cssi/SciSciGPT-SciSciNet huggingface dataset:
Static analysis of ADA tasking programs: models and algorithms

Static analysis of Ada tasking programs aims at finding evidence of errors introduced by the use of tasking constructs. To this end, a program is abstracted to a model that is then analyzed. The typical and major abstraction involved is that of ignoring the variables to an extent. This thesis presents a survey of models for static analysis of Ada tasking programs and shows these to be equivalent to finite state automata in this context. The models discussed are Task Flowgraphs (by Taylor), Task Interaction Graphs (by Clarke and Long), Petri Nets (by Petri), and Constrained Expressions (by Avrunin, Dillon et al.). Process algebras will be briefly discussed on a general level. The thesis discusses three important recent methods to alleviate the state space explosion problem, that is, the complexity of the reachability graph generation. It presents a new application of data structures for Binary-Decision Diagrams (BDDs) to software verification by discussing the use of these in generating a generalized reachability graph of safe Petri nets. The reachability graph is an explicit graph representation of the state space of the model. The generalization employed allows multiple initial markings for the net, which is useful in e.g. fault-tolerant systems where the initial state of the system may only be partially known. Furthermore, Valmari's algorithm for finding a stubborn set at a marking is extended to operate on a set of markings. This potentially reduces the number of redundant interleavings of actions considered, which still hampers the reachability analysis using BDDs. Jensen's equivalent marking or symmetry method is also presented and the use of BDDs in it are discussed. The combination of the latter two methods for ordinary reachability graph generation is discussed and justified. These contributions extend the scope of the reachability graph generation, the principal method of analysis applied to the models for static analysis of Ada tasking programs. The wide applicability of Petri nets even outside computer science provides also for a wider applicability of the results.
Acetylation Is Crucial for p53-Mediated Ferroptosis and Tumor Suppression

Although previous studies indicate that loss of p53-mediated cell cycle arrest, apoptosis, and senescence does not completely abrogate its tumor suppression function, it is unclear how the remaining activities of p53 are regulated. Here, we have identified an acetylation site at lysine K98 in mouse p53 (or K101 for human p53). Whereas the loss of K98 acetylation (p53K98R) alone has very modest effects on p53-mediated transactivation, simultaneous mutations at all four acetylation sites (p534KR: K98R+ 3KR[K117R+K161R+K162R]) completely abolish its ability to regulate metabolic targets, such as TIGAR and SLC7A11. Notably, in contrast to p533KR, p534KR is severely defective in suppressing tumor growth in mouse xenograft models. Moreover, p534KR is still capable of inducing the p53-Mdm2 feedback loop, but p53-dependent ferroptotic responses are markedly abrogated. Together, these data indicate the critical role of p53 acetylation in ferroptotic responses and its remaining tumor suppression activity.
Influences on U.S. Higher Education Programs Educating the Infant-Toddler Workforce

In this paper we introduce the Collaborative for Understanding the Pedagogy of Infant/toddler Development (CUPID), a multi-disciplinary group of more than 50 scholars across 28 U.S. colleges and universities who have joined together in a Scholarship of Teaching and Learning (SOTL) effort to understand how to better support the professional needs of the infant/toddler workforce. One of the goals of CUPID is to make visible key issues faced by institutions of higher education (IHEs) in the U.S. in addressing the training of the infant/toddler workforce. Challenges facing those in higher education include the U.S. policy context, and the federal and state structures for supporting and credentialing the infant/toddler workforce. This work is made more challenging by the historical context of the field, and by the changing views on the goals for early care and education including the call for increased educational qualifications for teachers.
From Accepting to Challenging the International Law of the Sea: China and the South China Sea Disputes

The international law of the sea has been a significant area of China’s engagement with an international legal order largely shaped by the West. China’s encounter with the international law of the sea progressed from bad beginnings in the nineteenth and much of the twentieth century, proceeded through a phase of “regime taking” when China engaged the international law of the sea regime largely on the latter’s terms near the end of the twentieth century, and has recently entered a more complicated and less acquiescent phase. The current period, associated with China’s rise as a great power, is marked by PRC positions and behavior that are in tension with status quo rules and norms. China has maintained a stance of ostensible conformity with existing law while launching ambiguous challenges to the status quo. China is not—or, at least, not yet—fully or openly revisionist, and it may become less so if, or as, its agenda shifts in response to its growing power and expanding interests.
Data center architectures

Data centers house the computational power, storage, networking, and software applications that form the basis of most modern business, academic, and government institutions. This chapter provides an overview of data center fundamentals, with particular emphasis on the role of optical data networking. The chapter begins with an introduction and brief history of data center design, followed by a discussion of environmental considerations including raised floors, fire suppression, energy consumption, and the role of containerized data centers. Industry standard data center classification tiers are presented. Application architectures are discussed, including client-server, peer-to-peer, high performance computing, and cloud computing infrastructure-as-a-service architectures. The physical architectures of Ethernet networked data centers are presented, including Layer 2 and Layer 3 design considerations (alternatives including Fibre Channel storage networks and InfiniBand are briefly mentioned). Network protocols are discussed, including ECMP, STP, transparent interconnect for lots of links (TRILL), shortest path bridging (SPB), and others, in the context of top-of-rack, middle-of-rack, leaf-spine, spline, and other topologies. Design considerations are discussed, including agility, flattened converged networks, virtualization, latency, oversubscription, energy efficiency, scalability, security, availability, and reliability (including database availability constructs). Finally, future design considerations for next generation data centers are presented, including software designed data centers, and the role of optical interconnects is presented, including industry roadmaps.
Increasing the fidelity of noncanonical amino acid incorporation in cell-free protein synthesis.

