cssi/SciSciGPT-SciSciNet huggingface dataset:
Mandarin Pop Meets Tokyo Jazz: Gender and Popular Youth Culture in Late-1960s Hong Kong Musicals

Critics have derided the Hong Kong Mandarin musical films of the 1950s and 1960s for their lack of strong male leads, particularly when it comes to singing and dancing. Scholar Stephen Teo (1993) has asserted ‘Few leading men ever carried a musical picture. [...] [I]n stark contrast to the women, the men were weak and sissified’ (Teo, 1993, p. 37). While the bulk of Hong Kong Mandarin musicals until the mid-1960s privilege the figure of the songstress, masculinity in Hong Kong Mandarin musicals gained unprecedented visibility during the late 1960s and early 1970s, most notably in Shaw Brothers productions helmed by Japanese emigre film-maker Inoue Umetsugu (1923–2010). Between 1967 and 1971, Inoue directed 17 Hong Kong Mandarin- language pictures for the successful studio, several of which were remakes of his previous Japanese works. The majority of these films celebrate youth culture, and combine spectacular musical performances with generic conventions found in comedies, melodramas and crime capers; to cite Rick Altman’s scholarship on film genre, they display the semantic features of musicals but syntactically function as other genres, most frequently melodramas.1 Unlike the earlier Mandarin musicals that almost exclusively centre on the songstress, Inoue’s films broaden to showcase collaborative male-female ensembles as well as dynamic male performers who in some instances even steal the spotlight from their female co-stars.
Individual God-Relationships and Ethics

Kierkegaard in several of his works develops the idea of an individual God-relationship. For Kierkegaard faith is essentially a relationship to God, a particularized relationship between an individual and God. And importantly it is a relationship that carries implications for religious praxis in that it generates individual religious duties. In this chapter we shall begin with a look at the main, distinguishing features of Kierkegaard’s understanding of individual God-relationships, and then, in the second section, we shall raise and confront the central problem it faces regarding the conflict between individual religious duties and universal ethical duties. In the third section we shall compare Kierkegaard’s Abraham, who acts in accordance with his individual religious duty, with other figures, superficially like Abraham, who proceed to do inspired murder. And in the last section I shall try to show that Kierkegaard, though he projects more than one model of faith in different works, never abandons his central idea that faith is an individual God-relationship.
mutLBSgeneDB: mutated ligand binding site gene DataBase

Mutations at the ligand binding sites (LBSs) can influence protein structure stability, binding affinity with small molecules, and drug resistance in cancer patients. Our recent analysis revealed that ligand binding residues had a significantly higher mutation rate than other parts of the protein. Here, we built mutLBSgeneDB (mutated Ligand Binding Site gene DataBase) available at http://zhaobioinfo.org/mutLBSgeneDB We collected and curated over 2300 genes (mutLBSgenes) having ∼12 000 somatic mutations at ∼10 000 LBSs across 16 cancer types and selected 744 drug targetable genes (targetable_mutLBSgenes) by incorporating kinases, transcription factors, pharmacological genes, and cancer driver genes. We analyzed LBS mutation information, differential gene expression network, drug response correlation with gene expression, and protein stability changes for all mutLBSgenes using integrated genetic, genomic, transcriptomic, proteomic, network and functional information. We calculated and compared the binding affinities of 20 carefully selected genes with their drugs in wild type and mutant forms. mutLBSgeneDB provides a user-friendly web interface for searching and browsing through seven categories of annotations: Gene summary, Mutated information, Protein structure related information, Differential gene expression and gene-gene network, Phenotype information, Pharmacological information, and Conservation information. mutLBSgeneDB provides a useful resource for functional genomics, protein structure, drug and disease research communities.
Sequence Alignment and Similarity Searching in Genomic Databases: BLAST and FASTA**The opinions expressed in this chapter are the author’s own and they do not necessarily reflect the opinions of the FDA, the DHHS, or the Federal Government.

Bioinformatic analyses, to a large extent, are predicated upon sequence alignment and comparison. Sequence identity as revealed by sequence alignment also sheds light on the evolutionary relationship between two sequences. This chapter explores the concept of sequence identity and sequence homology. The misuse of the term sequence homology in common scientific parlance is discussed. Different aspects of sequence alignment, such as global versus local, and pairwise versus multiple sequence alignments are reviewed, with examples. Scoring matrices are also discussed, along with the statistical significance of sequence alignment. Lastly, BLAST and FASTA and different forms of BLAST are briefly discussed.
Privacy Implications of DNSSEC Look-Aside Validation

To complement DNSSEC operations, DNSSEC Look-aside Validation (DLV) is designed for alternative off-path validation. While DNS privacy attracts a lot of attention, the privacy implications of DLV are not fully investigated and understood. In this paper, we take a first in-depth look into DLV, highlighting its lax specifications and privacy implications. By performing extensive experiments over datasets of domain names under comprehensive experimental settings, our findings firmly confirm the privacy leakages caused by DLV. We discover that a large number of domains that should not be sent to DLV servers are being leaked. We explore the root causes, including the lax specifications of DLV. We also propose two approaches to fix the privacy leakages. Our approaches require trivial modifications to the existing DNS standards and we demonstrate their cost in terms of latency and communication.
Modeling Emergency Managers’ Hurricane Evacuation Decisions

