cssi/SciSciGPT-SciSciNet huggingface dataset:
Convergence of Heteromodal Lexical Retrieval in the Lateral Prefrontal Cortex

Abstract Lexical retrieval requires selecting and retrieving the most appropriate word from the lexicon to express a desired concept. Prior studies investigating the neuroanatomic underpinnings of lexical retrieval used lesion models that rely on stereotyped vascular distributions, functional neuroimaging methods that lack causal certainty, or awake brain mapping that is typically limited to narrow cortical exposures. Further, few studies have probed lexical retrieval with tasks other than picture naming and when non-picture naming lexical retrieval tasks have been applied, both convergent and divergent models emerged. Because of this existing controversy, we set out to test the hypothesis that cortical and subcortical brain regions specifically involved in lexical retrieval in response to visual and auditory stimuli represent overlapping neural systems. Fifty-three patients with dysnomic aphasia due to dominant-hemisphere brain tumors performed four language tasks: picture naming, auditory naming, text reading, and describing line drawings with correct syntax. A subset of participants also underwent the Quick Aphasia Battery which provides a validated measure of lexical retrieval via the word finding subtest. Generalized linear modeling and principal components analysis revealed multicollinearity between picture naming, auditory naming, and word finding, implying redundancies between the linguistic measures. Support vector regression lesion-symptom mapping across participants was used to model accuracies on each of the four language tasks. Picture naming and auditory naming survived cluster-level corrections. Specifically, lesions within overlapping clusters of 8,333 voxels and 21,512 voxels in the left lateral PFC were predictive of impaired picture naming and auditory naming, respectively. These data indicate a convergence of heteromodal lexical retrieval within the PFC. Importance of the Study Lexical retrieval (i.e., selecting and retrieving words to convey desired concepts) is a crucial component of language processing. However, existing studies of the neuroanatomic underpinnings of lexical retrieval lack causal relationships and have provided conflicting evidence, suggesting both convergent and divergent models. In order to resolve these conflicting models, we used lesion-symptom mapping to investigate lexical retrieval in 53 patients with dominant-hemisphere brain tumors. We observed significant associations between performance on visual and auditory naming tasks. Further, performance on these tasks predicted performance on a validated neuropsychological measure of lexical retrieval. Critically, multivariate, nonparametric lesion-symptom mapping within a brain tumor framework revealed that lesions in overlapping regions of the left lateral prefrontal cortex (PFC) predict impaired visual and auditory naming. In a clinical context, this approach to identifying causal brain-behavior relationships could help to guide brain tumor therapies such as cytoreductive surgery and supportive rehabilitation services.
Time for two annual Turing awards

It is the season when we recognize an extraordinary research contribution to computing with the ACM A.M. Turing Award. I propose a change.
Chiplet/Interposer Co-Design for Power Delivery Network Optimization in Heterogeneous 2.5D ICs

In this article, we present an effective methodology for co-design, co-analysis and the system-level optimization of chiplet/interposer power delivery network (PDN) in 2.5D IC designs. In our methodology, we first generate a commercial-grade heterogeneous 2.5D IC designs including full signal routing and power delivery. We then perform our PDN co-analysis in frequency and time domains on the entire PDN to evaluate various mechanisms added to our PDN designs. Based on our co-analysis results, we perform the system-level optimization on both interposer and chiplet PDNs with the stable performance of power delivery. Finally, we perform power, performance and area (PPA) analysis and power integrity (PI) on our 2.5D designs and discuss tradeoffs in chiplet and interposer levels due to PDN optimization. Our experiments show 27.17% improvement in the overall IR-drop in the optimized 2.5D IC design by increasing the interposer PDN occupancy by 5.52% and inserting the additional PDN grids in chiplet designs. However, we also observe tradeoffs in terms of PPA and PI. By PDN optimization, the optimized design has 11.6% increase of the total power, while the area of 2.5D design remains the same. Moreover, from the perspective of PI, the tradeoffs are shown by 0.6% reduction of power efficiency, 32.6% higher output ripple, and 31.5% higher initial ringing because of an inductive behavior of interposer PDN in the optimized design.
Erratum to: Open Clusters

We have used the Lund catalogue of Open Cluster Data, kindly supplied by Gosta Lynga (1987) and updated by Kenneth Janes (1989). This data has been used by Lynga and Palous (1987) to describe the local kinematics of open star clusters, and by Janes, Tilley, and Lynga (1988) to describe the general properties of the open cluster system. The galactic distribution of open clusters was discussed by Janes and Adler (1982).
Unsupervised learning applied to image coding

We examine the performance of several neural network vector quantization (VQ) methods on image coding. The VQ methods we look at are Kohonen's Self-Organizing Feature Map (KSOFM), Frequency-Sensitive Competitive Learning (FSCL), and Self-Creating and Organizing Neural Network (SCONN). We also look at variations of these algorithms by combining different methods. Our simulation results show that the best performance is achieved by the SCONN and the combination KSOFM and FSCL.
Abstract 2755: Aggressive thyroid carcinomas are intrinsically resistant to apoptosis but can be effectively targeted by a Bcl2 family inhibitor