Abstract Background Cell-free protein synthesis provides a robust platform for co-translational incorporation of noncanonical amino acid (ncAA) into proteins to facilitate biological studies and biotechnological applications. Recently, eliminating the activity of release factor 1 has been shown to increase ncAA incorporation in response to amber codons. However, this approach could promote mis-incorporation of canonical amino acids by near cognate suppression. Methods We performed a facile protocol to remove near cognate tRNA isoacceptors of the amber codon from total tRNAs, and used the phosphoserine (Sep) incorporation system as validation. By manipulating codon usage of target genes and tRNA species introduced into the cell-free protein synthesis system, we increased the fidelity of Sep incorporation at a specific position. Results By removing three near cognate tRNA isoacceptors of the amber stop codon [tRNALys, tRNATyr, and tRNAGln(CUG)] from the total tRNA, the near cognate suppression decreased by 5-fold without impairing normal protein synthesis in the cell-free protein synthesis system. Mass spectrometry analyses indicated that the fidelity of ncAA incorporation was improved. Conclusions Removal of near cognate tRNA isoacceptors of the amber codon could increase ncAA incorporation fidelity towards the amber stop codon in release factor deficiency systems. General significance We provide a general strategy to improve fidelity of ncAA incorporation towards stop, quadruplet and sense codons in cell-free protein synthesis systems. This article is part of a Special Issue entitled “Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O’Donoghue.
Local impacts, global sources: The governance of boundary-crossing chemicals:

Over the last half century, a multijurisdictional, multiscale system of governance has emerged to address concerns associated with toxic chemicals that have the capacity to bioaccumulate in organisms and biomagnify in food chains, leading to fish consumption advisories. Components of this system of governance include international conventions (such as the Stockholm Convention on Persistent Organic Pollutants and the Minamata Convention on Mercury), laws enacted by nation states and their subjurisdictions, and efforts to adaptively manage regional ecosystems (such as the U.S.-Canadian Great Lakes). Given that many of these compounds - including mercury, industrial chemicals such as polychlorinated biphenyls, and pesticides such as toxaphene - circulate throughout the globe through cycles of deposition and reemission, regional efforts to eliminate the need for fish consumption advisories cannot be successful without efforts to reduce emissions everywhere in the world. This paper argues that the scientific community, by monitoring the concentrations of these compounds in the atmosphere and by modeling their fate and transport, play an important role in connecting the various jurisdictional scales of governance. In addition, the monitoring networks that this community of scientists has established can be visualized as a technology of governance essential in an era in which societies have the capacity to produce and release such chemicals on an industrial scale.
Diamagnetic antimatter storage

Abstract The prime candidate for fueling relativistic starships is antimatter and reaching the stars will require antimatter storage on board of a spacecraft in a compact form, most likely liquid or solid antihydrogen. The problem is how to store antimatter in a container made of conventional matter. The solution is an energy barrier on the inner surface of the tank wall preventing antimatter from contacting the wall. Diamagnetic antihydrogen can be kept apart of conventional matter, if a gradient magnetic barrier is created near the inner surface of a tank. In this article, various magnetic barriers induced by arrays of current-carrying superconductive loops are studied by numerical simulations such as mosaics of rectangular loops, arrays of concentric circular loops (top and bottom of a cylindrical container), arrays of identical circular loops that form the cylinder element of the container, and arrays of loops distributed over sphere. The force acting on liquid and solid antihydrogen and the maximum height of antihydrogen ‘fuel’ in a tank are calculated. The problems and challenges caused by antihydrogen vapors are discussed.
Linear decomposition of the optical transfer function for annular pupils

A technique for decomposing the Optical Transfer Function (OTF) into a novel set of basis functions has been developed. The decomposition provides insight into the performance of optical systems containing both wavefront error and apodization, as well as the interactions between the various components of the pupil function. Previously, this technique has been applied to systems with circular pupils with both uniform illumination and Gaussian apodization. Here, systems with annular pupils are explored. In cases of annular pupil with simple defocus, analytic expressions for the OTF decomposition coefficients can be calculated. The annular case is not only applicable to optical systems with central obscurations, but the technique can be extended to systems with multiple ring structures. The ring structures can have constant area as is often found in zone plates and diffractive lenses or the rings can have arbitrary areas. Analytic expressions for the OTF decomposition coefficients again can be determined for ring structures with constant and quadratic phase variations. The OTF decomposition provides a general tool to analyze and compare a diverse set of optical systems.
First-generation annotations for the fathead minnow (Pimephales promelas) genome