Emergency management and decision support system (EMDSS) tools play an important role in assisting emergency managers with making important decisions about the movement of people to safety when a jurisdiction is threatened by a storm. One of the important components of an EMDSS is an evacuation demand model that predicts whether and when households will evacuate when they are threatened by a storm. A critical input to that model is an emergency manager’s decision to issue an evacuation notice. No existing mathematical models predict whether and when an emergency manager will issue an evacuation notice on the basis of a hurricane forecast and other contextual factors. To fill this gap, this research study sought to develop a model that would predict if and when an emergency manager would issue an evacuation notice when a jurisdiction was threatened by a storm. Data from poststorm assessment surveys and newspaper archives were used to retrieve past decisions made by evacuation managers for five storms in 45...
Runtime Monitoring of Safety and Performance Requirements in Smart Cities

With the increasing number of smart services implemented in smart cities, it is important yet challenging to dynamically detect service conflicts with respect to safety and performance requirements. In this paper, we propose a framework for monitoring the operation of smart cities and services at runtime. We formalize a set of typical safety and performance requirements from different domains in smart cities (e.g., transportation, emergency, and environment) using Signal Temporal Logic. We present a case study based on a smart city simulator, in which actions of smart services and their predicted effects on city states are converted into signal traces over time and monitored continuously using formal specifications. The experimental results demonstrate the feasibility of using runtime monitoring to detect various conflicts of smart services.
Historical Trends of Benthic Invertebrate Biodiversity Spanning 182 Years in a Southern New England Estuary

Benthic invertebrates support numerous ecosystem functions and services including shellfish production, energy flow to fishes, and biogeochemical cycles. The decline of marine biodiversity worldwide has raised concerns about effects on ecosystems. To examine biodiversity trends of Narragansett Bay over time, a list was compiled of all benthic invertebrate species collected from the bay since 1834. The list covers 104 studies spanning 182 years and currently holds 1214 unique taxa from 21 phyla, the majority of all animal phyla on Earth. A permuted estimator of number of species suggested there are about 300 more yet to be discovered. Widely varying sampling gear and sieve mesh sizes precluded the use of abundance data. Instead, multidimensional scaling and taxonomic distinctness were used with presence-absence data to examine biodiversity trends. The changes in community composition and decline of benthic biodiversity (p < 0.01) since 1855 are what would be expected of a community that gradually deteriorated in the face of increasing anthropogenic stressors. Taxonomic distinctness had negative correlations (p < 0.05) with human population in the watershed, total nitrogen inputs, and inputs of metals. This loss of benthic biodiversity has implications for ecosystem functions and services. As some of the stressors waned in the last two or three decades, following passage of environmental legislation in the 1970s, biodiversity appeared to show a partial recovery. An inventory of species, how it has changed over time, and understanding what caused those changes are important for assessing whether remediation programs are achieving improved water quality and ecosystem health.
Atmospheric deposition and exceedances of critical loads from 1800-2025 for the conterminous United States.

Atmospheric deposition of nitrogen (N) and sulfur (S) has increased dramatically over pre-industrial levels, with many potential impacts on terrestrial and aquatic ecosystems. Quantitative thresholds, termed "critical loads" (CLs), have been developed to estimate the deposition rate above which damage is thought to occur. However, there remains no comprehensive comparison of when, where, and over what time periods individual CLs have been exceeded. We addressed this knowledge gap by combining several published data sources for historical and contemporary deposition, and overlaying these on six CL types from the National Critical Loads Database (NCLDv2.5; terrestrial acidification, aquatic acidification, lichen, nitrate leaching, plant community composition, and forest-tree health) to examine exceedances from 1800 to 2011. We expressed CLs as the minimum, 10th, and 50th percentiles within 12-km grid cells. Minimum CLs were relatively uniform across the country (200-400 eq·ha-1 ·yr-1 ), and have been exceeded for decades beginning in the early 20th century. The area exceeding minimum CLs peaked in the 1970s and 1980s, exposing 300,000 to 3 million km2 (depending on the CL type) to harmful levels of deposition, with a total area exceeded of 5.8 million km2 (~70% of the conterminous United States). Since then, deposition levels have dropped, especially for S, with modest reductions in exceedance by 2011 for all CL types, totaling 5.2 million km2 in exceedance. The 10th and 50th percentile CLs followed similar trends, but were not consistently available at the 12-km grid scale. We also examined near-term future deposition and exceedances in 2025 under current air quality regulations, and under various scenarios of climate change and additional nitrogen management controls. Current regulations were projected to reduce exceedances of any CL from 5.2 million km2 in 2011 to 4.8 million km2 in 2025. None of the additional N management or climate scenarios significantly affected areal exceedances, although exceedance severity declined. In total, it is clear that many CLs have been exceeded for decades, and are likely to remain so in the short term under current policies. Additionally, we suggest many areas for improvement to enhance our understanding of deposition and its effects to support informed decision making.
Normative Patterns of Diurnal Urination Across 6 Age Decades