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Poorly differentiated thyroid cancer (PDTC) is a very aggressive and invasive neoplasm that arises from the thyroid follicular cells and is characterized by a poor prognosis due to its resistance to current therapeutic modalities, including radioiodine and chemotherapy. Therefore, targeted therapy for this type of cancer is an area of high interest and several kinase inhibitors are currently in clinical trials. However, these inhibitors present certain limitations due to intrinsic or acquired drug resistance. Thus, targeted therapy using drug combinations to increase efficiency and prevent resistance is an attractive strategy. However, one major obstacle to our understanding of the molecular mechanisms leading to tumor aggressiveness and drug resistance in PDTCs has been the relative rarity of this disease and the absence of relevant mouse models. By simultaneously activating Kras and deleting p53 in thyroid follicular cells, we have generated a novel mouse model that develops papillary thyroid cancer invariably progressing to PDTC. These tumors are morphologically and functionally similar to their human counterparts and depend on MEK/ERK signaling for proliferation. Driver pathway inhibition in primary mouse carcinomas as well as carcinoma-derived cells, using the FDA approved MEK inhibitor, Trametinib, shows that these tumors are intrinsically resistant to cell death, due at least in part to their high levels of expression of the anti-apoptotic Bcl2 family members Bcl2a1 and Mcl1. Similar overexpression of anti-apoptotic molecules is observed in a large subset of human thyroid carcinomas. Our in vitro and in vivo studies show that Obatoclax, a small molecule pan inhibitor of the anti-apoptotic Bcl2 family members, induces cell death in mouse PDTC cell lines as well as in human thyroid cancer cells. This effect is even greater when combining Obatoclax with Trematinib. Furthermore, Obatoclax also synergizes with chemotherapeutic drugs such as doxorubicin and paclitaxel, currently used in the treatment of thyroid cancer. Therefore, our study, using a new PDTC mouse model as well as human thyroid cancer cell lines, shows that overexpression of anti-apoptotic Bcl2 family members marks aggressive thyroid carcinomas which can be targeted by inhibitors such as Obatoclax, alone or in combination with other therapeutic approaches. These data support the development of novel effective treatment options for aggressive thyroid carcinomas, which can be rapidly translated to the clinical setting. Citation Format: Devora Champa, Ronald Ghossein, Antonio Di Cristofano. Aggressive thyroid carcinomas are intrinsically resistant to apoptosis but can be effectively targeted by a Bcl2 family inhibitor. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2755. doi:10.1158/1538-7445.AM2014-2755
Periodical Pedagogy in the Undergraduate Classroom

This essay considers methods for encouraging students at smaller, regional universities to engage in Victorian periodicals research. Even at institutions where access to hardcopy originals and digitized resources is limited, students desire training in research methodology in order to engage with the vast amount of material available to them in the wake of the “digital revolution.” Instructors at these institutions should work to develop teaching collections of hardcopy originals in order to complement digitized resources and to enable students to engage with the materiality of print culture.
Inhibition of the High Affinity Fc Receptor (FcγRI) on Human Monocytes by Porphyrin Photosensitization Is Highly Specific and Mediated by the Generation of Superoxide Radicals

Abstract p72 high affinity receptors (Fc gamma RI) for the Fc portion of IgG molecules on human peripheral blood monocytes mediate a variety of beneficial functions, but also have deleterious effects in certain clinical situations. In the present study, the photosensitizing porphyrins hematoporphyrin derivative and dihematoporphyrin ether (DHE), which are known to preferentially affect the cell membrane, were found to significantly inhibit binding of mouse IgG2a antibodies to the ligand binding site of Fc gamma RI on human peripheral blood monocytes and the U937 human monocytic cell line. Fc gamma RI receptors could be identified with a monoclonal antibody which recognizes an epitope distinct from the ligand binding site, indicating that photosensitization induced a structural alteration rather than loss of the receptor molecule from the cell surface. The effect of DHE and light appeared to be highly specific, since binding of monoclonal antibodies to other surface structures was not decreased. DHE plus light-induced modulation of Fc gamma RI was found to be mediated by superoxide anions, since addition of a mimic of superoxide dismutase restored both binding of mouse IgG2a to Fc gamma RI as well as human monocyte accessory cell function. These studies identify porphyrin photosensitization as a unique mechanism by which to selectively down-regulate Fc gamma RI-mediated functions.
Analytical Tools for Natural Algorithms

We introduce an analytical tool to study the convergence of bidirectional multiagent agreement systems and use it to sharpen the analysis of various natural algorithms, including flocking, opinion consensus, and synchronization systems. We also improve classic bounds about colored random walks and discuss the usefulness of algorithmic proofs.
History, Contemporary Outcomes, and Future of Penile Prostheses: A Review of the Literature