Ab initio gene prediction and evidence alignment were used to produce the first annotations for the fathead minnow (Pimephales promelas) genome. We also describe a genome browser, hosted by the Society of Environmental Toxicology and Chemistry, that provides simplified access to the annotation data in context with the genomic sequence. The present study extends the utility of the fathead minnow genome and supports the continued development of this species as a model organism for predictive toxicology. Environ Toxicol Chem 2017;9999:1–7. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.
Bias-selectable three-color short-, extended-short-, and mid-wavelength infrared photodetectors based on type-II InAs/GaSb/AlSb superlattices.

A bias-selectable, high operating temperature, three-color short-, extended-short-, and mid-wavelength infrared photodetector based on InAs/GaSb/AlSb type-II superlattices on GaSb substrate has been demonstrated. The short-, extended-short-, and mid-wavelength channels' 50% cutoff wavelengths were 2.3, 2.9, and 4.4 μm, respectively, at 150 K. The mid-wavelength channel exhibited a saturated quantum efficiency of 34% at 4 μm under +200 mV bias voltage in a front-side illumination configuration and without any antireflection coating. At 200 mV, the device exhibited a dark current density of 8.7×10-5 A/cm2 providing a specific detectivity of ∼2×1011 cm·Hz1/2/W at 150 K. The short-wavelength channel achieved a saturated quantum efficiency of 20% at 1.8 μm. At -10 mV, the device's dark current density was 5.5×10-8 A/cm2. At zero bias, its specific detectivity was 1×1011 cm·Hz1/2/W at 150 K. The extended short-wavelength channel achieved a saturated quantum efficiency of 22% at 2.75 μm. Under -2 V bias voltage, the device exhibited a dark current density of 1.8×10-6 A/cm2 providing a specific detectivity of 6.3×1011 cm·Hz1/2/W at 150 K.
Computational Thinking in the Context of Science and Engineering Practices: A Self-Regulated Learning Approach

Computational thinking has often been overlooked in the K-12 settings, particularly in the Next Generation Science Standards (NGSS). In this chapter, we present a social cognitive self-regulated learning approach for infusing computational thinking into teaching settings using science and engineering practices of NGSS. Self-regulated learning related to computational thinking is viewed as a goal-directed process whereby a learner is required to identify a problem, examine relevant data to inform a solution, develop a solution, and evaluate the solution. Illustrations on how self-regulated learning cycles can become mechanisms to model and assess student computational thinking as students are engaged in science and engineering practices are provided.
Amyloid-β - a reflection of risk or a preclinical marker?

In a recent study, individuals with brain amyloid-β accumulation but no cognitive impairment were classified as being at risk of Alzheimer disease, yet amyloid-β is widely considered to be a pathological biomarker of Alzheimer disease rather than a risk factor — it cannot be both.
Distributed VLSI Design Education Using MOCA: the Multimedia On-line Collaboration Architecture

MOCA is a suite of Internet tools to facilitate group-work in a distance learning environment, built using standard Java utilities. MOCA allows several users to work simultaneously on multimedia documents using a multimedia whiteboard and text-based chat. The system has been targeted for an advanced VLSI chip design course with student design teams composed of undergraduates and graduates at the University of Massachusetts at Amherst as well as off-campus students at a variety of industrial sites (e.g. Intel, IBM, Compaq, AMD). Advisors include University professors and teaching assistants as well as industrial mentors.
Predicting Renal Function Outcomes After Partial and Radical Nephrectomy.

Abstract Background Partial nephrectomy (PN) is generally favored for cT1 tumors over radical nephrectomy (RN) when technically feasible. However, it can be unclear whether the additional risks of PN are worth the magnitude of renal function benefit. Objective To develop preoperative tools to predict long-term estimated glomerular filtration rate (eGFR) beyond 30d following PN and RN, separately. Design, setting, and participants In this retrospective cohort study, patients who underwent RN or PN for a single nonmetastatic renal tumor between 1997 and 2014 at our institution were identified. Exclusion criteria were venous tumor thrombus and preoperative eGFR Intervention RN and PN. Outcome measurements and statistical analysis Hierarchical generalized linear mixed-effect models with backward selection of candidate preoperative features were used to predict long-term eGFR following RN and PN, separately. Predictive ability was summarized using marginal R GLMM 2 , which ranges from 0 to 1, with higher values indicating increased predictive ability. Results and limitations The analysis included 1152 patients (13 206 eGFR observations) who underwent RN and 1920 patients (18 652 eGFR observations) who underwent PN, with mean preoperative eGFRs of 66ml/min/1.73m2 (standard deviation [SD]=18) and 72ml/min/1.73m2 (SD=20), respectively. The model to predict eGFR after RN included age, diabetes, preoperative eGFR, preoperative proteinuria, tumor size, time from surgery, and an interaction between time from surgery and age (marginal R GLMM 2 = 0.41 ). The model to predict eGFR after PN included age, presence of a solitary kidney, diabetes, hypertension, preoperative eGFR, preoperative proteinuria, surgical approach, time from surgery, and interaction terms between time from surgery and age, diabetes, preoperative eGFR, and preoperative proteinuria (marginal R GLMM 2 ). Limitations include the lack of data on renal tumor complexity and the single-center design; generalizability needs to be confirmed in external cohorts. Conclusions We developed preoperative tools to predict renal function outcomes following RN and PN. Pending validation, these tools should be helpful for patient counseling and clinical decision-making. Patient summary We developed models to predict kidney function outcomes after partial and radical nephrectomy based on preoperative features. This should help clinicians during patient counseling and decision-making in the management of kidney tumors.
Cannot Find Internal Opening of Fistula-in-Ano