AbstractThe patterns and frequency of diurnal urination were studied in 412 male and 244 female participants in the Baltimore Longitudinal Study of Aging. Men urinated less often (mean 4.8 voids per day) than women (mean 5.6 voids per day). There was no main effect for age decade. However, an age by sex interaction showed that voiding in men increased across the decades and in women it decreased. The highest frequency was found in women in their 30s (mean 6.2) and the lowest was in men in their 30s (mean 4.3). Men and women in the 70 and older age group had the same voiding frequency (mean 5.0). In men frequency of urination was related to benign prostatic enlargement and 2 of 4 symptoms of urinary obstruction (change in the force of the urinary stream and having to urinate again shortly after voiding). In women frequency was related negatively to a history of pregnancy complications but not to parity. In both sexes frequency was unrelated to the reported daily ingestion of coffee, tea or diuretics, and n...
pAd5-Blue: direct ligation system for engineering recombinant adenovirus constructs.

We have engineered a new vector that makes use of direct ligation for the generation of replication-defective recombinant adenovirus constructs. In the pAd5-Blue vector, unique yet common restricti...
Doppler Wavefront Distortion Effects Due to Continuous Dynamic Array Focusing

Use of continuous dynamic focusing in an ultrasonic linear phased array system can cause doppler distortion of the received signals. This distortion results from variation of the effective beamformer delay during signal reception, and can affect both the received signal frequency and synthesized beamwidth.
A Novel Method to Study the Topography of Transmembrane Proteins Using Pyridoxal 5-Phosphate

A method has been devised for the selective labeling of cytoplasmic domains of transmembrane proteins with pyridoxal phosphate (PLP). Sealed vesicles are loaded with 3H pyridoxine phosphate (PNP) and pyridoxine phosphate oxidase (PNPoxidase) by freezing-thawing (FT) and PLP is generated intravesicularly by enzymatic oxidation. Results obtained using acetylcholine receptor (AcChR) vesicles as a model are summarized.
MicroRNAs are Critical Regulators of Osteoclast Differentiation.

Our goal is to comprehensively review the most recent reports of microRNA (miRNA) regulation of osteoclastogenesis. We highlight validated miRNA-target interactions and their place in the signaling networks controlling osteoclast differentiation and function. Using unbiased approaches to identify miRNAs of interest and reporter-3′UTR assays to validate interactions, recent studies have elucidated the impact of specific miRNA-mRNA interactions during in vitro osteoclastogenesis. There has been a focus on signaling mediators downstream of the RANK and CSF1R signaling, and genes essential for differentiation and function. For example, several miRNAs directly and indirectly target the master osteoclast transcription factor, Nfatc1 (e.g., miR-124 and miR-214) and Rho-GTPases, Cdc42, and Rac1 (e.g., miR-29 family). Validating miRNA expression patterns, targets, and impact in osteoclasts and other skeletal cells is critical for understanding basic bone biology and for fulfilling the therapeutic potential of miRNA-based strategies in the treatment bone diseases.
Behavioral Genetics: Psychological Perspectives

This article is a revision of the previous edition article by R. Plomin, volume 2, pp. 1100–1105, © 2001, Elsevier Ltd.
Lower Eyelid Reconstruction: A New Classification Incorporating the Vertical Dimension.

BACKGROUND Lower eyelid defects are traditionally classified based on depth and 25 percent increments in defect width. The authors propose a new classification system that includes the vertical defect component to predict functional and aesthetic outcomes. METHODS A retrospective review of patients who underwent lower lid reconstruction performed by a single surgeon was performed. Defects were classified into four categories based on the vertical component: (1) pretarsal; (2) preseptal; (3) eyelid-cheek junction; and (4) complex pretarsal/preseptal. Preoperative and postoperative central and lateral marginal reflex distance-2 values were obtained. Aesthetic outcomes were evaluated by three blinded reviewers. Outcomes were compared using one-way analysis of variance and analysis of covariance with Bonferroni corrected post hoc comparisons to control for defect area and width. RESULTS Thirty-four patients underwent reconstruction of lower eyelid defects. There were 12 pretarsal defects (type I), nine preseptal defects (type II), nine eyelid-cheek defects (type III), and four complex pretarsal/preseptal defects (type IV). Postoperative retraction was highest in the complex pretarsal/preseptal group at 75 percent, with a significantly greater change from preoperative to postoperative central and lateral marginal reflex distance-2 compared with the other groups (p < 0.01) and worse postoperative mean aesthetic scores (p < 0.001). Type IV patients had significantly more revision operations (mean, 5.5) compared with the other groups (p < 0.001). CONCLUSIONS The vertical dimension of lower eyelid defects is an important variable. A new classification system is proposed that supplements width-based methods for improved surgical planning and prediction of postoperative outcomes in lower eyelid reconstruction. CLINICAL QUESTION/LEEVL OF EVIDENCE Therapeutic, IV.
Quantized Mechanisms for Gaussian Multiple Access Wiretap Channels

Economic mechanisms have been widely studied for allocating network resources while accounting for the incentives of self-interested users. Indeed, the well known Vickrey-Clarke-Groves (VCG) mechanism provides an elegant solution to such problems with a strong incentive guarantee. However, VCG mechanisms can incur high communication costs. Recent work has shown that via quantization, one can reduce the communication costs of VCG while maintaining its incentive guarantees for allocating a single divisible resource. However, in many information theoretic settings, the underlying resource constraints are more complex. Here, we consider developing similar quantized mechanisms for one such setting: a Gaussian multiple access wiretap channel. Namely, we seek to allocate secure rates to a set of users assuming that all users employ a superposition coding scheme. This results in an achievable rate region that we show is a polymatroid. We utilize this characterization to design a quantized mechanism with strong incentive properties.
CUL-4A Short Hairpin RNA (shRNA) Impairs Normal Hematopoiesis of Human Cord Blood CD34+ Cells In Vitro and In Vivo.