Abstract Introduction Since their introduction, penile prostheses have consistently remained a superior treatment option for men with erectile dysfunction (ED) refractory to conservative measures. Ongoing enhancements to prosthetic design, materials, and surgical techniques have resulted in improved outcomes. Aim To review available literature on notable historical advancements and improvements of the penile prosthesis, summarize contemporary outcomes of recent devices, and discuss possible future directions of the penile prosthesis. Methods A PubMed search was performed of all articles published from 1960 to present relating to penile prosthesis. Priority was given to series with 12 months of follow‐up or greater, larger series, and studies reporting on outcomes of more recent prosthetic models. Main Outcome Measures Main outcomes included historical review of improvements leading to, and contemporary series reporting on rates of mechanical failures, infections, and satisfaction with penile prostheses. Results Penile prostheses have undergone numerous enhancements since initial reports of synthetic materials utilized in the 1950s. Among others, recent notable device enhancements include Parylene coating, Bioflex® material, Inhibizone TM antibacterial impregnation, hydrophilic coating, lockout valves, and easy release pump mechanisms, all of which have improved mechanical reliability, reduced infection rates, and/or improved patient satisfaction with penile prostheses. Contemporary series of 3‐piece penile prostheses report mechanical survival of 81–94%, 68–89%, and 57–76% at 5, 10, and 15 years, respectively. Infection rates of current devices are 1–2% in first‐time, low‐risk populations, and 2–3% for higher risk groups, with patient and partner satisfaction at 92–100% and 91–95%, respectively. Two‐piece and malleable devices are associated with slightly higher mechanical reliability and decreased patient satisfaction. Minimal data currently exist on the outcomes of selected patient populations, including Peyronie's disease and corporal fibrosis. Conclusions Penile prostheses are associated with excellent, long‐term outcomes and remain the gold‐standard treatment for men with refractory ED. Additional research with prospective studies utilizing objective measures and standardized questionnaires is required. Trost L and Hellstrom WJG. History, contemporary outcomes, and future of penile prostheses: A review of the literature. Sex Med Rev 2013;1:150–163.
Nicodemus and The Samaritan Woman: Contrasting Models of Discipleship

An investigation of the narratives within the first six chapters of the Fourth Gospel indicates that Nicodemus and the Samaritan woman function as foils within the larger typology of persons from G...
Proposals for standardization of total protein assays.

The Standards Committee of the AACC presents a discussion of the nature of total serum protein and the problems associated with its determination. Proposals are made that protein be defined as polypeptide material, and that a reference preparation be promulgated for interlaboratory use. The reference material suggested is bovine serum albumin, produced to rigid specifications and distributed as a stable 7% (w/v) solution, the concentration of which has been established by careful dry weight assay. Comments of readers are invited.
Inclusions in membranes

Recent work on membrane-inclusion and inclusion-inclusion interactions has focused on models of the membrane based on curvature elasticity. The resulting deformation profiles are non-monotonic and lead to either attractive or repulsive interactions. In addition, considerations of thermal membrane fluctuations and the membrane-inclusion contact angle have led to predictions of new long-range interactions.
Expression Platforms for Producing Eukaryotic Proteins: A Comparison of E. coli Cell-Based and Wheat Germ Cell-Free Synthesis, Affinity and Solubility Tags, and Cloning Strategies

Vectors designed for protein production in Escherichia coli and by wheat germ cell-free translation were tested using 21 well-characterized eukaryotic proteins chosen to serve as controls within the context of a structural genomics pipeline. The controls were carried through cloning, small-scale expression trials, large-scale growth or synthesis, and purification. Successfully purified proteins were also subjected to either crystallization trials or 1H–15N HSQC NMR analyses. Experiments evaluated: (1) the relative efficacy of restriction/ligation and recombinational cloning systems; (2) the value of maltose-binding protein (MBP) as a solubility enhancement tag; (3) the consequences of in vivo proteolysis of the MBP fusion as an alternative to post-purification proteolysis; (4) the effect of the level of LacI repressor on the yields of protein obtained from E. coli using autoinduction; (5) the consequences of removing the His tag from proteins produced by the cell-free system; and (6) the comparative performance of E. coli cells or wheat germ cell-free translation. Optimal promoter/repressor and fusion tag configurations for each expression system are discussed.
Classification and Structural Analysis of Live and Dead Salmonella Cells Using Fourier Transform Infrared Spectroscopy and Principal Component Analysis

Fourier transform infrared spectroscopy (FT-IR) was used to detect Salmonella Typhimurium and Salmonella Enteritidis food-borne bacteria and to distinguish between live and dead cells of both serotypes. Bacteria cells were prepared in 10(8) cfu/mL concentration, and 1 mL of each bacterium was loaded individually on the ZnSe attenuated total reflection (ATR) crystal surface (45° ZnSe, 10 bounces, and 48 mm × 5 mm effective area of analysis on the crystal) and scanned for spectral data collection from 4000 to 650 cm(-1) wavenumber. Analysis of spectral signatures of Salmonella isolates was conducted using principal component analysis (PCA). Spectral data were divided into three regions such as 900-1300, 1300-1800, and 3000-2200 cm(-1) based on their spectral signatures. PCA models were developed to differentiate the serotypes and live and dead cells of each serotype. Maximum classification accuracy of 100% was obtained for serotype differentiation as well as for live and dead cells differentiation. Soft independent modeling of class analogy (SIMCA) analysis was carried out on the PCA model and applied to validation sample sets. It gave a predicted classification accuracy of 100% for both the serotypes and its live and dead cells differentiation. The Mahalanobis distance calculated in three different spectral regions showed maximum distance for the 1800-1300 cm(-1) region, followed by the 3000-2200 cm(-1) region, and then by the 1300-900 cm(-1) region. It showed that both of the serotypes have maximum differences in their nucleic acids, DNA/RNA backbone structures, protein, and amide I and amide II bands.
Modeling binaural responses in the auditory brainstem to electric stimulation of the auditory nerve.