This chapter reviews options when the internal opening of the fistula-in-ano cannot be located.
Google Searches and Detection of Conjunctivitis Epidemics Worldwide.

Purpose Epidemic and seasonal infectious conjunctivitis outbreaks can impact education, workforce, and economy adversely. Yet conjunctivitis typically is not a reportable disease, potentially delaying mitigating intervention. Our study objective was to determine if conjunctivitis epidemics could be identified using Google Trends search data. Design Search data for conjunctivitis-related and control search terms from 5 years and countries worldwide were obtained. Country and term were masked. Temporal scan statistics were applied to identify candidate epidemics. Candidates then were assessed for geotemporal concordance with an a priori defined collection of known reported conjunctivitis outbreaks, as a measure of sensitivity. Participants Populations by country that searched Google’s search engine using our study terms. Main Outcome Measures Percent of known conjunctivitis outbreaks also found in the same country and period by our candidate epidemics, identified from conjunctivitis-related searches. Results We identified 135 candidate conjunctivitis epidemic periods from 77 countries. Compared with our a priori defined collection of known reported outbreaks, candidate conjunctivitis epidemics identified 18 of 26 (69% sensitivity) of the reported country-wide or island nationwide outbreaks, or both; 9 of 20 (45% sensitivity) of the reported region or district-wide outbreaks, or both; but far fewer nosocomial and reported smaller outbreaks. Similar overall and individual sensitivity, as well as specificity, were found on a country-level basis. We also found that 83% of our candidate epidemics had start dates before (of those, 20% were more than 12 weeks before) their concurrent reported outbreak’s report issuance date. Permutation tests provided evidence that on average, conjunctivitis candidate epidemics occurred geotemporally closer to outbreak reports than chance alone suggests (P Conclusions Conjunctivitis outbreaks can be detected using temporal scan analysis of Google search data alone, with more than 80% detected before an outbreak report’s issuance date, some as early as the reported outbreak’s start date. Future approaches using data from smaller regions, social media, and more search terms may improve sensitivity further and cross-validate detected candidates, allowing identification of candidate conjunctivitis epidemics from Internet search data potentially to complementarily benefit traditional reporting and detection systems to improve epidemic awareness.
Echocardiographic Assessment of Left Ventricular Diastolic Dysfunction: Differentiating a Pulmonary Vascular From a Pulmonary Venous Origin of Pulmonary Hypertension

Pulmonary hypertension (PH) is a heterogeneous condition that may be due to a primary pulmonary arteriolar vasculopathy (pulmonary arterial hypertension or PAH: Group I), or secondary to left heart...
New Diagnosis of Obstructive Sleep Apnea Following Anterior Cervical Discectomy Complicated by Rheumatoid Arthritis: A Case Report.

Obstructive sleep apnea (OSA) is the most common variant of sleep-disordered breathing that often goes undiagnosed. OSA is characterized mainly by anatomical obstruction or partial collapse of upper airways during sleep. The obstruction is multifactorial, and a lesser-known fact is that damage to the pharyngeal plexus during head and neck procedures or placement of hardware in the cervical area can lead to narrowing or collapse of the upper airway. We present such a case of a 59-year-old female who developed new-onset OSA after undergoing anterior cervical discectomy and fusion (ACDF). The severity of OSA worsened with the progression of her rheumatoid arthritis (RA) in the cervical region. This case report aims to raise awareness of such an association among clinicians to enable them to screen appropriate patients for sleep-disordered breathing and treat them accordingly.
3.6 µm Quantum Cascade Laser based on low-interface-scattering active region design

We discuss a solution to the dilemma of high confinement energy and the high interface-scattering rate for the high-barrier InGaAs-InAlAs-AlAs QCLs, operating at wavelengths substantially shorter than 4 µm. The new design includes fewer quantum wells within a single cascade and operates at 3.6 µm. Otherwise, its performance is very similar to the best of recently-shown QCLs at 4.6 µm and 4.0 µm using the same material system.
Assessing the Structures and Interactions of γD-Crystallin Deamidation Variants