Abstract The CUL-4A ubiquitination machinery regulates the stability of HOXA9 by promoting its ubiquinitation and proteasome-dependent degradation. Our previous study showed the perturbation of CUL-4A biosysthesis in 32D cells by RNA-mediated interference increased an accumulation of HOXA9, and impaired G-CSF-induced terminal differentiation to granulocytes. HOXA9 is preferentially expressed in primitive hematopoietic cells and downregulates with differentiation. In this study, a lentiviral vector expressed both CUL-4A shRNA and GFP was constructed and was used to transduce cord blood (CB) CD34+ cells (GFP-shCUL-4A-CD34+ cells). The ability of GFP-shCUL-4A-CD34+ cells to form CFC colonies, to differentiate into myeloid, erythroid, B-lymphoid and T-lymphoid cells in vitro, and to engraft in irradiated NOD/SCID mice was evaluated. Our results showed that knockdown of CUL-4A m-RNA dramatically inhibited hematopoisis both in vivo and in vitro. In the CFC assay, FACS-sorted GFPbright-shCUL-4A-CD34+ cell formed fewer colonies (5%) that were smaller size ( 500 cells/colony comparing to that of GFPdim-CD34+ cells. After transplanting the GFP-shCUL-4A-CD34+ cells into irradiated NOD/SCID mice for 6 weeks, GFP-shCUL-4A-CD45+ cells decreased more than 80% in the mouse bone marrow. These human GFP-shCUL-4A CD45 + cells were capable of forming GFP+-CFC but with >80% reduction in their potency. No reduction in % of GFP-CD45+ cells and GFP+-CFC was observed in the GFP-CD34+ cells group pre- and post-transplantation. The in vitro culture systems showed that knockdown of CUL-4A mRNA in CB CD34+ cells resulted in the developmental impairment in monocytic, megakaryocytic, erythroid, B lymphoid and T-lymphoid lineages. This impairment is a time- and shCUL-4A dose-dependent process. Further study using cell cycle analysis indicated that transduction of CUL-4A shRNA to HL-60 or CD34+ cells induced apoptosis. Our results, for the first time, demonstrate an essential role of the CUL-4A ubiquitin ligase in maintaining cell survival to ensure proper differentiation of normal human stem and progenitor cells into different hematopoietic lineages both in vivo and in vitro.
Finding a unifying SLE expression signature in a sea of heterogeneity.

The heterogeneity of systemic lupus erythematosus (SLE) confounds the diagnosis and treatment of this disease, and attempts at disease stratification are nascent. Researchers have identified a common set of biomarkers in patients with SLE that could identify new therapeutic targets and lead to new clinical assays to help address this issue.
16 – Sulfur bioavailability

Publisher Summary Sulfur is distributed widely in nature as a component of proteins and numerous other organic compounds and, consequently, it has many structural and regulatory functions in common with nitrogen. Utilization of absorbed inorganic sulfur has been demonstrated in avian species and probably occurs in most other species. The predominant need for the element, however, is in the form of sulfur-bearing amino acids which must be provided preformed for the nonruminant or either provided preformed or synthesized by ruminal microflora for the ruminant. True absorption of sulfur in dairy steers fed a concentrate containing urea (0.21% sulfur) and corn silage (0.20% sulfur) was 68%. Supplementation of lactating dairy cows with sulfur as sodium sulfate, methionine hydroxy analog, or dynamate increased apparent and true sulfur absorption. Apparent absorption of sulfur was similar when either sodium or calcium sulfates was supplemented to lactating dairy cattle. Dietary proteins with their sulfur-containing amino acids provide a major dietary source of sulfur for animals. Interactions among mineral elements including copper, molybdenum, and sulfur and those involving sulfur and selenium influence the utilization of sulfur. Factors that change the population of ruminal microflora may also affect the availability of inorganic sulfur. Sulfur is a more critical nutrient for ruminants than nonruminants from the standpoint of potential deficiency. Organic forms including the isomers of methionine and methionine hydroxy analog have provided sulfur equal in availability to that in sodium sulfate. Elemental sulfur and sodium sulfate were not utilized when tested in both cattle and sheep.
Robust computational design and evaluation of peptide vaccines for cellular immunity with application to SARS-CoV-2