Bilateral cochlear implants (CIs) provide improvements in sound localization and speech perception in noise over unilateral CIs. However, the benefits arise mainly from the perception of interaural level differences, while bilateral CI listeners’ sensitivity to interaural time difference (ITD) is poorer than normal. To help understand this limitation, a set of ITD-sensitive neural models was developed to study binaural responses to electric stimulation. Our working hypothesis was that central auditory processing is normal with bilateral CIs so that the abnormality in the response to electric stimulation at the level of the auditory nerve fibers (ANFs) is the source of the limited ITD sensitivity. A descriptive model of ANF response to both acoustic and electric stimulation was implemented and used to drive a simplified biophysical model of neurons in the medial superior olive (MSO). The model’s ITD sensitivity was found to depend strongly on the specific configurations of membrane and synaptic parameters for different stimulation rates. Specifically, stronger excitatory synaptic inputs and faster membrane responses were required for the model neurons to be ITD-sensitive at high stimulation rates, whereas weaker excitatory synaptic input and slower membrane responses were necessary at low stimulation rates, for both electric and acoustic stimulation. This finding raises the possibility of frequency-dependent differences in neural mechanisms of binaural processing; limitations in ITD sensitivity with bilateral CIs may be due to a mismatch between stimulation rate and cell parameters in ITD-sensitive neurons.
Statistical activities of the organization of American States and the inter-American statistical institute

Abstract The Organization of American States (OAS) and the Inter-American Statistical Institute (IASI) are two related organizations which have long been involved in statistical activities and publishing. One of IASI's major contributions has been in the Census of the Americas program. The Committee for the Improvement of National Statistics, created by IASI, has recently been active in the area of household surveys. The Inter-Ameriean Statistical Conferences foster cooperative activities among OAS members. The Inter-American Center for the Teaching of Statistics is jointly sponsored by IASI and the University of Chile. The OAS experience shows a growing collaboration with other international organizations in the field of statistics collection and compilation.
Pathways of Pacific water across the Chukchi Sea: A numerical model study

[1] Pathways of Pacific Water flowing from the North Pacific Ocean through Bering Strait and across the Chukchi Sea are investigated using a two-dimensional barotropic model. In the no-wind case, the flow is driven only by a prescribed steady northward flow of 0.8 Sv through Bering Strait. The resulting steady state circulation consists of a broad northeasterly flow, basically following the topography, with a few areas of intensified currents. About half of the inflow travels northwest through Hope Valley, while the other half turns somewhat toward the northeast along the Alaskan coast. The flow through Hope Valley is intensified as it passes through Herald Canyon, but much of this flow escapes the canyon to move eastward, joining the flow in the broad valley between Herald and Hanna Shoals, another area of slightly intensified currents. There is a confluence of nearly all of the flow along the Alaskan coast west of Pt. Barrow to create a very strong and narrow coastal jet that follows the shelf topography eastward onto the Beaufort shelf. Thus in this no-wind case, nearly all of the Pacific Water entering the Chukchi Sea eventually ends up flowing eastward along the narrow Beaufort shelf, with no discernable flow across the shelf edge toward the interior Canada Basin. Travel times for water parcels to move from Bering Strait to Pt. Barrow vary tremendously according to the path taken; e.g., less than 6 months along the Alaskan coast, but about 30 months along the westernmost path through Herald Canyon. This flow field is relatively insensitive to idealized wind-forcing when the winds are from the south, west or north, in which cases the shelf transports tend to be intensified. However, strong northeasterly to easterly winds are able to completely reverse the flows along the Beaufort shelf and the Alaskan coast, and force most of the throughflow in a more northerly direction across the Chukchi Sea shelf edge, potentially supplying the surface waters of the interior Canada Basin with Pacific Water. The entire shelf circulation reacts promptly to changing wind conditions, with a response time of ∼2–3 days. The intense coastal jet between Icy Cape and Pt. Barrow implies that dense water formed here from winter coastal polynyas may be quickly swept away along the coast. In contrast, there is a relatively quiet nearshore region to the west, between Cape Lisburne and Icy Cape, where dense water may accumulate much longer and continue to become denser before it is carried across the shelf.
Cleaving mercury-alkyl bonds: a functional model for mercury detoxification by MerB.

The extreme toxicity of organomercury compounds that are found in the environment has focused attention on the mechanisms of action of bacterial remediating enzymes. We describe facile room-temperature protolytic cleavage by a thiol of the Hg-C bond in mercury-alkyl compounds that emulate the structure and function of the organomercurial lyase MerB. Specifically, the tris(2-mercapto-1-t-butylimidazolyl)hydroborato ligand [TmBut], which features three sulfur donors, has been used to synthesize [TmBut]HgR alkyl compounds (R = methyl or ethyl) that react with phenylthiol (PhSH) to yield [TmBut]HgSPh and RH. Although [TmBut]HgR compounds exist as linear two-coordinate complexes in the solid state, 1H nuclear magnetic resonance spectroscopy indicates that the complexes exist in rapid equilibrium with their higher-coordinate [κ2-TmBut]HgR and [κ3-TmBut]HgR isomers in solution. Facile access to a higher-coordinate species is proposed to account for the exceptional reactivity of [TmBut]HgR relative to that of other two-coordinate mercury-alkyl compounds.
Single-boss crevice former for studying crevice corrosion of UNS S32003 in chloride-containing solution at high temperature

