cssi/SciSciGPT-SciSciNet huggingface dataset:
Engineering therapeutic antibodies to combat infectious diseases

Serum therapy fell out of favor 80 years ago, but antibodies against infectious diseases are now experiencing a renaissance. With the evolution of antibiotic-resistant bacteria, the emergence of new pathogens, and a growing population of immunocompromised individuals coupled with improvements in antibody manufacturing and biological efficacy, antibodies are an increasingly attractive therapeutic option. In this review, we highlight successful clinical strategies and discuss recent applications of advanced antibody engineering approaches to combat infectious diseases. Case studies include antibody mixtures to neutralize Staphylococcus aureus; bispecific antibodies promoting Pseudomonas aeruginosa clearance; antibody-antibiotic conjugates to eradicate S. aureus from protected intracellular niches; and novel anti-RSV antibodies with extended serum half-life. These new designs are powerful strategies for targeting infectious diseases due to their abilities to target multiple antigens and induce novel clearance mechanisms.
Fungemia caused by Aureobasidium pullulans in a patient with advanced AIDS: a case report and review of the medical literature.

Introduction. Aureobasidium pullulans is a dematiaceous, yeast-like fungus that is ubiquitous in nature and can colonize human hair and skin. It has been implicated clinically as causing skin and soft tissue infections, meningitis, splenic abscesses and peritonitis. We present, to our knowledge, the second case of isolation of this organism in a patient with AIDS along with a review of the literature on human infection with A. pullulans. Case presentation. A 49-year-old man with advanced AIDS and a history of recurrent oesophageal candidiasis was admitted with nausea with vomiting, and odynophagia. He was treated as having a recurrence of oesophageal candidiasis. Given prior Candida albicans isolate susceptibilities and chronic suppression with fluconazole, he was started on micafungin with eventual improvement in his symptoms. A positive blood culture from admission was initially reported to be growing yeast, but four days later the isolate was recognized as a dematiaceous fungus. The final identification of A. pullulans was not available until 1 month after admission. He had completed a 3-week course of micafungin prior to the identification of the isolate, and repeat cultures were negative. Conclusion. A. pullulans fungemia is rare but can occur in patients with immune suppression or indwelling catheters. The significance of isolating A. pullulans from a blood culture in terms of whether it is the causative agent of a state of disease often cannot be determined because skin colonization is possible. Further work is needed to clarify the clinical implications of A. pullulans fungemia.
Factors for Tolerance Limits which Control Both Tails of the Normal Distribution

A special type of tolerance limits for a normal distribution is presented. The limits have the property that with probability y no more than a specified proporation p1 of a normal population is below the lower limit and at the same time no more than a s..
Creating a Student-Centered Learning Environment Online.

Shortly after we created a face-to-face, student-centered, general education classroom at the University of Kentucky, we were asked to create a similar environment online. In this article, we descr...
Lung epithelial protein disulfide isomerase A3 (PDIA3) plays an important role in influenza infection, inflammation, and airway mechanics

Protein disulfide isomerases (PDI) are a family of redox chaperones that catalyze formation or isomerization of disulfide bonds in proteins. Previous studies have shown that one member, PDIA3, interacts with influenza A virus (IAV) hemagglutinin (HA), and this interaction is required for efficient oxidative folding of HA in vitro. However, it is unknown whether these host-viral protein interactions occur during active infection and whether such interactions represent a putative target for the treatment of influenza infection. Here we show that PDIA3 is specifically upregulated in IAV-infected mouse or human lung epithelial cells and PDIA3 directly interacts with IAV-HA. Treatment with a PDI inhibitor, LOC14 inhibited PDIA3 activity in lung epithelial cells, decreased intramolecular disulfide bonds and subsequent oligomerization (maturation) of HA in both H1N1 (A/PR8/34) and H3N2 (X31, A/Aichi/68) infected lung epithelial cells. These reduced disulfide bond formation significantly decreased viral burden, and also pro-inflammatory responses from lung epithelial cells. Lung epithelial-specific deletion of PDIA3 in mice resulted in a significant decrease in viral burden and lung inflammatory-immune markers upon IAV infection, as well as significantly improved airway mechanics. Taken together, these results indicate that PDIA3 is required for effective influenza pathogenesis in vivo, and pharmacological inhibition of PDIs represents a promising new anti-influenza therapeutic strategy during pandemic and severe influenza seasons.
Response of Fraser's Photinia Stem Cuttings to Selected Rooting Compounds

Selected compounds applied to terminal, semi-hardwood cuttings of Fraser's photinia (Photinia x fraseri Dress) promoted rooting. Concentrated indole-3-butyric acid (IBA) solutions were more effecti...
Progression-Free Survival for Real-World Use of Palbociclib in Hormone Receptor-Positive Metastatic Breast Cancer