We present a combinatorial machine learning method to evaluate and optimize peptide vaccine formulations, and we find for SARS-CoV-2 that it provides superior predicted display of viral epitopes by MHC class I and MHC class II molecules over populations when compared to other candidate vaccines. Our method is robust to idiosyncratic errors in the prediction of MHC peptide display and considers target population HLA haplotype frequencies during optimization. To minimize clinical development time our methods validate vaccines with multiple peptide presentation algorithms to increase the probability that a vaccine will be effective. We optimize an objective function that is based on the presentation likelihood of a diverse set of vaccine peptides conditioned on a target population HLA haplotype distribution and expected epitope drift. We produce separate peptide formulations for MHC class I loci (HLA-A, HLA-B, and HLA-C) and class II loci (HLA-DP, HLA-DQ, and HLA-DR) to permit signal sequence based cell compartment targeting using nucleic acid based vaccine platforms. Our SARS-CoV-2 MHC class I vaccine formulations provide 93.21% predicted population coverage with at least five vaccine peptide-HLA hits on average in an individual (≥ 1 peptide 99.91%) with all vaccine peptides perfectly conserved across 4,690 geographically sampled SARS-CoV-2 genomes. Our MHC class II vaccine formulations provide 90.17% predicted coverage with at least five vaccine peptide-HLA hits on average in an individual with all peptides having observed mutation probability ≤ 0.001. We evaluate 29 previously published peptide vaccine designs with our evaluation tool with the requirement of having at least five vaccine peptide-HLA hits per individual, and they have a predicted maximum of 58.51% MHC class I coverage and 71.65% MHC class II coverage given haplotype based analysis. We provide an open source implementation of our design methods (OptiVax), vaccine evaluation tool (EvalVax), as well as the data used in our design efforts.
Expanding the Limits-Improving Penile Length With Inflatable Penile Prosthesis Implantation: A Review.

Abstract Introduction Erectile dysfunction is a multifactorial disorder that increases in prevalence as men age. When medical therapy fails or when men are unwilling to try it, surgical intervention becomes the urologist's next best tool. However, the loss of penile length is of great concern to many patients, and there have been a myriad of ways to try to combat this fear from both patients and the surgeons themselves. In this review, we evaluate the current literature of these various approaches to improve penile length in penile prosthesis surgery. Objectives To review novel techniques in penile prosthesis implantation surgery. Methods A literature search using PubMed was conducted to identify relevant peer-reviewed studies to penile prosthesis surgery. Search terms included penile prosthesis, penile shortening, sliding technique, Peyronie's Disease, erectile dysfunction, nondegloving, penile length, and Multiple Slice Technique. Results Novel techniques included preoperative techniques such as use of vacuum-assisted erection device, intraoperative techniques of aggressive dilatation and maximal sizing, ventral phalloplasty and/or scrotoplasty, suprapubic fat pad excision, relaxing tunica albuginea incisions, a sliding or slicing technique, or the postoperative use of penile rehabilitation. In addition, recognizing recall bias or inconsistencies in measurement techniques is important when evaluating men with possible penile shortening after penile prosthesis surgery. Conclusions Advancements in surgical techniques and managing patient expectations can be crucial in the success of penile prosthesis surgery. Panuganti S, Kannady C, Wang R, Expanding the Limits-Improving Penile Length With Inflatable Penile Prosthesis Implantation: A Review. Sex Med Rev 2021;9:498–506.
The not-so-great transformation

Many have attributed the excesses of private power in the digital age to the internet’s “lawlessness.” Julie Cohen’s Between Truth and Power explains why this is a dangerous misconception. The law has not sat idle during the rise of informational capitalism; it has undergone extensive transformation and now facilitates corporate surveillance and manipulation on a global scale. Meanwhile, legal institutions have taken a turn towards managerialism and away from democratic accountability. Recognizing these transformations and the ideologies that motivate them is critical to grappling with the legal challenges of the digital era.
Acute Demyelinating Encephalomyelitis Following Measles Infection Due to Vaccine Failure: A Case Report.

Author(s): McMickle, Robert J.; Fryling, Lauren; Fleischman, Ross J. | Abstract: Introduction: Local outbreaks of measles infection are primarily mediated by international travel of persons from endemic areas, with subsequent spread of the virus via undervaccinated populations. Recent resurgences of measles in communities where vaccination rates are non-ideal secondary to philosophical objections require the emergency physician to more routinely consider the diagnosis. In cases of measles complicated by acute encephalitis or encephalopathy, the diagnosis can be especially difficult to make due to lack of a reliable primary historian.Case report: Here we present a case of altered mental status and new-onset bilateral lower extremity weakness in a fully vaccinated young woman diagnosed with measles infection caused by acute disseminated encephalomyelitis in the setting of vaccine failure.Conclusion: Despite a documented history of immunization, acute measles infection and its uncommon sequelae are possible. Recognizing vaccine failure and appropriately isolating patients are of paramount importance.
Markovian Weighted Ensemble Milestoning (M-WEM): Long-time Kinetics from Short Trajectories