Abstract We studied crevice corrosion of UNS S32003 using a single-boss crevice former. This crevice assembly with a single boss at the center is a modification of the commonly used multiple-crevice assembly (MCA). This design effectively prevents unwanted crevice corrosion outside the crevice of interest. Our single-boss crevice assembly produces comparable repassivation potentials obtained using cyclic potentiodynamic polarization (CPP), Tsujikawa–Hisamatsu Electrochemical (THE), potentiodynamic–galvanostatic–potentiodynamic (PD–GS–PD), and potentiostatic (PS) techniques. Considering the degree of attack, we found that the THE technique is the most powerful for forming a deep, wide, and continuous crevice corrosion site, while the PS technique is the least powerful technique at potentials slightly above the repassivation potential. A galvanostatic hold in step 2 of the THE and PD–GS–PD techniques successfully grows a deep localized corrosion site, as indicated by a deep crevice corrosion attack found in samples tested with these techniques. The PS step (step 3) in the THE technique allows the grown localized corrosion site formed by a previous step (a galvanostatic hold) to propagate inward and along the crevice mouth, creating a wide and continuous crevice corrosion attack along the crevice mouth. Metastable pits play a role in crevice corrosion of UNS S32003 alloy in this study, as indicated by a large number of metastable pits in the crevice region. The ferrite phase is preferentially attacked by metastable pits.
A Semi-Analytical Model and Characterization Techniques for Concentrated Photovoltaic Multijunction Solar Cells

A semi-analytical model for multijunction solar cells is established by extending the detailed balance model to include nonradiative recombination and other aspects of actual devices. Novel characterization techniques for multijunction solar cells are described.
Ultraviolet radiation and skin cancer in man.

Abstract Skin cancers are the most common malignant tumors of white-skinned people. It is well established that nonmelanoma skin cancer is almost entirely caused by chronic exposure to solar ultraviolet radiation (uvr), and malignant melanoma is strongly related to ultraviolet radiation exposure. In the U.S.A., 300,000–400,000 new skin cancers develop per year, almost all of which are preventable. About 5,000 deaths per year are due to nonmelanoma skin cancer, and a similar number are due to malignant melanoma. Reducing outdoor exposure during the 2 hr between 11 am and 1 pm will prevent 50% of the daily carcinogenic uvr dose from reaching the skin. Most of the skin cancers occur in a small proportion of the population (particularly Irish, Scottish, and Welsh) who are genetically predisposed to sunburning and who suntan little. Anthropogenic disturbance of the stratospheric ozone layer by aircraft exhaust and chlorofluorocarbons may result in a significant increase in solar uvr reaching earth and may cause an increase of 60% or more in skin cancer incidence early in the next century.
GCNF‐dependent repression of BMP‐15 and GDF‐9 mediates gamete regulation of female fertility

To determine the function of germ cell nuclear factor (GCNF) in female reproduction, we generated an oocyte-specific GCNF knockout mouse model (GCNFfl/flZp3Cre+). These mice displayed hypofertility due to prolonged diestrus phase of the estrous cycle and aberrant steroidogenesis. These reproductive defects were secondary to a primary defect in the oocytes, in which expression of the paracrine transforming growth factor-β signaling molecules, bone morphogenetic protein 15 (BMP-15) and growth differentiation factor 9 (GDF-9), were up-regulated in GCNFfl/flZp3Cre+ females at diestrus. This was a direct effect of GCNF, as molecular studies showed that GCNF bound to DR0 elements within the BMP-15 and GDF-9 gene promoters and repressed their reporter activities. Consistent with these findings, abnormal double-oocyte follicles, indicative of aberrant BMP-15/GDF-9 expression, were observed in GCNFfl/flZp3Cre+ females. The Cre/loxP knockout of GCNF in the oocyte has uncovered a new regulatory pathway in ovarian function. Our results show that GCNF directly regulates paracrine communication between the oocyte and somatic cells by regulating the expression of BMP-15 and GDF-9, to affect female fertility.
Proteolytic dissection of rat brain hexokinase: determination of the cleavage pattern during limited digestion with trypsin