Abstract Background Additional use of cyclin-dependent kinase 4/6 inhibitors with endocrine therapy improves progression-free survival (PFS) in advanced hormone receptor (HR)-positive HER2-negative breast cancer. However, neutropenia is a common reason for dose reductions, leading to concerns about palbociclib efficacy at lower doses. A safety analysis confirmed no PFS differences between palbociclib doses in the second-line setting, but to our knowledge, this has not been evaluated for first-line treatment. Patients and Methods In this retrospective, single-center cohort study we evaluated real-world use of first-line palbociclib with aromatase inhibitor (AI) treatment in HR-positive, HER2-negative metastatic breast cancer patients who received treatment between February 2015 and July 2017. The primary objective was to determine PFS of treatment with palbociclib and an AI in a real-world first-line setting. Secondary objectives included determining the PFS for patients treated with palbociclib on the basis of final doses, time to first dose reduction, time to treatment failure (TTF), and safety. Results Seventy patients were included in the final analysis. Median PFS was 26.4 months. No significant differences in PFS were observed on the basis of final doses of palbociclib (P = .77). Time to first dose reduction was 2.3 months. Median TTF was 26.1 months. Dose delays, reductions, and Grade 3/4 neutropenia were common (63%, n = 44; 57%, n = 40; and 62%, n = 43, respectively). Conclusion Real-world first-line palbociclib treatment produced outcomes similar to those in PALOMA-2 (Palbociclib and Letrozole in Advanced Breast Cancer) (median PFS 26.4 months vs. 24.8 months) despite more dose reductions (57%, n = 40 vs. 36%, n = 160) and shorter time to first dose reduction (2.3 vs. 3.0 months). No significant differences in PFS were observed for the varying palbociclib doses. Palbociclib dose reductions might not significantly affect PFS in the first-line setting.
Biliary Tract and Primary Liver Tumors: Who, What, and Why?

Biliary tract and primary liver tumors can be divided into intrahepatic and extrahepatic sites. Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma are the most common primary liver malignancies, making up 75% and 15% of cases, respectively. In the United States, there has been an increase in incidence of HCC and cholangiocarcinoma over the last 2 decades, and it is probable that the incidence of both will continue to climb. Gallbladder cancer, however, is the most frequent biliary tract cancer, comprising 80% to 90% of biliary tract cancers worldwide. Underlying epidemiology and cause are discussed.
Clinical data capture: OMR and OCR and your flatbed scanner.

Clinical order entry and data capture are 2 of the most arduous tasks that physicians face when working with an electronic medical record, or EMR. Of the various technologies available to automate order entry, the use of paper forms that are scanned electronically is the least disruptive to clinicians accustomed to working with traditional charts. Many physicians have resisted using electronic forms on tablet PCs, voice recognition, and other technologies that are used to implement Computerized Physician Order Entry (CPOE) systems. From a clinical perspective, paper forms that are scanned by nonclinical workers in the background can be minimally disruptive to the clinical practice, especially if there is little or no modification of existing forms. Moving from a system based on paper charts to an EMR involves dealing with legacy data. For example, even if a physician happens to work in a hospital or clinic that has a full EMR, most patients who were seen by that doctor for even just a few years had some sort of print chart. If only part of a patient's record is online, then many of the advantages of an EMR – including timely access to pertinent data and the ability to search for past diseases and drug allergies – are obviated. One solution is to keep the paper chart around and summarize it as much as possible. The other is to move the pertinent data to the EMR by scanning the paper chart and converting the data to machine-readable and searchable text with Optical Character Recognition (OCR) software. This article explores clinical data capture options offered by OCR and by Optical Mark Recognition (OMR) software.
Exploration of petrographic, elemental, and material properties of dynamic failure-prone coals.

Abstract The purpose of this study is to explore how the geochemical and petrographic components of coal may impact its physical properties and how these correlate with a history of reportable dynamic failure in coal mines. Dynamic failure events, also termed bumps, bounces, or bursts, are the explosive failures of rock in a mining environment. These events occur suddenly and often with no warning, resulting in worker injury up to and including fatality in greater than 60% of reportable cases through the Mine Safety and Health Administration (MSHA). A database of variables was compiled using publicly available datasets, which includes compositional geographic, strength, and Hardgrove grindability index (HGI) data. Results indicated that bumping coals were less mature, lower in carbon, higher in oxygen, softer, and less well cleated than coals that did not bump. High liptinite content was found to correlate with higher average uniaxial compressive strength (UCS) values. However, no clear and direct correlation between UCS and dynamic failure status was observed. The findings of this study established that differences existed between coals that had versus had not experienced reportable dynamic failure accidents. These differences were inherent to the coal itself and were independent of mining-induced risk factors. Results further illuminated how compositional attribute of coal influenced physical properties and began to clarify potential links between geochemistry and dynamic failure status. Only through the better understanding of risk can more effective mitigating strategies be enacted.
What Moves the

Conventional wisdom suggests that partisanship is the “unmoved mover” in the minds of American voters. Revisionist theories hold that party updating is conditional on individual/contextual factors. By delimiting the scope conditions of the Michigan model, conditional models of party revision do not fundamentally challenge the classic view. This paper proffers an unconditional model of party revision. We theorize that beliefs about government activism –– operational ideology –– are widely available, heuristically efficacious, and easily mapped onto party labels. As such, operational ideology should drive party updating. Using data from eight panel studies covering 1990-2012, we demonstrate that (1) party shapes operational ideology; (2) operational ideology shapes party; (3) the ideology-to-party effects are much larger than party-to-ideology effects; and (4) political awareness does not condition these relationships. These results push the revisionist model of party farther than it has gone before and suggest operational ideology is a core predisposition in mass belief systems.
When Do Legislators Pass On