We introduce a rare-event sampling scheme, named Markovian Weighted Ensemble Milestoning (M-WEM), which inlays the weighted ensemble framework within a Markovian milestoning theory to efficiently calculate thermodynamic and kinetic properties of long-timescale biomolecular processes from short atomistic molecular dynamics simulations. We then showcase the application of this method to the Muller Brown potential model, the conformational switching in alanine dipeptide, and the millisecond timescale protein-ligand unbinding in the trypsin-benzamidine complex. Not only can we predict the kinetics of these processes with quantitative accuracy, but we also present a scheme to reconstruct a multidimensional free energy landscape, along additional degrees of freedom which are not part of the milestoning progress coordinate. For the ligand-receptor system, the experimental residence time, association and dissociation kinetics, and binding free energy could be reproduced using M-WEM approach within a few hundreds of nanoseconds simulation time, which is a fraction of the computational cost of other currently available methods, and close to four orders of magnitude less than the experimental residence time. Due to the high accuracy and low computational cost the M-WEM approach can find potential application in kinetics and free energy based computational drug design.
The Shadow of the Tsunami : and the Growth of the Relational Mind

Schore, Foreword. Preface. Part I: Affect Regulation and Clinical Process. Shrinking the Tsunami. Part II: Uncertainty. "It Never Entered My Mind." "Mentalize This!" Minding the Dissociative Gap. Part III: Stumbling Along and Hanging In. Truth and Human Relatedness. If This Be Technique, Make the Most of It! "Grown-up" Words: A Perspective on Unconscious Fantasy. Part IV: The Reach of Intersubjectivity. "The Nearness of You": A Personal Book-end.
Comparative Genomics: Tools for Study of Complex Diseases

Comparative genomic tools provide the means to compare model organism genomes with the human genome. In our studies of the genetics of complex diseases we have employed a number of these tools to identify syntenic quantitative trait loci , putative regulatory elements , conserved gene coding sequence domains, polymorphic elements in coding and noncoding sequences, and conserved gene networks . My colleagues and I have integrated these comparative genomic tools with classical genetic tools to identify genes that influence variation in complex disease traits . In this chapter, I will present examples of the use of these tools for genetic studies relevant to cardiovascular disease. The marked reduction in sequencing costs will soon provide additional data on numerous individuals within multiple species that will again significantly expand the information gained using the comparative genomic tools described here, will increase the information gained, and increase the hypotheses that can be developed using these methods.
Immune Function and Recurrent Pregnancy Loss

Recurrent pregnancy loss (RPL), defined as two or more consecutive miscarriages, is attributable to multiple causes. However, in 50% of cases no known cause is found. Although endometritis is a known cause of miscarriage, other inflammatory processes may play a role in idiopathic, recurrent loss. The fetoplacental unit evades rejection by the maternal immune system by poorly understood mechanisms. Despite this seemingly immune-privileged state for the fetus, human implantation requires inflammatory mediators for attachment and implantation. This review describes how the immune system must simultaneously permit and restrict trophoblastic invasion for healthy implantation and maintenance of pregnancy. Included in this review is a detailed description of the immune milieu in the decidua and abnormalities that are associated with RPL. Finally, autoimmune states associated with RPL and their treatment in an obstetrical setting are reviewed.
Maize streak virus genes essential for systemic spread and symptom development.

Abstract The entire genome of single component geminiviruses such as maize streak virus (MSV) consists of a single-stranded circular DNA of ~2.7 kb. Although this size is sufficient to encode only three average sized proteins, the virus is capable of causing severe disease of many monocots with symptoms of chlorosis and stunting. We have identified viral gene functions essential for systemic spread and symptom development during MSV infection. Deletions and gene replacement mutants were created by site-directed mutagenesis and insertion between flanking MSV or reporter gene sequences contained in Agrobacterium T-DNA derived vectors. Following Agrobacterium-mediated inoculation of maize seedlings, the mutated MSV DNAs were excised from these binary vectors by homologous recombination within the flanking sequences. Our analyses show that the capsid gene of MSV, while not required for replication, is essential for systemic spread and subsequent disease development. The `+' strand open reading frame (ORF) located immediately upstream from the capsid ORF and predicted to encode a 10.9 kd protein was also found to be dispensable for replication but essential for systemic spread. By this analysis, MSV sequences that support autonomous replication were localized to a 1.7 kb segment containing the two viral intergenic regions and two overlapping complementary `-' strand ORFs. Despite the inability of the gene replacement mutants to spread systemically, both inoculated and newly developed leaves displayed chlorotic patterns similar to the phenotype observed in certain developmental mutants of maize. The similarity of the MSV mutant phenotype to these developmental mutants is discussed.
Changes in morphology of γ-Al2O3-supported Pt clusters under reaction conditions: Evidence from In-Situ EXAFS spectroscopy

Pt clusters on γ-Al 2 O 3 , MgO, and SiO 2 , with average diameters of 11, 20, and 45 , were characterized by EXAFS spectroscopy in the presence of H 2 , ethene, propene, O 2 , and ethane as well as ethene + H 2 and propene + H 2 (undergoing catalytic reaction). Adsorption of alkenes (but not alkanes) or oxygen led to flattening of the smallest clusters (on γ-Al 2 O 3 ) but to essentially no changes in the larger clusters (on MgO or SiO 2 ); the changes were reversible. The morphology of the smallest pt clusters depends on the gas composition in alkene hydrogenation catalysis.
An Experimental Study on Confidence Measures for Robust Speech Recognition