Abstract Limited treatment of rat brain hexokinase (ATP: d -hexose-6-phosphotransferase; EC 2.7.1.1) with trypsin causes cleavage of the Mr 98K enzyme into three major fragments having molecular weights of 10K, 40K, and 50K, with intermediates of Mr 60K and 90K being detected. This information, in conjunction with N- and C-terminal analysis of the intact enzyme and tryptic cleavage products, has established the tryptic cleavage pattern as where T1 and T2 indicate tryptic cleavage sites; cleavage at only T1 or T2 gives rise to the 90K or 60K intermediate, respectively. Confirmation of this cleavage pattern has been provided by two-dimensional peptide mapping using Staphylococcus aureus V8 protease, and epitope mapping with two monoclonal antibodies directed against rat brain hexokinase. The epitopes recognized by one of the monoclonal antibodies is located within the 40K C-terminal fragment while the epitope for the other monoclonal antibody lies within the 50K fragment. A two-dimensional peptide mapping-immunoblotting technique has permitted a more defined localization of these epitopes to specific regions within these major tryptic cleavage fragments. Complete tryptic cleavage of the enzyme occurs with only modest (~20%) loss of catalytic activity, and the cleaved enzyme retains many of the properties of intact hexokinase. Specifically, there was no effect of cleavage on the Km for Glc or the Ki for Glc-6-P, though a slight decrease in Km for ATP was consistently noted to result from cleavage. Furthermore, like the intact enzyme, cleaved hexokinase retained the ability to bind to outer mitochondrial membranes in a Glc-6-P-sensitive manner. Under nondenaturing conditions, the cleaved fragments remain associated by noncovalent forces. Thus, the cleaved enzyme sedimented at a rate comparable to intact enzyme during centrifugation on sucrose density gradients, and migrated only slightly faster when electrophoresed on gradient acrylamide gels under nondenaturing conditions.
Evidence That Receptor Activator of Nuclear Factor (NF)-κB Ligand Can Suppress Cell Proliferation and Induce Apoptosis through Activation of a NF-κB-independent and TRAF6-dependent Mechanism

The receptor activator of NF-kappaB ligand (RANKL), a recently identified member of the tumor necrosis factor (TNF) superfamily, has been shown to induce osteoclastogenesis and dendritic cell survival. Most members of the TNF superfamily suppress cell proliferation and induce apoptosis, but whether RANKL does so is not known. We demonstrate that treatment of monocyte RAW 264.7 cells with RANKL induces dose-dependent growth inhibition (IC50 = 10 ng/ml) as determined by dye uptake and [3H]thymidine incorporation methods. Suppression of RANKL-induced NF-kappaB activation by dominant-negative IkappaBalpha or by the NEMO-peptide had no effect on RANKL-induced cell growth inhibition. Inhibition of RANKL-induced JNK activation, however, abolished the RANKL-induced apoptosis. Suppression of interaction of RANK with TRAF6 by TRAF6-binding peptide abrogated the anti-proliferative effects of RANKL, suggesting the critical role of TRAF6. Flow cytometric analysis of cells treated with RANKL showed accumulation of cells in G0/G1 phase of the cell cycle, and this accumulation correlated with a decline in the levels of cyclin D1, cyclin D3, and cyclin E and an increase in cyclin-dependent kinase inhibitor p27 (Kip). Flow cytometric analysis showed the presence of annexin V-positive cells in cultures treated with RANKL. RANKL-induced apoptosis was further confirmed using calcein AM/ethidium homodimer-1 dye and cleavage of poly(ADP-ribose) polymerase (PARP), procaspase 3, and procaspase 9; benzyloxycarbonyl-VAD, the pancaspase inhibitor, suppressed the PARP cleavage. Thus, overall, our studies indicate that RANKL can inhibit cell proliferation and induce apoptosis through a TRAF-6-dependent but NF-kappaB-independent mechanism.
Developmental Features of Rapid Aiming Arm Movements Across the Lifespan

Using a lifespan approach, the authors investigated developmental features of the control of ballistic aiming arm movements by manipulating movement complexity, response uncertainty, and the use of precues. Four different age groups of participants (6- and 9-year-old boys and girls and 24- and 73-year-old men and women, 20 participants in each age group) performed 7 types of rapid aiming arm movements on the surface of a digitizer. Their movement characteristics such as movement velocity, normalized jerk, relative timing, movement linearity, and intersegment intervals were profiled. Analyses of variance with repeated measures were conducted on age and task effects in varying movement complexity (Study 1), response uncertainty (Study 2), and precue use (Study 3) conditions. Young children and senior adults had slower, more variant, less smooth, and less linear arm movements than older children and young adults. Increasing the number of movement segments resulted in slower and more variant responses. Movement accuracy demands or response uncertainty interacted with age so that the 6- and 74-year-old participants had poorer performances but responded similarly to the varying treatments. Even though older children and young adults had better performances than young children and senior adults, their arm movement performance declined when response uncertainty increased. The analyses suggested that young children's and senior adults' performances are poorer because less of their movement is under central control, and they therefore use on-line adjustments. In addition, older children and young adults use a valid precue more effectively to prepare for subsequent movements than do young children and senior adults, suggesting that older children and young adults are more capable of organizing motor responses than are young children and senior adults.
Preface: Fidelity to the Unruly

The late twentieth century witnessed unprecedented attention to ethics in literary studies. The notion of an “Ethical Turn” was in fact coined to attest to this burgeoning academic interest. Unfortunately this kind of designation, while useful in pointing to a perceived shift in the concerns of interpretive communities, risks homogenizing the unruly voices responsible for such a turn.1 A genealogy of the turn quickly reveals its contested origin, its fraught beginnings. Is/was the “Ethical Turn” a mere moment in the cyclical history of interpretive turns, situated between the “Linguistic Turn” and the nascent “Aesthetic Turn,” with the “Cultural Turn” eagerly waiting in the hermeneutic queue?2 While debates over the function of literary criticism surely date back to the very inception of literature, Frank Kermode detects in today’s generation of critics an unparalleled hostility to both the ethical value of criticism (which, in the past, “was extremely important; it could be taught; it was an influence for civilization and even for personal amendment” [“Literary Criticism” 194]) and the aesthetic value of literature in its own right:
Na+ channel β1 subunit mRNA expression in developing rat central nervous system