The authors examine a unique public spending program that is proliferating across developing countries, the constituency development fund, to investigate when legislators exert more effort on behalf of their constituents. Using data from India, they find that legislator effort is significantly lower in constituencies where voters are more attached to political parties. They are also lower in constituencies that are reserved for members of socially disadvantaged groups (lower castes), specifically in those reserved constituencies that are candidate strongholds. This result is robust to controls for alternate explanations and implies that legislators pass on pork when voters are more attached to political parties or influenced by identity issues. These findings have implications for the evaluation of constituency development funds. They also provide a new answer to a central issue in political economy, the conditions under which legislators seek to"bring home the pork"to constituents, that attaches great importance to the role of political parties.
The value of immunotherapy: Comparison of annual cost per patient receiving immunotherapy versus chemotherapy in patients with non-small cell lung cancer.

e19364Background: Checkpoint Inhibitors (CPI) has revolutionized cancer treatment but financial toxicity can be incurred due to high cost. We performed a population-based analysis examining the cos...
Abstract 2157: Generation of Rab27ako and PD-L1ko tumor cells to evaluate potential suppression of exosomal PD-L1 on host immune components involved in cancer immunotherapy

Exosome is a kind of tiny membrane vesicles containing small molecules such as mRNA, miRNA, and proteins. It was showed that exosomes participate in cancer progression and metastasis by transferring bioactive molecules between cancer and various cells in the tumor microenvironment. We isolated exosomes from murine melanoma D5 tumor cell culture media by differential ultracentrifuge, and verified the isolated exosomes by transmission electron microscopy and nanoparticle tracking analysis as well as by exosome markers, e.g. CD63, HRS, ALIX, and TSG101. Using these isolated exosomes, we tested their ability to promote tumor growth. C57BL/6J mice were inoculated with D5 cells on day 0, and were then divided into two groups: treated (i.v.) with PBS vs. PBS containing isolated exosomes every 3 days starting from day 7 for 2 weeks. We found that D5-derived exosomes considerably promoted the tumor growth and notably reduced animal survival. It was reported recently that exosomes could function as immunosuppressive factors in immune responses. To test this in our animal models, we generated Rab27ako D5 and F10 cells to delete exosomes by CRISPR/Cas9 gene editing system. Rab27a knockout significantly decreased the exosome production from D5 and F10 tumor cells as demonstrated by nanoparticle tracking analysis. In addition, it was also reported that exosomes mediate immune suppression via its expression of PD-L1. To address this issue in our animal models, we also generated PD-L1ko D5 and F10 cells. While PD-L1 was expressed in both wild type tumor cells and tumor-derived exosomes, it was absent in the PD-L1ko D5 and F10 cells and the exosomes isolated from the PD-L1ko cells as evident by western blot and flow cytometry. Furthermore, IFNγ failed to augment the PD-L1 expression in D5 and F10 cells treated with PD-L1-trageted CRISPR/Cas9, confirming the knockout of PD-L1 gene in these tumor cells. Deletion of Rab27a or PD-L1 did not affect the proliferation of the tumor cells. Knockout of PD-L1 did not influence exosome secretion, nor did the knockout of Rab27a influence cell-surface PD-L1 expression. Although the immune suppression of exosome on T cells is well-known, such suppression of exosome on other immune cells is largely unknown. Based on our initial experimental results as described above, utilizing the Rab27ako and PD-L1ko D5 and F10 cells generated in our lab will allow us to evaluate the potential suppression of exosomal PD-L1 on host T cells as well as other immune components involved in cancer immunotherapy. Citation Format: You Qin, Kexing Lyu, Sifei Yu, Ming Lin, Max Wicha, Alfred E. Chang, Qiao Li. Generation of Rab27ako and PD-L1ko tumor cells to evaluate potential suppression of exosomal PD-L1 on host immune components involved in cancer immunotherapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2157.
Some sharp performance bounds for least squares regression with L1 regularization

We derive sharp performance bounds for least squares regression with L regularization from parameter estimation accuracy and feature selection quality perspectives. The main result proved for L 1 regularization extends a similar result in [Ann. Statist. 35 (2007) 2313-2351] for the Dantzig selector. It gives an affirmative answer to an open question in [Ann. Statist. 35 (2007) 2358-2364]. Moreover, the result leads to an extended view of feature selection that allows less restrictive conditions than some recent work. Based on the theoretical insights, a novel two-stage L 1 -regularization procedure with selective penalization is analyzed. It is shown that if the target parameter vector can be decomposed as the sum of a sparse parameter vector with large coefficients and another less sparse vector with relatively small coefficients, then the two-stage procedure can lead to improved performance.
Assessment of test-retest reproducibility of [ 18 F]SynVesT-1, a novel radiotracer for PET imaging of synaptic vesicle glycoprotein 2A