One of the most critical components in a practical speech recognition system is a reliable confidence measure. In this paper, we report a number of experiments we conducted to improve confidence measures for large-vocabulary speaker-independent speech recognition. We first studied the behavior of confidence measures for mispronounced words during the user enrollment phase. Acoustic features at word, phoneme and senone level were examined. We developed a transformation function based system using sub-word features for high performance confidence estimation. Discriminative training was used to optimize the parameters of the transformation function. In comparison to the baseline system, our experiments show that the proposed system reduced the equal error rate by 15% and the false acceptance error by 40% at a number of fixed false rejection rates. Secondly, we augmented our feature vectors for speech recognition error detection. With multi-dimensional features and a linear classifier, our experiments show that the false acceptance error can be reduced by 80% in comparison with our single feature baseline system. Finally, we investigated how we could use confidence measures to reject noise. With our explicit noise modeling and a secondary classifier, we have reduced the noise rejection error down to 7% - a 68% error reduction over our baseline system.
Diversity, Power and Influence: Multiple Perspectives on the Ethics of School Leadership.

The intersection and clash between prevailing norms of schooling and increasing sensitivity to diversity raises a host of previously ignored ethical considerations for school administrators. These ...
The Ground Axiom (GA)

A new axiom is proposed, the Ground Axiom, asserting that the universe is not a nontrivial set forcing extension of any inner model. The Ground Axiom is first-order expressible, and any model of ZFC has a class forcing extension which satisfies it. The Ground Axiom is independent of many well-known set-theoretic assertions including the Generalized Continuum Hypothesis, the assertion V=HOD that every set is ordinal definable, and the existence of measurable and supercompact cardinals. The related Bedrock Axiom, asserting that the universe is a set forcing extension of a model satisfying the Ground Axiom, is also first-order expressible, and its negation is consistent.
Tolerance to cocaine's effects following chronic administration of a dose without detected effects on response rate or pause.

To observe tolerance to drug effects on operant behavior, the dose that researchers have often selected for chronic administration is one that disrupts, but does not abolish, responding. Some evidence suggests that tolerance may develop after chronic administration of relatively smaller doses. The purpose of the present experiment was to assess systematically effects of chronic administration of a dose without detected effect on responding. Specifically, response rates and postreinforcement pauses of five pigeons key pecking under a three-component multiple fixed-ratio schedule of food reinforcement were observed under chronic cocaine administration. We evaluated the effects of a range of doses (1.0 mg/kg to 17.0 mg/kg) during acute administration. The largest dose that failed to alter responding acutely then was administered chronically (1.0 mg/kg for one pigeon, 3.0 mg/kg for three pigeons, and 5.6 mg/kg for one pigeon). After 30 consecutive sessions of chronic administration, smaller and larger doses occasionally were substituted for the chronic dose. Pigeons then received presession saline administration for 30 consecutive sessions, and the postchronic effects of the series of doses on responding were determined. All subjects developed tolerance to doses of cocaine that initially had caused large decreases in rate, with the magnitude of the effects varying across components of the multiple schedule and subjects. Specifically, tolerance generally was greatest in the components with smaller ratios. Following postchronic saline administration, tolerance was usually diminished. Overall, the results demonstrate that under these conditions, repeated experience with disruptive effects of cocaine on food-maintained responding is not a necessary factor in the development of tolerance.
Cultural values and substance use in a multiethnic sample of California adolescents.

As the U.S. becomes increasingly multicultural, traditional values from various cultures will influence health-related attitudes and behaviors for a greater number of adolescents in the U.S. Unfortunately, few scales exist to measure cultural influences on adolescent health behaviors. This study developed a Multiethnic Cultural Values Scale to assess some cultural attitudes and beliefs relevant to adolescent health behaviors. In a multiethnic sample of 211 California adolescents, the associations between cultural values and substance use were examined. Filial piety and familism were associated with a lower risk of substance use. Machismo was associated with a higher risk of substance use among boys and a lower risk among girls. Collectivism and fatalism were not significantly associated with substance use. Cultural values may influence adolescents' decisions about substance use. Prevention programs in multicultural settings may be more effective if they address these cultural values.
Intracerebroventricular treatment with an antisense oligodeoxynucleotide to κ-opioid receptors inhibited κ-agonist-induced analgesia in rats

Abstract In vivo treatment with an antisense (AS) phosphorothioate oligodeoxynucleotide (oligo) to the rat κ-opioid receptor selectively inhibited κ-mediated analgesia in the rat cold-water tail-flick test. Intracerebroventricular (i.c.v.) AS oligo significantly inhibited the analgesic effect of i.c.v. spiradoline, but not that of μ- or δ-opioid agonists. The dose-effect curve for s.c. spiradoline was shifted to the right after AS, but not missense or sense oligo treatment. Thus, AS oligos provide another technique with which to selectively manipulate opioid receptors and further support the role of non-μ opioid receptors in mediating analgesia in rats.
Self-assembly of graphenes

Abstract Given the technological significance of graphene, various aspects of graphene have been recently explored. Here, we demonstrate the self-assembly of graphene fragments in water using molecular dynamics simulation. We observe that graphene fragments dispersed in water are assembled into a single aggregate. The assembly process is investigated by using the potential of mean force analysis and the significance of the enthalpic and entropic contributions is described. Other fundamental quantities such as hydrogen bonding and excluded volume are also examined. We anticipate that the fundamental finding in this paper can be extended to design the assembly process of complex carbon-based structures.
The causes and consequences of partial prey consumption by wolves preying on moose