The sodium channel beta 1 subunit (Na beta 1) is a component of the rat brain voltage-dependent sodium channel. We have used nonradioactive in situ hybridization cytochemical techniques to demonstrate that transcript levels of Na beta 1 are differentially upregulated during postnatal development of several CNS regions, with selective labeling of specific neuronal populations. In the hippocampus, labeling of the pyramidal cell layer (particularly in the CA3 region) and dentate granule cells was initially observed at postnatal day 2 (P2) and P10, respectively, and became progressively more intense with maturation. Labeled cells were first observed in the hilus at P10. In the developing cerebellum, transient labeling was observed in the external granule cell layer beginning at P1 while label increased in the internal granule cell layer up to P21. Purkinje cells showed significant label beginning at P4 and increasing up to P21. Weak signal was seen in neurons of deep nuclei at P1 and increased up to P21. Na beta 1 labeling in the spinal cord was first observed in the ventral horn at P2, and the intensity of labeling in these large motoneurons gradually increased. In addition, there was a ventral-dorsal gradient in this region, with label appearing subsequently in neurons of Rexed laminae IX, VII and VIII, and in the dorsal horn (Rexed laminae I-VI). In these regions, the labeling reached a plateau within the first 2-3 weeks after birth and persisted into the adult rat. The time course and regional heterogeneity of Na beta 1 expression are consistent with the hypothesis that the expression of mature Na+ channels, including Na beta 1, contributes to the development of circuitry that supports complex patterns of electrogenesis.
Physical studies of tissue anaphylaxis.

Abstract The domain of anaphylaxis in the atrium and oviduct is described and modeled. Mast cells are identified as the primary source of histamine in atrial and tubal anaphylaxis. The granules in the mast cells of these tissues carry ionically bound histamine which is readily released following the loss of granules from the cell. The extent to which histamine is released is shown to depend on the kinetics of sensitization and challenge. For any bulk phase concentration of antibody there is a single concentration of antigen which maximizes histamine release. A mechanism of mediator cell activation is proposed which is based on optimum stimulation of the mast cell membrane.
Effect of acute feeding of diets of varying fatty acid composition on intestinal apolipoprotein expression in the newborn swine.

The purpose of this study was to determine the effects of dietary fatty acids of varying chain lengths and degrees of saturation on intestinal apolipoprotein (apo) B and A-I expression in the newborn piglet. Two-day-old female piglets received one of three isocaloric formulas containing 48% of total calories (120 kcal/kg/24 h) as medium-chain triglycerides (MCT) from MCT oil, intermediate-chain saturated triglycerides (ICST) from coconut oil, or long-chain polyunsaturated triglycerides (LCPUT) from safflower oil by continuous duodenal infusion for 24 h. After in situ radiolabeling, jejunal and ileal mucosal apo B-48 and A-I were immunoprecipitated, and synthesis was expressed as percentage of total protein synthesis. Mucosal apo B and A-I mass was measured by ELISA as nanograms of apoprotein/μg of total protein. Fifty percent less apo B jejunal synthesis was present in the ICST group versus the MCT and LCPUT groups (0.67 ± 0.07, 1.19± 0.20, and 1.25 ± 0.15, respectively, mean ± SEM,p < 0.05). Jejunal apo B mass was lower in the MCT groupversus the ICST and LCPUT groups (0.10 ± 0.02, 0.21 ± 0.03, and 0.16 ± 0.03, respectively, p < 0.05). Ileal apo B synthesis was lowest in the ICST group. No differences were found in ileal apo B mass. Two-fold higher jejunal apo A-I synthesis was found in the LCPUT group versus the MCT and ICST groups (14.18 ± 1.69, 7.56± 2.63, and 6.36 ± 0.58, respectively, p < 0.01). No differences were found for jejunal apo A-I mass. In the ileum, the only difference was a higher apo A-I mass in the LCPUT group (p < 0.05). We conclude that in the newborn piglet intestinal apo B and A-I expression is acutely and differentially regulated by dietary lipid varying in fatty acid chain length and saturation. The patterns of regulation are complex and vary among specific apolipoproteins and regions of the small intestine and include co- and posttranslational mechanisms.
Quaternary Palynology of the Pacific Slope of Washington