Synaptic abnormalities are associated with many brain disorders. Recently, we developed a novel synaptic vesicle glycoprotein 2A (SV2A) radiotracer [18F]SynVesT-1 and demonstrated its excellent imaging and binding properties in nonhuman primates. The aim of this study was to perform dosimetry calculations in nonhuman primates and to evaluate this tracer in humans and assess its test-retest reliability in comparison with [11C]UCB-J. Three rhesus monkeys underwent whole body dynamic PET scanning to estimate the absorbed dose. PET scans in six healthy human subjects were acquired. Time-activity curves (TACs) were generated with defined regions of interest (ROI). Reproducibility of distribution volume (VT) values and its sensitivity to scan duration were assessed with the one-tissue compartment (1TC) model. Non-displaceable binding potential (BPND) was calculated using centrum semiovale as the reference region. The dosimetry study showed high uptake in the urinary bladder and brain. In humans, [18F]SynVesT-1 displayed high uptake with maximum SUV of ~10 and appropriate kinetics with a quick rise in tracer uptake followed by a gradual clearance. Mean 1TC VT values (mL/cm3) ranged from 3.4 (centrum semiovale) to 19.6 (putamen) and were similar to those of [11C]UCB-J. Regional BPND values were 2.7–4.7 in gray matter areas, and mean BPND values across all ROIs were ~ 21% higher than those of [11C]UCB-J. The absolute test-retest variability of VT and BPND was excellent (< 9%) across all brain regions. [18F]SynVesT-1 demonstrates outstanding characteristics in humans: fast and high brain uptake, appropriate tissue kinetics, high levels of specific binding, and excellent test-retest reproducibility of binding parameters. As such, [18F]SynVesT-1 is proved to be a favorable radiotracer for SV2A imaging and quantification in humans.
Genetic testing and genetic discrimination: Public policy when insurance becomes “too expensive”

Abstract We examine public policy toward the use of genetic tests by insurers when a positive test makes actuarially fair insurance too expensive for some consumers. With state-dependent utility, consumers may decline actuarially fair insurance if the probability of becoming ill exceeds a threshold. In markets with adverse selection, a positive genetic test may cause all or some high risks to drop out of the market (complete and partial genetic discrimination, respectively). Full participation in the market by all consumers requires cross-subsidization. We show that the consent law and mandatory testing are equivalent. Under complete genetic discrimination, the duty to disclose is never Pareto dominated, but either the code of conduct or consent law can yield the same outcome. Under partial genetic discrimination, the duty to disclose is never Pareto dominated. However, partial genetic discrimination and cross-subsidization imply the information ban is noncomparable to the other policy alternatives.
Heat Transfer Mechanisms and Tunable Thermal Conductivity Anisotropy in Two-Dimensional Covalent Organic Frameworks with Adsorbed Gases

Two-dimensional covalent organic frameworks (2D COFs) are a novel class of materials that are ideal for gas storage and separation technologies due to their high porosities and large surface areas. In this work we study the heat transfer mechanisms in 2D COFs with the addition of gas adsorbates, demonstrating the remarkably tunable anisotropic response of the phonon thermal conductivity in 2D COFs during gas adsorption. More specifically, our results from atomistic simulations on COF-5/methane systems show that, as the gas density increases, the cross-plane thermal conductivity along the direction of the laminar pores increases, whereas the in-plane thermal conductivity along the 2D sheets is monotonically decreased. We show that a large portion of heat is conducted along the laminar pore channels by the gas molecules colliding with the solid framework and is directly related to the gas diffusivities.
Novel nuclear interaction of EGFR and STAT3 in the activation of iNOS/NO pathway

Proc Amer Assoc Cancer Res, Volume 45, 2004 1440 EGF receptor (EGFR) has been detected as a full-length protein in the nucleus of highly proliferative tumor cells and primary tumor specimens for the past decade. The nuclear function of EGFR, however, was not revealed until recently by our laboratory (Nat. Cell Biol. 3:802, 2001) to involve direct activation of cyclin D1 gene promoter. Despite with significant transactivational activity, EGFR lacks a putative DNA binding domain and, therefore, requires transcription co-factor with DNA-binding ability for its transcriptional function. Additionally, in some tumor types, EGFR over-expression has been shown to correlate with high levels of nitric oxide (NO), both properties commonly associate with tumorigenesis and tumor growth. However, the molecular mechanism underlying this correlation remains unknown. We report here, for the first time, that nuclear EGFR directly activates inducible NO synthase (iNOS) gene via its physical and functional cooperation with signal transducers and activators of transcription 3 (STAT3), following EGF stimulation. Cell-surface EGFR rapidly translocated into the nucleus of tumor cells following activation by EGF and interacted significantly with STAT3 as shown by immunofluorescent microscopy/deconvolution and co-immunoprecipitaiton analyses. Nuclear EGFR/STAT3 complex bound to iNOS gene promoter in vitro and in vivo, as indicated by gel shift/supershift assays and chromatin immunoprecipitation (ChIP) methods, respectively. Using RT-PCR and western blot analyses, we observed EGF significantly enhanced iNOS gene expression by 5-fold in MDA-MB-468 breast cancer cells. Consistently, EGF increased the activity of a 7.2 kb iNOS promoter by approximately 30-fold compared to that of the promoter-less construct. Promoter deletion/mutation studies further identified a region in the iNOS promoter to be required for its responsiveness to EGF and to contain both EGFR and STAT3 binding sites. Immunohistochemical analyses of a cohort of 130 breast carcinomas showed that patients with high nuclear EGFR in their tumors had worse overall survival than those stained negative (33.4 + 14.6 vs. 47.8 + 15.3 months; p=0.009). Consistently, we found a direct correlation (p<0.001) between high levels of nuclear EGFR and Ki-67, a measure of active proliferation. In contrast, no significant correlation was found between the levels of non-nuclear EGFR and nuclear EGFR suggesting a complex mechanism underlying nuclear transport of cell-surface EGFR. Together, these findings describe a novel mode of transcriptional control that involves cooperated efforts of STAT3 and its novel transcription partner, nuclear EGFR. Our work also indicates that nuclear EGFR is an important prognostic indicator for breast cancer patients as well as a positive regulator of the NO pathway, suggesting de-regulated iNOS expression may, in part, contribute to the malignant behavior in tumors with increased nuclear EGFR.
Possible Origin of Gravity and the Holographic Principle