For a wide range of taxa, partial prey consumption (PPC) is a frequent occurrence. PPC may arise from physiological constraints to gut capacity or digestive rate. Alternatively, PPC may represent an optimal foraging strategy. Assessments that clearly distinguish between these causes are rare and have been conducted only for invertebrate species that are ambush predators with extra-intestinal digestion (e.g., wolf spiders). We present the first strong test for the cause of PPC in a cursorial vertebrate predator with intestinal digestion: wolves (Canis lupus) feeding on moose (Alces alces). Previous theoretical assessments indicate that if PPC represents an optimal foraging strategy and is not caused by physiological limitations, then mean carcass utilization is negatively correlated with mean kill rate and the utilization of individual carcasses is uncorrelated with time between kills. Wolves exhibit exactly this pattern. We explore how the typical portrayal of PPC by wolves has been not only misleading but also detrimental to conservation by promoting negative attitudes toward wolves.
Cross-tolerance to phenobarbital following chronic ethanol polydipsia☆

Abstract Using contingent food pellet delivery, rats were trained on a discriminative motor control task requiring that a force transducer be held steadily within a force band. Motor performance following pre-task doses of phenobarbital (40, 60 or 80 mg/kg) both before and after 4 months of chronic ethanol polydipsia (mean intake = 11.1 g/kg/day) indicated the development of cross-tolerance from ethanol to phenobarbital. Days on which saline control injections were given in place of phenobarbital injections (on injection days ethanol was withdrawn 5 hr pre-injection) revealed the development of a mild physical dependence on ethanol polydipsia. Chronic ethanol polydipsia did not alter the time course of phenobarbital elimination from the serum, indicating that the cross-tolerance probably was due to central nervous system changes.
Pharmacokinetic and pharmacodynamic properties of beta-blocking drugs influencing choice in treatment of systemic hypertension.

Diuretics and beta blockers are the mainstay in treating mild and moderate systemic hypertension, but there is controversy as to which should be used first. Recent evidence of an increase in sudden death and a greater number of intolerable side effects in the diuretic-treated groups in the Multiple Risk Factor Intervention Trial in the U.S. and the Medical Research Council Trial in Great Britain has prompted some to suggest beta blockers as first-line therapy. However, beta blockers also have side effects, such as decreased ventricular function in patients with mild heart failure, increased airways resistance in those with chronic obstructive lung disease, increased plasma lipids, in particular low density lipoprotein cholesterol, and increased problems in patients with peripheral vascular disease and those with diabetes requiring insulin treatment. Many new beta-blocking drugs with different pharmacokinetic and pharmacodynamic properties allow the physician to choose the best one for each patient. beta-blocking drugs with long durations of action, high levels of bioavailability, beta 1 selectivity and intrinsic sympathomimetic activity appear most suitable for therapy. Cardioselectivity is suggested for patients with obstructive lung disease and peripheral vascular disease, and diabetic patients who take insulin. Long durations of action permit infrequent administration and recently agents with intrinsic sympathomimetic activity have been shown to have less effects on plasma lipid levels. Acebutolol also reduces ventricular arrhythmias, and may therefore be used to reduce sudden death in patients with coronary artery disease. The pharmacokinetic and pharmacodynamic properties of beta-blocking drugs can indicate the most appropriate choice for hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Molecular Determinants of Dysregulated GABAergic Gene Expression in the Prefrontal Cortex of Subjects with Schizophrenia

Background Prefrontal deficits in gamma-aminobutyric acid (GABA)ergic gene expression, including neuropeptide Y (NPY), somatostatin (SST), and parvalbumin (PV) messenger RNAs (mRNAs), have been reported for multiple schizophrenia cohorts. Preclinical models suggest that a subset of these GABAergic markers (NPY/SST) is regulated by brain-derived neurotrophic factor (BDNF), which in turn is under the inhibitory influence of small noncoding RNAs. However, it remains unclear if these mechanisms are important determinants for dysregulated NPY and SST expression in prefrontal cortex (PFC) of subjects with schizophrenia. Methods Using a postmortem case-control design, the association between BDNF protein, NPY/SST/PV mRNAs, and two BDNF-regulating microRNAs (miR-195 and miR-30a-5p) was determined in samples from the PFC of 20 schizophrenia and 20 control subjects. Complementary studies were conducted in cerebral cortex of mice subjected to antipsychotic treatment or a brain-specific ablation of the Bdnf gene. Results Subjects with schizophrenia showed deficits in NPY and PV mRNAs. Within-pair differences in BDNF protein levels showed strong positive correlations with NPY and SST and a robust inverse association with miR-195 levels, which in turn were not affected by antipsychotic treatment or genetic ablation of Bdnf . Conclusions Taken together, these results suggest that prefrontal deficits in a subset of GABAergic mRNAs, including NPY, are dependent on the regional supply of BDNF, which in turn is fine-tuned through a microRNA (miRNA)-mediated mechanism.