Cataracts involve the deposition of the crystallin proteins in the vertebrate eye lens, causing opacification and blindness. They are associated with either genetic mutation or protein damage that accumulates over the lifetime of the organism. Deamidation of Asn residues in several different crystallins has been observed and is frequently invoked as a cause of cataract. Here, we investigated the properties of Asp variants, deamidation products of γD-crystallin, by solution NMR, X-ray crystallography, and other biophysical techniques. No substantive structural or stability changes were noted for all seven Asn to Asp γD-crystallins. Importantly, no changes in diffusion interaction behavior could be detected. Our combined experimental results demonstrate that introduction of single Asp residues on the surface of γD-crystallin by deamidation is unlikely to be the driver of cataract formation in the eye lens.
ICTV Virus Taxonomy Profile: Redondoviridae

Viruses in the family Redondoviridae have a circular genome of 3.0 kb with three open reading frames. The packaged genome is inferred to be single-stranded DNA by analogy to related viruses. Redondoviruses were discovered through metagenomic sequencing methods in samples from human subjects and are inferred to replicate in humans. Evidence of redondovirus infection is associated with periodontitis and critical illness, but redondoviruses have not been shown to be the causative agent of any diseases. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Redondoviridae, which is available at ictv.global/report/redondoviridae.
Predicting the response of a potato-grain production system to climate change for a humid continental climate using DSSAT

Abstract Climate change presents both challenges and opportunities for crop production. This study evaluated the vulnerability of potato (Solanum tuberosum L.) and barley (Hordeum vulgare L.) to climate change for 2050 to 2079 in Maine, U.S.A., and the potential of changing variety and planting date as climate adaptation strategies. The DSSAT model v4.7 was calibrated and evaluated for contrasting varieties of potato (Atlantic, a mid-season variety, and Russet Burbank, a late-season variety) and barley (Robust, a 6-row feed variety, and Newdale, a 2-row malting variety) using 99 field experiments conducted in Maine. The model accurately simulated observed final yield for each variety with modeling efficiencies (EF) ranging from 0.60 to 0.84 and coefficients of determination (r2) above 0.98. Climate change simulations compared crop yield across multiple planting dates for one baseline period (1989-2018) and four future climate scenarios (two emissions scenarios, RCP 6.0 and 8.5, with and without elevated CO2). In the absence of elevated CO2, yield of the potato variety Atlantic, and both barley varieties declined by 6 to 27% under elevated temperature and precipitation, but increased by 5% for the potato variety Russet Burbank. However, under future climate conditions and elevated CO2, yield of all potato and barley varieties increased or were unchanged. Optimal planting date for each variety was consistent across climate scenarios. These results suggest that climate change may favor longer-season varieties such as Russet Burbank, but adjusting planting date may not be an effective climate change adaptation strategy in this region. Elevated CO2 boosted crop growth and development across all varieties for a humid continental climate and for the time period studied. The models used do not address climate change's possible effects on crop quality or losses due to plant diseases and pests.
Genome-wide identification of genes important for growth of Dickeya dadantii and D. dianthicola in potato (Solanum tuberosum) tubers

Dickeya species are causal agents of soft rot diseases in many economically important crops, including soft rot disease of potato (Solanum tuberosum). Using random barcode transposon-site sequencing (RB-TnSeq), we generated genome-wide mutant fitness profiles of Dickeya dadantii 3937, Dickeya dianthicola ME23, and Dickeya dianthicola 67-19 isolates collected after passage through several in vitro and in vivo conditions. Tubers from the potato cultivars "Atlantic", "Dark Red Norland", and "Upstate Abundance" provided highly similar conditions for bacterial growth. Using the homolog detection software PyParanoid, we matched fitness values for orthologous genes in the three bacterial strains. Direct comparison of fitness among the strains highlighted shared and variable traits important for growth. Bacterial growth in minimal medium required many metabolic traits that were also essential for competitive growth in planta, such as amino acid, carbohydrate, and nucleotide biosynthesis. Growth in tubers specifically required the pectin degradation gene kduD. Disruption in three putative DNA-binding proteins had strain-specific effects on competitive fitness in tubers. Though the Soft Rot Pectobacteriaceae can cause disease with little host specificity, it remains to be seen the extent to which strain-level variation impacts virulence.
Implementing Palliative Care Interdisciplinary Teams: Consultative Versus Integrative Models

Interdisciplinary teams are at the core of intensive care unit palliative care consultation. They allow health professionals of different disciplines to collaborate in a synergistic fashion to achieve the goals of patients and their families. Interdisciplinary teams can have a variety of members depending on available resources and the goals for its function. There are multiple benefits to highly functioning teams, as well as challenges that may be faced when trying to provide patient care in a team-based setting. Interdisciplinary teams of different structures may provide the ideal support for complex cases in critical care settings.
Survival of hamster tissue culture cells after freezing and thawing. Interactions between protective solutes and cooling and warming rates.