Assuming the holographic principle, the gravitational force can be formulated thermodynamically as an entropic force, but the mechanism by which the attraction between two masses occurs is not clear. The physical basis for the holographic principle is also unknown. My primary assumption is that empty space consists of discrete countable units that have on the order of one bit of entropy per cubic Planck unit. The basic idea here is simply that rather than matter just occupying empty space, the presence of matter excludes discrete units of space that have entropy. I argue that this volume exclusion of empty space leads to an attractive gravitational force and to the holographic principle.
IBM China Development Lab Shanghai: Capability by Design

When IBM shifted from a traditional territory-based multinational organization to what it called a globally integrated enterprise, it established its headquarters for "Growth Markets" in Shanghai and "Established Markets" in New York. This positioned its China Development Labs (CDL) in Shanghai as a key platform for serving growth markets including the BRIC countries and other rapidly developing regions. Though quite young, CDL Shanghai had grown to become one of IBM's largest labs. The case examines IBM's early-mover establishment of its corporate research lab and CDL, and through the examination of three product development vignettes looks at the systematic approach taken to the development of lab personnel and capabilities.Learning Objective: Examine the deliberate strategy of capability development within the China lab of a large multinational.
Center-Level Experience and Kidney Transplant Outcomes in HIV-Infected Recipients.

Excellent outcomes among HIV+ kidney transplant (KT) recipients have been reported by the NIH consortium, but it is unclear if experience with HIV+ KT is required to achieve these outcomes. We studied associations between experience measures and outcomes in 499 HIV+ recipients (SRTR data 2004-2011). Experience measures examined included: (1) center-level participation in the NIH consortium; (2) KT experiential learning curve; and (3) transplant era (2004-2007 vs. 2008-2011). There was no difference in outcomes among centers early in their experience (first 5 HIV+ KT) compared to centers having performed >6 HIV+ KT (GS adjusted hazard ratio [aHR]: 1.05, 95% CI: 0.68-1.61, p = 0.82; PS aHR: 0.93; 95% CI: 0.56-1.53, p = 0.76), and participation in the NIH-study was not associated with any better outcomes (GS aHR: 1.08, 95% CI: 0.71-1.65, p = 0.71; PS aHR: 1.13; 95% CI: 0.68-1.89, p = 0.63). Transplant era was strongly associated with outcomes; HIV+ KTs performed in 2008-2011 had 38% lower risk of graft loss (aHR: 0.62; 95% CI: 0.42-0.92, p = 0.02) and 41% lower risk of death (aHR: 0.59; 95% CI: 0.39-0.90, p = 0.01) than that in 2004-2007. Outcomes after HIV+ KT have improved over time, but center-level experience or consortium participation is not necessary to achieve excellent outcomes, supporting continued expansion of HIV+ KT in the US.
Bacteriorhodopsin-based volumetric optical memory

We explore the use of the protein bacteriorhodopsin as the recording medium in an all-optical three-dimensional memory. Three-dimensional memory architectures offer as much as a thousand-fold improvement in memory storage over current storage technology. Although bacteriorhodopsin has been used previously as the active memory element in a number of three-dimensional architectures (e.g. holographic and two-photon), a sequential single-photon volumetric architecture employing a photochemical branching reaction characteristic of the protein is currently showing the most promise. This unique branching reaction allows for long-term storage by the protein. During the past two years, a prototype has been constructed by using a number of commercially available components, including spatial light modulators and microdiode lasers. Chemical, genetic, and optical technologies optimize the writing and reading efficiencies of the protein based memory. For example, gray-scale and polarization multiplexing are capable of increasing the storage capacity ten-fold. Although a number of issues still must be resolved with respect to commercialization, cost, and performance, the promise of both increased speed (via parallel reading and writing operations) and storage density, make volumetric memories a potentially viable alternative to conventional technologies.
Acyl-HSL signal decay: intrinsic to bacterial cell-cell communications.

The structure of the signaling molecule of Vibrio fischeri, N-3-(oxohexanoyl) homoserine lactone (3OC6HSL), was determined and was the first representative of a large family of molecules, the acylhomoserine lactones (acyl-HSLs). For microbes that degrade acyl-HSL signals but are not responsible for accumulation of acyl-HSLs or have quorum-sensing systems, acyl-HSL degradation could provide a means to compete with acyl-HSL-producing, quorum-sensing neighbors in the environment. Acyl-HSL quorum signal degradation is important if the presence and concentration of these signaling molecules are important for several microbial group behaviors. Acyl-HSL-degrading microbes that use acyl-HSLs as either a sole carbon source or carbon and nitrogen source could gain an additional advantage in soil environments where nutrients are limited. The possibility that acyl-HSL-mediated quorum sensing is widespread suggests that it may be seeing tip of the iceberg in terms of microbes and organisms with acyl-HSL-degrading potential.
The North Atlantic circulation in the early 1980s. An estimate from inversion of a finite-difference model