Abstract Quaternary deposits on the Pacific slope of Washington range in age from the earliest known interglaciation, the Alderton, through the Holocene. Pollen stratigraphy of these deposits is represented by 12 major pollen zones and is ostensibly continuous through Zone 8 over more than 47,000 radiocarbon yr. Before this, the stratigraphy is discontinuous and the chronology less certain. Environments over the time span of the deposits are reconstructed by the comparison of fossil and modern pollen assemblages and the use of relevant meteorological data. The Alderton Interglaciation is characterized by forests of Douglas fir (Pseudotsuga menziesii), alder (Alnus), and fir (Abies). During the next younger interglaciation, the Puyallup, forests were mostly of pine, apparently lodgepole (Pinus contorta), except midway in the interval when fir, western hemlock (Tsuga heterophylla), and Douglas fir temporarily replaced much of the pine. Vegetation outside the limits of Salmon Springs ice (>47,00034,000 yr BP) varied chiefly between park tundra and forests of western hemlock, spruce (Picea), and pine. The Salmon Springs nonglacial interval at the type locality records early park tundra followed by forests of pine and of fir. During the Olympia Interglaciation (34,00028,000 yr BP), pine invaded the Puget Lowland, whereas western hemlock and spruce became manifest on the Olympic Peninsula. Park tundra was widespread during the Fraser Glaciation (28,00010,000 yr BP) with pine becoming more important from about 15,000 to 10,000 yr BP. Holocene vegetation consisted first of open communities of Douglas fir and alder; later, closed forests succeeded, formed principally of western hemlock on the Olympic Peninsula and of western hemlock and Douglas fir in the Puget Lowland. Over the length of the reconstructed environmental record, climate shifted between cool and humid or relatively warm, semihumid forest types and cold, relatively dry tundra or park tundra types. During times of glaciation, average July temperatures are estimated to have been at least 7°C lower than today. Only during the Alderton Interglaciation and during the Holocene were temperatures higher for protracted periods that at present.
Titanium alloys in total joint replacement—a materials science perspective

Abstract Increased use of titanium alloys as biomaterials is occurring due to their lower modulus, superior biocompatibility and enhanced corrosion resistance when compared to more conventional stainless steels and cobalt-based alloys. These attractive properties were a driving force for the early introduction of α (cpTi) and α + β (Ti–6Al–4V) alloys as well as for the more recent development of new Ti-alloy compositions and orthopaedic metastable β titanium alloys. The later possess enhanced biocompatibility, reduced elastic modulus, and superior strain-controlled and notch fatigue resistance. However, the poor shear strength and wear resistance of titanium alloys have nevertheless limited their biomedical use. Although the wear resistance of β -Ti alloys has shown some improvement when compared to α + β alloys, the ultimate utility of orthopaedic titanium alloys as wear components will require a more complete fundamental understanding of the wear mechanisms involved. This review examines current information on the physical and mechanical characteristics of titanium alloys used in artifical joint replacement prostheses, with a special focus on those issues associated with the long-term prosthetic requirements, e.g., fatigue and wear.
The Obesity Paradox in Chronic Heart Failure: What Does It Mean?

Heart failure (HF) is a growing health problem, at least in part due to the concurrent obesity epidemic plaguing developed countries. However, once a patient develops HF, an elevated BMI appears to confer a survival benefit – a phenomenon termed the “obesity paradox.” The exact explanation for this paradox has been difficult to ascertain. Numerous plausible mechanisms have been asserted, including the fact that obese patients tend to be younger and more symptomatic, leading them to seek medical attention earlier in the course of their HF. Obese patients may also have larger energy reserves that help to offset the catabolic changes seen with HF. Other hypotheses highlight the limitations of BMI as an obesity classifier. The purpose of this review is to examine the various theories for the obesity paradox in HF and discuss the implications for the clinical management of obese patients with HF.
Coulomb corrections to the extrinsic spin-Hall effect of a two-dimensional electron gas

We develop the microscopic theory of the extrinsic spin Hall conductivity of a two-dimensional electron gas, including skew-scattering, side-jump, and Coulomb interaction effects. We find that while the spin-Hall conductivity connected with the side-jump is independent of the strength of electron-electron interactions, the skew-scattering term is reduced by the spin-Coulomb drag, so the total spin current and the total spin-Hall conductivity are reduced for typical experimental mobilities. Further, we predict that in paramagnetic systems the spin-Coulomb drag reduces the spin accumulations in two different ways: (i) directly through the reduction of the skew-scattering contribution (ii) indirectly through the reduction of the spin diffusion length. Explicit expressions for the various contributions to the spin Hall conductivity are obtained using an exactly solvable model of the skew-scattering.
Time-Resolved Analysis of Coronary Vein Motion and Cross-Sectional Area

Purpose: To quantify periods of low motion and cross-sectional area changes of the coronary veins during the cardiac cycle for planning magnetic resonance coronary venograms (MRCV). Materials and Methods: Images were acquired from 19 patients with coronary artery disease (CAD) and 13 patients scheduled for cardiac resynchronization therapy (CRT). The displacement and cross-sectional area of the coronary sinus was tracked, and periods of low motion were defined as consecutive time points during which the position of the coronary sinus remained within a 0.67-mm diameter region. Patients were classified as systolic dominant or diastolic dominant based on the relative duration of their low motion periods. Results: All CRT patients were classified as systolic dominant, and 32% of these had no separate diastolic rest period. All CAD patients with ejection fraction 35%were diastolic dominant. In 77% of all subjects, the cross-sectional area of the coronary sinus was larger in systole than in diastole. Conclusion: The movement of the coronary sinus can be used to classify patients as either having a longer systolic or diastolic rest period. The classification of the CRT patients as systolic dominant suggests that MRCVs be acquired in systole for CRT planning; however, each patient's low motion periods should be categorized to ensure the correct period is being used to minimize motion artifacts. J. Magn. Reson. Imaging 2011;. © 2011 Wiley-Liss, Inc.