Summary The usual procedure for preserving the viability of nucleated mammalian cells by freezing involves suspending them in a presumably permeating additive such as glycerol and cooling them at about 1°C per min. This procedure was found to be highly deleterious to Chinese hamster cells. The optimal cooling velocity when 0.1-ml quantities of cell suspension were rapidly thawed was closer to 100°C per min than to 1°C per min. Furthermore, about 25% of rapidly cooled cells survived freezing to −196°C without any additive. However, even in the presence of an additive, the 0.1-ml samples of rapidly cooled cells survived poorly when warming was slower than 1100°C per min. “Rapid” warming with quantities larger than 0.1 ml is often considerably slower than 1100°C per min, a fact that might make the sequence of rapid cooling and “rapid” warming risky to use as a routine procedure for cell preservation. The highest survivals of slowly cooled cells were obtained not by using glycerol, but by using two additives (PVP and sucrose) that are apparently unable to penetrate the cells. Furthermore, one of these (PVP) has too high a molecular weight for one to be able to ascribe its ability to protect to its molar concentration.
Expression, isolation, and characterization of an active site (serine 528----alanine) mutant of recombinant bovine prothrombin.

An active site mutant bovine prothrombin cDNA (Ser528—-Ala) has been constructed, subcloned, and expressed in Chinese hamster ovary cells. The recombinant mutant prothrombin, expressed at the level of 1.5-2.0 micrograms/ml of cell medium, was fully carboxylated (9.9 +/- 0.4 mol of gamma-carboxyglutamic acid/mol of prothrombin). The mutant prothrombin could be activated to thrombin by Taipan snake venom and activated to meizothrombin by ecarin in a manner comparable to native bovine prothrombin or recombinant wild-type bovine prothrombin. The mutant meizothrombin thus formed was stable and did not autolyze. The initial rate of cleavage of mutant prothrombin catalyzed by the full prothrombinase was only 28% of the rate of cleavage of native prothrombin, while recombinant wild-type prothrombin was cleaved at the same rate as the native molecule. The mutant thrombin, obtained from the mutant prothrombin in situ by prothrombinase or Taipan snake venom activation, showed no enzymatic activity toward either fibrinogen or a synthetic chromogenic substrate, D-phenylalanyl-L-pipecolyl-L-arginine-p-nitroanilide dihydrochloride (S2238). The mutant thrombin also bound dansylarginine-N-(3-ethyl-1,5-pentanediyl)amide, a specific fluorescent inhibitor of the thrombin active site, with a weaker binding affinity (kd = 5.4 x 10(-8) M) than did native thrombin (kd = 1.7 x 10(-8) M). These results indicate that the mutant recombinant prothrombin described here is a useful tool for the study of meizothrombin or thrombin without the complications arising from the proteolytic activities of these molecules. Study of the activation of this mutant has already revealed a functional link between the site of initial cleavage by the prothrombinase and the conformation at the nascent active site of prothrombin.
Characterization of a keratinocyte-specific extracellular epitope of desmoglein. Implications for desmoglein heterogeneity and function

Despite the presumed importance of desmoglein, a 160-kDa glycoprotein, in desmosome formation and its possible involvement in certain blistering skin diseases, the precise location and function of this protein have not yet been firmly established. We describe here the characterization of a new monoclonal antibody, AE23, against an extracellular epitope of desmoglein. Both the AE23 epitope and another epitope, defined by the previously characterized DG3.4 antibody, reside on a 160-kDa human epidermal desmoglein as evidenced by their identical solubility profile, their coexistence in a 130-kDa desmoglein degradative product, their coadsorption by an AE23 immunoaffinity column, and the identical changes in the two antigens' electrophoretic mobility after air oxidation and deglycosylation. The AE23 epitope is resistant to various endoglycosidases, suggesting that sugar moieties are not involved. Characterization of several proteolytic fragments of this epidermal desmoglein enabled us to map the DG3.4 epitope to a 96-kDa intracellular domain and the AE23 epitope to an extracellular domain flanked by the plasma membrane and the distal N-glycosylation site(s). However, these two epitopes do not always coexist on the same desmoglein molecule. For example, tissue surveys showed that although the DG3.4 epitope is present in the desmogleins of all epithelial cell types, the AE23 epitope is limited to normal keratinocytes. Moreover, electron microscopic localization data indicate that whereas the DG3.4 epitope is detected in the submembranous plaques of desmosomes, the AE23 epitope is present in the intercellular space of both desmosomal and nondesmosomal areas. These results raise the possibility that there exist several biochemically closely related isoforms of desmoglein, one (AE23+/DG3.4+) restricted to epidermal desmosomes, one (AE23+/DG3.4-) uniformly distributed along the keratinocyte cell surface, and another (AE23-/DG3.4+) present in desmosomes of simple epithelia and basal cells of cultured keratinocytes. The uniform distribution of at least one desmoglein-related antigen in the intercellular space of keratinocytes coupled with the realization that different isoforms of desmogleins form a subfamily of cadherins suggest that desmoglein(s) may play a more general role in keratinocyte adhesion than previously appreciated.
Tumor-Specific CD4+ T Cells Are Activated by “Cross-Dressed” Dendritic Cells Presenting Peptide-MHC Class II Complexes Acquired from Cell-Based Cancer Vaccines