A finite-difference model of the North Atlantic is constructed for the purpose of making an estimate of the circulation through an inverse calculation. The data base is eclectic, and includes hydrography, oxygen, nutrients, current meter and float records, atmospheric momentum, heat and water vapor transfers, as well as estimates of certain integral fluxes. Owing to the available hydrographic database, the model resolution is restricted to 1 deg at best, and is much coarser in many aspects. This limited resolution is a major obstacle to accurate estimates of climatological fluxes. In its final form, there are about 9000 constraints in 29,000 formal unknowns plus 9000 noise unknowns. The system is solved as a tapered least-squares system by a sparse conjugate gradient algorithm. With the exception of a few float velocities, all constraints are found to be consistent within error estimates. The model produces estimates of large-scale fluxes and flux divergences for all conventional properties including heat and nutrients as well as carbon dioxide and alkalinity. Meridional fluxes of carbon are found to be indistinguishable from zero, whereas the North Atlantic tends to export nutrients to the south, but carry heat to the north. Traditional oceanographic depictions of the circulation through combination of nonsynoptic data into steady models may have reached their useful limit in the present calculation, as the conflicts between the data and physical requirements become quantitatively apparent.
Septal cells and post-natal development of rat lungs, electron microscopic and biochemical studies.

Elektron- und lichtmikroskopische Studien wurden an den Septalzellen der Lungen von Ratten in verschiedenen Stadien der Entwicklung ausgefuhrt: Die Studien waren an embryonischen, neugeborenen, nach der Entwohnung saugenden und erwachsenen Ratten. Biochemische Analysen dieser Lungengewebe wurden gleichfalls gemacht. Die Septalzellen der Lunge stammen von unentwickelten Zellen des Mesenchyms. In fruherer Periode der Entwicklung der alveolaren respiratorischen Einheit veranderten sich die mesenchymalen Zellen von kubischer oder ovaler Form zu spindelartige Zellstruktur. Wahrend dieser ganzen Entwicklung wurde eine Ansammlung von Fett und Glykogen in den Septalzellen beobachtet. Die Ablagerung von Fett in diesen Zellen nahm progressiv zu und erreichte das Maximum ungefahr am 15. Lebenstag und nahm von da an allmahlich ab. Es ist nicht bewiesen, das das Fett in den Zellen, ein Produkt aus dem zirkulatorischen Fett, abgelagert wurde. Daher muss man annehmen, das das Fett in den Septalzellen auf neue Fett-Syntheses zuruckzufuhren ist.Kollagen des Interstitiums wurde unmittelbar nach der Geburt beobachtet. Elastische Fasern dagegen konnten erst nach ungefahr 17 Tagen nach der Geburt gefunden werden. DNS-Gehalt der Lunge vermehrte sich sehr schnell vor der Entwohnung, dann langsamer. Die Proportionen von RNS zu DNS waren grosser nach 18-20 Tagen. Diese Daten deuten darauf hin, das Elastin und Kollagen erst nach der Differenzierung der Septalzellen synthetisiert werden. Im Verlaufe dieser Differenzierung konnen die mesenchymale Zellen der Lunge in ein Fett-Ansammlungsstadium eintreten, ahnlich wie andere Zellen mesenchymalen Ursprungs zeigen. Spater jedoch andern these Zellen ihre Struktur and funktionieren als die Septalzellen. Die Fett-tragenden Septalzellen spielen wahrscheinlich eine bedeutende Rolle in der neonatalen Periode der Entwicklung der Lunge.
Crystal structures of aspartate aminotransferase reconstituted with 1-deazapyridoxal 5'-phosphate: internal aldimine and stable L-aspartate external aldimine.

The 1.8 A resolution crystal structures of Escherichia coli aspartate aminotransferase reconstituted with 1-deazapyridoxal 5′-phosphate (deazaPLP; 2-formyl-3-hydroxy-4-methylbenzyl phosphate) in th...
A review of explosive accelerators for hypervelocity impact

Abstract A technical overview of experimental methods using high explosive techniques for conducting hypervelocity impact studies is presented. The explosive techniques use the explosive detonation fronts as means of accelerating the projectile, or as means of compressing a light gas which is then used to launch the projectile. The explosive launchers are in six subdivisions: high explosive pellet accelerators, flyer plate accelerators, shaped charges, explosive-formed projectiles, fragment and microparticle accelerators, and explosive gas guns. Each one of the subdivisions presents the various techniques, their advantages and disadvantages, the range of mass and velocity capable of being accelerated, and whether the technique can be scaled for larger or smaller masses.
Effect of Potential on the Corrosion Fatigue Crack Growth Rate in AISI 304 Stainless Steel in Sodium Sulfate Solution at 250 C

Abstract The corrosion fatigue crack growth (FCG) behavior of sensitized AISI 304 stainless steel was studied in 0.01M Na2SO4 solution at 250 C. Crack growth rates at different frequencies ranging from 1.0 to 8×10−3 Hz, and at different electrochemical potentials, were measured with a sinusoidal loading waveform at a load ratio (R=pmin/pmax) of 0.5. The results show that both the FCG rate and the fracture morphology depend on the frequency and the applied potential. At low frequencies (below 8×10−2 Hz), there is a critical potential (between −450 and −200 mVH) above which the FCG rates are significantly enhanced over those observed at lower potentials. Fracture morphology of sensitized AISI 304 stainless steel depends on the potential as well as the frequency. At low potentials and/or higher frequencies, transgranular cracking is the principal mode of failure; however, at high potentials and/or at low frequencies, the fatigue cracks propagate intergranularly.
Review of Research on Self-Management Interventions in Supported Employment Settings for Employees With Disabilities

