction appropriate for the Dirac-Fock-Slater formalism is obtained straightforwardly by using the vector-spherical-harmonics expansion technique.
The asymptotic behavior of quadratic forms in heavy-tailed strongly dependent random variables☆

Abstract Suppose that Xt = ∑∞j=0cjZt−j is a stationary linear sequence with regularly varying cj's and with innovations {Zj} that have infinite variance. Such a sequence can exhibit both high variability and strong dependence. The quadratic form Q n = ∑ n t 1 s=1 \ gh(t − s)X t X s plays an important role in the estimation of the intensity of strong dependence. In contrast with the finite variance case, n − 1 2 (Q n − EQ n ) does not converge to a Gaussian distribution. We provide conditions on the cj's and on \ gh for the quadratic form Qn, adequately normalized and randomly centered, to converge to a stable law of index α, 1
Influence of injected psychoactive drugs on cyclic AMP levels in mouse brain and lung following microwave irradiation.

Abstract Psychoactive drugs were injected into mice, at specified time periods, the animals were sacrificed by exposure to 500 msec irradiation and tissues from lung, cerebral cortex and diencephalon were analyzed for adenosine cyclic 3',5'-monophosphate (cyclic AMP) content. Chlorpromazine, chlorpromazine sulfoxide, p-OH-amphetamine, caffeine, papaverine, pargyline and amitriptyline caused an increase in the cyclic AMP in the cerebral cortex while α-methyl p-tyrosine produced a decrease and reserpine elicited no change. In the diencephalon, cyclic AMP was elevated by reserpine, chlorpromazine and caffeine, depressed by α-methyl p-tyrosine and chlorpromazine sulfoxide while the remaining agents caused no change. The following agents were observed to raise cyclic AMP in pulmonary tissue: reserpine, α-methyl p-tyrosine, papaverine, chlorpromazine, chlorpromazine sulfoxide and amitriptyline. Cyclic nucleotide content in the lung was reduced by amphetamine, p-OH-amphetamine, pargyline and D-lysergic acid diethylamide (LSD). These findings show that in vivo, psychoactive drugs influence steady-state levels of cyclic AMP in a manner that can differ from their action in vitro. Furthermore, the same drug does not affect the cyclic nucleotide levels in an identical manner in different regions within the brain or in the lung.
Tuberculosis and the Health Care Worker: A Historical Perspective

Many hospital outbreaks of tuberculosis have occurred in recent years in the United States, resulting in tuberculosis infection and disease among health care workers and patients. Several hospital workers have died of nosocomially acquired multidrug-resistant tuberculosis. Assuring the safety of the health care worker with respect to tuberculosis has become an urgent priority. A review of the medical literature of the past 100 years reveals that our current view of tuberculosis care as an occupational hazard emerged only in the 1950s, after a fierce and extensive debate. Many authorities had felt that care of the tuberculous patient conferred a health advantage to the care provider. This paper reviews this debate and considers steps taken decades ago, before our current environmental interventions were available to ensure the safety of the health care worker.
A preliminary examination of the "Real Men. Real Depression" campaign

This study reports on a preliminary evaluation of the National Institute of Mental Health (NIMH)-sponsored “Real Men. Real Depression” (RMRD) campaign. Two- hundred-nine men with a range of help-seeking attitudes and gender-role conflict (GRC) reviewed the RMRD brochure, a similar brochure excluding
Analysis and correction of ground reflection effects in measured narrow‐band sound spectra using cepstral techniques

Ground reflections generate undesirable effects on acoustic measurements such as those conducted outdoors for jet noise research, aircraft certification, and motor vehicle regulation. Cepstral techniques developed in speech processing are adapted to identify echo delay time and to correct for ground reflection effects. A sample result is presented using an actual narrowband sound pressure level spectrum. The technique can readily be adapted to existing fast Fourier transform type spectrum measurement instrumentation to provide field measurements/of echo time delays.