Tumor cells that constitutively express MHC class I molecules and are genetically modified to express MHC class II (MHC II) and costimulatory molecules are immunogenic and have therapeutic efficacy against established primary and metastatic cancers in syngeneic mice and activate tumor-specific human CD4+ T lymphocytes. Previous studies have indicated that these MHC II vaccines enhance immunity by directly activating tumor-specific CD4+ T cells during the immunization process. Because dendritic cells (DCs) are considered to be the most efficient APCs, we have now examined the role of DCs in CD4+ T cell activation by the MHC II vaccines. Surprisingly, we find that DCs are essential for MHC II vaccine immunogenicity; however, they mediate their effect through "cross-dressing." Cross-dressing, or peptide-MHC (pMHC) transfer, involves the generation of pMHC complexes within the vaccine cells, and their subsequent transfer to DCs, which then present the intact, unprocessed complexes to CD4+ T lymphocytes. The net result is that DCs are the functional APCs; however, the immunogenic pMHC complexes are generated by the tumor cells. Because MHC II vaccine cells do not express the MHC II accessory molecules invariant chain and DM, they are likely to load additional tumor Ag epitopes onto MHC II molecules and therefore activate a different repertoire of T cells than DCs. These data further the concept that transfer of cellular material to DCs is important in Ag presentation, and they have direct implications for the design of cancer vaccines.
Comparison of Predicted and Experimental Heat Transfer on a Film-Cooled Rotating Blade Using a Two-Equation Turbulence Model

A three-dimensional Navier-Stokes code has been used to compare the heat transfer coefficient on a film-cooled, rotating turbine blade. The blade chosen is the ACE rotor with five rows containing 93 film cooling holes covering the entire span. This is the only film-cooled rotating blade over which experimental data is available for comparison. Over 2.278 million grid points are used to compute the flow over the blade including the tip clearance region, using Coakley’s q-ω turbulence model. Results are also compared with those obtained by Garg and Abhari (1996) using the zero-equation Baldwin-Lomax (B-L) model. A reasonably good comparison with the experimental data is obtained on the suction surface for both the turbulence models. At the leading edge, the B-L model yields a better comparison than the q-ω model. On the pressure surface, however, the comparison between the experimental data and the prediction from either turbulence model is poor. A potential reason for the discrepancy on the pressure surface could be the presence of unsteady effects due to stator-rotor interaction in the experiments which are not modeled in the present computations. Prediction using the two-equation model is in general poorer than that using the zero-equation model, while the former requires at least 40% more computational resources.Copyright © 1997 by ASME
Cultural criminology and its practices: a dialog between the theorist and the street researcher

This paper sets out to explain to a sociological/criminological audience the theory and practice of what has become known as cultural criminology. The authors have approached this task as a dialog, a conversation, that brings together the critiques and abstractions of the theorist (Jock Young), with his 30-year involvement in the deviance field and the empirical data and experiences of the urban street researcher (David Brotherton) who has spent much of the last 12 years studying and working with gang members. Our aim is to show how this approach to the study of deviance is more appropriate in this period of late modernity than that which currently dominates the field, a positivistic fundamentalism bent on rendering human action into the predictable, the quantifiable, and the mundane.
Unusual manifestations of severe sick sinus syndrome

An extremely athletic 56-year-old male physician was found to have profound sinus bradycardia. His only symptom was markedly increased alertness while actively exercising. During pacemaker insertion he had an episode of prolonged sinus arrest terminated by a precordial thump. This case suggests that exercise can alter autonomic tone and increase cardiac output in sick sinus syndrome, causing improvement in possibly unrecognized, subtle, cerebral symptoms. It also appears that patients with profound sinus bradycardia should be given a substantial dose of atropine prior to pacemaker insertion in an effort to prevent prolonged sinus arrest.
Worthy Goal...Unlikely Reality: The Principal as Instructional Leader.

Strong instructional leadership, although a worthwhile goal, is unlikely for most principals as the position is currently prac ticed, says this writer. Unless some alternative paths are fol lowed to achieve instructional leadership, it will likely remain an illusion.
Endothelial cell heterogeneity and atherosclerosis

Vascular diseases are the most common causes of morbidity and mortality in the Western world. These conditions, whether they involve small and/or large vessels, invariably manifest as localized lesions within the vascular tree. For example, atherosclerosis preferentially affects arteries at branch points, the outer wall of bifurcations, and the inner walls of curvatures. An important question is how systemic alterations in blood-borne factors (eg, those associated with cardiac risk factors) result in focal vasculopathy. A clue to the answer lies in the complex spatial and temporal dynamics of the endothelium. The goal of this review is to highlight concepts of endothelial cell heterogeneity and to apply these principles to an understanding of the pathogenesis, diagnosis, and treatment of atherosclerosis.
Ceramic style analysis in archaeology and ethnoarchaeology: Bridging the analytical gap