Self-management strategies involve the use of antecedent cue regulation, self-monitoring, self-determined consequences, or a combination of any of these techniques to facilitate job-skill acquisition, maintenance, and generalization. The purpose of this article is to review the empirical literature related to self-management strategies in supported employment settings for individuals with disabilities and offer guidelines for implementation. Best practices, limitations of current research, and needs for future research are offered.
Role of Mitofusin 2 in the Renal Stress Response

The role of mitofusin 2 (MFN2), a key regulator of mitochondrial morphology and function in the renal stress response is unknown. To assess its role, the MFN2 floxed gene was conditionally deleted in the kidney of mice (MFN2 cKO) by Pax2 promoter driven Cre expression (Pax2Cre). MFN2 cKO caused severe mitochondrial fragmentation in renal epithelial cells that are critical for normal kidney tubular function. However, despite a small (20%) decrease in nephron number, newborn cKO pups had organ or tubular function that did not differ from littermate Cre-negative pups. MFN2 deficiency in proximal tubule epithelial cells in primary culture induced mitochondrial fragmentation but did not significantly alter ATP turnover, maximal mitochondrial oxidative reserve capacity, or the low level of oxygen consumption during cyanide exposure. MFN2 deficiency also did not increase apoptosis of tubule epithelial cells under non-stress conditions. In contrast, metabolic stress caused by ATP depletion exacerbated mitochondrial outer membrane injury and increased apoptosis by 80% in MFN2 deficient vs. control cells. Despite similar stress-induced Bax 6A7 epitope exposure in MFN2 deficient and control cells, MFN2 deficiency significantly increased mitochondrial Bax accumulation and was associated with greater release of both apoptosis inducing factor and cytochrome c. In conclusion, MFN2 deficiency in the kidney causes mitochondrial fragmentation but does not affect kidney or tubular function during development or under non-stress conditions. However, MFN2 deficiency exacerbates renal epithelial cell injury by promoting Bax-mediated mitochondrial outer membrane injury and apoptosis.
SCLERAL BUCKLING SURGERY FOR STAGE 4B RETINOPATHY OF PREMATURITY

Results of scleral buckling in 15 consecutive eyes of 13 infants with stage 4B retilnopathy of prematurity (ROP) were reviewed. Ten of 15 retinas achieved macular reattachment with a single scleral buckling procedure. Four of 15 retinas unable to be attached by scleral buckling were reattached after the addition of a single vitreous operation. One of 15 retinas was unable to be reattached despite both a scleral buckling and a single vitreous procedure. Despite macular attachment in all except one eye, visual results were disappointing. Fix and follow visual acuity was present in 3 eyes, light perception in 11 eyes, and no light perception in 1 eye. Average follow-up was 10 months. Possible causes for poor visual outcomes despite retinal reattachment include retinal abnormalities as a result of detachment and amblyopia.
Current and emerging concepts in non-invasive and minimally invasive management of spine metastasis

To provide a comprehensive review on the presentation, work-up and the management of spine metastasis with or without epidural spinal cord compression with focus on the roles of surgery and radiotherapy. Emphasis has been laid on the technological advances with recent development of stereotactic body radiotherapy (SBRT) or radiosurgery (SRS) and minimally invasive surgical approaches like kyphoplasty and vertebroplasty.
CALORIMETRIC EVIDENCE FOR A SINGLET GROUND STATE IN CuCr AND CuFe

Heat-capacity measurements show that the entropy reduction associated with the formation of the spin-compensated state in $\mathrm{Cu}\mathrm{Cr}$ is $R\mathrm{ln}(2S+1)$. The magnetic field dependence of the heat capacity of $\mathrm{Cu}\mathrm{Fe}$ suggests that at $T\ensuremath{\ll}{T}_{K}$ the susceptibility has the form $\ensuremath{\chi}={\ensuremath{\chi}}_{0}\ifmmode\times\else\texttimes\fi{}[1\ensuremath{-}15{(\frac{T}{{T}_{K}})}^{2}]$, which is consistent with the third law of thermodynamics.
Signatures of phase coherence in the low-temperature transport properties of multiwall carbon nanotubes

Four-terminal low-temperature measurements of the electrical transport of multiwall carbon nanotube devices with low-resistance contacts reveal features that signify the presence of phase coherent transport. Sharp resonances in the differential resistance as a function of dc bias are observed that are due to the interference of electron paths that are directly transmitted through the nanotube and paths that are transmitted via resonant states, the so-called Fano resonance. The metastability of these resonances indicates that the resonant states most likely arise from potentials created by metastable defects in the device. Correlations between the nanotube conductance and the simultaneously measured conductance of the contacts hint that the defects may be located at the contacts, although the nonlocality introduced by the long-range phase coherence makes an absolute determination of the location of the impurities by this technique impossible.
Self-directed Mindfulness Training and Improvement in Blood Pressure, Migraine Frequency, and Quality of Life:

Background:Interest in case studies has undergone a resurgence concurrent with increasing prioritization of illustrations of patient-centered care. However, substantial inclusion of the patient in these reports remains limited. Here, a doctor and patient collaborate to present her case report of self-directed mindfulness training and the subsequent changes in blood pressure, migraine frequency, and quality of life.Methods:After receiving encouragement from her naturopathic doctor, the patient initiated an 8-week program in mindfulness training following the Kabat-Zinn protocol and logged her daily blood pressure and symptoms before and after meditation sessions over an 11-week period.Results:Patient-reported outcomes included decreased perceived stress, increased focus, and a newfound sense of centeredness and calm. Changes in objective outcomes were clinically and statistically significant, including reductions in mean systolic and diastolic blood pressure between week 1 and week 11 (P = .0001 and P = .0...
Effects of coronary angioplasty using progressive dilation on ostial stenosis of the left anterior descending artery.