Abstract A refitting study with a sample of sherds from Broken K Pueblo indicates that at least some of the “patterning” in the assemblage identified by Hill (1970, Anthropological Papers of the University of Arizona 18) results from unrecognized whole vessels and large conjoinable sherds. It is argued that contemporary stylistic analyses are based on many of the same analytical methods employed in the Broken K study and that research findings of ethnoarchaeology are rarely applied in the analysis of prehistoric ceramics. Despite archaeologists' increasing awareness of formation processes, spurred by ethnoarchaeological research, analytic methods that identify and take into account the effects of these processes on archaeological ceramic assemblages are underdeveloped. Suggestions are offered to resolve this problem, for both archaeological and ethnoarchaeological ceramic analysis, that may permit archaeologists to discover in prehistoric assemblages the same types of relationships identified in systemic assemblages.
Diffuse nodular lymphoid hyperplasia of the colon: polyposis syndrome or normal variant?

Diffuse nodular lymphoid hyperplasia (DNLH) has long been recognized in the pediatric population and in adults with common variable immunodeficiency (CVID).1 More recently, an association with HIV has been described.2 Little is known about the prevalence, natural history, and clinical significance of DNLH in immunocompetent adults. DNLH is a rare lymphoproliferative disorder of unknown etiology. Typically, numerous polypoid nodules composed of hyperplastic benign lymphoid tissue are present in the small and/or large intestinal mucosa.3 Although often an incidental finding, presentation is variable and depends on the size and extent of the nodules, as well as the presence or absence of underlying immunodeficiency. Treatment is directed at associated conditions because the disorder itself generally requires no intervention. Though considered benign by most investigators, several case reports document an association with malignant intestinal lymphoma.3,4 When DNLH is found predominantly in the colon, it can mimic a variety of polyposis syndromes but does not have the high risk of malignancy of familial adenomatous polyposis (FAP).5 This underscores the importance of obtaining biopsy specimens for histopathologic diagnosis and the need for increased awareness of this poorly understood entity.
NONINVASIVE THROMBOLYSIS USING PULSED ULTRASOUND CAVITATION THERAPY - HISTOTRIPSY

Clinically available thrombolysis techniques are limited by either slow reperfusion (drugs) or invasiveness (catheters) and carry significant risks of bleeding. In this study, the feasibility of using histotripsy as an efficient and noninvasive thrombolysis technique was investigated. Histotripsy fractionates soft tissue through controlled cavitation using focused, short, high-intensity ultrasound pulses. In vitro blood clots formed from fresh canine blood were treated by histotripsy. The treatment was applied using a focused 1-MHz transducer, with five-cycle pulses at a pulse repetition rate of 1kHz. Acoustic pressures varying from 2 to 12MPa peak negative pressure were tested. Our results show that histotripsy can perform effective thrombolysis with ultrasound energy alone. Histotripsy thrombolysis only occurred at peak negative pressure >or=6MPa when initiation of a cavitating bubble cloud was detected using acoustic backscatter monitoring. Blood clots weighing 330mg were completely broken down by histotripsy in 1.5 to 5min. The clot was fractionated to debris with >96% weight smaller than 5mum diameter. Histotripsy thrombolysis treatment remained effective under a fast, pulsating flow (a circulatory model) as well as in static saline. Additionally, we observed that fluid flow generated by a cavitation cloud can attract, trap and further break down clot fragments. This phenomenon may provide a noninvasive method to filter and eliminate hazardous emboli during thrombolysis.
REACTIONS OF DNA PURINES WITH DIRHODIUM FORMAMIDINATE COMPOUNDS THAT DISPLAY ANTITUMOR BEHAVIOR

The synthesis and characterization of products from reactions of Rh2(form)2(O2CCF3)2(CH3CN)2 (form = N,N‘-p-ditolylformamidinate, N,N‘-diphenylformamidinate) and the partially solvated [Rh2(DTolF)2(CH3CN)6][BF4]2 (DtolF = N,N‘-p-ditolylformamidinate) with the DNA purine analogues, 9-ethylguanine, and 9-ethyladenine are described. X-ray crystallography was used to characterize Rh2(DTolF)2(O2CCF3)2(CH3CN)2 (1) which crystallizes in the space group P21/n with a = 10.849 (3) A, b = 21.435 (6) A, c = 18.677 (3) A, V = 4340 A3, Z = 4, R = 0.0451, and Rw = 0.0904. The two rhodium centers are bridged by four O2CCF3- ligands with a Rh−Rh distance of 2.24743(5) A. Compound 1 reacts with 9-ethylguanine to form Rh2(DTolF)2(9-EtGH)2(O2CCF3)2 (3) which exists as two isomers, namely head-to-head and head-to-tail as confirmed by 1H NMR spectroscopy. [Rh2(DTolF)2(CH3CN)6][BF4]2 (5) crystallizes in the Pbca space group with a = 21.646 (3) A, b = 31.272 (3) A, c = 14.561(4) A, V = 9857 A3, Z = 8, R = 0.046, and Rw = 0.063. ...