Abstract Percutaneous transluminal coronary dilation of left anterior descending (LAD) ostial stenoses has been considered a high-risk procedure, because of its proximity to the left main, and an increased trend toward abrupt closure.1,2 Dilation of ostial lesions in general has not been advocated based on data3 available on right coronary ostial stenoses, which showed an increased rate of acute complications, a low primary success rate and a relatively high restenosis rate. We retrospectively analyzed our experience in 40 consecutive patients undergoing coronary angioplasty of ostial stenosis in the LAD to test the hypothesis that progressive coronary dilation may also enable safer dilation of stenoses at the origin of the LAD (i.e., lesions in which balloon positioning causes left main occlusion).
Hydrogen as a process control index in a pilot scale anaerobic digester

A 6m3 pilot scale anaerobic contact digester treating brewery effluent was subjected to volumetric shock loadings. The concentration of hydrogen in the biogas was monitored and was shown to have the potential of being a sensitive and rapid indicator of perturbation within the digester.
Effects of Government Spending on Research Workforce Development: Evidence from Biomedical Postdoctoral Researchers

We examine effects of government spending on postdoctoral researchers’ (postdocs) productivity in biomedical sciences, the largest population of postdocs in the US. We analyze changes in the productivity of postdocs before and after the US government’s 1997 decision to increase NIH funding. In the first round of analysis, we find that more government spending has resulted in longer postdoc careers. We see no significant changes in researchers’ productivity in terms of publication and conference presentations. However, when the population is segmented by citizenship, we find that the effects are heterogeneous; US citizens stay longer in postdoc positions with no change in publications and, in contrast, international permanent residents (green card holders) produce more conference papers and publications without significant changes in postdoc duration. Possible explanations and policy implications of the analysis are discussed.
Effective leukocyte removal from platelet preparations by centrifugation in a new pooling bag.

A pooling bag (Leukotrap, Cutter Laboratories, Berkeley, CA) with a protruding pocket at the bottom into which heavier cellular elements are collected after centrifugation at 390 × g for 10 minutes, was studied. The tab is clamped before transfusion. Varying numbers of platelet concentrates (PC) that had been stored for different durations were pooled and centrifuged in the bags. When 4 or more units of PC were studied, the results were independent of the number of units and the duration of storage. Approximately 90 percent of the contaminating leukocytes (WBC) were removed with a platelet loss of less than 10 percent. Similar results were obtained with single-donor platelets (WBCs decreased 93%; range, 77–99%; n = 12). Posttransfusion increments were similar to those with unmodified platelets; in four patients, febrile platelet transfusion reactions were eliminated by the WBC removal. Thus, the bags represent a simple, reproducible, and effective means of reducing WBC and red cell contamination of platelet preparations with acceptable platelet losses.
REFLECTIONS ON EARLY DAYS IN ELECTRON TRANSFER

As an introduction to this NATO workshop, some of the early electron transfer days, beginning with the late 1940s, are recounted.
Cholestanol-loaded-cyclodextrin improves the quality of stallion spermatozoa after cryopreservation

This study was to compare the effect of adding cholesterol or cholestanol loaded cyclodextrins in stallion sperm prior to cryopreservation to optimize sperm cryosurvival. Ejaculates from each of eight stallions were diluted to 120 million cells in a S-MEDIUM diluent. The diluted sperm were sub-divided into three treatments: no additive (control); 0.75mg of cyclodextrin pre-loaded with cholesterol (CLC)/120 million sperm (positive control); 1.5mg CLC/120 million sperm; 0.75mg of cyclodextrin pre-loaded with cholestanol (CnLC)/120 million sperm; and 1.5mg CnLC/120 million sperm. To set the experiments, the treated sperm were incubated for 15min at 22°C to allow for the incorporation of cholesterol or cholestanol. In each experiment, treated sperm incubated for 15min at 22°C to allow for incorporation of cholesterol or cholestanol. The samples were then diluted 1:5 (v/v) with Lactose-Egg Yolk diluent and cooled to 5°C over a 2h period. Loaded into 0.25ml polyvinylchloride straws, frozen in liquid nitrogen vapor for 10min, and then plunged into liquid nitrogen until further use. Higher percentages of motile sperm and viable cells were achieved after thawing for stallion sperm treated with CLC and CnLC compared to control (P<0.05). Addition of CnLC also resulted in more number sperm binding to chicken egg perivitelline membrane (CEPM) after cryopreservation than cholestanol and control sperm (P<0.05). In conclusion, CnLC and CLC improved the percentage of post-thaw motility of equine sperm and CnLC provided greater binding efficiency.